Forum Médical Suisse Swiss Medical Forum

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Seite 1
Forum Médical Suisse
Schweizerisches Medizin-Forum
7.5. 2008
Swiss Medical Forum
Supplementum 40
76e Assemblée annuelle
ad Swiss Medical Forum
2008;8(18–19)
de la Société Suisse de Médecine Interne
Médecine et Société
Medizin und Gesellschaft
Beaulieu Lausanne, 21–23 mai 2008
Editores Medicorum Helveticorum
Offizielles Fortbildungsorgan der FMH www.medicalforum.ch
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S O M M A I R E / I N H A LT
Forum Med Suisse 2008;8(Suppl. 40)
1S
S1–S4
Communications libres SSMI Session 1: Système de soins
Freie Mitteilungen SGIM Session 1: Betreuung und Pflege
3S
S5–S8
Communications libres SSMI Session 2: Qualité des soins
Freie Mitteilungen SGIM Session 2: Qualität der Pflege
4S
S9–S15
Communications libres SSMI Session 3: Prédiction des risques
Freie Mitteilungen SGIM Session 3: Risikovorhersage
5S
S16–S21
Communications libres SPSG
Freie Mitteilungen SFGG
7S
S22–S27
Communications libres SSMI Session 4: Santé publique
Freie Mitteilungen SGIM Session 4: Public health
9S
S28–S31
Communications libres SSMI Session 5: Stratégie diagnostique
Freie Mitteilungen SGIM Session 5: Diagnostik
11 S
S32–S35
Communications libres SSMI Session 6: Stratégie thérapeutique
Freie Mitteilungen SGIM Session 6: Therapeutisches Vorgehen
12 S
S36–S39
Communications libres SSMI Session 7: Communication et psychosocial
13 S
Freie Mitteilungen SGIM Session 7: Kommunikation et psychosoziale Aspekte
S40–S47
Communications libres SSHé: Clinical Hematology
Freie Mitteilungen SGH: Clinical Hematology
14 S
S48–S53
Communications libres SSHé:
Hemostasis, Vascular Biology and Transfusion Medicine
Freie Mitteilungen SGH:
Hemostasis, Vascular Biology and Transfusion Medicine
17 S
S54–S61
Communications libres SSHé: Experimental Hematology
Freie Mitteilungen SGH: Experimental Hematology
19 S
SGH1–SGH2
Prix scientifiques SSHé 2008
Wissenschaftliche Preise SGH 2008
21 S
P1–P3
Poster SSMI: Diabétologie
Posters SGIM: Diabetologie
22 S
IMPRESSUM
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S O M M A I R E / I N H A LT
Forum Med Suisse 2008;8(Suppl. 40)
2S
P4–P6
Posters SSMI: Endocrinologie
Posters SGIM: Endokrinologie
23 S
P7–P19
Posters SSMI: Métabolisme
Posters SGIM: Stoffwechsel
24 S
P20–P23
Posters SSMI: Néphrologie
Posters SGIM: Nephrologie
28 S
P24–P26
Posters SSMI: Gastroentérologie
Posters SGIM: Gastroenterologie
29 S
P27–P28
Posters SSMI: Hépatologie
Posters SGIM: Hepatologie
30 S
P29–P35
Posters SSMI: Communication et psychosocial
Posters SGIM: Kommunikation und psychosoziale Aspekte
31 S
P36–P39
Posters SSMI: Systèmes de soins
Posters SGIM: Betreuung und Pflege
33 S
P40–P60
Posters SSMI: Maladies cardiovasculaires
Posters SGIM: Kardiovaskuläre Erkrankungen
34 S
P61–P63
Posters SSMI: Pneumologie
Posters SGIM: Pneumologie
40 S
P64–P112
Posters SSMI: Médecine interne générale
Posters SGIM: Allgemeine Innere Medizin
41 S
P113–P127
Posters SSMI: Infectiologie
Posters SGIM: Infektiologie
56 S
P128–134
Posters SSMI: Oncologie
Posters SGIM: Onkologie
61 S
P135–P143
Posters SSHé: Transplantation Hematology
Posters SGH: Transplantation Hematology
63 S
P144–P152
Posters SSHé: Clinical Hematology
Posters SGH: Clinical Hematology
66 S
P153–P161
Posters SSHé: Experimental and Laboratory Hematology
Posters SGH: Experimental and Laboratory Hematology
69 S
P162–P170
Posters SSHé: Hemostasis and Transfusion Medicine
Posters SGH: Hemostasis and Transfusion Medicine
72 S
P171–P177
Posters SPSG
Posters SFGG
75 S
P178–P191
Session interactive des posters SPTC
Interaktive Postersession SKPT
77 S
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
S1
Accuracy of drug advertisements in Swiss medical journals
Nordmann A. J., Gonzalez Santiago M., Bucher H. C. (Basel)
Background: The accuracy of drug advertisements quoting a reference study in Swiss medical journals is unknown.
Methods: We screened all issues of six Swiss medical journals published in the year 2005 (Swiss Medical Weekly, Swiss Medical Forum,
Schweizerische Ärztezeitung, Ars Medici, Therapeutische Umschau,
Therapiewoche Schweiz) to identify all drug advertisements for pain
killers, gastroenterological and psychopharmacological drugs. Two
reviewers then independently evaluated all drug advertisements
referring to at least one publication according to prespecified criteria.
The pharmaceutical claim was rated as being supported, potentially
biased or or not supported by the quoted study according to prespecified criteria. Disagreement between the two reviewers was
resolved by consensus. Kappa statistics were calculated to measure
the agreement between the reviewers.
Results: We identified 78 claims referring to a published study (32
claims [41%] referred to pain killers, 30 [38%] to psychopharmacological drugs, and 16 [21%] to gastrointestinal drugs. Overall, 53%
of all claims were rated to be biased (n = 25, 32%) or not supported
(n = 16, 21%) by the quoted reference study. Thirty-seven (47%)
claims were supported by the corresponding reference study. The
kappa statistics for supported, not supported and potentially biased
claims were 0.77, 0.73, and 0.71, respectively, demonstrating substantial agreement between the two reviewers. Studies with potential
conflict of interest had a higher probability to support the corresponding claim than studies without identified conflict of interest (62 vs
23% p = 0.001). Similarly, studies funded by the industry had a trend
towards a higher probability to support the corresponding claim than
studies without information about their financial source (56 vs 34%,
p = 0.055).
Conclusions: More than half of all pharmaceutical claims assessed
were potentially biased or not supported by the quoted reference
study. Physicians need to be aware that they can not blindly trust
drug advertisement claims even when they seem to refer to scientific
studies.
Forum Med Suisse 2008;8:(Suppl. 40)
3S
S3
Adverse drug event rates in six community hospitals in
Massachusetts: frequency before implementing computerized
physician order entry
Hug B.L., Witkowski D.J., Sox C.M., Keohane C.A., Seger D.L.,
Yoon C., Matheny M.E., Melin J.A., Bates D.W.
(Basel, Melrose, Boston, Burlington)
Background: Medications represent a major cause of harm and are
costly in hospitalized patients, but more is known about these issues
in tertiary care hospitals than community hospitals.
Objective: To assess the incidence of adverse drug events (ADEs)
in six community hospitals prior to implementing computerized
physician order entry (CPOE).
Design: Multicenter, retrospective cohort study.
Setting: Six eastern Massachusetts community hospitals with
135 to 285 beds.
Patients: A random selection of adult patients hospitalized from
January, 2005 through August 2006. Main Outcome
Measures: ADEs and preventable ADEs.
Methods: Presence of an ADE using an adaptation of the trigger
instrument developed by the Institute for Health Care Improvement.
Two independent reviewers assessed the preventability.
Results: Patients with ADEs were older (mean age, 74.6 years,
p = 0.04), more often female (60.3%, p <0.001) and were more often
Caucasian (96.5%, p = 0.006) than patients without ADEs. Of 841
incidents detected (70.1/100 admissions), 65.8% were near misses
(41.6/100 admissions) and 21.4% were ADEs (15.0/100 admissions).
Of the ADEs, 75.0% were judged preventable. ADEs were rated as
serious in 49.4% and life threatening in 11.7%. Of preventable ADEs,
81.5% were judged preventable by implementation of computerized
physician order entry (CPOE).
Conclusions: The incidence of ADEs in these community hospitals
admissions was higher than in tertiary referral hospitals, and more
ADEs were preventable, mostly through CPOE. These data suggest
that CPOE may be beneficial in this setting.
S2
S4
Inventory and description of disease management programs
in Switzerland
Peytremann Bridevaux I., Burnand B.
(Lausanne, Lausanne and Montreal)
Background: Disease management, a system of coordinated health
care interventions for populations with chronic diseases in which
patient self-care is a key aspect, has been shown to be effective for
several conditions. Little is known on the supply of disease management programs in Switzerland.
Objectives: To systematically search, record and evaluate data on
existing disease management programs in Switzerland.
Methods: Programs met our operational definition of disease management if their interventions targeted a chronic disease, included a multidisciplinary team and lasted at least 6 months. To find existing programs, we searched Swiss official websites, Swiss web-pages using
Google, medical electronic database (Medline), and checked references
from selected documents. We also contacted personally known individuals, those identified as possibly working in the field, individuals working in major Swiss health insurance companies and people recommended by previously contacted persons (snow ball strategy). We
developed an extraction grid and collected information pertaining to the
following 8 domains: patient population, intervention recipient, intervention content, delivery personnel, method of communication, intensity
and complexity, environment and clinical outcomes (measures?).
Results: We identified 8 programs fulfilling our operational definition
of disease management. Programs targeted patients with diabetes,
hypertension, heart failure, obesity, alcohol dependence, psychiatric
disorders or breast cancer, and were mainly directed towards patients.
The interventions were multifaceted and included education in almost
all cases. Half of the programs included regularly scheduled follow-up,
by phone in 3 instances. Healthcare professionals involved were physicians, nurses, case managers, social workers, psychologists and dietitians. None fulfilled the 6 criteria established by the Disease Management Association of America.
Conclusions: Our study shows that disease management programs,
in a country with universal health insurance coverage and little incentive
to develop new healthcare strategies, are scarce, although we may
have missed existing programs. Nonetheless, those already implemented are very interesting and rather comprehensive. Appropriate
evaluation of these programs should be performed in order to build
upon them and try to design a generic disease management framework
suited to the Swiss healthcare system.
Impact d’un soutien informatique sur le traitement
de la douleur aiguë aux urgences
Palhais N., Achour S., Tamchès E., Trueb L., Decosterd I.,
Yersin B., Hugli O. (Lausanne)
L’oligoanalgésie reste un problème significatif dans les centres
d’urgence, malgré les recommandations de pratique clinique (RPC)
édictées par de nombreuses sociétés médicales. Or, si une application informatique aide de nombreux centres d’urgences dans leur
gestion quotidienne des patients (flux, recueille de données cliniques
dont l’intensité de la douleur, etc.), elle n’est que rarement employée
comme une aide à la bonne pratique médicale. But de l’étude: déterminer si le développement d’un module informatique spécifiquement
dédié à la prise en charge de la douleur améliore le traitement médical de la douleur aiguë aux urgences. Méthode: étude prospective
pré- et post-déploiement d’un module informatique activant, lors de
l’installation du patient en zones de soins, l’ouverture automatique
dans l’application informatique de fenêtres surgissantes (pop-up)
diffusant des messages rappelant aux soignants d’évaluer la douleur,
à la traiter selon les RPC, et à adapter l’antalgie après réévaluation
de la douleur; l’algorithme gérant ces fenêtres est basé sur les RPC
de notre service (1); critères d’évaluation de l’intervention: prescription par les médecins et administration d’antalgique en zones de
soins. Données recueillies par revue des dossiers médico-infirmiers.
Inclusion de tous patient >= 16 ans admis avec une douleur <8 jours
ou ayant développé une douleur durant leur séjour aux urgences.
Analyses par statistiques descriptives; comparaison pré et postintervention par test exact de Fisher pour les données catégorielles,
par test de t pour échantillons non-appariés pour les données continues; p bilatéral <0,05 indicateur de différences significatives. Résultats: 183 patients inclus dans chacune des phases. Âge moyen (43,8
et 45,3 ans; p = 0,56), proportion de femmes (49 et 45%; p = 0,46), et
intensité de la douleur à l’admission par EVA (6,4 et 6,2 cm; p = 0,63).
Modification amenée par l’intervention entre les phases pré et postintervention: amélioration de 60 et 71% des patients recevant une
antalgie (p = 0,048); augmentation de 0,98 à 1,38 prescription d’antalgique/patient (p = 0,003) ; augmentation de 8 à 21% de la proportion
des patients recevant de la morphine pour des douleurs modérées
à sévères (p <0,001). Conclusion: le soutien informatique permet
d’améliorer de façon significative la quantité et la qualité de l’antalgie
administrée par les médecins lors de douleur aiguë aux urgences.
1 E.Tamchès et al. Swiss Med Wkly. 2007;137:223–7.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
S5
Quality assessment in gastroenterology: prospective analysis
of early and delayed complications of sphincterotomy
at a single center
Sagmeister M., Schelling M., Binek J., Borovicka J., Boller D.,
Knellwolf C., Meyenberger C. (St. Gallen)
Most studies on endoscopic sphincterotomy (EST) assess only procedure related morbidity and mortality and there is lack for data on delayed
complications. Our aim was to assess early and delayed complications of
EST in a prospective registry allowing quality control and outcome
assessment in our institution.
Methods: All patients with EST were included within a prospective registry (inclusion rate: 100%) over a time period of 2 years (Sept.1, 2005 –
Aug. 31, 2007). The registry is part of a multiinstitutional registry and
allows outcome comparisons with different hospitals. Procedure related
complications were assessed immediately after the examination by the
endoscopist. Follow up data were collected two weeks after the procedure by a trained study nurse. Follow up of patients was assessed by the
help of a structured questionnaire.
Results: A total of 462 EST were analysed. 95% of EST were successful
(cannulation of the intended duct) within the first examination. In 15.8%
of all EST a precut sphincterotomy was necessary to cannulate the
intended duct. The total complication rate (CR) was 10.4%. We documented severe or moderate pancreatitis in 0.9% of EST, perforations in
1.3% of EST, mild pancreatitis in 5.6% of EST, hemorrhage in 2.2% of
EST and cholangitis in 0.4% of EST. We observed a procedure related
mortality of 0.43% (2 deaths: 1 patient died of post EST pancreatitis and
1 patient died due to cardiorespiratory insufficiency with multiorgan
failure after EST). There was a non-procedure related hospital mortality of
2.38% (11 deaths: mainly patients with end stage cancer disease). The
main risk factors for complications of EST were: former ERCP pancreatitis (CR: 66.7%), recent stone passage (CR: 29.2%), sphincter of Oddi
dysfunction (CR: 20%), combined sedation with propofol,
benzodiazepines and opiates (CR 18.1%), precut sphincterotomy (CR:
19.2%), number and intensity of pancreas duct contrast injections (CR:
up to 50% with contrast injections up to the pancreas tail).
Conclusion: The study confirmed a considerable early and delayed
procedure related complication rate of EST. We could identify specific
risk factors for EST related complications. We conclude that there is a
need for permanent quality control and outcome assessment for invasive
procedures like EST.
S6
Evolution of diagnostic errors in a primary referral hospital
over a ten-year period assessed by autopsy
Hoess C., Moll C., Thurnheer R., Widmer F., Krause M.
(Münsterlingen)
The advances in modern imaging techniques and diagnostic laboratory
tests allow to obtain detailed information about diseased organs and help
to recognize various conditions such as pulmonary embolism, heart
failure and myocardial damage. It is not clear, however, whether our
diagnostic performance has really improved along with the development
of these advances. To answer this question, we compared autopsy findings with pre-mortem main diagnoses over a ten year period and
assessed the frequency of diagnostic discrepancies over time.
Results: From January 1997 to December 2006 the autopsy rate was
50.1% resulting in 1035 autopsies. There were 60% males, the mean age
at death was 73.1 years. Oncologic and cardiovascular diseases were the
most common disorders diagnosed at postmortem exam, followed by
infectious and neurological diseases. The overall main diagnosis discrepancy rate was 9.1%. Myocardial infarction, pulmonary embolism, aortic
disease and endocarditis were most commonly missed. In cardiovascular
diseases errors occurred in 18.7%, followed by infectious diseases in
12.9%, oncology in 3.6% and neurology in 1.8%. The error rate of all
diseases categories dropped from 15% in 1997/98 to 6.1% in 2005/06
(Figure). This improvement was mainly due to less erroneous cardiovascular diagnoses which decreased from 33% to 13%. Among the study
intervals, patient characteristics, autopsy frequency and diseases categories did not differ signifi-cantly excluding a bias. During the 10 year
study period, various cardiovascular diagnostics were introduced at our
institution including D-dimer, Troponin T, brain natriuretic peptide, comprehensive doppler-echo studies, multislice-CT and MRI as well as algorithms for thromboembolic diseases and acute coronary syndrome.
Conclusion: In patients who die in the hospital, the diagnostic performance improved significantly over a ten year period. This was mainly due
to more accurate diagnoses in cardiovascular diseases. This suggests
that the introduction of new cardiovascular biomarkers, imaging techniques and diagnostic algorithms is associated with better diagnostic
performance.
Figure 1
Error rate
Forum Med Suisse 2008;8:(Suppl. 40)
4S
S7
Age-related differences in the use of guideline-recommended
medical and interventional therapies for acute coronary
syndromes: a cohort study
Schoenenberger A.W., Radovanovic D., Stauffer J.-C., Windecker S.,
Urban P., Eberli F.R., Stuck A.E., Gutzwiller F., Erne P.
(Bern, Zürich, Lausanne, Genf, Luzern)
Introduction: Recent guidelines for patients with acute coronary
syndromes (ACS) recommend early medical and interventional therapies for older patients. We therefore compared the use of guidelinerecommended medical and interventional therapies in older vs.
younger patients with ACS.
Methods: In this prospective cohort study, 11932 patients with ACS
were enrolled between March 1, 2001, and June 30, 2006 in 55 hospitals in Switzerland. ACS definition included ST-segment elevation
myocardial infarction (STEMI), non-ST-segment elevation myocardial
infarction (NSTEMI), and unstable angina (UA). We measured the use
of medical and interventional therapies determined after exclusion of
patients with contraindications and after adjustment for comorbidities. Multivariate logistic regression models were used to calculate
odds ratios (OR) per year increase in age.
Results: Elderly patients were less likely to receive acetylsalicylic acid
(OR, 0.976 [95% CI, 0.969–0.980]) or beta-blockers (OR, 0.985 [95%
CI, 0.981–0.989]). No age-dependent difference was found for
heparin use. Elderly patients with STEMI received less percutaneous
coronary interventions (PCI) or thrombolysis (OR, 0.955 [95% CI,
0.949–0.961]). Elderly patients with NSTEMI/UA less often underwent
PCI (OR, 0.943 [95% CI, 0.937–0.949]).
Conclusion: Elderly patients across the whole spectrum of ACS were
less likely to receive guideline-recommended therapies even after
adequate adjustment for comorbidities. Prognosis of elderly patients
with ACS may be improved by increasing adherence to guidelinerecommended medical and interventional therapies.
S8
“Do not reanimate” (DNR) and “cardio-pulmonary resuscitation”
(CPR) orders: descriptive analysis of 206 cases
Elger B.E., Becerra M., Cochet S., Junod Perron N., Hurst S.A.
(Genève)
Background: In Switzerland, studies on “Do Not Resuscitate” or
“Cardio-Pulmonary Resuscitation” orders (DNR/CPR) are rare. The
Clinical Ethics Council of the University Hospital of Geneva (UHG) has
issued guidelines on how patient autonomy should be respected in
DNR decisions. Consequently, a procedure was implemented in the
Internal Medicine Department requiring physicians to specify at
patients’ admission whether a patient is “DNR” or “CPR” and document the decision on a standardized form in the medical record. This
study evaluates how such decisions are made.
Methods: During one year (2004/2005) 206 consecutive cases were
obtained in six internal medicine wards: it included four groups
according to DNR/CPR status, and whether they were discussed with
the patient (dp), or not (ndp). Residents in charge of the patients were
interviewed about how the 206 orders were established.
Results: Over 90% of decisions were made within two days of
admission. Mean patient age ranged from 63 years for ndp CPR
orders to 77 years for dp DNR orders (p <0.001). Ten percent of
patients with ndp CPR orders and 41% of patients with ndp DNR
orders were incompetent. Two weeks after admission, 18% of
patients with ndp DNR orders, and 2–6% of the remaining patients
had died (p = 0.009). Ndp DNR orders were discussed with the chief
resident most often (82%), and ndp CPR orders least often (38%,
p <0.001). Orders were rarely (8%) documented in the nursing files.
Nurses participated in 7% of the 206 CPR/DNR decisions. Treating
physicians were involved in 9%. Family participated in 31% of all
DNR decisions, 20% of dp CPR and 6% of ndp CPR orders
(p = 0.004). For both dp CPR and dp DNR orders, a “real” discussion
took place with 87% of the patients. In the other cases patients were
only informed. In 95% of dp orders physicians felt it was “good”
to have included the patient in the decision. Physicians’ comments
about the usefulness of the DNR/CPR forms were overall positive.
Conclusions: The DNR/CPR forms help clarify decisions about
resuscitation. However, nurses too often remain uninformed of
DNR/CPR decisions. Moreover, in many cases residents do not
include competent patients in the DNR/CPR decision. Although the
UHG ethics council admits some cases for ndp orders regarding
competent patients (CPR for patients with good prognosis and DNR
orders shortly before death), decision making without including competent patients should remain the exception. Specific training may be
useful.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
S9
Subclinical thyroid dysfunction is not associated with the risk
of coronary heart disease and mortality
Ochs N., Auer R., Bauer D.C., Gussekloo J., Cornuz J., Rodondi N.
(Lausanne, San Francisco, Leiden)
Background: Subclinical thyroid dysfunction (defined as abnormal
TSH and normal thyroid hormone levels) is common, particularly in
older adults and in women, but controversy persists as to whether
screening and treatment of subclinical thyroid dysfunction is warranted. As previous studies have been conflicting, we performed a
meta-analysis of prospective studies to determine whether subclinical
thyroid dysfunction is associated with coronary heart disease (CHD)
and mortality (total or cardiovascular).
Methods: We searched MEDLINE from 1950 to June 2007, and the
bibliographies of key articles in the field and those included in this
review. Two authors independently reviewed each potential study for
eligibility and extracted the data. We assessed methodological study
quality and performed sensitivity analyses.
Results: 11 prospective studies met our eligibility criteria, 10 examining subclinical hypothyroidism, with 2136 CHD events and 2822
deaths, and 6 examining subclinical hyperthyroidism, with 1399 CHD
events and 2021 deaths. Overall, subclinical hypothyroidism was not
associated with the risk of CHD (summary relative risk [RR] = 1.20,
95% confidence interval [CI], 0.96–1.49) with weak evidence for
heterogeneity (p for heterogeneity = 0.14, I2 = 33.4%). However, risk
estimates were lower when pooling higher quality studies (RR from
1.02 to 1.08). Subclinical hypothyroidism was associated with CHD
risk among subjects <65 years (RR for studies with a mean age <65
years = 1.51, 95%CI, 1.09–2.09; vs. 1.05, 95%CI, 0.90–1.22 for studies with a mean age 065 years; p for meta-regression by age = 0.02).
Results did not meaningfully differ in other sensitivity analyses. Subclinical hypothyroidism was not associated with cardiovascular mortality (RR = 1.18, 95%CI, 0.98–1.42) or total mortality (RR = 1.12,
95%CI, 0.99–1.26). Subclinical hyperthyroidism was not significantly
associated with CHD (RR=1.36, 95%CI, 0.92-2.01), cardiovascular
mortality (RR = 1.36, 95%CI, 0.86–2.18) or overall mortality (RR =
1.19, 95%CI, 0.95–1.48; for all: p for heterogeneity >0.20, I2 <30%),
but confidence intervals were wider than for subclinical hypothyroidism.
Conclusion: This systematic review of prospective cohort studies
with a large number of outcomes included indicates that subclinical
hypothyroidism and hyperthyroidism are not associated with CHD
risk and mortality, but subclinical hypothyroidism may be associated
with increased CHD risk among those <65.
S10
Vascular dysfunction in apparently healthy adolescents
conceived by assisted reproductive technologies
Sartori C., Rimoldi S., Bloch J., Duplain H., Stuber T., Kriemler S.,
Germond M., Nicod P., Allemann Y., Scherrer U. (Lausanne, Bern,
Basel)
Environmental influences acting early in life predispose to cardiovascular disease in adulthood. In developed countries, assisted reproductive technologies (ART) account for 1–4% of births. There is growing evidence that the preimplantation mammalian embryo is sensitive
to environmental conditions and ART has been found to modulate the
epigenome. The safety of ART for long term health is, therefore, of
utmost importance, but there is little information. This may be related,
at least in part, to the young age of the progeny, since clinically manifest chronic disease may not yet have had time to develop. Hypoxia
induces exaggerated pulmonary hypertension and systemic vascular
dysfunction in persons displaying endothelial dysfunction. We sought
to capitalize on this observation and hypothesized that high-altitude
exposure may facilitate the detection of vascular dysfunction in children born after ART. We measured endothelium-dependent vasodilation (high-resolution ultrasound) and vascular stiffness (pulse wave
velocity) of the brachial artery, and pulmonary-artery pressure (echoDoppler) in 20 apparently healthy singletons born from ART (mean
age 13 ± 2 y) and 28 age-, sex- and birth weight-matched controls
exposed to high-altitude (Jungfraujoch, 3450 m). The major new
finding was that healthy adolescents born after ART displayed
marked vascular dysfunction both in the systemic and the pulmonary
circulation. Brachial artery flow-mediated vasodilation was roughly 30
percent smaller (6.3 ± 1.8 vs. 8.9 ± 1.8%, p <0.001) and pulse wave
velocity significantly faster (8.5 ± 2.2 vs. 7.2 ± 1.2 m/s, p = 0.01) in
children born after ART than in controls. Similarly, the systolic right
ventricular to right atrial pressure gradient was roughly 33 percent
Forum Med Suisse 2008;8:(Suppl. 40)
5S
higher in offspring of ART than in controls (36 ± 14 vs. 27 ± 7 mm Hg,
p = 0.01). This vascular dysfunction was not related to more severe
hypoxemia since arterial oxygen saturation was comparable in the
2 groups. These findings demonstrate for the very first time that ART
has long lasting effects on vascular function in humans that may
predispose to premature cardiovascular disease later in life. We speculate that epigenetic mechanisms may underpin the vascular dysfunction in offspring of ART. If so, the observed vascular dysfunction
may not be limited to the present generation of persons born after
ART, but could also be transmitted to their progeny. The scientific,
societal and ethical challanges at stake here appear tremendous.
S11
Improved prediction of coronary heart disease with markers
of atherosclerosis and of inflammation in older adults?
Rodondi N., Marques-Vidal P., Butler J., Cornuz J., Sutton-Tyrrell K.,
Satterfield S., Ferrucci L., Harris T.B., Vittinghoff E., Bauer D.C.,
Newman A. (Lausanne, Atlanta, Pittsburgh, Memphis, Bethesda,
San Francisco)
Background: Several markers of atherosclerosis and of inflammation
have been shown to predict coronary heart disease (CHD) individually. However, the utility of markers of atherosclerosis and of inflammation on prediction of CHD over traditional risk factors has not been
well established, especially in the elderly.
Methods: We studied 2202 men and women, aged 70–79, without
baseline cardiovascular disease over 6-year follow-up to assess the
risk of incident CHD associated with baseline noninvasive measures
of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity
[aPWV]) and inflammatory markers (interleukin-6 [IL-6], C-reactive
protein [CRP], tumor necrosis factor-a [TNF-a]). CHD events were
studied as either nonfatal myocardial infarction or coronary death
(“hard” events), and “hard” events plus hospitalization for angina, or
the need for coronary-revascularization procedures (total CHD
events).
Results: During the 6-year follow-up, 283 participants had CHD
events (including 136 “hard” events). IL-6, TNF-a and AAI independently predicted CHD events above Framingham Risk Score (FRS) with
hazard ratios [HR] for the highest as compared with the lowest quartile for IL-6 of 1.95 (95%CI: 1.38–2.75, p for trend <0.001), TNF-a of
1.45 (95%CI: 1.04–2.02, p for trend 0.03), of 1.66 (95%CI: 1.19–2.31)
for AAI 0.9, as compared to AAI 1.01-1.30. CRP and aPWV were not
independently associated with CHD events. Results were similar for
“hard” CHD events. Addition of IL-6 and AAI to traditional cardiovascular risk factors yielded the greatest improvement in the prediction
of CHD; C-index for “hard”/total CHD events increased from
0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition,
0.65/0.63 for AAI, and 0.66/0.64 for IL-6 combined with AAI. Being in
the highest quartile of IL-6 combined with an AAI 0.90 or >1.40
yielded an HR of 2.51 (1.50–4.19) and 4.55 (1.65–12.50) above FRS,
respectively. With use of CHD risk categories, risk prediction at 5
years was more accurate in models that included IL-6, AAI or both,
with 8.0, 8.3 and 12.1% correctly reclassified, respectively.
Conclusions: Among older adults, markers of atherosclerosis and of
inflammation, particularly IL-6 and AAI, are independently associated
with CHD. However, these markers only modestly improve cardiovascular risk prediction beyond traditional risk factors.
S12
Oxidative stress induced fetal programming of hypoxic
pulmonary hypertension
Bloch J., Jayet P-Y., Duplain H., Schwab M., Dessen P., Monney A.,
Mathieu C., Tolsa J-F., Sartori C., Scherrer U. (Lausanne)
The long term prognosis of pulmonary hypertension remains poor,
and its pathogenesis remains incompletely understood. In line with
Barker’s concept of a fetal programming of adult disease, preeclampsia predisposes the offspring to pulmonary endothelial dysfunction
and exaggerated hypoxic pulmonary hypertension later in life, but the
underlying mechanisms remain unknown. In women suffering from
preeclampsia, reactive oxygen species (ROS) are elevated and contribute to endothelial dysfunction and arterial hypertension. We
hypothesized that ROS may pass the placental barrier and induce
endothelial dysfunction in the developing pulmonary vasculature of
the fetus that may predispose to a pathologic response later in life. To
test this hypothesis, C57/Bl6 mice were put on a restrictive diet (75%
of normal food intake) during the last 2 weeks of pregnancy, a condition known to induce exaggerated oxidative stress during pregnancy.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
Adult male offspring of restricted diet pregnancy were kept in hypoxic
cages (FiO2, 12.5%) for 2 weeks. Mice were then sacrificed, and the
main pulmonary arteries were dissected. The pulmonary artery rings
were suspended in organ chambers for the measurement of endothelium-dependent pulmonary vasodilation (cumulative dose-response
to acetylcholine, 10-8–10-4 mol/L). We found that pulmonary vasodilatation to acetylcholine was markedly impaired in offspring of restrictive diet pregnancies when compared to control mice (ANOVA p
<0.0001). Pulmonary-artery endothelial dysfunction was associated
with increased oxidative stress, as evidenced by a roughly 50%
increase of the TBARS plasma concentration (50.9 ± 3.1 vs. 33.4 ±
5.1 nmol/ml, P <0.01, restrictive diet vs. controls). To test for the
pathogenic role of oxidative stress in this setting, we examined the
effects of the addition of the antioxidant Tempol (10-4 M) on pulmonary artery responsivness in vitro. Tempol completely restored the
pulmonary-artery vasodilatation in vitro (ANOVA p <0.0001). Most
importantly, we also found that administration of Tempol (10-2 M in
the drinking water) during restrictive diet pregnancy completely prevented pulmonary endothelial dysfunction in the offspring. These data
provide the first evidence for a fetal programming of exaggerated
hypoxic pulmonary hypertension in mice. The pulmonary endothelial
dysfunction in the offspring is induced by increased oxidative stress
because administration of an antioxidant prevented this pathologic
response.
Forum Med Suisse 2008;8:(Suppl. 40)
6S
(55%, n = 16) and/or inhospital mortality (14%, n = 4) had significantly
higher median PCT values on admission (4.27 (IQR 2.46–9.48) vs 0.97
(IQR 0.29–2.44, p = 0.01), while CRP values (282 (IQR 218-343,
p = 0.28) vs 201 (IQR 147–279, p = 0.28) and leukocyte counts (12
(IQR 10–21) vs 12 (IQR 9–15), p = 0.58) were similar. In receiver operating curves, PCT concentrations on admission had a high prognostic
accuracy (AUC 0.78 (95%CI 0.61–96) as compared to CRP (0.61
(95%CI 0.39–0.84, p = 0.19), leucocyte count (0.57 (95%CI 0.35-0.78,
p = 0.12), the PSI (0.72 (95%CI 0.52-0.91, p = 0.23) and the CURB65
score (0.58 (95%CI 0.36–0.80, p = 0.18). Kaplan Meier curves
(Figure 2) demonstrated that patients with PCT values above the
optimal cut off of 1.5ng/ml had a significantly higher risk of adverse
outcome above (p = 0.003).
Conclusion: In patients with community-acquired pneumonia due to
Legionella pneumophila, PCT levels on admission values could be an
interesting predictor for adverse medical outcomes.
Figure 2
S13
Are the guidelines appropriate to the cardiovascular risk
stratification among women before 66-year in Switzerland?
Berthoud M., Depairon M., Stauffer I., Darioli R. (Lausanne)
The primary prevention of cardiovascular diseases (CVD) is based on
the individual risk assessment by using Framingham and similar
algorithms derived mainly from European or US male populations.
The purpose of this prospective study was to compare the appropriateness of three different common guidelines for cardiovascular risk
stratification when using subclinical-atherosclerosis as a surrogate of
CV risk. The study population included 560 women (W), aged from 20
to 65 years, non diabetic and without established CVD, who were
consecutively were referred to our Lipid Clinic for therapeutic advices.
CV- risk factors were systematically screened for each subject,
including medical history, physical examination and clinical chemistry.
Their estimated 10-year CV-risk assessment was obtained by using
the guidelines of Swiss-AGLA (AGLA), NCEP-ATP-3 (ATP-3) and 3th
JES-ESC (ESC) guidelines (GL). B-mode ultrasounds on carotid and
femoral arteries was performed to detect atherosclerotic plaques
(focal thickening of intima-media >1.2 mm). W with plaques on >2
carotid and/or femoral sites were considered as high CV risk (HR).
The proportions of W stratified as high 10-year CV-risk by the GL
were the following: 5% (AGLA), 2% (ESC) and 24% (ESC). The comparative values (area under the ROC-curve, 95% IC) of GL to detect
the 160 HR-W with subclinical atherosclerosis (29%) was significantly
higher for AGLA-GL (0.7869, 0.75–0.82) than for ATP-3-GL (0.75,
0.71–0.79) or than for ESC-GL (0.73, 0.68–0.77).
In conclusion, the results suggest that current AGLA-GL
recommended by the Swiss Society of Cardiology are the most
appropriate to identify HR-W requiring more intensive therapy for the
primary prevention of CVD.
S14
Prognostic value of procalcitonin in Legionella pneumonia
Haeuptle J., Zaborwsky R., Fiumefreddo R., Trampuz A., Steffen I.,
Frei R., Christ-Crain M., Müller B., Schuetz P. (Basel)
Background: The diagnostic reliability and prognostic implications
of procalcitonin (PCT) on admission in patients with communityacquired pneumonia (CAP) due to Legionella pneumophila are
unknown.
Patients and methods: We retrospectively analyzed PCT values in
29 patients with microbiologically proven Legionella-CAP admitted to
the University Hospital in Basel, Switzerland, between 2002 and 2007
and compared them to other markers of infection, namely C-reactive
protein (CRP) and leukocyte count, and two prognostic severity
assessment scores (PSI and CURB65).
Results: Laboratory analysis demonstrated that PCT values on
admission were >0.1 ng/ml in over 93%, >0.25 in over 86% and >0.5
in over 82% of patients with Legionella-CAP. Patients with adverse
medical outcomes (59%, n = 17) including need for ICU admission
S15
The Pulmonary Embolism Severity Index (PESI): prospective
validation of a clinical prognostic model for pulmonary embolism
Donzé J., Cornuz J., Righini M., Perrier A., La Gal G., Roy P.M.,
Sanchez O., Verschuren F., Meyer G., Aujesky D. (Lausanne, Genève,
Brest, Angers, Paris, Bruxelles)
Background: Using data from U.S. patients, we previously derived
the Pulmonary Embolism Severity Index (PESI), a clinical prognostic
model that accurately identifies patients with pulmonary embolism
(PE) who are at low-risk of mortality and who are potential candidates
for outpatient care. Our objective was to externally validate the PESI
in a European patient sample with PE.
Methods: We prospectively validated the PESI in 357 patients objectively diagnosed with PE at 6 European emergency departments. All
patients received an initial treatment with heparin, followed by a
vitamin K antagonist for at least 3 months. We used baseline data
for the model’s 11 prognostic variables to stratify patients into 5 risk
classes (I–V) of increasing risk of mortality. The study outcome was
overall mortality at 3 months after presentation. We calculated the
proportion of patients classified as low-risk (classes I and II) based on
the PESI. To assess the accuracy of the PESI to predict overall mortality, we estimated the sensitivity, specificity, predictive values and
likelihood ratios for low (risk classes I and II) versus higher-risk
patients (risk classes III–V). We assessed the discriminatory power of
the PESI to predict overall mortality using the area under the receiver
operating characteristic curve.
Results: Overall mortality was 5.9% (21/357). Fifty-two per cent of
patients (186/357) were classified as low-risk (PESI classes I and II).
Low-risk patients had a mortality of only 1.1% (2/186). When
dichotomized as low (classes I and II) versus higher-risk (classes
III–V), the PESI had a high sensitivity (91%, 95% confidence interval
[CI]: 71–97%) and a very high negative predictive value (99%, 95%
CI: 96–100%) and negative likelihood ratio (0.20, 95% CI: 0–0.70) for
predicting overall mortality. Because this cutoff point was specifically
chosen to identify low-risk patients (i.e. to rule out short-term mortality), the specificity (55%, 95% CI: 49–60%) and the positive predictive
value (11%, 95% CI: 7–17%) were low. The area under the receiver
operating characteristic curve for overall mortality was 0.78 (95%
CI: 0.70–0.86).
Conclusions: The PESI reliably identifies low-risk patients with PE
who are potential candidates for outpatient treatment or a brief hospital stay. The effectiveness and safety of an outpatient treatment strategy of low-risk patients based on the PESI should be evaluated in a
randomized trial.
C O M M U N I C AT I O N S L I B R E S S P S G
FREIE MITTEILUNGEN SFGG
S16
L’hypoglycémie du sujet âgé diabétique: une maladie
silencieuse?
Dr M. Coutaz, Dr J. Morisod (St-Maurice)
Introduction: Le vieillissement entraîne une modification des réponses de contre-régulation à l’hypoglycémie, amenant une symptomatologie peu spécifique (faiblesse, vertiges, confusion) attribuée à tort
à d’autres co-morbidités de type neurologique ou psychiatrique,
sous-estimant probablement la fréquence des épisodes d’hypoglycémie.
Méthode: Afin de mieux évaluer ce risque nous avons inclus prospectivement 100 patients volontaires diabétiques, au bénéfice d’un
traitement d’antidiabétiques oraux et/ou d’Insuline, hospitalisés dans
un service de gériatrie aiguë.
5 mesures de glycémie capillaire (07 h – 11 h – 17 h – 22 h – 03 h) ont
été effectuées dans les premières 24 h du séjour hospitalier, sans
aucune modification du traitement habituel. L’hypoglycémie était
définie par une valeur de glycémie inférieure à 4 mmol/l.
Résultats: L’incidence de survenue d’une hypoglycémie s’est révélée
très élevée, de l’ordre de 24% pendant les premières 24 h d’hospitalisation. 24 patients ont présentés 33 épisodes d’hypoglycémie (glycémie la plus basse: 1,9 mmol/l), dont le tiers survient à 3 h du matin.
Les facteurs de risques habituels d’hypoglycémie décrits chez la
personne âgée (insulinothérapie, âge avancé, insuffisance rénale,
polymédication, fragilité) n’ont aucune valeur prédictive significative
selon les résultats de notre étude (cf. tableau). Par ailleurs, ni l’adjonction d’un médicament au pouvoir hypoglycémiant (acide acétylsalicylique, acenocoumarol, cotrimoxazole, tricyclique), ni le suivi
d’un régime antidiabétique n’ont constitué un indice prédictif valable
de survenue d’une hypoglycémie.
Conclusion: Selon les résultats de notre étude, les facteurs de risque
habituels décrits sont insuffisants pour aider au dépistage de l’hypoglycémie du diabétique âgé traité, qui court un risque sérieux d’hypoglycémie lors de chaque hospitalisation (1/4 des patients de notre
collectif). L’absence de symptômes clairement individualisables et le
manque d’outils de dépistage nous incitent à recommander des
profils glycémiques serrés, incluant la glycémie nocturne, lors de
toute hospitalisation.
Tableau
S17
Marital status, living place and income are major determinants
of first hip fracture age occurrence
Chevalley T., Guilley E., Herrmann F., Hoffmeyer P., Rapin C.-H.,
Rizzoli R. (Genève)
We previously reported that the risk of hip fracture was higher in
communities with low income, and/or in urban as compared to rural
areas. However, the influence of socioeconomic risk factors on the
age of first hip fracture has not been specifically analyzed in homedwelling elderly. Therefore, we investigated the impact of marital
status, living place and income on the age at first hip fracture in 2320
home-dwelling women and men aged 50 and older discharged from
1991 to 2000 with a diagnosis of a first hip fracture at the Geneva
University Hospital. Income of hip fractured patients corresponded to
the median household incomes of the patient’s Zip code area at the
time of the fracture. These median household incomes were based
on the 1990 Census and obtained from the Geneva State statistical
office. Age of patients was analyzed by analysis of variance according to gender, marital status (unmarried – single, widowed, divorced –
or married), rural/urban residence and 3 income categories of similar
numbers of patients with no difference in women/men ratios (<53’170
CHF, 53’170–58’371, 058’371). First hip fracture occurs at an earlier
age for unmarried men compared to married men (–3.13 year; 95% CI
= -5.07– -1.19; p = 0.002) while it occurs at a latter age for unmarried
women compared to married women (4.61 year; 95% CI = 3.55–5.67;
Forum Med Suisse 2008;8:(Suppl. 40)
7S
p = <0.001). Patients from urban areas were younger when sustaining
their fractures (-1.63 year; 95% CI = -2.89– -0.38; p = 0.011). As
compared to the patients living in areas with the highest income
category, hip fractures occurred at an earlier age (–1.36 year; 95%
CI = -2.41 – -0.30; p = 0.012) among home-dwelling residents of the
lowest income category. Women who sustained a fracture at the
earliest age (76.5 years) are married and living in an urban area with
the lowest income category while those sustaining a fracture at the
latest age (83.8) were unmarried and living in a rural area with the
highest income category (7.3 year difference; 95% CI = 4.8–9.8;
p <0.001). Men with the worse profile (unmarried and living in urban
communities with the lowest income) had a fracture at 73.2 years
while those with the best profile (married and living in rural communities with the highest income) were 78.8 years old (5.6 year; 95% CI =
1.4–9.8; p = 0.008). In conclusion, these results indicate that in homedwelling elderly in Geneva, marital status, living place and income are
major determinants of the age at first hip fracture, in a gender-specific
way.
S18
Outcomes in elderly patients with proximal femoral or humeral
fractures treated in an orthogeriatric rehabilitation unit
Carmona G., Rizzoli R., Ammann P. (Genève)
The benefits of orthogeriatric intervention on recovery following a
fracture of the proximal femur in the elderly are well documented.
Whilst fractures of the proximal humerus are associated with a
marked decrease in functional independence, there is a noticeable
lack of literature regarding the influence of orthogeriatic intervention
in elderly patients who sustain a proximal humeral fracture. We performed a retrospective observational study in patients admitted to an
orthogeriatric unit between 2002 and 2006, with a diagnosis of extraor intracapsular hip fracture (HIP#, n = 291; mean age 83 ± 7 yrs) or
proximal humeral fracture (HUM#, n = 73; mean age 81 ± 7 yrs). The
rehabilitation program was administered by an interdisciplinary team,
integrating walking/balance exercises, muscle strengthening and
daily life-training activities. Functional capacity during rehabilitation
was evaluated by the functional independence measure (FIM) at
admission, after two weeks, and just prior to discharge (median 33
days). To further evaluate the functional outcomes, we separated the
functional motor items (MOTOR FIM) into upper and lower limb items
(UPPER and LOWER FIM). Values are means (SD) and differences
tested using ANOVA and Student’s t-test. At admission, age and all
motor functional independence scores were significantly higher in
patients with HIP# (83.3 ± 6.9 vs. 81.5 ± 6.9 yrs; p = 0.04, MOTOR
38.2 ± 11 vs. 33.6±11; p = 0.002, UPPER 18.9 ± 4 vs. 12.8 ± 4; p
<0.0001 and LOWER FIM 16.6 ± 6 vs. 12.9 ± 4; p <0.0001). At discharge, similar scores were observed for FIM and overall MOTOR FIM
in both groups, indicating a positive effect of the rehabilitation program. The effect on both fracture types was observed for UPPER and
LOWER FIM, highlighting a global effect of orthogeriatric intervention.
The kinetics of functional gain in MOTOR FIM differed between the
groups; in the HIP# the functional gain was significantly higher during
the two first weeks, while those in HUM# group improved constantly
throughout the observation period. Similar trends were observed for
the other parameters tested. This study indicates that early global
orthogeriatric rehabilitation programs improve the functional performance of elderly patients who sustain hip or humeral fractures. The
kinetics of these positive effects differs in the second half of the
recovery period depending on the anatomical location of the fracture.
S19
Effets de la menace d’une pandémie de grippe aviaire sur les
taux de vaccination de la grippe et du pneumonocoque chez les
personnes âgées
Dreher R., Bosshard W., Martin E., Büla Ch. (Gilly, Cully, Epalinges)
But: La menace de pandémie de grippe aviaire a attiré toute l’attention des médias et des recommandations de vaccination contre la
grippe spécifiques ont été divulguées. Le but de cette étude est
d’évaluer l’effet de ces recommandations sur les taux de vaccination
contre la grippe et pneumocoque chez les personnes âgées.
Méthode: les participants (N = 659, âge moyen 81,2 ± 7,4 ans,
69,2% de femmes) sont des personnes âgées hospitalisés dans un
service de réadaptation pendant les mois d’hiver entre 1999 et 2007.
C O M M U N I C AT I O N S L I B R E S S P S G
FREIE MITTEILUNGEN SFGG
Le status fonctionnel, cognitif, l’utilisation de soins à domicile, les
données démographiques et le status vaccinal ont été récoltés à
l’admission. Les taux de vaccination avant et après les recommandations de menace de grippe aviaire (2006) ont été comparés.
Résultats: Avant l’émission des recommandations contre la grippe
aviaire, le taux de vaccination contre la grippe est resté stable entre
1999 et 2005 avec un taux moyen de 64,9% (63,7–66,1%). Après la
publication de recommandations spécifiques contre la grippe aviaire
le taux de vaccination contre la grippe a augmenté à 73,2% (p = ,07).
Une analyse plus approfondie montre que le taux de vaccination a
significativement augmenté chez les personnes ne recevant pas
d’aide à domicile passant de 57,8% à 73,2% (p = ,02) après publication des recommandations. Chez les personnes recevant de l’aide à
domicile il n’y a pas eu d’augmentation du taux de vaccination (71,4
vs 73,1%, p non significatif). Une analyse multivariée restreinte aux
personnes ne recevant pas d’aide à domicile, la probabilité d’être
vacciné contre la grippe doublait après 2006 (adj OR 1,99; 95% IC
1,08–3,7; p = ,03), ceci indépendamment de l’âge , du sexe et du
status fonctionnel et cognitif. Il n’y pas eu d’effet «pandémique»
semblable pour le pneumocoque, le taux de vaccination demeurant
stable sur toute la période étudiée (6%).
Conclusion: La présence d’une menace de grippe aviaire a clairement augmenté le taux de vaccination contre la grippe chez les personnes âgées. Cet effet a été particulièrement marqué chez les personnes ne bénéficiant d’aucune aide à domicile ce qui suggère une
prise de conscience accrue chez les personnes ayant peu de contact
avec des professionnels de la santé. Le faible taux de vaccination
contre le pneumocoque reste préoccupant.
S20
Does falls efficacy predict gait performance in high-functioning
older people?
Rochat S., Martin E., Aminian K., Ganea R., Hoskovec C., Ionescu A.,
Seematter-Bagnoud L., Najafi B., Piot-Ziegler C., Santos-Eggimann
B., Büla C.J. (Lausanne)
Introduction: Falls efficacy, defined as confidence in performing
activities without falling, is a measure of fear of falling associated with
gait impairment, falls and functional decline in frail older people. This
relationship has not been well studied in high-functioning older people.
Objective: To evaluate the relationship between falls efficacy and gait
performance in a cohort of high-functioning older people.
Methods: Subjects (N = 864) were a subsample of communitydwelling older people aged 65 to 70 years, enrolled in the “Lc65+”
cohort, who completed gait assessment at baseline. Data were collected on demographics, functional, cognitive, affective, and health
status. Falls efficacy was assessed using the Falls Efficacy ScaleInternational (FES-I) that measures confidence in performing 16 activities of daily life (ADL) without falling (score from 16 to 64, higher
score indicates lower confidence). Gait parameters were measured
over a 20 m walk at preferred gait speed using Physilog, an ambulatory gait monitoring system.
Results: Participants (mean age 68.0 ± 1.4 years, 55.0% women) had
excellent physical (92.2% independent in basic ADL, mean gait
speed 1.13 ± 0.16 m/sec) and cognitive (98.0% with MMSE 024)
performance. Nevertheless, 22.1% reported depressive symptoms
and 16.1% one or more fall in the previous year. Mean FES-I score
was 18.8 ± 4.1. Falls efficacy was associated with gait speed (Spearman rho –0.23, P <.001) and gait variability (Spearman rho 0.10,
P = .006), measured by the coefficient of variation of stride velocity.
These associations remained in multivariate analysis for both gait
speed (adj [beta] coeff: –0.008, 95%CI –0.005 to –0.010, P <.001) and
gait variability (adj [beta] coeff 0.024, 95%CI 0.003 to 0.045, P = .023)
independent of gender, falls, functional, affective, cognitive, and frailty
(Fried’s criteria) status. On average, compared to subjects with poor
confidence in performing one ADL without falling, those with full
confidence had a 0.02 m/sec (2%) faster gait speed and a 2%
decrease in gait variability.
Conclusion: Even in high-functioning older people, poor falls efficacy
is associated with reduced gait speed and stability, independent of
health, functional, and frailty status. The direction of this relationship
needs to be investigated prospectively to determine causality and
design interventions to improve gait performance, reduce fall risk,
and prevent functional decline.
Forum Med Suisse 2008;8:(Suppl. 40)
8S
S21
Caractéristiques associées à la vaccination contre la grippe
chez les personnes âgées
Bosshard W., Dreher R., Martin E., Büla C.J. (Lausanne)
Objectifs: Décrire les caractéristiques associées à la vaccination
contre la grippe dans la population âgée.
Méthodes: Les participants (N = 515) étaient les patients admis en
réadaptation durant les hivers 2002–2003 à 2005–2006. Des données
socio-démographiques, médicales, fonctionnelles, affectives, cognitives et concernant l’utilisation de soins formels à domicile ont été
récoltées. Le statut vaccinal a été déterminé par interview avec le
patient.
Résultats: En moyenne, 64.9% des patients (âge moyen 81,3 ± 7,4
ans, 70,1% femmes, 53,0% recevant des soins formels à domicile)
rapportaient être vaccinés contre la grippe. Comparés aux autres, les
patients vaccinés étaient plus âgés (81,4 ± 7,2 vs 79,9 ± 7,8 ans,
P = .007), moins fonctionnels dans les activités de la vie quotidienne
de base (5,2 ± 1,1 vs 5,4 ± 0,9, P = ,023), et instrumentales (4,6 ± 2,5
vs 5,3 ± 2,4, P = ,004), et bénéficiaient plus fréquemment de soins
formels à domicile (71,4 vs 57,8%, P = ,002). Les patients vaccinés
rapportaient plus souvent des symptômes dépressifs (73,0 vs 63,8%,
P = ,098), et présentaient moins fréquemment des troubles cognitifs
(MMSE <24: 39,8 vs 32,9%, P = ,161), mais ces différences n’étaient
pas statistiquement significatives. En analyse multivariée, la vaccination contre la grippe restait associée avec un âge plus avancé (adjOR
1,6, 95%CI 1,1–2,4, P = ,021 pour un âge >80 ans), la présence
d’une aide formelle des soins à domicile (adjOR 1,7, 95%CI 1,1–2,5,
P = .012), et l’absence de troubles cognitifs (adjOR 1,6, 95%CI
1,0–2,4, P = ,053). Une analyse secondaire révèle que les hommes
bénéficiant de soins formels à domicile avaient un taux de vaccination 3 fois supérieur à celui des autres patients (80,7 vs 62,7%, adjOR
3,1, 95%CI 1,2–8,0, P = ,019). Similairement, les patients souffrant de
troubles cognitifs étaient un peu plus fréquemment vaccinés s’ils
bénéficiaient de soins formels à domicile (69,0 vs 65,0%, adjOR 1,6,
95%CI 0,7–3,8, P = ,329), mais ce résultat n’était pas statistiquement
significatif.
Conclusions: La vaccination contre la grippe est plus fréquente chez
les patients âgés de plus de 80 ans, ceux sans troubles cognitifs, et
ceux bénéficiant de soins formels à domicile, en particulier s’ils sont
de sexe masculin. Des stratégies spécifiques ciblant les patients âgés
de 65 à 79 ans ne bénéficiant pas de soins formels à domicile
devraient être développées pour améliorer les taux de vaccination de
ce groupe.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
Forum Med Suisse 2008;8:(Suppl. 40)
9S
S22
S24
The association between cigarettes smoking, cannabis use and
alcohol consumption in a population of young men
Willi C.*, Cornuz J., Gaume J., Gmel G., Daeppen J.-B. (Lausanne)
The Association between Cigarettes Smoking, Cannabis Use and
Alcohol Consumption in a Population of Young Men.
Background: Some studies suggest that cigarette smoking may have
an influence on other risky behaviors but little is known about their
chronology of occurrence. The aim of this study was to assess, by
young men, what were the other risky behaviors associated with
cigarette smoking and the joint prevalence and chronology of occurrence of those risky behaviors.
Method: Cross-sectional analyses of a population-based census of
3526 young men attending the recruitment for the Swiss army, aged
between 17 and 25 years old, who filled a self reported questionnaire
about their habits. Actual smoking was defined as either regular
smoking (01 cigarette/day, on every day) or occasional smoking,
binge drinking as six or more drinks at least twice a month, at risk
drinking as 21 drinks or more per week, and recent cannabis use as
cannabis consumption at least once during the last month.
Results: In this population of young men, the prevalence of actual
smoking was 51,2%. More than half of the participants (53,8%) had a
risky alcohol consumption considered as either binge or at risk drinking, two third (60.1%) ever used cannabis and 25,2% had a recent
use of cannabis. In a multivariate logistic regression, odds ratios for
smoking were increased for cannabis users (OR 3,10, 95% CI:
2.48–3.88), binge drinkers (OR: 1.77, 95% CI: 1.44–2.17), at risk
alcohol drinkers (OR 2.26, 95% CI: 1.52–3.36) and ever users of illicit
drugs (OR: 1.56, 95% CI: 1.20–2.03). The majority of young men
(57.3%) initiated smoking before cannabis and mean age at onset
was 13.4 years old, whereas only 11.1% began to use cannabis
before smoking cigarettes and mean age at onset was slightly older
(14.4 years old). About a third of participants (30.5%) did have a
cluster of risky behaviours (smoking, at risk drinking, cannabis use).
More than half of the smokers (59.6%) did cumulate cannabis use
and at risk alcohol drinking whereas only 18.5% of non-smokers did.
Conclusions: The majority of young smokers initiated their risky
behaviors by first smoking and then by other psychoactive drugs.
Smokers had an increased risk to present other risky behaviors such
as cannabis use, at risk alcohol consumption and illicit drug use
compared to non-smokers. Prevention by young male adults should
focus on smoking and also integrate interventions on other risky
behaviors.
Screening undocumented immigrants in Switzerland for
tuberculosis and latent tuberculosis infection using the
interferon-g assay
Bodenmann P., Vaucher P., Tribolet F., Favrat B., Zellweger J.P.
(Lausanne)
Background: Undocumented immigrants are a potential source of
tuberculosis (TB) and latent tuberculosis infection (LTBI), but are
difficult to screen and treat. In Western Switzerland, there are an
estimated 20,000 immigrants/1 million inhabitants, and 90% of them
lack medical insurance. Dedicated medical centers for
undocumented immigrants facilitate interaction with this population
group. In this study, we used the interferon-g assay to assess the
prevalence of LTBI in a population of immigrants visiting two urban
healthcare centers. We also assessed adherence to preventive or
curative treatment, if prescribed.
Methods: All consecutive new patients attending two healthcare
centers for undocumented immigrants in Lausanne, Switzerland,
between January and July 2007 were offered TB and LTBI screening
using a questionnaire on risk factors and current symptoms. The
nurse practitioners also offered the interferon-g assay (T-Spot.TB™,
Oxford Immunotec). Patients with a positive T-Spot.TB™ or TB symptoms were examined by a physician and had a chest X-ray
performed. Adherence to treatment for TB or LTBI was evaluated
monthly at visits to the tuberculosis service of the Department of
Ambulatory Care and Community Medicine.
Results: Of 161 undocumented immigrants, 131 (81.4%) agreed to
be screened; 125 had a complete examination. Of these 125, 51.2%
were from South America and 19.2% from Sub-Saharan Africa. Most
patients (83.2%) entered Switzerland without passing the official
screening procedure for TB for asylum seekers and refugees, and
52% of the patients had been in Switzerland for less than two years.
Twenty-four of the 125 patients (19.2%; CI95% 12.7; 27.2) had a
positive T-Spot.TB™, and 2/125 had active TB (1.6%; CI95% 0.2;
5.7). Of the 18 patients with LTBI, 4 did not show up for a second
visit. Ten patients had an indication for standard isoniazide or
rifampicine preventive therapy, but 5 interrupted their treatment
before the scheduled end (50% completion rate).
Conclusion: Screening for active and latent tuberculosis in this hardto-reach population is feasible using dedicated clinics, and the prevalence of TB and LTBI in this population is high. However, the low
adherence to treatment for LTBI is an important public health concern, and new strategies are needed to address this.
S23
S25
No healthy heart for heavy drinkers: a population-based study in
Switzerland
Foerster M., Marques-Vidal P., Gmel G., Daeppen J.-B., Cornuz J.,
Hayoz D., Pécoud A., Mooser V., Waeber G., Vollenweider P.,
Paccaud F., Rodondi N. (Lausanne, Philadelphia)
Background: Low to moderate alcohol consumption has been associated with lower coronary heart disease (CHD) risk, an effect mainly
mediated by an increase in HDL-cholesterol levels. However, data on
the CHD risk associated with high alcohol consumption are conflicting.
Methods: In a population-based study of 5,769 men and women,
aged 35–75 years, without cardiovascular disease in Switzerland, last
week alcohol consumption was categorized into 0, 1–6, 7–13, 14–20,
21–27, 28–34, 035 drinks/week and into nondrinkers (0 drink/week),
moderate (1–13), high (14–34) and very high drinkers (035). Blood
pressure, lipids and high sensitivity C-reactive protein (hs-CRP) were
measured, and the 10-year CHD risk was calculated according to the
Framingham risk score.
Results: 73% (n = 4,214) of the participants consumed alcohol; 16%
(n = 909) were considered as high drinkers and 2% (n = 119) as very
high drinkers. In multivariate analysis, increasing alcohol consumption
was associated with higher HDL-cholesterol (from 1.57 ± 0.01
[adjusted mean ± SE] in nondrinkers to 1.88 ± 0.03 mmol/L in very
high drinkers); triglycerides (1.17 ± 1.01 to 1.32 ± 1.05 mmol/L), and
systolic and diastolic blood pressure rose significantly (127.4 ± 0.4 to
132.2 ± 1.4 and 78.7 ± 0.3 to 81.7 ± 0.9 mm Hg, respectively, all p for
trend <0.001). Predicted 10-year CHD risk increased from 4.31 ± 0.10
to 4.90 ± 0.37 (p = 0.03) with increasing alcohol use, with a J-shaped
relationship.
Conclusion: As measured by the 10-year CHD risk, the protective
effect of alcohol consumption disappears in very high drinkers,
namely because the beneficial increase in HDL-cholesterol may be
blunt by a rise in blood pressure levels.
Prevalence of vitamin B12 deficiency and vitamin B12 depletion:
a population based study in a central european country
Risch L., Zerlauth M., Bernasconi L., Saely CH., Risch M., Risch G.,
Nydegger U. (Liebefeld/Feldkirch, Schaan, Pregassona/Aarau,
Feldkirch/Triesen, Liebefeld/Schaan, Liebefeld)
Background: A negative vitamin B12 balance is associated with
haematological, neuropsychiatric and cardiovascular symptoms. The
condition is diagnosed with laboratory measurement of total vitamin
B12 (B12), and, if B12 concentrations are within the grey zone
(125–300 pmol/L), more sensitive markers, such as Holotranscobalamin (active B12; aB12). Not much is known about the prevalence of
Vitamin B12 deficiency and Vitamin B12 depletion (grey zone B12,
aB12 <35 pmol/L) in Central Europe.
Methods: Thus, a cross sectional study was conducted among
inhabitants of the principality of Liechtenstein. 7427 consecutive
outpatients (mean 48 ± 19 years, range 1–101; 66% female; 19.1% of
the country’s entire population) undergoing B12 measurement (Beckman Coulter Unicel) for investigation of B12 deficiency were included
into the study.
Results: Crude analysis revealed 13.4% of the patients with B12
levels <125 pmol/L indicating B12 deficiency, whereas 74.2% of the
patients had B12 within the grey zone. When looking at a subset of
patients with aB12 measurement (n = 1328; Abott Axsym), 26.6% had
a grey zone B12 together with a low aB12 concentration <35 pmol/L,
indicating B12 depletion. Fitting a logistic regression model indicates
female gender (p <0.001) and age (p = 0.01) to be significantly associated with B12 deficiency. An interaction term female gender*age (p
<0.001) indicates that the association between B12 deficiency & age
is stronger among men than among women. The crude period prevalence of B12 deficiency in the entire population amounts at least
2.6% and varies according to age and gender from 0.1–7.1%. Analogously, the period prevalence of patients with B12 depletion can be
estimated at 5.1%, varying from 0.2–14.2%.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
Conclusions: About 40% of outpatients investigated for B12 deficiency exhibit either B12 deficiency (13.4%) or B12 depletion
(26.6%). The respective crude period prevalence among the general
population can be estimated at 7.7% (2.6% B12 deficiency/5.1% B12
depletion). Increasing age and female gender are associated with a
negative B12 balance.
S26
Sudden death of recreational sportsman myth or reality?
Katz E., Potin M., Kehtari R., Sierro C., Fishman D., Niquille M.,
Garcia W., Kocher A., Metzger J.-Th. (Lausanne, Neuchâtel, Sion,
Genève, Fribourg, Delémont)
Background: Sudden Death (SD) in the athlete is extremly visible
phenomenon because of the high profile of professional athletes.
Less is known about SD during recreational sport activities. The aim
of the present study was to investigate SD among amateur sportsmen in the French-speaking part of Switzerland.
Methods: Data were provided by RRACE cardiac arrest registry
which enlisted the help of >1500 general practitioners (GPs), 26
Emergency Medical Services (EMS), 4 alarm centrals and 23 hospitals
to consecutively include the data about every adult (>18 years) outof-hospital SD of non traumatic origin in the French-speaking part
Switzerland. (Area covered >12000km2; adult population 1.5 mln).
Results: After 6 months 14 SD (3% of total amount of out-of-hospital
SD) during recreational sport activities were identified, all SD were of
cardiac origin. All victims were males, mean age 61.6 years (SD 15.4).
Every second victim was known for heart disease (mostly coronary
artery disease) and every third suffered from diabetes. Most of victims
10/14 (71%) were jogging or cycling when they suffered from SD.
Witnesses were present during 12 events (85%) and every second
witness initiated cardio-pulmonary resuscitation (CPR). First recorded
rhythm was ventricular fibrillation in 8 victims (57%) and only 2 persons (14%) survived, both in good neurological conditions.
Conclusions: SD during recreational sport activities is not uncommon. Amateur athletes seeking high performance and amateur athletes known for heart disease and diabetes should be strongly
advised to enter preparticipational screening programm before starting sporting activities. Since most of sporting activities are practiced
in group members of sport societies should be trained to identify
cardiac arrest premonitoring symptoms and to initiate CPR.
Forum Med Suisse 2008;8:(Suppl. 40)
10 S
S27
Depression and anxiety disorders are prevalent in younger
patients requesting a check-up exam
Sulger Büel E., Hunziker S., Langewitz W., Nüesch R., Battegay E.,
Zimmerli L. (Basel, Zürich)
Objective: Patients who request a general check-up are often motivated by specific symptoms and health concerns and rarely seek out
physicians for preventive issues. Furthermore, anxiety and mood
disorders may prompt patients to ask for a check-up exam. We
hypothesized that psychiatric disorders are more prevalent in “checkup” patients compared to patients who schedule an appointment for
other reasons than a check-up exam.
Design and method: We screened 66 patients who requested a
check-up exam (43 men and 23 women, mean age 45±16 years) and
100 patients who scheduled an appointment for other reasons than
“check-up” (61 men and 39 women, mean age 45 ± 17 years) for
anxiety disorders and depression. Three validated easy-to-administer
tools to screen for psychiatric disorders such as anxiety disorders
and depression were used: the PRIME-MD, Hospital Anxiety and
Depression Scale, and Brief Symptom Inventory. All patients were
asked to fill out the questionnaires before their first medical consultation at the Outpatient Department of the University Hospital Basel.
Results: The prevalence of anxiety disorder or depression using
these screening questionnaires was similar between check-up and
control patients (29% vs. 41%, p = 0.11). In control patients there
was no difference in prevalence of anxiety disorder or depression
between younger and older individuals. However, in check-up
patients psychiatric disorders were more prevalent in patients
younger than 40 years of age (p = 0.02 for depression and anxiety
disorder, respectively): in this age group, screening tools were positive for anxiety disorders in 31% and depression in 41% of patients.
Conclusions: Psychiatric comorbidities are frequent in a general
internal medicine outpatient setting. There is no difference in prevalence between check-up patients and patients who schedule an
appointment for reasons other than check-up. However, younger
patients who request a check-up exam demonstrate increased psychiatric comorbidity.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
Forum Med Suisse 2008;8:(Suppl. 40)
11 S
S28
S30
Diagnosing pulmonary embolism by multi-detector computed
tomography alone or combined with lower limb venous
ultrasonography: a randomized non-inferiority trial
Righini*M., Le Gal G., Aujesky D., Roy P-M., Sanchez O., Verschuren
F., Rutschmann O., Nonent M., Cornuz J., Thys F., Petit Le Manach
C., Revel M.-P., Poletti P.-A., Meyer G., Mottier D., Perneger T.,
Bounameaux H., Perrier A. (Genève, Brest, Lausanne, Angers, Paris,
Bruxelles, Genève Md)
Background: Recent data suggest that multi-slice computed tomography (MSCT) combined with D-dimer measurement may safely rule
out pulmonary embolism. We compared this combination with a
strategy in which both a negative lower limb vein ultrasonography
and a negative MSCT were required to rule out pulmonary embolism.
Methods: We included 1819 consecutive outpatients with clinically
suspected pulmonary embolism in a multicentre non-inferiority randomized controlled trial comparing two strategies: clinical probability
assessment and either 1) D-Dimer measurement and computed
tomography (DD-CT strategy) or 2) D-Dimer measurement, lower limb
vein compression ultrasonography and computed tomography (DDUS-CT strategy). The main outcome was the 3-month thromboembolic risk in patients left untreated based on the exclusion of
pulmonary embolism by the diagnostic strategy.
Findings: The prevalence of PE was 21% in both study arms. In the
per-protocol analysis, the 3-month thromboembolic risk was 0.3%
(95% CI: 0.1–1.1) in the DD-US-CT arm and 0.3% (95% CI: 0.1–1.2)
in the DD-CT arm, a non-significant difference (0.0; 95% CI: –0.9 to
0.8). Results were similar in the intention-to-diagnose analysis. In the
DD-US-CT arm, ultrasonography showed a deep venous thrombosis,
hence allowing foregoing MSCT, in 9% of patients. The mean cost
per patient was 20 to 30% higher in the DD-US-CT strategy.
Interpretation: The strategy combining D-Dimer and MSCT is as safe
as the strategy combining D-dimer, MSCT and lower limb vein compression ultrasonography for excluding pulmonary embolism.
Although the diagnostic yield of ultrasound is low when performed
before MSCT, it may remain of interest in patients with a contraindication to CT.
Prevalence of reduced estimated Glomerular Filtration Rate
(eGFR) in the anemic elderly
Risch L., Saely Ch., Gouya G., Hoefle G., Kiss D., Zerlauth M., Risch
G., Nydegger U., Drexel H., Risch M. (Liebefeld, Feldkirch, Liestal,
Schaan)
The clinical importance to identify even mild chronic kidney disease
(CKD) in older people is centered on prevention of progression to
endstage renal failure, anemia, renal osteopathy and to cardiovascular disease. Whereas decreased production of erythropoietin in
chronic kidney disease (CKD) is well known as a potential cause of
anemia, the contribution of CKD to anemia has not yet fully been
defined on a public health basis. We therefore investigated a representative homogenous patient group (N = 8.410, 38% of Liechtenstein’s entire population) seeking clinical attention for non-nephrological care. This group was screened for anemia (WHO criteria
employing haemoglobin cutoffs m/f <130/120 g/L). In addition, renal
function was assessed by means of the abbreviated MDRD equation.
Creatinine was measured by an alkaline picrate method revealing
concentrations traceable to the reference method IDMS (Cobas Integra, Roche Diagnostics, Rotkreuz). Anemia was present in 15.7%
(n = 1324) of the patients. An eGFR <60 ml/min/1.73 m2 was found
in 8.8%. Twenty-seven percent of the patients with anemia had an
eGFR <60 ml/min/1.73 m2. In crude analysis, there was a strong
association between the presence of anemia and an eGFR <60
ml/min/1.73 m2 (OR 6.5, 95% CI 5.56, 7.65). In a logistic regression
model, age (OR 1.036, 96%CI 1.032, 1.040/year), female gender (OR
1.33, 05% CI 1.17, 1.52) and an eGFR <60 ml/min/1.73 m2 significantly predicted presence of anemia, the latter criterion being the
strongest predictor (OR 3.025I, 95% 2.53, 3.61). An interaction term
age*GFR category reached significance (p <0.001), pointing to an
association between impaired renal function and anemia which was
significantly stonger among elderly compared to younger patients. It
is concluded that a reduced eGFR <60 ml/min/1.73 m2 is a prevalent
circumstance in patients with anemia. Moreover, such prevalence
increases with age, reaching about 50% in patients aged >80 yrs. It
may be concluded, that recognition of anemia imperatively should
prompt evaluation for kidney function, especially in elderly patients.
S29
A simple score for estimating ischemic heart disease in patients
with non-traumatic chest pain in primary care
Gencer B., Herzig L., Verdon F., Vaucher P., Burnand B., Bischoff T.,
Mühlemann N., Favrat B. (Lausanne, Epalinges, Neuchâtel, Bex)
Background: Modelling epidemiological knowledge in validated
clinical scores is a practical mean of integrating EBM to usual care.
Existing scores about cardiovascular disease have been largely
developed in emergency settings, but few in primary care. Such a toll
is needed for general practitioners (GP) to evaluate the probability of
ischemic heart disease (IHD) in patients with non-traumatic chest
pain.
Objective: To develop a predictive model to use as a clinical score
for detecting IHD in patients with non-traumatic chest-pain in primary
care.
Methods: A post-hoc secondary analysis on data from an observational study including 672 patients with chest pain of which 85 had
IHD diagnosed by their GP during the year following their inclusion.
Best subset method was used to select 8 predictive variables from
univariate analysis and fitted in a multivariate logistic regression
model to define the score. Reliability of the model was assessed
using split-group method.
Results: Significant predictors were: age (0–3 points), gender
(1 point), having at least one cardiovascular risks factor (hypertension,
dyslipidemia, diabetes, smoking, family history of CVD; 3 points),
personal history of cardiovascular disease (1 point), duration of chest
pain from 1 to 60 minutes (2 points), substernal chest pain (1 point),
pain increasing with exertion (1 point) and absence of tenderness at
palpation (1 point). Area under the ROC curve for the score was of
0.95 (IC95% 0.93; 0.97). Patients were categorised in three groups,
low risk of IHD (score under 6; n = 360), moderate risk of IHD (score
from 6 to 8; n = 187) and high risk of IHD (score from 9–13; n = 125).
Prevalence of IHD in each group was respectively of 0%, 6.7%,
58.5%. Reliability of the model seems satisfactory as the model
developed from the derivation set predicted perfectly (p = 0.948) the
number of patients in each group in the validation set.
Conclusion: This clinical score based only on history and physical
exams can be an important tool in the practice of the general physician for the prediction of ischemic heart disease in patients complaining of chest pain. The score below 6 points (in more than half of our
population) can avoid demanding complementary exams for selected
patients (ECG, laboratory tests) because of the very low risk of IHD.
Score above 6 points needs investigation to detect or rule out IHD.
Further external validation is required in ambulatory settings.
S31
Accuracy of diagnosis and awareness of cardiovascular risk
factors and metabolic syndrome in doctors and patients
Gschwend S., Stöckli R., Schöbi N., Nüesch R., Battegay E.,
Zimmerli L. (Basel, Zürich)
Objective: The metabolic syndrome (MS), a clustering of several
commonly occurring abnormalities that include abdominal obesity,
hypertriglyceridemia, low high-density lipoprotein level, hypertension,
and hyperglycemia has gained attention due to its impact on cardiovascular diseases and its increasing prevalence. Adequate awareness
of MS is a key first step that enables patients to address their risk
factors (RF). We hypothesized that patients are inadequately informed
about their own RF, and that their treating physicians underdiagnose
the presence of the MS.
Design and method: We prospectively examined a total of 415 consecutive patients (210 women and 205 men, mean age 46 ± 17 years,
range 16–86 years) during their first medical consultation at the Outpatient Department of the University Hospital Basel. Based on the
physical exam and the patient’s history treating physicians had to
judge whether MS might be present or not. After the consultation the
components defining MS were measured in all patients. The ATP IIIdefinition of MS was used. Patients were asked to recall as many
cardiac RF as possible.
Results: The observed prevalence of MS was 18% (32/210 women
and 41/205 men). The probability of MS was 57% [95% CI 48–66],
given a positive judgement by the physician (positive predictive
value), and the probability of absence was 92% [95% CI 90–94],
given a negative judgement (negative predictive value). In patients,
mean RF knowledge was 2.5 ± 1.4 (median 3) out of a possible 12.
Smoking (64%), physical inactivity (49%) and obesity (43%) were the
RF most commonly reported whereas lipid abnormalities (22%),
hypertension (21%) and diabetes (12%) were mentioned by a minority
of patients. Patients affected by RF did not recall them more often
than patients without the corresponding RF.
Conclusions: Physicians’ judgment of MS based on physical exam
and patient’s history is accurate, i.e. only few cases are missed (good
NPV). However, to increase PPV laboratory findings should be incorporated in the judgement. Patients have limited knowledge about
cardiovascular RF, whether affected by them or not.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
Forum Med Suisse 2008;8:(Suppl. 40)
12 S
S34
S32
Eligibility for statin therapy in primary prevention: discrepancies
using different guidelines in a population-based study in
Switzerland
Nanchen D., Chiolero A., Cornuz J., Firmann M., Marques-Vidal P., Mooser V.,
Paccaud F., Waeber G., Vollenweider P., Rodondi N. (Lausanne, Collegeville)
Introduction: Recommendations for statin use for primary prevention of coronary heart disease (CHD) are based on estimation of the 10-year CHD risk. We
compared the 10-year CHD risk assessments and eligibility percentages for
statin therapy using three scoring algorithms currently used in Switzerland.
Methods: We studied 5683 women and men, aged 35–75, without overt cardiovascular disease (CVD), in a population-based study in Lausanne, Switzerland.
We compared the 10-year CHD risk using three scoring schemes, i.e., the
Framingham risk score (FRS) from the U.S. National Cholesterol Education
Program’s Adult Treatment Panel III (ATP III), the PROCAM scoring scheme from
the International Atherosclerosis Society (IAS), and the European risk SCORE
for low-risk countries, without and with extrapolation to 60 years as recommended by the European Society of Cardiology guidelines (ESC). With FRS and
PROCAM, high-risk was defined as a 10-year risk of fatal or non-fatal CHD
>20% and a 10-year risk of fatal CVD >= 5% with SCORE. We compared the
proportions of high-risk participants and eligibility for statin use according to
these three schemes. For each guideline, we estimated the impact of increased
statin use from current partial compliance to full compliance on potential CHD
deaths averted over 10 years, using a success proportion of 27% for statins.
Results: Participants classified at high-risk (both genders) were 5.8% according to FRS and 3.0% to the PROCAM, whereas the European risk SCORE
classified 12.5% at high-risk (15.4% with extrapolation to 60 years). For the
primary prevention of CHD, 18.5% of participants were eligible for statin therapy using ATP III, 16.6% using IAS, and 10.3% using ESC (13.0% with extrapolation) because ESC guidelines recommend statin therapy only in high-risk
subjects. In comparison with IAS, agreement to identify eligible adults for
statins was good with ATP III, but moderate with ESC (Figure). Using a population perspective, a full compliance with ATP III guidelines would reduce up to
17.9% of the 24’310 CHD deaths expected over 10 years in Switzerland,
17.3% with IAS and 10.8% with ESC (11.5% with extrapolation).
Conclusion: Full compliance with guidelines for statin therapy would result
in substantial health benefits, but proportions of high-risk adults and eligible
adults for statin use varied substantially depending on the scoring systems
and corresponding guidelines used for estimating CHD risk in Switzerland.
Figure
Molecular and cellular effects of dietary alpha-linolenic acid
on atherogenesis and membrane lipid profiles
Matter C.M., Scheeder M.R., Lohmann C., Lüscher T.F., Beer J.H.
(Uni Zürich, ETH Zürich, KS Baden)
Background: The beneficial effects of long-chain n-3 fatty acids (LC-n-3 FA) of
marine origin on lipids, cardiac arrhythmia and cardiovascular events are well
documented. However, the relevance of plant-derived C18:3n3 FA (alphalinolenic acid, ALA) remains uncertain. Furthermore, the capacity for chain
elongation is thought to be very limited in mammals. We have recently reported
on increased concentrations of ALA in alpine cheese and on its potential benefits (“The alpine paradox”).
Aims: We tested the hypothesis that a) an ALA-rich diet reduces atherosclerosis and b) a conversion of ALA into LC-n-3 FA can be detected in the membrane FA profile.
Methods and results: Eight weeks old male ApoE-/- mice were fed a standardized, 0.15% cholesterol diet for 16 weeks containing either a high ALA (HI,
7g%; n = 14) or standard low ALA diet, (LO, 0.03%; n = 12). ALA was offered as
flaxseed oil, while the control was compensated with cocoa butter. Plaque area
in the aortic arch, as quantified by oil-red O staining was significantly reduced
(119,009 um2 vs. 69,026 um2; p = 0.006). T cell content (CD3 positivity) was
also significantly decreased (902 um2 vs. 128 um2; p = 0.004) The macrophage
content (CD68 positivity) was non-significantly reduced. Weight gain was similar
in both groups. The conversion of ALA into LC-n-3 FA was analyzed by gas
chromatography and is given as the FA percentage in red cell membranes
(Table). The data indicate an increased membrane incorporation of ALA, a 7x
shift in the n6/n3 ratio and a 5x shift in the LC-n-3 FA content (EPA, DPA and
DHA). On the other hand, arachidonic acid (ARA) content was only 1/5 of the
LO-population.
Conclusions: A diet rich in ALA reduces atherosclerosis and T cell infiltration in
ApoE-/- mice. It induces an important chain elongation into LC-n-3 FA resulting
in a favourable FA profile. Given the limited fishery resources, ALA may represent a (cost)-effective and attractive nutritional supplement.
Table 1
S35
Akutes Nierenversagen – ist die intermittierende Hämodialyse
bei schwer kranken Patienten noch gerechtfertigt?
Rupprecht C., Bleisch J., Ursprung T., Stäubli M., Franzen D.
(Zollikerberg)
S33
Cost-effectiveness and cost-utility of risedronate for
osteoporosis treatment and fracture prevention in women:
a swiss perspective
Wasserfallen J-B., Krieg M-A., Greiner R-A., Lamy O. (Lausanne, Lörrach)
Introduction: Risedronate has been shown to reduce the risk of fractures in
postmenopausal osteoporotic women. We assessed its cost-effectiveness and
cost-utility along different risk profiles using computer modelling.
Methods: A previously validated Markov model was used and populated with
mortality, fracture incidence and cost data specific to Switzerland, as well as
published utility values, and run on a population of 1000 women of 70 years
with previous vertebral fracture, treated over 5 years with risedronate 35 mg
weekly (base case). Another 119 scenarios were investigated in 5 cohorts
(according to age at the start of therapy) with 8 risk factor distributions and
3 lengths of residual effects after end of risedronate administration. Sensitivity
analyses included the effect of input parameter variation on key outcomes. The
outcomes were cost per hip fracture averted, cost per any fracture averted and
cost per quality-adjusted life year (QALY) gained.
Results: Risedronate therapy proved to be the dominant strategy in base case
population. In the presence of a previous vertebral fracture risedronate was
dominating in all scenarios from age 65 and even at age 60 when assuming a
5 year residual effect. For all osteoporotic women >60 years of age with at least
one risk factor, cost-utility ratio ranged from below CHF 50,000 to cost-saving.
Age at start of therapy and fracture risk profile had a significant impact on
results. Sensitivity analysis did not markedly change the results.
Conclusions: Assuming a 2 year residual effect, cost-utility ratio of risedronate
in women with postmenopausal osteoporosis is below accepted thresholds
from age 60 and even cost saving above the age of 65 for all risk scenarios.
Hintergrund: Das akute dialysepflichtige Nierenversagen ist mit einer hohen
Mortalität von 35–80% assoziiert. Bei der Behandlung stehen zwei Nierenersatzverfahren zu Verfügung: kontinuierliche Hämo(dia)filtration und intermittierende Hämodialyse (IHD). Die Überlegenheit eines der beiden Verfahren wird
in Bezug auf die Mortalität und die Nierenerholungsrate kontrovers diskutiert.
Im Rahmen eines Multiorganversagens (MODS) wird jedoch das kontinuierliche
Verfahren bevorzugt, mit der Begründung, dass gehäuft arterielle Hypotonien
während der IHD auftreten. Ist die IHD bei schwer kranken Patienten mit MODS
noch gerechtfertigt?
Methoden: Im Zeitraum von 6 Jahren wurden 53 Patienten (Durchschnittsalter
68 Jahre) retrospektiv analysiert, welche aufgrund eines akuten Nierenversagens auf der Intensivstation einer IHD unterzogen wurden. In 53% trat das
Nierenversagen im Rahmen eines MODS auf. Der durchschnittliche APACHE II
Score betrug 20. Häufigste Ursache war eine Tubulusnekrose (85%). Die IHD
wurde in der Regel täglich (77%) mit einer durchschnittlichen Ultrafiltrationsrate
von 507 ml/h durchgeführt.
Resultate: Die Mortalität betrug 30,2%. Signifikante Risikofaktoren stellen ein
MODS (p = 0,001), metabolische Azidose (p = 0,0001), mechanische Beatmung
(p = 0,003) und arterielle Hypotonie (p = 0,0001) dar. Zu Komplikationen kam es
in 32%, wobei die arterielle Hypotonie am häufigsten war (24%). Risikofaktoren
für hämodynamische Zwischenfälle während der IHD waren ein MODS
(p = 0,009), ARDS und Beatmungspflicht (p = 0,015 bzw. 0,003), hohe Ultrafiltrationsraten (p = 0,032) sowie die tägliche (im Vergleich zur alternierenden)
Hämodialysefrequenz (p = 0.002).
Schlussfolgerung: Auch bei Patienten mit MODS und/oder arterieller Hypotonie kann die IHD zur Behandlung des akuten Nierenversagens durchaus
empfohlen werden. Denn trotz hohem Anteil an Patienten mit MODS ist die
Mortalität im vorliegenden Krankengut im Vergleich zur Literatur tief. Somit kann
davon ausgegangen werden, dass die Auswahl des Nierenersatzverfahrens in
Bezug auf die Mortalität nicht massgebend ist. Vielmehr sind die genannten
Risikofaktoren (MODS, metabolische Azidose, respiratorische Insuffizienz und
arterielle Hypotonie) für die Prognose entscheidend. Diese gilt es früh zu
erfassen und zu therapieren. In diesem Zusammenhang sind geringere Ultrafiltrationsraten mit kompensatorisch verlängerter Hämodialysedauer zu
empfehlen.
C O M M U N I C AT I O N S L I B R E S S S M I
FREIE MITTEILUNGEN SGIM
Forum Med Suisse 2008;8:(Suppl. 40)
S36
Congruence between referring and hospital physicians about
the reasons for admission in a supportive care unit – comparison
with cancer patients’ evaluation of their main symptoms
Luthy C., Cedraschi C., Chouiter A., Konrad-Mugnier B., Rapiti E.,
Allaz A.F. (Geneva)
Background: Patients admitted in a supportive care unit often present
with intricate somatic and psychosocial problems. In this context, congruence between referring and hospital physicians on how they prioritize
symptoms and treatments raises important issues. Whether these priorities correspond to the patients’ views remains an open question.
Objective: To assess the level of congruence between referring and hospital physicians regarding the identified reasons for admission of patients
hospitalized in a supportive care unit, and to compare these reasons with
the main symptoms patients identify.
Methods: Data concerning 83 consecutive patients were collected by
means of a structured questionnaire: the reasons for admission according
to the referring physician and to the physician in charge of the hospital
unit were assessed in nine categories not mutually exclusive. Patients
were asked to complete a questionnaire evaluating their main symptoms
at the time of admission. Socio-demographic and clinical characteristics
of the patients were also recorded. Kappa statistics were used to compare
the agreement between physicians; and between the physicians and the
patient.
Results: 67% of the patients were men; mean age was 65 years (SD =
14). A wide range of cancer diagnoses were represented; 23% had primary local diseases, 42% had local recurrences, and 35% had metastatic
diseases. Median time since diagnosis was 1.8 years (range = 0.1–12.5
years). Identified main reasons for admission were similar in both groups
of physicians and Kappa values indicated a fair (K between 0.4 and 0.7)
to good (K >0.7) congruence. Asthenia was the most frequently mentioned
reason (33% in referring physicians vs 55% in physicians in charge,
K = .49), followed by functional problems (30% vs 53%, K = .48), pain (37%
vs 49%, K = .71), nutrition (19% vs 38%, K = .47), dyspnoea (17% vs
20%, K = .78). Complications of oncological treatment, psychosocial
difficulties, and behavioural problems were less frequently mentioned.
Fatigue was also the main symptom reported by the patients, although
with a much higher prevalence (85%), followed by pain (44%), nutrition
(40%), anxiety (38%), and dyspnoea (35%). Congruence between
patients’ evaluation and physicians was poor (K <0.4).
Conclusions: The level of congruence between referring and hospital
physicians regarding the reasons for admission of patients hospitalized in
a supportive care unit was satisfactory. This is important in terms of coordinated care between ambulatory and hospital settings and may contribute to continuity of care. However, patients’ reports put a different
emphasis on the symptoms they experience thus illustrating the challenges of shared goal-setting.
S37
Perceptions and use of communication skills in outpatient and
inpatient settings: implications for training
Junod Perron N., Sommer J., Hudelson P., Demaurex F., Luthy C.,
Nendaz M., Dolmans D., Van der Vleuten C., de Grave W.
(Geneva, Maastricht)
Background: Understanding how the working setting influences physicians’ perception and use of communication skills is important for designing effective training programmes in this field.
Objectives: to explore how physicians perceive and use communication
skills in in-patient and out-patient settings.
Methods: A self-administered questionnaire and 4 focus groups were
conducted with residents and clinical supervisors in two inpatient services
and one outpatient clinic of the Geneva University Hospitals. Descriptive
statistics were used for the questionnaire. Focus groups were audio
taped, transcribed verbatim and analyzed in a thematic way using Winmax
software for qualitative data analysis.
Results: Outpatient physicians tended to be older, more trained in and
more receptive to communication skills. These physicians reported that
communication skills were especially useful in addressing chronic diseases and patients’ social problems, and thought that the use of good
communication skills could be therapeutic for the patient. In contrast, inpatient physicians valued communication skills because they contributed
to their own well-being and helped them keep control of the situation. In
particular, they emphasized the importance of good communication skills
for dealing with family conflicts, end of life issues and patients with substance-abuse problems. The areas in which physicians desired more
training reflected their perceptions of the utility of communication skills:
inpatient physicians wanted more training in how to break bad news,
manage conflicts and inform patients while outpatient physicians gave
priority to listening skills, showing empathy, exploring patients’ perspectives and structuring the consultation.
Conclusion: Differences in service priorities and demands, as well as
physicians’ professional development process must be taken into consideration when developing a training program in communication skills.
13 S
S38
Psychosocial vulnerability in fibromyalgia patients:
a role for COMT polymorphism?
Desmeules J., Piguet V., Besson M., Chabert J., Rapiti E.,
Rebsamen M., Rossier M., Dayer P., Cedraschi C. (Genève)
Introduction: Fibromyalgia (FM) is a chronic musculoskeletal syndrome,
and patients experience functional impairments, emotional distress and a
negative quality of life. The frequent polymorphism Val158Met of the gene
encoding catechol-O-methyltransferase (COMT) is associated with a
reduction in the enzyme activity that influences pain regulation and anxiety
and may participate in chronic painful diseases. We investigated the
influence of COMT polymorphism on psychosocial variables in FM
patients and healthy controls.
Methods: 198 patients underwent a quantitative sensory testing requiring
2 weeks medication withdrawal; 137 were classified as able to stop medication (ASM) and 61 were classified as unable to stop medication (USM);
99 healthy controls were included. Psychosocial aspects were investigated by means of questionnaires investigating health related quality of
life, physical activities, and mood (Fibromyalgia Impact Questionnaire,
Psychological General Well-Being, SF-36, State-Trait Anxiety Inventory,
Beck Depression Inventory, and Catastrophizing Scale). Assessment of
the control group included the same questionnaires, except FIQ. The
COMT Val158Met polymorphism was assessed by TaqMan PCR.
Results: Most subjects were middle-aged females, with a 10 year mean
duration of symptoms. Over half were either on sick-leave or on disability
pension. Clinical measures indicated moderate to severe pain in both
groups of FM; 49% of the ASM group was on antidepressant medication
prior to the entry in the study and nearly all the USM (92%) were using
antidepressants (p <0.001). The measures of psychosocial and functional
aspects showed severe impairments in FM patients as compared to
controls (p <0.05, for all scales) and indicated that the USM patients
suffered more severe functional, cognitive and emotional limitations than
ASM. The distribution of the COMT polymorphism was similar in controls
and in FM patients. However, when considering FM subgroups, the
Met/Met genotype was clearly over-represented in USM patients (36% vs
19% in ASM and 25% in controls; p <0.05). Analysis of ASM patients with
a Met/Met genotype showed systematically worse scores on all
psychosocial variables.
Conclusion: These results suggest a role of the COMT Val158Met polymorphism in the increased psychosocial vulnerability (i.e. anxiety, catastrophizing, depression) observed in FM patients. This may be of importance as identifying patient subgroups is a major challenge in the
treatment of FM.
Supported by the SNSF (NRP53–4049-405340-104645/1)
S39
Assessment of doctors’ medical and cultural competence using
virtual patients
Junod Perron N., Perneger T., Kolly V., Hudelson P. (Genève)
Background: As patient populations become increasingly diverse, physicians need not only to master biomedical aspects of care, but also to be
sensitive to the ways in which culture and language can influence clinical
communication and care. The goal of our study was to examine physicians’ use of appropriate biomedical and cultural skills during clinical
encounters with migrant patients, and the relationship between the two
skill sets.
Methods: We developed two detailed patient “stories” or scenarios and
incorporated them into an interactive, computer-based program (VIPS)
designed to test clinical skills. Participants (doctors and medical students
in their clinical years) could ask any number of questions to arrive at their
diagnosis. For each scenario, we constructed two scores to assess
whether physicians asked questions that were appropriate from a biomedical and from a cultural standpoint. These scores were based on an a
priori determination of appropriateness of each question.
Results: Each virtual patient was assessed by 111 and 99 participants;
92 participants assessed both. The participants asked on average 8.4
(SD 2.6) and 7.9 (SD 3.5) medically indicated questions and 1.4 (SD 1.0)
and 2.3 (SD 1.4) culturally appropriate questions. Correlations of the
medical scores (r = 0.49, p <0.001) and of the cultural scores (r = 0.46,
p <0.001) were moderate but statistically significant. Within each virtual
patient, the medical and cultural scores were less correlated (r = 0.26
and 0.39, both p <0.005). No respondent characteristics were consistently
associated with higher or lower scores.
Conclusions: The VIPS program appears to be reliable. However, we
found only a modest correlation between physicians’ use of appropriate
biomedical and cultural skills, and scores were not associated with years
of experience. These results raise several questions regarding the operationalization of biomedical and cultural skills in this study and the relationship between the two skill sets.
C O M M U N I C AT I O N S L I B R E S S S H é
FREIE MITTEILUNGEN SGH
S40
Clonal analysis of deletions on chromosome 20q and JAK2V617F in MPD suggests that del20q acts independently
and is not one of the pre-disposing mutations for JAK2-V617F
Schaub F., Looser R., Tiedt R., Hermouet S., Kralovics R., Girodon F.,
Tichelli A., Skoda RC. (Basel, Nantes, Wien, Dijon)
Deletions on the long arm of chromosome 20 (del20q) are the most
common chromosomal aberration in myeloproliferative disorders
(MPD) and can be found in the bone marrow from 0.2% of patients
with essential thrombocythemia (ET), 8% of polycythemia vera (PV)
and 7% of primary myelofibrosis (PMF). The common deleted region
has been mapped, but no gene mutations have been detected to
date. The del20q and JAK2-V617F can occur simultaneously in the
same patients. We previously described two such patients and found
that the size of the del20q clone by far exceeded the size of the clone
carrying JAK2-V617F, suggesting that del20q preceded the acquisition of the JAK2-V617F mutation. To address the role of del20q and
JAK2V617F mutations in the pathogenesis of MPD, we studied their
temporal order of occurrence using clonogenic assays. We screened
DNA from granulocytes of 666 MPD patients (263 PV, 320 ET, 83
PMF) for the presence of del20q using a quantitative gene copy number PCR assay with primers placed in two different exons of L3MBTL,
a gene located in the common deleted region. Since this assay is
positive only if the majority of granulocytes have lost a copy of
L3MBTL, this method selects for del20q events that dominate in the
peripheral blood. Del20q was found in a total of 19/666 MPD patients
(2.9%) and 17 of these 19 patients were also positive for JAK2-V617F.
The frequency of del20q was 3/320 (0.9%) in ET, 7/263 (2.7%) in PV,
and 9/83 (11%) in PMF. Samples that showed a decrease in copy
number in the initial screen were validated using primers in neighbouring genes or comparative genomic hybridization using highdensity oligonucleatide arrays. We performed colony assays in
methylcellulose with peripheral blood from 5 patients positive for
del20q, of which 4 were also positive for JAK2-V617F. To determine
the clonal distribution, single BFU-E colonies grown in the presence
of erythropoietin were picked and analyzed individually for the presence of del20q and/or JAK2-V617F. We found that in 2 patients
del20q occurred before JAK2-V617F, whereas in 2 other cases
del20q was acquired after the acquisition of JAK2-V617F. The lack of
a consistent temporal pattern of occurrence of del20q in respect to
JAK2-V617F suggests that del20q acts independently and is not one
of the pre-disposing mutations for JAK2-V617F.
S41
Dependency of survival on additional karyotype anomalies and
bone marrow blast count in patients suffering from
myelodysplastic syndromes with 5q deletion
Blum S., Hildebrandt B., Jotterand M., Schapira M., Giagounidis A.,
Aul C., Germing U. (Lausanne, Düsseldorf, Duisburg)
The 5q deletion syndrome is described as having a favourable outcome in MDS. Little data is available concerning del(5q) and additional karyotype anomalies or bone marrow blast count. We screened
the our MDS registries to obtain data on patients with karyotype
anomalies including del(5q). 1073 patients were karyotyped at diagnosis. 198 patients with del(5q) with or without other karyotype
anomalies and 105 patients with complex karyotype without del(5q)
were analysed. 106 patients showed del(5q) as single anomaly, 23
had 1 additional anomaly, 69 had 2 or more additional anomalies and
were classified as complex karyotype. In del(5q) only, mean survival
was 76 months as compared to 42 months in normal karyotype. In
the group with 1 additional anomaly mean survival was 47 months
(p = 0.02), in the group with 2 or more additional anomalies 7 months
(p = 0.0005). Survival differed significantly in each subgroup for
patients with more or less than10% of bone marrow blasts. Patients
with del(5q) only show a median survival of 12 months when presenting with more than 10% medullary blasts. Patients with a complex
karyotype including del(5q) with less than 5% medullary blasts had a
median survival of 12 months, but median survival was only 6 months
in patients with elevated medullary blasts. By multivariate analyses,
we found that additional karyotype anomalies, followed by an elevated medullary blast count above 10% are the most important independent prognostic parameters. We compared the group del(5q) and
2 or more additional anomalies (n = 69) to patients with complex
karyotype anomalies not including del(5q) (n = 105). Median survival
of the group including del(5q) was 7 months as compared to 12
months in the group without del(5q) (p = 0.02). 12 months after diag-
Forum Med Suisse 2008;8:(Suppl. 40)
14 S
nosis, 30% of the group with del(5q) in a complex karyotype was
alive as compared to 45% of the group with a complex karyotype
without del(5q). Disease related death was noted in 77% of patients
with a complex karyotype and del(5q) and 73% without del(5q). Our
data show that survival in patients with del(5q) is dependent on the
number of additional karyotype anomalies as well as medullary blast
count. The prognosis of MDS with del(5q) is associated with an
extremely poor prognosis when diagnosed within a complex karyotype. Although there are no substantial differences in clinical,
haematological and morphological data between patients with or
without del(5q), the median survival differs significantly.
Figure 1: KM Plots presenting survival of patients with a complex
karyotype with or without inclusion of del(5q)
S42
Junctional adhesion molecule C (JAM-C) constitutes a new
diagnostic marker for B cell lymphoproliferative syndromes
Matthes T., Ody C., Jungblut-Ruault S., Cossali D., Barnet M.,
Aurrands-Lions M., Imhof BA. (Genève, Marseille)
Differentiation of naïve B cells into plasma cells or memory cells
occurs in the germinal centers (GC) of lymph follicles or alternatively
via a GC- and T cell independent pathway. It is currently assumed
that B cell lymphomas correlate to normal B cell differentiation
stages, but the precise correlation of several B cell lymphomas to
these two pathways remains controversial. We recently described the
junctional adhesion molecule C (JAM-C), a molecule originally identified at the cell-cell border of endothelial cells, as a new B cell marker
with a tightly regulated expression during B cell differentiation: immature CD10+ B cell in the bone marrow do not express JAM-C; naïve,
mature, peripheral blood B cells express it weakly; CD27+ memory
B cells strongly; and bone marrow plasma cells are again JAM-C
negative (Leukemia; 2007 Jun; 21(6):1285–93). Of particular interest,
JAM-C expression divides CD27+ tonsillar B cells into two subpopulations: JAM-Cneg cells, with a phenotype of germinal center B cells
and a high expression of BCL-6, a nuclear proto-oncogene with a
pivotal role in GC-formation, and JAM-Cpos cells, corresponding to
non-germinal B cells, derived partly from the marginal zone. In vitro
cultures of the different tonsillar B cell subpopulations (CD27+JamC+, CD27+JAM-Cneg, CD27negJAM-C+) confirmed these results,
since Ig-secretion measured after 7 days of culture, was minimal in
naïve CD27neg cells, CD27+Jam-C GC cells produced mainly IgG,
and non-GC JAM-C+CD27+ B cells mainly IgM. Simultaneous analysis of JAM-C and CD27 expression in peripheral blood lymphocytes
(PBLs) from a series of 86 patients with various lymphoproliferative
syndromes (LPSs) allowed a clear classification into two types of B
cell malignancies: JAM-Cneg lymphomas (CLL, follicular lymphoma,
DLBL, multiple myeloma, and B-ALL), and JAM-C expressing lymphomas (mantle cell lymphoma, marginal zone B cell lymphoma, hairy
cell leukemia). In 13 LPSs a clear diagnosis could not be obtained
using classical surface markers, immunohistology, and cytogenetic
analyses, in particular in cases on the borderline between MCL, CLL
and MZBL. The use of JAM-C in the diagnostic work-up of these
cases will be discussed. In conclusion, we suggest that JAM-C constitutes a new diagnostic marker for the characterisation of lymphoproliferative B cell syndromes, and in particular for the positive diagnosis of lymphomas derived from the marginal zone.
C O M M U N I C AT I O N S L I B R E S S S H é
FREIE MITTEILUNGEN SGH
S43
Significantly Shorter Telomeres in T-Cells of ZAP-70+CD38+
Patients with Chronic Lymphocytic Leukemia (CLL):<br>An
Important Role of T-Cells in this Subgroup of CLL?
de Beer D., Röth A., Nückel H., Sellmann L., Dührsen U., Dürig J.,
Baerlocher G.M. (Bern, Essen)
Background: Chronic lymphocytic leukemia (CLL) is not only characterized by a clonal expansion of specific B-cells, but also by an
increase in non-leukemic T-cells, most likely involved in sustaining the
growth of the leukemic B-cell clone. Based on ZAP-70, CD38 and the
IgVH mutation status, two prognostic groups of CLL patients can be
identified. Our aim was to characterize the replicative histories of the
B- and T-cells in the two groups of CLL patients compared to healthy
individuals.
Patients and methods: Blood samples from 73 patients with CLL
(ZAP-70-CD38-: n = 29, ZAP-70+CD38+: n = 30, ZAP-70/CD38 discordant: n = 14) were analyzed. The quantity and characteristics of
the lymphocyte subsets was assessed by a cell counter and by
immunophenotypic analysis. The replicative histories of naive and
memory T-cells as well as B-cells was determined by measurements
of telomere length by automated multicolor flow-FISH.
Results: As expected the average telomere length of the clonal
B-cells was short. The telomere length was, however, significantly
shorter for the ZAP-70+CD38+ patient samples (2.46 ± 1.08 kb) than
for the ZAP-70-CD38- patient samples (5.06 ± 1.76 kb, p <6.7 x 109). Interestingly, also the naive and memory T-cells from ZAP70+CD38+ CLL patients exhibited significantly shorter average telomere lengths (mean ± std: 4.85 ± 1.58 kb; 4.39 ± 1.09 kb) than T-cells
from ZAP-70-CD38- CLL patients (6.64 ± 1.72 kb, p <2.2 x 10-4 ;
6.22 ± 1.5 kb, p <7.4 x 10-6 ). These results are in line with the
observed higher absolute T-cell numbers in the ZAP-70+CD38+ CLL
patients compared to ZAP-70-CD38- CLL patients (3817 ± 3828/µl
vs. 1549 ± 441/µl). When we compared the telomere length to healthy
individuals (n >400, age: 0–102) practically all telomere length values
of the naive and memory T-cells from the ZAP-70+CD38+ CLL
patients fell below the 50th percentile, whereas the values of naive
and memory T-cells from the ZAP-70-CD38- CLL patients were within
the normal distribution.
Conclusions: We can confirm significantly shorter telomere length
values for the B-cells of the ZAP-70+CD38+ CLL patients. In addition,
we can also demonstrate significantly shorter telomeres in T-cells of
ZAP-70+CD38+ CLL patients, which are below the 50th percentile
compared to controls. Our observations imply an extensive expansion of the T-cell compartment in ZAP-70+CD38+ CLL patients and
suggest an important role of T-cells in this subgroup of CLL patients.
S44
Outcome of chronic myeloid leukemia patients with allogeneic
hematopoietic stem cell transplantation and a low risk score in
the imatinib era. A report from the EBMT Chronic Leukemia
Working Party and the European Leukemia Net
Heim D., Brand R., Olavarria E., Apperley J., Crawley C., Devergie A.,
Aljurf M., Holowiecki J., Ruutu T., Brinch L., Kolb H., de Witte T.,
Hehlmann R., Gratwohl A. (Basel, Leiden, London, Cambridge, Paris,
Riyahd, Katowice, Helsinki, Oslo, Munich, Nijmegen, Mannheim)
Allogeneic hematopoietic stem cell transplantation (HSCT) as first line
therapy for patients with chronic myeloid leukaemia (CML) has been
replaced by imatinib. The role as second line therapy in patients who
failed imatinib treatment is a matter of debate. Second generation
Tyrosine Kinase Inhibitors (TKI) have already proven their efficacy in
this setting. Early transplant related mortality of allogeneic HSCT is
considered to be too high. However, no outcome data on recently
transplanted CML patients has been published. In order to better
counsel patients with a HLA-identical sibling confronted with this
situation we performed a retrospective analysis of transplants
reported to the EBMT between 2002 and 2005. We selected for
patients who had a low risk score for transplant related mortality and
who were transplanted from an HLA identical sibling. We analysed the
outcome of those only who were transplanted in 1st chronic phase
and who received best current treatment, defined as standard conditioning, no T-cell depletion and bone marrow as stem cell source. 214
patients (8% of all 2737 patients transplanted for CML in this time
period) with a median follow up of 12 months (0–60 months) who
fulfilled these criteria were identified. They were 46% males and 54%
females with a medium age of 31 years (range 6 to 59 years). 21%
(46 patients) were less than 20 years old and 20% were above the
Forum Med Suisse 2008;8:(Suppl. 40)
15 S
age of 40. The time interval from diagnosis to transplantation was
less than 1 year in 86% of patients. About one third each had an
EBMT risk score 0, 1 or 2. Data were obtained from 81 teams in 33
countries. The probability of survival at 5 years in a competing risk
model was 88% (95% c.i. 83-93) with a cumulative incidence of
death without relapse of 10% at 14 months and no additional death
from transplant related mortality thereafter until 60 months of followup (Figure 1). 5-years post HSCT, 27% of patients were estimated to
be alive after relapse (and hence the relapse free survival was 61%).
These results show the current transplant outcome which is achievable by selecting only patients with a low risk for transplant related
mortality. In this context, the data shown is valid even without information on pre- and/or posttransplant therapy. Allogeneic HSCT is a
valuable option as second line therapy after imatinib failure for CML
patients with a low transplantation risk.
Figure 1
S45
Impact of H-Y as a minor histocompatibility antigen in kidney
transplantation
Gratwohl A., Döhler B., Stern M., Opelz G. (Basel, Heidelberg)
Background: A higher risk of graft-versus-host disease in male recipients of female grafts, an increased risk of rejection of male grafts in
female recipients, and specific T-cell and antibody reactivity against
H-Y encoded gene products have been documented in haematopoietic stem cell transplantation. In kidney transplantation, in contrast,
the role of H-Y as a minor histocompatibility antigen has been disputed.
Patients and methods: We investigated the probability of graft survival in 202,304 recipients of a deceased donor allograft transplanted
between 1985 and 2004. Using multivariate statistical methods, we
compared 1- and 10-year graft survival rates of female or male donor
kidneys in female or male recipients.
Results: Multivariate analysis revealed complex gender influences:
female gender of donors was identified as a significant factor of graft
loss (p <0.001) on both time periods. Female gender of recipients was
associated with a decreased graft failure rate during the period from
2–10 years (p <0.001). Compared with all other gender combinations,
male donor kidneys transplanted into female recipients was associated with a significantly increased risk of graft failure during the first
year (hazard ratio HR = 1.07, 95% confidence interval CI 1.03–1.12,
p = 0.002; death censored: HR = 1.10, CI 1.04–1.16, p <0.001) as well
as during the years 2–10 (HR = 1.07, CI 1.02–1.11, p = 0.001; death
censored: HR = 1.10, CI 1.05–1.16, p <0.001).
Conclusions: These findings provide the missing link between
haematopoietic stem cell transplantation and solid organ transplantation. They are indicative of a significant HY effect in clinical kidney
transplantation. They confirm the role of HY as a clinically relevant
minor histocompatibility antigen in organ transplantation, solid organ
and hematopoietic stem cell transplantation, in general. They provide
an argument for more close cooperation between solid organ transplant physicians and hematologists as it is pllend with the Swiss
Transplant Cohort Study.
C O M M U N I C AT I O N S L I B R E S S S H é
FREIE MITTEILUNGEN SGH
Forum Med Suisse 2008;8:(Suppl. 40)
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S46
S47
Severe donor events after allogeneic hematopoietic stem cell
donation
Halter J., Kodera Y., Urbano Ispizua A., Greinix H.T., Schmitz N., Favre
G., Baldomero H., Niederwieser D., Apperley J.F., Gratwohl A. (Basel,
Nagoya, Sevilla, Wien, Hamburg, Leipzig, London, Basel for the EBMT
activity survey office)
Background: The risk for donors of allogeneic hematopoietic stem
cells (HSC) is generally considered negligible. Scattered reports of
severe complications and a recent controversy on hematopoietic
malignancies after GCSF administration for peripheral stem cell donation have challenged this opinion.
Methods: In two consecutive retrospective surveys conducted in
2003 and 2006, 338 allogeneic transplant teams from 38 European
countries were asked to report their donor deaths, severe adverse
events (SAE’s) and hematological malignancies in a donor.
Findings: 262/338 teams (77.5%) responded to the first survey
(1993–2002) and 169/262 (65%) teams to the second one
(2003–2005). They performed a total of 51’024 first allogeneic
hematopoietic stem cell transplantations (HSCT), 27’770 bone marrow (BM) and 23’254 peripheral blood (PB) HSCT. They observed five
donor deaths, 1 after BM and 4 after PB donation (incidence 0.98 per
10’000 donations; 95% CI 0.32–2.29), 37 SAE’s (7.25/10’000; 95% CI
5.11–9.99), 12 in BM (4.32/10’000; 95% CI 2.24–7.75) and 25 in PB
donors (10.76/10’000; 95% CI 6.97–15.85; p <0.02). Total observation
time is 300’661 person-years. 20 hematological malignancies, 8 after
BM and 12 after PB donation were reported. Incidence rates for
developing hematological malignancies were 0.40 per 10’000 personyears for BM and 1.20 per 10’000 person-years for PB donation.
Related PB donors are about 10 years older and related and unrelated PB donors have a shorter follow up. This observed incidence
corresponds to the expected incidence in an age and sex adjusted
population (SEER data).
Conclusion: HSC-donation is associated with a small but definite risk
for death and SAE’s. Donors have to be informed even if the risks are
small. Hematological malignancies do occur in BM and PB donors.
There are no indications that these events exceed the risk of a normal
population. The higher event rate in PB donors is likely to be
explained by their higher age. These data underline the need for a
continuous life long standardized donor follow up.
Occurrence of autoimmune diseases before or after severe
aplastic anemia diagnosis. Is there any connection?
Stalder M., Rovó A., Halter J., Heim D., Arber C., Buser A., Meyer
Monard S., Rischewsky J., Stern M., Tichelli A., Gratwohl A. (Basel
Stem Cell Transplant Team)
Acquired aplastic anemia (AA) is considered a T-cell mediated
autoimmune disorder (AID). Its association with other AID has been
described. The link between both types of AID and the impact of the
AA treatment on the concomitant AID remain unclear. We conducted
a retrospective single centre cohort study of 243 patients with severe
AA (SAA) treated between 1974 and 2006 at the University Hospital of
Basel. We looked for other AID, diagnosed before and after SAA, its
prevalence and possible risk factors. Only clinical AID defined
according to international diagnostic criteria were included. Patients
with isolated elevation of antibody titers without further clinical signs
of a disease were not included. Treatment strategy was uniform
throughout the observation period. Patients below the age of 40
years (y) with a matched sibling donor (57 patients, 23%) received
allogeneic hematopoietic stem cell transplantation (HSCT), all others,
186 patients (77%) were treated with antithymocyte globulin (ATG)
with or without Cyclosporin A as primary therapy. Due to refractoriness or relapse, 30% needed further therapies. The median age was
22 y (2-80 y). 115 patients (47%) were female. The median follow up
time was 9.4 y (0–33 y). AID was diagnosed in 24/243 patients (10%),
9 of them (37.5%) were female. Four patients had more than one AID.
Autoimmune gastritis and autoimmune thyroiditis were the most
frequently found AID (6 patients each). Amongst the analyzed factors
for an association with AID (age at diagnosis of SAA, sex, severity of
the AA, presence of HLA-DR15, type of first-line therapy, splenectomy and follow up time) only age showed a significant association.
The median age was 51.5 y (9-75y) in patients with, versus 20 y
(1-80y) (p = 0.00013) in patients without AID. All 13 patients with AID
before SAA were treated with ATG. 2/12 showed remission of both
diseases, AID and SAA; whereas in 10 patients the AID persisted.
Concomitant AID did not impair outcome of SAA. After ATG therapy,
an AID was diagnosed in 11 patients, with a median time to occurrence of 7 y (0.03–27.5y). Two patients developed AID after HSCT, in
both the donors did not have an AID. In conclusion, simultaneous AID
is seen in 10% of patients with SAA. Coincidence is unlikely to be
sufficient explanation. Response to therapy in contrast, is independent and AID can persist despite full remission of SAA. This indicates
that SAA and AID most likely are triggered by independent immune
mechanisms.
C O M M U N I C AT I O N S L I B R E S S S H é
FREIE MITTEILUNGEN SGH
Forum Med Suisse 2008;8:(Suppl. 40)
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S48
S49
Angiogenesis and VEGF-/Receptor expression in
myeloproliferative diseases: correlation with clinical parameters
and JAK2-V617F mutational dtatus
Medinger M., Gratwohl A., Theocharides A., Buser A., Heim D.,
Skoda R., Dirnhofer S., Tichelli A., Tzankov A. (Basel)
Angiogenesis is essential for malignant tumor growth. This has been
documented for solid tumors and there is emerging evidence that
progression of haematological malignancies also depends on the
induction of new blood vessels. The most important pro-angiogenic
factor is vascular endothelial growth factor (VEGF), activating the
VEGF receptor 1 (VEGFR-1) and receptor 2 (VEGFR-2). Therefore
VEGF and its receptors may provide a target for therapy in hematological malignancies. In Bcr-Abl negative myeloproliferative diseases
(MPD) there are only few data about the role of angiogenesis. We
studied 100 patients with MPD, including polycythemia vera (PV),
essential thrombocythemia (ET) and primary myelofibrosis (PMF) by
immunohistochemical assessment of microvessel density (MVD) and
the expression of VEGF and its receptors VEGFR-1, VEGFR-2 and
VEGFR-3 in bone marrow (BM) sections (table 1). The normal controls
(NC) consisted of 10 BM which were free of abnormalities. MVD, as
assessed by CD34 staining, was calculated as the mean number of
stained vessels in 5 fields at 200 magnification. Expression of VEGF/receptors was assessed as mean of the number of positively staining
cells in 5 fields. Our study showed a significantly higher degree of
angiogenesis in PMF, PV and ET compared with NC (table 1;
P <0.001, P <0.0007 and P <0.001, respectively). Angiogenesis was
higher in PMF than PV and ET (P <0.001 and P <0.001). Increased
angiogenesis correlated with higher VEGF expression compared to
NC (P <0.009). VEGFR-2 expression was significantly higher in MPD
than in NC (P <0.001) and, in particular, in PMF (P <0.001) and PV
(P <0.001). There were no significant differences between VEGFR-1
and VEGFR-3 expression compared to NC. MVD and VEGF expression was significantly higher in JAK2-V617F mutation positive MPD
[30 (12-39) vs. 22 (9-31) mean vessels per 1 mm2 field (range);
P <0.001 and 49% (20–65) vs. 32% (19–42) mean %VEGF positive (+)
cells (range); P <0.001] than in negative MPD, but there was no difference regarding VEGF receptors expression. In conclusion, this study
showed increased angiogeneis in MPD patients as expressed by
increased VEGF and VEGFR-2 expression. Patients with the JAK2V617F mutation had a higher MVD and VEGF expression than
patients without the JAK2-V617F mutation. Our data support the
hypothesis of an autocrine VEGF/VEGFR-2 loop in the pathogenesis
of MPD. Inhibition of angiogenesis could constitute a novel strategy
for the treatment of MPD.
Table 1
Targeted disruption of GAS6-Mertk pathway leads to defects
in physiological clearance of expelled nuclei from erythroblasts
by bone marrow macrophages
Kadi L., Burnier L., Sugamele R., Carmeliet P., Lemke G., Earp H.S.,
Matsushima G.K., Schapira M., Angelillo-Scherrer A. (Lausanne,
Leuven [Belgium], La Jolla CA (USA), Chapel Hill NC (USA)
Late in erythropoiesis, nuclei are expelled from erythroblasts and
engulfed by macrophages in the blood island. Expelled nuclei expose
phosphatidylserine (PS), which is used as an “eat me” signal for their
engulfment by macrophages. PS opsonins milk-fat-globule EGF8
(MFG-E8) and GAS6 together with their respective receptors avb5
(and avb3) and Axl/Mertk/Tyro3 are involved in the phagocytosis of
apoptotic cells. Because fetal liver and bone marrow macrophages
do not express MFG-E8, GAS6-Mertk pathway might constitute the
main pathway for the engulfment of nuclei expelled from erythroblasts. To test this hypothesis, we isolated nuclei from splenic latestage erythroblasts and tested the capacity of bone marrow-derived
macrophages (BMDM) from mice deficient in GAS6 (GAS6-/-), Axl
(Axl-/-), Mertk (Mertkkd), Tyro3 (Tyro3-/-) to internalize these nuclei.
Nuclei were obtained after disconnection from reticulocytes by
mechanical shaking and identified by flow cytometry according to
their size and their positive staining for the erythroid lineage marker
Ter119 and Annexin V for PS labelling. Purity of the preparation was
double-checked by morphological examination. BMDM isolated from
wild-type (WT) controls and GAS6-/-, Axl-/-, Mertkkd, Tyro3-/-,
Axl/Tyro3-/-, Axl-/-/Mertkkd mice were incubated with nuclear preparation, washed to remove un-engulfed nuclei, analyzed in bright field
and stained with May-Grünwald-Giemsa. Phagocytosis was determined by counting the number of BMDM with ingested nuclei and the
phagocytosis index revealed the number of engulfed nuclei per
macrophage. We found that GAS6-/- BMDM cleared 30% less nuclei
than WT BMDM (p <0.01). We observe a slight decrease of internalization capacity for Axl-/- BMDM, whereas Tyro3-/- BMDM engulfed
the nuclei as efficiently as WT BMDM. In contrast, Mertk deficiency
nearly abolished nuclei phagocytosis (p <0.001). Axl/Tyro3-/- and
Axl-/-/Mertkkd BMDM were tested in comparison with WT BMDM
and single knockouts, and did not show any cumulative effects when
compared to single knockouts. Thus, Mertk was critical for the
phagocytosis of nuclei from erythroblasts whereas the role of Axl and
Tyro3 appeared to be negligible. In conclusion, GAS6 and Mertk are
involved in late erythropoiesis when nuclei are expelled from the
erythroblasts and engulfed by BMDM in the blood island. Indeed,
GAS6 binding to nuclei exposing PS on their surface might form a
bridge between PS and Mertk on BMDM, allowing their efficient
clearance.
S50
The effect of DDAVP on platelet function: Enhancement
of procoagulant COAT platelet formation
Conte T., Pavicic M., Barizzi G., Lämmle B., Keller P., Alberio L. (Bern)
Introduction: Desmopressin (DDAVP) is clinically efficacious in
patients with disorders of the platelet function. This effect might be
mediated by the release of von Willebrand factor (VWF) from
endothelial cells. However, the documented efficacy of DDAVP in
patients with Bernard-Soulier syndrome who lack the GPIb-IX-V
complex (the platelet receptor for VWF) suggests that other mechanisms may be involved.
Methods: We investigated platelet function by flow-cytometry in
6 patients with a bleeding diathesis who received a test dose of
DDAVP (0.3 mg/kg body weight). Following phenotypic and functional
platelet characteristics were studied (at baseline and 2 hours after
DDAVP): 1) Surface glycoprotein (GP) Ib and GPIIb-IIIa (fibrinogen
receptor). 2) Content of delta-granules and their secretion upon
platelet activation by thrombin (T). 3) Secretion of alpha-granules
and GPIIb-IIIa activation by graded concentrations of ADP, convulxin
(CVX, a specific agonist of the collagen receptor GPVI), or T. 4)
Generation of procoagulant COAT platelets induced by combined
activation with CVX and T (Blood 2000;95:1694).
Results: 1) Surface-expression of GPIb increased by 8.5% (median),
GPIIb-IIIa did not change. 2) Delta-granules content decreased by
2.2% and their T-induced secretion increased by 6.3%. 3) Secretion
of alpha-granules and GPIIb-IIIa activation by ADP decreased by
26.7% and 19.5% respectively; both end-points induced by CVX
decreased by 29.0% and 8.3%; secretion of alpha-granules induced
by T decreased by 13.7% and GPIIb-IIIa activation increased by
C O M M U N I C AT I O N S L I B R E S S S H é
FREIE MITTEILUNGEN SGH
2.2%. 4) Percentage of generated COAT platelets increased by
45.2% and the intensity of negatively charged phospholipids
expressed on their surface increased by 35.0%.
Conclusion: We show that DDAVP selectively and markedly
enhances the ability to form COAT platelets. Therefore, the beneficial
haemostatic effect of DDAVP is not limited to an increase in large
VWF multimers; an increased platelet procoagulant activity appears
to be an additional and – at least in platelet disorders – possibly more
important mechanism.
S51
Dosing lepirudin in patients with heparin-induced
thrombocytopenia and various degrees of renal function
impairment
Tschudi M., Lämmle B., Alberio L. (Bern)
Introduction: Heparin-induced thrombocytopenia (HIT) is a severe
prothrombotic complication of heparin treatment. Lepirudin is a direct
thrombin inhibitor approved for its treatment. Late in 2000 we
observed that patients receiving the recommended doses of lepirudin
were over-anticoagulated.
Methods: Starting in 2001 we treated 51 consecutive patients diagnosed with HIT administering lepirudin without initial bolus and reducing the recommended dose by 1/3. In addition, lepirudin dose was
further adjusted according to the calculated creatinine clearance
(CCL). The intensity of anticoagulation was monitored with thrombin
times (TT) and aPTT, its efficacy was assessed with measurements
of the platelet count (PC) and D-dimers (DD).
Results: Patients with a normal renal function (CCL >60 ml/min)
which had TT within the therapeutic range at first monitoring 4 hours
after lepirudin start (15/29) received a median lepirudin dose of 0.087
mg/kg/h. The efficacy of this treatment was documented by a median
aPTT-prolongation of 2.03 times at first control, by a PC increase from
median 75 G/l at d0 to 115 G/l (d1), 137 G/l (d3), 232 G/l (d5) and by a
decrease of DD from median 4599 µg/l at day 0 to 1810 µ-g/ml at
follow-up. Patients with a moderately impaired renal function (CCL
30–60 ml/min) which had therapeutic TT at first monitoring (5/15)
received a median lepirudin dose of 0.040 mg/kg/h. The efficacy of
this treatment was documented by a median aPTT-prolongation of
2.09 times, by a PC increase from median 52 G/l (d0) to 93 G/l (d1),
164 G/l (d3), 204 G/l (d5) and by a decrease of DD from median 3634
µ-g/l to 1540 µ-g/ml. Patients with a severely impaired renal function
(CCL <30 ml/min) which had therapeutic TT (6/7) received a median
lepirudin dose of 0.012 mg/kg/h. The efficacy of this treatment was
documented by a median aPTT-prolongation of 2.11 times, by a PC
increase from median 54 G/l (d0) to 74 G/l (d3), 173 G/l (d5) and by a
decrease of DD from median 2508 µ-g/l to 1568 µ-g/ml.
Conclusion: The reported data confirm that the recommended
dosage schedule for lepirudin is to high. According to our experience,
it is safe to avoid the initial bolus and to administer about 0.08
mg/kg/h to patients with normal renal function, about 0.04 mg/kg/h
for those with moderate impairment and about 0.01 mg/kg/h for
those with severe impairment of renal function.
S52
Increased variation in the autoantigen ADAMTS13 is associated
with the development of pathogenic autoantibodies in acute
acquired TTP
Meyer S.C., Largiadèr C.R., Jin S., Zheng X.L., Dahinden C.A.,
George J.N., Lämmle B., Kremer Hovinga J.A. (Bern, Philadelphia,
Oklahoma City)
Background: Acquired thrombotic thrombocytopenic purpura (TTP)
is an autoimmune disorder caused by autoantibodies against
ADAMTS13, the protease regulating von Willebrand factor multimeric
size. The syndrome is characterized by life-threatening microvascular
thrombosis. Acquired TTP represents an excellent human disease
model to investigate the characteristics of a single autoantigen which
contribute to the development of an autoimmune response. Therefore, we searched for particularities in the ADAMTS13 autoantigen in
patients with acquired TTP.
Forum Med Suisse 2008;8:(Suppl. 40)
18 S
Methods: We analyzed the ADAMTS13 gene in 37 patients with
acute TTP and acquired severe ADAMTS13 deficiency, and in 60
healthy controls. Furthermore, 15 short tandem repeats (STR) not
linked to the ADAMTS13 gene were analyzed. ADAMTS13 haplotypes
were identified based on genotypic data of 25 ADAMTS13 polymorphisms. The inter-allelic variation was assessed by counting the
heterozygous positions for 25 ADAMTS13 polymorphisms and 15
STR loci separately. ADAMTS13 mutations were expressed in COS-7
cells and studied for their effect on biosynthesis, secretion and proteolytic activity.
Results: 4 patients were identified as heterozygous carriers of
ADAMTS13 missense mutations P457L, found twice, R1096H and
A1145T. Expression studies revealed intact secretion of mutant
ADAMTS13 in comparison to wild-type protease. Activity of P457L
and A1145T was reduced to 44% and 11%, respectively, but was
normal for R1096H. A particular ADAMTS13 haplotype (designated
H6) was significantly more frequent in patients (p = 0.0053). Moreover,
ADAMTS13 inter-allelic variation was significantly higher in patients
versus controls (p = 0.012). Primarily, non-synonymous SNPs contributed to this phenomenon (p = 0.0014). Increased inter-allelic variation was restricted to and specific for the ADAMTS13 gene, as interallelic variation at 15 neutral STR loci was not different between
patients and controls.
Conclusions: Heterozygous ADAMTS13 mutations are prevalent in
patients with acquired TTP. P457L, R1096H and A1145T either
reduce baseline ADAMTS13 activity and / or may promote autoantibody formation. The ADAMTS13 haplotype H6 and particularly the
increased inter-allelic variation represent risk factors for ADAMTS13
autoimmunity and acute acquired TTP. As autoantigens in general
contain higher numbers of SNPs, increased inter-allelic variation may
represent an important pathophysiological feature also in other
autoimmune disorders.
S53
Healthy blood donors with a positive Coombs test: Naturally
occurring anti-C3 and framework-specific, anti-idiotypic
antibodies together lower complement dependent phagocytosis
of the senescent red cells and thereby prolong their in vivo life
span
Lutz H.U., Frey B.M., Stammler P., Kradolfer M., Alaia V. (Zürich)
Coombs-positive red blood cells (RBC) from healthy blood donors
carry elevated numbers of IgG molecules, as is known for many years
(for a review see: Garratty. Gerontology. 1991;37:68–94). The majority
of IgG molecules was associated with dense RBC from Coombspositive healthy blood donors. These blood donors had more dense
RBC than aged-matched controls and some of their RBC were even
denser than the densest cells of controls. Their densest cells were in
fact older than the oldest cells of controls based on the band 4.1a/b
ratio. Phagocytosis of senescent RBC from these donors was 1.5 to 2
fold higher than that of senescent control cells, implying that
Coombs-positive old RBC carried more opsonins. In contrast to this,
their old RBC were less efficiently phagocytosed than senescent
control cells in an in vitro assay in which FcR-mediated phagocytosis
was suppressed by physiological concentrations of whole human
IgG. The additional IgG molecules on Coombs-positive RBC from
healthy blood donors comprised anti-C3 and framework-specific antiidiotypic naturally occurring antibodies (NAbs), which were elevated
in plasma of these blood donors. Hence, binding of anti-C3 together
with framework-specific anti-idiotypic NAbs to senescent RBC may
have suppressed their complement-dependent phagocytosis and
prolonged their in vivo life span. Suppression of complementdependent phagocytosis was achieved by binding of this pair of
NAbs to senescent RBC via two possible modes: 1) by binding to
senescent cell-associated anti-band 3 NAbs (Lutz, Fasler, Stammler,
Bussolino, and Arese. Blood Cells 1988;14:175–195), which otherwise would have preferentially captured C3b (Lutz, Stammler, and
Fasler. J. Biol.Chem. 1993;268:17418–17426), and 2) by binding to
otherwise cell-associated C3 fragments.
C O M M U N I C AT I O N S L I B R E S S S H é
FREIE MITTEILUNGEN SGH
S54
Transmigration and trapping of activated human T lymphocytes
in a closed environment under mesenchymal multipotent stromal
cells (MSC) are required for their inhibition in vitro
Kindler V., Granavel C., Suva D., Brouwers N., Passweg J. (Genève)
MSC are post natal stem cells that differentiate into many cell lineages and can control allogenic T lymphocyte (TL) stimulation. Such a
property has been used to inhibit steroid-resistant graft versus host
disease (GVHD) that may occur after allogenic hematopoietic stem
cell transplantation (HSCT). Recently we showed that MSC-driven
inhibition was associated, in vitro, with TL transmigration through the
MSC layer (J Cell Physiol ahead pub, sept 2007). We further investigated this issue to assess whether other mechanisms were involved
in TL inhibition. CFSE-labeled, highly purified TL were seeded over
allogenic MSC previously plated in regular 24-well plates, or in chambers whose basement consisted in 0.2 or 3.0-micron pore-sized
membranes (mm), in presence or absence of TL mitogens (PHA+IL-2,
anti-CD3 and -CD28 mAb immobilized on beads). TL proliferation
was assessed after 5 days by monitoring CFSE dilution. In coculture
with 3-mm, TL migrated from 48 hours on through the MSC layer and
the membrane. After 5 days of culture with mitogens, TL recovered in
the lower chamber had significantly proliferated, and were only marginally inhibited by MSC. When 0.4-mm were used, TL did not cross
the membrane and remained tightly associated with MSC, as trypsination was necessary to harvest them. Despite their localization
nearby the MSC, these TL responded efficiently to mitogens, and
were only marginally inhibited by MSC. By contrast duplicate cultures
performed in regular hard plastic-bottomed wells showed that MSC
were fully inhibitory in such a setting. These observations demonstrate that TL inhibition occurs only when transmigration targets TL
under MSC bound to a waterproof surface. When TL transmigrate
under MSC that adhere to a membrane allowing metabolite exchange
(0.4mm), or when TL can run away from MSC after transmigration
(3mm), no significant inhibition ensues. This suggests that TL have to
be sequestrated for at least 48 hours in a hermetically sealed volume
under MSC in order to be inhibited. This is consistent with the observation that MSC induce TL inhibition via the activation of the intracellular enzyme indoleamine 2,3 oxygenase that metabolizes L-tryptophan. Small sealed volumes under – or engulfed in – MSC certainly
represent a privileged environment to induce efficient L-tryptophan
depletion and LT inhibition. These data suggest that infused MSC
may transiently build up a similar microenvironment to inhibit GVHD
in leukemic patients.
S55
CLLU1 expression distinguishes chronic lymphocytic leukemia
from other lymphoproliferative disorders
Oppliger Leibundgut E., Dissler D., de Beer D., Schuller J., Röth A.,
Baerlocher G.M. (Bern, Essen)
Distinction of chronic lymphocytic leukemia (CLL) from other lymphoproliferative disorders, especially from leukemic forms of mantle cell
or marginal cell lymphoma, can be a challenge, and the correct diagnosis has important prognostic and therapeutic implications.
Recently, the novel gene CLLU1 has been shown to be exclusively
upregulated in CLL cells, and its expression has prognostic significance in CLL. We aimed to assess the specificity and sensitivity of
CLLU1 expression and its utility to distinguish CLL from other B-cell
lymphoproliferative disorders. CLLU1 expression was measured by
quantitative RT-PCR in a total of 96 patients with lymphoproliferative
disorders including CLL (n = 71), mantle cell lymphoma (n = 14),
diffuse large B-cell lymphoma (n = 5), follicular lymphoma (n = 5) and
marginal cell lymphoma (n = 1). Based on the CLLU1 expression of
healthy controls (n = 17), a range for normal expression was defined.
Overexpression of CLLU1 was observed in 60/71 cases of CLL
(85%). 15% of CLL cases and 32% of lymphomas exhibited CLLU1
expression within the normal range. Interestingly, in the majority of
the lymphoma patients (17/25), no CLLU1 expression was detectable.
Our results demonstrate a specific expression pattern of CLLU1 in
lymphoproliferative disorders: CLLU1 was high in patients with CLL
(Median: 185.2, range: 0.08-18879), low in patients with non-Hodgkin
lymphoma (Median: 0.0001, range: <0.0001–8.7) and intermediate in
healthy controls (Median: 0.53, range: 0.02-3.2). All three groups
differed significantly from each other (p <0.01). CLLU1 overexpression was highly specific for CLL (specificity = 0.96, positive predictive
value = 0.98), whereas absent CLLU1 expression was highly predictive for non-Hodgkin lymphoma (specificity = 1, positive predictive
value = 1). Clinically, high CLLU1 expression has been shown to
identify patients with an unfavorable disease. In our cohort of CLL
Forum Med Suisse 2008;8:(Suppl. 40)
19 S
patients, high CLLU1 was significantly associated with bad prognostic markers such as unmutated IgVH (p <0.01), CD38, ZAP70,
del(17p) and del(11q), confirming the prognostic value of this marker.
We conclude that CLLU1 overexpression is highly specific for CLL,
and lack of CLLU1 expression is significantly associated with nonHodgkin lymphomas. Analysis of CLLU1 expression by RT-PCR is a
simple novel diagnostic tool that enables distinction of CLL from
other lymphoproliferative disorders, especially in cases where known
diagnostic parameters fail to establish the diagnosis.
S56
Expression of cyclin A in childhood acute lymphoblastic leukemia
cells reveals no evidence for a disturbed G1/S phase transition
and passage through S phase
Hirt A., Schmid A.-M., Julmy F., Leibundgut K. (Bern)
Acute lymphoblastic leukemia (ALL) of childhood is characterized by
a loss of cell differentiation with retained proliferative activity. The
majority of ALL cells reside in the G1 phase of the cell cycle and
express a hyperphosporylated form of the retinoblastoma protein
(Rb). This suggested a position in late G1 phase at or beyond the
restriction point resulting in a commitment to mitosis and an unresponsiveness to differentiation-inducing agents. Cells in late G1
phase should be prepared to enter S phase and, therefore, the
assessment of cyclin A expression starting at the G1-S phase transition was of interest. Expression of cyclin A in ALL cells was tightly
correlated with the percentage of cells in S phase as determined by
bromo-deoxy-uridine (BrdU) incorporation (r = 0.981; p <0.0001).
Flow cytometric analyses of ALL cells stained with a fluorescent anticylin A anibody confirmed that positive cells had a higher than modal
DNA content. To corroborate these findings smears were simultaneously stained for cyclin A expression and BrdU incorporation. Of all
BrdU-positive S phase cells, 97.2 ± 1.4% (mean ± 1SD) were positive
for cyclin A, compared with only 1.1 ± 0.5% cyclin A expressing cells
in the non-S phase cell population (G0/G1 or G2). Of all cyclin
A-positive cells, 10.3 ± 3.2% were not in S phase and by morphology
corresponded to large blast cells, assumed to be in G2 phase.
Together with the flow cytometric analyses these results confirmed
that cyclin A expression in ALL cell populations was restricted to S
and G2 phase cells and that there was no evidence of a disturbed
expression of cyclin A in ALL cells entering and progressing through
S phase. It can be concluded that the accumulation of ALL cells in G1
phase is not the result of a disturbed G1-S phase transition. Taking
into consideration the changed substrate specificity of cyclin
D/cdk4,6 kinase in ALL cells described earlier, hyperphoshorylation
with a partial inactivation of Rb functions could occur already in mid
G1 phase resulting in a loss of differentiation but not yet in a commitment to mitosis.
S57
Blocking the tumor suppressor Hypermethylated In Cancer 1
(HIC1) impairs neutrophil development and its low expression
in AML is not due to hypermethylation
Jenal M., Britschgi C., Britschgi A., Torbett B.E., Tobler A., Fey M.F.,
Tschan M.P. (Bern, La Jolla)
A hallmark of acute myeloid leukemia (AML) is a block in differentiation caused by deregulated gene expression. HIC1 is a transcriptional
repressor, which is epigenetically silenced in solid cancers. We found
HIC1 mRNA expression to be significantly low in 128 patient samples
of AML and CD34+ progenitor cells when compared to terminally
differentiated granulocytes. Furthermore, HIC1 mRNA was induced in
a patient with t(15;17)-positive acute promyelocytic leukemia (APL)
receiving all-trans retinoic acid (ATRA) therapy. We therefore asked
whether HIC1 plays a role in granulocytic differentiation and whether
HIC1 loss-of-function might contribute to the differentiation block in
AML. We evaluated HIC1 mRNA levels in NB4, HL-60 and U-937 cells
upon ATRA-induced differentiation and in CD34+ progenitor cells after
G-CSF-induced differentiation. In all models of granulocytic differentiation we observed significant HIC1 induction. When HIC1 mRNA was
suppressed in HL-60 cells using stably expressed short hairpin RNA
targeting HIC1, granulocytic differentiation was altered as assessed
by CD11b expression. Bisulphite sequencing of CpG islands in the
HIC1 promoter provided evidence that the observed suppression in
HL-60 and NB4 cells is not due to promoter hypermethylation. This
may shed some light on earlier, controversial reports about epigenetic
silencing of HIC1 in myeloid leukemias. Generally, our findings point
to a role for the tumor suppressor gene HIC1 in granulocytic differen-
C O M M U N I C AT I O N S L I B R E S S S H é
FREIE MITTEILUNGEN SGH
tiation. Low expression of HIC1 may very well contribute to pathogenic events in leukemogenesis. We are currently investigating alternative silencing mechanism of HIC1 in AML.
Forum Med Suisse 2008;8:(Suppl. 40)
20 S
platform. Our work so far suggests that MN1 is overexpressed in a
significant fraction of childhood acute leukemia and that MN1 expression plays a role for the biology of the leukemic clone as cooperating
oncogene presumably by mediating aberrant self-renewal properties
through a distinct yet to be determined gene expression program.
S58
Green tea extract EGCG causes cell death in myeloid leukemic
cells and enhances ATRA-induced differentiation through
upregulation of DAPK2
Britschgi A., Fey M.F., Tobler A., Tschan M.P. (Bern)
Epigallocatechin-3-gallate (EGCG), the main polyphenolic compound
present in green tea, has been reported to have chemopreventive and
chemotherapeutic effects in different malignancies. EGCG inhibits cell
growth and induces apoptosis in cancer cells without adversely
affecting normal cells. Moreover, EGCG has recently been shown to
upregulate the death-associated protein kinase 2 (DAPK2) in multiple
myeloma cells. We have previously identified this pro-apoptotic
kinase as an enhancing factor during granulocytic differentiation and
as an important cell death mediator in epithelial cancer cells. Thus,
we were wondering whether EGCG might also cause cell death via
DAPK2 in myeloid leukemic blast cells. We found that EGCG treatment of myeloid leukemic blasts led to a dose-dependent increase of
DAPK2 mRNA and protein. This increase was accompanied by 75%
cell death as measured by XTT assay and by a 4.5-fold induction of
caspase3/7 activity. Knocking down DAPK2 in NB4 and HL60 acute
myeloid leukemic (AML) cell lines significantly protected the cells from
EGCG-induced cell death. Since we previously observed enhanced
differentiation of NB4 blasts in response to all-trans retinoic acid
(ATRA) when DAPK2 is ectopically expressed, we were asking if
EGCG treatment might support ATRA-induced differentiation by
further increasing endogenous DAPK2 levels. Indeed, combination
treatment of ATRA and EGCG dose-dependently enhanced neutrophil
differentiation compared to ATRA-treatment alone, as assessed by
CD11b, CD15, G-CSF-R and C/EBPÂ expression using FACS and
quantitative RT-PCR analysis. Further, knocking down DAPK2 in
these cells significantly reversed enhanced differentiation. Additionally, we found that EGCG induces cell death in ATRA-resistant NB4
and HL60 cells. In summary, we show that EGCG efficiently kills
leukemic blast cells via DAPK2. Moreover, EGCG enhances ATRAinduced differentiation in AML blasts most likely by killing ATRAresistant cell populations. Currently, we are investigating whether
EGCG-induced killing of ATRA-resistant cells is dependent on
expression of the “green tea receptor” 67 kD laminin receptor 1 present on these cells. We conclude that application of catechins such as
EGCG, may help to optimize current chemotherapeutic treatment
protocols for acute promyelocytic leukemia.
S60
The unfolded protein response is activated in AML and induces
the RNA-binding protein calreticulin
Schardt J.A., Eyholzer M., Häfliger S., Helbling D., Fey M.F.,
Mueller B.U., Pabst T. (Bern)
Deregulation of the myeloid key transcription factor CEBPA is a common event in AML patients. We previously reported that the RNA
binding protein calreticulin efficiently blocks CEBPA translation and
that calreticulin is specifically induced in core binding factor (CBF)
leukemias. In addition, the chaperone calreticulin is a crucial component of the unfolded protein response (UPR). The UPR is triggered by
the accumulation of unfolded or misfolded proteins within the endoplasmatic reticulum (ER) leading to ER-stress. It includes the induction of chaperon genes promoting protein folding and induction of the
ER-associated degradation (ERAD) system. In vitro studies suggest
that the UPR is activated in various types of cancer and thereby
involved in tumor development. However, the role of the UPR during
leukemogenesis has not been addressed so far. Here, we determined
by RT-PCR and Western blot analysis the expression of key members
of the UPR in the ER such as calreticulin, GRP78, and Gadd153, as
well as the induction of the XBP1 spliced variant (XBP1s) in leukemic
cells at diagnosis from 100 consecutive AML patients of all subtypes.
We found that the members of the UPR were induced in 18 of 100
patients (18%). AML patients with activated UPR had lower white
blood cell count (8.2 vs. 23.9 G/L), less blasts in peripheral blood
(46% vs. 72%), were more frequently evolving from MDS (16.5% vs.
3.5%), and were rarely detected in monocytic (M4/5) subtypes of
leukemia (5.5% vs. 30%) as compared to AML patients with uninduced UPR. Remarkably, the relapse rate at two years was significantly lower in AML patients with activated UPR (28% vs. 45%). At
the molecular level, we identified two complex elements in the calreticulin promoter mediating sensitivity to ER stress. In particular, activation of both elements through the ATF6 pathway cooperating with
additional partner proteins appeared to be crucial for calreticulin
induction in myeloid cells. Taken together, these results provide evidence that the UPR is activated in a subset of AML patients. Induction of calreticulin as a key effector of the UPR is mediated through
activation of the ATF6 pathway, thereby ultimately suppressing
CEBPA translation and thus leading to a block in differentiation during
leukemogenesis.
S59
S61
Meningeoma 1 (MN1) in childhood acute myeloid leukemia
Liu T., Jankovic D., Ehret D., Baty F., Rossi V., Biondi A., Schwaller J.
(Basel, Monza)
Fusion genes involving the MLL1 gene such as MLL/ENL or MLL/AF4
resulting from t(11;19) or t(4;11) are frequent genetic alterations in
childhood acute leukaemia. Retroviral expression of MLL/ENL in the
murine bone marrow induces an acute leukaemia phenotype that
strongly mimics the human phenotype. Retroviral integration site
analysis demonstrated deregulation of Meningeoma 1 (MN1) expression in a mouse with acute leukaemia induced by MLL/ENL. Expression of MN1 in murine bone marrow mediates aberrant self-renewal
capacity as demonstrated by serial replating assays. Transplantation
of bone marrow cells expressing MN1 induced an acute myeloid
leukaemia (AML)-like disease in mice after 3 months. Co-expression
of MN1 with MLL/ENL significantly reduced the latency to develop a
clonal AML-like disease within 30 days demonstrating functional
cooperation in leukemogenesis. In order to analyze the role of MN1 in
human leukaemia we determined MN1 expression by Q-PCR in a
cohort of childhood acute leukaemia. Elevated MN1 expression (>2x
over normal bone marrow) was found in 6/14 cases of pediatric AML.
Interestingly, 9 of 10 infant leukaemias carrying MLL-X translocations
showed high levels of MN1 expression. In order to study the role of
MN1 in leukaemic transformation, we have identified human cell lines
carrying MLL-X fusion genes that express high levels of MN1. Knockdown of MN1 expression in RS4;11 and MOLM-13 cells (MLL-Xpositive AML) by lentivirally delivered specific siRNAs (or scramble
siRNAs) reduced cellular proliferation and clonal expansion. As MN1
has been previously proposed to exert its function through aberrant
transcription, we are currently comparing putative downstream targets in i) murine bone marrow transiently overexpressing MN1, ii)
leukemic blasts induced by MN1 and iii) leukemic blasts expressing
MN1 and MLL/ENL by gene expression profiling using an Affymetrix
A distal single nucleotide polymorphism dysregulates
NF-kappaB mediated activation of the myeloid key transcription
factor PU.1 in AML patients
Bonadies N., Fos J., Neururer C., Fey M.F., Pabst T.,
Mueller B.U. (Bern)
Timely regulation of the key transcription factor PU.1 is crucial for
normal hematopoiesis. We previously showed that PU.1 expression
is specifically suppressed in AML-M3 patients and restored after
retinoic acid treatment. In addition, targeted disruption of an
upstream regulatory element (URE) located 15 kb upstream in the
PU.1 promoter was reported to decrease PU.1 expression by 80%
and lead to AML in mice. Here, we screened AML patients for mutations in the entire upstream regulatory element of PU.1 by direct
sequencing. We detected two polymorphisms in 4 out of 120 AML
patients (3.3%) and in 1 out of 141 healthy volunteers (0.7%). Both
polymorphisms were localized within 10 bp in the distal homology
region of the URE. In this region we identified a NF-kappaB binding
site. We found that NF-kappaB p50/p65 heterodimers and p50/p50
homodimers were indeed binding to this site, and that NF-kappaB
p50/p65 activated PU.1 expression through this site in the URE.
Remarkably, NF-kappaB mediated activation was abolished by the
polymorphisms detected in AML patients. Furthermore, NF-kappaB
synergistically activated PU.1 together with CEBPbeta whereas this
synergy was lost in the presence of the polymorphisms. Finally, AML
patients with the polymorphic NF-kappaB sequence showed suppressed PU.1 mRNA expression. Our results demonstrate that NFkappaB mediated activation of PU.1 is deregulated by
polymorphisms in the URE of PU.1, which are more frequent in AML
patients than in healthy individuals. Moreover, our study suggests that
an insertion of a single base pair in a distal element critically affects
the regulation of a tumor suppressor gene and thus the development
of cancer.
PRIX SCIENTIFIQUES SSHé 2008
WISSENSCHAFTLICHE PREISE SGH 2008
Forum Med Suisse 2008;8:(Suppl. 40)
21 S
SGH1
SGH2
Homozygous ADAMTS13 mutations in the C-terminal
protease domains severely affect protein secretion
and cause congenital TTP
Meyer S.C., Jin S., Zheng X.L., Lämmle B., Kremer Hovinga J.A.
(Bern, Philadelphia)
Background: Thrombotic thrombocytopenic purpura (TTP) is a
devastating syndrome characterized by occlusive thrombosis in the
microcirculation. Severe deficiency of ADAMTS13 proteolytic activity
results in persistence of thrombogenic ultra-large von Willebrand
factor multimers (ULVWF). Compound heterozygous or homozygous
ADAMTS13 gene mutations cause ADAMTS13 deficiency in congenital TTP. Homozygous mutations are of particular interest in order to
elucidate the correlation of causative ADAMTS13 genotypes and
clinical disease phenotypes.
Methods: We studied 4 ADAMTS13 missense and 1 stop mutation
identified in homozygous form in patients suffering from congenital
TTP. Patients homozygous for W688X, R692C or C804R became
manifest with serious disease in early childhood. In presence of
R1060W, milder courses with adult onset were observed. G1239V
was found with childhood attacks, but led to an attenuated manifestation in adulthood. Recombinant ADAMTS13 mutants were
expressed in COS-7 cells and their impact on protein biosynthesis
and secretion was studied. Proteolytic activity was measured by
FRETS-VWF73 assay. Intracellular localization of mutant ADAMTS13
was determined by immunofluorescent microscopy.
Results: The mutants R692C, C804R, R1060W and G1239V migrated
at 190 kDa like wild-type ADAMTS13, but revealed severely reduced
secretion. The mutant W688X showed a molecular weight of 97 kDa
and was secreted more efficiently than wild-type protease. Immunofluorescent staining showed ADAMTS13 within endoplasmatic reticulum and Golgi apparatus, consistent with the distribution of secretory
proteins. All mutants had a specific activity comparable to wild-type
ADAMTS13, except for the mutant W688X, which showed a severely
reduced activity.
Conclusions: Our data demonstrate that all 5 ADAMTS13 mutations
are causative for congenital ADAMTS13 deficiency. The homozygous
mutations at the C-terminal ADAMTS13 primarily affect secretion of
the protease. However, the truncating mutation impairs enzymatic
activity. Analysis of cleavage activity towards multimeric VWF under
fluid shear stress will provide deeper insight into the functional significance of the C-terminal domains of ADAMTS13 and will further elucidate the role of ADAMTS13 genotypes for the clinical presentation of
congenital TTP.
Premature aging of hematopoietic cells in long term survivors
after HSCT with chronic GVHD and a female donor
Baerlocher G.M., Rovo A., Müller A., Matthey S., Stern M., Halter J.,
Studt J.D., Arber C., Gratwohl A., Tichelli A. (Bern, Basel)
The establishment of donor-derived hematopoiesis in recipients of
hematopoietic stem cell (HSC) transplantation (HSCT) involves extensive proliferation of HSCs and might lead to premature aging of
hematopoietic cells. Telomere shortening as indicator of cell proliferation has been described after HSCT. The telomere attrition has mainly
been observed during the first year after allogeneic HSCT. Thereafter,
telomere length dynamics of recipients appeared not to differ from
their donors. The aim of our cross-sectional study was to evaluate the
telomere attrition in leukocyte subsets of very long term survivors
(LTS) after HSCT in relation to donor/recipient age, sex, cell counts in
peripheral blood, number of transplanted nucleated cells (NTNC), and
occurrence of acute and chronic graft versus host disease (GVHD).
Automated multicolor flow-FISH was used to measure the telomere
length in subsets of leukocytes of 44 LTS and their HLA-identical
sibling donors. At HSCT the median age of donors and recipients was
25.8 (2-46) and 26.8 years (5-50). The median follow-up after HSCT
was 17.5 years (11-26). Four patients received HSCT for aplastic
anemia, 40 for hematological malignancies. All patients received bone
marrow as source of HSC and TBI was part of the conditioning in 39
(89%). Acute GVHD was observed in 31 (70%), and chronic GVHD in
22 (50%) patients. The telomere length (mean std) was significantly
shorter in recipients as compared to their donors (p <0.01) for granulocytes (6.50.9 vs 7.10.9), T-cells (5.71.2 vs 6.61.2), B-cells (7.11.1
vs 7.81.1) and NK/NKT-cells (4.81.0 vs 5.61.3). The mean telomere
length of all subsets of cells was significantly shorter for males compared to females even though this difference was small. Age, sex of
recipient, NTNC, and acute GVHD had no impact on telomere attrition. In all cell types we found a significant telomere shortening in
recipients transplanted with a female donor (p <0.04) and in those
with chronic GVHD (p <0.04). The telomere length difference between
donor/recipient was most pronounced for recipients with the combination of a female donor and chronic GVHD (Figure 1) and is more
than twice compared to those with a male donor without chronic
GVHD. The more pronounced telomere attrition with a female donor
and chronic GVHD corresponds to approximately 30-60 years of cell
aging and raises the question of cellular immuno-senescence and its
consequences in LTS of HSCT.
Figure 1
POSTERS SSMI
POSTERS SGIM
P1
An anthropological study on diabetes and vulnerable populations
Spahr N., Rossi I., Ruiz J., Bodenmann P. (Lausanne)
Background: To address the issue of a chronic condition like diabetes, it could be interesting to integrate a complementary approach
between social and medical sciences. Taking into account the different social situations of patients, the two main objectives were first to
study patient’s perceptions around diabetes and the impact of their
illness on their daily life; and secondly to compare specialists and
general practitioner’s perceptions and their difficulties around diabetes management with these diverse populations.
Methods: This study was an interdisciplinary qualitative research
including 3 weeks of direct observation of the medical consultations,
10 individual face-to-face interviews and 4 focus groups with patients
(5 migrants and 4 natives) and therapists (8 specialists and 8 physicians) of CHUV and PMU to collect information for the thematic
analysis.
Results: Comparing native and migrant populations, we observed
that the initial step of diagnosis has a considerable impact on
patient’s long term adhesion to the medical treatment. Diabetes management is related with lifestyle modifications, migration process and
previous experiences, which have a significant influence on patient’s
compliance. For physicians, serious modifications implied by
diabetes present some major difficulties and have an impact in the
complexity of therapeutic management of this chronic illness: it is in
particular hard to manage enough time to investigate their patient’s
perceptions respecting at the same time guidelines or still to evolve
as guides promoting Diabetes-Self-Management. Compared to
natives, migrants used strangely enough more medical references
than emotional perceptions to explain their illness. Considering all
these different priorities, relationships between patients and medical
staff could be improved.
Discussion: The migration process and the socio-cultural diversity
have an impact on the patient’s perception and the management of
diabetes. In their medical practice, general practitioners have a more
global view to manage their patients but use less the networks of
collaborators than specialists. To improve diabetes management and
prevention, our study suggests to develop a systemic approach to
support a better negotiation between the health professionals and the
patient’s environment and also to encourage the therapeutic education and transcultural competences training on medical education
programs.
P2
Effet du diabète et d’une consultation spécialisée en
Diabétologie sur le management du diabète dans un service
de Médecine Interne
Garcia E., Nguyen S., Comte-Perret S., Gaillard R.C, Waeber G.,
Ruiz J. (Lausanne)
Introduction: Les patients diabétiques sont des sujets à risque de
complications lors d’une hospitalisation. De nombreuses études
montrent que l’hyperglycémie en soi est associée à une morbi-mortalité plus élevée et que son contrôle permet de réduire la mortalité,
la durée de séjour (DS) et les coûts. Le but de l’étude est d’évaluer
l’impact du diabète sur la DS et la morbi-mortalité ainsi que l’effet
d’une consultation spécialisée en diabétologie (CS) sur ces paramètres.
Méthodes: Il s’agit d’une étude d’observation rétrospective portant
sur 800 patients consécutifs admis directement dans le Service de
MI, entre janvier et septembre 2005. Les paramètres suivants ont été
évalués: motifs d’admission, DS, traitements médicaux, contrôles
glycémiques, jour de la CS et morbi-mortalité. Nous avons différencié
les diabétiques connus (DMC) et les diabétiques non diagnostiqués
(DMND), mais répondant aux critères de l’OMS, sur la base d’une
glycémie 011,1 mmol/l pendant le séjour.
Résultats: L’âge médian du collectif est de 74 ans (59–83), 51% sont
des hommes, décès 10%. Les diagnostics principaux sont: affections
respiratoires (21%), insuffisance cardiaque (12%), affections oncologiques (11%), infections (10%). La DS médiane est de 12 jours
(8–17). Le groupe DMC représente le 21% des patients (n = 168), le
groupe DMND 4,5% (n = 36), soit 18% de tous les diabétiques. Le
taux de mortalité est de 9% dans le groupe non diabétique, 11%
chez les DMC, 16% chez les DMND (p = 0,11). Dans le groupe des
DMC ayant eu une CS, le taux de mortalité est de 0% vs 15% sans
CS (p = 0,015). Le groupe DMC ayant eu une CS reste 4,5 jours de
Forum Med Suisse 2008;8:(Suppl. 40)
22 S
plus que celui sans CS (15,5 j vs 11 j, p = 0,0017). Parmi les patients
ayant bénéficié d’une CS dans les 3 premiers jours, on observe
que 75% d’entre eux voient leur séjour significativement diminué
(p = 0,0007). Parmi les DMC, 20% n’ont pas reçu de traitement hypoglycémiant pendant le séjour, malgré un contrôle métabolique altéré.
Conclusions: Cette étude relève une DS plus longue chez les diabétiques. Parmi ces patients, 18% ont été diagnostiqués rétrospectivement. L’absence de CS n’était pas toujours justifiée par une affection
terminale. La mise en place d’un programme structuré de prise en
charge précoce des patients diabétiques en milieu hospitalier pourrait
permettre de réduire la morbi-mortalité, la DS et par conséquent les
coûts liés au diabète.
P3
L’adhérence thérapeutique: première cause de
décompensations diabétiques aiguës
Nguyen S., Waeber G., Schaller M-D., Trueb L., Gaillard R.C.,
Ruiz J. (Lausanne)
Introduction: Les décompensations acido-cétosiques (ACD) et
hyperosmolaires (EHH) sont les complications aiguës parmi les plus
graves du diabète. Ces complications restent associées à des taux
de mortalité élevés (ACD <5%, EHH = 15%). Le but de cette étude
est d’analyser les facteurs déclenchants, les complications intrahospitalières, le traitement, la durée de séjour (DS), la mortalité et
l’impact d’une consultation spécialisée de diabétologie dans le
CHUV.
Patients et méthodes: Il s’agit d’une étude rétrospective de 152
patients admis pour ACD, EHH ou décompensation acido-cétosique
et hyperosmolaire (ACD-EHH) dans le service de Médecine Interne du
CHUV entre 1995 et 2006. Les décompensations ont été définies
selon les critères 2004 de l’ADA, i.e. ACD = glycémie plasmatique
014 mmol/L, pH artériel 97,30 et présence de corps cétoniques sanguins ou urinaires; EHH = glycémie plasmatique 033,3 mmol/L et
osmolalité sérique 0320 mOsm/kg, ACD-EHH = combinaison des
deux.
Résultats: Age médian (p 25–75): 54 ans (37,5–76,5), sexe masculin:
53%; ACD: 62%, EHH: 22%, ACD-EHH: 16%. Principaux facteurs
déclenchants: non adhérence (42%), infections (26%), diabète inaugural (18%), indéterminé (9%), cardiovasculaire (7%). Les patients
non adhérents avaient plus d’ACD que d’EHH ou ACD-EHH (29,7%
vs. 11,9%, OR = 1,71, p = 0,038), tout comme les diabétiques de
type 1 (38,1% vs. 6%, OR = 4,49, p = 0,001). DS médiane: 9 jours
(6–14), les diabétiques de type 2 étant hospitalisés plus longtemps
que les types 1 (12 vs.7 j, p <0,0001). Les patients avec une ACD
avaient une DS médiane plus courte que les autres (7 vs. 10 j,
p = 0,037). Mortalité intra-hospitalière: ACD-EHH = 12,5%, ACD =
8,1%, EHH = 4,6%. Une consultation de diabétologie était associée
à une réduction significative de la mortalité aussi bien en analyse
univariée (4,5% vs. 66,7%, OR = 0,09, p <0,0001), que multivariée
(p <0,0001).
Conclusion: Nous mettons en évidence pour la première fois que
l’adhérence thérapeutique est la cause principale d’ACD, EHH et
ACD-EHH, contrairement à la littérature où prédominaient les infections. L’ACD-EHH avait la mortalité la plus élevée, ce que nous expliquons par le plus grand déséquilibre métabolique existant dans ce
groupe. Une consultation de diabétologie est associée à une diminution importante de la mortalité. Nous recommandons une évaluation
éducative des patients diabétiques, ainsi qu’une consultation de
diabétologie dès leur admission afin de réduire le risque de récidive.
POSTERS SSMI
POSTERS SGIM
P4
Effects of the adrenal function on endothelial integrity and
on the hemostasis system in the perioperative setting
Henzen C., Studer F., Schüpfer G., Bründler J., Briner V., Brander L.
(Luzern, Bern)
Background: The adequate response of the cortisol axis to stress,
i.e. the rapid increase of the adrenal cortisol secretion, is essential to
maintain vascular tone and endothelial function. Furthermore, the
perioperative regulation of the volume balance and the amount of
blood loss correlate with the adequacy of the adrenal function. In the
present study we evaluated the association of the adrenal response
to ACTH and markers of endothelial and hemostatic function in
patients undergoing elective abdominal surgery.
Methods: A low-dose (1 mcg) ACTH test was performed on the day
before surgery, during surgery (30 min after the initiation), on the day
after surgery and before discharge. Patients with a history of glucocorticoid treatment or induction of anesthesia with etomidate,
endocrine diseases and acute illness were excluded. Soluble vascular
cell adhesion molecule-1 (sVCAM-1) and thrombomodulin were
measured as markers of endothelial function. Fibrinogen, von Willebrand factor (vWF), factor VIII and thrombocytes were measured to
evaluate hemostasis. Data are mean (+ SD) and median [interquartile
range] resp., and differences were tested by Student’s t-test and
Mann-Whitney test, resp.
Results: A total of 82 patients (50 M/32 F) were included in the study.
The mean age was 63,8 (15) years, the median length of the operation
and of the intubation were 144 [80–165] mins and 223 [150–290]
mins, resp. The median decrease of the hemoglobin was 24,8 [16,1]
g/l. A deficient adrenal response to ACTH was diagnosed in 24
patients (29%). These patients had increased postoperative levels of
sVCAM-1 (p = 0,033). However, there were no significant differences
in the concentrations of thrombomodulin (p = 0,056), fibrinogen
(p = 0,11), factor VIII (p = 0,6), vWF antigen (p = 0,59), and thrombocytes (p = 0,79) in patients with normal and deficient adrenal function.
The amount of blood loss, infusions of packed red cells and fresh
frozen plasma, and the hemoglobin concentrations before and after
surgery were similar in patients with normal and deficient adrenal
function.
Conclusion: An insufficient rise of plasma cortisol to ACTH is common in patients undergoing elective abdominal surgery. Although
there may be subtle changes in the endothelial function, there were
no effects on the hemostatic system and the clinical outcome in this
defined stress situation.
P5
Treatment with cinacalcet in patients with surgically not
resectable primary hyperparathyroidism
Widmer I., Neidert S., Simon-Vermot I., Henzen C. (Luzern)
Background: Primary hyperparathyroidism (pHPT) leading to hypercalcaemia results from excessive secretion of parathyroid hormone
(PTH), in about 80% of the cases by a single parathyroid adenoma.
However, in some patients pHPT persists after surgery when the
parathyroid adenoma can not be localised or parathyroid hyperplasia
occurs as part of familial endocrinopathies. The calcimimetic agent
cincalcet reduces hypercalcaemia in patients with inoperable
parathyroid carcinoma.
Methods: Our study describes the effect of the treatment with
cinacalcet in patients in whom surgery of pHPT was not successful.
In patients with persistent postoperative hypercalcaemia the following
clinical and laboratory variables were assessed before and under
treatment with cinacalcet: quality of life, psychiatric and
musculosceletal symptoms; serum calcium, phosphorus and PTH
levels, and calciuria. Treatment with cinacalcet aimed to lower the
serum calcium concentration into the normal range. The study was
approved by the local institutional ethics committee.
Results: Our cohort study comprised 5 patients (4 males). The mean
age was 53.8 [30 to 65] years. The mean serum concentration of
calcium before treatment was 3.1 [2.88 to 3.67] mmol/l (normal range
2.1 to 2.7), of posphorus 0.83 [0.69 to 0.98] mmol/l (normal 0.9 to
1.5), of intact PTH 480.1 [53 to 2019] pg/ml (normal 15 to 65), and the
mean urinary calcium excretion was 8.9 mmol/d. Depression was
diagnosed in 3/5 patients, sleeping disturbances in 2/5, muscle
weakness or myalgias in 4/5, arthralgias in 4/5; osteoporosis/
osteopenia in 3/5, pancreatitis in 1/5, and kidney stones in 1/5. The
mean dose of cinacalcet was 144 [60 to 360] mg. The mean serum
calcium concentration under treatment with cinacalcet was 2.73
Forum Med Suisse 2008;8:(Suppl. 40)
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[2.41 to 2.94] mmol/l, the mean PTH 465.5 [48 to 1627] pg/ml.
Psychiatric and musculoskeletal symptoms disappeared apart from
sleeping disturbances in 2/5 and arthralgias in 2/5. Apart from nausea
(1/5) no side effects were recorded.
Conclusion: Treatment with cinacalcet is effective in reducing hypercalcaemia in patients with persistently elevated PTH secretion after
surgery. Furthermore, clinical signs and symptoms of pHPT are significantly reduced.
P6
The epidemiology of pituitary adenoma: a study in an urban
agglomeration of the west of Switzerland
Fontana E., Gaillard R.C. (Fribourg, Lausanne)
Enzo Fontana M.D.°*; R.C.Gaillard M.D.* °*Diabetic and Metabolic
unit of the Medical Clinic, Fribourg Hospital, and *Endocrine, Diabetic
and Metabolic Service; University hospital (CHUV), Lausanne,
Switzerland
Introduction: Epidemiological data concerning pituitary adenomas
are very scarce and in some cases reports are even conflicting.
Previous papers focusing on this rare condition described a prevalence of 1 case in every 4,000–6,000 people. This opinion is at present disputed as there is some evidence of a greater prevalence than
formerly believed. The aim of this study was to evaluate, in an urban
area of Switzerland, the prevalence of relevant clinical pituitary
adenoma in patients followed by their own doctor (GP, endocrinologist or gynaecologist).
Methods: This analysis was made on May 31st 2007 after a collection period between April 1st 2006 and May 31st 2007 in the agglomeration of Fribourg (the city of Fribourg as well as the surrounding
urban districts of Givisiez, Marly and Villars-sur-Glâne, Switzerland).
This agglomeration has a resident population of approximately 54607.
General practitioners, endocrinologists and gynaecologists were
questioned concerning any patient within this agglomeration presenting with a pituitary micro- or macro- adenoma. Others points determined were: age, sex of each patient and the existence of a neurosurgical procedure or medical treatment for this condition. 75 doctors
in this area were consulted by questionnaire out of which 63 replied.
22 different doctors followed the 45 patients detected.
Results: 45 patients were reported. Of these, 44 presented a clinically significant pituitary adenoma and 1 patient had a Rathke cyst,
which was excluded from the analysis. In the studied area we found
a prevalence of 80.5 pituitary adenomas per 100,000. 73% of the
adenomas were reported in women. Among the 44 adenomas, we
observed 13 non secreting macro-adenomas, 25 prolactinomas
(9 macros and 16 micros), 4 cases of acromegaly and 2 of ACTHdependant Cushing disease.
Conclusion: Our study concords with a recent finding demonstrating
a greater prevalence of pituitary adenomas than previously believed.
The prevalence of this condition, in an urban area of the west of
Switzerland, is 1 case per 1241 which is about a 4 fold increase compared to the prevalence given in textbooks.
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P7
A reduced bmi cut-off for estimating obesity prevalence based
on self-reported height and weight: a validation study
Kossovsky M., Dauphinot V., Naudin F., Wolff H., Gaspoz J.M.
(Genève, Saint Etienne)
Background: The estimation of obesity prevalence and its temporal
trend in the population is important when assessing public health and
economic burden. It has already been demonstrated that selfreported heights and weights do not allow a correct estimation of the
true prevalence of obesity.
Methods: A cross sectional study conducted in France in 2002–03
comparing self-reported with measured data showed that obesity
prevalence determined by body mass index (BMI) calculated from
self-reported weight and height was underestimated: 30.1% of men
and 34.3% of women not considered obese according to their selfreports were classified as such by measurements. We proposed to
lower the self-reported BMI threshold defining obesity to 29.0 kg/m2
for men and 28.4 kg/m2 for women. This yielded to an estimation of
obesity prevalence similar to the one obtained using measurements
(15.1% vs. 14.4%, p = 0.21) and was the best compromise between
sensitivity (83.5%) and specificity (96.4%).
Results: A validation procedure was performed on a different population. From 1993 to 2004, a sample of 13,266 men and women (500
each per year) was recruited in Geneva, Switzerland. Self-reported
and measured BMI were routinely collected. As already observed,
almost one third (33.6% among men and 27.5% among women) of
the subjects not considered obese according to their self-reports
were classified as such by measurements. The reduced threshold for
obesity based on self-reported data was applied and its performance
compared to measured data. The reduced obesity threshold could
correctly classify subjects in 95.5% of cases, with a sensitivity of
88.9% and specificity of 96.5% (Figure). Positive and negative
predictive values were respectively 78.6% and 98.4%.
Conclusions: Subjects in population studies tend to underestimate
their weight and to overestimate their height. This yields to erroneous
obesity prevalence in populations where this estimation is based on
self-reports only. Contrasting with corrective equations, this readily
applicable reduced threshold does not require collection of additional
data. Its applicability to other European or American countries
requires further validation.
P8
MedGem – ein einfaches Gerät zur Bestimmung des
Ruheenergieumsatzes
Rüfenacht U., Rühlin M., Imoberdorf R., Ballmer P.E. (Winterthur)
Einleitung: Um bei schwer Kranken eine bedarfsgerechte Ernährung
zu gewährleisten ist es unerlässlich den Energiebedarf ermitteln zu
können. Als Goldstandard zur Messung des Energieumsatzes gilt die
klassische indirekte Kalorimetrie, deren Durchführung im Spitalalltag
sehr aufwendig ist. Seit einigen Jahren ist ein handliches, indirektes
Kalorimeter auf dem Markt, welches den Ruheenergiebedarf allein
durch Messung des Sauerstoffverbrauchs in kurzer Zeit und unter
einfacher Handhabung ermittelt. In der vorliegenden Pilotstudie
haben wir die Messwerte dieser zwei Techniken verglichen.
Methoden: Es wurden gesunde Personen sowie Patienten mit verschiedenen Krankheitsbildern eingeschlossen. Zunächst wurde die
Messung mit dem indirekten Kalorimeter Vmax 29n (Sensor Medics,
Yorba Linda, CA, USA) vorgenommen und danach mit dem MedGem
(MedGem, Healthetech, Golden, CO, USA). Beide Messungen fanden
am ruhig liegenden Patienten unter gleichen und für die indirekte
Kalorimetrie vorausgesetzten Bedingungen statt. Zudem wurden die
klassischen Formeln von Harris-Benedict und Ireton-Jones mit den
Messwerten des Vmax verglichen.
Resultate: Der Ruheenergieumsatz betrug mit Vmax bei den Gesunden (n = 11) 1531 ± 247 kcal, bei den Patienten (n = 22) 1428 ± 384
kcal, mit MedGem 1558 ± 324 kcal (p = 0,896 gegenüber Werten mit
Vmax), bzw. 1482 ± 390 kcal (p = 0,481). Zwischen Vmax und
MedGem bestand eine hochsignifikante positive, lineare Korrelation,
sowohl bei den Gesunden (r = 0,85, p <0,001) als auch den Patienten
(r = 0,88, p <0,001). Beim Vergleich mit den Formeln ergab sich ebenfalls eine signifikante Korrelation, allerdings mit tieferen Korrelationskoeffizienten.
Diskussion: Die Messungen mit MedGem korrelieren sehr gut mit
denjenigen der Messung mittels klassischer indirekter Kalorimetrie.
Die individuellen Werte müssen jedoch mit Vorsicht interpretiert wer-
Forum Med Suisse 2008;8:(Suppl. 40)
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den, da sie deutlich voneinander abweichen können. Die Resultate
sollen immer unter Einbezug der klinischen Verlaufsbeurteilung
genutzt werden. Der gezielte Einsatz von MedGem beim schwer
Kranken ermöglicht eine einfache und schnelle Ermittlung des
Energieumsatzes im Spitalalltag.
P9
Ernährungsmanagement-Studie: Vorläufige ScreeningDatenanalyse
Iff S., Leuenberger M., Gutzwiller JP., Mühlebach S., Perrig M.,
Stanga Z. (Bern)
Hintergrund: Mangelernährung (ME) wird bisher in den Spitälern
ungenügend wahrgenommen, Risikopatienten werden nicht früh
genug erfasst und werden folglich zu spät adäquat behandelt. Es
fehlen fundierte Studien, welche die Wirksamkeit der Ernährungstherapie belegen.
Methode: Klinische, prospektive, randomisierte Interventionsstudie
mit den Hauptendpunkten Aufenthaltsdauer und Lebensqualität. Die
Studie findet auf den Abteilungen der Klinik für Allgemeine Innere
Medizin des Universitätsspital Bern statt. Studiendauer: 02/07 bis
03/08. Bei Spitaleintritt wurde jeder Patient mittels Nutrition Risk
Score (NRS) 2002 nach Kondrup erfasst. Die maximale Punktezahl
dieser Screening-Methode beträgt 7. Eine Punktzahl 03 weist auf eine
schwere Mangelernährung oder ein hohes Risiko für Mangelernährung hin und darauf, dass der Patient von einer Ernährungstherapie
profitiert.
Bisherige Resultate: Vom 02/07 bis 01/08 wurden 1671 neueintretende Patienten (n = 100%) mittels NRS auf ME gescreent. Die Prävalenz der Patienten mit einem NRS-Gesamtscore von 03 betrug
51% (n = 860). Demographische Daten der Patienten (MW ± s): Alter
63,1 ± 17,9 J, Grösse 1,69 ± 0,1 m, Gewicht 73,2 ± 17,2 kg, BMI
25,4 ± 5,9 kg/m2, NRS-Gesamtscore 2,9 ± 1,4 Punkte, Energiebedarf
(Grundumsatz + 20% Aktivität) 1752 ± 336 kcal. Die Risikogruppe
war signifikant älter (64,2 ± 17,7 vs. 61,9 ± 18 J, p = 0,01), hatte einen
signifikant tieferen BMI (24 ± 5,7 vs. 27 ± 5,7 kg/m2, p <0,001) und
einen tieferen Energiebedarf (1679 ± 312 vs. 1835 ± 343 kcal,
p <0,001). Das hohe Risiko für ME war gleich in jeder Altersgruppe.
Altersmässig waren 40,5% (n = 665) der Patienten 070 J. Der
Appetitverlust in den letzten 7 Tagen sowie der Gewichtsverlust in
den letzten 3 Monaten waren die häufigsten Gründe für mehr Punkte
im NRS. Nur 8% (n = 122) hatten einen hohen NRS wegen isoliert
tiefem BMI (<18,5 kg/m2). Ein leichter metabolischer Stress, bedingt
durch die Grundkrankheit, wurde bei 84,9% (n = 1416) der Patienten
beobachtet; 14.4% (n = 240) der Patienten hatten einen erhöhten
Stressfaktor.
Schlussfolgerung: Die hohe Prävalenz der schweren ME oder des
hohen Risikos für ME auf den universitären internistischen Abteilungen weist eindrücklich auf den dringenden Handlungsbedarf im
Kampf gegen die ME hin. Die Frage nach Gewicht- und Appetitverlust
identifiziert den grössten Teil der mangelernährten Patienten. Wie
hoch der klinische Benefit der Ernährungstherapie (Outcome) sein
wird, kann erst nach der Entblindung der Studie evaluiert werden.
P10
Selective Effects of High Fat Diet on Vascular Reactivity
Modulates to Endothelin: Involvement of NADPH-Oxidase
subunit Nox2
Damjanovic M., Rasi J., Bhattacharya I., Haas E., Barton M. (Zürich)
High dietary fat intake is associated with structural and functional
alterations in the kidney, promoting development of renal diseases.
The renal artery, which is central in renal perfusion, is highly sensitive
to vasoactive factors. Renal endothelin-1 (ET-1) has been shown to
be associated with activation of renin-angiotensin system (RAS) in the
kidney in obesity. However, the role of NADPH oxidase Nox2
(gp91phox) in ET-1-mediated contraction in the renal artery is not
known. Therefore, the aim of this study was to find out whether Nox2
is involved in modulation of ET-1-mediated contraction in the renal
and femoral artery, and whether this is affected by high-fat diet.
Experiments were performed with male C57BL/6J (wild-type control
and Nox 2–/–) mice, which were fed with either standard chow or high-
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fat diet (41% kcal from fat) for 15 weeks, starting at 4 weeks of age.
Rings from renal artery and femoral artery were pre-incubated with
nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester
(L-NAME; 3x10–4 M) for 30 min, followed by treatment with ET-1 in a
concentration-dependent manner (10–11 – 10–7 M). In wild-type mice
on a control diet, the maximum contraction to ET-1 was similar
between renal and femoral artery. Interestingly, high-fat diet reduced
ET-1-mediated contractions in the renal artery (p <0.05 vs. control
diet) but not in the femoral artery. In Nox2-deficient animals (Nox2–/–)
on a control diet, the contraction mediated by ET-1 was reduced in
the renal artery (p <0.05 vs. wild-type), an effect unaffected by highfat diet (ns). Contractions to ET-1 in the femoral artery were affected
neither by high-fat diet nor by Nox2-deficiency. In conclusion, the
data presented here suggests that the renal artery but not the femoral
artery is highly susceptible to the changes mediated by high-fat diet
and that Nox2 modulates ET-1-dependent vascular contractility only
in the renal artery. This study further suggests that during the early
stages of obesity the renal artery is highly sensitive and susceptible
to changes, which may propagate renal dysfunction and diseases
associated with it.
Forum Med Suisse 2008;8:(Suppl. 40)
25 S
muscle cell proliferation was strongly enhanced by LDL (up to 5-fold,
P <0.001 versus control), whereas cells stimulated with insulin
showed only small changes (less than 1.5-fold). In cells exposed to
submaximal concentrations of LDL, the proliferative response was
potentiated in the presence of insulin (approximately 3-fold, P
<0.0001 for LDL and insulin versus LDL alone). Insulin caused PKB
phosphorylation, whereas LDL had no effect. LDL concentrationdependently inhibited insulin-induced PKB and IRS-1 tyrosine phosphorylation (P <0.05 for insulin plus LDL versus insulin alone). In
contrast, both insulin and LDL induced phosphorylation of ERK1/2.
Interestingly, inhibition of the PKB signaling pathway in insulin-stimulated cells with the phosphatidylinositol-3-kinase inhibitor LY294002,
similar to LDL inhibited PKB phosphorylation, increased insulinmediated cell proliferation. These data indicate that physiological
levels of LDL found in human plasma suppress insulin-mediated PKB
activation without affecting the mitogenic ERK1/2 pathway. Since
PKB signaling is required to maintain vascular smooth muscle cells in
a quiescent, differentiated state, inhibiton of the metabolic insulin
signaling pathway by LDL may become important in insulin resistant
individuals and diabetics with concommitant hypercholesterolemia
accelerating atherosclerosis development in these patients.
P11
High-fat diet increases mouse BMI and endothelial prostanoid
contractions but does not impair nitric oxide bioactivity
Bhattacharya I., Damjanovic M., Perez-Dominguez A., Gut A.,
Hager S., Haas E., Barton M. (Zürich)
Intake of diets rich in fat is a major cause of obesity, which accelerates the development of cardiovascular diseases. The aim of this
study was to establish a method to quantify mouse obesity and to
investigate the effect of high-fat diet on basal nitric oxide bioactivity
and on prostanoid contractility in the mouse carotid artery. Male
C57BL/6J mice received either control diet (standard chow; 12.5 kcal
from fat) or high-fat diet (58% kcal from fat) for 30 weeks, starting at
4 weeks of age. Analogous to human BMI (kg/(weight in m2), mouse
BMI was defined by mouse weight (g)/height (mm)2. Relative insulin
resistance was measured using glucose tolerance test. Vascular
functional experiments were performed in carotid arterial rings treated
either with or without NG-nitro-L-arginine methyl ester (L-NAME;
3x10–4 M) for 30 min followed by treatment with phenylephrine (PE;
3x10-8 M) and acetylcholine (ACh; 10–10-10–5 M). Contractile response
to PE was normalized to KCl (100 mM) and endothelium-dependent
contraction was normalized to maximal PE contraction. After high-fat
diet BMI increased from 30 ± 0.4 to 34 ± 0.6 (P <0.05 vs. control),
indicating obesity. Obese animals showed glucose intolerance
(P <0.05 vs. control). High dietary fat intake increased the contraction
to PE (3 x10–8 M, P <0.05 vs. control) and to prostanoid-mediated
endothelium-derived contracting factors, (ACh-10–7 M, P <0.05 vs.
control). In contrast, ACh-mediated endothelium-dependent relaxation was similar in control and obese animals. Treatment with LNAME caused a 2-fold increase in PE-mediated contraction in both
control and obese animals. In conclusion, we present a novel method
for measuring mouse BMI. High dietary fat intake increases mouse
BMI and prostanoid-mediated vascular contractility without affecting
basal NO bioactivity.
P13
Opposing effects of diets rich in plant or animal fat on renal
regulation of genes implicated in cellular redox balance
Haas E., Winklehner A., Bhattacharya I., Minotti R., Damjanovic M.,
Barton M. (Zürich)
Glomerular damage is enhanced by obesity, which is associated with
low-grade inflammation and increased production of reactive oxygen
species (ROS). In obesity-associated renal injury the effect of plantfat or animal-fat on expression of genes involved in redox regulation
is not known. The aim of the study was to quantify and compare renal
cortex gene expression of pro- and antioxidant enzymes and the
inflammation-associated adhesion molecule ICAM-1 in C57BL/6J
mice fed with standard diet (SD), or diets rich in animal-fat (AFD; milk
fat) or plant-fat (PFD; coconut oil) for 15 weeks. Body weight was
monitored and glucose tolerance (ip GGT) was determined. Feeding
of both high-fat diets resulted in a comparable weight gain and glucose intolerance (n.s., AFD vs. PFD). In the renal cortex, the expression levels of the pro-inflammatory genes (NO synthase 2, NOS2;
catalytic subunit of the phagocytic NADPH oxidase, Nox2; intracellular adhesion molecule-1, ICAM-1) were more than 30-fold lower
compared to anti-oxidant genes (gluthatione peroxidase, GPX and
Cu/Zn superoxide dismutase, SOD1) and the regulatory subunit of the
NADPH oxidase complex p22phox. Treatment with AFD but not with
PFD increased mRNA expression of NOS2, Nox2, and ICAM-1. Interestingly, PFD but not AFD treatment was associated with upregulation of the antioxidant genes SOD1 and GPX and reduction of
p22phox. In conclusion, these data suggest that plant-fat diet, in
contrast to animal-fat diet, may contribute to an anti-oxidative/inflammatory state in the renal cortex despite development of obesity.
P12
P14
Low density lipoprotein-mediated vascular smooth muscle
cell growth is potentiated by insulin: role of protein kinase B
Haas E., Minotti R., Raselli C., Hoehn A., Hranac M., Barton M.
(Zürich)
Metabolic diseases, including diabetes and obesity, are associated
with hyperinsulinemia and insulin resistance. These pathophysiologic
conditions accelerate atherosclerosis development, which is associated with proliferation of vascular smooth muscle cells. This study
investigated the effects of physiological levels of insulin and low
density lipoprotein (LDL) on the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (PKB), and insulin
receptor substrate -1 (IRS-1), and on the proliferation of VSMC. Phosphorylation of signaling molecules was measured by Western blot
analysis using phospho-specific antibodies, and cell proliferation was
quantified by [3H]-thymidine incorporation assay. Vascular smooth
Relationship between cigarette smoking and abdominal
obesity
Willi C.*, Chiolero A., Faeh D., Cornuz J., Marques-Vidal P.,
Paccaud F., Waeber G., Vollenweider P. (Lausanne)
Background: Although smokers tend to have a lower body-mass
index (BMI) than non-smokers, smoking may affect body fat (BF)
distribution. Some studies have assessed the association between
smoking, BMI and waist circumference (WC), but, to our knowledge,
no population-based studies assessed the relation between smoking
and BF composition. We assessed the association between amount
of cigarette smoking, BMI, WC and BF composition.
Method: Data was analysed from a cross-sectional population-based
study including 6’187 Caucasians aged 32–76 and living in Switzerland. Height, weight and WC were measured. BF, expressed in percent of total body weight, was measured by electrical bioimpedance.
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Abdominal obesity was defined as a WC 0102 cm for men and 088
cm for women and normal WC as <94 cm for men and <80 cm for
women. In men, excess BF was defined as %BF 028.1, 28.7, 30.6
and 32.6 for age groups 32–44, 45–54, 55–64 and 65–76, respectively; the corresponding values for women were 35.9, 36.5, 40.5 and
44.4. Cigarette smoking was assessed using a self-reported questionnaire.
Results: 29.3% of men and 25.0% of women were smokers. Prevalence of obesity, abdominal obesity, and excess of BF was 16.9%
and 26.6% and 14.2% in men and 15.0%, 33.0% and 27.5% in
women, respectively. Smokers had lower age-adjusted mean WC and
percent of BF compared to non-smokers. However, among smokers,
mean age-adjusted WC and BF increased with the number of cigarettes smoked per day: among light (1–10 cig/day), moderate (11–20)
and heavy smokers (>20), mean ± SE %BF was 22.4 ± 0.3, 23.1 ± 0.3
and 23.5 ± 0.4 for men, and 31.9 ± 0.3, 32.6 ± 0.3 and 32.9 ± 0.4 for
women, respectively. Mean WC was 92.9 ± 0.6, 94.0 ± 0.5 and 96.0 ±
0.6 cm for men, and 80.2 ± 0.5, 81.3 ± 0.5 and 83.3 ± 0.7 for women,
respectively. Compared with light smokers, the age-adjusted odds
ratio (95% Confidence Interval) for excess of BF was 1.04 (0.58 to
1.85) for moderate smokers and 1.06 (0.57 to 1.99) for heavy smokers
in men (p-trend = 0.9), and 1.35 (0.92 to 1.99) and 2.26 (1.38 to 3.72),
respectively, in women (p-trend = 0.04). Odds ratio for abdominal
obesity vs. normal WC was 1.32 (0.81 to 2.15) for moderate smokers
and 1.95 (1.16 to 3.27) for heavy smokers in men (p-trend <0.01), and
1.15 (0.79 to 1.69) and 2.36 (1.41 to 3.93) in women (p-trend = 0.03).
Conclusion: WC and BF were positively and dose-dependently associated with the number of cigarettes smoked per day in women,
whereas only WC was dose dependently and significantly associated
with the amount of cigarettes smoked per day in men. This suggests
that heavy smokers, especially women, are more likely to have an
excess of BF and to accumulate BF in the abdomen compared to
lighter smokers.
P15
Impact of smoking and quitting on adipose tissue metabolism in
smokers
Gonseth S., Willi C., Bize R., Cornuz J. (Lausanne)
Background: Weight gain following cessation is a frequent reason
argued by smokers to continue to smoke or to relapse. Some metabolic parameters might mediate or modulate weight gain. Our objective was to explore the evolution of three metabolic parameters such
as leptin and insulin among sedentary adults smokers who participated to a randomized controlled trial assessing moderate-intensity
physical activity (PA) as an aid for smoking cessation. Whereas the
primary outcome, i.e. continuous smoking abstinence, was similar in
both groups at one-year follow-up, we performed secondary analyses
to estimate impact of smoking and quitting on adipose tissue metabolism in smokers.
Methods: 481 participants divided in two groups attended a 9-week
program with a weekly 15-min. smoking cessation intervention (counseling and prescription of NRT). The intervention group attended a
60-min. moderate-intensity PA program, whereas the control group
attended 60-min. health education program to ensure equal contact
conditions. A visit was scheduled at 12th week and at 6 and 12
months follow-up. Blood fasting serum insulin and leptin levels were
assessed.
Results: There were no age, smoking habits, socio-demographic
data and metabolic parameters baseline differences between the two
groups (leptin: 8.6 and 10.1 mg/l, insulin: 10.6 and 11.4 mU/l, in control and intervention groups respectively, all p values NS). The mean
body weight gain from baseline to week 52 was 3.6 kg and 2.9 kg for
control and intervention groups respectively (p = 0.11). The intervention group performed a higher weekly volume of PA than the control
group (e. g., at week 12: 2285.6 METS *min/ week vs. 1746.7
METS*min/week, p <0.05). At week 52, more participants achieved
PA recommendations in intervention vs. control groups (77.8% vs.
60.3%, p = 0.005). Leptin level increased among participants of both
groups between the first visit and visits at weeks 12, 24 and 52, and
this increase was greater in control than in intervention groups: +2.4
vs. +1.8 mg/l at week 12 (p = 0.6), +3.2 vs. +1.7 mg/l at week 24,
(p = 0.03), + 3.2 vs. +1.2 mg/l at week 52 (p = 0.05). The p values of
the trend test were NS. Insulin level also tended to increase among
participants during follow-up (control vs. intervention values): +0.4 vs.
+0.4 mU/l at week 12, +0.7 vs. +0.8 mU/l at week 24, + 2.4 vs.
Forum Med Suisse 2008;8:(Suppl. 40)
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+1.8 mU/l at week 52 (all p values NS). The trend tests were significant for control (p = 0.01) and borderline for intervention groups
(p = 0.07).
Conclusion: Leptin level increased after smoking cessation and this
increase was greater among smokers of the control group who practiced lower weekly volume of PA. Leptin might be a potential causal
factor explaining weight gain following smoking cessation. Insulin
level showed a statistically significant increase only among smokers
of the control group. Insulin may also be involved in weight gain
following smoking cessation.
P16
Verbesserung vaskulärer Risikofaktoren nach
Adipositas-Behandlung mittels bariatrischer Chirurgie
Wieland T., Villiger P., Reinhart W.H. (Chur)
Die Adipositas stellt in unserer Gesellschaft ein wichtiges und
zunehmendes Problem dar. Sie ist mit einer erhöhten
kardiovaskulären Morbidität und Mortalität vergesellschaftet. Mit der
bariatrischen Chirurgie besteht heute die Möglichkeit einer effizienten
Behandlung bei einem Body Mass Index (BMI) >40 kg/m2. Damit
kommt es zur Verbesserung von kardiovaskulären Risikofaktoren und
zu einer Abnahme an vaskulären Todesfällen. Wir haben an unserem
Kollektiv von 20 PatientInnen (18 Frauen, 2 Männer, Alter 42 ± 8
Jahre) ein Jahr nach bariatrischem Eingriff kardiovaskuläre Risikofaktoren untersucht. 19 hatten eine Operation nach Sugerman (Magenverkleinerung, Gastrojejunostomie und Anastomisierung des proximalen Jejunums mit dem distalen Ileum), eine Patientin ein Gastric
banding erhalten. Der BMI betrug vor der Operation 46,5 ± 6,5. Innerhalb eines Jahres nahmen die PatientInnen 42 ± 13 kg ab, was den
BMI auf 31,3 ± 6,3 senkte (p <0,0001). Der BD sank systolisch von
137 ± 13 auf 128 ± 12 mm Hg (p <0,02), diastolisch von 82 ± 8 auf
77 ± 10 mm Hg (p <0,05). Das C-reaktive Protein (CRP) sank von
8,4 ± 6,7 auf 1,6 ± 2,3 mg/l (p <0,0001, n = 18). Das Gesamt-Cholesterin fiel von 4,93 ± 0,71 auf 4,00 ± 0,71 mmol/l (p <0,01, n = 14).
In einer Untergruppe von acht Patienten wurden auch LDL und HDL
gemessen und ein tendentieller Abfall von LDL von 3,59 ± 0,62 auf
2,56 ± 0,05 mmol/l und ein Anstieg von HDL von 1,29 ± 0,34 auf 1,39
± 0,31 mmol/l (n.s.) gefunden. Die Harnsäure sank von 373 ± 137 auf
285 ± 77 µmol/l (p <0,01, n = 11).
Wir schliessen aus diesen Daten, dass bariatrisch-chirurgisch behandelte PatientInnen mit einer morbiden Adipositas ein Jahr nach Eingriff ein deutlich verbessertes kardiovaskuläres Risikoprofil aufweisen.
Das Absinken des CRP ist eine neue Beobachtung, welche darauf
hindeuten könnte, dass das Fettgewebe eine systemische
entzündliche Reaktion unterhalten kann.
P17
Spleen derived vascular progenitor cell transfer restores
metabolic and vascular insulin sensitivity in high-fat diet
insulin resistant mice
Bloch J., Schwab M., Duplain H., Dessen P., Monney A., Mathieu C.,
Sartori C., Scherrer U. (Lausanne)
Type 2 diabetes, insulin resistance and its associated cardiovascular
complications are reaching epidemic proportions worldwide, but the
underlying mechanisms remain incompletely understood. Endothelial
dysfunction related to defective NO synthesis contributes to metabolic insulin resistance by leading to impaired insulin stimulation of
blood flow and substrate delivery to skeletal muscle tissue. Circulating endothelial progenitor cells (EPC) play a role in endothelial repair
and function, and represent a marker of endothelial dysfunction
Administration of functional EPC restores this defect. Diabetes and
insulin resistance are associated with a decreased number and dysfunctional EPC, but it is not clear whether this is a cause or merely a
consequence of the disease. We hypothesized that transfer of functional EPC improves insulin sensitivity in insulin resistant mice. Six
weeks old splenectomized C57/Bl6 mice were put on a high-fat diet
(UAR, France) for 8 weeks. 4 and 6 weeks after the start of the diet,
mice received an i.v. injection of 200 Mio vascular progenitor cells in
normal saline, or vehicle. The cells were prepared by extracting the
monocytic fraction from spleens of C57/Bl6 mice. 2 weeks after the
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second injection, we assessed insulin sensitivity (intraperitoneal
insulin injection, 0.5 U/kg). We also measured insulin stimulation of
muscle blood flow in vivo, and skeletal muscle glucose uptake in
vitro. The major new findings were that EPC transfer markedly
improved both metabolic and vascular insulin sensitivity in insulinresistant mice. The decrease in basal glycemia 15 min after insulin
injection was more than twice as large in EPC-treated than in vehicletreated mice (–26.1 ± 3.0% vs. –10.8 ± 4.2%, P = 0.012). The insulininduced stimulation of skeletal muscle blood flow in vivo was more
than 4 times larger in the EPC-treated than in the control mice (95.4 ±
22.1% vs. 22.4 ± 9.7% P <0.01), whereas the basal and insulin stimulated glucose uptake in isolated muscle in vitro was similar in the two
groups (P = 0.97). Here we show for the very first time that heterologous transfer of circulating vascular progenitor cells markedly
improves insulin sensitivity in insulin resistant mice. This favorable
metabolic effect appears to be related, at least in part, to restoration
of the endothelium-dependent vasodilation insulin stimulation of
blood flow and substrate delivery in skeletal muscle tissue.
P18
An unusual case of hyperammonemia and coma without liver
dysfunction
Ritter S., Senn A., Isler P., Meier C.A., Frick S. (Zurich)
Background: Ammonia is a neurotoxin mainly produced in the gastrointestinal tract and cleared almost completely from the portal vein
by the liver. Hence, hepatic encephalopathy due to hyperammonemia
typically occurs in patients with advanced liver disease and impaired
ammonia clearance.
Case: A 65-year old comatose patient (GCS score 4) with a bilateral
positive Babinski sign had to be intubated for airway protection.
Because of a depressive mood disorder she had been treated with
haloperidol and valproic acid (Depakine® 300 mg daily). Head CT
scan and analysis of cerebrospinal fluid were both normal. EEG
showed a deep coma curve without evidence of epileptic activity.
Laboratory test revealed a normal blood glucose and normal liver
function, except for an increased INR under therapy with oral anticoagulation. Toxicology screening was negative. All medication was
then stopped including valproic acid (serum level 176 micromol/L;
therapeutic range 340–690). One day after admission, serum ammonia level was found to be elevated at 69 micromol/L (normal range
11–32). Without further interventions the patient became conscious
and was successfully extubated. EEG showed considerable improvement. The ammonia level decreased gradually within the next few
days following withdrawal of valproate. Thus, the diagnosis of valproate-related hyperammonemic encephalopathy was made.
Discussion: After acute overdose or chronic use of valproic acid
(VPA; 2-propylpentanoic acid) hyperammonemia may occur, but is
not always accompanied by liver dysfunction. Propionic acid, a
metabolite of VPA, inhibits mitochondrial carbamyl phosphate synthetase which is necessary for ammonia elimination via the urea
cycle. If the action of this enzyme is impaired, ammonia accumulates
and may lead to encephalopathy. VPA may also raise ammonia levels
through an interaction with carnitine. Serum ammonia concentrations
actually inversely correlate with serum levels of carnitine. In addition
to the discontinuation of VPA, therapy with carnitine could possibly
be a therapeutic option in suspected metabolic encephalopathy.
Conclusion: Symptomatic hyperammonemia with severe neurological impairment may occur under therapy with valproic acid
(Depakine®, Orfiril®, Convulex®) without abnormalities of liver function
tests. When valproate-related hyperammonemic encephalopathy is
suspected, the drug must be stopped immediately. This condition is
rare and usually reversible when valproate is discontinued.
Forum Med Suisse 2008;8:(Suppl. 40)
27 S
P19
Das Berner Modell: Resultate der Integrativen
Adipositasbetreuung 2003 bis 2007
Egermann U., Cottagnoud P., Laederach-Hofmann K. (Bern)
Als Epidemie des 21. Jahrhunderts stellt die Adipositas eine
zunehmende medizinische Herausforderung dar. Auch in ökonomischer Hinsicht kommen durch die resultierenden kardiovaskulären,
neoplastischen, degenerativen und psychiatrischen Folgeerkrankungen erhebliche Mehrbelastungen auf das öffentliche Gesundheitswesen zu. Zahlreiche verschiedene Interventionen weisen teils eindrückliche Anfangserfolge hinsichtlich der Gewichtsreduktion auf, lassen
aber eine Nachhaltigkeit und vor allem einen Effekt auf die kardiovaskulären Erkrankungen vermissen. Aus diesem Grund wird in dem
seit 2003 etablierten «Berner Modell» ein interdisziplinäres Therapiekonzept für adipöse Patienten mit einem BMI >30 kg/m2 verfolgt.
Neben einer Gruppentherapie wird auch eine Einzeltherapie bestehend aus internistischer, psychosomatischer, ernährungstherapeutischer und physiotherapeutischer Betreuung angeboten. Gegebenenfalls erfolgt eine adjuvante medikamentöse Therapie. Zusätzlich
zu Bewegungstherapie und Körperwahrnehmungsschulung kommen
verhaltenstherapeutische Ansätze bei Essstörungen zum Einsatz.
Dem präventiven Aspekt wird durch Einbezug von Angehörigen und
Unterstützung für Selbsthilfegruppen von Patienten Rechnung getragen. Aktuell nehmen über 700 Patienten am Programm teil. Davon
konnten im Jahr 2007 die ersten 113 Patienten das 3jährige ambulante Programm abschliessen. Die 35 Patienten des Gruppenprogramms erreichten eine nichtsignifikant grössere Gewichtsabnahme
verglichen mit 78 Patienten aus dem Einzelprogramm.
Demographisch unterscheiden sich weder die Patienten des Gruppen- oder Einzelprogrammes, noch die ausgeschiedenen Patienten:
76% der Patienten sind weiblich. Das Alter reicht von 25 bis 75
Jahren (Mittelwert 46 Jahre). Der Median liegt bei 48 Jahren. Die
vergleichsweise hohe Anzahl von 130 Patienten, die in den ersten
3 Jahren aus dem Programm ausgeschieden sind, setzt sich
zusammen aus Gruppenwechseln, Weiterbetreuung in einem
wohnortnäheren Zentrum, Einleitung einer bariatrischen Therapie und
drop-outs. Im Verlauf des Jahres 2008 werden erste Aussagen zur
Beeinflussung des kardiovaskulären Risikoprofils möglich sein.
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P20
Patients under Scrutiny for Renal Function point to
Holotranscobalamin (HoloTc; active B12) rather than Methyl
Malonic Acid (MMA) to elucidate Vitamin B12 Deficiency
Risch L., Zerlauth M., Risch M., Bernasconi L., Flahaut F., Weber M.,
Risch G., Michel-Blanco M., Nydegger U. (Liebefeld, Schaan,
Pregassona)
Cobalamin, i.e. Vitamin B12 governs DNA synthesis, deficient states
resulting in megaloblastic nuclear-cytoplasmic asynchrony. Quantitative estimations of holotranscobalamin (HoloTc, the biologically active
fraction of vitamin B12) and MMA (a protein breakdown-metabolite)
are frequently used in early diagnosis of vitamin B12 deficiency but
the predictive value of the latter remains a matter of debate. It has
been suggested that renal insufficiency may cause elevation of MMA.
The present study was designed to estimate the relative importance
of HoloTc and MMA as markers for early stages of vitamin B12 deficiency in a homogenous study population under scrutiny for kidney
function. Vitamin B12 status of adults was evaluated using the
UniCel® Beckman Coulter (Nyon), HoloTc was was measured using
the Axsym Abbott Diagnostics (Baar) and MMA was measured by
gaschromatography/massspectrometry. A modified kinetic Jaffe
method available on a Cobas Integra (Roche Diagnostics, Rotkreuz)
for creatinine level measurements was used to estimate kidney function; the glomerular filtration rate (GFR) was calculated using the
abbreviated, simplified equation to predict GFR (Modification of Diet
in Renal Disease Study Group, MDRD). The 232 patients (59.9%
female; mean age 57 + 17 years) expressed a mean concentration of
vitamin B12 of 277 pmol/L, 50 pmol/L of holoTc and 197 nmol/L
MMA, considering levels of B12 <125 pmol/L, holoTc <35 pmol/L or
MMA >271/L to indicate clinically relevant vitamin B12 deficiency.
Correlating GFR (eGFR 30–60 ml/min/1.73m2: 8.2%; eGFR 60–90
ml/min/1.73m2: 34.5%) to the markers of Vitamin B12 deficiency
revealed a significant association between kidney function and MMA
(r = 0.31, p <0.001), whereas no such association could be seen
between kidney function and concentrations of total vitamin B12 and
HoloTc. Vitamin B12 deficiency and chronic kidney disease are frequent conditions among elderly patients. Our study in a rather
homogenous study population under investigation for kidney function
lends further support to the view that holoTc measurements rather
than MMA direct the way to meaningful diagnosis of vitamin B12
deficiency.
Forum Med Suisse 2008;8:(Suppl. 40)
28 S
Case study: A 41-year-old female patient with a history of depression
and multiple suicide attempts was admitted to our emergency department after deliberate ingestion of 60 to 80 pills of Lithiofor®, containing 12 mmol lithium each. Initial therapy comprised intravenous rehydration and administration of purgatives. The patient was intubated
due to vomiting and mechanical ventilation was started. An emergency haemodialysis session was begun after the lithium level had
reached 3.5 mmol/l. The lithium level dropped to 3.0 mmol/l after
4.5 h of intermittent haemodialysis. Due to rebounds (levels reaching
4.5 mmol/l, 3.2 mmol/l respectively), a second and third dialysis
session were mandatory. As we found out later, three of the analysed
samples were taken from test tubes containing lithium-heparin,
elevating the lithium level artificially. A falsely elevated lithium level
had led to an unnecessary third haemodialysis session.
Discussion: The correct sampling of lithium levels in patients with
suspected lithium intoxication is crucial. Heparin test tubes (green)
contain lithium-heparin and therefore indicate falsely elevated lithium
levels. In our case, one dialysis session was performed because of an
incorrectly measured high drug level due to a sampling error. Presence of lithium-heparin can lead to remarkable differences in lithium
level results and hence to unnecessary, potentially dangerous therapeutic procedures. The difference is estimated to lie between 0.88
mmol/l (reference value) and 1.5 mmol/l (literature). In our case the
difference amounted to 1.1 mmol/l.
Figure 1: Lithium level
P21
P23
Acrocyanosis: an unusual manifestation of pheochromocytoma
Weiss L., Schleyerbach P., Rutishauser J., Glück Z. (Biel)
A 44 year-old male was referred by his family physician because of
newly diagnosed hypertension detected during routine examination.
Blood pressure had been as high as 247/114 mm Hg. The patient
gave a history of headaches for the past year and diaphoresis for the
past six months. He reported no palpitations. For around 6 months
prior to referral, he had experienced Raynaud’s phenomenon on his
fingers, and for a few days he had noticed bluish discoloration of his
nose, elbows, knuckles, and ankles. Apart from episodes of low back
pain, his past medical history was uneventful. Upon referral, the
patient was sweating, blood pressure was 174/117 mm Hg, and the
heart rate was regular at 79/min. The rest of the cardiovascular physical examination was normal. His nose, knees, elbows, finger tips, and
toes were cyanotic and cool. The lesions were not palpable and nontender. Laboratory analysis revealed massively elevated plasma levels
of free normetanephrine 12760 pM (reference range: 120–917),
whereas the level of plasma free metanephrine was normal at 120 pM
(reference range: 61-608). A biochemical diagnosis of pheochromoyctoma was made. Upon MRI, a 5 cm left adrenal mass was identified.
The patient was instructed to keep a salt-rich diet and started on
phenoxybenzamine in increasing doses for 14 days. Under this therapy, the skin lesions started to regress. The mass was succefully
removed by laparoscopic adrenalectomy. Histologic workup confirmed a pheochromocytoma. Postoperatively, the patient’s blood
pressure returned to normal, and the acrocyanosis disappeared
within 7 days. The skin manifestations observed in our patient are not
commonly associated with pheochromocytoma. Most likely, they
were caused by arteriolar vasoconstriction due to the (alpha) – sympathomimetic effect resulting from the isolated production of large
amounts of norepinephrin by the tumor.
Decreased kidney function and the coronary angiographic
state independently predict future vascular events
Risch L., Saely C.H., Rein P., Hoefle G., Gouya G., Aczel S.,
Vonbank A., Drexel H. (Feldkirch & Liebefeld, Feldkirch & Triesen,
Hohenems, Feldkirch)
Background: Despite the fact that impaired kidney function represents a cardiovascular risk factor, data on the relationship between
kidney function markers, angiographic state and future cardiovascular
events in coronary patients are scarce.
Aims: To investigate the relationship between kidney function and the
presence of coronary artery disease. In addition, we wanted to investigate the relationship between several markers of kidney function
and the occurrence of cardiovascular events.
Methods: We investigated 195 consecutive patients (age 63+/-10
years; 30.3% female) undergoing coronary angiography for the evaluation of stable coronary artery disease (CAD) and assessed kidney
function by means of several markers (cystatin C, cysC / beta-2–
microglobulin, B2M / beta-trace protein, BTP, all measured with
PENIA on Prospec, Dade-Behring; urea, Ur / creatinine, Cr, photometric measurements with Roche reagents on Hitachi 717 or 911; eGFR
calculated with MDRD and Mayo Clinic Quadratic, MCQE, equations).
All patients had kidney function tests performed on samples taken
right before coronary angiography. Prospectively, we recorded major
coronary events and cumulative vascular events over 6 years.
Results: 61.5% of the patients had significant coronary stenoses with
a lumen narrowing >/ = 50%. With the exception of Cr (p = 0.002),
there were no significant differences among the different kidney function markers between patients with CAD and those in whom angiography did not show CAD. In logistic regression adjusting for age, sex,
BMI, the presence of diabetes mellitus, smoking, hypertension, CRP,
LDL & HDL, none of the investigated kidney function parameters was
associated with significant coronary stenoses. Prospectively, the risk
of future vascular events, as assessed by Cox regression analysis
was significantly increased with CysC,B2M, UR, and Cr-based methods, independently from coronary angiographic status (p <0.05 for
all).
Conclusions: In coronary patients, there is no relationship between
the investigated kidney function markers and coronary status.
Prospectively, however, CysC, B2M, UR, and creatinine-based methods for estimation of GFR independently from coronary angiographic
status predict future vascular events.
P22
Pseudohyperlithiemia
Meyer-Heim T., Gerber L., Hanhart A., Heuss L.T., Bleisch J.A.
(Zollikerberg)
Background: Therapy of lithium intoxication not only relies on clinical
assessment but also on drug levels. Incorrect sampling methods can
lead to falsely elevated values.
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Forum Med Suisse 2008;8:(Suppl. 40)
29 S
P24
P25
Fibrosing colonopathy – Late-onset gastrointestinal
complication of cystic fibrosis?
Franzen D., Went P., Bühlmann U. (Zollikerberg, Zürich)
Cystic fibrosis is an autosomal recessive disease affecting exocrine
glands of the respiratory and gastrointestinal system. Cystic fibrosis
is associated with several serious complications in the lower intestinal
tract including rectal prolapse, distal intestinal obstruction syndrome
(DIOS), intussusception, Crohn’s disease, carcinoma, volvulus, (silent)
appendicitis, and fibrosing colonopathy (FC). It seems to be confirmed, that high-strength or even low-strength pancreatic enzymes
are the leading cause of FC. The large majority of the published
patients were children receiving pancreatic enzymes. The incidence
of FC in adults is much lower, and the pathogenesis is – analogous to
paediatric patients – typically associated with the use of pancreatic
enzyme substitution in patients with cystic fibrosis. But, patients with
enzyme substitution because of other reasons than cystic fibrosis
have not been associated with FC. We present a case of a 43 years
old female cystic fibrosis patient suffering from FC, who had never
been exposed to pancreatic enzyme supplementation. This case
emphasizes that FC also occurs in absence of pancreatic enzyme
substitution and pancreas insufficiency. It could therefore be considered a late-onset gastrointestinal complication of cystic fibrosis in its
natural course of disease. Consequently, the age could be a risk
factor for the appearance of FC in all patients with cystic fibrosis.
Case report: splanchnic arteriovenous malformation
as a cause of protein loosing enteropathy
Pasche A., Cosma-Rochat M., Doerig C., Moradpour D., Qanadli S.,
Vollenweider P. (Lausanne)
Introduction: Arteriovenous malformations (AVM) constitute a rare
cause of upper gastrointestinal (GI) bleeding. AVM can also induce
functional portal hypertension and, secondarily, stasis within
lympathic vessels of the intestinal wall leading to protein loosing
enteropathy (PLE).
Case report: A 61-year-old man with a longstanding PLE of unknown
origin, without chronic hepatic disease, was admitted for massive
upper GI hemorrhage. Endoscopy revealed large varices of the gastric fundus with difficult-to-control acute bleeding. Selective arteriography showed active bleeding from an extensive AVM located in the
gastric wall. Repeated selective embolizations of the left gastric and
splenic arteries feeding the AVM allowed to control the hemorrhage.
Transhepathic portography performed after the embolizations documented the absence of portal hypertension. The clinical condition
of the patient improved and there was no recurrence of GI bleeding.
The patient was able to eat again normally and gained 7 kg within 7
weeks following hospital discharge. Common causes of PLE, including celiac disease, Crohn’s disease and ulcerative colitis, were
excluded. The macroscopic appearance of the duodenum and the
proximal small bowel was compatible with lymphangiectasia.
Interpretation: AVM of the left gastric and splenic arteries induced a
massive increase in blood flow to the portal system which resulted in
portal hypertension. This may have caused venous and lymphatic
stasis of the small intestine, resulting in PLE. Correction of the shunt
and portal hypertension should lead to the reversal of the PLE in this
patient. Short-term follow-up seems to confirm this hypothesis but
we will carefully monitor this patient for long-term weight gain and
correction of iron, vitamin and protein deficiencies.
P26
Figure 1
CT scan abdomen
Figure 2
Histopathology
Viscosity of human bile from the common bile duct sampled
during endoscopic retrograde cholangiography
Näf G., Werth B., Reinhart W.H. (Chur)
Background: Bile flow is determined by its viscosity. While hepatic
bile has a low viscosity (slightly higher than water), water reabsorption
and mucin secretion leads to a several-fold higher bile viscosity in the
gallbladder. We measured the viscosity of bile from the common bile
duct during endoscopic retrograde cholangiography (ERC).
Methods: In patients undergoing ERC for various clinical reasons,
bile was aspirated immediately after cannulation of the papilla vateri.
The samples were deep-frozen at –80°C and later thawed prior to
viscosity measurements at 37°C. A Couette-type viscometer (Contraves LS30) was used with a broad range of shear rates (0.08–69.5
s–1). If not stated otherwise, the value at the shear rate of 0.95 s–1 was
taken into account.
Results: Bile from the common bile duct of 138 patients was measured. The majority (64.5%) had bile viscosities between water (0.7
mPa.s) and the lower limit of plasma (1.1 mPa.s). At these low viscosities, bile showed a Newtonian behaviour, i.e. the viscosity was
independent of the shear rate. 20 patients (14.5%) had a bile viscosity above that of plasma (>1.4 mPa.s). These bile samples showed a
Non-Newtonian behaviour, i.e. the viscosity increased exponentially
with decreasing shear rate. Cholecystectomized patients had a lower
bile viscosity, which is explained by the absence of viscous bile from
the gallbladder. Bile viscosity was similar in patient groups with either
choledocholithiasis, sludge, cholangitis, biliary pancreatitis, or carcinoma of the pancreas or cholangiocarcinomas.
Discussion and conclusions: Bile viscosity in the common bile duct
is lower than that of plasma in 65% of patients undergoing ERC. In
15% it is higher than plasma viscosity, which is caused by the mucin
content of bile. Such viscous bile is a Non-Newtonian fluid, i.e. its
viscosity increases exponentially with decreasing flow rate, which
may lead to a vicious cycle in cholestasis. Bile viscosity showed a
large variation independent of the underlying disease.
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P27
Hyperferritinämie-Katarakt-Syndrom
Pohl D., Tutuian R., Baechli E., Gubler C. (Uster, Zürich)
Fallbeschreibung: Ein 32jähriger Patient stellte sich bei chronischer
Müdigkeit beim Hausarzt vor. Im Blut imponierte eine Hyperferritinämie (1314 mg/l) bei normaler Transferrinsättigung (23,3%),
woraufhin die Zuweisung zur Leberbiopsie erfolgte. In der Anamnese
kein Anhalt für eine Hepatopathie; Noxen, insbesondere
Alkoholabusus werden verneint. Weiterhin ergaben sich keine Hinweise für einen M. Gaucher, M. Still, eine Hyperthyreose oder eine
Hämophagozytose. Die Transaminasen waren normal; eine Genetik
betreffend Hämochromatose (HFE) zeigte eine Heterozygotie für
H63D, was eine HFE unwahrscheinlich macht. Die Histologie zeigte
einen Normalbefund; eine Eisentrockengewichts-Bestimmung konnte
wegen ungenügender Materialmenge nicht durchgeführt werden.
Aufgrund einer Hyperferritinämie ohne hepatische Eisenüberladung
wurde nach einem Katarakt gefragt: Der Patient leidet seit früher
Kindheit an einem beidseitigem Katarakt (Abb. 1); die daraufhin
erhobene Familienanamnese zeigt Abb. 2.
Hintergrund und Diskussion: Das hereditäre HyperferritinämieKatarakt Syndrom ist eine seltene autosomal-dominante Erkrankung,
die oft als hereditäre Hämochromatose misdiagnostiziert wird. Sie ist
durch erhöhte Serumferritinwerte bei normaler Transferrinsättigung in
der Abwesenheit hepatischer Eisenüberladung charakterisiert und
führt bereits in jungem Alter zur okulären Kataraktbildung. Andere
Organmanifestationen insbesondere Hepatopathien oder Symptome
sind nicht bekannt. Die Linsentrübungen entstehen laut aktueller
Literatur auf dem Boden einer Akkumulation von Ferritin-Leichtketten
(LFT) respektive Ihrer Metaboliten. Die genetisch verantwortliche
Region liegt um die 5‘UTR-Region des Gens, welches für FerritinLeichtketten kodiert und kann multipel verändert sein. Die genetische
Diagnostik des aktuell vorgestellten Patienten ist noch ausstehend.
Nach Ausschluss einer sekundären Hyperferritinämie sollte mittels
Bestimmung der Transferrinsättigung und ggfs. einer Leberbiopsie
eine hepatische Eisenüberladung gesucht werden. Nach Ausschluss
derselben sollte differentialdiagnostisch eine Acoeruloplasminämie
respektive das beschriebene Syndrom mit juvenilem Katarakt in
Betracht gezogen werden.
Abb. 1
Beispiel eines Linsenkatarakts
Abb. 2
Familienstammbaum, rot kennzeichnet Patient, schwarz weitere
Katarakt-Träger
Forum Med Suisse 2008;8:(Suppl. 40)
30 S
P28
Indikationen zur Detektion und Charakterisierung fokaler
Leberläsionen mittels Kontrastmittelsonographie –
eine retrospektive Analyse von 158 Untersuchungen
Schiemann U., Tshering D., Kunz A., Patak MA., Stickel F.,
Szuecs Z. (Bern)
Hintergrund: Die Sonographie mit Echosignalverstärkern
(Kontrastmitteln) hat das Potential, die Detektionsrate und die
Charakterisierung von fokalen Leberläsionen deutlich zu verbessern.
Ziel unserer Studie war die deskriptive Erfassung der Indikationen zu
kontrastmittelsonographischen Untersuchungen und die Dokumentation der entsprechenden Befunde.
Methode: In einer retrospektiven Analyse wurden die Daten von
Kontrastmittelsonographien der Leber (Siemens Sequoia, SonoVue
fraktioniert 5 ml intravenös) bei 158 Patienten (Durchschnittsalter 55
Jahre +/- 14,5 SD) zu ihren Indikationen und den Befunden ausgewertet. Die Indikationen für die Kontrastmittel-Sonographie waren im
Einzelnen: a) B-Bild-sonographisch nachgewiesene Läsion (n = 30),
b) abklärungsbedürftige Läsion als Zufallsbefund im CT oder MR
(n = 18), c) Patienten mit Malignom-oder Metastasenverdacht (n = 30)
und d) Routineuntersuchung von Patienten mit einer Leberzirrhose
oder Status nach Lebertransplantation (HCC-Screening) (n = 80).
Ergebnisse: Basierend auf der B-Bild-Sonographie und der Kontrastmitteldynamik liessen sich mit hoher diagnostischer Sicherheit nachweisen: 39 Hämangiome, 4 Adenome, 2 fokal noduläre Hyperplasien
(FNH), 19 fokale Minder- oder Mehrverfettungen, 8 Regeneratknoten
bei Leberzirrhose, 2 Abszesse, 2 unkomplizierte Zysten, 9 Fälle mit
Lebermetastasen und 12 HCC. Von letzteren wurden 9 durch Screening von Patienten mit Leberzirrhose detektiert. In 61 Fällen konnte
eine fokale Leberläsion ausgeschlossen werden.
Schlussfolgerung: Die Kontrastmittelsonographie ist eine preiswerte
und nebenwirkungsarme Untersuchungsmethode zur Charakterisierung von bildgebend nachgewiesenen Leberläsionen sowie zur
Metastasensuche. Ein systematisches Screening von Patienten mit
Leberzirrhose führte in immerhin 11% zum Nachweis einer HCCverdächtigen Läsion.
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P29
Physician speciality and pain reduction in patients with
depressive symptoms under treatment with venlafaxine
Begré S., Traber M., Gerber M., von Känel R. (Bern, Zug, Unterägeri)
Excessive pain perception may lead to unnecessary diagnostic testing or invasive procedures to result in iatrogenic complications and
prolonged disability. Naturalistic studies on depressed patients with
chronic pain investigating the impact of medical speciality on treatment outcome in a primary care setting are lacking. Venlafaxine and
other antidepressants may alleviate pain in depressed patients. In this
observational study, we examined whether the magnitude of pain
reduction in 444 depressed patients under venlafaxine would differently relate to the medical speciality of the 122 treating physicians,
namely psychiatrists (n = 110 patients), general practitioners
(n = 236 patients), and internists (n = 98 patients). Independent of
demographic factors, comorbidity, severity of pain and illness at
study entry, and the duration of pain and depression, patients
seemed to profit significantly less in terms of pain reduction (p <.001)
and of reduction in severity of their illness by psychiatrists as compared to general practitioners (p <.019) and internists (p <.002). The
findings suggest that patients referred to psychiatrists are more difficult to treat than those referred to general practitioners and internists.
Therefore, psychiatrists could particularly profit from educational
programs targeting at improving their capacities in treating pain of
their depressed patients.
P30
Physical pain in patients with depressive symptoms in
switzerland: a field report from clincal practice
Begré S., Traber M., Gerber M., von Känel R. (Bern, Zug, Unterägeri)
The present study is a cross-sectional observation of 601 depressed
pain patients from all over Switzerland who were treated with Venlafaxin in 122 medical practices. Pre-existing or other additional, antidepressant medication was not taken into account. Diagnosis of
depression was determined by a regular clinical interview, pain intensity was estimated using a visual analogue scale (VAS), and severity
of disease was rated by the Clinical Global Impression scale (CGI).
Age, gender, duration of depression, and all clinically approved diagnoses for comorbid somatic and mental disorders (i.e. the first digit
according to ICD-10) were listed. The use of opioid and non-opioid
analgesics and the number of therapies in addition to those targeting
depression and pain were also recorded. Compared with Central
European patients, those from the Balkans and Southern Europe
appear to present with more intense, overall pain mainly affecting the
head, extremities and back, whereas Southern Europeans tend to
suffer even more frequently from chest pain compared with their
Central European peers. There is no difference in terms of pain intensity between patients from the Balkans and those from Southern
Europe.
Forum Med Suisse 2008;8:(Suppl. 40)
31 S
rents professionnels de santé. Dans cette dernière tâche en particulier, le rôle de l’Université est majeur et devrait fortement se concrétiser dans l’interaction que devraient avoir les Instituts de Médecine
Sociale et Préventive chargés de l’enseignement de la santé publique
dans les Facultés et les Hôpitaux universitaires, incontournables pour
l’obtention d’un FMH et de plus en plus impliqués dans la formation
continue. Différentes formes de collaborations sont discutées, ainsi
que les possibilités très concrètes de rotations au sein des Instituts
pour des médecins praticiens désirant s’investir dans des problématiques communautaires.
P32
Clinical supervisors’ perceived needs for teaching
communication skills in clinical practice
Junod Perron N., Sommer J., Hudelson P., Demaurex F., Luthy C.,
Nendaz M., Dolmans D., Van der Vleuten C., de Grave W. (Geneva,
Maastricht)
Background: Lack of faculty training is often cited as the main obstacle to post-graduate teaching in communication skills.
Objectives: To explore clinical supervisors’ needs and perceptions
regarding their role as communication skills trainers.
Methods: Four focus group discussions were conducted with clinical
supervisors from two inpatient and one outpatient medical services
from the Geneva University Hospitals. Focus groups were audio
taped, transcribed verbatim and analyzed in a thematic way using
Winmax software for qualitative data analysis.
Results: Clinical supervisors said they frequently addressed communication issues with residents but tended to intervene as rescuers,
clinicians or coaches rather than as formal instructors. They felt their
own training did not prepare them to teach communication skills.
Other barriers to communication skills teaching include lack of time,
competing demands, lack of interest and experience on the part of
residents, and lack of institutional priority given to communication
issues. Respondents expressed a desire for experiential and reflective
training in a work-based setting and emphasized the need of a non
judgmental learning atmosphere.
Conclusions: Results suggest that organisational priorities, culture
and climate strongly influence the degree to which clinical supervisors may feel comfortable to teach communication skills to residents.
Attention must be given to these contextual factors in the development of an effective communication skills teaching program for clinical supervisors.
P33
P31
Pour une plus grande place de l’enseignement de santé
communautaire dans les cursus de médecine clinique
Motamed S., Rougemont A. (Genève)
Les déterminants sociaux de la santé ont une importance majeure sur
l’état de santé de notre population. Pourtant, les objectifs d’enseignements en médecine sociale et préventive sont, de notre avis, encore
trop peu représentés dans les programmes d’enseignements postgradués de médecine interne et de médecine générale. De plus, les
médecins déjà formés et pratiquant en cabinet sont peu exposés à
cette problématique dans les offres de formation continue, en raison
d’un cloisonnement trop important entre médecine clinique et santé
publique. Pourtant, l’évolution des besoins de notre population
devrait imposer de revoir à la fois la part des financements dévolus
aux différents déterminants de la santé, ainsi que le profil des diffé-
Wieviel Salz enthält ein Nahrungsmittel oder die
Unverständlichkeit der Lebensmittelettiketierung
Käppeli S., Cajacob A., Brändli O., Suter P.M. (Zürich)
Hintergrund: Verschiedene Ernährungsfaktoren sind in der Pathogenese und Therapie der chronischen Erkrankungen von zentraler
Bedeutung. Salz (NaCl) kann beim vorliegen einer Salzsensitivität zum
Bluthochdruck beitragen. Die Kenntnis des Salzgehaltes von
Nahrungsmitteln ist für den Konsumenten von zentraler Bedeutung. In
dieser Studie wurde das Ernährungswissen respektive die Kenntnisse
über den Salzgehalt anhand der Aufschrift auf Nahrungsmittelpackungen (Foodlabels, FL) evaluiert.
Methodik: 459 Besucher (m/f = 275/148, Alter 47 ± 17,3 Jahre, BMI
24 ± 3,8 kg/m2, Mittelwerte ± SD) des Präventionsbuses der Lungenliga Zürich wurden mittels eines strukturierten Interviews nach dem
Verständnis und der Anwendung von FL befragt. Ein Orginal-FL
wurde zur Interpretation vorgelegt u.a. zur Angabe resp. Berechnung
des Salzgehaltes basierend auf den Angaben des FL (i.e. dem aufgelisteten Natriumgehalt).
Resultate: Der korrekte NaCl Gehalt gemäss Foodlabel konnte von
5 Personen (1,2%) richtig angegeben werden, 418 (98,8%) kamen zu
POSTERS SSMI
POSTERS SGIM
einem falschen Ergebnis. 154 der befragten Studienteilnehmer
(36,4%) wussten den Zusammenhang zwischen Natrium und Salz
nicht. 4 Personen, welche das richtige Ergebnis erhielten, verfügten
über einen Hochschulabschluss, 1 Person absolvierte eine Berufslehre.
Diskussion: Die vorliegende Arbeit zeigt, dass das Verständnis der
Angaben der Nahrungszusammensetzung bezüglich des Natriumrespektive Salzgehaltes unverständlich sind. Ein weiterer Grund für
die «Unverständlichkeit» ist aber auch das fehlende ErnährungsGrundwissen um Empfehlungen umzusetzen. Um das Risiko chronischer Erkrankungen präventiv angehen zu können, sollten nicht nur
Ernährungsempfehlungen gemacht werden, sondern es sollte
anwendbares Ernährungswissen vermittelt werden.
P34
Quelle information sur le paracétamol d’un simple clic sur
Internet?
Piguet V., Cedraschi C., Besson M., Chabert J., Luthy C., Dayer P.,
Desmeules J. (Genève)
Contexte: Internet offre un volume énorme d’informations sur les
médicaments largement utilisées par le public. La qualité des sites
concernant les médicaments n’est pas bien définie alors qu’Internet
joue un rôle croissant dans l’information et la prise de décision des
patients au sujet de leur traitement. Cette étude évalue, selon des
critères de qualités reconnus, les informations concernant le paracétamol fournies sur des sites facilement accessibles sur Internet.
Méthode: évaluation de la qualité de 140 sites obtenus par le moteur
de recherche Google à partir du terme «paracétamol» ainsi que de 17
noms de marque de médicaments contenant du paracétamol et
vendus en Suisse. Des scores ont été établis sur la base des échelles
DISCERN et Netscoring, développées dans le contexte de l’évaluation des informations destinées aux patients à propos de la santé et
des traitements. Ces scores jugent d’une part le contenu en termes
d’objectifs et de crédibilité et d’autre part des aspects liés au design
et à l’interactivité du site, au moyen d’échelles de Likert. Deux
codeurs indépendants ont procédé à l’évaluation, l’accord s’est avéré
très bon (K >0,85).
Résultats: Les sites sont d’origine diverses: 80% commerciale et/ou
à but lucratif; 7% association non lucrative; 6% gouvernementale;
5% blog et forum personnels; 2% universitaire. Des annonces publicitaires apparaissent sur 50% des sites. Les scores mesurant la
qualité du contenu et de la forme des sites sont faibles: moyennes 20
(DS 17) pour le score DISCERN (score = 16 à 80) et de 108 (DS 40)
pour le score Netscoring (score = 0 à 312). Des inexactitudes voire
des erreurs pharmacologiques ont été relevées dans 5% des sites
(e.g. mode d’action, posologie et interactions).
Conclusion: selon les critères définis, la majorité des sites offrent une
information de qualité moyenne voire anecdotique et bombardent les
visiteurs de publicités diverses sans relation avec l’information
recherchée. Aucun site ne présente une information de qualité intégrant tous les potentiels originaux offerts par cette nouvelle technologie de communication.
Forum Med Suisse 2008;8:(Suppl. 40)
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P35
Impact sur le personnel d’une interdiction totale de fumer
dans un hôpital
Humair J.P., Benz Duborgel V., Mascarini J., Kupferschmid S.,
Scherrer F., Borrero P. (Genève)
Introduction: L’interdiction de fumer dans les lieux publics et de
travail est une stratégie efficace pour réduire l’exposition à la fumée
passive et la prévalence du tabagisme. Cette étude évalue l’impact
de cette politique aux Hôpitaux Universitaires de Genève (HUG) sur
le personnel et le comportement des employés fumeurs.
Méthodes: Depuis le 1.1.2006, les HUG ont adopté une interdiction
totale de fumer à l’intérieur des locaux. Elle comprend aussi une
campagne d’information, une interdiction de la vente de tabac, la
mise en place d’une signalétique aux entrées et de cendriers à l’extérieur, un programme de formation du personnel soignant, d’accueil et
de sécurité et des mesures d’aide aux patients et employés fumeurs.
On propose aux collaborateurs fumeurs une consultation gratuite
d’orientation au service de santé du personnel, l’accès à la consultation de désaccoutumance au tabac et la vente à prix réduit de substituts nicotiniques par la pharmacie. 14 mois après le début de l’interdiction, un questionnaire anonyme, suivi d’un rappel aux
non-répondeurs, a été envoyé par courrier à 4500 des 9619 collaborateurs avec un taux de réponse de 64%.
Résultats: La majorité du personnel approuve l’interdiction (92%)
et a bien compris qu’on ne peut pas fumer à l’intérieur des locaux
(92%). 61,5% des employés sont informés sur les services d’aide à
l’arrêt du tabac. La prévalence du tabagisme du personnel a baissé
à 15%; comparativement à une enquête de 1999, elle a diminué de
22% à 15% sur le site hospitalier pour soins aigus. 16% des
employés fumeurs le 1.1.2006 ont cessé le tabac après cette date,
mais peu ont utilisé des services d’aide (4,6%). 49% des fumeurs
actuels disent avoir baissé leur consommation de tabac et 71% ont
modifié leurs habitudes en prenant leur pause à l’extérieur. Malgré
l’interdiction, 27% des collaborateurs sont encore exposés à la
fumée passive et 22% en sont gênés.
Conclusions: Après 14 mois, l’interdiction de fumer aux HUG a un
impact positif sur le personnel avec une large adhésion à la nouvelle
politique et une diminution significative de la prévalence du tabagisme. Mais un non-respect de l’interdiction de fumer persiste à
certains endroits avec une exposition importante à la fumée passive.
La mise en place d’un hôpital non fumeur est un réel défi nécessitant
la poursuite des efforts dans la durée et la recherche de nouvelles
stratégies pour faire respecter l’interdiction de fumer et réduire
l’exposition à la fumée passive.
POSTERS SSMI
POSTERS SGIM
P36
Implementing a program of supportive care in cancer
through collaborative action
Luthy C., Chouiter A., Konrad-Mugnier B., Grivel A., Delaloye S.,
Cedraschi C., Allaz A.F. (Geneva)
Aim: Confronted with cancer patients undergoing multiple
treatments, we describe the development, implementation, and
progress of an in-hospital supportive care program to improve the
quality of care.
Setting & Method: The program was implemented in the Division of
General Medical Rehabilitation of the Geneva University Hospitals,
in collaboration with the Division of Oncology. The following priorities
were identified: 1) reduce the morbidity related to the disease and the
treatment; 2) improve the quality of life; 3) improve hospital coordination of care and psychosocial support; 4) provide continued education and supervision for the team; 5) develop follow-up indicators
(i.e. expectations and needs of the patients, satisfaction with care,
adjustment to the disease and coping strategies).
Description of the program: Various actions were taken: initiating
regular multidisciplinary staff meetings; developing new strategies
to organize day-to-day patients’ care (pain management, nutrition,
psychological support); implementing guidelines and improved data
collection forms for the health care providers; elaborating leaflets for
patients. A database has been implemented to allow for the characterization of the patients. Diverse educational interventions were
conducted. Special off-site seminars and tutorials were offered to the
medical and nursing team in collaboration with ambulatory and inhospital expert partners (e.g. specialised training for specific devices,
administration of chemotherapy, massage therapy, psychological
supervision). A particular emphasis was put on sharing information
and discussing the program in order to promote collaborative work
within the team and to address the specificities of the aims and contents of the supportive care program in the clinical pathway.
Discussion: The implementation of such a supportive care program
highlights some of the challenges faced by health professionals when
attempting to improve the quality of care in this field as well as the
extent of their needs. Clinical mentors have proven to be a key factor
in effecting day-to-day practice and to empower nurses. Such a
program requires considerable time and energy to plan actions and
tasks according to the available knowledge and know-how, to
acknowledge and positively reinforce these competences and to
develop them where and when necessary and possible.
P37
Changer le fonctionnement médical d’un service de
médecine interne et réaliser des économies: le défi relevé
Hagmann N., Burnand J., Calderari F., Schnorf M., Waeber G.,
Lamy O. (Lausanne)
Introduction: Les coûts de la médecine hospitalière continuent à
augmenter. Différents types d’interventions ont montré la possibilité
de les diminuer: guidelines pour diminuer les durées moyennes de
séjours (DMS), contrôler la prescription médicamenteuse, etc. Le but
de notre étude est de tester un fonctionnement différent et autonome
d’une unité de médecine et d’en mesurer les effets en améliorant les
interfaces (équipe infirmière, secrétariat).
Méthode: Nous avons comparé prospectivement le fonctionnement
d’une unité standard (US) témoin de médecine interne générale universitaire aiguë à celui d’une unité autonome (UNAU) en modifiant
l’organisation médicale. L’US a 27 lits, l’UNAU 25, et les deux unités
accueillent le même type de patients. Pendant les jours ouvrables,
l’US fonctionne avec trois médecins assistants (MA) et un chef de
clinique (CDC), et l’UNAU avec un MA aîné, un CDC et une assistante
médicale, en respectant le cadre horaire défini. Plusieurs indicateurs
ont été suivis: DMS, mortalité, coûts des examens paracliniques, etc.
Résultats: Du 1er avril 2006 au 31 mars 2007, 1335 patients ont été
hospitalisés dans les deux unités. Ils étaient identiques en terme
d’âge et de sexe dans les deux unités. La DMS était de 12,2 jours
dans l’UNAU et de 11,6 dans l’US (ns). La mortalité était respectivement de 4,4% et de 6,1%. L’économie salariale annuelle était de
CHF 110 577.– dans l’UNAU. Les coûts par patient des examens
paracliniques ont diminué de 21 à 25% dans l’UNAU: radiologie CHF
414.– vs 553.–; chimie clinique, hématologie et immunologie CHF 421
vs 532.–; examens microbiologiques CHF 131.– vs 166.–. Pour un
service de médecine interne générale de 25 lits, l’économie annuelle
réalisée en tenant compte uniquement des salaires de l’équipe médi-
Forum Med Suisse 2008;8:(Suppl. 40)
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cale, des examens de radiologie et de laboratoire (chimie, hématologie, etc.) est de CHF 336 593.–. L’organisation du travail est meilleure
dans l’UNAU (respect des horaires) que dans l’US. La satisfaction du
personnel soignant de l’UNAU était meilleure après l’introduction du
nouveau mode de fonctionnement. Les médecins de l’UNAU ont
suivi moins d’heures de formation post-graduée que ceux de l’US.
Conclusion: Si ce mode de fonctionnement autonome offre des
avantages économiques et en terme de satisfaction, des améliorations sont à apporter sur la formation des médecins. L’absence
d’effet sur la DMS s’explique probablement par l’âge élevé des
patients et les nombreuses co-morbidités.
P38
Prise en charge de la douleur aiguë aux urgences: impact
d’un soutien informatique sur la documentation de la douleur
Hugli O., Palhais N., Achour S., Tamchès E., Trueb L., Yersin B.
(Lausanne)
Un hiatus perdure entre les recommandations de pratique clinique
(RPC) pour l’antalgie aux urgences et leur mise en pratiques par les
soignants (1). Or de nombreux centres d’urgences emploient une
application informatique pour la gestion clinique de leurs patients
(flux, recueille de données cliniques, notamment l’intensité de la
douleur). But de l’étude: déterminer si le développement d’un module
informatique spécifiquement dédié à la prise en charge de la douleur
améliore la documentation de la douleur aiguë aux urgences.
Méthode: Étude prospective pré- et post-mise en place d’un algorithme activant l’ouverture automatique de fenêtres surgissantes
(pop-up) par notre application informatique au tri et en zones de
soins; les fenêtres contenaient des messages enjoignant les
soignants à évaluer la douleur et à suivre son évolution; l’algorithme
gérant ces fenêtres est basé sur les RPC de notre service (2). Critères
d’évaluation de l’intervention: documentation et quantification de la
douleur au tri, et dans les zones de soins. Données recueillies automatiquement par l’application informatique, complétées par données
recueillies dans le dossier médico-infirmier et auprès du patient.
Inclusion de tous patient >= 16 ans admis avec une douleur de <8
jours ou ayant développé une douleur aux urgences. Analyses par
statistiques descriptives habituelles; comparaison pré et post-intervention par test exact de Fisher pour les proportions, par test de t
pour échantillons non-appariés pour les valeurs continues. Une valeur
de p bilatéral <0,05 indicateur de différence significative.
Résultats: 203 patients ont été inclus en phase pré et 219 en phase
post-intervention; patients similaires pour l’âge (43 et 45 ans; p = 0,65),
la proportion de femmes (48 et 47%; p = 0,72), et l’intensité de la
douleur à l’admission par échelle visuelle analogique (6,2 et 6,0 cm;
p = 0,6). La documentation de la douleur au tri a passé de 59% à
91% (p <0,001), dans le dossier médical de 26% à 37% (p = 0,013),
et de 66% à 81% dans le dossier infirmier (p <0,001). La réévaluation
infirmière de la douleur a passé de 37 à 49% (p = 0,01).
Conclusion: le soutien informatique améliore la documentation de la
douleur aiguë par les soignants aux urgences, particulièrement au tri.
L’étude se poursuit afin de déterminer si l’impact positif se maintient
dans le temps.
(1) I. Decosterd et al: Ann Emerg Med. 2007;50:462–71.
(2) E. Tamchès et al. Swiss Med Wkly. 2007;137:223–7.
P39
Soins palliatifs: définitions et pratique
Rivier E., Pfister JA., Frueh D., Bovard CL., Rosselet F.,
Péclard J. (Vevey, St-Saphorin)
La notion des soins palliaitifs (SP) évolue, ainsi que la frontière entre
soins curatifs et SP. Il en va de même des domaines de la médecine
dans lesquels des SP peuvent être considérés. Notre équipe a ressenti le besoin de faire table rase des données acquises et de reprendre le problème de façon fondamentale, en s’appuiant sur les livres
de référence, sur la littérature médicale et sur les référentiels qualité
disponibles de nos jours. Sans prétendre être exhaustif, ce travail
débouche sur la pratique que notre équipe entend suivre dans ce
domaine, en élaborant de façon détaillée des notions telles que les
besoins, la dignité ou l’autonomie d’un patient, la notion de travail en
partenariat et en înterdisciplinarité, et la démarche qualilté nécessaire
pour entreprendre de tels soins.
POSTERS SSMI
POSTERS SGIM
Forum Med Suisse 2008;8:(Suppl. 40)
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P40
P42
Inhibition of macrophage phagocytotic activity by a
receptor-targeted polymer vesicle-based drug delivery
formulation of pravastatin
Broz P., Ben-Haim N., Grzelakowski M., Marsch S., Meier W.,
Hunziker P. (Basel/Biel, Basel)
Objective: Complications of atherosclerosis such as heart attack and
stroke are leading causes of death, but even drugs like statins
achieve event reductions of only 30%. Dose-limiting adverse effects
in remote organs such as lethal rhabdomyolysis prohibit achieving
higher drug levels known to have strong beneficial effects on the cells
populating the atherosclerotic plaque, in particular macrophages. We
hypothesized that receptor-specific statin targeting using polymer
vesicles would allow cell-selective high-dose treatment for improved
efficacy, while minimizing toxicity in other cells.
Methods: The statin pravastatin, at high doses known to suppress
macrophage lipoprotein (LDL) uptake, a key process in atherosclerosis progression, was packaged into synthetic nanosize polymer vesicles. A ligand for the macrophage scavenger receptor A1 was used
for targeting, while the vesicle’s stealth properties practically eliminated interaction with other cell types like skeletal muscle cells,
responsible for toxicity.
Results: Vesicle uptake by target cells but not other cell types and
slow intracellular content release was observed. A major improvement in biologic efficacy, measured as dose with 50% reduction of
macrophages active in LDL uptake (ED50), was observed for polymer
vesicles compared to free drug (ED50: 0.15 mmol/L versus 11
mmol/L). In contrast, drug toxicity on skeletal muscle cells was apparent at 2–3 times ED50 for free pravastatin, while no toxicity was
observed for all pravastatin vesicle concentrations.
Conclusion: Such high-dose, targeted therapy of statins through
cell-specific polymer vesicles allows novel treatment paradigms not
only for atherosclerosis, but appears promising for a wide range of
drugs and diseases.
Ergometrie versus Kardiogoniometrie in der Diagnostik
der koronaren Herzkrankheit
Schüpbach M., Loretan P., Meier B., Sanz E. (Bern, Zäziwil)
Einleitung: Die Kardiogoniometrie (KGM) ist ein nicht-invasives orthogonales vektorkardiographisches Verfahren, das in der Diagnostik
der koronaren Herzkrankheit (KHK) eingesetzt werden kann. Bisherige
Daten zeigen einen Vorteil der KGM gegenüber dem Ruhe-EKG für
die Sensitivität und die Akkuranz bei gleich hoher Spezifität für beide
Methoden. Wir vergleichen die KGM mit dem Belastungs-EKG
(Ergometrie) in der Diagnostik der KHK.
Methode: Bei 163 Patienten (53 Frauen), die nach Durchführung
einer Ergometrie zu einer elektiven Koronarographie zur Abklärung bei
Verdacht auf eine KHK zugewiesen wurden, wurde vor der Koronarographie eine KGM, ein Ruhe-EKG und eine Ergometrie durchgeführt.
KGM und Ruhe-EKG wurden nach standardisierten Kriterien und
verblindet befundet. Sensitivität, Spezifität und diagnostische Treffsicherheit (Akkuranz) der drei Methoden wurden verglichen. Der
angewandte KGM-Score wurde vorgängig prospektiv validiert. Ein
verbesserter retrospektiver KGM-Score wurde anschliessend erstellt.
Die Ergometrie wurde als positiv gewertet, wenn entweder der
klinische oder der elektrische Befund als positiv beurteilt wurde.
Die Diagnose einer KHK basierte auf der Koronarographie (Vorliegen
signifikanter, d.h. 070%iger Stenosen).
Ergebnis: Die Ergometrie hat eine höhere diagnostische Sensitivität
(78%) als die Untersuchungen ohne Belastung; die Ergometrie war
aber sehr unspezifisch in der untersuchten Kohorte (29%). Die Sensitivität der KGM ist besser als die des Ruhe-EKGs, der anderen nichtinvasiven Untersuchung in Ruhe (51% versus 39%). Die KGM und
das Ruhe-EKG sind spezifisch (KGM 92%, EKG 80%). Der revidierte
KGM-Score hat eine deutlich höhere diagnostische Sensitivität (71%)
bei unverändert guter Spezifität. Die Akkuranz des prospektiv validierten KGM-Scores (67%) ist besser als die der Ergometrie (53%) und
des Ruhe-EKGs (56%); die Akkuranz der KGM konnte im revidierten
Score weiter verbessert werden (78%). Der positiv (PPV) und negativ
(NPV) prädiktive Wert der KGM war höher als derjenige von Ruheund Belastungs-EKG (Tabelle).
Schlussfolgerung: Bei Patienten mit Verdacht auf eine KHK, die zur
weiteren Abklärung zuerst mit Ergometrie abgeklärt werden, hat die
KGM eine höhere diagnostische Treffsicherheit (Akkuranz) und prädiktive Aussagekraft als das Ruhe- und Belastungs-EKG. Die KGM kann
als ergänzende diagnostische Methode bei Verdacht auf KHK hilfreich
sein, zumal es sich um eine risikolose und wenig aufwendige Untersuchung handelt.
P41
L’arrêt cardio-respiratoire (ACR) au cabinet médical est-il
une réalité et y a-t-il nécessité de s’équiper d’un défibrillateur
semi-automatique (DSA)?
Potin M., Pittet V., Staeger P., Vallotton L., Burnand B., Yersin B.
(Lausanne)
Introduction: Cette étude a pour but de déterminer la fréquence de
survenue de l’arrêt cardio-respiratoire (ACR) au cabinet médical qui
constitue un élément de décision quant à la justification de la présence d’un défibrillateur semi-automatique (DSA) au cabinet médical.
Matériel et Méthode: Analyse rétrospective des fiches d’intervention
pré-hospitalière des ambulances et des SMUR (Service Mobile d’Urgence et de Réanimation) du canton de Vaud (650’000 habitants)
entre 2003 et 2006 qui relataient un ACR. Les variables suivantes ont
été analysées: chronologie de l’intervention, mesures de réanimation
cardio-pulmonaire (RCP) appliquées, diagnostic présumé, suivi à
48 heures.
Résultats: 17 ACR (9 么, 8 乆) ont eu lieu dans les 1655 cabinets médicaux du canton de Vaud en 4 ans sur un total de 1753 ACR extrahospitaliers, soit 1% de ces derniers. Tous ont motivés une intervention
simultanée d’une ambulance et d’un SMUR. L’âge moyen était de
70 ans. Le délai entre l’ACR et l’arrivée sur site d’un DSA était en
moyenne de plus de 10 minutes (min-max: 4–25 minutes). Dans 13
cas évaluables, une RCP était en cours à l’arrivée des renforts, mais
seulement 7 étaient qualifiées d’efficaces. Le rythme initial était une
fibrillation ventriculaire (FV) dans 8 cas et ont tous reçu un choc électrique externe (CEE), dont 1 avant l’arrivée des secours administré
dans un cabinet équipé d’un DSA. Le diagnostic était disponible pour
9 cas: 6 cardiopathies, 1 embolie pulmonaire massive, 1 choc
anaphylactique et 1 tentamen médicamenteux. Le devenir de ces
patients a été marqué par 6 décès sur site, 4 décès à l’admission
à l’hôpital et 7 vivants à 48 heures. Les données ne permettent
pas d’avoir un suivi ni à la sortie de l’hôpital ni ultérieurement.
Conclusions: Bien que la survenue d’un ACR soit très rare au cabinet médical, il mérite une anticipation particulière de la part du médecin. En effet, le délai d’arrivée des services d’urgences nécessite
la mise en œuvre immédiate de mesures par le médecin. En outre,
comme professionnel de la santé, il se doit d’intégrer la chaîne de
survie en procédant à une alarme précoce du 144 et initier des gestes
de premier secours («Basic Life Support»). La présence d’un DSA
pourrait être envisagée en fonction notamment de l’éloignement de
secours professionnels équipés d’un DSA.
Tabelle
P43
Cryoballon – eine wirksame ablative Therapie des
paroxysmalen Vorhofflimmerns
Meyer B.J., Hoffmann P., Maurer M., Raab J. (Bern, D-Landau)
Einleitung: Die Cryoablation von paroxysmalem Vorhofflimmern (PAF)
mit dem Cryo-Ballon-Kathetersystem Arctic Front (CryoB) hat sich als
sicheres Therapieverfahren zur elektrischen Isolierung der Pulmonalvenenostien (PV) etabliert; ohne dass eine kostensteigernde Kombination mit einer elektrophysiologisch geführten «on-top-Therapie»
zur Eliminierung von Restpotentialen mittels zusätzlicher Ablationskatheter erforderlich ist. Wir untersuchten in einer Pilotstudie die
Therapieeffektivität einer Intervention mit einer CryoBTechnik
allein ohne zusätzliche segmentale PV-Ablation auf den Erhalt
des Sinusrhythmus (SR) 3 Monate nach Intervention.
Methodik: Es wurden 6 konsekutive Patienten (1 Frau, 5 Männer,
Alter 62,7 ± 10,9 J.) eingeschlossen, die an einem therapierefraktären
(3,0 ± 1,0 Antiarrhythmika) PAF von 71 ± 62 Monaten Dauer litten.
Die transseptale PV CryoB-Ablation erfolgte mit Hilfe der angiographischen Darstellung und Dichtigkeitskontrolle (KontrastmittelWashout) der entsprechenden PV. Der Therapieeffekt wurde nur
selektiv mit Elektroden-Kathetern geprüft. Patienten, die im 3Monats-Follow-up PAF-Rezidive aufweisen, wird ein Zweiteingriff
mit gleicher Technik (kleinere Ballongrösse) und Touch-up angeboten.
POSTERS SSMI
POSTERS SGIM
Primärer Endpunkt war Sinusrhythmus im 3 Monats FU (Dokumentation mittels 12-Kanal-EKG, 24h-Langzeit-EKG, Ereignis-Recorder,
Arrhythmieanamnese).
Ergebnisse: Es wurden 24 Pulmonalvenen mit insgesamt 48 CryoApplikationen behandelt (2,0 ± 0,0 Cryoabgaben pro PV). Hierdurch
konnten 100% der Pulmonalvenen isoliert werden (angiographischanatomische Kontrolle). Die Interventionsdauer betrug 162 ± 21 min.
Komplikation wie Paresen des N. phrenicus, Koronarläsionen oder
Thromboembolien traten nicht auf. Nach 112 ± 52 Tagen wiesen
100% (n = 6) der Patienten SR auf. Bei einem Patienten traten häufige
Episoden von Vorhofflattern auf; ein Zweiteingriff mittels klassischer
Isthmusablation führte zur Arrhythmiefreiheit. Mittlere Arzt- und
Spitalkosten: CHF 17’900 (1 7400).
Schlussfolgerung: Eine alleinige Cryoballon-Therapie mit dem Arctic
Front System erreicht bei Patienten mit paroxysmalem Vorhofflimmern eine 3-Monats-Erfolgsrate die mindestens vergleichbar ist mit
der Radiofrequenz-Standardtherapie. Gemäss den zweijährigen internationalen Erfahrungen ist die Methode sicher und kann bei Patienten
mit entsprechender Indikation nach den neuesten Richtlinien mit
vergleichbar geringem Zeitaufwand und mit vertretbaren Kosten zur
Anwendung kommen.
P44
Akute Cholezystitis und kompletter AV-Block. Koinzidenz
oder gibt es einen kardiobiliären Reflex?
Franzen D., Jung S., Fatio R., Brunckhorst C. (Zollikerberg, Zürich)
Akute Cholezystitiden sind selten (auch ohne strukturelle Herzerkrankung) mit EKG-Veränderungen, wie Arrhythmien oder unspezifischen
ST-T-Alterationen assoziiert. Ein kompletter AV-Block ist in diesem
Zusammenhang eine Rarität.
Wir berichten über einen 48-jährigen bis anhin gesunden Patienten,
welcher sich wegen massiver Oberbauchschmerzen im Rahmen einer
akuten Cholezystitis vorstellte. Bei normalem Eintritts-EKG wurde die
Indikation zur Cholezystektomie gestellt. Präoperativ erlitt der Patient
zweimalige Synkopen mit nachfolgendem Bewusstseinsverlust von
mehreren Sekunden, weshalb eine telemetrische EKG-Überwachung
durchgeführt wurde. In der Aufzeichnung (Abb.) zeigte sich dann ein
Übergang eines AV-Block 2. Grades (2:1) in einen kompletten AVBlock ohne Ersatzrhythmus mit einer Dauer von 9 Sekunden, was
weder beobachtet noch subjektiv wahrgenommen wurde. Serologisch und elektrokardiografisch fanden sich keine Hinweise für ein
akutes koronares Syndrom. Nach laparaskopischer Cholezystektomie
einer gangränös veränderten Gallenblase wurde der Patient schliesslich während 4 Tagen telemetrisch überwacht ohne weitere synkopale
oder rhythmogene Ereignisse. Die transthorakale Echokardiografie,
das Belastungs-EKG, die Carotis-Massage und die Koronarangiografie waren unauffällig. Die elektrophysiologische Untersuchung zeigte
eine unauffällige AV-Knotenphysiologie mit normaler HV-Zeit. Auf eine
Schrittmacherimplantation wurde daher verzichtet. Der Patient ist
auch 3 Monate nach dem Ereignis wohlauf und frei von Synkopen
oder Schwindel. Synkopale Ereignisse im Rahmen eines vasovagalen
Reflexes sind bei massiver Schmerzsensation bekannt. Auch im
Rahmen einer akuten Cholezystitis wurden bereits von Synkopen mit
Bradykardie und Hypotonie oder von asymptomatischen EKG-Veränderungen berichtet. Ursächlich wird dafür ein vagal vermittelter kardio-biliärer Reflex im Rahmen der Gallenblasendehnung postuliert.
Durch die Vagusreizung entstehende AV-Blockierungen sind schon
mehrfach beschrieben worden. Ein kompletter AV-Block im Rahmen
einer akuten Cholezystitis wurde erst einmal beschrieben, wobei es
nach der Cholezystektomie ebenfalls zum spontanen vollständigen
Verschwinden der AV-Blockierung kam. Ein abwartendes Verhalten
ohne Schrittmacherimplantation kann daher nach Ausschluss aller
anderen Ursachen in dieser Situation empfohlen werden.
Abb. 1
Telemetrie-EKG
Forum Med Suisse 2008;8:(Suppl. 40)
35 S
P45
Buccal skinfold thickness – a proxmarker for body fatness
and fat distribution
Thaler Th., Suter P.M. (Zürich)
Background: Obesity is characterized by an increase in fat mass.
Usually in the setting of overweight and obesity fat is deposited in all
body locations. Abdominal obesity – reflected in an increased waist
circumference – is associated with an increased health risk. A positive
relation exists between the body mass index (BMI), the total fat mass
(TFM) as well as the waist circumference (WC). For cultural reasons
patients often do not want to undress or refuse even anthropometric
measurements. In this study the relationship between buccal skin fold
thickness (BSF) with TFM, BMI and WC was studied in young adults.
Methods: 409 students (m/f = 179/230) at the age of 15–22 years
(BMI 21.09 ± 1.81 kg/m2) were examined. Body weight, WC and BMI
were measured according to the usual guidelines. The BSF was
measured vertically in the middle of cheek between tragus and angulus oris using a calliper (Holtain LDT Crymych, UK). The average of
three measurements was used. TFM was determined by bioimpedance (Tanita BF-410, Japan).
Results: The correlation coefficient (r) for the relationship between
the different variables was for males/females: BSF (mm) and kg:
0.44/0.35
BSF (mm) and BMI (kg/m2): 0.43/0.36
BSF (mm) and WC (cm): 0.48/0.4
BSF (mm) and TFM (%): 0.47/0.35
p for all <0.01
Discussion/conclusions: A significant relationship was found
between BSF and body weight, BMI, WC and TFM. The relationship
was strongest between BSF and WC in male (r = 0.48). Our data
suggest that the measurement of the BSF might be a useful easy
accessible proxy marker for the assessment of fat distribution in
patients who do not want anthropometric measurements for cultural
reasons.
P46
Prevalence of sub-clinical atherosclerosis across age
and gender in West of Switzerland
Depairon M., Stauffer I., Berthoud M., Darioli R. (Lausanne)
Atherosclerosis (ATS) is a focal and disseminated disease of arterial
wall with asymptomatic progression for many years until its first clinical manifestation such as an acute coronary syndrome or a stroke.
Since more than 60% of victims of a first cardiovascular events (CVE)
were stratified with a coronary risk of less than 20% of risk, clinicians
should consider other tests to identify high risk patients (HR-P).
Among them, B-mode ultrasounds on carotid was developed to
predict the risk of CVE beyond the traditional RF assessment alone.
However, epidemiological data on subclinical atherosclerosis are
lacking. The purpose of this prospective study was to evaluate the
prevalence of subclinical atherosclerosis on femoral and or carotid
atherosclerosis across age and gender among adults.
The study population included 1620 asymptomatic patients aged
from 20 to 70 years (mean = 48 ± 12), without established CVD, who
were consecutively referred from West of Switzerland for therapeutic
advices. Cardiovascular risk factors (CV-RF) were systematically
screened for each subject, including medical history, physical examination and clinical chemistry. B-mode ultrasounds on carotid and
femoral arteries was performed by two investigators to detect atherosclerotic plaques (focal thickening of intima-media >1.2 mm). The
prevalence of ATS achieved respectively 61% in men and 48% in
women (p <0.001), with a significant correlation with the number
of the traditional CV-RF (r = 0.31, p <0.001). However, no ATS was
detected in 30% of P with >3 CV-RF. As illustrated in the table 1,
there was an increased prevalence of ATS across age in both genders
(p <0.001).
Table 1
Prevalence of subclinical atherosclerosis across age and gender
Age (yr)
Women (n = 641)
Men (n = 979)
20–29
5.5%
6.1%
30–39
18.1%
35.2%
40–49
42.4%
60.1%
50–59
61.0%
73.3%
60–70
77.6%
88.9%
In conclusion, the results indicate that, beyond the epidemiology
of the traditional CV-RF, more research should be performed on
subclinical ATS in order to improve the primary prevention of CVD.
POSTERS SSMI
POSTERS SGIM
Forum Med Suisse 2008;8:(Suppl. 40)
36 S
P47
P49
Impact of renal function on long-term mortality of ICD patients
with nonischemic heart disease
Wolber T., Schefer T., Binggeli C., Holzmeister J., On C.-J.,
Brunckhorst C., Duru F. (Zürich)
Background: Randomized trials have demonstrated that implantable
cardioverter defibrillator (ICD) therapy may reduce the risk of death in
patients with nonischemic cardiomyopathy. However, the long-term
benefit of ICD therapy in a routine clinical setting has not been investigated in these patients.
Methods: We performed a single-center longitudinal study to assess
the outcomes of 176 patients with nonischemic cardiomyopathy who
were implanted with an ICD for primary or secondary prevention of
cardiac death.
Results: The cumulative survival rate after 1, 2, 5 and 10 years was
91%, 87%, 78%, and 65%. Mortality risk was similar among patients
with primary and those with secondary prevention indication for ICD
implantation. Atrial fibrillation, recurrent ventricular arrhythmias requiring ICD therapy, and right ventricular pacing, but not delayed intrinsic
ventricular conduction was associated with higher risk. Impaired
systolic left ventricular function with ejection fraction <35% (HR 3.3,
p = 0.01), New York Heart Association (NYHA) functional class >= III
(HR 2.5, p = 0.03), and renal insufficiency with estimated glomerular
filtration rate < 60 ml/min/1.73 m2 (HR 5.9, p <0.001) were independent predictors of mortality.
Conclusion: In ICD patients with non-ischemic cardiac disease, atrial
fibrillation, recurrent ventricular arrhythmias, and right ventricular
pacing are associated with adverse outcome. Impaired left ventricular
function, NYHA functional class and renal insufficiency are independent predictors of mortality. Patients with impaired renal function are at
highest risk.
Mikroalbuminurie bei Hypertonikern in der Schweizer
Hausarztpraxis und Reduktion durch Telmisartan
Eine offene Beobachtungs- und Risikostratifizierungsstudie
bei 827 Hypertonikern
Martina B., Barth P., Tetyusheva M., Diedrich J.P. (Basel, Freiburg i.Br.)
Einleitung: Jeder 2. Hausarztpatient hat eine arterielle Hypertonie.
Bereits 50% dieser Hypertoniker befinden sich in einer Hochrisikosituation. Dazu haben 25% aller Hypertoniker eine Mikroalbuminurie
(MA), die isoliert schon eine Hochrisikosituation darstellt. Dennoch
wird die MA generell viel zu selten bestimmt, obwohl gerade Patienten mit bestehender MA zur Prognoseverbesserung eine gezielte
medikamentöse Therapie benötigen. Der Angiotensin-II-Antagonist
Telmisartan reduziert die MA bei Diabetes, Nephropathie und Hypertonie. Wir berichten über eine grössere hausärztliche Beobachtungsstudie mit Hypertoniepatienten, bei welchen der Verlauf der MA unter
Therapie mit Telmisartan untersucht wurde.
Methoden: Bei 827 Hausarztpatienten (in 129 Schweizer Praxen)
mit diagnostizierter Hypertonie wurden das kardiovaskuläre Risiko
und die MA (Quotient: Albumin/Kreatinin im Urin) vor Beginn und
4 Monate nach Therapieumstellung auf Telmisartan untersucht. 57%
der Patienten wurden mit Telmisartan und 41% mit Telmisartan/HCTZ
behandelt. Eine Risikostratifizierung wurde nach den WHO/ISH
99/2003 Kriterien vorgenommen (ein sehr hohes Risiko bedeutet ein
>30%iges, ein tiefes Risiko ein <15%iges Risiko für das Auftreten
eines Hirnschlags oder Herzinfarktes innerhalb der nächsten 10
Jahre). Veränderungen von Blutdruck und MA wurden mit Hilfe des
parametrischen T-Tests geprüft.
Resultate: Die Hypertoniker waren im Mittel 60 (18–95) Jahre alt;
52% männlich. 31% Diabetiker, und 78% hatten ein Hochrisiko aufgrund ihrer Komorbiditäten. 50% wiesen zu Beginn eine MA auf.
56% der Patienten ohne MA erfüllten ebenfalls die Hochrisiko-Kriterien. Der Anfangs-Blutdruck betrug 160+15 / 96+10 mm Hg und fiel
nach 4 Monaten Behandlung mit Telmisartan signifikant auf 138 + 10
/ 84 + 7 mm Hg (p <0,0001). Die MA reduzierte sich nach 4 Monaten
Therapie mit Telmisartan bei den Patienten ohne vorbehandelte
Hypertonie signifikant von 9,5 + 16 mg/mmol auf 6,5 + 13 mg/mmol
und bei den vorbehandelten Patienten von 8,7 + 14 mg/mmol signifikant auf 6,1 + 11 mg/mmol (beide p <0,0001).
Konklusion: Sehr viele Hypertoniker in Hausarztpraxen sind Hochrisikopatienten. Diese Feststellung entspricht Ergebnissen der hausärztlichen schweizerischen Hypertoniekohorte und Untersuchungen
anderer europäischer Länder. Wenn, wie in vorliegender Untersuchung, zusätzlich die MA bestimmt wird, steigt der Anteil der behandlungsbedürftigen Hochrisikopatienten auf 78% an. Die Ergebnisse
unterstreichen die unterschätzte Bedeutung der gezielten MABestimmung in der Hausarztpraxis. In unserer Untersuchung wurde
ferner gezeigt, dass bei hausärztlichen Hypertonikern durch Therapie
mit Telmisartan neben einer starken Blutdrucksenkung das Mikroalbumin im Urin, hochsignifikant gesenkt werden kann.
P48
Paradoxe Koronarembolie und Lungenembolien bei einem
Patienten mit hereditärer hämorrhagischer Teleangiektasie
Frasnelli M.E., Müller-Burri S.A., Kurz D.J., Tüller D., Eberli F.R.,
Brühlmann W., Meier C.A. (Zürich)
Fall: Ein 46jähriger Patient mit hereditärer hämorrhagischer Teleangiektasie (HHT) wurde knapp eine Woche nach einer Meniskektomie
wegen Thoraxschmerzen und Dyspnoe beim Hausarzt vorstellig.
Bei inferiorem ST-Hebungs-Myokardinfarkt im EKG zeigte sich in der
Koronarangiographie ein distaler Verschluss des R. interventricularis
posterior bei sonst nicht relevanter Koronaratheromatose. Die wegen
persistierender Beschwerden durchgeführte Computertomographie
ergab parazentrale Lungenembolien und mehrere, für die HHT typische, pulmonale arteriovenöse Malformationen (AVM). Nach Ausschluss eines intrakardialen Shunts und eines offenen Foramen ovale
interpretierten wir den Verschluss des R. interventricularis posterior
als Folge einer paradoxen Embolisation über die AVM im Rahmen
eines durch die postoperative Immobilisation getriggerten thromboembolischen Ereignisses. Nach interventionellem Verschluss der
pulmonalen AVM mittels Coils wurde der Patient mit einer oralen
Antikoagulation entlassen.
Diskussion: Die HHT (Osler-Weber-Rendu Syndrom) ist mit einer
Inzidenz von 1/5000–8000 eine seltene, autosomal dominant vererbte
Krankheit. Mutationen im Gen für Endoglin oder activin-receptor-like
kinase 1 (ALK1) führen zu Gefässmissbildungen in verschiedenen
Organen. Charakteristisch für die HHT sind mukokutane Teleangiektasien, Epistaxis, gastrointestinale Blutungen und eine Eisenmangelanämie. Etwa 30% der Patienten zeigen zudem AVM der Lunge
und/oder der Leber und etwa 10–20% im ZNS. Häufige Komplikationen der pulmonalen AVM sind hämodynamisch relevante rechts-links
Shunts, Blutungen (Hämoptyse, Hämatothorax) und paradoxe Embolien mit Hirnabszess und -infarkt. Bei den vereinzelt beschriebenen
kardialen Komplikationen der HHT handelte es sich jeweils um ischämische Ereignisse bei Aneurysmata der Aa. coronariae. Unser Fall
beschreibt erstmals das Auftreten eines Myokardinfarktes bei einem
Patienten mit HHT als Folge einer paradoxen Embolie. Dabei waren
die pulmonalen AVM die pathogenetische Verknüpfung, welche zum
gleichzeitigen Auftreten der Lungenembolien und des Herzinfarktes
führte.
P50
An unusual case of congestive heart failure
Manser C.N., Zbinden R., Meier C.A., Gerber B. (Zürich)
We report the case of a 52 year old female diabetic patient with
known sensorineural hearing-loss, presenting with congestive heart
failure and severe lactic acidosis. Echocardiographic findings
revealed severe systolic and diastolic dysfunction and a strikingly
hyperechogenic myocardium, suggesting restrictive, infiltrative cardiomyopathy. Common systemic illnesses showing cardiac envolvement, such as amyloidosis, storage diseases and iron overload, could
be ruled out. The combination of restrictive cardiomyopathy, diabetes
mellitus, deafness and sustained lactic acidosis finally led to the
hypothesis of a mitochondrial disorder which was confirmed by
genetic testing. Analysis of mitochondrial (mt) DNA showed an A-to-G
mutation in the tRNALeu(UUR) gene at nucleotide position (np) 3243.
This mt DNA 3243(A-G) mutation has originally been reported in
patients presenting with mitochondrial encephalomyopathy, lactic
acidosis and stroke like episodes (MELAS), but is also known to be
associated with early onset diabetes mellitus. Some authors even
claim that this mutation may be present in up to 0.5–2,8% of the
diabetic population. Clinical findings in patients with mt DNA 3243
(A-G) mutation are heterogenous: A Japanese study of 113 mutant
diabetic patients demonstrated neurosensory deafness in 92%,
POSTERS SSMI
POSTERS SGIM
basal-ganglia calcification in 71%, neuromuscular disorders in 23%
and neuropsychiatric disturbances in 16% of all cases. Cardiomyopathy was present in 30% of all patients with dilated (18%) and hypertrophic (8%) cardiomyopathy being the most common disorders.
Cardiac conduction abnormalities were detected in 27%. Even
though cardiomyopathy seems to be an important complication in
patients with mt DNA 3243(A-G) mutation, it appears to be even more
common in mt DNA 3260(A-G) and 3303(C-G) mutations.
Conclusion: In restrictive cardiomyopathy a mitochondrial disorder
should be considered if a combination of clinical features such as
early-onset diabetes, hearing loss, lactic acidosis and neuropsychological abnormalities is present. Genetic counselling of affected
individuals and families is essential.
P51
Fünf Fälle einer Thrombolyse unter CPR nach fulminanter
Lungenembolie mit Kreislaufstillstand
Frank B., Mang G. (Männedorf)
Wir präsentieren eine Serie von fünf Patienten, welche in den letzten
4 Jahren in unserer Klinik einen Kreislaufstillstand (PEA) aufgrund
einer fulminanten Lungenembolie (LE) erlitten hatten und unter
cardiopulmonaler Reanimation (CPR) einer Thrombolyse unterzogen
wurden.
Methode: Zusammenstellung aller Fälle, welche im Spital Männedorf
seit 2003 nach einem Kreislaufstillstand aufgrund einer LE unter CPR
thrombolysiert worden sind. Mit Blick auf die Anamnese, das Outcome und Komplikationen. Das Vorgehen wurde gewählt, wenn aus
der unmittelbaren Anamnese eine LE vermutet werden musste,
oder eine solche durch indirekte echokardiographische Zeichen
hochwahrscheinlich war und die konventionellen Massnahmen der
CPR nicht zum Wiedererlangen eines spontanen Kreislaufes geführt
hatten. Die Lyse wurde mit Alteplase durchgeführt. Im Anschluss
daran erfolgte die therapeutische Liqueminisierung.
Resultate: Bei sämtlichen Patienten konnte initial ein suffizienter
Kreislauf wiedererlangt werden. In keinem Fall wurden Blutungskomplikationen beobachtet, obschon eine Patientin 3 Tage zuvor einem
grossen viszeralchirurgischen Eingriff unterzogen worden war (Whipple Operation). 4 der 5 behandelten Patienten überlebten und konnten aus dem Spital entlassen werden, 1 Patientin verstarb wenige
Stunden post reanimationem am Rechtsherzversagen. 3 Patienten
zeigten keine neurologischen Defizite, 1 Patientin litt während
2 Wochen an einem regredienten, brachial betonten motorischen
Hemisyndrom der linken Seite, welches jedoch nach einem Monat
nicht mehr objektivierbar war.
Schlussfolgerung: Ein Kreislaufstillstand nach fulminanter
Lungenembolie hat eine schlechte Prognose, die Literatur spricht von
Überlebensraten unter 40%. Unsere Serie zeigt, dass die Thrombolyse nach erfolgloser konventioneller CPR die Prognose verbessern
kann, dies betrifft sowohl das Überleben als auch das neurologische
Outcome. Ausserdem konnte gezeigt werden, dass dieses Vorgehen
auch Patienten im unmittelbar postoperativen Status nicht a priori
vorenthalten werden sollte, da es nicht obligat zu Blutungskomplikationen kommt. Unsere Ergebnisse decken sich weitgehend mit der
vorhandenen Literatur, sowie mit den Reanimationsrichtlinien von
2005 des European Resuscitation Council.
Forum Med Suisse 2008;8:(Suppl. 40)
37 S
range to >6 mcg/l). Cardiac ultrasonography revealed moderate
inferobasal left ventricular hypokinesia, with normal ejection fraction,
and cardiac CT scan demonstrated moderate coronary atherosclerosis. LDL cholesterol levels were found to be extremely low at 0.23
mmol/l (HDL3 subfraction), with total cholesterol (3.4 mmol/l), LDL
cholesterol (2.29 mmol/l) and triglyceride levels (1.72 mmol/l) in the
normal range. Testing on first-degree relatives of the proband showed
that both mother and father had low HDL cholesterol levels (0.55
mmol/l and 0.66 mmol/l, respectively). One paternal uncle and two
maternal uncles had low HDL cholesterol levels (0.59 mmol/l, 0.69
mmol/l, and 0.71 mmol/l, respectively). Genetic analysis on the
proband (sequencing after amplification) revealed a new nonsense
mutation on codon 84 (Q84R, glutamine to arginine) of the
apolipoprotein A-I gene, a site previously identified for a Q84X mutation leading to premature CV events. Not only has this mutation never
been previously reported, but the proband is homozygous. Homozygosity for codon 84 nonsense mutation should be considered the
cause of the low HDL cholesterol levels in the present case. We are
currently analysing the kindreds, several among which present with
premature coronary heart disease, to understand the segregation of
this new hypoalphalipoproteinemia. Furthermore, this new mutation
could be added to the list of relevant mutations that are searched for
in cases of familial apolipoprotein A-I deficiency.
P53
Left ventricular diverticulum associated with Tako-Tsubo
cardiomyopathy: role of cardiac MRI
Oberson M., Wyttenbach R., Di Valentino M., Santini P., Moccetti M.,
Gallino A. (Bellinzona)
Clinical case: We report the case of a 61-year-old woman with atypical chest pain associated with typical ECG changes (T-wave inversion
in V2-V6 and I-II-aVL; with left ventricular apical dysfunction at
transthoracic echocardiography and normal cardiac enzymes. Coronary angiography was normal. At left ventricular angiography the
apical akinesia was confirmed and was associated with the presence
of a large antero-basal diverticulum of the left ventricle. At cardiac
magnetic resonance (CMR) performed 7 days after admission, the
dyskinetic dysfunction disappeared completely and there was no
evidence of delayed enhancement suggestive for fibrosis due to
previous myocardial infarction or inflammation. CMR also confirmed
the presence of an antero-basal, left ventricular trabeculated diverticulum communicating with the left ventricle by a large “collet” and
exhibiting a synchronous contraction with the left ventricle. No paradoxical systolic expansion was appreciated. The patient was treated
with atenolol, enalapril and aspirin. At a follow-up visit after 2 months,
the patient complained of no symptoms, ECG was normal.
Conclusion: Our case is compatible with a form of Tako-Tsubo cardiomyopathy associated with the unusual concomitant presence of a
large antero-basal diverticulum. CMR was crucial in defining localization and morphology of the left ventricular diverticulum. CMR was
also important in detecting and clearly defining the transitory dyskinetic apical area without evidence of late enhancement.
P52
P54
Premature coronary heart disease due to a codon
84 nonsense mutation of the apolipoprotein A-I gene
Zimmermann S., Hayoz D. (Fribourg)
Apolipoprotein A-I (apo A-I) deficiency leading to low or very low HDL
cholesterol levels is a cause of increased risk of coronary heart
disease, restenosis after angioplasty and death from cardiovascular
causes. Affected patients have a primary depression in HDL cholesterol to below the tenth percentile compared with age and sexmatched controls. A disturbance in lipoprotein metabolism is often
familial. We report the case of a 28 year old male patient, without any
know cardiovascular risk factors, who presented with acute coronary
syndrome (NSTEMI with troponin Ic elevated to above the normal
Extrinsic compression of the pulmonary artery by a large
mediastinal mass: the role of TTE in the decision making for
urgent thoracic surgery
Oberson M., Menafoglio A., Guerra A., Alerci M., Zucca E.,
Di Valentino M., Moccetti M., Mazzucchelli L., Gallino A.
(Bellinzona, Locarno)
Clinical case: We report the case of a 19-year-old man, ice-hockey
player who presented with a 2-months history of asthenia and nonspecific chest pain. At admission, EKG was completely normal, clinical evaluation did not reveal evident signs of infection, bacterial blood
cultures remained negative. Laboratory analysis indicated only an
elevated ESR, whereas CRP was only slight increased. Chest X-ray
POSTERS SSMI
POSTERS SGIM
revealed a large mass located in the anterior mediastinum. Urgent
transthoracic echocardiography (TTE) showed pulmonary hypertension (45 mm Hg) without enlargement of the right ventricle and confirmed the presence of a large anterior mediastinal hypoechogenic
mass compressing the right ventricular outflow tract during diastole.
There was a systolic gradient over the right compressed pulmonary
artery of 30 mm Hg. These findings were confirmed on subsequent
contrast-enhanced multi-detector Computed Tomography (MDCT)
of the chest which showed a large tumor of 13 x 8.5 x 8.0 cm which
surrounded the outflow tract of the great arteries with severe compression of the right ventricular outflow tract. Due to increased risk
of sudden death, an urgent surgical removal of the mediastinal mass
followed by a biopsy was successfully performed; the patient recovered immediately and leaved the hospital 4 days later only. Histologically, the tumor was diagnosed as a mediastinal B giant cell lymphoma. The patient was serially followed up with chemotherapy.
Conclusion: This case illustrates the important role of TTE in the
decision making of urgent removal of the mediastinal mass.
Forum Med Suisse 2008;8:(Suppl. 40)
38 S
P56
Coronary fibromuscular dysplasia: an elusive diagnosis
Oberson M., Kosmidis S., Mahler F., Alerci M., Wyttenbach R.,
Tutta P., Di Valentino M., Moccetti M., Sartori F., Gallino A. (Bellinzona)
Fibromuscular dysplasia (FMD) is a disorder that generally affects the
renal arteries. Involvement of FMD occurs less often in other arterial
territories such as carotid, subclavian, iliac or mesenteric arteries.
Involvement of the coronary arteries is extremely rare. A 46-year-old
woman with a history of typical chest pain at rest four weeks before
admission, was referred by her general practitioner because of the
presence of inverted T-waves (in V3-V5). Cardiac enzymes, D-dimer
and CRP values, were in the normal range. No atherosclerotic risk
factors were present. Coronary angiography showed an isolated
(1-1-1 smooth) 60% lesion at the bifurcation of the third diagonal
branch of the LAD. Selective angiography of the renal arteries performed during the same invasive procedure, showed the typical
pattern of FMD with “string of beads” appearance of the right renal
artery. Cardiac-MRI indicated a small area of delayed enhancement
compatible with a previous small antero-septal non-transmural
myocardial infarction with no evidence of residual myocardial
ischemia during adenosine perfusion. Given the association of a
single distal lesion of the LAD and the typical pattern of renal FMD,
as well as the lack of risk factors, we postulated the tentative
diagnosis of coronary FMD, although concomitant “trivial” coronary
atherosclerosis cannot be completely excluded.
P55
Systemic arterial embolism in a young body-builder
Moccetti M., Wyttenbach R., Alerci M., Oberson M., Santini P.,
Di Valentino M., Tutta P., Lepori M., Gallino A. (Bellinzona)
A 31 one year old man without cardiovascular risk factors was
referred in 2001 to our emergency division because acute arterial
ischemia of the left lower extremity. The patient was a well known
bodybuilder (former swiss champion) with active consume of anabolic
drugs (positive test in urine for anabolic steroids, negative for
cocaine). Screening for thrombophilia was negative and search for
embolic sources was negative (TEE) although TTE showed the
presence of a small isolated apical hypokinesia without thrombi which
was not considered a plausible cause of the clinical picture. The
acute ischemia was attributed to a popliteal artery entrapment syndrome with massive hypertrophy of the gastrocnemi muscles and to
a putative hypercoagulable state associated with active consume of
anabolic drugs. The patient was successfully treated with percutaneous thrombus extraction an local lysis of the popliteal artery. The
unusual case was interesting enough to be published as a letter in a
peer reviewed journal (N Engl J Med: 2002:346:1254). The patient
was discharged with oral anticoagulation for 3 months and the advice
to quit the use of anabolic drugs and restrain from body building.
The patient was then lost of follow-up. He was admitted urgently in
2007 with bilateral acute ischemia of the lower legs and acute arterial
embolism of the left renal artery. The patient underwent successful
percutaneous recanalisation of the femoropopliteal arteries and
was anticoagulated with e.v non fractionated heparin,clopidogrel
and aspirin. He was still an active bodybuilder and anabolic steroid
metabolites in urine were again positive.Cardiac MRI showed the
presence of a small apical LV akinesia (without visible thrombi) with
transmural late enhancement compatible with a previous myocardial
infarction. Coronary angiography showed normal epicardial vessels.
The hypothesis that the apical akinesia may be the cause of the
repetitive arterial embolisations, in absence of other sources, remains
the most probable although the cause of the LV apical infarction
remains elusive. A contributing factor may be a putative
thrombophilic state associated with the use of anabolic steroids.
This case show an unusual form of systemic arterial embolisation in a
body builder. It also show how during the diagnostic initial reasoning
an important finding (LV apical hypokinesia at TTE) may be disregarded while focussing to much on the initial clinical presentation
and may mislead from the right diagnosis.
P57
Après une fracture ostéoporotique: quelle prise en charge et
quelle risque de récidive? Résultat d’une enquête lausannoise
Lamy O., Simard N., Krieg M.-A. (Lausanne)
Introduction: L’événement fracturaire est associé à un haut risque de
récidive fracturaire. Il se situe, après une année, entre 8 et 20%, selon
la localisation de la fracture, l’âge et le sexe des patients. L’introduction d’un traitement spécifique de l’ostéoporose réduit le risque fracturaire vertébrale de 50%, non vertébral de 20 à 30%. L’ostéoporose
reste une maladie sous-diagnostiquée et sous-traitée. Le but de cette
étude est de connaître le devenir des patients une année après la
survenue d’une fracture.
Méthode: Pendant une année, tous les patients de plus de 50 ans
admis au CHUV pour une fracture ont été interviewés (données
démographiques, type de traumatisme, traitement de l’ostéoporose,
réalisation d’une densitométrie osseuse (DXA)). Les patients et leurs
médecins-traitants ont reçu une information écrite sur l’opportunité
d’effectuer un bilan et éventuellement un traitement de l’ostéoporose.
Les patients ont été contactés téléphoniquement une année plus
tard.
Résultats: Sur les 600 patients inclus (femmes 73%; âge moyen
74 ± 13 ans; fractures atraumatiques 84%, hospitalisation 79%), des
informations ont été obtenues une année plus tard pour 356. 285
patients (80%) vivent à domicile, 23 (7%) en EMS et 46 (13%) sont
décédés. 297 patients (73 ± 12 ans) ont répondu au questionnaire
téléphonique. Le nombre de patients ayant eu une DXA a passé de
32 (11%) à 66 (22%). Le nombre de patients traités par calcium±vitamine D a passé de 83 (28%) à 129 (43%), et ceux sous bisphosphonates de 21 (7%) à 55 (19%). 23 patients (73 ± 12 ans) ont eu au
moins une nouvelle fracture, atraumatique chez 22. Les sites de
fractures étaient: hanche 30%, avant-bras 30%, squelette axial 13%,
humérus 9%, tibia/péroné 9%. Le risque annuel de nouvelle fracture
était plus élevé si la première fracture était typiquement ostéoporotique: 9% vs 3%. La proportion de patients traités était la même pour
ceux ayant eu et ceux n’ayant pas eu de nouvelles fractures.
Conclusion: Chez les hommes et femmes de plus de 50 ans ayant
présenté une fracture ostéoporotique, une DXA est rarement réalisée
et un traitement spécifique de l’ostéoporose rarement initié. Le risque
de nouvelle fracture à une année est relativement élevé, ce qui devrait
d’autant plus motiver une prise en charge médicale agressive.
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P58
Cardiac rehabilitation improves patients’ risk factor
awareness and risk perception
Merz K., Hoffmann A., Büchi S., Battegay E., Zimmerli L.
(Basel, Zürich)
Objective: Most patients with coronary artery disease (CAD) have
treatable atherogenic risk factors (RF) such as lipid abnormalities,
hypertension, diabetes, and smoking. Adequate awareness of RF is
a key first step that enables patients to address their risk factors.
We hypothesised that RF awareness improves after a cardiac
rehabilitation programme.
Design and method: A total of 90 patients (17 women and 73 men)
aged 62 ± 11 years with CAD confirmed by coronary angiogram were
assessed at the beginning and 65 of them at the end of a 12-week
outpatient exercise-based comprehensive cardiac rehabilitation
programme at the University Hospital Basel. Patients were asked to
recall as many cardiac RFs as possible and to rate the risk of seven
given RFs. For RF rating a visualisation technique, PRISM (Pictorial
Representation of Illness and Self Measure), was used.
Results: The mean RF knowledge at the beginning of the rehabilitation programme was 4.2 ± 1.8 (median 4) out of a possible 12. Smoking (81%), excess stress (60%) and lack of exercise (48%) were the
most common factors reported whereas the other well known RFs
such as lipid abnormalities (48%), hypertension (29%) and diabetes
(16%) were mentioned by a minority of patients. Patients affected by
RFs did not recall them more often than patients without the corresponding RF. In patient-perceived risk of seven given RF, smoking
was perceived to have the greatest risk, followed by hypertension,
lipid abnormalities and excess stress. Family history of CAD was
perceived as low risk by patients. After the rehabilitation programme
RF knowledge improved to 5.2 ± 1.6 (median 5, p <0.001); positive
family history and cholesterol were perceived to have greater risk
than at entry (p = 0.03 and p = 0.06, respectively).
Conclusions: Patients with CAD have limited knowledge about RFs
of their disease, whether affected by them or not. In particular, knowledge about traditional RFs such as hypertension, diabetes and lipid
abnormalities is low in general prompting. This is in contrast to the
high patient-perceived risk of these RFs when they are specifically
asked about them. A cardiac rehabilitation programme can improve
RF knowledge and modify risk perception in patients. Therefore, highrisk patients, such as patients with CAD, should be specifically targeted with educational strategies in order to improve RF knowledge
and behavioural modification.
P59
Histoire clinique: asystolie ictale lors d’une crise épileptique
inaugurale
Pannatier M., Faucherre M., Hecker E., Hayoz D. (Fribourg)
Un patient de 69 ans, ayant pour seul antécédent neurologique un
accident ischémique cérébral transitoire, présente, dans les suites
d’une opération de résection vésicale transurétrale, 3 malaises avec
mouvements toniques. L’enregistrement électroencéphalographique
(EEG) a permis d’objectiver lors d’un malaise similaire des ondes
alpha-thêta au niveau temporal gauche avec généralisation secondaire. Parallèlement, l’enregistrement électrocardiographique (ECG)
simultané met en évidence, quelques secondes après le début de la
crise épileptique, une asystolie de 23 secondes consécutives. Ce cas
d’asystolie ictale a fait l’objet d’un consilium entre neurologues et
cardiologues à l’issue duquel la décision d’implanter un pacemaker a
été prise, compte tenu de la cardiopathie ischémique dont souffre le
patient. Sous traitement d’acide valproïque, il n’a plus présenté de
crise épileptique et se porte bien. Une base de données [1] ayant
monitoré 6285 patients par enregistrement EEG-ECG-vidéo a relevé
une incidence de 0,27% d’asystolie ictale. Sur les 10 cas, 8 sont
survenus lors d’épilepsie temporale et 2 lors d’épilepsie extratemporale. Dans les 8 cas d’épilepsie temporale, les patients ont présenté
une atonie soudaine de 42 secondes en moyenne, typique d’une
hypoperfusion cérébrale, survenant à partir de périodes d’asystolie
supérieures à
8 secondes. L’issue fatale possible de cette condition (Sudden Unexplained Death in Epilepsy, SUDEP) rend son dépistage et sa reconnaissance cruciaux. Ainsi, la survenue d’atonie, communément atypique lors d’épilepsie temporale se traduisant cliniquement par une
chute ou une syncope tardive au cours d’une crise d’épilepsie typi-
Forum Med Suisse 2008;8:(Suppl. 40)
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que doit faire rechercher une asystolie secondaire. Les options
thérapeutiques sont à discuter de cas en cas, se limitant à un traitement médicamenteux adéquat pour les patients qui y répondent, à
l’option plus radicale de l’implantation d’un pacemaker pour les cas
de résistance pharmacologique ou les patients présentant un terrain
préalable de cardiopathie. La physiopathologie sous-jacente a fait
l’objet d’une autre étude qui postule comme cause de ces asystolies
ictales une augmentation du tonus vagal médiée par l’effet parasympathique de la stimulation corticale de l’hémisphère gauche.
1 Neurology 2007;69:434–441.
P60
Pericarditis constrictiva after cardiac surgery:
a report of two cases
Stähli C., Moll C., Krause M., Widmer F. (Münsterlingen)
Introduction: During the last decades, the predominant cause
of constrictive pericarditis shifted from infectious (eg tuberculous)
to therapy-related aetiologies. Cardiac-surgery and radiotherapy
account for most cases today. The constriction develops from
pericardial effusion to fibro-elastic, subacute pericarditis which still
may be reversible. When the disease progresses to a rigid, shell-like
chronic pericarditis, only surgery may be successful. Echocardiography plays a pivotal role in the diagnosis of constrictive pericarditis,
however, differentiation between constrictive and restrictive impairment may be difficult. We report two patients with rigid-shell constriction after cardiac surgery and the immediate hemodynamic normalization after surgical pericardectomy.
Patient 1: Male, age 80; 17 months after aortic valve replacement,
he presented with relapsing bilateral pleural effusion, orthopnea and
jugular vein distention (NYHA IV, BNP 284 ng/ml). There was no evidence of LV or valve dysfunction. Doppler studies revealed an expiratory increase of enddiastolic flow reversal in hepatic veins and a lack
of respiration dependent variation of transmitral and transtricuspidal
flow (Figure). The diagnosis of pericardial constriction was confirmed
by catheterisation. A NSAR trial over 3 months did not improve the
symptoms.
Patient 2: Male, age 62; two months after aortic valve replacement,
he presented with dyspnea, anasarca and jugular vein distention
(NYHA III, BNP 674 ng/ml). LV- and valve function were normal.
Doppler studies showed an expiratory increase of enddiastolic flow
reversal in hepatic veins. Cardiac catheterisation confirmed the diagnosis of pericarditis constrictiva. Impaired renal function forestalled
drug therapy with NSAR.
Therapy: Both patients underwent surgical pericardectomy which
resulted in immediate normalisation of hemodynamics and echodoppler studies. Histologically, pericardial inflammation and fibrosis
was found.
Comments: Cardiac impairment after successful cardiac surgery may
be due to evolving pericardial constriction. Jugular vein distension,
anasarka and characteristic doppler-echocardiography signs support
the diagnosis of pericarditis constrictiva. An invasive confirmation of
the diagnosis is mandatory. If the constrictive features do not resolve
by NSAR, surgical pericardectomy is the therapy of choice.
Figure 1
Pericarditis
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P61
Übelkeit und Erbrechen als Zeichen einer akuten
Bronchoobstruktion bei ASS-Intoleranz
Dürr C., Michel S., Fricker M., Helbling A. (Bern)
Hintergrund: Die Inzidenz einer Aspirinintoleranz in der Allgemeinbevölkerung wird zwischen 0,6–2,5%, bei Asthmatikern bis zu 11%
angegeben. Kontrollierte Provokationstestungen (inhalativ oder oral)
mit Acetylsalicylsäure (ASS) oder nichtsteroidalen Antirheumatika
(NSAR) sind das diagnostische Mittel der Wahl. Die Symptome einer
ASS-Intoleranz sind mannigfaltig und reichen von akutem Bronchospasmus, akuter Urtikaria, Angioödem, Flushing, akuter Rhinitis oder
Konjunktivitis über Myokardischämie bis zum anaphylaktischen
Schock.
Kasuistik: Ein 42jähriger Patient mit chronisch obstruktiver Nasenatmungsbehinderung wurde uns zur Abklärung zugewiesen. Bereits
zweimal wurde wegen rezidivierender Polyposis nasi ein operativer
Eingriff durchgeführt, allerdings ohne anhaltenden Erfolg. Ein Asthma
war nicht bekannt. Anamnestisch traten nach Einnahme von
ASS/NSAR wiederholt Übelkeit, Erbrechen oder eine akute Urtikaria
auf. Im Blutbild bestand keine Eosinophilie, das eNO (Niox) in der
Ausatmungsluft war normal (<20 ppb), der Metacholinbronchoprovokationstest (>2,4 mg) wie auch der inhalative L-ASS-Provokationstest
(>60 mg) fielen negativ aus. Daher wurde eine orale Provokationstestung mit ASS, beginnend mit 80 mg, durchgeführt. Bei der kumulativen Dosis von 240 mg ASS wurde ein Peakflow-Abfall (PEF) von 580
auf 470 l/min. verzeichnet. Der Patient beklagte keinerlei, insbesondere aber keine respiratorischen Beschwerden, so dass die Testung
fortgeführt wurde. Nach kumulativ 400 mg ASS äusserte er plötzlich
Übelkeit ohne respiratorische Symptome. Der PEF betrug 320 l/min.
und eine Bradykardie von 54/min wurde festgestellt. Nach heftigem
Erbrechen realisierte der Patient ein thorakales Engegefühl, das er
dem Erbrechen zuordnete. Weil eine bronchiale Obstruktion offensichtlich war, wurde dem Patienten inhalativ Salbutamol und Adrenalin sowie peroral Levocetirizin und intravenös Methylprednisolon
verabreicht, was zu einer raschen klinischen Besserung führte
(PEF 550 l/Min).
Konklusion: Übelkeit und Erbrechen können einen akuten Bronchospasmus bei ASS-Intoleranz maskieren. Aufgrund der begleitenden
Bradykardie, Nausea und akutem Erbrechen ist eine vagale Stimulation die wahrscheinlichste Erklärung dieser «gastro-bronchialen»
Reaktion.
P62
«...dieses Antibiotikum macht Brustschmerz....»
Kröger A., Alfaré C., Bachmann U., Gubler C. (Uster)
Eine 83jährige Patientin wird mit akut aufgetretener Dyspnoe und
rechtsthorakalen Schmerzen zugewiesen. In der konventionellen
Röntgenaufnahme des Thorax zeigt sich eine Atelektase des rechten
Unterlappens (Abb. 1). Bei klinischem Verdacht auf Lungenembolie
wird ein CT des Thorax durchgeführt. Hier findet sich eine
stenosierende Raumforderung im Bereich des rechten Unterlappens
(Abb. 2). Eine Lungenembolie kann ausgeschlossen werden. Bei
einem bekannten Nikotin-abusus steht der Verdacht auf ein malignes
Geschehen im Raum. Zur weiteren Abklärung wird eine
Bronchoskopie durchgeführt. Hier sieht man eine den Bronchus
intermedius verlegende Tablette (Abb. 3), welche in gleicher Sitzung
via Bronchoskop entfernt werden kann. Nach erneutem Befragen der
Patientin stellt sich heraus, dass die Beschwerden unmittelbar nach
Einnahme eines Antibiotikums wegen eines Harnwegsinfektes aufgetreten waren. Es war offensichtlich zu einer Aspiration der Tablette
gekommen. Retrospektiv betrachtet, handelte sich bei dem Tumor
«nur» um eine aspirierte Tablette (Abb. 4), deren Einnahme eigentlich
einen kurativen Zweck hatte. Nach antibiotischer, symptomatischer
und physio-therapeutischer Therapie der durch Tabletten-Aspiration
verursachten poststenotischen Pneumonie und Unterlappenatelektase, kommt es innerhalb von 2 Wochen zur Genesung der Patientin
Die Verlaufsbronchoskopie zeigt einen unauffälligen Befund. Fremdkörperaspirationen sind bei Kindern nicht so selten und werden differentialdiagnostisch bei der Abklärung von Atelektasen in Betracht
gezogen [1]. Typischerweise ist die Anamnese bland und die Kinder
3–10 Jahre alt [2]. Bei Erwachsenen ist die Fremdkörperextraktion
eine Seltenheit; weniger als 1% aller Bronchoskopien werden wegen
einem Fremdkörper indiziert [3]. Die Diagnose kann mit der Computertomographie idealerweise als virtuelle 3D Rekonstruktion gestellt
werden [4], eine Missinterpretation als endoluminaler Tumor ist allerdings nicht selten [5]. Fremdkörper sind meist Essensbestandteile
(Knochen) und Zahnimplantatteile oder Zähne [6]. Therapie der Wahl
Forum Med Suisse 2008;8:(Suppl. 40)
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ist die flexible bronchoskopische Entfernung, die in 99% gelingt [7].
Dieser Fall unterstreicht die Wichtigkeit einer genauen Anamneseerhebung. Die Patientin war nicht überrascht vom Bronchoskopiebefund: «..ich habe doch gesagt, dieses Antibiotikum ist schuld an
diesen Brustschmerzen …».
Referenzen
1 Int J Pediatr Otorhinolaryngol 2007 Feb;71(2):241–6.
2 Eur J Cardiothorac Surg. 2005 Sep;28(3):369–74
3 Eur Respir J. 1999 Oct;14(4):792–5.
4 Semi Ultrasound CT MR 2005 Oct;26(5):364–73
5 Respiration 2006;73(6):826–9
6 Pneumologie 2005 Mar;59(3):174–7.
7 Ann Saud Med 2006 Jul-Aug;26(4):283–7
P63
Die Behandlung eines 24jährigen Patienten mit fortgeschrittener,
kavernöseer multiresistenter Lungentuberkulose
Sladovnik P., Shang Meier H., Rossi M., Pfyffer G.E., Karrer W.
(Crans-Montana, Luzern)
Einleitung: Anfang 2007 reiste der 24jährige Asylsuchende aus der
Elfenbeinküste in die Schweiz (CH), um seine Tuberkulose (TB)
behandeln zu lassen. In seinem Heimatland wurde die Behandlung
wegen Mangel an Medikamenten wiederholt unterbrochen, was zu
Resistenzproblemen führte. Seit 2005 wird in der CH bei Asylsuchenden kein TB-Screening mehr durchgeführt. Jedoch findet ein Interview durch ausgebildete Pflegefachkräfte statt [1]. Der Patient wurde
in ein lokales Spital eingewiesen.
Methoden: Die Behandlung erfolgte mit Isoniazid (INH), Rifampizin
(RMP), Ethambutol (EMB) und Pyrazinamid (PZA), ergänzt wegen
vermuteter Resistenz mit Amikacin. Aufgrund der Resistenzprüfung
wurde eine ausgedehnt resistente TB (Extensively Drug Resistant TB
XDR-TB) diagnostiziert. Bis heute registrierte man in der CH keine
XDR-TB. Nach 10 Wochen stationärer Therapie wurde das Sputum
direkt negativ und der Patient ohne weitere Kontrollmassnahmen in
eine Asylantenunterkunft nach Luzern verlegt. Erst mit erneut
mikroskopisch positivem Sputum wies ihn der zugezogene Heimarzt
sofort ins Luzerner Kantonsspital (LUKS) ein, von wo er anschliesend
zur Behandlung in die Luzerner Höhenklinik Montana verlegt wurde.
Resultate: Die Resistenzprüfung im LUKS ergab Empfindlichkeit auf
EMB, Moxifloxacin (MFX) und Amikacin (AMK), was nach internationalen Richtlinien einer multiresistenten TB (Multi Drug Resistant TB
MDR-TB) entspricht, mit einer deutlich besseren Prognose. Das
Resistenzmuster zeigte, dass eine Behandlung nur noch mit INH,
EMB, AMK, MFX und Linezolid möglich war. Nach 9 Wochen konnte
eine Lobektomie des linken Oberlappens durchgeführt werden um die
Masse des Infektionsherdes zu verkleinern. Nach 5 Monaten Behandlung wurden aufgrund mehrfach negativer Sputumkulturen und schwerwiegender Nebenwirkungen (Ototoxizität, Polyneuropathie) AMK
und Linezolid sistiert. Die Behandlung mit INH, EMB und MFX wird
1 Jahr weitergeführt.
Schlussfolgerung: 1. Ungenügende Medikation führte zur MDR-TB.
2. Die MDR-TB hat in Entwicklungsländern eine schlechte Prognose.
3. Die XDR-TB hat auch in westlichen Ländern eine sehr schlechte
Prognose, welche sich derjenigen der Vor-Tuberkulostatika Ära
annähert. Deshalb ist eine genaue Einteilung aufgrund des Resistenzmusters prognostisch entscheidend.
(1) Mathez Ch et al. Active screening for pulmonary tuberculosis by
chest x-ray among immigrants at the Swiss border. Swiss Med Wkly.
2007;137:649–654.
Abbildung 1
Multiresistente, kavernöse
Lungentuberkulose
Abbildung 2
Lungentuberkulose.
St.n. Oberlapenresektion links
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P64
P66
Piqûre d’insect aux urgences: toujours une banalité?
Lepori M., Kistler M. (Bellinzona)
Background: Les piqûres d’insectes sont une cause fréquentes
de consultations en urgences pendant les mois d’été. Leur prise en
charge n’est pas standardisée et les données de la littérature sont
rares en dehors de ceux concernant la prise en charge des anaphylaxies graves.
Buts: Analyser l’incidence, les modalités de prise en charge et
l’évolution clinique des patients consultant un centre d’urgences
pluridisciplinaire, à la suite d’une piqûre d’insecte.
Methodes: Analyse prospective par formulaire standard, sans directives diagnostique ou thérapeutiques, des cas entre le 1er juin et le
31 août 2006.
Resultats: Pendant la période d’observation nous avons enregistré
128 cas (3,5% des consultations): Seulement 4 patient avaient une
anamnèse d’allergie aux hyménoptères. Un seul patient utilisait une
protection anti-insectes au moment de la piqûre. Le nombre de
patients avec réaction systémique était de 19 (20%) et le nombre
d’hospitalisation (>24 heures) de 13 (10%). Trois patients ont été
hospitalisé en Soins Intensifs avec un choc anaphylactique. 109
patients présentaient uniquement une réaction locale dont 16%
avaient en plus des signes de surinfection (lymphangite, adénopathie
satellite ou signes d’abcédassions). Plus de 70% des patients ont
reçu des anti-H1, 47% des stéroïdes, 35% des antibiotiques et 12%
un rappel antitétanique. Malgré 22 cas de piqûre par tique aucune
prophylaxie par doxycicline à été proposée. Un seul cas d’erythema
migrans a été observé .
Conclusions: 1 La piqûre d’insecte est un motifs de consultation
fréquent pendant l’été. 2. Les cas graves avec manifestations systémiques nécessitant une hospitalisation ne sont pas rares, et ne sont
pas strictement liés à un’ anamnèse préalable d’allergie. 3. La prise
en charge de ces patients est très hétérogène et l’utilisation de certains traitements, en particulier les antibiotiques les stéroïdes et le
rappel antitétanique, est probablement exagérée. 4. Une plus grande
utilisations par les patients de moyens de protection contre les insectes pourrait diminuer la fréquence des cas
«BRUDABAK» oder: Wie die sorgfältige,
ärztliche Untersuchung Mehrwert generiert
Biedermann B.C. (Bruderholz)
Im Zeitalter modernster Medizintechnologie und molekularer, komprehensiver Untersuchungsverfahren (den sogenannten «-omics») droht
die ärztliche Untersuchung, d.h. die Anamnese, der Status und einfache Zusatzabklärungen (Thoraxröntgenbild, EKG, Labortests), mehr
und mehr vernachlässigt zu werden. Dennoch bildet sie immer noch
den unmittelbarsten Zugang zur Krankheit eines Patienten. Es stellt
sich die Frage, wie präzise diese Untersuchungsmittel Krankheiten
wirklich erfassen können. Am Beispiel der häufigen Krankheit «Arteriosklerose» wurde geprüft, ob mit Hilfe einer umfassenden, standardisierten internistisch-ärztlichen Untersuchung diese Krankheit bei
hospitalisierten Patienten zuverlässig diagnostiziert werden kann.
Wenn Daten der ärztlichen Untersuchung nach den Regeln der Differenz-Analyse verarbeitet werden, kann einerseits ein patientenbezogenes, individuelles klinisches Krankheitsprofil für die Arteriosklerose
hergeleitet und andererseits für jeden Patienten ein ArterioskleroseAktivitätsscore bestimmt werden. Dieser Aktivitätsscore ist verglichen
mit der konventionellen, kardiovaskulären Risikoeinschätzung oder
mit modernen Biomarkern mindestens gleichwertig als Diagnoseverfahren. Mit Hilfe des klinischen Krankheitsarrays lassen sich Untergruppen systematisch vergleichen und objektive Klassifizierungskriterien erkennen. So zeigen sich beispielsweise signifikant
unterschiedliche Phänotypen bei Patienten mit koronarer
Herzkrankheit, zerebrovaskulärer Insuffizienz oder peripher arterieller
Verschlusskrankheit. Auch der Phänotyp von Männern und Frauen
mit symptomatischer Arteriosklerose, d.h. mit einer Arteriosklerose,
die sich durch kardiovaskuläre Ereignisse manifestiert, zeigt teils
erwartete, teils unerwartete Unterschiede. Schliesslich identifiziert der
klinische Korrelationsplot Krankheitszustände, die mit der symptomatischen Arteriosklerose assoziiert sind (zum Beispiel die
Osteoporose). Mit Hilfe eines IT-basierten Erfassungsinstrumentes
für klinische Daten können individuelle Krankheitsprofile, der
Krankheitsaktivitäts-Score, Krankheitsarrays, oder Korrelationsplots
für definierte, häufige Krankheiten zeitverzugslos und für eine ökogeographisch relevante Patientenpopulation erstellt werden. Diese
Technik basiert auf erschwinglichen, verfügbaren oder bereits vorhandenen, empirischen Daten und visualisiert komplexe, medizinische
Zusammenhänge auf eine intuitiv nachvollziehbare Weise.
Abbildung 1
Krankheitsprofil und Aktivitätsscore der Arteriosklerose
P65
Characteristics of bleeding complications in patients
with anticoagulant treatment
Rothschild S., Seifert B., Conen D. (Aarau, Zürich)
Background/Aims: Anticoagulation treatment is effective in the
prevention of stroke as well as deep venous thrombosis (DVT) and
pulmonary embolism (PE). Its preventive benefit is to balance against
possible bleeding complications. We sought to assess risk factors
for the severity of bleeding events in patients under anticoagulant
treatment.
Methods and patients: Clinical characteristics, type of anticoagulant
treatment, bleeding site, risk factors, and additional drugs taken by
patients were analysed in 87 bleeding complications during an
observation period of 12 months.
Results: Eighty-seven bleeding complications in 84 patients (mean
age, 79 years; 51% female) were observed from January to December 2005 at the Department of Internal Medicine at the Cantonal
Hospital of Aargau. Most bleeding complications occurred in the
gastrointestinal tract (54%). The median time interval from the
beginning of the anticoagulant treatment to the bleeding event was
34 months. Forty-nine percent of events occurred after a treatment
time above 36 months. Age was not found to influence the severity
of bleeding but the duration of anticoagulant treatment before the
occurrence of a complication was significantly longer for older
patients (p = 0.001).
Conclusions: Our study shows no influence of age on severity of
bleeding complications. Furthermore in patients with advanced age
complications occurred later in the treatment course than in younger
patients. Overall we assessed many bleeding events in patients
treated for over three years. Therefore we emphasize to closely
control patients with anticoagulant treatment also in the later course
of treatment and to mind the anticoagulation when order new drugs.
POSTERS SSMI
POSTERS SGIM
P67
Triptane & Troponin
Weder C., Schneemann M. (Zürich)
Eine 67jährige Patientin wurde uns wegen Thoraxschmerzen notfallmässig zugewiesen. In der persönlichen Anamnese der Patientin war
eine Migräne bekannt, welche unter einer Bedarfsmedikation mit
Naratriptan befriedigend eingestellt war. Die Patientin hatte am Vorabend des Spitaleintritts unter einer akuten Migräneattacke mit Kopfschmerzen und Übelkeit gelitten und daraufhin wie gewohnt 2,5 mg
Naratriptan eingenommen. Darunter klangen die Kopfschmerzen ab.
30–60 Minuten nach der Naratriptan- Einnahme verspürte die Patientin erstmalig Thoraxschmerzen. Die Schmerzen nahmen im Verlauf
der folgenden Nacht zu und strahlten in den Hals aus. Die Patientin
stellte sich am Morgen bei ihrer Hausärztin vor, welche die Patientin
mit einem akuten Koronarsyndrom bei elektrokardiographisch
T-Wellen-Inversion über der Vorderwand und erhöhtem Troponin ans
Universitätsspital Zürich zuwies. Im Eintritts- EKG waren die T- Wellen
über der Vorderwand invertiert, die CK lag bei 518U/l (Norm <167U/l)
und das Troponin bei 0,42 ug/l (Norm <0,1 ug/l). In der Koronarangiographie kamen normalkalibrige, glattwandige Koronararterien zur
Darstellung. Die Ventrikulographie ergab eine EF von 59%. Somit
gingen wir als Ursache des akuten Koronarsyndroms von einem
Koronarspasmus unter Naratriptan aus. Triptane haben sich in der
Anfallsbehandlung der Migräne etabliert. Sie führen durch Aktivierung
der 5HT1B/1D-Rezeptoren zu einer Vasokonstriktion der bei einem
Migräneanfall erweiterten zerebralen Blutgefäße. Zudem hemmen sie
die Ausschüttung vasoaktiver Peptide und vermindern die Ausbreitung von Schmerzreizen über die Hirnrinde. Obwohl Triptane ihre
Wirkung vor allem an den zerebralen Blutgefässen entfalten, wurden
auch koronar, pulmonal und systemisch Vasokonstriktion beschrieben. Unter Triptanen treten zwar häufig (1–7%) Thoraxschmerzen auf,
welche aber meist transient, mild und ohne ischämisches Korrelat
sind. Die Häufigkeit von Myokardinfarkten unter Triptanen wird als
sehr gering eingeschätzt. Der Grossteil der publizierten Fallberichte
betrifft das Auftreten von Myokardinfarkten unter Sumatriptan, wobei
angiographisch sowohl stenosierte wie auch normalkalibrige Koronararterien nachgewiesen wurden. Nebst Sumatriptan ist das Auftreten
von Myokardinfarkten unter Zolmitriptan beschrieben. Triptane sollten
bei bekannter koronarer Herzkrankheit nicht verschrieben werden.
Heftige, nicht nachlassende Thoraxschmerzen unter Triptanen sind
abklärungsbedürftig.
P68
Ambulances et SMUR en cas d’urgences vitales au cabinet
médical: implications pour la formation et l’équipement du
médecin de premier recours
Potin M., Pittet V., Staeger P., Vallotton L., Burnand B., Yersin B.
(Lausanne)
Introduction: Tout praticien est confronté quotidiennement à des
urgences. Parmi celles-ci, les urgences vitales peuvent avoir des
conséquences majeures pour le patient et pour le praticien. Le but de
cette analyse est de déterminer la fréquence de survenue des urgences vitales au cabinet médical qui motivent l’intervention d’une
ambulance, avec ou sans médicalisation par un SMUR (Service
Mobile d’Urgence et de Réanimation) et d’en évaluer des conséquences en terme de mise en place de procédures, d’équipements ainsi
que de formations post-graduée ou continue spécifiques.
Matériel et méthode: Etude rétrospective des fiches d’intervention
pré-hospitalière des services d’ambulances et des missions des
SMUR du canton de Vaud (650’000 habitants) entre 2003 et 2006
pour les missions dont la prise en charge d’un patient a eu lieu dans
le cadre d’un cabinet médical.
Résultats: Entre 2003 et 2006, 2’224 interventions avec ambulances
ont eu lieu dans un des 1’655 cabinet médical vaudois (= 2,3% de
l’ensemble des missions) et, dans >90% des cas, dans un délai de
20 minutes. Parmi les interventions, on relève les urgences suivantes
(n =, % des interventions): cardio-vasculaires: 755 (= 33,9%), dont
17 arrêts cardio-respiratoires (ACR); respiratoires: 165 (= 7,4%);
neurologiques: 138 (= 6,2%); psychiatriques: 129 (= 5,8%); traumatologiques: 475 (= 21,4%), dont 261 (= 54,9%) concernent les extrémités; diverses: 205 (= 9,5%); autres: 359 (= 16,1%). Sur ces interventions, 634 (= 28,5%) ont bénéficié d’une médicalisation par un SMUR,
dont 440 (= 70% des missions SMUR au cabinet) pour des urgences
cardio-vasculaires. Il y a eu 6 cas de décès au cabinet.
Forum Med Suisse 2008;8:(Suppl. 40)
42 S
Discussion: Les urgences cardio-vasculaires au cabinet représentent
un tiers des interventions faisant appel à une ambulance, mais plus
des deux tiers des interventions nécessitant une médicalisation, soit
plus que pour les autres sites d’interventions médicalisées dans la
communauté (46%).
Conclusions: Les urgences vitales au cabinet médical ne sont pas
négligeable, peuvent avoir des conséquences lourdes (ACR, décès)
et perturber significativement son fonctionnement. Dès lors, une
formation appropriée tant pour le médecin que pour son personnel,
ainsi qu’un équipement adéquat (par ex. salle équipée avec défibrillateur, appareil d’aérosol, attelles pour les extrémités) devraient être
encouragés et généralisés auprès du corps médical.
P69
La maladie de Creutzfeldt-Jakob sporadique: présentation
clinique et diagnostique
Truong M.H., Ruffieux A., Hayoz D., Betticher D. (Fribourg)
Introduction: La maladie de Creutzfeldt-Jakob est une maladie infectieuse rare du système nerveux central. La forme sporadique, la plus
fréquente (85%), se manifeste par une démence et des troubles
neurologiques diffus d’évolution rapide sur quelques mois. L’issue est
fatale dans tous les cas.
Cas clinique: Une femme de 61 ans présente des troubles mnésiques de survenue rapide. Le MMS est à 19/30 et le test de l’horloge
à 2/7points. Le bilan étiologique de routine de la démence est normal.
L’évolution clinique est rapide avec apparition d’une aphasie, d’un
parkinsonisme, d’une ataxie à la marche et de myoclonies diffuses.
L’EEG met en évidence des complexes triphasiques pseudo-périodiques. L’IRM cérébrale avec séquences de diffusion objective un
hypersignal sous forme de ruban cortical et au niveau de la tête des
noyaux caudés et des putamens prédominant à droite. L’analyse du
liquide céphalo-rachidien ramène des traces de la protéine 14-3-3.
Sur la base de ces résultats, nous suspectons une maladie de
Creutzfeld-Jakob sporadique. La patiente décèdera neuf mois après
le début des symptômes. L’examen anatomo-pathologique confirmera le diagnostic par la spongiose, gliose, perte neuronale et présence de la protéine prion anormale au niveau du cortex, des noyaux
gris centraux et du thalamus,
Description: La maladie de Creutzfeldt-Jakob sporadique touche
des patients entre 50–70 ans et se manifeste par une démence précoce avec des symptômes peu spécifiques au début de la maladie
(troubles de la personnalité, du sommeil, psychiatriques, visuels),
d’où la difficulté de poser un diagnostic de certitude. L’évolution est
rapidement progressive avec l’apparition de symptômes plus spéficiques (myoclonies, ataxie, signes pyramidaux et extra-pyramidaux,
cécité corticale et mutisme akinétique).
Diagnostic: Le diagnostic probable est basé sur la clinique, la présence de la protéine 14-3-3 dans le liquide céphalo-rachidien et les
lésions caractéristiques à l’EEG (complexes triphasiques, périodiques
et généralisés) et à l’IRM (hypersignal sous forme de ruban cortical et
au niveau des noyaux caudés et putamens). Le diagnostic définitif
repose sur les résultats de l’examen anatomo-pathologique (gliose,
spongiose, perte neuronale et présence de la protéine prion anormale).
P70
Fortuite discovery of a right atrium mass
Zaugg D., Jaussi A. (Lausanne)
During performing a transthoracic echocardiography (TTE) to evaluate
left ventricular function and follow-up of a moderately severe calcified
aortic valvular stenosis to a 55-years old smoker known for a metabolic syndrom, who has had a myocardial infarction at 40, a right
atrium (RA) mass was incidentally found by the cardiologist. The
mass was highly mobile prolabing in the right ventricule and in contiguity with a mass of low echodensity in the inferior vena cava (IVC)
where an accelerated flow was documented. The biological results
showed a polycythemia with hemoglobin (Hb) to 200g/l, an hematocrit (Ht) to 59%, erythropoietin (EPO) was elevated to 41 U/l
POSTERS SSMI
POSTERS SGIM
(5–25 U/l), as well as interleukin-6 (Il-6) to 48.6 pg/l (<0.3 pg/ml) and
alpha-foetoprotein (AFP) >12’000kU/l (<0.5 kU/l). Those values associated with IVC and RA mass pointed first to a renal cell carcinoma,
but a CT-scan showed a huge hepatic mass, also objectivated at
abdominal ultrasound examination, corroborating the diagnosis of
hepatocellular carcinoma (HCC). A case control study from the USA
demonstrated that an alcohol exposure of >1500 g-years, tobacco
>20 pack-years, a body mass index >30 Kg/m2, and patients with
diabetes mellitus were independent risk factors for HCC. During a
clinical course of HCC, patients may develop several paraneoplasic
syndromes such as hypoglycemia, hypercholesterolemia, hypocalcaemia and erythrocytosis. The incidence of erythrocytosis is highest
in renal cell carcinoma, rather low in HCC. It seems to be linked with
high level of AFP, large tumour and poor prognosis. This report represents the discovery of a RA mass while performing a TTE to evaluate
left ventricular function and follow-up of a moderately severe calcified
aortic valvular stenosis. The biological elevations of Hb, EPO, Il-6 was
reminiscent of a renal cell carcinoma. However CT-scan and abdominal ultrasound established the diagnosis of HCC. This case confirms
that TTE is a sensitive examination for the diagnosis of RA mass.
Secondly, we should consider that patients with risk factors should
be controlled for HCC, by performing hepatic ultrasound and AFP.
Furthermore, understanding the mechanism of HCC growth and
angiogenesis could improve the survival time of patients with HCC.
Forum Med Suisse 2008;8:(Suppl. 40)
43 S
sore tongue without glossitis that was reversible after treatment. Rare
hematological abnormalities included pancytopenia. Cobalamin deficiency can arise due to nutrition (e.g. vegans), malabsorption syndrome (e.g. pernicious anaemia) or from other gastrointestinal causes
(e.g. bacterial overgrowth syndrome). The diagnosis is based on a low
cobalamin level, but elevated methylmalonate and homocysteine
levels are more sensitive diagnostics than is low serum cobalamin.
Patients with pernicious anaemia have anti-intrinsic factor and antiparietal cell antibodies. Treatment is intramuscular or oral and lasts a
lifetime.
Figure 1: peripheral blood smear
P72
Figure 1
RA mass
Figure 2
A huge hepatic mass
P71
From sore tongue to pancytopenia
Chapuis T., Favrat B., Bodenmann P. (Lausanne)
Objectives: Recognize non-neurological signs of cobalamin (vitamin
B12) deficiency, identify hematological findings and establish diagnosis and treatment for pernicious anaemia.
Case: A 52-year-old man native to the Congo presented to the emergency ward after 14 days of shortness of breath and a sore tongue.
He had no cough or fever, and no relevant information in his medical
history. The physical examination was unremarkable.
Clinical Course: A chest X-ray and a full blood count were ordered.
The chest X-ray was normal. The full blood count showed pancytopenia: the hemoglobin was 75 g/L with a MCV of 107fl, and the absolute
reticulocyte count was 31 G/L. The WBC was 3.6 G/L, with 27%
neutrophils, 63% lymphocytes and 96 G/L platelets. The peripheral
blood smear (figure 1) revealed anisocytosis and hypersegmented
neutrophils. The findings were low cobalamin (52 pmol/L; 133-675)
and folate (4.2 nmol/L; >6.8) levels, and high homocysteine (101
mmol/L; 5-15) and methylmalonate (1.12 mmol/L; <0.28) levels. Iron,
ferritin levels were normal, as were the other findings. A gastroscopy
with biopsy showed atrophic gastritis. Anti-parietal cell and antiintrinsic factor antibodies were positive. Cobalamin (1000 mcg i.m.)
was given daily for 7 days, then every week for 4 weeks and then
maintained at 1000 mcg every month. Daily folate was also given.
Correction of the deficiencies led to a reticulocytosis (200 G/L) 10
days later. Six months later, the patient was asymptomatic and the
peripheral blood smear was normal. Cobalamin, folate,
methylmalonate and homocysteine levels were normal.
Discussion: The differential diagnosis of pancytopenia included
cobalamin and folate deficiency, hyperslenism, myeloproliferative
disorders, hypothyroidism, HIV. Pernicious anaemia was our leading
diagnosis. Our patient developed non-neurological symptoms and a
Subclaviathrombose auf der Grundlage eines ovariellen
Hyperstimulationssyndroms (OHSS)
Keller C., Ballmer P. E. (Winterthur)
Fallpräsentation: Eine 32jährige Patientin wurde zur Abklärung
linksseitiger Nackenschmerzen mit progredienter Schwellung supraclaviculär links zugewiesen. Die Patientin befand sich nach einer in
vitro-Fertilisation (IVF) in der 8. Schwangerschaftswoche und war
4 Wochen zuvor wegen eines OHSS mit Pleuraerguss, Aszites und
zystischen Ovarien hospitalisiert. In der klinischen Untersuchung
zeigte sich eine 10x10 cm grosse, dolente und livide Schwellung
supraclaviculär links mit Umgehungskreislauf bei sonst unauffälligem
Status. Ausser einer Leukozytose (23,0x109/l) und einer Erhöhung
des CRP (44 mg/l) bestanden keine Laborauffälligkeiten. Duplexsonografisch konnte eine Thrombose der V. subclavia und jugularis interna
links bestätigt werden. In der MRI zeigte sich neben der
Subclaviathrombose eine ausgedehnte, hyperintense Infiltration
der umliegenden Weichteilstrukturen.
Diagnose, Therapie und Verlauf: Wir stellten nach Ausschluss
anderweitiger Ursachen die Diagnose einer Thrombose der V. subclavia und jugularis links mit ausgeprägtem Weichteilödem auf
der Basis eines OHSS Grad III, und verabreichten therapeutisch
Fragmin®. Nach erfreulichem klinischem Verlauf konnte die Patientin
nach 1 Woche entlassen werden.
Diskussion: Das OHSS wird in der Regel durch exogen zugeführte
Hormone im Rahmen einer IVF ausgelöst. Milde Formen wurden auch
im Zusammenhang mit Hypothyreose oder polyzystischem Ovarsyndrom beschrieben. Die Klinik des OHSS ist geprägt durch eine Vergrösserung der Ovarien mit Zystenbildung infolge Stimulation einer
übermässigen Follikelanzahl und durch gesteigerte Kapillarpermeabilität mit Extravasation. In Abhängigkeit der Ovargrösse, der Klinik und
der Oestrogenkonzentration werden 3 Schweregrade unterschieden.
Normalerweise ist das OHSS innerhalb von 10 bis 14 Tagen spontan
regredient, kann aber zu Komplikationen wie hypovolämischem
Schock, Nierenversagen und ARDS führen. Thromboembolische
Komplikationen im Bereich der V. axillaris bis jugularis und der
Mesenterialgefässe, welche im Rahmen eines OHSS unabhängig
von einer Thrombophilie 7–10 Wochen nach IVF auftraten, wurden
beschrieben. Die Therapie beschränkt sich auf ein symptomorientiertes Vorgehen, im Falle einer Thrombose auf die Anwendung von
Heparinen.
POSTERS SSMI
POSTERS SGIM
P73
Multidisziplinäres Management nach totaler Dünndarmresektion
Keller C., Rühlin M., Müller Ch., Haller A., Jaeggi M., Ballmer P.E.,
Imoberdorf R. (Winterthur)
Hintergrund: Ein Langzeitüberleben nach totaler Dünndarmresektion
ist seit Etablierung der totalen parenteralen Ernährung (TPE) möglich.
Diese ist mit hoher Morbidität und grosser psychischer Belastung
assoziiert, was eine umfassende, multidisziplinäre Betreuung des
Patienten voraussetzt.
Fallbeschreibung: Aufgrund einer akuten Mesenterialischämie
wurde bei einem 44jährigen Mann eine totale Dünndarmresektion und
Hemikolektomie rechts (mit Blindverschluss) durchgeführt. Die Ursachensuche mittels Holter-EKG, Echokardiografie, Vaskulitisscreening
(ANA, ANCA, anti-native-DNA, anti-mitochondriale-AK, TPHA-Test)
und Bestimmung der Antikardiolipin-Antikörper blieb erfolglos. Die
TPE wurde mit Nutriflex lipid peri® (Braun Medical, Switzerland),
Polyvitaminen, Spurenelementen und Flüssigkeit via Porth-à-cath mit
8 Stunden Verabreichungspause pro Tag eingestellt. Zur Drainage der
Sekrete des oberen Gastrointestinaltraktes wurde eine PEG-Sonde
implantiert. Unter intensiver Schulung durch eine Ernährungsberaterin
und Homecarespezialistin erlernte der Patient die korrekte Handhabung der TPE. Regelmässige Nachkontrollen ergaben ein stabiles
Körpergewicht im Normbereich (BMI 22 kg/m2) ohne Anzeichen einer
Malnutrition oder Störung des Hydratationszustandes. Ein Anstieg
der Cholestasewerte auf ein im weiteren Verlauf stabiles Niveau (GGT
204 U/l, Referenzbereich (RB) 11–50 U/l; AP 293 U/l, RB 45–122 U/l)
bei konstanter, milder Erhöhung der Transaminasen (GOT 45 U/l, GPT
81 U/l; RB: <40 U/l) und sonografisch leichter Steatose führten wir
auf die TPE zurück. Trotz erfreulichem klinischem Verlauf und eingehender Aufklärung über die Risiken einer Dünndarmtransplantation
konnte die psychische Belastung des Patienten mit zunehmender
Depression und intensivem Wunsch nach einem Transplantationsverfahren kaum beeinflusst werden. Deshalb erfolgte die Anmeldung
an die Transplantationssprechstunde des USZ.
Diskussion: Aufgrund ungenügender Erfahrung hinsichtlich Dünndarmtransplantation ist nach einer totalen Dünndarmresektion die
TPE die Therapie der ersten Wahl, obwohl diese mit schweren Komplikationen wie Leberversagen, katheterassoziierten Infektionen und
Stoffwechselstörungen assoziiert sein kann. Eine Transplantation
kommt gemäss den internationalen Richtlinien nur nach Versagen der
TPE in Frage, wobei letzteres allein durch die psychische Entwicklung
des Patienten bedingt sein kann.
Forum Med Suisse 2008;8:(Suppl. 40)
44 S
active substance alone or in combination with calcium and/or
vitamin D supplements increased from 11.4% to 23.8% after
fracture in women and from 4.7% to 13.8% in men.
Conclusion: In patients aged 50 years and older presenting with
a fragility fracture osteoporosis remains underdiagnosed and undertreated in Switzerland.
P75
Obstruktives Schlafapnoesyndrom –
gebessert nach Therapie einer Akromegalie
Fausch K., Jeker R., Kuhn M., Reinhart W. H. (Chur)
Fallbeschreibung: Bei einer 68jährigen Patientin wurde 2005 im
Rahmen einer Abklärung eines chronischen Schmerzsyndroms die
Diagnose einer Akromegalie gestellt. Der Insulin like growth factor
(IGF) betrug 985 ng/ml (Normwerte: 100–300 ng/ml), das Growth
Hormone (GH) war mit oraler Glucosebelastung nicht supprimierbar.
Fremdanamnestisch bestand bei der Patientin Schnarchen und
nächtliche Apnoephasen, klinisch fiel unter anderem eine
Makroglossie auf. In der respiratorischen Polygraphie zeigte sich das
Bild eines mittelschweren obstruktiven Schlafapnoesyndroms (OSAS)
mit einem Apnoe-/Hypopnoe-Index von 30/Stunde, es kam zu massiven Entsättigungen (transkutane Sauerstoffsättigung <60%). Nach
Therapie der Akromegalie mittels Entfernung eines Mikroadenoms in
der Hypophyse persistierte weiterhin ein nächtliches Schnarchen,
jedoch wurden fremdanamnestisch keine Atempausen mehr
beobachtet. Die Tagesmüdigkeit besserte sich deutlich. Eine respiratorische Polygraphie bestätigte die Verbesserung des OSAS: Der
Apnoe-/Hypopnoe-Index sank auf 9/Stunde, die nächtliche Sauerstoffsättigung auf minimal 70% mit Werten von 80–90% während
87% der Zeit. Die Entsättigungen dürften einerseits durch die
vorbestehende chronische obstruktive Lungenerkrankung und
andererseits durch eine Verteilungsstörung bei ausgeprägter Adipositas (BMI 37 kg/m2) bedingt sein.
Diskussion: Aufgrund der Überproduktion von Wachstumshormonen
kommt es zu einer Zunahme der Weichteile im Bereich des Rachens
und zu einer Makroglossie. Nach erfolgreicher Therapie der Akromegalie sind solche Weichteilhypertrophien regredient, weshalb wir eine
deutliche Besserung des obstruktiven Schlafapnoesyndroms dokumentieren konnten. Dies trug massgeblich zur Verbesserung des
Allgemeinzustandes und der Lebensqualität der Patientin bei, indem
die Tagesmüdigkeit deutlich reduziert werden konnte.
P74
Management of fragility fractures in Switzerland:
a prospective study
Lamy O., Suhn N., Lippuner K. (Lausanne, Basel, Bern)
Introduction: There is a worldwide consensus that patients aged
50 years and older presenting with a fragility fracture should undergo
diagnostic workup for osteoporosis. They benefit from measures
aiming at reducing the risk for further fractures. Recent studies suggest that osteoporosis remains generally underdiagnosed and undertreated. A nationwide survey was conducted to assess the quality
level of osteoporosis management in patients >50 years presenting
with a fragility fracture to the emergency ward.
Methods: During a timeframe ranging from 8 to 16 months, all consecutive patients >50 years presenting with a fracture to the emergency ward in eight hospitals (Basel, Bern, Estavayer, Fribourg, Lausanne, Luzern, Riaz, Sankt-Gallen) were recruited between 2004 and
2006. Of the 4966 consecutive male (N = 1368, mean age 69.0 years)
and female (N = 3598, mean age 73.9 years), 3667 were considered
as having 3897 fragility fractures and included in the survey.
Results: The included patients presented with a fracture of the upper
limbs (30.7%), the lower limbs (26.4%), the axial skeleton (19.5%)
or at another localization, including malleolar fractures (23.4%). 1185
patients (data available for 3099 patients, 38.5%) reported one or
more anamnestic fractures during adulthood. The average length
of stay of the 2941 (80.2%) hospitalized patients was 9.0 ± 7.0 days.
Only 49.8% returned home after discharge, 32.7% went to a rehabilitation clinic, 17.1% went to a nursing home or were transferred to
another hospital, and 0.4% died. DXA measurement was available
for 1152 (31.4%) patients. Of those 46.0% had an osteoporosis and
35.1% an osteopenia. The mean of the lowest T-score values was
–2.34 in women and –2.16 in men. The treatment rate with a bone
P76
Trimethoprim-induzierte cholestatische Hepatitis
bei Compound-Heterozygotie für familiäre Haemochromatose
Pfister R., Jeker R., Reinhart W.H. (Chur)
Fallbeschreibung: Ein 62jähriger Patient wurde zugewiesen wegen
eines subakuten, 2 Wochen nach Therapie mit Trimethoprim/Sulfamethoxazol aufgetretenen, schmerzlosen Ikterus. Die Laboruntersuchungen zeigten das Bild einer cholestatischen Hepatitis mit einer
direkten Hyperbilirubinämie von 552 mmol/, einer 2-fach über der
Norm erhöhten alkalischen Phosphatase und Transaminasen, welche
im Verlauf auf das 4fache der Norm anstiegen. Eine virale oder
autoimmune Hepatitis konnte ausgeschlossen werden, Coeruloplasmin und Alpha-1-Antitrypsin waren normal. Es bestand eine
Hyperferritinämie (1207 mg//l) mit einer deutlich erhöhten Transferrinsättigung (82%), sodass eine mögliche Haemochromatose
weiter abgeklärt wurde. Die Leberhistologie war mit einer Gallenabflusstörung vereinbar, es konnte eine Gallengangsschädigung und
-proliferation sowie eine Siderose nachgewiesen werden. Aufgrund
der ananmnestischen Angaben und der wiederholten unauffälligen
sonografischen Befunden von Leber und Gallenwege war aber eine
extrahepatische obstruktive Cholestase ausgeschlossen. Molekulargenetisch wies man eine sogenannte Compound-Heterozygotie
nach, d. h. eine gleichzeitige heterozygote Mutation von C 282Y und
H63D. Angesichts des zeitlichen Ablaufes und in Kenntnis der potentiell hepatotoxischen Wirkung von Trimethoprim gingen wir von einer
POSTERS SSMI
POSTERS SGIM
medikamentös induzierten Hepatitis aus. Die Erkrankung verlief protrahiert, wegen zunehmender psychomentaler Belastung aufgrund
des anhaltenden therapierefraktären Pruritus musste der Patient
während 3 Wochen hospitalisiert bleiben. Wir behandelten symptomatisch mit Cholestyramin und Naloxon. Die Cholestaseparameter
waren erst im Verlaufe von 2 Monaten regredient (Gesamtbilirubin
nach 2 Monaten 56 mmol/), die Hyperferritinämie persistierte aber
unverändert hoch (2017 mg//l).
Diskussion: Bei diesem Patienten mit Trimethoprim-induzierter
cholestatischer Hepatitis und Compound-Heterozygotie für familiäre
Haemochromatose zeigte sich ein protrahierter Erkrankungsverlauf
mit persistierend hohen Ferritinwerten auch nach Abklingen der
Hepatitis. Bekannt ist, dass die Compound Heterozygotie eine
Risikosituation für zusätzliche lebertoxische Situationen ist und somit
ein Zusammenhang zwischen einem protrahiertem Verlauf einer
medikamentösen Hepatitis und der Heterozygotie postuliert werden
kann, obwohl es in der Literatur keine solchen Fallbeschreibungen
gibt.
P77
Physicians’ ability to estimate patient’s compliance with
antihypertensive medication in primary care: pilot study
Martina B., Battegay E., Tschudi P. (Basel, Basel und Zürich)
Background: The ability of primary care physicians to estimate
patients’ compliance with cardiovascular medication is barley
investigated.
Objective: To determine physicians’ accuracy to predict their
patients’ compliance with antihypertensive therapy.
Methods: In a prospective observational study patients with the
clinical diagnosis of hypertension were recruited by general practitioners or by hospital-based physicians from a Medical Outpatient
Department. Doctors were asked to give an unaided estimation of the
compliance with medication of their patients by using a visual analogue scale (VAS). Compliance was monitored by using a medical
event monitoring system (MEMS 6, AARDEX Ltd, Zug, Switzerland).
Patients were asked to self-estimate the accuracy of medication
taking on a VAS on the day of recruitment. Outcome measures were
MEMS monitored compliance and estimated compliance using a
VAS consisting of a horizontal line, which was 100 mm in length.
Results: Three general practitioners and six hospital-based physicians took part and estimated medication taking of 42 of their
patients. Patients were monitored by MEMS on 42 days (±14) on
average. Nine out of ten subjects were on a once daily regimen and
85% of participants have taken their medication for more than one
year. Mean MEMS measured compliance for timing compliance
(± SD, range), correct dosing, and taking compliance was 82% (±27,
0–100%), 87% (±24, 4–100%), and 94% (±18, 4–108%), respectively.Physicians’ estimation of their patients’ compliance was 92%
(±15) on average. Spearman rank correlation coefficient for the association between physician’s estimation and MEMS measured timing
compliance, correct dosing, and taking compliance was 0.42
(p = 0.006), 0.47 (p = 0.002), and –0.02 (p = 0.888), respectively.
Patients self-estimated their accuracy of medication taking at a value
of 98% (±2, range 83 to 100%). Spearman coefficients were 0.27
(p = 0.08) for timing compliance, 0.25 (p = 0.12) for correct dosing,
and 0.11 (p = 0.51) for taking compliance.
Conclusion: Physicians’ estimation of their patients’ compliance with
antihypertensive medication showed a low to modest, but significant
correlation to MEMS measured compliance. Data suggest that physicians tend to overestimate the accuracy of patients’ medication
taking. However, physicians’ judgment of medication taking seems
to be more accurate than patients’ self-estimation.
P78
Advice and counselling to stop smoking in patients admitted
on a general internal medicine ward
Miedinger D., Nester N., Schafroth S., Tamm M., Stolz D.,
von Garnier C., Leuppi J.D. (Basel, Bern)
Introduction: Smoking is a major harm to health. Being hospitalized
may trigger attemps to stop smoking.
Forum Med Suisse 2008;8:(Suppl. 40)
45 S
Aims: To determine smoking behaviour, willingness to quit smoking
and to participate in a smoking cessation program. To determine if
patients were told to stop smoking and offered help to quit smoking
by doctors before the current hospitalization.
Methods: Interviewer administered questionnaire. Subjects: Patients
hospitalized on a general internal medicine ward from beginning of
September 2006 until middle of October 2006 at the University
Hospital in Basel, Switzerland.
Results: 338 patients were admitted an a general internal medical
ward during the study period. In 289 (86%) the questionnaire could
be completed. 58 (20%) of 289 patients were smoking in the last
seven days before admission, 124 (43%) were never-smokers and
107 (37%) were former smokers. Current smokers mean age was
53 years (range 19–85 years), 41 (71%) were male. The mean Fagerstroem of nicotine dependency score was 4,2 (SD 2,6). 34 (59%) were
willing to stop smoking and 26 (45%) were willing to participate in a
smoking cessation program. Before hospitalisation, 29 (50%) have
been told to stop smoking and 17 (29%) have been offered help to
stop smoking by a doctor.
Conclusion: Every second smoker on a general internal medicine
ward would like to stop smoking. Only half of them have been told to
stop smoking before by a doctor and only a third have actually been
offered help in doing so. Hospital-based smoking cessation intervention might be provided systematically to all smokers admitted on a
general internal medicine ward.
P79
Schweregrad der Hymenopterengiftallergie in Bezug
zum basalen Serumtryptase-Wert
Meier R., Haeberli G., Müller U.R., Helbling A. (Bern)
Einleitung: Die Assoziation zwischen erhöhter basaler Serumtryptase
(bsT) und dem Schweregrrad einer allergischen Allgemeinreaktion
nach einem Bienen- oder Wespenstich ist gut etabliert. Eine bsT
Konzentration >11,4 ng/ml (95-Perzentile) gilt als erhöht. Gemäss
einer kürzlich publizierten Leitlinie (Allergo J 2004;13:440–2) können
allerdings schon bsT zwischen 8 und 10 ng/ml ein erhöhtes Risiko für
eine Systemreaktion nach einem Hymenopterenstich bedeuten. In
dieser Untersuchung wollen wir die Verteilung der bsT bezogen auf
den Schweregrad einer allergischen Reaktion – inklusive schwere
Lokalreaktion – bei Hymenopterengift-allergischen Patienten
analysieren.
Methode: 736 Patienten mit einer gesicherten Hymenopterengiftallergie und vorhandener bsT aus den Jahren 2003 bis 2005 sind
eingeschlossen. Die bsT wurde mittels UniCAP Tryptase Fluoroenzyme Immunoassay bestimmt (Pharmacia Diagnostic, Uppsala,
Sweden). Basierend auf dem sbT wurden die Patienten folgenden
Gruppen zugeteilt: 639 Pat. (86,8%) hatten eine bsT <8,0 ng/ml
(durchschnittlich 4,2 ng/l), 48 Pat. (6,5%) eine bsT zwischen 8 und
11,4 ng/ml (durchschnittlich 9,6 ng/l) und 49 Pat. (6,6%) eine bsT
>11,4 ng/ml (durchschnittlich 16,8 ng/ml; range 12,0–33,9 ng/ml).
Ergebnisse: Die Verteilung der bsT in Bezug zum Schweregrad der
allergischen Reaktion (nach H.L. Mueller) ist in Figur 1 aufgeführt.
Konklusion: Eine Erhöhung der bsT findet sich primär bei Patienten
mit einer schweren Allgemeinreaktion nach einem Hymenopterenstich. Interessant ist aber, dass die Inzidenz einer erhöhten bsT bei
Schweregrad III und jenen mit einem Schweregrad I/II ähnlich ist.
Bemerkenswert ist ferner, dass eine Korrelation nicht nur bei Patienten mit bsT-Werten >11,4 ng/ml, sondern auch bei jenen mit bsTWerten 08,0 ng/ml beobachtet werden konnte. Diese Daten zeigen,
dass einer bsT-Konzentration 08,0 ng/ml bereits eine Bedeutung
hinsichtlich Auftreten einer Systemreaktion nach einem
Hymenopterenstich zukommen kann.
Abbildung 1
POSTERS SSMI
POSTERS SGIM
P80
Medical and pharmacological direct costs over 12 weeks
of stopping cigarette smoking
Digon P., Cornuz J., Wasserfallen J-B. (Lausanne)
Introduction: Stopping smoking is difficult, associated with numerous relapses despite pharmacological nicotin replacement therapy
(NRT), and costs of quitting are not well known.
Patients and Methods: The 481 patients involved in a program to
stop smoking were followed-up for 12 weeks. Personal characteristics, number of outpatient visits, dosage and frequency of use of NRT
as well as date of relapse were prospectively collected. Unit costs of
visits and NRT were identified from official tariffs, and individual cost
of care until relapse or program end as well as cost per week of follow-up were computed. Comparisons were carried out between the
groups of patient finishing or leaving prematurely the program, as well
as between the groups with or without relapse at the end of the
program.
Results: Of the 209 men and 272 women included, 347 patients
(72%) finished the program. Among them, 240 patients (70%) succeeded in quitting, and 107 patients (30%) relapsed. As compared
with the group leaving prematurely the program (134 patients), the
group with complete follow-up (347 patients) was older (mean age
43.7 ± 9.6 years vs 40.8 ± 9.9 years, p = 0.003), the percentage of
patients living in couple higher (64% vs 47%, p = 0.001), and the
number of attempts to quit during the previous year lower (26% vs
36%, p = 0.033). Mean weekly costs of visits were lower (CHF 80.3 ±
6.7 vs 86.8 ± 12.2, p <0.001), mean weekly costs of NRT higher
(CHF 24.6 ± 13.7 vs 17.2 ± 14.3, p <0.001), so that mean total costs
per week were similar (CHF 104.9 ± 16.7 vs 104.0 ± 15.4, p = 899).
As compared with the group relapsing at the end of the program
(107 patients), the group succeeding in quitting (240 patients) was
more often living in couple (68% vs 55%, p = 0.029). Their mean
weekly costs of visits were higher (CHF 81.2 ± 6.1 vs 78.4 ± 7.6,
p = 0.001), while their mean weekly costs for NRT were similar
(CHF 24.2 ± 12.6 vs 25.4 ± 15.9, p = 0.711). Mean total costs per
week were similar (CHF 105.4 ± 15.4 vs 103.8 ± 19.4, p = 0.252).
More intensive NRT at week 4 increased the probability not to relapse
at the end of the program.
Conclusions: Over 12 weeks, medical and pharmacological costs
of stopping smoking are low. Good medical and social support as
well as adequate NRT seem to play a role in successful quitting.
Forum Med Suisse 2008;8:(Suppl. 40)
46 S
P82
Szintigrafischer Nachweis von multiplen peripheren
Lungenembolien bei pulmonal arterieller Hypertonie und
unauffälliger Angio-Computertomografie
Bochsler S.C., Wertli M., Ballmer B.E. (Winterthur)
Fallpräsentation: Bei einer 75jährige Patientin mit schwerem Parkinson Syndrom wurden im Rahmen der Abklärungen nach akutem
cerebrovaskulärem Ereignis (CVI) mit sensomotorischem Hemisyndrom rechts, Aphasie und Neglect, rezidivierende periphere arterielle
Hypoxämien festgestellt. Die Ursache dafür war echokardiografisch
eine schwere pulmonal arterielle Hypertonie (PAH) mit einem RV/RAGradienten von 77 mm Hg. Die arterielle Blutgase zeigte eine respiratorische Partialinsuffizienz (pO2 6,5 kPa, pCO2 4,5 kPa, pH und BE
normal) und es bestand eine Polyglobulie (Hämoglobin 17,5 g/dl,
Hämatokrit 58%). Die weitere Ursachenabklärung des Insults schloss
eine Carotisstenose oder eine Rhythmusstörung aus. Die nächtliche
Oxymetrie bestätigte die Hypoxämien (wach leichte, nachts
mittelschwere), Hinweise auf ein Schlafapnoesyndrom oder eine
Cheyne-Stokes-Atmung lagen nicht vor. Eine Lungenfunktionsprüfung zeigte keine grobe Pathologie und eine Schilddrüsenfunktionsstörung konnte ausgeschlossen werden. Computertomografisch
fanden sich keine Lungenembolien und keine interstitielle
Pneumopathie als Ursache der PAH. Die ergänzend durchgeführte
Lungenperfusionsszintigraphie mit 99m-Tc zeigte multiple bilaterale
Defektzonen in beiden Lungen, mit multiplen peripheren Lungenembolien vereinbar.
Diagnose: Chronische thromboembolische pulmonale Hypertonie
(CTEPH).
Diskussion: Als Ursache für eine periphere Hypoxämie fand sich im
Rahmen einer Abklärung bei CVI echokardiographisch eine schwere
PAH. Da die CTEPH eine potentiell heilbare Erkrankung ist, sollte sie
in jedem Fall gesucht werden. Auch neuere Untersuchungen zeigen,
dass die Szintigrafie zum Nachweis peripherer Lungenembolien der
Computertomografie überlegen ist. Unser Fall zeigt eindrücklich, wie
die Szintigrafie trotz unauffälliger Computertomographie multiple
Defekte, entsprechend multiplen peripheren Lungenembolien,
nachweisen konnte. Bei Patienten mit Parkinson Syndrom sollte
an rezidivierende thromboembolische Ereignisse gedacht werden.
Sie zählen neben den Pneumonien zu den zweithäufigsten Todesursachen.
P83
P81
Lymphom der Prostata – Diagnose auf den «2. Stich»
Vetsch G., Baumann C., Kläy M., Leupin N., Rentsch C.,
Müller-Garamvölgyi E., Bürgi U., Schiemann U. (Bern)
Hintergrund: Maligne Lymphome der Prostata sind eine klinische
Rarität. In der Literatur werden insgesamt nur etwa 165 Fälle
beschrieben, in denen ein primäres Lymphom oder eine sekundäre
Infiltration der Prostata durch ein Lymphom vorlag.
Fallbeschreibung: Berichtet wird der Fall eines 59jährigen Patienten
mit einer unscharf begrenzten Raumforderung im Bereich der Prostata bei normalem PSA, einer Wirbelkörperfraktur und bilateralen
Nebennierenvergrösserungen. Eine zweizeitige Prostatastanzbiopsie
erbrachte den Befund eines diffusen grosszelligen B-Zell-NonHodgkin-Lymphoms. Weitere Staging-Untersuchungen ergaben
Anhaltspunkte für das Vorliegen eines epiduralen Befalls. Es wurde
eine Polychemotherapie inklusive intrathekaler Applikation initiiert,
unter der sich die Lymphommanifestationen bei einem ersten Zwischenstaging nach 4 Zyklen deutlich zurückgebildet hatten.
Schlussfolgerung: Bei einer Raumforderung im Bereich der Prostata
muss neben einem Prostatacarcinom als weitaus häufigste Tumorentität, auch an ein primäres Lymphom oder eine sekundäre Lymphominfiltration der Prostata gedacht werden, insbesondere bei einem
normalen PSA.
Kryptokokken-Meningoenzephalitis bei nichtimmunsupprimiertem Patienten
Hodel Th., Müller M., Rossi M., Stellmes P., Briner V. (Luzern)
Fallbericht: Ein 1968 geborener Mann wurde im Herbst 2007 wegen
Erbrechen und Agitiertheit hospitalisiert. Zuvor hatte er bereits seit
sechs Monaten intermittierend unter Übelkeit, Kopfschmerzen und
Verwirrtheit gelitten. Bei Spitaleintritt bestanden frontale Kopf- und
ziehende Nackenschmerzen ohne Meningismus. Psychopathologisch
fiel ein pseudoneurasthenes Syndrom auf. Die neurologischen
Befunde, der internistische Status und die Laboruntersuchungen
inklusive Entzündungsparameter fielen normal aus. Bei normalem
Druck wies der l Zellen (normalμLiquor 170/ <4), vorwiegend polynukleär, einen Gesamteiweisswert von 2,99 g/l (normal <0,45) und
eine Glucosekonzentration von 1,1 mmol/l auf. Die mikrobiologischen
und serologischen Liquoruntersuchungen fielen negativ aus. Das EEG
zeigte diskrete frontotemporale Verlangsamungsherde. Im MRI nahmen die perimesencephalen Leptomeningen Kontrastmittel auf.
Unter Steroidmedikation mit 100 mg Prednisolon täglich liessen die
Beschwerden des Patienten vorübergehend nach. Zwei Wochen
später erfolgte eine erneute Hospitalisation mit Meningismus und
Hirndruckzeichen. Bei erhöhtem Liquordruck über 55 cmH2O liess
sich nun im Liquor kulturell Cryptococcus neoformans als Ursache
für die chronisch verlaufende Meningoenzephalitis nachweisen. Hinweise für eine Immunsuppression bestanden nicht. Wir behandelten
während zehn Tagen mit Amphotericin B und anschliessend wegen
einer erhöhten Hemmkonzentration für Fluconazol mit Voriconazol
oral unter ausschleichender Steroidmedikation mit Dexamethason
bei regredienten Druck- und Entzündungswerten des Liquors.
Diskussion: Kryptokokken sind bekapselte Sprosspilze, die weltweit
vor allem in Vogelkot vorkommen. Die Infektion beim Menschen
erfolgt aerogen. Die Erreger weisen eine ausgesprochene Affinität für
das zentrale Nervensystem auf. Nicht-immunsupprimierte Patienten
leiden oft während Wochen bis Monaten unter unspezifischen Sym-
POSTERS SSMI
POSTERS SGIM
ptomen bis zur Diagnosestellung, welche direkt mittels Tuschepräparat oder Antigennachweis im Liquor erfolgt.
Schlussfolgerung: Eine Kryptokokken-Infektion ist in der Differentialdiagnose subakut oder chronisch verlaufender Meningoenzephalitiden selbst bei immunkompetenten Patienten zu berücksichtigen.
Die medikamentöse Behandlung erfolgt mit Amphotericin B, bei
schwerem Verlauf kombiniert mit Flucytosin, bis die Liquorkulturen
negativ werden. Anschliessend ist eine orale Therapie mit einem
Triazol-Antimykotikum während drei bis sechs Monaten fortzusetzen.
P84
Impact d’un schéma de mobilisation précoce après infarctus
myocardique aigu sur la durée de séjour et l’utilisation des
ressources
Moret C., Simard N., Waeber G., Lamy O. (Lausanne)
Contexte: Malgré les récentes avancées dans la prise en charge
de l’infarctus myocardique aigu – angioplastie primaire, les recommandations internationales – la durée moyenne de séjour (DMS)
des patients hospitalisés a peu évolué en Suisse. Elle se situe entre
9 et 11 jours.
Objectif: Evaluer l’impact sur la DMS et la faisabilité d’un schéma de
monitoring simplifié et de mobilisation précoce appliqué aux patients
avec infarctus myocardique aigu à faible risque de complications
(IMFRC): âge <76 ans, maladie coronarienne mono- ou bi-tronculaire
complètement revascularisée, sans symptômes d’insuffisance cardiaque ni troubles du rythme.
Méthodes: Etude prospective observationnelle incluant les patients
avec IMFRC admis au CHUV. Les patients transférés des ou vers les
hôpitaux périphériques ont été exclus. Ces résultats ont été comparés à la prise en charge effectuée en 2005. Le devenir des patients
3 mois après la sortie de l’hôpital est analysé.
Résultats: De janvier à décembre 2007, 105 patients avec IMFRC
ont été admis au CHUV dont 68 transférés en périphérie ont été
exclus. Les 7 femmes et 30 hommes avaient un âge moyen de 57 ±
11 ans. La DMS était de 6,6 ± 3,4 jours avec une médiane de 5 jours.
La répartition du séjour était en moyenne: 1,3 ± 0,7 jours aux soins
intensifs; 0,8±1,1 jours aux soins continus et 4,3 ± 2,6 en division
générale. Par rapport à l’année 2005 où les 55 patients inclus avaient
les mêmes caractéristiques, la DMS était significativement plus longue: 8,0 ± 4,0 jours (p <0,05) avec une médiane de 7 jours. Les
séjours en 2005 se répartissaient en: 1,8 ± 0,8 jours aux soins intensifs (p = 0,05); 1,5±1,8 jours aux soins continus (p <0,05) et 4,8 ± 3,5
jours (p >0,05) en division générale. Il n’y a pas eu de différence dans
la survenue de complications hospitalières entre 2005 et 2007. L’économie réalisée en 2007 est d’environ 4000 francs par patient, soit une
diminution des coûts par patient de 25% par rapport à l’année 2005.
Conclusions: Malgré les difficultés d’introduction du schéma, un
monitoring simplifié et une mobilisation précoce post-infarctus ont pu
être appliqués à la majorité des patients avec IMFRC. Il a permis non
seulement de diminuer la DMS mais surtout de mieux utiliser les
ressources, notamment en diminuant la durée d’occupation des lits
de soins intensifs et de soins continus, et ceci sans augmenter le
risque de complications.
P85
Nicht jede gastroösophageale Varize bedeutet das Vorliegen
einer Leberzirrhose. Eine ungewöhnliche Differentialdiagnose
einer massiven oberen GIT-Blutung
Weder C., Jochum W., Schneemann M. (Zürich)
Ein aus Syrien stammender 25jähriger Asylbewerber wurde wegen
endoskopisch unstillbarer oberer Gastrointestinalblutung bei Ösophagusvarizen zugewiesen. Trotz endoskopischer Varizenligierung und
Einlage einer Sengstaken-Sonde persistierte die Blutung. Es musste
ein transjugulärer intrahepatischer portosystemischer Stent (TIPS)
eingelegt werden. Dabei wurde ein auf 55 mm Hg erhöhter Pfortaderdruck gemessen (Norm: 2–6 mm Hg). Klinisch ergab sich kein Hinweis auf eine Ursache der portalen Hypertonie (Alkoholabusus,
Hepatitis B/C, Schistosomiasis, Budd-Chiari-Syndrom). Histologisch
wurde in der Leberbiopsie weder eine Zirrhose noch eine chronische
Lebererkrankung nachgewiesen, so dass die Diagnose einer
Forum Med Suisse 2008;8:(Suppl. 40)
47 S
idiopathischen portalen Hypertonie gestellt wurde. Die idiopathische
portale Hypertonie zeichnet sich durch einen erhöhten Druck im
Portalkreislauf ohne Vorliegen einer Leberzirrhose aus. Verschiedene
Faktoren wurden mit der Entwicklung dieser Erkrankung in
Verbindung gebracht: Infektionen, Arsen-Vergiftung,
Autoimmunerkrankungen. Man nimmt an, dass diese Faktoren bei
genetisch prädisponierten Personen zu Mikroembolien in kleinen
Portalvenenästen führen. Histologisch gibt es keine pathognomonischen Veränderungen; folgende Befunde wurden jedoch beschrieben:
Portalfibrose, Intimafibrose in mittleren und kleinen intrahepatischen
Portalvenenästen mit Obliteration des Lumens, Dilatation der Sinusoide und noduläre Hyperplasie der Hepatozyten. Klinisch präsentieren sich die Patienten mit oberer Gastrointestinalblutung bei
Varizen, Splenomegalie, Hypersplenismus (Zytopenien) und erhaltener Leberfunktion. Aszites, Ikterus oder eine hepatische
Enzephalopathie entwickeln sich selten. Die Behandlung richtet sich
nach den vorliegenden Komplikationen. Bei Varizen ist eine Primärprophylaxe mit Beta-Blocker / endoskopischer Sanierung und nach
Blutung eine Sekundärprophylaxe mit endoskopischer Sanierung der
Varizen indiziert. Nicht stillbare Blutungen und eine symptomatische
Hypersplenie sollten chirurgisch, oder wie in unserem Fall, mit Einlage
eines TIPS angegangen werden. Im Gegensatz zu Indien und Japan
wird die Diagnose einer idiopathischen portalen Hypertonie in Europa
nur selten gestellt. Unsere Fallbeschreibung zeigt jedoch, dass diese
Differentialdiagnose bei Patienten mit oberer Gastrointestinalblutung
bei Varizen auch in der Schweiz in Betracht gezogen werden muss.
P86
Klinik-externe und -interne Determinanten der
Spitalaufenthaltsdauer
Prof. Ballmer P.E. (Winterthur)
Fragestellung: Im Zusammenhang mit der bevorstehenden
Einführung der APDRG (All Patient Diagnosis Related Groups), ist es
Ziel dieser Studie, Faktoren, welche die Spitalaufenthaltsdauer (LOS;
length of hospital stay) von Patienten an einer allgemein-internistischen Klinik beeinflussen, zu erfassen. Damit soll Einsicht gewonnen
werden, wie die LOS ohne Beeinträchtigung der Behandlungsqualität
vermindert werden kann.
Methodik: Die LOS wurde entsprechend der NCHS (National Center
for Health Statistics) definiert als: 1.Quotient der gesamten Anzahl
Hospitalisationstage einer Patientengruppe zur gesamten Anzahl
Entlassungen und 2. Quotient der gesamten Anzahl Pflegetage einer
Patientengruppe zur gesamten Anzahl Entlassungen. Bei der ersten
Gleichung wird die gesamte Hospitalisationsdauer mittels Ein- und
Austrittsdatum erfasst. Bei der zweiten Gleichung wird das Eintrittsjedoch nicht das Austrittsdatum berücksichtigt. Anstelle des Austrittsdatums wird hier das Ende der benötigten Pflegetage erfasst,
was dem medizinisch frühest möglichen Entlassungsdatum
entspricht. Bei allen Patienten zweier internistischer Stationen wurden
während 2 Monaten die Zeitintervalle vom Eintritt bis Diagnosestellung (T-1), Therapiebeginn (T-2), frühest möglichen Entlassungstag
(T-3) und wirklichem Entlassungstag (T-4) prospektiv untersucht.
Resultate: Wir präsentieren präliminäre Resultate der ersten
26 Patienten. Von diesen Patienten wiesen lediglich 10 eine LOS
ohne Verzögerungen (38,5%) auf, während es bei 16 zu Verzögerungen (61,5%) kam. Die LOS aller Patienten betrug 230 Tagen, wovon
77 Tage (33,5%) durch Verzögerungen verursacht wurden. Untersuchungen (total 75) führten in 8 Fällen (10,7%) zu einer Verzögerung
(Klinik-intern), während post-stationäre Massnahmen (total 8) in
5 Fällen (62,5%), durch Wartezeiten auf Verlegungen (Klinik-extern) in
Pflegeheime, Rehabilitationen u.a.m., die LOS verlängerten. Weitere
Verzögerungen ergaben sich durch Wochenenden in denen der
diagnostische oder therapeutische Prozess still stand (29,0%), durch
Komplikationen, palliative Situationen sowie durch andere Klinikexterne Faktoren.
Schlussfolgerung: Unsere Interimsanalyse zeigt, dass sich
Verzögerungstage gleichmässig auf Klinik-interne (46,8%) und Klinikexterne Ursachen (53,2%) verteilen. Klinik-interne Verzögerungsfaktoren lassen sich durch Optimierung des Patientenprozesses beeinflussen, während die Klinik-externen Faktoren (z.B. Warten auf einen
Pflegeplatz) kaum von uns beeinflusst werden können.
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P87
Zeuge Jehovas lehnt vital indizierte Bluttransfusion ab –
Was ist zu tun? Entwicklung einer transparenten
Behandlungsleitlinie
Roggo A., Kramer D., Seidl Ch. (Bern, Würzburg [D], Visp)
Fragestellung: Im Rahmen einer in dieser Dimension erstmals erstellten Feldstudie wurde die reelle forensische Erfahrung im Zusammenhang mit zwar vital indizierter, jedoch abgelehnter Bluttransfusion
bei Angehörigen der Zeugen Jehovas erhoben, um daraus mögliche
Vorgehensweisen für die Praxis abzuleiten.
Methode: Zur Evaluation eines Beobachtungs-Zeitraums von 20
Jahren (1986–2005) wurden 529 standardisierte Fragebogen versandt. Befragt wurden schweizweit alle Akutspitäler, kantonalen
Gerichte erster und zweiter Instanz und das Bundesgericht; zudem
die kantonalen Vormundschaftsbehören, Sanitätsdirektoren und
Kantonsärzte. Ergänzend wurden Interessengruppen der medizinischen Fachgesellschaften und Haftpflichtversicherer im Gesundheitswesen einbezogen.
Resultat: Total 382 Fragebogen wurden zurückgesandt, somit eine
überdurchschnittlich hohe Quote von 72%. Insgesamt wurden nur
6 Ereignisse festgehalten: Eine Meldung von einem Kantonsarzt;
5 aus Akutspitälern (in einer Situation mit Todsfolge wurde diese als
Offizialdelikt strafrechtlich anhängig gemacht, das Verfahren beim
Untersuchungsrichter eingestellt). Keines der antwortenden 205
Gerichte hatte jemals über einen entsprechenden Streitfall zu entscheiden. Bei Haftpflichtversicherungen bzw. Standesorganisationen
gingen keine Meldungen ein.
Erkenntnis und Schlussfolgerung: Wir können davon ausgehen,
dass nur eine Minderheit der Bevölkerung im Ernstfall eine Bluttransfusion ablehnen würde, aus welchen Gründen auch immer. Dennoch
ist die inhaltliche Brisanz für Ärzte im Einzelfall hoch, da ein Entscheid
erwartet wird. Diese sind einer beinahe unlösbaren, paradoxen juristischen Pflichtenkollision (handeln zur Lebensrettung / unterlassen in
Achtung des Selbstbestimmungsrechts?) und damit einem Spannungsfeld zwischen «juristischem Recht» und dem geleisteten «hippokratischen Eid» ausgesetzt. Oft entsteht gerade aus dieser Pflichtenkollision und einer verbreiten Grauzone bezüglich Rechtssicherheit
ein Gewissensnotstand, der den meisten Ärzten hinlänglich bekannt
ist. Die Abteilung für Medizinrecht / Institut für Rechtsmedizin Universität Bern trägt den in der Feldstudie erhobenen Resultaten und der
allgemeinen Problematik Rechnung. An hand eines strukturierten
Lösungsweges werden entsprechend Algorithmen vorgestellt: Vital
indizierte Bluttransfusion Ja / Nein bei einem Urteilsfähigen / Nichturteilsfähigen in einer Elektiv- / Notfall-Situation.
P88
Behandlungsleitlinien im Falle der Verweigerung einer vital
indizierten Bluttransfusion in der Elektiv- / Notfallsituation beim
Urteilsfähigen/Nichturteilsfähigen
Roggo A., Kramer D., Seidl Ch. (Bern, Würzburg [D], Visp)
Die Behandlungsleitlinien bei Verweigerung einer vital indizierten
Bluttransfusion für die Elektivsituation bzw. Notfallsituation beim
Urteilsfähigen / Nichturteilsfägigen werden in Form zweier so genannter «Decision Tree Algorithms» in Ergänzung zum Referat: Zeuge
Jehovas lehnt vital indizierte Bluttransfusion ab – Was ist zu tun?
Entwicklung einer transparenten Behandlungsleitlinie vorgestellt und
zur praktischen Umsetzung im klinischen Alltag empfohlen bzw.
persönliche Erfahrungen der Kongressteilnehmer eingeholt.
P89
Seltene Manifestation einer Lymphomerkrankung
Maile S., Semadeni G.M., Imoberdorf R., Dommann-Scherrer C.,
Müller A. (Winterthur)
Fall: Eine 66jährige Patientin klagte 6 Monate über anhaltende
Müdigkeit und Zustandsverschlechterung. Im Labor fanden sich
erhöhte Entzündungsparameter, in umfassenden Abklärungen konnte
keine Ursache für die Beschwerden gefunden werden. Plötzlich trat
ein febriler Zustand sowie ein teleangiektatisches Erythem und
Forum Med Suisse 2008;8:(Suppl. 40)
48 S
Ödem am Stamm, an den Mammae und Oberschenkeln auf. Unter
dreiwöchiger Therapie mit verschiedenen Antibiotika erfolgte keine
Besserung, das CRP blieb hoch. Beim stationären Eintritt zeigten sich
am Hals links und infraclaviculär vereinzelte vergrösserte Lymphknoten.
Diagnose: Es wurden Hautbiopsien sowie ein vergrösserter Lymphknoten (Hals) entnommen. In der Haut morphologisch Nachweis von
intravasalen blastären Zellen, immunhistochemisch CD20+, CD5+,
bcl-6+, 100%Ki-67+: Infiltration eines ausschliesslich intravasalen
grosszelligen B-Zell-Lymphoms. Im Lymphknoten ausgedehnte Infiltration durch ein diffuses grosszelliges Lymphom der B-Zellen,
CD20+, CD5+, bcl-6+, 90%Ki-67+. Als Nebendiagnosen Prolaktinerhöhung (Mikroadenom Hypophyse), hypophysäre Hypothyreose
und Nebennierenrindeninsuffizienz. Im CT keine weiteren Lymphknotenvergrösserungen, im Liquor, MRI Schädel und Knochenmark
kein Hinweis auf Lymphominfiltration.
Verlauf: Eine Polychemotherapie mit Zusatz des CD20-Antikörpers
Rituximab (R-CHOP) führte zu einer vollständigen Remission. Ebenso
wurde eine intrathekale Prophylaxe mit Ara-C durchgeführt. Zur
Prolaktinsenkung wurde Cabergolin verabreicht, Thyroxin bei Hypothyreose. Innerhalb von 3 Wochen wurden 20 kg Hautödem ausgeschwemmt, das Erythem ist verschwunden, die Müdigkeit ist
regredient.
Diskussion: Das intravaskuläre Lymphom (IVL) ist durch eine
intravaskuläre Proliferation von Lymphomzellen charakterisiert,
welche auf einen besonderen Homing-Mechanismus hinweist. In
diesem Fall wurde konkomitierend eine klonale Vergesellschaftung
mit einer soliden Lymphomkomponente im Lymphknoten zervikal
festgestellt. Häufigste Manifestationen der Erkrankung sind unspezifische Entzündungszeichen. Prädominant weist das IVL einen kutanen und zerebralen Befall auf, das periphere Blut ist selten betroffen.
Bei Diagnosestellung ist das IVL eine disseminierte Erkrankung, bei
dieser Patientin liegt ein Stadium IVB vor. Nach Polychemotherapie
haben rein kutane Varianten eine bessere Prognose. Rezidive sind
nach kompletter Remission häufig. Ein Drittel dieser betreffen das
zentrale Nervensystem, weshalb eine intrathekale Prophylaxe indiziert
ist.
P90
Paraneoplastische cerebelläre Degeneration (anti-Yo-positiv) –
eine ungewöhnliche Primärmanifestation eines Tubenkarzinoms
Schmid S., Stillhard G., Grabherr R., Federspiel B.
(Horgen, Wädenswil)
Fall: Eine 51jährige Frau wurde wegen seit 2 Wochen progredientem
Schwankschwindel und Gangunsicherheit zugewiesen. Neurologisch
fiel eine Dysarthrie, undulierende Diplopie und eine generalisierte
Schwäche aller Extremitäten bei normaler motorischer Nervenleitgeschwindigkeit des N. peroneus und N. medianus beidseits auf. Das
Schädel MRI war unauffällig. Im Liquor fand sich eine leichte Pleozytose mit Eiweisserhöhung. Die Borrelien-Serologie, inkl. intrathekale
AK und die Herpes-PCR im Liquor waren negativ, ebenso die Serologien auf CMV, EBV, HIV und Mycoplasmen. Innert zwei Wochen
rasche Krankheitsprogression mit Steh- und Gangunfähigkeit, deshalb Bestimmung von onkoneuronalen Antikörpern. Es konnten antiYo-AK nachgewiesen werden. Zusammen mit einem eindrücklichen
cerebellären blickmotorischen Syndrom mit intermittierend vertikalen
Doppelbildern, Dysarthrie, progredienter Stand-/Gang- und Rumpfataxie konnte die Diagnose einer anti-Yo-positiven paraneoplastischen cerebellären Degeneration (PCD) gestellt werden. Die folgende
Tumorsuche mit Mammographie, CT Thorax und Abdomen, Gastround Koloskopie, Bronchoskopie und Zystoskopie blieb ohne Hinweis
für eine Neoplasie. In einer diagnostischen Laparaskopie präsentierte
sich ein 2,3x1,5x1,2 cm kleiner Tumor im Bereich der linken Tube, der
histologisch einem wenig differenzierten serösen Adenocarcinom
entsprach.
Diskussion: Die cerebelläre Degeneration gehört zu den klassischen
paraneoplastischen neurologischen Syndromen (PNS). Für die Diagnosestellung gelten folgende Kriterien: Entwicklung eines schweren
pancerebellären Syndroms in weniger als 12 Wochen ohne kernspintomographisch sichtbare cerebelläre Atrophie. Erstes Symptom ist
häufig eine zunehmende Gangataxie. Typischerweise findet sich in
der Frühphase der Erkrankung nur eine unspezifische Pleozytose im
Liquor. In unserem Fall fanden sich anti-Yo-AK, welche in über 98%
der Fälle mit einem Mamma-, Ovarial- oder Endometriumkarzinom,
selten Adenocardinom assoziiert sind und deshalb eine aggressive
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Tumorsuche verlangen. Da die natürliche Immunantwort gegen den
Tumor oft biologisch effektiv ist, können die Tumore für lange Zeit
klein und klinisch inapparent bleiben, was die Suche wie in unserem
Fall zu einer grossen Herausforderung macht. Leider ist das klinische
Ansprechen auf eine Antitumortherapie und/oder Immunsuppression
bei der anti-Yo-positiven PCD nur wenig erfolgsversprechend.
P91
Critical incidence reporting System (CIRS): Erfahrungen
in der Einführungsphase einer medizinischen Klinik
Rochat Ph., Frauchiger B. (Frauenfeld)
Die Erfassung von kritischen Ereignissen (Critical Incidents, CI) mit
potentiellem Schaden für die Patienten wird zur Reduktion von
Systemfehlern im Qualitätsmanagement von Spitälern eingesetzt.
Wir berichten über unsere bisherigen Erfahrungen.
Methodik: Einführung in unserer 80-Betten-Klinik im April 05 mittels
Papierformular (obligate Angabe nur Beschreibung des CI). Im Januar
2007 Wechsel auf spitalweit eingesetzte, anonyme Informatiklösung.
Analyse der Meldefrequenz, der CI und der daraus getroffenen
Massnahmen. Quartalsweise klinikinterne Konferenzen (Pflege, Ärzte)
mit Fokussierung auf Lösungsansätze.
Resultate: Nach wenigen Tagen trafen die ersten Meldungen ein,
bei Papierversion immer mit Personalien (Patient + Meldende). Die
Meldefrequenz stieg von 1,1/Wo (2005) auf 1,3/Wo (2006) und nach
Wechsel auf Informatikprogramm auf 2,9/Wo. Die Pflege (65%, 60%,
82%)* meldete häufiger als die Ärzte (31%, 34%, 17%)* und war
auch häufiger Ursprung (56%, 54%, 74%)* der CI. Die häufigsten CI
umfassten falsche Medikamentendosis (28%, 36%, 34%)*, Patientenverwechslungen (16%, 18%, 9%)*, Beschriftungsfehler (14%, 4%,
2%)*, Dokumentationsfehler (12%, 10%, 25%)*, Medikamentenverwechslungen (5%, 10%, 4%)*. (7%, 24%, 12%)* der CI betrafen
Antikoagulantien, insb. Heparin (Infusomatenproblem). 2007 wurden
13 falsche Insulinapplikationen erfasst. Als häufigste Ursachen wurden verminderte Aufmerksamkeit (49%, 58%, 33%)*, Arbeitsstress
(23%, 22%, 12%)* und Kommunikationsprobleme (25%, 20%, 19%)*
genannt. «Wissen/situative Aufmerksamkeit» waren der Hauptgrund
zur Verhinderung einer Komplikation (31%, 42%, 50%)*. Die CI wurden meist als «vermeidbar» beurteilt (75%, 92%, 92%)*. 5 technische
und 11 organisatorische Massnahmen wurden umgesetzt.
Schlussfolgerungen: 1) Konstruktiver und offener Umgang mit CI
führte von Anfang an zu einer breiten Akzeptanz mit gutem Meldeverhalten. 2) Die Meldefrequenz stieg mit Einführung der Informatiklösung (Anonymität, leichterer Zugang?, DD: zunehmender Arbeitsanfall). 3) Was häufig gemacht wird, wird auch häufig falsch gemacht.
4) Bekannte Fehler werden eher wieder gemeldet. 5)Weniger Kontrollmechanismen, mehr vielschrittige Handlungen und besseres
Meldeverhalten bei Pflege führen zu dort mehr erfassten CI. 6) Aus
den Resultaten lassen sich praktische Massnahmen ableiten und
umsetzen. 7) CIRS ist auf allen Stufen zu einem wichtigen Werkzeug
zur Qualitätsverbesserung geworden.
*(chronologisch für 2005, 2006, 2007)
P92
Transiente Globale Amnesie: nicht so selten
Hutter A., Bächli E.B., Waespe W., Berli R. (Uster, Zollikerberg)
Einleitung: Die Transiente Globale Amnesie (TGA) ist ein klinisches
Syndrom, das durch eine plötzliche antero- und retrograde Amnesie
bei unauffälligem neurologischen Status und kompletter Remission
innert 24 h charakterisiert ist. Die Patienten (Pat) sind zeitlich desorientiert, jedoch durchwegs geordnet in ihrem Verhalten und können
komplexe Vorrichtungen ausüben. Die TGA ist für den Pat und
dessen Angehörige ein traumatisches Erlebnis. Die Pathogenese ist
unklar. Differentialdiagnostisch (ddx) muss die TGA von einem komplex partiellen epileptischen Anfall, einem postiktalen Zustand, einer
psychogenen Amnesie, einer cerebralen Durchblutungsstörung und
einer medikamentös induzierten Amnesie abgegrenzt werden.
Patienten und Methode: Retrospektive Analyse aller im Schwerpunktspital Uster hospitalisierten Pat zwischen 1/2005–10/2007. Das
Spital ist für die Primärversorgung von ca. 160 000 Pat verantwortlich.
Unter den 8166 Pat waren 22 mit 23 Episoden einer TGA, die zusam-
Forum Med Suisse 2008;8:(Suppl. 40)
49 S
men mit dem Neurologen diagnostiziert wurden. Bei allen erfolgte ein
follow up nach 2–22 Monaten.
Resultate: Bei den 22 Pat war das Durchschnittsalter 66 Jahre
(Range 58–86), 57% waren Frauen. Ein Pat erlitt ein Rezidiv und
wurde erneut hospitalisiert. Die durchschnittliche Hospitalisationsdauer war 2 Tage (Median). Alle 23 Epiosoden hatten die antero- und
retrograde Amnesie, die sich innert 24 Stunden zurückbildete. In 18%
trat die TGA nach einer körperlichen Anstrengung, 22% bei einem
emotionalen Stress und in 60% konnten keine speziellen Umstände
eruiert werden. Bei sämtlichen Pat wurde ein CT und in 3 Fällen
zusätzlich ein MRI durchgeführt. In 47% wurde eine Duplexuntersuchung der hirnzuführenden Arterien durchgeführt. Bei keinem
wurde primär ein EEG durchgeführt. Bei keinem lag eine medikamentöse Ursache zu Grunde. Risikofaktoren für eine Arteriosklerose
bestanden bei 77% (61% art. Hypertonie, 26% Dyslipidämie, 22%
Nikotinabusus). Bei allen Pat wurde eine EKG Untersuchung und in
39% wurde eine Rhytmusüberwachung durchgeführt. Im follow up
wurde bei 2 Pat ein Rezidiv diagnostiziert, somit erlitten 14% der
Pat ein Rezidiv. Dies entspricht einer Inzidenz der TGA von
7,5/100000/Jahr, dies in Übereinstimmung mit der in der Literatur
beschriebenen Inzidenz von 5/100 000/Jahr und einer Rezidivrate von
15%.
Schlussfolgerung: Die TGA ist ein Syndrom, das den Internisten
der Notfallstationen bekannt sein muss. Die TGA ist nicht selten und
die Diagnose kann klinisch gestellt werden.
P93
Documentation of patient’s medication at hospital admission:
How good are we? Evaluation in patients admitted for elective
coronary angiography
Frei P., Huber L.C., Simon R.W., Bonani M., Lüscher T.F. (Zürich)
Objective: Errors in medication might happen at hospital admission
when hospital doctors are not adequately informed about a patient’s
established medication. Here we wanted to assess differences
between admission letters from referring practioners, personal medication lists and oral informations provided by the patient at hospital
entry.
Methods: The medication of 103 patients who were electively admitted for coronary angiography was assessed. Discrepancies between
admission letters, written instructions (personal medication lists) and
what patients told about their medication were analyzed. Brand
names/generics, dosages and frequencies were noted.
Results: Patients took a mean of 5 ± 3 drugs. 9% of all drugs taken
could only be discovered by systematic medication anamnesis, but
were not stated in admission letters or medication lists. Only 88% of
admission letters reported whether the patient is on any medication
(and if yes, on which medication). 23% of all drugs were generics, but
21% of generics were stated as original compounds in the admission
letter. Less than 50% of patients taking 4 or more drugs had a written
instruction how to take their medication. 76% of patients brought
their medication with them at hospital admission which facilitates
medication assessment. By comparing data from all three different
sources in order to find out the putative established medication, we
found that a total of 86 medications were not identical, leaving uncertainties to the hospital doctors how outpatient medication should be
continued. Medication was modified in 25% of all patients at hospital
discharge.
Conclusion: Instructions for patients taking multiple drugs need to
be improved. This might increase compliance and reduce uncertainties about medication at hospital admission, thereby decreasing
medication errors in the hospital and allowing useful changes in medication when necessary.
P94
Sarcoïdose et tératome ovarien, nouvelle entité?
Geismann F.I., Masset C., Blondel N., Betticher D. (Fribourg)
Cas clinique: Une patiente de 39 ans est adressée dans le service de
gynécologie pour une tumeur de 10cm de diamètre au niveau de
l’ovaire droit avec infiltration intestinale, ainsi que des nodules hépatiques, spléniques et pulmonaires suggestifs de métastases. Les mar-
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POSTERS SGIM
queurs tumoraux ([beta]-HCG, [alpha]-FP, CA125) sont négatifs et
colonoscopie et gastroscopie sont normales. Dans ses antécédents,
elle déclare être connue pour une toux allergique depuis l’adolescence. Dix huit mois auparavant, la patiente avait présenté une myocardite au décours d’une infection respiratoire. Le bilan cardiologique
effectué montrait une dysfonction cardiaque modérée avec des coronaires saines et l’IRM mettait en évidence une myocardite étendue.
Un bilan pneumologique comprenant des fonctions pulmonaires
complètes avec DLCO et radiographie du thorax était alors normal.
Une laparotomie est pratiquée avec annexectomie et biopsie hépatique. L’histologie ovarienne révèle un tératome (kyste dermoïde) sans
signe de malignité, et la biopsie hépatique montre des granulomes à
cellules épitheloïdes et giganto-cellulaires de type Langhans, avec
des infiltrats lymphocytaires, sans nécrose (coloration Ziehl-Neelsen
et PCR négatives pour Mycobacterium), compatibles avec une sarcoïdose. Il n’y a pas d’atteinte ophtalmologique ni cutanée. Dans un
deuxième temps, une biopsie cardiaque est pratiquée et l’histologie
montre elle aussi des lésions compatibles avec une sarcoïdose.
Discussion: L’association entre tumeur germinale et sarcoïdose a été
décrite dans plus de 50 cas dans la littérature. Nous rapportons le
premier cas d’un tératome ovarien associé à une sarcoïdose. Les
granulomes pulmonaires sans adénopathie hilaire ni infiltration interstitielle représentent un stade radiologique III atypique, mais cet
aspect de métastatisation diffuse hépato-spléno-pulmonaire est
rarement décrit. Seuls 5% des patients souffrant de sarcoïdose ont
une atteinte cardiaque symptomatique, cependant ce diagnostic est
probablement sous-estimé. Une corticothérapie doit être instituée
dans une telle situation et l’implantation d’un défibrillateur devrait
probablement être considérée au vu du risque élevé d’arythmies.
Forum Med Suisse 2008;8:(Suppl. 40)
50 S
präsentierten sich neben 23 intakten ein teilweise entleertes
Päckchen. Die Analyse eines der intakten Päckchens ergab eine
Mischung von Kokain und Diltiazem im Verhältnis von 9:1.
Abb. 2
«Geplatztes» Päckchen
Kommentar: Die Beigabe von Diltiazem als Streckmittel zu Kokain
soll gelegentlich vorkommen (Wissenschaftlicher Dienst der Stadtpolizei Zürich). In unserem Fall wurde dadurch eine notwendige
Operation verzögert aufgrund der irreführenden Klinik. Es scheint,
als hätte die Beigabe von Diltiazem die kardiovaskulären Effekte des
Kokains unterdrückt [3]. Unseres Wissens ist kein Fall bekannt, bei
dem sich eine schwere Intoxikation durch ein geplatztes Body-pack
mit einer Kokain-Diltiazem Mischung so atypisch präsentierte.
1. Prognosis of cocaine body-packers. Prost N, Lefebvre A, Questel
F, Roche N, Pourriat JL, Huchon G, Rabbat A; Intensive Care Med
2005; 31:955–8.
2. Cocaine-body-packing. Infrequent indication for laparotomy.
Schaper A, Hofmann R, Ebbecke M, Desel H, Langer C; Chirurg –
Vol. 74, Issue 7, Jul 2003, Pages 626–31.
3. Calcium channel blockers antagonize some of cocaine’s cardiovascular effects, but fail to alter cocaine’s behavioral effects; Schindler
CW, Tella SR, Prada J, Goldberg SR.J Pharmacol Exp Ther. 1995
Feb;272(2):791–8.
P95
Erhöhte Kokain-Spiegel bei Body-packing:
Alarmzeichen oder Innocent Bystander?
Fretz G., Traupe T., Senn A., Hofer C., Frick S. (Zürich)
Fallbeschreibung: Eine 18jährige Patientin wurde wegen starker
Agitation und Dyskinesien der Gesichtsmuskulatur auf die Notfallstation eingewiesen. BD 116/55 mm Hg, P 79/min. Der restliche
Status sowie das Labor war bis auf eine leicht erhöhte CK von
676IU/L normal. Auf der Notfallstation setzte die Patientin 7
Päckchen Kokain ab, worauf die Diagnose des Body packings
radiologisch bestätigt werden konnte.
Abb. 1
Nachweis der Body-packs
Klinische Fragestellung: Die qualitative Urin-Analyse war positiv
für Kokain. Bei persistierender Verwirrung und schweren Dyskinesien,
jedoch normalen Vitalparametern stellte sich die Frage, ob das
Kokain im Urin von der Patientin separat eingenommen wurde oder
aus einem geplatzten Päckchen stammte. Letzteres hätte eine
notfallmässige Operation bedingt [1, 2].
Verlauf: Nach 12 h Überwachungszeit lagen die quantitativen UrinAnalysen vor: der Kokain-Spiegel betrug 1761 ug/l, die Metaboliten
waren ebenfalls im hoch-toxischen Bereich (Benzoylecgonin 6204
ug/l, Methylecgonin 1408 ug/l). Ausserdem wurden überraschenderweise hohe Konzentrationen von Diltiazem und seinen Metaboliten im
Urin gefunden. Auf Grund der stark erhöhten Kokainkonzentrationen
im Serum war die Indikation zur Operation gegeben. Intraoperativ
P96
Necrobiosis lipoidica eine Präkanzerose?
Gogos G., Gütling M., Pless M., Ballmer P. E. (Winterthur)
Wir präsentieren die Kasuistik einer 62jährigen Patientin, welche uns
zur Abklärung von diffusen Abdominalbeschwerden zugewiesen
wurde. Eine computertomographische Untersuchung zeigte eine
ausgeprägte generalisierte Lymphadenopathie abdominal, retroperitoneal und inguinal beidseits. Der histologische Befund einer Lymphknotenexzision inguinal rechts ergab die Diagnose eines verhornenden Plattenepithelkarzinoms. In der Folge wurde intensiv nach der
Herkunft dieser Lymphknotenmetastase gesucht; sowohl anal wie
auch im Urogenitaltrakt konnten keinerlei Hinweise auf einen Primärtumor gefunden werden. Die Patientin litt seit 1972 an einer ausgeprägten Necrobiosis lipoidica beider Unterschenkel, seit 1999 traten
zunehmend auch Ulzerationen auf. Ein Diabetes mellitus war nicht
vorhanden. Gemäss dermatologischer Beurteilung lag der Primärtumor mit sehr hoher Wahrscheinlichkeit im Bereich der exulzerierten
Fläche am distalen Unterschenkel rechts. Da beim metastasierendem
Plattenepithelkarzinom als einzige Therapieoption eine systemische
Chemotherapie in Frage kam, wurde auf eine diagnostische Biopsie
im Wundbereich verzichtet. Insgesamt wurden 4 Chemotherapiezyklen mit Cisplatin durchgeführt. Initial zeigte sich ein Ansprechen auf
die Therapie mit grössenregredienten Lymphknoten. Im weiteren
Verlauf war das Tumorleiden wieder progredient mit neuen ossären
Metastasen, sowie paraneoplastischen Lungenembolien. Die Patientin verstarb 6 Monate nach der Erstdiagnose des Plattenepithelkarzinoms. Die Entstehung eines Plattenepithelkarzinoms auf der Basis
einer Necrobiosis lipoidica ist extrem selten (A. Stein et al; Plattenepithelkarzinome als seltene Folgeerkrankungen auf kutanem Lichen
ruber und Necorbiosis lipoidica. Akt Dermatol 2003;Heft 08/09,V30),
weltweit sind sehr wenige Fälle publiziert. Meistens handelte es sich,
wie bei unserer Patientin, um die ulzerative Form einer langjährigen
Necrobiosis lipoidica.
POSTERS SSMI
POSTERS SGIM
Forum Med Suisse 2008;8:(Suppl. 40)
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P97
P98
Vermeintliche Meningeosis carcinomatosa bei Neuroborreliose
Gogos G., Rodic B., Ballmer P. E. (Winterthur)
Wir präsentieren die Kasuistik einer 87jährigen Patientin, welche uns
bei neuroradiologischem Verdacht auf Meningeosis carcinomatosa
zur weiteren Abklärung zugewiesen wurde. Anamnestisch berichtete
sie über ein chronisches lumbales Schmerzsyndrom mit Ausstrahlung
ins rechte Bein, sowie über einen seit zwei Monaten aufgetretenen
bandförmigen, nicht atemabhängigen Schmerz in der Mitte der Brustwirbelsäule. Dieser zeigte sich therapieresistent auf hochdosierte
Analgetika. Seit der Kindheit bestehen eine thorakale Skoliose, sowie
zahlreiche Hautknoten an den Extremitäten, wobei die Familienanamnese bezüglich fibromatöser Erkrankungen positiv war. Klinisch
fanden sich ausser einer leichten Gangataxie, welche topographisch
nicht eingeordnet werden konnte, sowie einem anamnestisch vorbestehendem partiellen Sensibilitätsverlust im Dermatom L5/S1 keine
fokalen Defizite. Die thorakalen Beschwerden waren mit einem radikulären/segmentalen Th6/7 Reizsyndrom vereinbar. In der auswärtigen MRT Untersuchung der lumbalen Wirbelsäule liessen sich diverse
Kontrastmittel aufnehmende intradurale Knoten entlang der Cauda
equina nachweisen, bei welchen vom radiologischen Aspekt her eine
Meningeosis carcinomatosa als Verdachtsdiagnose im Vordergrund
stand. Die MRT Untersuchung der restlichen Wirbelsäule und des
Schädels waren unauffällig. Ein Primärtumor konnte nach ausgiebigem Screening nicht gefunden werden. Auch die mehrfach durchgeführte Liquoruntersuchung ergab keine Anhaltspunkte für maligne
Zellen, zeigte jedoch eine lymphozytäre Pleozytose. Sowohl die IgG
als auch die IgM Borrelia burgdorferi-Antikörper konnten im Serum
und Liquor als reaktiv nachgewiesen werden, weshalb zusammen mit
den klinischen Befunden (thorakale Radikulitis) und der lymphozytären Meningitis von einer Neuroborreliose im Frühstadium (Stadium II,
Garin-Bujadox-Bannwarth-Syndrom) ausgegangen wurde. Nach einer
vierwöchigen intravenösen Therapie mit Ceftriaxon (2 g/24 h) zeigten
sich die Schmerzen regredient. Zwei Monate später war die Patientin
praktisch beschwerdefrei. Die Aetiologie der intraduralen Knoten
bleibt noch offen. Möglicherweise handelt es sich um Schwannome
(allenfalls bei einer rudimentären Form einer Neurofibromatose Typ 1),
differentialdiagnostisch kämen aber auch kleine Abszesse im Rahmen
der Neuroborreliose in Frage. Die geplante MRT Kontrolluntersuchung
in drei Monaten wird die Aetiologie hoffentlich klären.
Liver failure in a patient with phaeochromocytoma crisis
Brauchlin A.E., Rudiger A., Maggiorini M. (Zürich)
We present a 50 year old man with malignant phaeochromocytoma in
whom the tumor was first diagnosed and resected at the age of
eleven. After years of remission, recurrent disease was diagnosed
four years ago. The current history started with somnolence and
jaundice. Initial treatment with labetalol failed, and the patient
required intubation. For further diagnostics and management, he was
transferred to our intensive care unit. On admission, the patient had a
blood pressure of 128/76 mm Hg, clammy skin and black toes. A CTscan showed the large (8 cm in diameter) intraabdominal tumor.
A portal vein thrombus with infarction of the right liver lobe was
detected. Laboratory-testing was remarkable for highly elevated liver
enzymes, a coagulopathy and lactatemia. A severely depressed left
ventricular function of less then 20% was revealed by echocardiography. Albeit normal blood pressure values at this time point, serum
norepinephrine-levels were seventy times the upper limit. The patient
was anuric, and impaired kidney perfusion was seen by ultrasound.
We begun treatment with high-dose intravenous phentolamin and
fluids. The peripheral circulation improved, the cardiac index
increased from 2,5 l/min/m2 to 4l/min/m2 and lactate values normalized within hours. After a day of effective treatment, repeat echocardiography showed recovery to baseline values. With restitution of
adequate arterial blood flow, liver function recovered and anticoagulation was initiated for the treatment of the portal vein thrombosis.
Under renal replacement therapy, creatinin-levels normalized. The
patient was extubated four days after admission. Antihypertensive
treatment was changed to a combined oral regimen with doxazosin,
carvedilol, lisinopril and nifedipin. However, sufficient blood pressurecontrol could only be achieved with doses above standard recommendations. A Fluor-Dopa-PET-Scan did not show additional
phaeochromocytoma metastasis, and the patient was scheduled for
surgical resection of the tumor. Portal vein thrombosis with liver
infarction is an exceptional presentation of phaeochromocytoma. We
hypothesize that volume depletion and low blood-flow let to this
complication. The case highlights the fact, that phaeochromocytoma
can present with multiorgan failure. Effective alpha-blocking treatment and fluid-administration are essential in order to maintain the
macro- and microcirculation and to prevent further deterioration.
Abb. 1
unklare Knoten 1
P99
Abb. 2
unklare Knoten 2
Contribution des colloques «Mortalité & Morbidité»
à l’amélioration de la qualité des soins
Carron P-N., Deriaz S., Ribordy V., Hugli O., Lamy O., Waeber G.
(Lausanne)
Introduction: La gestion des risques et l’amélioration de la qualité
des soins passent par l’identification de situations critiques et par
l’analyse de leurs causes. À cet égard, les colloques «Mortalité &
Morbidité» (M&M) constituent un extraordinaire outil d’enseignement.
A la lumière d’une situation critique, nous présentons la stratégie
mise en place dans le service de médecine interne et le centre des
urgences, services affiliés dans la prise en charge des patients et la
formation des médecins.
Méthode: Des colloques d’une durée d’une heure réunissent mensuellement l’ensemble des médecins des deux services. Un cas
concret survenu dans les dernières semaines est présenté par un
chef de clinique et discuté avec les participants. Pour dépasser la
notion de faute, le secret médical et l’anonymat des intervenants sont
garantis. Les facteurs favorisants, ainsi que les moyens permettant
d’éviter à l’avenir un incident similaire sont identifiés. En parallèle, les
bases théoriques de gestion de risque, de survenue d’erreurs humaines et de travail en équipe sont abordées.
Cas clinique: Un homme de 28 ans est admis aux urgences pour un
sevrage éthylique. À l’anamnèse, on relève une consommation d’un
litre d’alcool fort par jour, ainsi qu’une hospitalisation aux soins intensifs lors d’un précédent sevrage. Dès l’entrée, il présente une crise
convulsive tonico-clonique, répondant rapidement à l’administration
de benzodiazépines. Le bilan paraclinique révèle une hypokaliémie,
ainsi qu’une hypomagnésémie. L’apparition d’un delirium tremens
nécessite l’instauration d’un traitement de lorazepam, puis de clorazepam iv. Le patient présente alors un arrêt cardio-respiratoire sur
une torsade de pointes (Fig. 1). La relecture a posteriori de l’ECG
confirme un intervalle QT prolongé à 510 msec. L’évolution est favo-
POSTERS SSMI
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rable après réanimation et correction de troubles électrolytiques.
Discussion: Le risque d’arythmies malignes et en particulier de torsades de pointes est largement décrit lors de sevrages alcooliques
compliqués. L’analyse du cas permet d’identifier plusieurs lacunes
dans le diagnostic, dans l’identification des critères de gravité et dans
la prise en charge thérapeutique (Fig. 2).
Conclusions: Les colloques M&M jouent un rôle essentiel dans le
développement d’une véritable culture de l’erreur. En ce sens, ils
répondent aux exigences de formation de la FMH et participent à
l’acquisition de compétences médicales modernes.
Fig. 1
Torsade de pointes
Forum Med Suisse 2008;8:(Suppl. 40)
52 S
dieses Syndrom (in 85–90% der Fälle nachweisbar), was einen Hinweis auf die Schädigung peripherer Myelinscheiden gibt. Das GQ1bEpitop wurde u.a. auch in Lipopolysacchariden von Campylobacter
jejuni gefunden (Pat. hatte einen reaktiv positiven Titer), so dass man
eine entsprechende Infektion als Trigger ansehen kann. Die Therapie
erfolgt in schweren Fällen analog zur Behandlung eines GuillainBarré-Syndroms (Immunglobuline, Plasmapherese). Die Spontanheilungsrate ist jedoch glücklicherweise relativ hoch, wie bei unserer
Patientin, so dass keine spezifische Therapie erforderlich war. 4
Monate nach der Hospitalisation waren alle körperlichen Beschwerden verschwunden, die Augenmotilität komplett wiederhergestellt.
Auch die thyreostatische Behandlung und Steroidtherapie konnten
gestoppt werden.
P101
Fig. 2
Trajectoire d’occasion
P100
Hartnäckige Doppelbilder – nur endokrine Ophthalmopathie
bei M. Basedow?
Vetsch G., Pato U., Fischli S., Lepper S., Loennefors T., Offinger A.,
Bürgi U., Schiemann U. (Bern)
Wir beschreiben den Fall einer 42jährigen Patientin mit einer gastrointestinalen Infektion Anfang 2007. Im weiteren Verlauf traten Schmerzen am Hals, eine Hyperosmie sowie Doppelbilder und Schwindel
auf. Laborchemisch fand sich die Konstellation einer hyperthyreoten
Stoffwechsellage mit einem supprimierten TSH (0,04 mU/l) und
erhöhten Werten für FT3 (12,1 pmol/l) und FT4 (36,1 pmol/l). Die TSHRezeptor-Antikörper (1,9 U/l) und mikrosomalen Antikörper (139 kU/l)
waren leicht erhöht. Das MR der Orbitae zeigte eine Schwellung der
Mm. recti inferiores. Unter der Diagnose eines M. Basedow mit
begleitender endokriner Ophthalmopathie wurde eine Behandlung
mit Carbimazol (20 mg tgl.), Propranolol (80 mg tgl.) und Prednison
(100 mg tgl.) begonnen. Der klinische Status besserte sich trotz Normalisierung der Laborwerte zunächst jedoch nicht. Die Augenmotilität
blieb erheblich eingeschränkt. Die Schilddrüsensonographie war
normal, zeigte insbesondere keine für den M.Basedow typische
Hypoechogenität des Parenchyms. Neurologischerseits fielen eine
Konvergenzschwäche und abgeschwächte Eigenreflexe auf. Das
EMG und der Mestinontest waren normal, die Acetylcholin-RezeptorAntikörper negativ. Die Anti-GQ1b-Antikörper waren mit einem Titer
von >15000 U/l massiv erhöht, so dass wir die Diagnose eines MillerFisher-Syndroms stellen konnten. Das Miller-Fisher-Syndrom ist eine
seltene Variante des Guillain-Barré-Syndroms und durch das kombinierte Auftreten von Ophthalmoplegie, Ataxie und Hyporeflexie
gekennzeichnet. Anti-Glykolipid-Antikörper sind hoch sensitiv für
Monoarticular septic arthritis due to Streptococcus
pneumoniae
Karathanasis S., Di Benedetto C., Chimchila Chevili S., Pons M.,
Bernasconi E. (Lugano)
Septic arthritis due to Streptococcus pneumoniae is rarely reported in
modern times. The incidence of pneumococcal septic arthritis in
patients with pneumococcal bacteremia is extremely low, ranging
from 0.5 to 0.7 percent in three different case series. A 76 year-old
man affected by Hodgkins disease (Ann Arbor Classification stage
IVB) presented with erythema, swelling and pain of the left ankle. The
patient was unable to walk due to the pain that was exacerbated by
light palpation. Because of a severe thrombocytopenia an arthrocentesis was not performed. However, in the blood cultures growth of
S. pneumoniae was detected. The initial antibiotic treatment with
Imipenem i.v. was changed to Ceftriaxone i.v. for a total of four weeks
with both clinical and laboratoristic improvement. The second case
refers to a 77 year-old man with hypertensive cardiopathy and
chronic atrial fibrillation that presented with fever, and chills in the last
48 hours. He developed a swelling of the right knee with local erythema and pain when moving. Blood cultures were taken and empirical treatment with Ceftriaxone was immediately started. One day later
an arthrocentesis was performed. S.pneumoniae grew in the blood
cultures, but not in the synovial fluid. However, eubacterial
polymerase chain reaction (16S rDNA directed PCR) was positive
and DNA sequencing confirmed the presence of S.pneumoniae in the
synovial fluid. Treatment with Ceftriaxone i.v. for five weeks combined
with a repeated surgical drainage resulted curative. S. pneumoniae
can cause suppurative joint infections, being the knee, wrists, ankles
and hips more commonly involved. One review of 190 cases of pneumococcal septic arthritis that occurred over 40 years noted that the
majority of cases were monoarticular, but polyarticular involment
occurred in 36 percent of cases. Even in the absense of a clinically
apparent focus of pneumoccoccal infection, e.g. pneumonia,
S. pneumoniae should be considered as a possible cause of
suppurative arthritis.
P102
Der Arbeitgeber als Ursache einer Blutdruckkrise
Signorell L., Wertli M., Weber M., Gubler J. (Winterthur)
Fallpräsentation: Zuweisung eines 44jährigen Patienten bei schwer
einstellbarer, arterieller Hypertonie unter ausgebauter Medikation.
Ein obstruktives Schlafapnoesyndrom wird behandelt, ebenso sind
sekundäre Ursachen (Nierenarterienstenose, Endokrinopathien) weitgehend ausgeschlossen worden. Hinweise auf weitere sekundäre
Hypertonieursachen wie NSAR-Einnahme, Äthyl- oder Drogenabusus
oder eine Malcompliance bestehen nicht. Als Endorganschaden zeigt
sich eine hypertensive Herzerkrankung mit erhaltener linksventrikulärer Funktion. Eine aussagekräftige Ergometrie (Doppelprodukt 2,8)
zeigt keine Belastungshypertonie. Die nachfolgende
24 Stunden Blutdruck (24h-BD)-Messung zeigt eine erhebliche
Hypertonie Grad 2–3 mit einer hypertensiven Gefahrensituation um
POSTERS SSMI
POSTERS SGIM
10:40 Uhr von 221/118 mm Hg (Tabelle 1: Messung 1). Die Befundbesprechung mit dem Patienten ergibt, dass ihm genau zu diesem
Zeitpunkt die Stelle gekündet wurde! Es liegt somit eine deutliche
vegetative Komponente vor, welche die Durchschnittswerte der Messung deutlich beeinflusst. Bestätigt wird dies in einer Verlaufsmessung (Tabelle 1: Messung 2), welche unter äquivalenter Therapie
deutlich niedrigere Blutdruckwerte demonstriert.
Diagnose: Sympathikotone Reaktion bei Dysstress als Fehlerquelle
der 24h-BD-Messung.
Diskussion: Bei schwer einstellbarer arterieller Hypertonie ist eine
24h-BD-Messung indiziert. Sie ermöglicht die Entdeckung weiterer
Ursachen (wie Malcompliance, Fehlmessungen, Sprechstundenhypertonie) sowie die Dokumentation des Schweregrades. Die differenzierte Auswertung der Messung ist jedoch von zentraler Bedeutung.
Wie im obigen Fall beschrieben, haben bekannte Stressoren wie
Arbeit, Sport (inklusive Fussballspiel am Fernsehen) und die Schlafqualität einen wesentlichen Einfluss auf das Blutdruckverhalten.
Ebenso können für Patient und Arzt unerwartete Ereignisse grosse
Auswirkungen haben.
Tabelle 1
Forum Med Suisse 2008;8:(Suppl. 40)
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P104
Decision making capacity in a general internal medicine
ward: competence or not? That’s the question
Fassassi S., Bianchi Y., Stiefel F., Waeber G. (Lausanne)
Background: Assessment of capacity to consent to treatment is an
important medical, legal and ethical issue in daily clinical practise.
Objective: To compare the results of an evaluation of patients’ competence by members of the medical team, a specific tool
(Silberfeld’s score) and a psychiatric expert.
Method: Over a 3 months period all of the 265 potentially eligible
patients admitted within the first 72 hours in a acute care setting of a
general internal medicine unit were prospectivally evaluated for their
decision making capacity (competence). For each enrolled patient a
research fellow (YB) gathered the different evaluations of the medical
team (junior doctor, senior doctor, nurses and referring general practitioner) and applied the Silberfeld and the MMSE (Mini Mental Status
Examination) and a psychiatrist (SF) assessed the patient independently with regard to his competence.
Results: 108 (40.8%) patients were excluded: 38 (14.4%) because
of evident incompetence (patients were unconscious or severely
cognitively impaired) and 70 (26.4%) were excluded for other reasons
(patient refusal, hemodynamic instability, language disabilities, etc.).
Of the 157 patients enrolled, 14 were considered incompetent by
the psychiatrist. This summs up to a total of 52 out of 265 inpatients
(19.6%) who had an impaired decision-making capacity. Agreement
between the psychiatric evaluation and the Silberfeld questionnaire
was poor (kappa 0.249) with a sensitivity of 35.7% and a specificity
of 91.6%. Experienced clinicians showed higher agreement (sensitivity of 57.1% and specificity of 96.5%) with the psychiatric evaluation.
The association of all of the treating team members showed even
higher sensitivity (78.6%).
Conclusions: Clinicians should be aware and trained to assess
patient’s competency. This study demonstrated that a specfic tool
like the Silberfeld is less useful than an interdisciplinary evaluation by
clinicians. Given the high percentage of incompetent patients admitted to General Internal Medicine, clinicians’ training should include
the evaluation of competency in order to fullfill current medico-legal
requirements.
P103
A medical mystery – a patient with malaise, headache
and altered mental state after loss of consciousness
with need for short resuscitation
Marsteller I., Hagara D., Massari I., Bernasconi E., Pons M. (Lugano)
Emergency medical services make efforts to improve quality and
promptness of preclinical care as well as trying to fix as early as
possible a probable diagnosis. Once arrived in hospital, the quality
of care is crucial for the clinical course and outcome of every patient.
We report the clinical case of a 61-year-old man who was admitted to
our emergency department after loss of consciousness with need for
short resuscitation outside the hospital. At arrival he presented with
malaise, headache and somnolence. Past medical history was
uneventful. We noted the absence of allergies and regular drug intake.
The patient took two tablets of Aspirin prior to admission. While
cardiovascular risk factors were absent, he admitted having drunk
little alcohol the day before. Initially the patient showed psychomotor
retardation with amnesia and referred vertical diplopia. The objective
neurological status and general physical examination showed no
abnormalities, haemodynamics were always stable. ECG, chest X-ray
radiograph and a cerebral CT scan revealed no pathologic findings.
There were no diagnostic hints in the routine laboratory tests. The
analysis of cerebro-spinal fluid showed no abnormalities. The patient
was hospitalised for monitoring of suspected transient ischemic
attack. Urine-drug-screening was only positive for benzodiazepines,
on enquiry the patient reported having taken Lorazepam 5 mg the
night before in order to fight job-related stress. Doppler ultrasound
of jugular and cervical arteries as well as cerebral MRI was negative.
The clinical course was favourable. Stumbling on the patient’s comment about work-related stress with implications on his family it was
offered a psychiatric consultation that he accepted willingly. In this
conversation the patient, now bright and lucent, revealed having
provoked most of his symptoms in order to obtain a complete medical “check-up” of “highest quality” that he would not have had with
his general practioner. The specialist did not diagnose any psychiatric
disease. The patient was discharged on the fourth day after admission. In conclusion, this report shows the difficulties we had in providing correct diagnosis despite explicit medical history, physical examination, neurological consultations and extensive technical tools. A
part from the mystery unravelled, possible implications for medical
reasoning, health policy and for the doctor-patient relationship are
discussed.
P105
Klossige Sprache und schwere Augenlider am Abend
Stempfle V., Bertschy S., Donati F. (Biel)
Eine 72jährige Patientin stellte sich auf unserer Medizinischen Notfallstation wegen Sprechproblemen bedingt durch «eine schwere
Zunge» seit 14 Tagen vor. In den letzten Tagen waren zusätzlich
Probleme beim Kauen und Schlucken aufgetreten, ausserdem eine
heisere Stimme und seit 2 Tagen eine Lidschwäche des linken Auges.
Die Kau/Schluckprobleme hatten dazu geführt, dass sie in den letzten
Tagen nur noch flüssige Nahrung zu sich nehmen hatte können und
Gewicht abgenommen hatte. Die persönliche Anamnese war bland,
ausser ihres Alters hatte sie keine kardiovaskulären Risikofaktoren. In
der klinischen Untersuchung fiel eine kachektische Patientin auf. Die
Lidspalte links war enger als rechts, eine fragliche Mundastschwäche
links, leichte Dysarthrie bei verlangsamter Zungenmotilität, erhaltene
Augenmotilität, die linke Pupille war diskret kleiner gegenüber rechts.
Die kardiopulmonale Untersuchung und der restliche Neuro-Status
waren unauffällig. Bei Verdacht auf Hirnstammpathologie veranlassten wir ein MRI des Schädels inklusive Angiographie, welches ausser
einer vaskulären Leukenzaphalopathie keine pathologischen Befunde
zeigte. Wegen diskreter Horner-Symptomatik links dachten wir ausserdem an eine Raumforderung intrathorakal; im CT-Thorax gab es
keine Hinweise hierfür. Während der Abklärungszeit auf der Notfallstation (es wurde Abend) kam es zu deutlicher Verschlechterung der
Symptomatik: die Sprache wurde klossig, die Patientin konnte ihren
Speichel kaum mehr schlucken und ihre Augenlider beidseits kaum
mehr heben. Bei dieser Dynamik mit beobachteter Verschlechterung
der Beschwerden am Abend kam differentialdiagnostisch eine
Myasthenia gravis in Betracht. Nach probatorischer Gabe von Pyridostigmin kam es zu prompter Verbesserung der Symptomatik. Weitere
Abklärungen zeigten positive Anti-Acetylcholin-Antikörper, womit die
Diagnose einer okulo-bulbären Myasthenia gravis gesichert werden
konnte. Einige Monate nach Therapiebeginn mit Pyridostigmin und
zusätzlich Steroiden ist die Patientin beschwerdefrei. Der relativ
häufige Beschwerdekomplex aus Dysarthrie vergesellschaftet mit
Schluckproblemen auf einer medizinschen Notfallstation wurde in
diesem Fall durch eine okulo-bulbäre Form der Myasthenia gravis
erklärt.
POSTERS SSMI
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P106
Muskelschmerzen als Erstsymptom einer disseminierten
Sarkoidose
Douleur musculaire, le premier symptome d’une sarcoïdose
disséminée
Muscle pain as first sign of a disseminated sarcoidosis
Müller C., Knudsen L., Nicod L.P., Schiemann U. (Bern)
Hintergrund: Die disseminierte Sarkoidose mit klinisch manifester
muskuloskelettaler Beteiligung ist relativ selten. In der Literatur geht
man von 0,5% aller Sarkoidosefälle aus.
Fallbeschreibung: Wir berichten über einen 39jährigen Patienten mit
Schmerzen der Schultergürtel- und der proximalen Oberschenkelmuskulatur beidseits, trockenem Husten sowie Gewichtsverlust von
6 kg in 6 Monaten. Histologisch wurde eine Sarkoidose im Muskelgewebe des Oberschenkels sowie im Lungenparenchym nachgewiesen.
Aufgrund weiterer klinischer, laboranalytischer sowie bildgebender
Untersuchungen vermuteten wir eine disseminierte Sarkoidose mit
Beteiligung von Myokard, Lunge, Lymphknoten, Augen, Milz, Leber,
Niere und Muskel. Zudem fand sich eine Hyperkalzämie und Hyperkalzurie. Unter Therapie mit Glucocorticoiden und Mycophenolatmofetil zeigte sich im Verlauf eine Verbesserung des Allgemeinzustandes und der Lungenfunktion (Vitalkapazität) mit Regredienz bis
Normalisierung vor Therapiebeginn pathologischer Laborparameter.
Konklusion: Bei Vorliegen einer Myopathie muss bei zusätzlichen
Hinweisen auf eine Systemerkrankung differentialdiagnostisch eine
Sarkoidose erwogen werden. Für die Sicherung der Diagnose ist die
Histologie mit Nachweis nicht-verkäsender Granulome wegweisend.
Schlüsselwörter: Myositis, disseminierte Sarkoidose
Abb. 1
MRI Oberschenkel
Forum Med Suisse 2008;8:(Suppl. 40)
54 S
eine entzündliche Erkrankung der Fissura orbitalis superior und des
Sinus cavernosus unklarer Aetiopathogenese, klinisch präsentiert
durch eine unilaterale schmerzhafte Parese der Hirnnerven III, IV, VI
und des N. ophthalmicus. Der Verlauf ist spontan rückläufig mit
Rezidivneigung. Die Diagnosesicherung erfordert jedoch immer
umfangreiche Untersuchungen, um eine sekundäre Ursache eines
ophthalmoplegischen Kopfschmerzes auszuschliessen.
P108
Prevalence and time-course of acute mountain sickness
in adolescents after rapid ascent to 3’450 m
Bloch J., Duplain H., Rimoldi S., Stuber T., Kriemler S., Allemann Y.,
Sartori C., Scherrer U. (Lausanne, Bern, Basel)
Facilitated by modern transportation, increasing numbers of children
and adolescents are visiting high-altitude tourist destinations. Acute
mountain sickness (AMS) is a frequent and debilitating complication
of high-altitude exposure, but there is little information on the prevalence and time course of AMS in children and adolescents after rapid
ascent by mechanical transportation to 3500 m, an altitude at which
major tourist destinations are located. We, therefore, performed serial
assessments of AMS (Lake Louise Score, LLS) in 48 healthy nonacclimatized adolescents with no previous high-altitude experience
(mean ± SD age, 13.7 ± 0.3 yrs; 20 girls and 28 boys) 6, 24, and 48
hrs after arrival at the Jungfraujoch high-altitude research station
(3450 m) reached after a 21⁄2 hr ascent by train. The major new finding
was that the prevalence of AMS during the first 3 days at no moment
of time was greater than 25%. The incidence of AMS was similar in
both genders and declined steadily during the stay (17% after 24 hrs,
8% after 48 hrs). None of the subjects had to be evacuated to lower
altitude and symptoms responded well to symptomatic treatment.
In conclusion, after rapid ascent to high altitude, the prevalence of
AMS in adolescents is relatively low, the clinical manifestations are
benign and if present, resolve rapidly. These findings suggest that
for the majority of healthy non-acclimatized adolescents, travel to
3500 m is safe and pharmacological prophylaxis for AMS may not be
needed.
P107
Schmerzhafte Ophthalmoparese: Tolosa-Hunt Syndrom
Semadeni G.-M., Rodic B., Löschhorn Ch., Ballmer P. E. (Winterthur)
Fall: Wir berichten über den Fall einer 45jährigen Frau mit bekannter
Migräne ohne Aura, die einen akuten retroorbitalen Kopfschmerz
rechts mit im Verlauf zunehmend aufgetretenen Doppelbildern und
Ptosis rechts entwickelt hat. Die neurologische Untersuchung ergab
eine partielle externe und interne Oculomotoriusparese des rechten
Auges mit ipsilateraler Mitbeteiligung des N. ophthalmicus und fraglich auch des N. opticus, bei gleichzeitig bestehender ausgeprägter
Schmerzsymptomatik des Auges bei Bewegung. Die morphologische
Evaluation des zentralen Nervensystems mittels Hirn-Kernspintomographie (MRT) und CT-Angiographie schloss einen parasellären Kompressionsprozess aus. Die Liquoranalyse zeigte eine leichte aseptische entzündliche Reaktion ohne Nachweis einer viralen, atypischen
oder bakteriellen Infektion bzw. einer autoimmunen entzündlichen
Reaktion mittels ergänzenden Laboruntersuchungen. Über
Ausschlusskriterien wurde die Verdachtsdiagnose eines Tolosa-Hunt
Syndroms gestellt und eine Steroidtherapie mit Prednison 1 mg/kg
KG/Tag begonnen. Innerhalb von 72 h kam es zur eindeutigen
Schmerzreduktion, nach 5 Tagen zeigte sich die Ophthalmoparese
rückläufig. In den folgenden Wochen wurde die Prednisondosis systematisch reduziert und 12 Wochen nach Beginn der Therapie abgesetzt. Zum Zeitpunkt der kranialen MRT-Kontrolluntersuchung,
4 Monate nach Beginn der Steroidtherapie, waren die Schmerzen und
die Augenmuskelparesen vollständig verschwunden, der intrakranielle
Befund war unverändert normal.
Diskussion: Die Differentialdiagnose einer schmerzhaften Ophthalmoparese ist sehr umfassend und beinhaltet zahlreiche Entitäten
inklusive neoplastische, vaskuläre, infektiöse und nicht-infektiöse
entzündliche Prozesse. Eine seltene Ursache mit negativer kranialer
Bildgebung ist das Tolosa-Hunt Syndrom. Dabei handelt es sich um
P109
What is the impact of an interactive course with detailed
feedback on the clinical skills in musculoskeletal medicine
of fourth year medical students?
Perrig M., Berendonk Ch., Hess R., Beyeler Ch. (Bern)
Background: Basic examination skills of the musculoskeletal system
(MS) are essential. Yet, many studies have demonstrated a low level
of clinical competence in MS, but only few studies looked at measures to improve.
Aims: To assess the immediate and long-term impact of an interactive course with formative feedback on the examination and
interpersonal skills of the MS.
Methods: Four consecutive groups with a total of 26 (out of 154)
fourth year medical students attended their 8 weeks clerkship in
internal medicine. Two groups (14 students) were randomly assigned
to the intervention (INT) of a 6x1 hour practical course of the MS
(interactive hands on examination of real patients; systematic,
detailed feedback to each student by the teacher and the peers). Two
groups (12 students) took part in the regular clerkship clinical activities only and served as controls (CO). In all four groups clinical skills
(CS) were assessed in an OSCE like station on a 4-point Likert scale
[total of 9 items] by two independent raters at the beginning (t0), at
the end (t1) and 5-12 months after (t2) the clerkship. They included
musculoskeletal examination skills (MSES) [7 items: inspection, palpation, global movement tests, active and passive joint movements,
trigger tests and comments on physical findings] and interpersonal
skills (IPS) [2 items: patient communication and behaviour]. Statistical
analyses included Mann-Whitney and Wilcoxon tests.
Results: All 26 students completed t0 and t1 tests. 13 students
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(6 INT, 7 CO) participated in the t2 test. At baseline t0 there were
no detectable differences between the INT- and CO-students for CS,
MSES and IPS (p = 0.78, p = 0.67 and p = 0.94, respectively). At the
end of the clerkship and several months later the CO-students
showed no significant changes of their CS, MSES and IPS (t1 p =
0.24, p = 0.56 and p = 0.09; t2 p = 0.50, p = 0.50 and p = 0.52, compared to t0). In contrast, the INT-students showed significantly
improved CS, MSES and IPS at the end of the clerkship (t1 p = 0.005,
p = 0.009 and p = 0.003) and even several months later for CS and
MSES, but not for IPS (t2 p = 0.03, p = 0.03 and p = 1.0, compared
to t0).
Conclusions: Specific interactive clinical skills courses with feedback
in addition to regular clinical activities on the ward improve CS, MSES
and IPS immediately after the teaching, as well as CS and MSES
several months later. We conclude that supplementary systematic
clinical teaching activities are worth the additional effort.
Figure 1
Results
Forum Med Suisse 2008;8:(Suppl. 40)
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P111
Stress during a simulated medical emergency
Hunziker S., Tschan F., Balestra G., Legeret C., Schumacher C.,
Semmer N., Hunziker P., Marsch S. (Basel, Neuchâtel, Bern)
Being involved in a medical emergency may be a stressful experience
for health-care workers. We aimed to assess subjective and objective
stress experienced during a scenario of simulated witnessed cardiac
arrest. Teams composed of three healthy volunteers (medical students) each participated. After the simulation participants rated the
degree of stress and the perceived realism of the scenario on a 10
point likert scale and indicated their emotions using a questionnaire
that measures 18 distinct emotions categorised on a intensity scale
from 1–5 (emotional wheel). Using Holter monitoring electrocardiographic data were obtained from one participant of each team. 120
medical students participated (37 male, median age 24 years). The
mean maximum and minimal heart rates (bpm) were 114 (SD 16) and
70 (SD 8.5). 37% of the students showed significant dynamic STsegment alterations with relevant J-Point-elevations (>0.1 mV) or Twave alterations (depressions greater than or equal to 1.0 mm). The
most relevant initial motion was concerns/distress (mean 4 out of 5).
After the manikin was “rescued” the experience of alleviation (4 out of
5) dominated. The median perceived stress and the median perceived
realism of the scenario were at 8 and 9 out of 10 respectively. Conclusions: A simulated medical emergency with a high perceived realism
caused substantial subjective stress. Stress was associated with
significant alterations in ST-segments in a high proportion of young
and healthy participants. The perceived emotional (di-)stress is maximal during the initial phase of high uncertainty easing off after the
successful handling of the event. Further studies are required to
elucidate the impact of the stress of health-care workers on their
performance in medical emergencies.
P110
Histoire clinique: Fistulisation d’un anévrisme de l’aorte
abdominale dans une veine rénale
Faucherre M., Lehmann B., Haftgoli N., Menth M., Hayoz D.,
Gaude J. (Fribourg)
Une patiente de 54 ans, connue pour hypertension et obésité (IMC à
34 kg/m2), se plaint d’une dyspnée NYHA III et d’oedèmes des membres inférieurs apparus progressivement. Les investigations en ambulatoire consistent en un électrocardiogramme qui met en évidence
une tachycardie sinusale avec bigéminisme ventriculaire permanent
et une échocardiographie qui montre une dilatation des oreillettes,
une hypertrophie ventriculaire concentrique gauche et une hypertension artérielle pulmonaire à 40 mm Hg. En l’absence d’amélioration
clinique sous diurétiques et béta-bloquants, la patiente est adressée
aux urgences. Au status, on note des hématomes au niveau des bras,
une décompensation cardiaque globale et un souffle abdominal. Le
bilan sanguin montre une coagulation intravasculaire disséminée, une
perturbation des tests hépatiques et une insuffisance rénale aiguë.
L’échographie révèle un anévrisme de l’aorte abdominale (AAA) sousrénal d’un diamètre de 4,2 cm et, postérieurement à ce dernier, une
structure vasculaire dans laquelle le doppler capte un signal pulsatile.
Le scanner abdominal montre une fistule entre la partie postérieure
de l’anévrisme de l’aorte et la structure vasculaire susmentionnée
correspondant à une veine rénale gauche. Cette fistule entre l’AAA
et la veine rénale est responsable de cette défaillance multiorganique.
La patiente bénéficie en urgence d’une intervention chirurgicale comprenant: un pontage de l’AAA par un tube droit et une ligature de la
veine rénale gauche rétro-aortique permettant l’exclusion de la fistule.
Une étude rétrospective? d’un institut italien de chirurgie générale et
cardio-vasculaire a décrit le site de rupture de 373 cas d’AAA (opérés
entre 1965 et 1992). En conclusion, les ruptures se font principalement au niveau du rétropéritoine (79,09%) et, plus rarement, dans le
péritoine (12,06%), les veines abdominales majeures (6,97%) et le
tractus intestinal (1,88%). Ce cas clinique est d’autant plus intéressant que la rupture de l’AAA s’est faite dans une veine rénale rétroaortique. Il rappelle aussi l’importance du status qui a permis de
poser précocement le diagnostic et de diminuer ainsi le risque opératoire. En effet, la prise en charge chirurgicale est le traitement de
choix; la présence d’un état de choc pré-opératoire augmente le taux
de mortalité [1].
1 J Cardiovasc surg 1993;34:39–47.
P112
Resultate einer Befragung niedergelassener Ärzte
zum Einfluss der Wirtschaftlichkeitsverfahren auf die ärztliche
Berufsausübung
Foglia R., Schaufelberger H., Uhr M., Mainieri F., Bernasconi O.,
Battaglia E., Pedrazzoli J., Fontana P., Cerny A. (Lugano, Paradiso)
Hintergrund: Das Bundesamt für Gesundheit hat die Kontrolle der
Wirtschaftlichkeit wie sie im Artikel 56 des KVG vorgesehen ist, dem
Dachverband der Krankenversicherer santésuisse übertragen. Die
Umsetzung dieser Kontrollfunktion wurde in den Kantonen unterschiedlich gelöst und erfolgte in der Regel durch Einsetzung einer
paritätischen Kommission zusammengesetzt aus Vertretern der Krankenkassen und der Ärzteschaft. Im Kanton Tessin waren in
den letzten Jahren eine unbekannte aber vermutlich hohe Anzahl
Wirtschaftlichkeitsverfahren aussergerichtlich abgewickelt worden.
Im Jahre 2007 war zudem eine besonders hohe Anzahl von neuen
Wirtschaftlichkeitverfahren ausgelöst worden was zu einer Verunsicherung der Ärzteschaft führte. Um eine genauere Analyse des
numerischen Umfangs aussergerichtlicher Verfahren machen zu
können und um den Einfluss derselben auf das ärztliche Verhalten zu
untersuchen wurde eine Umfrage bei den niedergelassenen Ärzten
im Tessin durchgeführt.
Methodik: An 519 niedergelassene Aerzte wurde ein Fragebogen
verschickt mit folgenden Fragen: «Mussten Sie jemals Zahlungen an
santésuisse Ticino im Rahmen eines aussergerichtlichen Wirtschaftlichkeitsverfahrens machen?» und «Fühlen Sie sich, in der aktuellen
Situation im Tessin frei, nach Wissen und Gewissen zum Wohle Ihrer
Patienten als Arzt zu arbeiten?» Die Fragebogen wurden verschickt
und die eingegangen Antworten durch einen Notar ausgezählt und
analysiert.
Resultate und Diskussion: Die Umfrage ist zum Zeitpunkt der Einreichung des Abstracts noch nicht abgeschlossen: bis zum 13.1.08 sind
196 der 519 verschickten Fragebogen eingegangen. Die definitive
Zahl und die Analyse der Antworten werden am Kongress präsentiert
werden. Limitationen der gewählten Methodik sind der fehlende
Vergleich mit Aerzten aus anderen Regionen und die Tatsache dass
nur zwei Fragen gestellt wurden, Faktoren welche eine detaillierte
Analyse der Problematik erschweren. Die Umfrage und die dabei
gewonnen Erkenntnisse sollen ähnliche Untersuchungen in anderen
Teilen unseres Landes anregen und eine breitere Diskussion des
Spannungsfeldes um Artikel 56 des KVG auslösen.
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P113
Caspofungin (CSP) for prophylaxis (Px) of intraabdominal
candidiasis (IC) in high-risk surgical patients (Pts): a pilot study
Senn L., Eggimann P., Ksontini R., Pascual A., Bille J., Calandra T.,
Marchetti O. (Lausanne)
Background: We have previously shown that 30–40% of surgical Pts
with recurrent gastrointestinal perforation/anastomotic leakage, or
acute necrotizing pancreatitis develop IC (Lancet 1989, 2:1437).
These Pts benefit of fluconazole Px (Crit Care Med 1999;27:1066).
A corrected Candida colonization index (CCI) 00.4 is a major risk
factor for IC (Ann Surg 1994;220:751). CSP, a new therapy for IC
including azole-resistant Candida spp., may be used for Px of IC.
Objective: To conduct a non-comparative pilot study on the efficacy
and safety of CSP for Px of IC in high-risk surgical Pts.
Methods: Inclusion criteria: age >18, surgery for recurrent gastrointestinal perforations/anastomotic leakage or acute pancreatitis.
Exclusion criteria: documented IC, fluconazole Px. CSP Px (70 mg,
then 50 mg/day) was given until resolution of the surgical condition.
Candida colonization was monitored 1x weekly at 03 sites and the
CCI calculated. Success was defined by the absence of IC during
CSP Px. Occurrence of CSP-related SAE was recorded.
Results: 19 Pts were enrolled: 16/3 males/females, median age 69
(range 40–84). Underlying surgical conditions were: recurrent gastrointestinal perforation/anastomotic leakage (n = 16), acute pancreatitis (n = 3). At study entry, 14 (74%) Pts were in the ICU (median
Simplified Acute Physiology Score II: 45, range 31–65), 19 (100%)
received antibacterial therapy and 17 (89%) were colonized with
Candida (C. albicans in 69%; CCI 00.4 in 1/17 case, 5%). Median
duration of CSP Px was 16 days (range 4–46). During CSP Px, 17
(89%) Pts remained colonized (C. albicans in 68%), but 0/17 developed a CCI 00.4. CSP was successful for prevention of IC in 18
(95%) Pts. Among 5 deaths, none was attributed to IC. No severe
CSP-related SAE requiring discontinuation of Px occurred.
Discussion: The results of this pilot study suggest that caspofungin
is efficacious and safe for prophylaxis of intra-abdominal candidiasis
in high-risk surgical patients.
P114
Chickenpox outbreak within a vulnerable population living
in crowded conditions
Bodenmann P., Vaucher P., Zanetti G., Masserey E., Cometta A.,
Daher O., de Vallière S. (Lausanne, Yverdon-les-Bains, Sainte-Croix)
Objectives: Describe how to manage an index case of chickenpox in
a Centre for Asylum Seekers (CAS).
Case: The index patient, a 33-year old male Eritrean asylum seeker
living in a CAS in Switzerland, was hospitalised with fever, rash, and
tachypnea. He was diagnosed with disseminated varicella zoster
virus (VZV) infection and AIDS. The case was reported to the public
health department.
Epidemiological follow-up: Secondary cases were to be isolated
and serology performed on all asymptomatic Eritrean adults. Two of
44 individuals were negative for prior VZV infection. Six secondary
cases, one adult and five children, manifested between days 14 and
23. Transfers to and from the centre were suspended. All residents
(n = 124) and staff received information on VZV; all persons at risk
were screened for VZV antibodies. Thereafter, VZV sero-negative
adults were tested for HIV test and pregnancy, as appropriate. VZV
serologies of adult asylum residents were positive in 107 of 111
(96.4%) persons. Ten of the 13 children had no previous VZV infection. One woman was diagnosed pregnant and abortion was induced.
All adults were HIV negative. Of the 14 sero-negative residents, only
one of the three vaccinated adults did not develop chickenpox within
the month (attack rate = 92.9%). Residents were to move freely
again. Surveillance was organised, having nurse practitioners from
centres report all new cases. Three independent cases were reported
from two other centres during the next six months.
Discussion: Asylum seekers are at higher risk for epidemics and for
severe varicella. Once a case is identified, these risks should be
evaluated. Reviewing the country of origin’s immunization policies,
reported regional outbreaks, and sero-negative prevalence can be
difficult, as there are no international surveillance systems for VZV.
This is not true for most other vaccine-preventable diseases. Screening all asylum seekers exposed to VZV is time consuming and inefficient for prophylactic therapy. Our experience suggests a framework
Forum Med Suisse 2008;8:(Suppl. 40)
56 S
for controlling transmission of VZV or other vaccine-preventable
disease in CAS: 1) help the staff recognise an index case quickly;
2) isolate the index case during the contagious period and until risk
analysis has been done; 3) investigate whether other residents are at
high risk within the next 48h (pregnancy, HIV, immunisation coverage
charts); and 4) “wait and see” or eventually focus screening on high
risk populations.
P115
Cutaneous vasculitis due to Ciprofloxacin
Maunz G., Zimmerli W. (Liestal)
Introduction: Systemic vasculitis is a rare disease with a broad differential diagnosis. We describe 2 patients in whom cutaneous vasculitis
appeared during ciprofloxacin treatment and gradually disappeard
after stopping.
Case 1: A 68-y-old man with a hematogenous total knee
arthroplasty-associated infection due to S. aureus was treated with
iv-flucloxacillin for 2 weeks, and then switched to oral ciprofloxacin
plus rifampicin. Seven days later, an erythematous palpaple purpuric
rash appeared at both legs. One week later, vasculitis with necrotic
skin lesions was clinically confirmed by a dermatologist and both
antibiotics stopped. Despite further treatment with flucloxacillin, and
later with fusidic acid plus rifampicin, all lesions gradually healed.
Case 2: A 74-y-old man with a vascular prosthesis-associated infection due to S. aureus was treated with iv-flucloxacillin. Two weeks
later, ciprofloxacin was added because of a nosocomial urinary tract
infection due to Klebsiella pneumoniae. Eight days later, hemorrhagic
lesions, palpaple purpura and erythema exsudativum multiforme
appeared. Remembering the former case, ciprofloxacin was immediately stopped, and the lesions gradually disappeared despite continuous flucloxacillin therapy.
Comment: Both cases had clinically confirmed vasculitis. Vasculitis
has been observed during infection such as chronic hepatitis C,
endocarditis, bacteremia due to meningoccci and gonococci, as well
as other chronic infections. The mechanism of infection-associated
vasculitis is vascular inflammation due to local immune complexes.
Our patients had both severe S. aureus infection. However, infection
could be ruled out as cause of the cutaneous vasculitis, since in both
cases appearance and diappearance strictly correlated with
ciprofloxacin use. In both cases there was no evidence of renal
involvment. Drug-induced immune-complex vasculitis is a smallvessel vasculitis involving postcapillary venules and arterioles. About
10 cases of ciprofloxacin-associated cutaneous and/or renal vasculitis have been published. However, this adverse event must be more
frequent in view of our 2 cases within 6 years. Clinicians should be
aware of quinolone-associated hypersensitivity vasculitis, because
continuation of ciprofloxacin therapy has reported to be fatal.
P116
Invasive mold infections in non-neutropenic patients
in a tertiary care hospital: an 11-year postmortem analysis
Imhof A., Gläser C., Schaer D.J., Schoedon G., Schneemann M.
(Zürich)
Objectives: Invasive mold infections (IMI) are an important and
increasing cause of morbidity and mortality in hospitalized patients.
Methods: To investigate the incidence of IMI and underlying diseases
in non-neutropenic patients hospitalized in a tertiary care hospital,
all protocols of autopsies performed during an 11-year period
(1997–2007) were reviewed.
Results: This retrospective analysis yielded 53 cases of IMI. There
were 37 males and 16 females. Median age was 60 years (range
24–85). 50 cases with IMI and 3 patients with aspergilloma were
diagnosed. The most frequent isolates in patient with IMI were
Aspergillus species (96%) followed by Fusarium species (2%), and
Scedosporium apiospermum (2%). Fungal etiology was entertained
clinically in only 14 (28%) of the patients. All 14 patients with diagnosed IMI were treated with mold-active antifungal agents (AF). Two
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patients with not diagnosed IMI received a prophylactic treatment
with a mold-active AF. However, in 40 (80%) patients IMI was the
primary cause of death. Infected sites were lung 40 (80%), disseminated IMI 9 (18%), sinus 1 (2%). The major underlying conditions
were: 12 (24%) patients after solid organ transplantation, followed by
11 (22%) patients with solid organ cancer, 7 (14%) patients with
rheumatologic or immunological disorders receiving high dose corticosteroids, 6 (12%) patients with prolonged ICU stays, 6 HIV patients
(12%), 5 (10%) patients hemato-oncological tumors, 3 (6%) with
chronic lung disease. 31 (66%) patients were hospitalized on intensive care units (ICU) for at least one day. The median SAPS II score
was 45 (range 8-79) and the median ICU stay was 11 days (1-53).
Conclusion: This survey found IMI to be frequent in patients with a
wide range of underlying conditions. The high incidence of not clinically entertained IMI should enhance the clinician’s awareness and
suspicion of potentially fatal invasive mold infections. Further, our
findings confirm the importance of autopsy as a tool for quality control in medical diagnostic and therapeutic activity.
P117
Leberversagen bei einer viszeralen Leishmaniose (VL) mit
sekundärer hämophagozytischer Lymphohistiozytose
Fehr R., Jeker R., Reinhart W.H. (Chur)
Fallbeschreibung: Ein 40jähriger Patient wurde mit Schüttelfrost und
Fieber seit ca. 2 Wochen hospitalisiert. Die Reiseanamnese ergab
einen Indienaufenthalt im Jahr zuvor. Es bestand keine Immunsuppression; ein HIV-Test war negativ. Klinisch fiel ein Status febrilis und
eine Hepatosplenomegalie, im Labor eine Panzytopenie sowie eine
Erhöhung der Transaminasen, Cholestaseparameter und LDH auf.
Das Ferritin war mit 12000 mg/l deutlich erhöht. Differentialdiagnostisch stand neben einem Lymphom eine tropische Infektionskrankheit
im Vordergrund. Eine Malaria wurde in 3 Blutausstrichen nicht gefunden. Serologisch ergab sich einzig ein Hinweis auf eine akute EBVInfektion mit 8222 RNA-Kopien/ml. Im Verlauf trat eine Leberinsuffizienz auf. Das Ferritin stieg auf 160000 µg/l. Serologisch und mittels
positiver RNA im Serum konnte eine Leishmanieninfektion diagnostiziert werden. Im Knochenmark war eine Hämophagozytose
ersichtlich. Unter hoch dosierten Steroiden, Etoposid sowie Ambisome kam es rasch zur klinischen Besserung und Normalisierung des
Ferritins.
Diskussion: Für die hämophagozytische Lymphohistiozytose sind die
Klinik mit rezidivierenden Fieberschüben und Hepatosplenomegalie
sowie die Panzytopenie und Hyperferritinämie typisch. Als Auslöser
sind in der Literatur sowohl akute EBV-Infektionen als auch eine VL
beschrieben. In unserem Fall bestand ein Co-Infektion. Wir denken,
dass die VL massgebend war, da erst die antiparasitäre Therapie den
Durchbruch brachte. Serologisch ist bei unserem Patienten eine EBVPrimoinfektion möglich, eine Reaktivierung einer chronischen EBVInfektion unter der Immunschwäche bei VL jedoch wahrscheinlicher.
Bei Kindern wurde ein signifikanter Zusammenhang zwischen VL und
EBV-Primoinfekt aufgezeigt. Diskutiert wird eine Abnahme der leishmaniziden Aktivität der infizierten Makrophagen durch eine
Verstärkung der TH2 Immunantwort durch das Virus. Dieser Fall zeigt
auf, dass bei einer Panzytopenie, Hepatosplenomegalie und einer
Hyperferritinämie eine VL serologisch und mittels PCR von Serum,
Knochenmark oder Leber gesucht werden muss, auch wenn man
serologisch Hinweise für eine EBV-Infektion hat. Denn das Verpassen
einer VL ist letal, die Therapie mit Ambisome hingegen relativ
untoxisch und wirkungsvoll. Eine VL und Leberversagen wurde
bisher nur in der pädiatrischen Literatur beschrieben.
P118
Invasive Aspergillosen bei Patienten ohne Granulozytopenie:
Risiko und prognostische Faktoren
Kaiser P., Moll C., Frauchiger B., Rochat P., Thurnheer R., Krause M.
(Münsterlingen, Frauenfeld)
Hauptrisikofaktor für die Invasion von Aspergillen ist das Fehlen von
Phagozyten. Deshalb kommen Aspergillusinfektionen am häufigsten
bei Leukämiepatienten vor, welche über längere Zeit in der Aplasie
sind. Wir beobachteten in den vergangenen Jahren wiederholt
Forum Med Suisse 2008;8:(Suppl. 40)
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Aspergillosen bei Patienten, welche keine Agranulozytose aufwiesen.
Ihre Charakteristika und Risikofaktoren wurden retrospektiv zusammengestellt.
Resultate: Von 1998–2007 wurden bei 14 Patienten eine Aspergilleninfektion bioptisch oder autoptisch diagnostiziert. Patienten mit
Aplasie oder mit nicht-invasiver Aspergillenkolonisation waren ausgeschlossen. Bei 7 Patienten fand sich eine auf ein Lungensegment
beschränkte Aspergilleninfektion und bei 7 eine multilobäre Lungeninfektion mit/ohne Dissemination. Bei 2 der 7 Patienten mit lokalisierter Aspergillenpneumonie handelte es sich um einen Zufallsbefund
post mortem, bei 5 Patienten erfolgte die Diagnose im Rahmen der
Abklärung eines Lungenbefundes. Bei 2 dieser 5 Patienten war das
Mass der Gewebsinvasion durch Aspergillus spp. unsicher. Vier der
5 Patienten wurden fungistatisch behandelt und bei 3 wurde eine
Lungenteilsresektion durchgeführt. Alle hatten als Prädisposition eine
vorbestehende Lungenpathologie (COPD, St. n. Tbc), jedoch erhielt
keiner länger dauernd systemische Kortikosteroide oder andere
Immunsuppressiva. Alle Patienten hatten einen günstigen Verlauf. Bei
allen 7 Patienten mit multilobärer Pneumonie war eine hochdosierte
Kortikosteroidtherapie über Wochen vorausgegangen. Bei 4 Patienten
bestand als Grundleiden ein metastasierendes solides Karzinom mit
Hirnmetastasen, bei 3 eine vaskulitische Erkrankung. Alle Patienten
verstarben, wobei die Aspergilleninfektion wesentlich zum Ableben
beitrug. Die Dissemination erfolgte bei 5 Patienten, es fanden sich
Pilzhyphen in Hirn, Niere und Herz.
Schlussfolgerung: Lokalisierte Infektionen in der Lunge kommen
vor allem bei vorbestehenden Lungenpathologien vor und haben bei
Einsatz von Fungistatika und Chirurgie eine gute Prognose. Im
Gegensatz dazu haben multilobäre Aspergilluspneumonien mit
Dissemination eine sehr hohe Mortalität. Hauptrisikofaktor dafür sind
hochdosierte Kortikosteroide über mehrere Wochen.
P119
Use of activated protein C in a patient with miliary
tuberculosis and multiorgan failure
Ribaudo G., Nisslé S., Piso R.J., Paganoni R., Bassetti S. (Olten)
Objectives: To describe a case of miliary tuberculosis (MT) with
multiorgan failure that was treated with recombinant human activated
protein-C (rhAPC, Drotrecogin alpha activated). Although rhAPC is
indicated for patients suffering from severe sepsis and septic shock
with a high risk of death, to our knowledge, only one case of miliary
tuberculosis treated with rhAPC has been described in the literature.
This patient died despite treatment. We report the first case of a
MT-patient successfully treated with rhAPC.
Methods: MT is a form of sepsis and refers to clinical disease resulting from the uncontrolled hematogenous dissemination of Mycobacterium tuberculosis. Sepsis due to tuberculosis is uncommon and
often goes unrecognized by clinicians. With the advent of HIV, there
is evidence that MT is becoming more prevalent. Despite effective
therapies for less severe forms of tuberculosis, MT still carries an
almost uniformly fatal prognosis if diagnosis is delayed. We describe
a case of MT in a 36-year-old HIV positive woman admitted to hospital with increasing fatigue, weakness, fever and cough. M. tuberculosis was cultured from bronchoalveolar lavage fluid, urine and faeces.
Chest radiograph in the course of hospitalisation demonstrated
diffuse bilateral interstitial infiltrates. 5 days after starting empiric
antimycobacterial therapy with rifampin, isoniazid, pyrazinamide and
ethambuthol, the patient developed respiratory insufficiency, septic
shock and disseminated intravascular coagulation, and had to be
intubated and transferred to the intensive care unit. Here she was
started on rhAPC treatment. Corticosteroids were also administered.
Results: All patient’s severe clinical manifestation of sepsis improved
markedly during or shortly after the treatment period on rhAPC, and
after 8 days our patient was extubated and finally survived the severe
sepsis.
Conclusion: Our case report supports the use for rhAPC in MT.
Although it is impossible to prove that the patient’s improvement was
due to rhAPC alone, her clinical improvement was atypical for MT and
corresponded temporally to the use of rhAPC. In placebo-controlled
trials rhAPC demonstrated significant mortality benefit in patients with
severe sepsis, but none of the trials included any patients with MT.
There is evidence that MT shares with other bacterial infections some
of the sepsis-pathways that are modulated by rhAPC. Therefore,
there is also a scientific rationale for the use of rhAPC in MT.
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Forum Med Suisse 2008;8:(Suppl. 40)
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Streptococcus oralis-Meningitiden mit Fokus im Hals-NasenOhrenbereich
Peternac D., Rochat Ph., Frauchiger B. (Frauenfeld)
Bakterielle Meningitiden mit S. oralis sind selten und wurden fast
ausschliesslich nach zahnärztlichen Eingriffen und selten nach neurochirurgischen Interventionen (Einlage externe Ventrikeldrainage,
Bandscheiben-Nukleolyse) beschrieben. Wir berichten über zwei Fälle
mit primärem Fokus im HNO-Bereich.
Fall 1: Ein 30jähriger Patient litt seit drei Tagen an Halsschmerzen und
entwickelte akut einsetzende, frontal betonte Kopfschmerzen. Klinisch bestand ein Meningismus. Die Leukozyten betrugen 12,1x109/l
und das CRP 24 mg/l. Die Zellzahl im Liquor war 2667x106/l (98%
Polynukleäre). Unter einer Behandlung mit Ceftriaxon und Dexamethason verbesserte sich der Zustand. In der Liquorkultur liess sich
S. oralis nachweisen. Im Verlauf trat eine Liquorrhoe auf mit Nachweis
von [beta]-2-Transferrin. Bereits mit 20 Jahren erkrankte der Patient
an einer bakteriellen Meningitis mit damals nicht nachweisbarem
Erreger. Durch eine zweite, hochauflösende Schädelcomputertomographie war ein 10x6 mm messender ossärer Defekt der rechten
Lamina cribrosa mit intrakranieller Kommunikation darstellbar. Eine in
der Kindheit berichtete passagere Rhinorrhoe dürfte damals bereits
einer Liquorrhoe entsprochen haben. Nach 15-tägiger Hospitalisation
mit residueller Gangataxie erfolgte eine erfolgreiche operative Dekkung des ossären Defektes.
Fall 2: Ein 61jähriger Patient wurde mit Meningismus und einer eitrigen Otorrhoe links zugewiesen. Das CRP war normal mit Leukozyten
von 12,4x109/l. Im trüben Liquor fanden sich 20’171x106/l polynukleäre Zellen. Das Schädel-CT ergab eine Otitis media mit Mastoiditis
links und in der Feinschichtung fand sich ein intrakranieller Durchbruch des lateralen Felsenbeines. Im Liquor waren keine Erreger
nachweisbar, in den Blutkulturen wuchs S. oralis. Unter der Behandlung mit Ceftriaxon verbesserte sich die anfängliche Vigilanzstörung
und das Fieber war rückläufig. Nach drei Tagen wurde eine Mastoidektomie mit Einlage einer Drainage durchgeführt.
Konklusion: S. oralis ist ein Keim der Mundflora und gehört zur
Gruppe der Viridans-Streptokokken. Bisher wurden gemäß unserer
Kenntnis noch keine S. oralis-Meningitiden ausgehend von einem
Primärfokus im HNO-Bereich in den uns zugängigen Datenbanken
publiziert. Neben den dafür bekannten Bakterien wie Pneumokokken,
Meningokokken, H. influenzae, Listeria monocytogenes und verschiedenen Viridans-Streptokokken kann neu auch S. oralis als Erreger in
Betracht gezogen werden.
Erythroblastopénie récidivante chez une patiente HIV positive
Calmy A., Wintsch J., Inoubli S., Mach-Pascual S., Verholen F.,
Lebeau O., Hirschel B., Beris P. (Genève)
Une patiente née en 1959, HIV + depuis 1986, sous traitement antirétroviral de darunavir/ritonavir, étravirine et enfuvirtide, a été hospitalisée en août 2007 pour fatigue extrême et dyspnée, sans notion de
saignements. Status: absence de fièvre, d’ictère, de lésion cutanée
ou de splénomégalie, petite adénopathie cervicale, pâleur. A l’entrée:
Hb 34 g/l, réticulocytes 1,4%0, plaquettes 39 G/l, leucocytes 2,5 G/l
(63% neutrophiles; 9% lymphocytes; 9% myélocytes). CRP, LDH,
fonctions hépatique et rénale sont dans la norme. Saturation de la
transferrine 108%, ferritine 440 microg/l, sTfR 0.4mg/l, B12 111
pmol/l, folates 5nmol/l, sérologie CMV IgM négatif, EBV négatif,
parvovirus B19 (PV B19) IgG positif 1/64. Cytométrie de flux: population B polyclonale; CD4/CD8 1/13, CD4 36 /microl. HIVRNA <40
copies. Ponction de moëlle: érythroblastes absents sauf rares proérythroblastes de grande taille avec parfois cytoplasme vacuolé. La
patiente a été transfusée puis mise sous B12 et folates. Au vu d’une
virémie DNA PV B19 très élevée (9,94 log copies/ml), elle a reçu des
immuno-globulines (Ig) polyclonales (dose totale de 2 g/kg). 15 jours
plus tard, les réticulocytes augmentent à 222 G/l et les plaquettes à
136 G/l. Un traitement d’entretien d’Ig (0,4 g/kg 1 fois par mois) est
donc instauré. On observe alors une récidive de l’anémie érythroblastopénique avec des taux de PV B19 qui continuent d’augmenter. Les
doses des Ig sont doublées, permettant la diminution de la virémie
PV B19, mais sans effet sur l’anémie (Hb 68g/l). Les CD4 restent très
bas (22 cellules/microl) et ce malgré un excellent contrôle de la virémie HIV. En conclusion, chez un patient sévèrement immunosupprimé, une infection à PV B19 (ou une réactivation) est une complication connue qui se manifeste essentiellement par une
érythroblastopénie. Des pancytopénies ont toutefois été décrites. La
persistance de la lymphopénie sévère prédit la récidive de l’anémie
une fois que l’effet des Ig à hautes doses s’épuise, comme c’est le
cas chez cette patiente. L’administration de la dose complète d’Ig
(2 g/kg/mois) nous paraît donc indiquée en absence d’option pour
favoriser la reconstitution immune. Une alternative thérapeutique
séduisante mais non documentée serait de lui transfuser un plasma
riche en anticorps anti-PV B19.
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Granulomatous hepatitis after intravescical Calmette-Guérin
bacillus treatment
Adami M., Marsteller I., Riglietti A., Mazzucchelli L., Cerny A.,
Bernasconi E. (Lugano, Locarno)
Local instillation of Calmette-Guérin bacillus (BCG) is an effective
therapy for superficial bladder cancer and adverse reactions are
uncommon. However, serious complications such as disseminated
infection with sepsis, granulomatous hepatitis, pneumonitis or
osteomyelitis, have been reported and should be considered in the
differential diagnosis of a deteriorating patient after BCG treatment.
We describe a 79 year-old man who presented at the emergency
department with mental confusion, chills, fever, tachypnea, tachycardia, jaundice and abnormal liver function tests, eight hours after a first
BCG intravescical instillation. Rapid clinical improvement was
observed. Cefepime and Acetaminophen treatment was continued
suspecting septicaemia. Blood and urine cultures were sterile, liver
function tests remained abnormal. Four weeks later he presented
again with fever, anorexia, jaundice and fatigue, as well as worsened
liver function tests. Abdominal ultrasound revealed normal liver structure and narrow bile ducts, whereas splenomegaly was detected.
Liver biopsy showed multiple non-caseating granulomas compatible
with a BCG hepatitis, even if Ziehl-Neelsen stain didn’t show alcoholacid fast bacillus. Anti-mycobacterial treatment with Rifampin, Isoniazid and Ethambutol was started and continued for a total of 6
months, with complete clinical recovery and marked improvement of
liver function tests. Neither the mechanism of action of BCG as an
immunotherapeutic agent in cancer nor the mechanism of systemic
infection is completely understood. In conclusion, we believe that the
first episode represents an hypersensitivity reaction, whereas further
clinical course and findings at liver biopsy strongly suggest secondary dissemination of BCG.
Aspergillose pulmonaire semi-invasive: challenge
diagnostique?
Carron P-N., Boillat N., Bille J. (Lausanne)
Introduction: L’aspergillose pulmonaire semi-invasive (APSI) est une
entité méconnue, concernant classiquement des patients faiblement
immunosupprimés. Un cas clinique récent permet d’en illustrer la
présentation clinique, ainsi que la démarche diagnostique.
Cas clinique: Une patiente de 63 ans est hospitalisée en raison d’une
décompensation diabétique, associée à des sudations nocturnes et
des infiltrats pulmonaires, ayant motivé l’introduction d’amoxicilline –
clavulanate (Fig. 1). Elle décrit également une perte pondérale de 6 kg
en six mois, ainsi qu’une dyspnée et une toux productive. On note
dans les antécédents un tabagisme actif (25 UPA), un ancien éthylisme et une pancréatite chronique avec un diabète secondaire. Le
bilan initial révèle un syndrome inflammatoire modéré, une cholestase
et des infiltrats pulmonaires nodulaires diffus. Un lavage bronchoalvéolaire, ainsi qu’une biopsie percutanée sous CT, révèlent des
infiltrats inflammatoires aspécifiques. Les cultures et recherches
microbiologiques par PCR, ainsi que le bilan immunologique sont
négatifs. Le diagnostic est finalement posé lors d’une biopsie pulmonaire par thoracotomie, mettant en évidence de nombreuses colonies
d’Aspergillus fumigatus (Fig. 2), associées à une invasion tissulaire
et des foyers de nécroses. L’évolution est favorable sous traitement
de voriconazole.
Discussion: Le diagnostique d’APSI est difficile et se base sur des
critères cliniques (symptômes pulmonaires ou systémiques chroniques), radiologiques (cavité pulmonaire avec infiltrats paracavitaires)
et microbiologiques (présence d’Aspergillus ou de précipitines aspergillaires). Dans 50% des cas, une biopsie pulmonaire chirurgicale est
nécessaire pour confirmer le diagnostic, les biopsies trans-bronchiques ou percutanées étant de rendement médiocre. Le dosage des
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antigènes galactomananes s’avère également le plus souvent négatif.
La présence d’Aspergillus dans les prélèvements permet d’orienter le
diagnostic et ne doit pas être considérée comme une simple colonisation.
Conclusions: L’APSI est vraisemblablement sous-diagnostiquée
dans la population hospitalière helvétique. Les prévalences élevées
de corticothérapie, de diabète, de bronchopneumopathie obstructive
ou d’éthylisme chronique constituent en effet des facteurs de risques
notables. Elle devrait être évoquée devant tout patient faiblement
immunosupprimé, présentant des symptômes pulmonaires ou systémiques chroniques, avec des infiltrats pulmonaires cavitaires.
Fig. 1
Infiltrats pulmonaire CT
Fig. 2
Aspergillus – coloration argentique
Forum Med Suisse 2008;8:(Suppl. 40)
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Clinical impact of renal function-dependent variability of
imipenem and cefepime blood levels in febrile neutropenic
patients
Lamoth F., Pascual A., Vora S., Bolay S., Calandra T., Marchetti O.
(Lausanne)
Background: Imipenem and cefepime are standard therapies in
febrile neutropenia. Renal clearance is the major elimination pathway
of these antibacterial agents. An important intra- and inter-individual
variability of drugs blood levels has been reported. Low or high drug
blood levels may result in decreased efficacy or toxicity, respectively.
Although therapy failure or adverse events occur frequently in febrile
neutropenic patients, their causes remain often unknown.
Objective: To evaluate the clinical impact of renal function-dependent
low and high trough blood levels of imipenem and cefepime in febrile
neutropenic patients.
Methods: Eighty-one therapy courses were studied retrospectively:
51 imipenem, 30 cefepime. Trough blood levels were interpreted as
i) low: <MIC or <MIC90 of the most common bacterial pathogens
(1 mg/L for imipenem, 2 mg/L for cefepime) or ii) high: >15 mg/L.
The clinical significance of low or high blood levels was evaluated by
clinical response of infection to therapy or presence of clinical signs
of toxicity, respectively.
Results: An important variability of drugs blood levels was observed.
22/51 (43%) imipenem trough levels were interpreted as low. In 4/51
cases (8%) lack of response of infection to therapy was attributed to
low drug levels and all responded to dose adjustment. 12/30 (40%)
cefepime trough levels were >15 mg/l: in 6/30 cases (20%) high levels
were associated with neurological toxicity and all completely recovered after dose decrease or therapy discontinuation. Imipenem
underdosing with lack of response (3/4, 75%) and cefepime overdosing with neurotoxicity (6/6, 100%) were mainly observed in patients
with creatinine clearance > and <70 ml/min, respectively, whereas
drugs dosing schedules were similar in patients with normal or
impaired renal function.
Conclusions: Low blood levels of imipenem and high levels of
cefepime are observed in febrile neutropenic patients with normal and
impaired renal function, respectively. Monitoring of blood levels of
beta-lactam antibiotics with individualized dose adjustments may
improve efficacy and safety of antibacterial therapy in febrile neutropenia.
Figure 1
Imipenem blood levels and renal function
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Six patients with herpes simplex type 2 central nervous
system infection
Rohacek M., Rossi M., Ziegler F., Hodel T., Bloetzer I., Elsasser S.,
Henzen C. (Luzern)
Case report: We report six patients with a herpes simplex type 2
(HSV-2) central nervous system (CNS) infection seen within one year
in our clinic. One 80 year old patient had chronic lymphatic
leukaemia, the other patients were immunocompetent, HIV negative
and were between 20 and 45 years old. One patient had a history of
sexual transmitted disease, but no patient had a history of genital
herpes. Two of them presented with meningoencephalitis including
fever, stupor and epileptic seizures, one of whom developped brain
edema and had to be intubated. Two patients presented with a first
episode of an aseptic meningitis, two patients had a recurrence. All
patients showed monocuclear pleocytosis ranging from 48 to 592
cells/ul and amplification of HSV-2 DNA in the cerebrospinal fluid
(CSF). The number of cells per ul CSF or the blood level of C-reactive
protein (CRP) did not correlate with symptom severity. All patients
were seropositive for HSV-IgG, but only one showed positive IgM.
After treatment with Acyclovir, all patients recovered well without
neurological deficites.
Comment: CNS-infections by HSV-2 are rare. There are only a few
data concerning epidemiology. The annual incidence rate of HSV-2
CNS disease is described to be 0.26 per 100,000. In one study of 49
patients with HSV-2 DNA in the CSF, 43 (88%) had meningitis of
whom eight (19%) had recurring lymphocytic meningitis. Only six
patients (12%) had encephalitis. HSV-2 is not a common cause for
encephalitis in contrast to HSV-1, varizella zoster virus (VZV), tickborne encephalitis virus or enterovirus.
Conclusion: HSV-2 does not only cause aseptic meningitis, but can
also cause severe encephalitis. The majority of our patients were
negative for HSV-IgM, so reactivation of the virus is probable to be
the cause of their disease.
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Figure 2
Cefepime blood levels and renal function
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Pylephlebitis associated with choledocholithiasis
Conzett Th., Graber P., Glauser Ph., Zimmerli W. (Liestal)
Background: Pylephlebitis (septic thrombophlebitis of the portal vein)
is a rare, life-threatening complication of intraabdominal infection.
Case report: A 73-year-old man was hospitalized in November 2007
because of abdominal pain in the right upper quadrant, chills, nausea
and anorexia. Treatment with ciprofloxacin was initiated by the general practicioner because of suspected pyelonephritis. On admission,
the patient was afebrile, blood pressure and pulse rate were normal.
Physical examination revealed a tender right subcostal region. Laboratory tests showed leucocytosis of 20.5x109/L (neutrophils 90%),
thrombocytosis of 423x109/L and a C-reactive protein of 17 mg/L.
Elevated alkaline phoshatase (147 U/L), gamma-GT (1914 U/L), amylase (1604 U/L), lipase (6775 U/L), AST (780 U/L) and ALT (407 U/L)
were compatible with acute biliary obstruction. Blood cultures were
negative. Contrast-enhanced CT-scan showed a prepapillary bile
duct stone, thrombosis of the right portal venous branch and a
hypointense zone in the right liver lobe. Treatment with
piperacillin/tazobactam was started. A follow-up CT-scan revealed
spontaneous clearance of the concrement; however, an increased
hypodense area, suggested liver abscess formation. CT-guided
drainage produced 500 ml pus growing monoculture of Bacteroides
fragilis. Long-term treatment with oral metronidazole was initiated,
and the patient gradually recovered.
Discussion: Pylephlebitis is an uncommon complication of suppurative infection (mainly diverticulits and appendicitis) in the portal
drainage area with a high mortality (>30%). Liver abscesses are a
frequent complication. In the literature, only one case has been associated with cholelithiasis. Contrast-enhanced CT-scan allows rapid
diagnosis. Empiric broad spectrum antibiotics are needed because
polymicrobial bacteremia is frequent. There are no data on a benefit
of anticoagulation.
Conclusions: Pylephlebitis should be suspected in patients with
severe intraabdominal infection. Raised clinical awareness, adequate
radiological imaging, and a thorough evaluation and treatment of a
primary or secondary bacterial focus are crucial.
Documentation of low voriconazole blood levels followed by
dose adjustment in patients with invasive fungal infections not
responding to therapy
Pascual A. A., Bolay S., Marchetti O. (Lausanne)
Background: Voriconazole (VRC) is a new standard for treatment of
invasive fungal infections (IFI). Inter-individual variability of VRC blood
levels has been described. Recent reports suggest that low blood
levels might be associated with failure of VRC therapy (Rx).
Objective: To assess the utility of documentation of low VRC blood
levels followed by dose adjustment in patients (Pts) not responding
to Rx.
Methods: Retrospective analysis of Pts receiving VRC for proven or
probable IFI (EORTC-BAMSG) over 2004–2006. Definitions: success
= partial or complete resolution, failure = persistent or progressing IFI.
VRC blood levels measured by HPLC. Failure in with a VRC trough
level 91 mg/L (MIC90 of the most fungal pathogens) was the trigger
for dose adjustment.
Results: 37 Pts (all caucasians) were studied. Median age: 60 (23 to
78). 68% had aspergillosis, 22% candidiasis and 10% other IFI.
Median VRC dose: 8 mg/kg/d for a median duration of 50 days.
Among 6 Pts with VRC failure and trough levels 91 mg/L, 4 had
proven (MIC of VRC <0.5 mg/L) and 1 probable aspergillosis; 1 had
probable candidiasis. VRC dose was increased in the 6 cases:
median follow-up VRC trough level was 2.1 mg/L (0.8 to 3.1). All Pts
had partial or complete response. 2 patients with VRC failure and
trough levels >1 mg/L responded to salvage Rx.
Conclusions: Documentation of low VRC blood levels followed by
dose increase may improve outcome in Pts with invasive fungal
infections not responding to Rx.
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Efficacy of patient versus healthcare provider based
interventions in increase screening rates, knowledge and
awareness of colorectal cancer screening: a systematic review
Dash C., Guessous I. (Atlanta, Lausanne)
Background: Interventions to increase knowledge of and awareness
about colorectal cancer (CRC) screening target patients or healthcare
providers, but it is unknown which approach is more effective. The
goal of our review was to identify and assess interventions aimed at
increasing awareness about CRC screening among average risk
patients and healthcare providers and to compare their efficacy.
Methods: Studies were identified by searching Medline between
1995 and June, 2007. Three comprehensive search themes were
developed and combined using the Boolean operator “and”. All intervention studies that had a component for increasing CRC awareness
in either patients or providers or both were selected for review.
Results: Fifty-two studies met the eligibility criteria. The majority
(66%) involved use of one or more multimedia components to provide
education on CRC risk factors and screening options. Interventions
among the 14 studies that targeted healthcare providers were
provider/clinician education (71%), provision of screening tool kits
(29%), questionnaires/reminders to identify patients that require
screening (21%), help with patient notification of test results (14%),
and organization level CRC screening quality improvement programs
(14%). Of the studies that reported screening outcomes, 73% (29/40)
reported a significant change in the outcome post-intervention. Components of awareness intervention directed towards screening recipients or patients that were found to be most effective were patient
navigators, in-person counseling by nurse/provider educators, and
targeted/tailored multimedia educational materials. Successful components of the healthcare provider based interventions were educational and other initiatives targeted to individual providers rather than
organizations. We found no evidence that studies targeting providers
were more likely to report significant effect of the intervention on the
screening outcome as compared to those targeting patients. We also
did not find enough evidence to conclude that studies targeting
providers were more likely to report significant effect of the intervention on attitude/knowledge outcomes compared to those targeting
patients
Conclusions: Most interventions are effective at increase CRC
screening rates. We did not find any statistically significant difference
between healthcare provider and patient based interventions in
increasing screening rates and knowledge.
Psychological adjustment in hospitalised cancer patients
Cedraschi C., Luthy C., Konrad-Mugnier B., Arigoni F., Rapiti E.,
Allaz A.F. (Geneva)
Background: Cancer patients experience distress and develop a
variety of cognitive and emotional reactions in their attempts to adjust
to disease and illness. An active or proactive adjustment may be
associated with less distress.
Objective: To investigate the association between mental adjustment
and the psychological impact of the disease in terms of anxiety and
distress in a supportive care setting.
Methods: 83 consecutive patients hospitalized in a supportive care
unit responded to a questionnaire including psychological dimensions
investigated by the Hospital Anxiety and Depression Scale (HADS),
the Distress Thermometer (DT) a graphic scale rated from 0–10, and
the Mental Adjustment to Cancer index (MAC). Socio-demographic
and clinical characteristics were also recorded, along with functional
aspects (Performance Status), and the Physician Global Clinical
Impression (PGCI) a numerical scale rated from 0–10 assessing the
estimated survival prognosis at the admission.
Results: 67% of the patients were men; mean age was 65 years (SD
= 14). A wide range of cancer diagnoses were represented. Median
time since diagnosis was 1.8 years (range = 0.1–12.5 years). A wide
range of cancer diagnoses were represented: head (7%) and neck
(7%), gastro-intestinal (22%), lung (28%), breast (9%), gynecological
(7%), genito-urinary tract (9%) hematological (4%) and other locations (7%); 23% had primary local diseases, 42% had local recurrences, and 35% had metastatic diseases. Anxiety and depression
rating scores were moderate to high (mean HADS: 10.5 ± 0.5 and
10 ± 0.5, respectively; mean DT score: 4.7 ± 0.2). The results of linear
correlation tests showed a statistically strong and inverse association
between the dimension referring to fighting spirit in the MAC and
anxiety and depression as measured by the HADS (p <0.001), by
the DT (p <0.001), and by specific subscales of the MAC (p <0.001).
Fighting spirit was also significantly associated with a better evaluation of patient’s performance status by the physician (p <0.01) as well
as with a better PGCI (p <0.01). On the contrary, hopelessness/ helplessness was associated, although not significantly, with a worse
PGCI.
Conclusions: Cancer patients hospitalized in a supportive care unit
experienced a high psychological impact of the disease both in terms
of anxiety and depression. Mental adjustment seemed to play a
buffering role insofar as mental adjustment strategies allowing for a
sense of control on the disease was related to a better psychological
well-being. Those patients who endorsed such an adjustment strategy were also those who gave rise to better global clinical prognostic
evaluations and performance status as evaluated by the physicians.
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Use of transdermal opioids in cancer patients referred
to a mobile palliative care team
Escher M., Besson M., Piguet V. (Genève)
Background: Although it is recommended to use short acting opioids
to rapidly relieve uncontrolled pain, slow-released morphine can also
be used effectively. Transdermal systems are slow-released devices
which prolong the apparent half-lives of opioids even more. The aim
of this study was to determine if cancer patients receiving transdermal opioids (TO), and referred to our palliative care team for uncontrolled pain could be maintained on TO.
Methods: Retrospective chart review of the cancer patients hospitalised in the Geneva University Hospitals between January 1st, 2006
and July 31st, 2007, and receiving transdermal buprenorphine or
fentanyl when first assessed.
Results: Among 158 patients, 29 patients (18.3%) were included.
Twenty-one were on transdermal fentanyl. Mean age was 60.5 +/14.6 years. Pain was mainly related to bone metastasis (n = 11) and
head and neck cancer (n = 6). Eight patients had abdominal pain due
to peritoneal carcinomatosis or primary cancer. TO were continued in
23 patients (79.3%). Reasons to stop TO were severe pain (n = 3),
lack of efficacy of TO (n = 2), and simplification of treatment (n = 1).
Pain tended to be more severe in patients whose TO was stopped
(mean VAS 90 vs 72 mm; p = 0.09) There was no difference in the
time needed to relieve pain.
Conclusions: Adequate pain relief can be obtained with transdermal
opioids despite their slow-released formulation. Appropriate assessment of the patient’s situation is the key factor for individualised
treatment.
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Ergebnisse eines Praxiserfahrungsberichtes zum
Management der chemotherapieinduzierten Anämie mit
Darbepoetin alpha in der Schweiz
Piguet D. (Biel)
Hintergrund: Die Anämie ist eine häufige Begleiterscheinung bei
Patienten mit Krebs. Verursacht wird diese häufig durch myelotoxische Effekte der Chemotherapie. Bei symptomatischen Patienten mit
einem Hb zwischen 9–11g/dl wird der Einsatz von ESAs (erythropoietic stimulating agents) empfohlen. Der Einsatz von ESAs hat zwei
Zielsetzungen: Verbesserung der Lebensqualität sowie Verhinderung
der Transfusion.
Methoden: In einem offenen nicht-randomisierten multizentrischen
Praxiserfahrungsbericht wurden zwischen November 2005 und
Dezember 2006 238 Patienten unter Chemotherapie aus 38 Zentren
eingeschlossen, bei denen der behandelnde Arzt die Indikation zur
Therapie mit ESA gestellt hatte. Ziel war die Untersuchung der
Effizienz der Transfusionsverhinderung durch Darbepoetin alpha unter
Praxisbedingungen.
Resultate: 19% der eingeschlossenen Patienten hatten Tumore der
Lunge, 12% Brustkrebs, jeweils 7% Multiples Myelom, Non-Hodgkin
Lymphom und Prostatakarzinom. Die eingesetzten Chemotherapien
waren sehr heterogen. 78% der Behandlungen wurden ohne Transfusion durchgeführt. Bei 37% der Patienten wurde die Therapie mit ESA
bei einem Hb-Wert um 10 g/dl initiiert. Bei 32% der Patienten lag der
Ausgangswert vor Therapiebeginn unter 10 g/dl. Die Chance nicht zu
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transfundieren korreliert mit der Höhe des Ausgangswerts des Hb.
Beträgt diese bei einem Ausgangswert von 11 g/dl noch rund 85%,
sind es bei 8 g/dl nur noch 44%. Umgekehrt proportional steigt der
Bedarf an transfundierten Erythrozyten-Konzentraten. Bei Patienten,
welche keine Transfusion benötigten, wurde der höchste Hb-Anstieg
auf die erste Gabe ESA bei einem Ausgangswert von 9 g/dl registriert
(0,8 g/dl). Der Appliktionsrhythmus liegt im Schnitt zwischen 3–4
Wochen, variiert jedoch stark. Die Zufriedenheit mit der Therapie ist
gut (88% zufrieden bzw. sehr zufrieden). Ein klarer Zusammenhang
zwischen Malignom oder Chemotherapie und der Chance nicht zu
transfundieren konnte nicht etabliert werden.
Schlussfolgerung: Die Analyse der dokumentierten Fälle deckt sich
mit den bisherigen Erkenntnissen aus der Therapie der Anämie mit
ESA bei Patienten mit Krebs. Der Therapieentscheid wird tendenziell
spät gefällt, knapp entsprechend den aktuellen EORTC-Richtlinien. In
diesem Praxiserfahrungsbericht war die Chance grösser, die Therapie
ohne Transfusion durchzuführen, wenn der Entscheid zum ESAEinsatz bei einem höheren Hb-Ausgangswert gefällt wurde.
Mit Unterstützung von Amgen Switzerland AG ermöglicht.
P132
Therapie der multizentrischen Castleman Krankheit bei
HIV-positiver Patientin: Fördert Rituximab die Progredienz
des Kaposi-Sarkoms?
Buchkremer J., Küng M., Chuard C., Betticher D. (Freiburg)
Die multizentrische, HIV -und HHV-8 (humanes Herpesvirus 8) –
assozierte Form des M. Castleman ist eine seltene lymphoproliferative Erkrankung mit schlechter Prognose. Aktuell existiert keine Standard-Therapie; die systemische Chemotherapie kombiniert mit dem
CD20-Antikörper Rituximab wurde in Studien als effizient
beschrieben. Fallberichte weisen darauf hin, dass die RituximabTherapie das Risiko erhöhen könnte, ein Kaposi-Sarkom zu
entwickeln.
Eine 51jährige, aus dem Kongo stammende, HIV-positive Patientin
(CDC-Stadium C3, Erstdiagnose 02/2007) wurde mit Fieber, generalisierter Lymphadenopathie, Splenomegalie sowie sehr schlechtem
Allgemeinzustand (PS 4) und folgenden Parametern hospitalisiert:
CRP 219 mg/l; Alb 21 g/l, LDH 494 U/l. Die axilläre Lymphknotenbiopsie zeigte regressiv veränderte, z.T. hyalinisierte Keimzentren
sowie eine vaskuläre Hyperplasie mit zahlreichen, reifen Plasmozyten,
vereinbar mit M. Castelman (gemischter Typ hyalin-vaskulär und
plasmozytär), HHV-8 assoziert. Bei einer tiefen CD4-Zahl (177
Zellen/mm3) und hohem viral load (379 000 copies/ml) wurde
eine HAART (Tenofir, Lamivudin und Efavirenz) eingeleitet. Unter
Chemotherapie mit CHOP (Cyclophosphamid, Doxorubicin, Vincristin
und Prednison) kombiniert mit dem CD20-Antikörper Rituximab in
3 wöchigen Abständen konnte eine rasche Verbesserung des Allgemeinzustandes, des inflammatorischen Syndroms und eine sehr gute
partielle Remission der Lymphadenopathien und der Splenomegalie
festgestellt werden. Beim 3. Chemotherapiezyklus wurden kutane
Läsionen festgestellt und bioptisch als Kaposi Sarkome bestätigt.
Die bisherige Chemotherapie wurde daraufhin durch liposomales
Doxorubicin ersetzt und die antivirale Therapie geändert (Efavirenz
durch Saquinavir und Ritonavir ersetzt), was nach 3 Zyklen zur Regredienz der Kaposi-Sarkome führte. Unter Wiederaufnahme der Rituximab-Therapie trotz Weiterführung des liposomalen Doxorubicins
kam es zur erneuten Progredienz der Kaposi-Sarkome. Der Verlauf
bei dieser HIV-positiven Patientin zeigt, dass Rituximab in der Therapie des multizentrischen M. Castleman hochaktiv ist. Hingegen wird
der Verdacht erhärtet, dass Rituximab die Progredienz des KaposiSarkoms nicht aufzuhalten vermochte, ja möglicherweise sogar
förderte.
P133
Long-term survival of a patient with advanced duodenal
solid cancer treated with neoadjuvant chemotherapy followed
by surgical resection: a case report
Roggero E., Palumbo A., Pelloni A., Huber O., Bigger P.,
Pedrazzini A. (Locarno, Geneva)
Neoplasia of the small bowel is rare, accounting in the literature and
in our hospital series in the last 5 years for about 2–3% of all gastrointestinal neoplasms. Diagnosis and treatment of these diseases
Forum Med Suisse 2008;8:(Suppl. 40)
62 S
are major challenges and the exact modalities to cure these neoplasms are still unknown. We present a case report of a patient with a
long-term survival of a locally advanced duodenal cancer treated with
chemotherapy followed by radical surgery. In April 2001, a 41-yearold man suffering from vomiting and sensation of nausea and high
abdominal obstruction attended our surgical-oncological department.
A solid mass of the third part of the duodenum was found with direct
compression of the pancreas and mesenteric vessels as confirmed
by CT and MRI. Biopsies of the duodenal obstructive mass (8 cm x
8 cm) were performed and histological features revealed an intermediate differentiated adenocarcinoma. Due to the extension of the
carcinoma, after multidisciplinary discussion, we decided to postpone surgery after a neoadjuvant chemotherapy. The patient was
treated with irinotecan (150 mg/m2) and gemcitabine (1000 mg/m2)
each lasting two weeks from June 2001 to March 2002. After ten
months a CT diagnosis showed a wide partial regression of the duodenal mass (3 cm x 2 cm). The patient then underwent a Wipple
resection. A histological examination confirmed an adenocarcinoma
of the duodenum infiltrating the intestinal wall with mucosal ulceration
and no tumoral invasion of the 24 examinated lymph nodes (stage T3
N0 M0). The postoperative course was complicated by a relaxation of
the pancreatico-jejunal anastomoses with a consequent hemorrhage
that necessitated an intervention of a total pancreatectomy and
splenectomy. Subsequently, thirty-five days after the first surgical
intervention the patient developed a cataclysmic hemorrhage with
hypovolemic shock due to perforation of the mesenteric artery and
relaxation of the gastro-enterostomy anastomosis resulting in a new
laparatomy and surgical management. No other chemotherapy was
done. Eighty-eight months after diagnosis the patient is free of duodenal neoplasia. The history of this case raises at least two points of
discussion. The first regards the schedule and duration of the treatment. In our case a long (ten months) neoadjuvant chemotherapy
treatment (with gemcitabine and irinotecan) seems to be associated
with extended tumor shrinkage and complete resection of a locally
advanced solid adenocarcinoma of the duodenum. The second
regards complications of treatments. Major life threatening complications were observed: the relaxations of the anastomoses and the
hemorrhages. In conclusion, because the rarity of this disease the
best therapeutic approach is not defined, however, the use of
chemotherapy before surgery should be discussed in these diseases.
P134
A new, automated, four-colour interphase FISH approach
for the simultaneous detection of specific aneuploidies of
diagnostic and prognostic significance in high hyperdiploid ALL
Talamo Blandin A., Muehlematter D., Bougeon S., Gogniat C.,
Porter S., Beyer V., Parlier V., Beckmann J. S., van Melle G.,
Jotterand M. (Lausanne)
In hyperdiploid acute lymphoblastic leukaemia (ALL), the simultaneous occurrence of specific aneuploidies confers a more favourable
outcome than hyperdiploidy alone. Interphase (I) FISH complements
conventional cytogenetics (CC) through its sensitivity and ability to
detect chromosome aberrations in non-dividing cells. To overcome
the limits of manual I-FISH, we developed an automated four-colour
I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for
chromosomes 4, 6, 10 and 17. Parameters established for automatic
nucleus selection and signal detection were evaluated (3 controls).
Cut-off values were determined (10 controls, 1000 nuclei/case). Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 ALL
patients (1500 nuclei/patient) were compared with those by CC.
Various combinations of aneuploidies were identified. All clones
detected by CC were observed by I-FISH. I-FISH revealed numerous
additional abnormal clones, ranging between 0.1% and 31.6%,
based on the large number of nuclei evaluated. Four-colour automated I-FISH permits the identification of concurrent aneuploidies
of prognostic significance in hyperdiploid ALL. Large numbers of cells
can be analysed rapidly by this method. Owing to its high sensitivity,
the method provides a powerful tool for the detection of small abnormal clones at diagnosis and during follow up. Compared to CC, it
generates a more detailed cytogenetic picture, the biological and
clinical significance of which merits further evaluation. Once optimised for a given set of probes, the system can be easily adapted
for other probe combinations.
POSTERS SSHé
POSTERS SGH
P135
Allogeneic HSCT for chronic lymphocytic leukemia:
a single center experience
Stern M., Arber C., Buser A., Halter J., Heim D., Favre G.,
Gratwohl A. (Basel, Liestal)
Current chemotherapy regimens for CLL incorporating nucleoside
analogues and monoclonal antibodies have high response rates.
However, CLL remains incurable by standard chemotherapy. While
allogeneic transplantation is potentially curative, high rates of early
transplant related mortality using myeloablative regimens have precluded its widespread use in CLL. We report the outcome of patients
treated with allogeneic transplantation at our institution since 2002.
Sixteen patients (7 female/9 male; median age 52 years) received
allogeneic HSCT between 2002 and 2007. Donors were HLA-identical
siblings in 14 cases, matched unrelated donors in the remaining two.
Indications for allogeneic transplantation were insufficient response
to treatment with nucleoside analogues (fludarabine or cladribine) in
8 patients, del17p in 3 patients, and other in the remaining 5 patients.
The conditioning regimen was Fludarabine/2 Gy TBI in six patients,
BEAM/Fludarabine/2Gy TBI in seven patients, and Fludarabine/
Cyclophosphamide in three patients. All transplants were T-cell
replete, GvHD prophylaxis consisted of cyclosporine/methotrexate or
cyclosporine/mycophenolate. Only one of the sixteen patients was in
complete remission at the time of transplant. Thirteen patients were
alive at last follow-up, three had died (two from infection, one from
graft rejection). Of the patients alive, 11 are in complete remission,
two have never achieved CR and are alive with progressive disease.
Kaplan-Meier estimated overall survival at 5 years was 78% (Figure 1).
Cumulative incidence of grade II or higher acute GvHD was 44%.
Chronic GvHD was seen in 6/12 patients evaluable and was extensive
in all patients. Allogeneic HSCT induced complete remission in the
majority of cases in this population of patients with high-risk CLL.
The survival rate compares favourably with literature data and with
outcome of non-transplant treatment modalities. Allogeneic should
be considered early in patients with high risk CLL.
Forum Med Suisse 2008;8:(Suppl. 40)
63 S
peripheral blood in the remainder. Patients above 60 were more frequently transplanted after 2001, were less likely to be transplanted
for CML but donor type did not differ between patients 50–60 years
of age and patients over 60. Overall survival at 5 years was 62 +/11% in patients 50–60 years old and 35 +/- 19% in patients over
60 (p = 0.007) (see figure). Treatment related mortality, defined as non
relapse mortality was 17 +/- 8% in patients 50–60 years old and 31
+/- 26% in patients over 60 (p = 0.6). In multivariate analysis adjusting
for age, disease and disease stage, year of transplant and donor type
the only factors associated with increased risks of death were age
>60 (RR: 2.1 p = 0.02) and advanced leukemia (RR 2.1, p = 0.07).
Of note, there were no differences in outcome when unrelated
(RR: 0.88, p = 0.7) were compared to sibling donors.
In conclusion: older patients undergoing allogeneic HSCT for
myeloid leukemia may present with interesting long term outcome
data. Comparison to other treatment modalities is needed, a randomized clinical trial comparing allogeneic HSCT to conventional
chemotherapy is planned.
Fig. 1
Figure 1
P137
P136
Outcome of allogeneic stem cell transplantation in elderly
patients with myeloid leukemias
Passweg J.R., Schanz U., Chalandon Y., Stussi G., Heim D.,
Halter J., Helg C., Tichelli A., Gratwohl A. (Genève, Zuerich, Basel)
The role of allogeneic hematopoietic stem cell transplantation (HSCT)
in the treatment of patients with myeloid leukemia is not clear. This is
particularly relevant in the elderly population given treatment related
mortality risks. Reporting of all transplants is a legal requirement in
Switzerland, and the STABMT (Swisstransplant Group for Blood and
Marrow Transplantation) maintains a registry since 1997. We report
here outcome data on 151 patients over the age of 50 having
received an allogeneic transplant since 1997. Transplants were for
acute myeloid leukemia (73, 40 in CR1, 33 with more advanced disease) chronic myeloid leukemia (24) or myelodysplastic/myeloproliferative syndromes (54). 111 patients were 50–60 years old, 40 were
over 60. Median age was 56 years (range 50–70). Median follow-up of
surviving patients was 25 months. Donors were siblings (112) unrelated (35) and others (4). Stem cell source was marrow in 13 and
Use of a comprehensive national database as a quality
control instrument
Passweg J.R., Bargetzi M., Halter J., Leoncini L., Leibundgut K.,
Pabst T., Chalandon Y., Duchosal M.A., Hess U., Seger R.,
Schanz U., Gratwohl A. (Genève, Aarau, Basel, Bellinzona, Bern,
Lausanne, St.Gallen, Zuerich)
The goal of JACIE is quality improvement in all aspects of hematopoietic stem cell transplantation (HSCT). Reporting of all transplants and
regular analysis of outcome is integral part of a quality management
system. Few analyses have been done to assess the impact of a
comprehensive HSCT data capture system on a national level and
to use data comparison as a quality control tool. We made use of the
legal requirement that all 9 HSCT teams in Switzerland, 1 allogeneic,
3 combined allogeneic-autologous and 5 autologous HSCT teams,
do adhere to JACIE guidelines and do report all transplants to the
STABMT (Swisstransplant Group for Blood and Marrow Transplantation) registry. From 1997–2006, 3868 HSCT, 29.4% allogeneic,
70.6% autologous were performed for 2987 patients, 60% male, 40%
female, median age 46 (0–76.years). Main indications were leukemia
(767 allo, 220 auto), lymphoproliferative disorders (138 allo, 1508
auto), solid tumors (8 allo, 333 auto) and non malignant disorders
(92 allo, 10 auto). As of December 2007, 1899 patients (64%) were
alive, 1079 (36%) had died, 249 (8.4%) from transplant related mortality (TRM) or 830 (27.9%) from disease progression. This corresponds to a survival probability of 50 +/- 3% in recipients of autologous HSCT and 57+/- 4% in recipients of allogeneic HSCT at 5 years
whilst TRM probabilities were 7 +/- 2% and 20 +/- 3% respectively.
Each team was assessed for survival and TRM data for each disease
category and transplant type and data were compared with outcomes
of all other teams combined. Data were adjusted in a multivariate
regression model for the impact of transplant center adjusting for
important factors associated with outcome, e.g. disease, disease
stage, age, and histocompatibility. Separate models were
constructed for allogeneic and autologous HSCT. There were no
significant differences among teams in overall survival of allogeneic
and autologous HSCT. There was a significant difference in models of
C O M M U N I C AT I O N S L I B R E S
FREIE MITTEILUNGEN
TRM due to 3 events in a small center for autologous HSCT but no
center difference in TRM for allogeneic HSCT. Reasons for this outlier
are being evaluated with the respective teams. These data show that
a consistently high quality may be achieved in data monitoring within
a country by a comprehensive database. Deviations are recognized
rapidly and discussed with the respective teams. Such regular comparisons within the professional HSCT organizations may serve as a
model for quality assurance.
P138
Physical but not mental health is inferior in very long term
survivors after HSC compared to their respective donors:
a pair analysis
Rovó A., Daikeler T., Stern M., Halter J., Studt J.D., Buser A., Heim D.,
Rischewski J., Medinger M., Tyndall A., Gratwohl A., Tichelli A. (Basel)
With the improvement of prognosis, health status and functional well
being of long term survivors after HSCT become an important issue.
We performed a prospective study on 44 long-term survivors and
their respective sibling donors at a median of 17.5 years (range
11–26) after HSCT. The median age of the recipients and donors at
time of the study was 44.3 (24–63) and 43.4 years (22–61) respectively. Both recipients and donors were seen on the same day for
evaluation with the short form-36® (SF-36) Health Survey, which
provides a generic health status measurement through 36 items
assessing 8 concepts of health. Three of the items measure physical
health (PF, RP, BP), two measure both physical and mental health
(GH, VT), and three measure mental health (SF, RE, MH). In addition
there are two summary scores for physical (PCS) and mental (MSC)
health. For statistical analysis norm-based scoring (NBS) was used,
where 50 is the mean score, and 10 the standard deviation of a
defined general population. Paired analysis between donors and
recipients were performed for detecting differences between donors
and recipients. All scored items of recipients as well as of the donors
were within the range of one standard deviation of the norm-based
population. All scores concerning physical well being except one,
(RP), were statistically lower in the recipients than in their donors. In
contrast, there was no difference in scores concerning mental well
being. This is confirmed by the summary measurements of physical
health (PCS) with 52,8 in the recipients and 57,1 in the donors
(p = 0.001) and mental health (MCS) with 50,8 versus 52,9 (p = 0.831).
Physical health (PCS) was lowest in patients with severe chronic
GvHD compared to their donors (47,2 versus 57,2) (p = 0.05), age
older than 25 years at HSCT 50,7 versus 56,2 (p = 0.024), older than
42 years at the last control 52,2 versus 55,63 (p = 0.05) and for
female patients 51,8 versus 57,7 (p = 0.024). None of the factors had
a statistical impact on mental heath status (MCS, P >0.05). In summary, quality of life of long term survivors after HSCT measured with
the SF-36 questionnaire is still within the normal variation of the general population. However, when compared to the respective donors,
the physical health status is significantly compromised in the recipients. Severe GvHD, older age at HSCT and at the time of filling out
the questionnaire and female gender are associated with an inferior
physical health status.
Table 1
Forum Med Suisse 2008;8:(Suppl. 40)
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P139
Tumour incidence in donors of haematopoietic stem cells
for their HLA identical siblings
Jeger A., Favre G., Lutz J.M., Usel M., Halter J., Stern M., Heim D.,
Rischewski J., Tichelli A., Gratwohl A. (Basel, Genf)
Introduction: Patients with a history of an allogeneic haematopoietic
stem cell transplant (HSCT) have an increasing risk to develop a
secondary cancer. The association of the HLA system to cancer is
well known. Sibling donors share the same HLA alleles, and the question is, if they have an increased tumour incidence compared to the
general population. This is of concern because the possibility of a
tumour induction as a result of mobilisation with G-CSF has been
discussed.
Methods: All HLA-identical sibling pairs with an HSCT from 1974 to
2001 for a malignant disease and living in Switzerland were evaluated. General data of the donors were taken from the patient’s charts
of the transplant unit. Donors were contacted per call or mail and
asked about their current health status. In case of a malignant cancer,
information on date of diagnosis,localisation,treatment was obtained.
Data were compared with the age-,and sex adapted cancer incidence
rate of the Swiss association of cancer registries (SACR). The same
information was retrieved for the patients.
Results: 318 pairs were identified, in 291(92%) the donors (142 men
(m), 149 women (w)) could be contacted. Median observation time
was 13.8 years (y) (range 5–32 y). 146 donors were <50 y, 89 between
50–59 y, 29 between 60–64 y, 20 between 65–69 y and 7 >70 y old,
hence 85% were <60 y old. Seventeen (6%) donors, 12 bone marrow
and 5 peripheral blood donors, had developed a total of 18 cancer of
9 different localisations (mamma, prostate, skin, bone marrow, colon,
bronchus, stomach, bladder, ORL). According to the incidence rate of
the SACR, 3.3 tumours in m and 6.8 in w would have been expected,
3 (m) (RR 0.91) and 4 tumours (w) (RR 0.84) were found in donors
between 0–49 y. In the age category 50–69 y, 4.5 tumours in m and
4.8 in w were expected and 5 (RR 1.11) respective 6 (RR 1.23)
observed. In the subgroup of men between 60–64 y 1.07 tumour were
expected and 4 observed (p <0.02). No donor >70 y developed a
tumour. 4 of the 291 donors had died, 3 from the tumour, 1 of cardiac
disease. In 12 patients a secondary tumour was diagnosed post
HSCT.
P140
Allogeneic hematopoietic stem cell transplantation (HSCT)
in mitochondrial neurogastrointestinal encephalomyopathy
(MNGIE)
Studt J.-D., Buser A., Halter J., Heim D., Kappeler L., Lehmann T.,
Mattle H. P., Stern M., Tichelli A., Tiercy J.-M., Schüpbach M.,
Gratwohl A. (Basel, Bern, Geneva)
Background: MNGIE is an autosomal recessive disease characterized by ophthalmoplegia, gastrointestinal dysmotility, cachexia,
peripheral polyneuropathy, and leukencephalopathy, usually leading
to death in early adulthood. It is caused by mutations of the ECGF1
gene encoding thymidine phosphorylase (TP) which result in virtual
absence of TP activity, accumulation of thymidine and desoxyuridine,
and subsequent instability of mitochondrial DNA. Reduction of thymidine and desoxyuridine levels is of therapeutic benefit, and was transiently achieved by transfusion of normal platelets. Experimental
allogeneic HSCT has thus been reported since 2006 in two patients.
Because of potential mitochondrial damage due to many drugs used
during and after the transplantation procedure, allogeneic HSCT
bears additional risks.
Patient and procedures: We report a 25 year old male patient suffering from MNGIE. His identical twin brother is also affected while a
triplet sister is not. An older brother had already died from MNGIE.
Allogeneic HSCT using bone marrow of an HLA 12 of 12 antigen
matched unrelated donor was performed. Due to the metabolic alterations in MNGIE, increased drug toxicity was expected for
substances with mitochondrial metabolization, e. g. nucleoside analogues, cyclophosphamide, paracetamole, certain antimetabolites,
and azole antifungals. Reduced intensity conditioning as reported by
Slavin et al. was therefore selected, consisting of fludarabine, intravenous busulfan, and anti thymocyte-globuline. Medication was
adjusted and restricted carefully, and daily platelet transfusions were
administered in order to provide TP substitution. To date, we did not
observe relevant drug toxicity. Engraftment was at day 26. Apart from
gastrointestinal bleeding occurring 6 weeks after HSCT, the subsequent course was uneventful without relevant infectious or immuno-
POSTERS SSHé
POSTERS SGH
logical complications. No graft versus host disease was observed.
Recovery of donor type hematopoiesis was normal 3 months after
HSCT.
Conclusions: We report a patient with allogeneic HSCT for the treatment of MNGIE. The selected conditioning regimen did not result in
an increased toxicity, and no relevant infectious or immunological
complications were observed yet. This confirms allogeneic HSCT as a
feasible therapeutic approach to MNGIE, provided a careful adjustment of conditioning and careful selection of medication. A longer
follow up will be required to evaluate the impact on the disease
course.
P141
Nephrotic syndrome after allogeneic hematopoietic stem
cell transplantation: a rare renal manifestation of chronic
graft-versus-host disease
Levrat E., Passweg J.R., Stucki A., Verholen F., Chalandon Y.,
Helg C. (Genève, Lausanne)
We report on two patients developing nephrotic syndrome (NS)
after allogeneic hematopoietic stem cell transplantation (HSCT).
Patient 1: a 51-year old man underwent T-depleted HSCT after
myeloablative conditioning from HLA-compatible unrelated donor for
acute myelogenous leukemia M2.The immunosuppression was withdrawn on day 77, without sign of graft-versus-host-disease (GvHD).
On day 188, the patient developed NS and kidney biopsy revelead a
minimal change glomerulonephritis.The patient was treated with
ciclosporine, prednisone, furosemide and lisinopril, with considerable
improvement in proteinuria.
Patient 2: a 31-year old man underwent non T-depleted HSCT after
nonmyeloablative conditioning from his HLA-identical brother for
mediastinal large B cell lymphoma.His course was complicated 30
days later, during immunosuppression withdrawal, by development of
cutaneous and digestive grade III acute GvHD and was treated with
ciclosporine and prednisone, with response and progression in extensive muco-cutaneous chronic GvHD. Immunosuppression could be
eventually withdrawn 6 years later. Seven months after withdrawal,
the patient developed NS and muco-cutaneous GvHD exacerbation.
The kidney biopsy revealed a membranous glomerulonephritis.The
patient was treated with tacrolimus, mycophenolate mofetil, prednisone, and lisinopril, with complete remission of the NS at two years
follow-up. Glomerular disease associated with NS is a rare complication of HSCT, most commonly in association with chronic GvHD.The
glomerular histology most frequently reported is membranous
glomerulonephritis, followed by minimal change glomerulonephritis.
The temporal relationship between cessation or tapering of immunosuppressive medication and onset of NS, suggests that glomerular
disease is a manifestation of the chronic GvHD and may, occasionally, be its only manifestation. Nonmyeloablative HSCT was identified
as a risk factor for NS (especially membranous nephropathy, with
basement membrane immune complex deposition) in one cohort
study and it was then suggested that host B cells and plasma cells
that survive reduced-intensity conditioning could play a role in the
pathophysiology of this condition, who probably represents a
humoral manifestation of chronic GvHD.The majority of reported
cases in the literature have a relatively benign course with resolution
or substantial improvement of NS following initiation of immunosuppressive therapy, as in our 2 case reports.
P142
Treatment of CLL with Alemtuzumab (MabCampath®)
in a patient with dialysis dependent renal failure
Heizmann M., Bock A., Varga D., Bargetzi M.J. (Aarau)
Background: Alemtuzumab (A) is a human IgG1 molecule, which is
not eliminated by dialysis (D). In this case report we describe for the
first time the use of A in a patient undergoing D for chronic renal
insufficiency.
Case report: A 67 y old female patient underwent therapy for CLL
with 6 cycles of fludarabine and rituximab. In cycle 6 of this treatment, platelet count dropped to 9 G/l and a multithrombotic syndrome with acute renal failure and cerebral ischemic lesions developed. Renal biopsy revealed glomerular fibrin thrombi. There was no
Forum Med Suisse 2008;8:(Suppl. 40)
65 S
evidence for HIT, antiphospholipid syndrome or decreased levels of
ADAMTS 13. Although hemolysis was not present, plasma exchanges
resolved this situation and therefore the clinical picture was considered as secondary microangiopathic syndrome. A correlation to fludarabine was possible. The patient remained D dependent and was
treated with hemodiafiltration (Fresenius FX 100 dialyzer, 3 x 4 hours
per week, blood flow 400 ml/min). 26 months after the last cycle,
relapse of CLL was observed in peripheral blood. Another 10 months
later, therapy became necessary due to rapid doubling time of lymphocytes to 87 G/l in 2 months and generalized lymphadenopathy.
Treatment with daily escalating doses of A (3, 10 and 30 mg) was
begun and continued with 30 mg 3x/w. Each dose was given subcutaneously 60 minutes prior to D. Premedication consisted of clemastine 2 mg and paracetamol 1000 mg orally 60 minutes prior to A.
During the first 3 weeks the patient received allopurinol 150 mg daily.
Prophylaxis with Bactrim forte® 1 tablet 3x/w, valacyclovir 500 mg
daily and fluconazol 200 mg 1x/w was given. Reactivation of CMV
was monitored every two weeks by PCR, but remained undetectable.
In the first weeks, treatment was well tolerated. Except for fatigue no
additional symptoms occurred. Lymphocytes decreased rapidly to
<0.1 G/l after only 5 days. Platelets fell transiently to 71 G/l and neutrophils to 1.1 G/l at nadir. Thrombocytopenia resolved after discontinuation of Bactrim. No fever or infection occurred. In week 8 of
therapy the patient had repeated chills after injection and therefore
refused further treatment. A total of 23 doses of A were administered.
Results of remission status will be reported.
Conclusion: This case reports for the first time the safety and
efficacy of treatment with alemtuzumab in a patient with D.
The D procedure does not need to be modified in this setting.
P143
Regression of debilitating hypertrophic osteoarthropathy
(HOA) by continuous nasal oxygen supplementation in a
patient with severe, normoxaemic bronchiolitis obliterans (BO)
after allogeneic hematopoietic stem cell transplantation
Halter J., Daikeler T., Cantoni N., Studt J.D., Stern M., Buser A.,
Häusermann P., Heim D., Tamm M., Gratwohl A., Brutsche M.H.
(Hematology, Rheumatology, Dermatology, Pneumology Basel)
HOA is associated with periostitis, periarthritis, painful swelling and
clubbing of affected limbs and evolve into a debilitating disease. It
occurs as a paraneoplastic phenomenon, in the context of a chronic
hypoxic heart or lung disease, or is associated with chronic liver
disease and inflammatory bowel disease. Hypoxia is thought to mediate release of growth-inducing peptides. Treatment is mainly directed
against the underlying disease. We report a 55 year old woman with
BO who developed severe debilitating HOA. She had normal oxygen
saturation as measured by repeated pulse oxymetry and arterial
blood gas analyses. She was previously diagnosed with chronic
myeloid leukemia blast crisis in 2004 and was treated with allogeneic
hematopoietic stem cell transplantation from an HLA-matched unrelated donor after myeloablative conditioning with
cyclophosphamid/busulfan. Acute cutaneous and intestinal graft
versus host disease (GVHD) developed after transplantation and was
treated with steroids. It evolved to chronic GVHD of the skin, oral and
vaginal mucosa. In November 2006 severe BO developed after a
respiratory viral infection still on low dose cyclosporine A. Despite
intensified immunosuppression with tacrolimus, mycophenolic acid
and steroids lung function remained severely impaired and deteriorated further after a pulmonary embolism four month later. She developed partial respiratory insufficiency with exercise-induced desaturation requiring intermittent nasal oxygen supplementation during
physical efforts. Her oxygenation was normal at rest. After a stable
disease course for further 6 months a painful swelling in several digits
of both hands started to develop. Radiographically a periostal reaction and subcutaneous swelling was observed. Extramedullary
leukemic relapse could be ruled out by biopsy. A bone scintigraphy
revealed several sites of uptake. After exclusion of other possibilities,
the diagnosis of HOA was made. Multiple attempts to control swelling
and pain failed. Clinical signs and symptoms progressed. Despite
documented normal oxygen saturation we postulated local tissue
hypoxia and introduced a continuous oxygen supplementation
(2 L/min via nasal cannula). About one week after initiation symptoms
and swelling decreased with ongoing improvement since then.
Conclusion: Despite normal oxygen saturation local tissue hypoxia
may have precipitated HOA in this patient with BO. Continuous application of oxygen proved to be a simple and in this patient very effective treatment. Pain, swelling and functional status of the digits
improved and the patient is now able again to care for herself.
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Forum Med Suisse 2008;8:(Suppl. 40)
66 S
P144
P146
Hematopoietic progenitor cell colony growth differentiates
chronic myelomonocytic leukemia from reactive monocytosis
Stern M., Birrer A., Jusufi F., Meyer-Monard S., Bernimoulin M.,
Tichelli A., Gratwohl A., Nissen-Druey C. (Basel)
In the absence of a cytogenetic abnormality or overt dysplasia,
chronic myelomonocytic leukemia (CMML) may be morphologically
difficult to distinguish from reactive monocytosis. Definitive diagnosis
of CMML is frequently based solely on the persistent presence of
peripheral blood monocytosis without any underlying disease. We
have previously described a typical growth pattern in CMML patients,
i.e. “pseudonormal” colonies resembling granulocytic colonies but
consisting entirely of monocytic cells when stained. To study the
utility of the colony forming unit cell (CFU-C) assay as a diagnostic
tool in patients with monocytosis, we analyzed a cohort of 48 consecutive patients referred to our institution between 1992 and 2005
with peripheral blood monocytosis. All patients had a complete
haematological workup including bone marrow aspirate, histology
and cytogenetics. Colony forming unit cells were analysed after two
weeks culture in standard conditions using commercially available
reagents. Median age at referral was 70 years; 17 patients were
female, 31 male. Thirty-six patients fulfilled the WHO criteria for
CMML; twelve patients were diagnosed with reactive monocytosis.
Of the patients with CMML, twenty-eight showed pseudonormal
growth with or without leukemic cluster growth, another four showed
exclusively leukemic growth. None of the patients with reactive
monocytosis showed either leukemic or pseudonormal growth. With
a specificity of 100% and a sensitivity of 89%, the CFU-C assay had
a unique potential to distinguish CMML from reactive monocytosis.
The CFU-C assay using standard culture conditions is a highly sensitive and specific method to distinguish CMML from reactive monocytosis.
Atypical presentation of acute myeloid leukemia:
intracardiac AML
Rigamonti F., Beris P., Sanchez A., Passweg J., Chalandon Y.
(Genève)
A 52 year-old man, presented with a 2 months history of dyspnea and
was hospitalized with bilateral pleural effusion and cardiomegaly. An
echocardiogram showed pericardial effusion with infiltration of inferolateral cardiac wall, right auricle and aortic arch by a mass of
unknown origin. Laboratory work up showed 1–2% blasts in the
blood, but bone marrow aspiration was dry and 2 bone marrow biopsies did not show any leukemic infiltration. MRI of the heart showed
infiltrative biventricular mass. Myeloid blasts that were MPO+ (21%)
and had a 47 add(Y) (q12) 4 dim 9 caryotype were found in the pericardial and pleural effusion. A cardiac biopsy showed CD34+ cells in
the myocardium. Flow cytometry analysis of the blood showed a
blast population of CD34+, CD33+, CD13+ and HLA-DR+ cells which
led to the diagnosis of extramedullary AML M1 or M2. Induction
chemotherapy was with Cytarabine, Mitoxantrone and Etoposide.
This was complicated by a cholecystitis, hemodynamic instability
with arrhythmia (atrio-ventricular bloc type II), febrile neutropenia
associated with mucositis grade 3. A control echocardiography
2 weeks after starting the treatment showed improvement with a
decreased cardiac infiltration involving the left and right ventricles
but associated with decreased ejection fraction to 40%. 4 weeks into
induction chemotherapy, with persistent febrile neutropenia, the
patient’s state deteriorated and he died of multiple parieto-occipital
and thalamo-mesencephalic hypodensities associated with hemorrhage with breakthrough into the ventricular space and multiples
spleens infarcts. Tumor embolism was suspected at this time as the
patient had been treated with large spectrum antibiotics and antifungals and no culture had been positive. Autopsy revealed angioinvasive disseminated lesions involving the spleen, the brain and the
heart caused by septic emboli, of probable fungal origin. There were
no residual leukemic cells in the patient organs, with residual fibrotic
scars in the myocardium. Extramedullary AML is a rare presentation
also called granulocytic sarcoma or chloroma that may either precede
or be concurrent with BM invasion. This may also be the first manifestation of relapse after chemotherapy or allogeneic HSCT. Cardiac
infiltration is very rare, and in myeloid leukemia only a few cases of
pericardial effusion, heart muscle infiltration or intracavitary masses
have been described. The prognosis seems to be poorer than in de
novo AML. The place of allogeneic HSCT as consolidation therapy is
not well defined due to the paucity of data. Chemotherapy may be
combined with local treatment such as radiotherapy or surgery. In a
few reported cases, local therapy has been sufficient to control localized extramedullary AML mainly in extramedullary relapse AML without BM involvement. Extramedullary AML with cardiac involvement is
a rare presentation of AML and rapid imaging associated with biopsy
reveals the diagnosis.
P145
ZAP-70 expression assessed by flow cytometry is a reliable,
reproducible and predictive marker for IgVH mutation status
in CLL patients if the ratio of B- to T-cell fluorescence intensity
(“ratiometric method”) is taken into account
Solenthaler M., Schällibaum C., Horn M., Keller P., Oppliger
Leibundgut E. (Bern)
ZAP-70 expression in B-CLL lymphocytes is a powerful prognostic
marker and is strongly correlated to IgVH mutation status (IgVHms)
as shown by gene expression profiling yielding concordance in 93%.
However, methods assessing ZAP-70 expression by flow cytometry
vary and results may differ considerably. Recently, a ratiometric
analysis method based on comparison of ZAP-70 expression in Band T-cells was described to circumvent intra-/interlaboratory variation, but cut-off values are not well established. On previously
acquired data, we compared retrospectively our standard (healthy
donor as an external control; cut-off >20% for positivity) with a ratiometric (mean fluorescence intensity of B-cells / T-cells x 100 [%])
analysis method (= “method”). If available, results were compared to
IgVHms. ZAP-70 was measured in the peripheral blood of 104 pts.
with SLL/CLL. The Mean + 3 SD of ZAP-70 expression of 84 normal
controls was 21% (B-cells) and 19.9% (B-/T-cells) with the standard
and ratiometric method, respectively. 37 pt. samples were ZAP-70
pos., 64 ZAP-70 neg. and 3 yielded borderline results. In 74 pts.
IgVHms was available: 28 pts. had unmutated IgVH and 46 mutated
IgVH. 80% of the ZAP-70 results were concordant to IgVHms (8 false
pos., 8 false neg.) with the standard, and 76% (5 false pos., 14 false
neg.) with the ratiometric method using the same cut-off (20%). However, ROC curve analysis was better for the ratiometric than for the
standard method (AUC 0.84 with a cut-off of 13.2% and 0.77 with a
cut-off of 22%, respectively). Combining both methods (cut-off >20%
for ZAP-70 positivity using standard or ratiometric method, cut-off
<= 20% or <=13.2% for ZAP-70 negativity using standard and ratiometric method, respectively, ratio = 1st priority) the concordance was
86% (5 false pos., 7 false neg.). 4 pts. had undergone ZAP-70 analysis at different time points with all results being concordant with the
combined but not the standard method (2 pts. discordant). 11 samples were remeasured after a median of 161 (78-238) days and
showed concordant results (Spearment’s coefficient with standard
and ratiometric method 0.74 [p = 0.02] and 0.94 [p = 0.003], respectively). The performance of ZAP-70 expression analysis by flow
cytometry in CLL patients can be improved by using the ratio of the
B- and T-cell expression (“ratiometric method”). This may be due to
methodology and/or by concomitant abnormal ZAP-70 expression in
the T-cells of some CLL patients.
P147
Hb H disease in combination with haemoglobin Pyrgos
in a woman from Thailand
Rüfer A., Frischknecht H., Rovo A., Tichelli A., Wuillemin WA.
(Luzern, Zürich, Basel)
We report a case of a 38-year old woman from Thailand who was
referred for an evaluation of a microcytic, hypochromic anaemia with
a haemoglobin of 98 g/l (normal range 115–148 g/l), MCV of 68fl
(80–97 fl), MCH of 20 pg (27–34 pg) and MCHC of 298 g/l (330–364
g/l). Ferritin was normal (108 mg/l) and did exclude iron deficiency,
and so were vitamin B12 and folic acid. The peripheral blood smear
showed marked anisopoikilocytosis, microcytosis, hypochromasia,
stomatocytes and a large number of target cells but no basophilic
stippling. In the brilliant cresyl blue stain there were HbH inclusion
bodies in 72% of the red blood cells. The high-performance liquid
chromatography showed a reduced HbA and HbA2, an increased
HbH of 6.1% and an abnormal haemoglobin of 56%. Using Gappolymerase chain reaction the deletional mutations (—SEA) and
(-[alpha]3.7) in the [alpha]-globin gene could be identified leading to
the diagnosis of Hb H disease. In view of the abnormal haemoglobin
the b-globin gene was sequenced and the b-globin variant haemoglobin Pyrgos (codon 83 GGC>GAC) was identified with no evidence of
any other mutations in the sequenced area of the b-globin gene (–160
to +1620) excluding an additional b+-thalassaemia that could explain
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the relatively high concentration of Hb Pyrgos. Hb Pyrgos was first
described in a Greek boy but was later found in Thailand, too. All the
carriers of Hb Pyrgos are clinically healthy. Coinheritance of Hb H
disease and several other uncommon b-globin chains has been
described. To our knowledge, this is the first description of a case of
Hb H disease in combination with Hb Pyrgos without any other mutations in the b-globin gene. The clinical picture in this patient is determined by the presence of Hb H disease, which is in the deletional
forms a mild disease although there is marked phenotypic variability.
Iron overload, hepatosplenomegaly and cholelithiasis are common
complications. The mild form of the thalassaemia in this case without
iron overload could be explained by the presence of a b-globin gene
defect decreasing the proportion of excessive b-globin chains. Folic
acid supplementation is recommended in view of the usually mild
haemolysis and increased erythropoiesis. In haemolytic crisis secondary to infection, aplastic crisis or during pregnancy transfusion
of red blood cell concentrates may be required. Genetic testing of the
partner and other family members for [alpha]- and b-thalassaemia
carrier status is recommended.
Forum Med Suisse 2008;8:(Suppl. 40)
67 S
des multiplen Myeloms. Das Phänomen wurde erstmals 1944
beschrieben, wobei bislang nur Myelome vom Typ IgG kappa oder
lambda publiziert worden sind. Histologisch handelt es bei den Spikulae um verhornende Paraproteinablagerungen. In mehreren Fällen
konnten gleichzeitig Kryoglobuline mit Livedo reticularis nachgewiesen werden.
Abb. 2
Knochenmarksbefund
P148
Hautveränderungen und Multiples Myelom
M. von Kietzell, M. Berger, S. Regenass*, L. Weibel**, L. French**,
U. Schanz, J. Fehr, J.S. Goede, G. Stüssi (Klinik für Hämatologie
UniversitätsSpital Zürich, *Klinik für klinische Immunologie
UniversitätsSpital Zürich, **Klinik für Dermatologie UniversitätsSpital
Zürich)
Wir präsentieren den Fall eines 41jährigen Patienten, der sich mit seit
etwa einem Monat bekannter progredienter nekrotisierender Livedo
racemosa und kutanen follikulären Spikulae auf der Dermatologie
präsentierte. Zusätzlich bestanden Arthralgien, eine leichtgradige
Anämie und B-Symptomatik. Der dermatologische Befund beschrieb
multiple follikulär angeordnete harte weissliche filiforme Spiculae
sowie eine Livedo reticularis an beiden Beinen mit multiplen, scharf
abgegrenzten, dunkel-lividen Plaques mit Ulzeration und Blasen.
Histologisch konnte an den Beinen eine leukozytoklastische Vaskulitis
und am Rücken in den Follikelostien ortho- parakeratotische Hornpfropfen gezeigt werden. Aufgrund der typischen perifollikulären
Spikulae wurde unverzüglich ein multiples Myelom gesucht: In der
Knochenmarksuntersuchung konnte eine 75% Infiltration mit blastoiden Plasmazellen nachgewiesen werden, die Proteinelektrophorese
und Immunfixation ergaben ein Paraprotein vom Typ IgG lambda von
42,7 g/l. Der konventionelle Röntgenstatus war unauffällig, die Nierenfunktion normal. Gleichzeitig konnte eine Kryoglobulinämie Typ I
nachgewiesen werden. In der Aufarbeitung der biopsierten Spikulae
konnten IgG-Ablagerungen nachgewiesen werden. Die ulcerativen
Hautveränderungen wurden im Rahmen der Kryoglobulinämie interpretiert. Bei Diagnose des multiplen Myelomes (Stadium II nach Durie
und Salmon) wurde mit Thalidomid/Dexamethason und begleitend
Pamidronat begonnen. Hierunter konnte ein rasches Verschwinden
der Spiculae und, unter ausschleichender Dauersteroidtherapie eine
protrahierte Abheilung der ulcerativen Hautläsionen beobachtet werden. Trotz initial unauffälligem konventionellen Skelettröntgen kam es
im Verlauf unter Therapie zu einer hyperkalzämischen Krise mit transientem Nierenversagen, worauf in einer CT-Untersuchung multiple
Osteolysen nachgewiesen wurden. Bei progredientem Markbefall
wurde auf Bortezomib, Adriamycin und Dexamethason umgestellt.
Darunter konnte erstmalig eine Reduktion des Paraproteins nachgewiesen werden, das Restaging unter dieser Therapie ist noch ausstehend. Perifollikuläre Spikulae sind eine seltene kutane Manifestation
Abb. 1
Hautbefund
P149
Iron deficiency without anemia in young female blood
donors: a reality that needs management
Waldvogel Abramowski S., Canellini G., Vedy D., Tissot J.D.
(Lausanne)
Background: Blood donation leads to iron depletion. According to
the recommendations in force, female donors safely could undergo 3
donations per year. Furthermore, iron storage, expressed by ferritin
value, is significantly lower in pre-menopausal women than
menopausal women. Menstruation is likely the main reason. In addition, iron supplementation, given to non-anemic women with low or
borderline ferritin levels, has recently shown to decrease fatigue. This
means, that subjective and negative symptoms can already be present before the onset of anemia. Here, we analyzed the impact of
donations on ferritin level among women of reproductive age.
Patients, methods: During one month (October 2007), a pre-donation blood venous sample was collected in all female blood donors
aged 18 to 50 years. Three groups were considered according to the
frequency of blood donations in the last 12 months (group 1: 0 donation; group 2: 1 donation; group 3: 2 donations). Serum ferritin was
measured by immuno-turbidimetry (Hitachi, Roche diagnostics, BSD
Bern).
Results: 699 women were enrolled in the study and median age was
29 years. Three hundred and eight were included in group 1, 241 in
group 2, and 150 in group 3. Mean ferritin level was 46 ng/ml, 33
ng/ml, and 24 ng/ml in group 1, 2 and 3, respectively. The difference
was significant between each group (one way analysis of variance
with Dunn’s correction, p<0.05). The prevalence of iron deficiency
without anemia (ferritin <16 ng/ml) was 9.4%, 19.1% and 35.3% in
group 1, 2 and 3, respectively.
Conclusion: In pre-menopausal female volunteers, categorized
according to the frequency of donations per year, the mean ferritin
level significantly decreases. This result suggests that premenopausal women need more time than expected to compensate
iron loss between two successive donations, and that a frequency of
3 donations per year might be too high. A new prospective study
evaluating the individual negative effect of blood donation on iron
store in this population is needed. A better understanding on how
repeated donations affect female donor’s health will allow to propose
more appropriate recommendations (nutrition care and frequency of
donations). Clinical and financial consequences of iron depletion for a
donor are probably underestimated and should not be neglected.
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P150
Severe pancytopenia in a 20 years old patient suffering from
congenital apple-peel-syndrome
Redondo M., Spalinger J., Criblez D., Wuillemin W. A. (Luzern)
Background: Apple-peel-syndrome (APS) is a rare congenital
disorder characterized by jejunal atresias, absence of a stomach
membrane so that the small bowel twists around the left branch
of the ileocolic artery.
Case report: We report a 20-years old male patient suffering from an
APS. He developed a short bowel syndrome after abdominal surgeries necessitating parenteral nutrition for 16 years. On this regimen he
developed severe liver fibrosis with portal hypertension and significant splenomegaly. Druing the following years the patient was
weaned from TPN and enteral nutrition was successfully established.
Stable pancytopenia (hemoglobin 133 g/l, leucocytes 1.4 G/l, neutrophiles 0.70 G/l, platelets 33 G/l) was observed for three years after
starting enteral nutrition, most probably due to hyperplenisme. Within
one year the patient then gradually developed severe megalobalstic
anemia (hemoglobin 51 g/l, MCV 109 fl, MCH 37 pg, reticulocytes 49
G/l), agranulocytosis (leucocytes 0.5 G/l, neutrophiles 0.12 G/l), but
still showed a stable platelet count (33 G/l). Vitamine B12- and folic
acid-levels were normal, ferritin increased (1359 microg/l). Bone
marrow showed increased cellularity with dysplastic changes of the
myelo- and erythropoesis with sideroachrestic changes. The caryotype was normal. Furthermore, aceruloplasminemia and decreased
copper plasma level of 0.5 micromol/l with normal urinary copper
excretion (0.24 micromol/24 h) was found, consistent with copperdeficiency. After starting copper-substitution intravenously blood cell
count returned to former values (hemoglobin 126 g/l, leucocytes 1.4
G/l, neutrophiles 0.82 G/l, platelets 48 G/l) within 16 days. MCV (95 fl)
and MCH (34 pg) normalized within 2 months.
Discussion: Several mechanism may play a role in copper deficiency
associated cytopenia. Downregulation of copper dependent enzymes
lead to dysfunction of iron incorporation into the hem molecule
(cytochrome C oxydase), downregulation of the superoxide dismutase causes increased damage of the red cell membrane by free
radicals. The correction of MCV and MCH during copper-substitution
suggests a copper-deficiency induced mechanism leading to a
megaloblastic anemia.
Conclusions: Copper deficiency should be excluded in patients with
cytopenia especially in patients with unaffected megakaryopoesis
and normal cytogenetics, chronic gastrointestinal disorders or neurological signs of a copper deficiency.
P151
Not a simple hypermenorrhea
Colucci G., Alberio L., Keller P., Rüsges-Wolter I., Lämmle B. (Bern)
A 55-year-old woman was hospitalised in a peripheral hospital for
hysterectomy because of uterus myomatosus and hypermenorrhea
since one year. The bleeding history was otherwise negative. The
recent medical history was characterized by cutaneous haematoma
after mild trauma, depression, dyspnea during exercise, dysphagia
and weight loss without a specific cause. A preoperative blood
screening showed a normal platelet count (304G/l), a prolonged
prothrombin time (Quick 30%) and a prolonged aPTT (158.1 s). The
patient was transferred to our hospital. Coagulation analysis confirmed the results and showed additionally a prolonged thrombin time
(33.2 s) and reptilase time (46.1 s), a low fibrinogen Clauss (0.42 g/l)
and factor V:C (11%) and elevated factor II:C (138%), factor VII:C
(173%), D-dimer (3472 ‘µ-g’/l) and thrombin-antithrombin-complex
(47.0 ‘µ-g’/l). Factor X:C was normal (85%). A diagnosis of disseminated intravascular coagulation (DIC) was made. The patient received
fresh frozen plasma and unfractionated heparin in a prophylactic
dose. During hospitalisation coagulation parameters showed no
significant changes and an extensive search of the cause of DIC was
inconclusive. An extension of analysis showed a severely decreased
‘[alpha]-2-antiplasmin’ (23%) and a therapy with tranexamic acid was
started improving the fibrinogen and factor V:C levels. Hypothesizing
that the cause of the DIC was a malignant tumor of the uterus, the
patient was subjected to hysterectomy. Intra- and postoperatively no
bleeding complication occurred. Postoperatively, coagulation markers
still showed DIC. Because of dysphagia a gastroscopy with mucosal
biopsy was performed. The Congo red staining showed multiple
amyloid deposits and a diagnosis of primary AL-amyloidosis was
Forum Med Suisse 2008;8:(Suppl. 40)
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made. The staging showed diffuse amyloid deposits within heart,
marrow, colon, stomach and kidney. This case shows hypermenorrhea as first manifestation of DIC with pronounced fibrinolysis in the
context of primary AL-amyloidosis with multiple organ involvement.
P152
Smouldering systemische Mastozytose als seltene Ursache
einer rezidivierenden Flushsymptomatik
Dhayat N., Koltai E. (Solothurn, Laufenburg)
Hintergrund: Die systemische Mastozytose (SM) ist eine polymorphe
Erkrankung mit Proliferation abnormer Mastzellen in diversen Geweben. Die Smouldering systemische Mastozytose (WHO-Klassifikation
2001) ist eine Unterform der indolenten systemischen Mastozytose.
Fallpräsentation: Der 50jährige Angestellte einer Tiefbaufirma
beklagte seit drei Jahren eine chronische Diarrhoe sowie zunehmend
häufiger auftretende Flushanfälle mit generalisierten Kribbelparästhesien, Hitzegefühl, Dyspnoe und unfreiwilligem Stuhlabgang.
Nach einem erneuten Flushanfall mit Präkollaps, Schwindel und
Kopfschmerzen blieb die Symptomatik trotz einer stationär durchgeführten Diagnostik mit Ausschluss gängiger Flush-Ursachen wie
Karzinoid und Phäochromozytom bei klinisch lediglich feststellbarer
passagerer Hautrötung weiterhin unklar.
Diagnostik: Erst eine ambulante systematische Diagnostik mit der
Suche nach seltenen Flush-Ursachen erlaubte die Diagnosestellung
einer Smouldering systemischen Mastozytose durch folgende
Befunde: kleinknotige Infiltration des Knochenmarks mit atypischen,
CD2/CD25 positiven Mastzellen, Nachweis der c-Kit-D816V-Punktmutation, Erhöhung der Serumtryptase, Osteoporose der LWS
Knochendensitometrie) und Splenomegalie (Abdomencomputertomographie). Als wahrscheinliche Triggerfaktoren wurden körperliche
Anstrengung sowie ein exzessiver Bierkonsum identifiziert.
Therapie und Verlauf: Unter der Therapie mit einem H1- und H2Rezeptor-Blocker sowie Alkoholrestriktion sistierten sowohl die
Diarrhoe als auch die Flushanfälle inklusive Begleitsymptomatik. Die
Osteoporose wird mit Calcium, Vitamin D und einem Bisphosphonat
behandelt. Wegen der Gefahr von anaphylaktischen Reaktionen
wurde ein Adrenalin-Auto-Injektor abgegeben. Regelmässige Kontrollen sind indiziert, da eine Krankheitsprogredienz mit Übergang in eine
aggressive SM möglich ist.
Schlussfolgerung: Die Differentialdiagnose von Flush-Reaktionen ist
sehr umfangreich und es bedarf häufig einer systematischen Diagnostik. Aufgrund der vielfältigen klinischen Präsentation wird die Diagnose einer SM oft nicht gestellt. Das Fehlen einer Urticaria pigmentosa, die bei der indolenten SM in über 90% der Fälle vorkommt,
verzögerte hier die Diagnosestellung erheblich. Die Therapie mit
einem H1- und H2-Blocker führte im vorliegenden Fall zu einer
Symptomkontrolle.
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P153
Inhibition of the myeloid tumor suppressor p15INK4b
by the centrosomal protein CEP70
Tschan M.P., Shan D., Arvidsson G., Tobler A., Fey M.F. (Bern)
A role for p15INK4b (hereafter p15) in myelopoiesis is suggested by the
frequent loss of its expression in myeloid malignancies. A common
p15 silencing mechanism in acute myeloid leukemias (AML) and in
myelodysplastic syndromes is promoter hypermethylation. Further,
the INK4b locus is directly silenced by the fusion gene product CBFbSMMHC in inv(16)+ AML samples. Interestingly, the INK4b locus
encodes two transcript variants, p10 and p15, both showing similar
inhibitory effects on cell growth. In an attempt to find direct regulators
of p10 and p15, we performed a yeast two-hybrid screen. We identified the centrosomal protein CEP70 as new binding partner of p10.
Preliminary gene expression studies using RT-PCR revealed that
CEP70 is frequently expressed in myeloid leukemic cells and healthy
CD34+ progenitor cells but not in normal granulocytes or
macrophages. In line, PMA- and ATRA-induced differentiation of
U937 myeloid leukemic cells towards macrophage- or neutrophil-like
cells resulted in downregulation of CEP70 mRNA paralleled by an
increase of p10 and p15 mRNA as measured by real-time RT-PCR. To
further investigate a role for CEP70 in myeloid differentiation, we
generated U937 CEP70 knockdown cells using lentivirus delivered
shRNA. Upon PMA treatment these cells showed markedly enhanced
macrophage development compared to control shRNA expressing
cells as assessed by morphology. Moreover, p10 and p15 protein
levels were significantly higher induced in PMA-treated CEP70
knockdown as compared to control cells. In addition, U937 CEP70
knockdown cells displayed significantly less cell death during PMA
treatment than control cells as shown by XTT assays.
In summary, we identified CEP70 as a new binding partner of
p10/p15 and demonstrate that downregulation of CEP70 is needed
for macrophage differentiation to occur in leukemic cells. We propose
a model where high CEP70 expression contributes to a leukemic
phenotype by inhibiting p10 and p15. Current experiments aim at
deciphering how the inverse regulation of these genes during myeloid
development affects centrosome function.
Forum Med Suisse 2008;8:(Suppl. 40)
69 S
host MSC, this suggests that when inflammation is low, NK do not kill
host MSC. Moreover NK are not inhibited by MSC as they can effectively eradicate the residual leukemic cells. Further understanding the
crosstalk between MSC and NK has to be achieved before cell therapies involving both cell types can be envisaged.
P155
Cryohydrocytosis: Increased activity of cation carriers
in red cells from a patient with a band 3 mutation
Goede J.S., Bogdanova A., Weiss E., Bernhardt I., Lutz H.U.
(Zurich, Saarbrücken)
Cryohydrocytosis is a dominantly inherited hemolytic anemia with a
phenotype easily leading to the misdiagnosis of spherocytosis. The
red blood cell (RBC) membranes from most cryohydrocytosis patients
contain normal stomatin levels, but mutations in a transmembrane
segment of the band 3 protein, the anion-transport protein (Bruce et
al. 2005. Nat Genet 37:1258–1263). Transfection experiments suggested that the mutation in the anion exchanger may convert the
anion exchanger into a non-selective cation channel. Unexpectedly,
RBCs from one of these patients with the mutation H734R in band 3
showed instead a rather controlled permeability increase. Outside
sodium ions prevented, while outside potassium ion enabled the
cold-induced swelling as studied by density gradients and ektacytometry. The swelling was not inhibited by the anion-transport
inhibitor DIDS. Measurements of the changes in cellular ion and water
content revealed that in NaCl-containing medium Na+/K+ exchange
prevailed whereas in potassium-containing medium swelling was
mediated by chloride-dependent potassium uptake. Unidirectional
potassium influx measurements showed that the cells have abnormally high activities of the K+(Na+)/H+ exchanger and K+,Cl-cotransporter that could account for the net movements of cations in NaCl
and KCl-containing media. These results suggest that a mutationmediated cross-talk between band 3 and other transporters might
increase cation permeability in cryohydrocytyosis.
P154
Crosstalk between human mesenchymal stromal cells
and allogenic natural killer cells
Pradier A., Villard J., Passweg J., Kindler V. (Geneva)
Background: Mesenchymal multipotent stromal cells (MSC) are postnatal stem cells that can inhibit steroid-resistant graft-versus-hostdisease (GVHD) occurring after allogenic hematopoietic stem cells
transplant. Natural killer cells (NK), infused once GVHD has subsided,
can eradicate the eventual leukemia relapse provoked by immune
suppression. So far the interplay between MSC and NK is not fully
understood. For this reason, we investigated the interactions between
MSC and NK in vitro.
Methods: NK were purified from buffy coat by Ficoll-Hypaque gradient centrifugation and negative selection using immuno-labeled magnetic beads. MSC were isolated from femur heads of patients who
underwent hip replacement surgery. CFSE-labeled NK were cultured
in a medium supplemented with 5% platelet lysate with IL-15 (0–25
ng/ml) in absence or presence of MSC. After 6 days NK proliferation
was assessed by CFSE dilution. NK cytotoxicity was tested using a
flow cytometry based assay.
Results: Optimal proliferation of NK was achieved using 25 ng/ml of
IL-15 (87% CFSE low cells). This value was reduced to 40% in presence of MSC (n = 5, p = 0.008, Mann-Whitney). However in these
conditions, NK were cytotoxic towards the MSC stroma. By contrast,
preliminary experiments (n = 2) performed under conditions that
sustained NK survival but not proliferation in absence of MSC,
showed that NK proliferation could be triggered by MSC. This suggested that MSC could also have a proliferative effect on NK.
Conclusion: These in vitro data indicate that the effect of MSC on NK
correlates with the activation status of the later, a fact that is consistent with in vivo observations on leukemic patients. Infused MSC
inhibit acute GVHD but are rarely detected in vivo, suggesting that NK
initially co-injected with the hematopoietic stem cells, optimally activated by the GVHD possibly kill them. By contrast delayed allogenic
NK infusion performed after GVHD has settled down, efficiently eradicates relapsing leukemia without inducing generalized inflammation
or impairing hematopoiesis. As hematopoiesis depends on functional
P156
Ultrafine diesel exhaust particles affect collagen-induced
platelet aggregation in a bimodal way
Forestier M., Sauvain J.J., Büchi L., Beer J.H. (Baden, Lausanne)
Background: There is robust evidence that air pollution with fine
(<2.5 mm; PM2.5) and ultrafine (<0.1 mm; UFP) particles are dosedependently associated with an increased incidence of cardiovascular events and a progressively reduced pulmonary function. Mechanisms include an inflammatory cytokine response and an elevated
procoagulant activity by alveolar macrophages and endothelial cells.
Hypothesis: We hypothesized that a direct platelet activating effect
by Diesel exhaust particles (DEP) could be operative since they easily
pass epi- and endothelial barriers. They may cause platelet activation
and may also contain divalent heavy metal ions, some of which are
known to activate GPIIb/IIIa (Zn++, Ca++, Mn++ etc.).
Methods: DEP was provided as standard SRM 1650 from the
National Institute of Standards and Technologies and was reconstituted in saline/0.1% Tween 20. Incubation of citrated normal whole
blood from healthy donors was performed for 60 min at room temperature in the presence of 0.1 mg/ml DEP or vehicle, which corresponds
to a daily absorbable respiratory dose of DEP. The DEP concentrations were increased stepwise 25–50 fold and platelet aggregation in
platelet rich plasma (PRP250) was analyzed vs. control samples in a
PACKS-aggregometer (Helena) with collagen, convulxin, ADP, ristocetin and arachidonic acid at typical standard concentrations. A
collagen concentration was chosen which induced a 70% aggregation (2.5–5 mg/ml).
Results: At daily respirable concentrations of DEP (0.1 mg/ml), collagen-induced aggregation was enhanced by 52 ± 9% (± S.E.M., p
<0.01, n = 5), while higher DEP concentrations of 2.5–5 mg/ml led to
an inhibition of collagen induced aggregation by ~40 ± 10% (p <0.05,
n = 8). The ADP-, arachidonic acid- and ristocetin-stimulated aggre-
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gation remained unaffected. Similarly as with collagen, the convulxininduced platelet aggregation was reduced by ~30% with the higher
DEP-concentrations.
Conclusion: DEP appears to influence collagen-induced platelet
aggregation. The stimulatory low dose effect is compatible with the
hypothesis and the clinical literature. The inhibitory effect at high
doses may be due to an interference with platelet GPVI, since convulxin-induced aggregation is selectively affected as well. Mechanisms are under investigation.
P157
Thalidomide increases tissue factor activity on human
umbilical vein endothelial cells in vitro
Valsami S., Leikauf M.S., Madon J., Fehr J., Asmis L.M. (Zürich)
Background: Current treatment protocols for multiple myeloma
include thalidomide. In the presence of varying thromboprophylactic
regimens, thalidomide treatment of myeloma patients is associated
with a high rate of venous thromboembolic events. The reported
event rate varies with co-medication including dexamethasone and
chemotherapy and ranges from 3 to 28%. Tissue factor (TF) is the
cellular receptor for clotting factor VII/VIIa and plays a central role in
the initiation of coagulation in vivo. Presently there is no consensus
regarding the optimal thromboprophylaxis strategy.
Study Hypothesis: Thalidomide alters endothelial thromboresistance
by increasing TF expression and function. Co-medication modifies
the thalidomide-induced effect.
Materials and Methods: We examined functional TF expression,
induced by thalidomide (Lipomed, Sigma) alone or in combination
with dexamethasone (Sigma), in human umbilical endothelial cells
(HUVEC, Lonza), under inflammatory conditions (in the presence of
TNFa), using functional coagulation assay (Actichrome TF, American
Diagnostica). HUVEC were of passage 5–8, cultured for 3 days, incubated for 24 hours and examined under sub-confluent conditions.
Thalidomide and dexamethasone concentrations used were similar to
therapeutic human plasma levels. Each experiment was repeated at
least 3 times.
Results: Constitutive TF activity in HUVEC is at the limit of detection.
TNFa induced an approximately 10-fold increase in functional TF
expression. In our study thalidomide, tested in three different concentrations, up-regulated TF coagulant activity under TNFa-induced
inflammatory conditions. Thalidomide at a concentration of 0.5 mM
induced a 25% mean increase of TF expression in each of 7 experiments. Higher concentrations of thalidomide (5 and 50 mM) also
increased TF expression compared to control but less than 0.5 mM.
The addition of dexamethasone modulated TF expression in a nonsynergistic way.
Conclusions: According to our data thalidomide increases TF procoagulant activity in endothelial cells in vitro. This TF up-regulation by
thalidomide may also occur on endothelial cells in vivo and could
thus be one of the underlying mechanisms of hypercoagulability in
patients with multiple myeloma receiving thalidomide containing
regimens.
Forum Med Suisse 2008;8:(Suppl. 40)
70 S
ized specialized hematology core labs need more time to bring out
results but supply very reliable and specialized results. We intended
to combine both advantages, speed and high quality by introducing a
fully automated hematology system, with 2 analyzers, performing
complete blood counts, 5-part differential, reticulocytes, and scattergrams (Advia 2120®). Each analyzer was linked to an automated slide
maker and strainer (Autoslide®) and connected to a robotic street
system offering a continuous flow processing, specimen distribution
to the instruments, and tube collection at the end of the testing.
A user-defined reflexive system initiated reticulocytes or slide making
in case of abnormal values. An electronic workstation (CentraLink®)
collected data from all instruments for validation and release. In order
to optimize turnaround time, automated validation and release was
organized for technically unproblematic results. The automation was
initiated in Sept. 2007 achieving full work capacity in <2 months. The
system works now in routine, 7 days a week, 24 hours a day. Within a
standard 7-day week, the performance of the system was 2950 complete blood counts, 305 reticulocytes, and 337 slides. Ninety-nine
(32%) of the reticulocytes and 175 (52%) of the slides were initiated
by the reflexive system. From all blood counts, 2310 (78%) were
validated and released automatically, 640 (22%) were withhold to be
validated manually. The time taken for the laboratory to process a
sample from admission to release on the central lab computer system
is illustrated in the figure. Ninety-one percent of the samples were
released within 30 minutes. These data prove that high technology
equipment with appropriate management can fulfill the requirements
for speed and high standards of an integrated quality system in a
University Hospital with high complexity. In near future routine coagulation tests will be integrated on the system.
Figure 1
Turnaround time of a sample from admission in the lab to release on
the lab computer. The continuous line represents the cumulative
percentage of the samples processed by time and the dotted line the
number of samples processed by time.
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P158
Total automation of peripheral blood cell analysis in a University
Hospital can provide rapid and high quality results to specialized
departments and avoid the need of satellite point-of-care
laboratories
Tichelli A., Rovó A., Schellhorn R., Marbet G., Meyer-Monard S.,
Arber C., Medinger M., Tsakiris D., Freidank H., Gratwohl A. (Basel)
A hematology laboratory of a University Hospital with diverse high
performance specialties requires an efficient, rapid and high quality
system for the routine analysis of peripheral blood counts. However,
speed and high quality results often seem incompatible. Implementation of point-of-care satellite laboratories in emergency departments
and hematology-oncology units appears attractive but is split from
integrative quality mechanisms. Hence, point-of-care testing provides
only simple results frequently with lower quality. In contrast, central-
A hook in the ferritin measurement in patients with
hemophagocytic syndromes
Keller P., Aregger F., Wermuth B., Lämmle B. (Bern)
Extensively increased serum ferritin levels are a hallmark of hemophagocytic syndromes. However, most commercially available ferritin
assays are optimized to rapidly detect low ferritin levels in the setting
of iron deficiency. We report on two patients with highly active hemophagocytic syndrome and erroneously normal ferritin levels. Patient A
was initially diagnosed with hemophagocytosis because of greatly
increased ferritin levels. When a high grade non-Hodgkin lymphoma
was found and successfully treated, symptoms resolved and ferritin
normalized. Four month later, the patient presented with symptoms
similar to the initial presentation. However, ferritin was only 270
[mikro]g/l. After talking to the laboratory, the serum was diluted,
remeasured and the result corrected to 598’000 [mikro]g/l. In patient
B, the treating physician suspected a hemophagocytic syndrome, but
serum ferritin was only 146 [mikro]g/l. We again informed the laboratory. After remeasuring ferritin using serum dilutions, the ferritin value
was corrected to 4225 [mikro]g/l. Many automated ferritin assays are
variants of the classical sandwich-ELISA. A solid phase-immobilized
anti-ferritin antibody captures the antigen from the test serum. Simul-
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taneously or timely delayed, but without prior washing, a second,
labeled anti-ferritin antibody is added. In a washing step, all labeled
antibody which is not bound to the solid phase through the first antibody and the antigen, is washed away. Finally, chemiluminescence or
an enzyme reaction on the detecting antibody reflects the amount of
bound antigen. Automated immunoassay systems are often not
designed to include a washing step before adding the second antibody. With very high excess of antigen, the capturing antibody is
saturated and most labeled detecting antibody is bound to free ferritin in the serum and will be lost with the final washing step, leading
to erroneously low or even normal ferritin values. This phenomenon
was first described by Miles et al. in 1974 with an immunoradiometric
assay. Today known as “Hook-effect”, it imposes a potentially dangerous problem in many immunoassays in the clinical laboratory.
Clinicians have to be aware of the possibility of erroneously low ferritin results in the diagnostic work-up of hemophagocytic syndromes.
If hemophagocytic syndrome is suspected, the laboratory has to be
informed and the measurement must be repeated with appropriately
diluted sera.
P160
Citrate toxicity in healthy donors for allogeneic peripheral
blood stem cell (PBSC) donation
Sigle J., Stern M., Infanti L., Halter J., Gähler A., Buser A.,
Gratwohl A. (Basel)
Objective: Citrate toxicity is the most common adverse event of
apheresis. Intravenous (iv) Ca-supplementation significantly reduces
its incidence. A Ca supplementation rate >0.5 mg Ca/ml ACD has
been proposed. We evaluated incidence and severity of citrate related
side effects and analysed contributing factors in donors undergoing
PBSC apheresis for allogeneic HSCT at our institution.
Methods: We analysed 68 collection procedures between October
2003 and October 2007 involving 53 donors (24 male, 29 female;
median age 49 years). All donors received iv Ca-supplementation.
Side effects were graded as mild (paraesthesia/flushing), moderate
(nausea/vomiting) or severe (tetany/seizure).
Results: Citrate toxicity occurred in 40/68 procedures (59%), 37 mild,
3 moderate. In univariate analysis, side effects were more frequent in
females (76% vs 37% in males, p = 0.001). Patients suffering from
side effects had a smaller body surface area (BSA, median 1.69 vs
1.94 m2, p <0.001) and smaller apheresis flow volume per minute
(53.2 vs 61.4 ml/min, p = 0.001). After normalization to BSA, quantity
of citrate infused (55 vs 54 mg/min/m2, p = 0.89) and initial calcium
infusion rate (1.21 vs 1.12 mg/min/m2, p = 0.26) were not associated
with side effects. Baseline albumin-adjusted serum calcium and
donor age were not associated with side effects. Patients receiving
calcium substitution at an initial rate of 0.5 mg Ca/ml ACD or higher
showed side effects at a comparable frequency to those receiving
lower dose Ca supplementation (57% vs 62%, respectively, p = 0.87).
In multivariate analysis, only female sex remained associated with
occurrence of side effects (OR vs males 4.67, 95% CI 1.47–14.9,
p = 0.009). Within the groups of female and male donors, those with
small BSA (below median) showed comparable rates of side effects
to those with large BSA, confirming the results of multivariate analysis
and suggesting that the increase in side effects in small BSA donors
was mainly due to a high frequency of females.
Conclusion: Despite routine intravenous Ca-supplementation,
citrate-related side effects were frequent in donors undergoing
apheresis for allogeneic HSC collection. Neither calcium supplementation rate, citrate infusion rate, nor their ratio predicted side effects.
Female gender emerged as main risk factor for citrate mediated
side effects. The pathophysiological mechanism for this observation
remains unclear.
Forum Med Suisse 2008;8:(Suppl. 40)
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P161
Febrile neutropenia and unexpected pathogens in bone
marrow smear... so what?
Schmidtko J., Solenthaler M., Garzoni C., Hahr M., Demarmels
Biasiutti F., Keller P., Alberio L., Lämmle B., Colucci G. (Bern)
A 24-year-old, one year ago kidney transplanted patient was hospitalized because of febrile neutropenia without focus. His recent medical
history was characterized by an aphthous ulcer in his mouth and a
progressive hyporegenerative anemia. The immunosuppressive therapy consisted of cyclosporine, mycophenolate mofetil and steroids.
History and clinical examination were unremarkable, in particular no
signs of sepsis were present. C-reactive-protein was 36 mg/l. Repetitive blood cultures and serologic testing for CMV, EBV, Parvovirus
B19 and HIV were negative. Urine culture remained sterile. A bone
marrow aspiration was performed and showed only in one out of 4
smears a region with dense accumulation of bacteria, microscopically
with different morphology (coccoid- and rod-like), plus monomorphic
unidentifiable cells that were possibly not bone marrow derived. An
empirical antibiotic therapy with cefepime and metronidazole was
started. The clinical situation remained stable. The finding of massive
bacterial invasion of the bone marrow was in contrast to the stable
clinical condition of the patient and a repeated bone marrow aspiration did not show any bacteria. Bone marrow cultures as well as an
eubacterial PCR using 16S rRNA amplification performed on bone
marrow material were negative. The bacterial distribution on the
smear was drop-like and the unidentifiable cells described were
compatible with enzymatic damaged bone-marrow cells. This finding
was interpreted as an external contamination during bone marrow
smear processing. Confronted with unexpected laboratory results,
a critical and comprehensive interpretation is needed. Pathologic
results have to be correlated with the clinical conditions. Contamination of diagnostic material should always be considered because of
its possible consequence related to unnecessary diagnostic procedures and therapy, as well as an increase in costs.
Figure 1
Dense accumulation of bacteria
Figure 2
Enlarged
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P162
Pharmacokinetics of dalteparin in prophylactic dosage in
patients with impaired renal function
Schmid P., Brodmann D., Fischer A.G., Wuillemin W.A. (Luzern)
Background: Low molecular weight heparins (LMWH) are safely used
for prophylaxis of venous thromboembolic disease. Impaired renal
function limits their use due to accumulation. The aim of this study
was to clarify the pharmacokinetics of dalteparin in patients with renal
insufficiency (RI).
Methods: Inpatients of a medical and surgical department with all
stages of RI (including peritoneal dialysis patients) were included into
a prospective observational cohort study. Glomerular filtration rate
(GFR) was estimated using plasma creatinine. Peak plasma anti-Xa
activity (AXa) was measured every 3 days and adjusted to applied
dalteparin dose and body weight. Data are shown as median
(interquartile range).
Results: Data of 42 patients (26 men) with all stages of RI could be
analyzed. Since there were only few peritoneal dialysis patients and
long term use of dalteparin, data of dialysis patients are shown separately. Median follow up of non dialysis patients (36 patients, 21 men)
was 10 days (range 4–20). Three groups were defined according to
renal function (A to C, see table 1 for definitions). The median daily
dalteparin dose was 74 (62–85) units / kg body weight without difference between the groups (p = 0.33). Adjusted anti-Xa values are
shown in table 1 and figure 1 for days 1 and/to 10. Relative increase
(i.e. accumulation) of adjusted anti-Xa from day 1 to 10 was not different between the groups (table 1). Median follow up of peritoneal
dialysis patients (CAPD, 6 patients, 5 men) was 5.5 days (range 4–19).
Median daily dalteparin dose was 58 (44–69) units / kg body weight.
Adjusted anti-Xa values are shown in figure 1. They were at day 4 for
patients with CAPD 5.9 x10-3 (4.8–6.4) compared with patients without RI 3.9 x10-3 (2.9–4.6; n = 0.008). Relative increase from day 1 to
4 was 17.5% (4 to 45) for CAPD, and 3.5% (–19 to 27; p = 0.48) for
patients without RI, respectively. However, there were 2 patients up
to 10 days and one patient up to 19 days with CAPD without signs of
clinically significant accumulation.
Conclusion: The use of dalteparin in prophylactic dosage showed
no clinically significant accumulation even in patients with severely
impaired renal function during median follow up of 10 days (range
4–20). Data showed that dalteparin may be suitable even in peritoneal
dialysis patients, although further studies of long term application are
needed in this population.
Forum Med Suisse 2008;8:(Suppl. 40)
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P163
Monitoring thrombin generation by a newly developed
electrochemical method identifies patients at high risk for
recurrent venous thromboembolism
Thürlemann C., Demarmels Biasiutti F., Lämmle B., Alberio L. (Bern)
Background: Screening patients after a first VTE for thrombophilia is
common clinical practice in order to optimize the long-term treatment. Recently, G. Hron et al. (JAMA 2006;296:397) demonstrated
that measurement of thrombin generation (TG) identifies patients at
low risk for recurrent VTE. We have developed a Biosensor-System
determining TG by electrochemistry. With this system coagulation
can be activated either extrinsicly (test strips A) or intrinsicly (test
strips B). We aimed to investigate the relationship between our new
procedure and VTE recurrences.
Method: In a retrospective cohort study we recorded TG in plasma
samples of 75 patients who had suffered a first idiopathic VTE. Oral
anticoagulant therapy (OAT) was discontinued at least one month
(median 2 months, inter-quartile range 1.3–3.6 months) before
thrombophilia screening. Median follow-up was 9.0 years (iqr 7.4–
11.5 years). During this period 16 patients (21%) suffered recurrent
VTE at a median of 5.7 years (iqr 4.2–8.4 years) after cessation of
OAT. We investigated the following TG parameters with our electrochemical Biosensor-System: lag-time (t-lag), time to maximum slope
(tS-max), value of maximum slope (S-max), time to peak (t-max),
maximum electric current, i.e. peak height (I-max), and ratio I-max /
t-max (TG-rate).
Results: A combination of two TG parameters, ‘TG-rate’ (test strips
A) and ‘t-max’ (test strips B), allows to identify patients with high risk
for recurrent VTE. Among 7 patients whose plasma samples showed
a ‘TG-rate’ greater than 0.14 and a ‘t-max’ shorter than 515 seconds,
6 (86%) suffered recurrent VTE versus 10 (15%) out of the remaining
68 patients (P <0.001).
Conclusions: Our Biosensor-System recording thrombin generation
by electrochemistry allows to identify patients at high risk for recurrent VTE.
P164
Table 1
Figure 1
Adjusted peak anti-Xa activity (AXa) for days 1 to 10
Stored erythrocytes have less capacity than normal
erythrocytes to support primary hemostasis
Zehnder L., Schulzki Th., Hayes J., Reinhart W.H. (Chur, Davos)
Background: Primary hemostasis after vessel injury is mediated
by platelet aggregation. Red blood cells (RBCs) are involved in this
process by pushing platelets towards the vessel wall during flow and
allow platelet adhesion. We hypothesized that stored RBCs could
have less capacity to support primary hemostasis by this way.
Methods: RBC units from 17 healthy volunteers were used. After 45
days of storage at 4°C, fresh citrated blood was taken again from the
same donors. Platelet-rich plasma (Platelet count 178 ± 40x103/µ-l)
was prepared, in which RBCs were resuspended with a constant
hematocrit (40%), but changing fractions of stored versus fresh autologous RBCs (0, 25, 50, 75, and 100%, respectively). A platelet function analyser PFA-100® was used to measure primary hemostasis.
This instrument closely simulates in vivo conditions with blood flowing at high shear rates through a membrane pore, which is coated
with collagen and either epinephrine (EPI) or ADP. Platelets, which are
pushed towards the wall by RBCs, adhere, aggregate, and form an
occluding plug, which stops blood flow and is measured as closure
time (CT).
Results: With increasing fractions of stored blood, the CT increased.
CT-EPI was 121 ± 17s for 100% fresh and 0% stored RBCs, 129 ±
32s for 25% stored RBCs, 164 ± 45s for 50%, (p <0.0001 compared
with 0% stored RBCs; ANOVA), 214 ± 54s for 75% (p <0.0001), and
273 ± 36s for 100% stored RBCs (p <0.0001). For CT-ADP the values
were 91 ± 22s, 95 ± 12s, 101 ± 13s, 124 ± 44s (p = 0.004), and 191 ±
72 s (p <0.0001) for 0. 25, 50, 75, and 100% stored RBCs, respectively.
Conclusions: Stored RBCs have less capacity than normal RBCs
to support primary hemostasis by platelet aggregation, suggesting a
decreased capacity of stored RBCs to bring platelets into close
contact with the wall to which they adhere. This mechanism may
contribute to sustained bleeding seen after mass transfusion.
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Forum Med Suisse 2008;8:(Suppl. 40)
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P165
P166
Efficacy of lower dose recombinant factor VIIa for massive
bleeding in off-label use
Schmid P., Lämmle B., Alberio L. (Bern)
Background: Recombinant factor VIIa is increasingly used for uncontrolled bleeding in patients without a pre-existing haemostatic disorder (off-label use). There is no clear evidence of the benefits of this
practice. Furthermore, the minimal effective dosage is not clear yet.
In order to optimize the use of rFVIIa at our institution we suggest to
administer 60 mcg/kg body weight for controlling massive bleeding
in off-label use.
Methods: Prospective cohort study collecting data of all patients
treated with rFVIIa in 2005 and 2006. Statistical analysis was done
with MedCalc. Values are given as median (interquartile range).
Results: Fifty-seven patients received rFVIIa off-label (total dose
286.6 mg). Clinical categories were: surgery 35%, obstetrics 23%,
trauma 21%, medicine 9% (unknown 12%). The administered single
dose was 64 (56–74) mcg/kg. The majority of the patients (82%)
received rFVIIa once, 18% twice. Severe haemorrhage was documented before rVIIa administration: estimated bleeding rate 850
(308–2500) mL/h, volume replacement with 4.0 (3.0–5.5) L crystalloids
and/or colloids, 10.5 (6–16.5) units packed red blood cells (RBC) and
8 (4–14) units fresh frozen plasma. According to the treating physicians a bleeding rate reduction was observed in 86% of the patients
and a quantitative estimate of the bleeding rate showed a significant
reduction (p = 0.002; figure 1). Transfused packed RBC significantly
decreased, as well (p <0.001; figure 2). Median fibrinogen at time of
rFVIIa administration was 1.30 (0.75–1.85) g/L; response to treatment
was similar in both patient groups with fibrinogen lower or higher than
1 g/L. Interestingly, there was a clear trend for better treatment
response if tranexamic acid was given in addition to rFVIIa. There
was only one venous thrombo-embolic complication reported (patient
without tranexamic acid). Eight patients (14%) died during the first
24 h: 40% among medical, 25% among trauma, none among surgical
and obstetrical patients.
Conclusion: A single injection of 60 mcg/kg rFVIIa, a lower dosage
than usually suggested, is efficacious in controlling massive bleeding
in off-label use. Our data show that rFVIIa is haemostically active
even at low fibrinogen levels. Additional data are required to confirm
the beneficial effect of co-administering tranexamic acid.
Recombinant human factor VIIa modulates endothelial
thromboresistance in vitro
Madon J., Ruf W., Leikauf M.S., Valsami S., Fehr J., Asmis L.M.
(Zürich, La Jolla)
Background: The hemostatic agent recombinant human FVIIa
(rhFVIIa) when used at pharmacologic doses is believed to interact
with TF on the surface of target cells such as activated platelets or
subendothelial TF+ cells at sites of vascular injury. We hypothesize
that in the presence of an inflammatory stimulus endothelial cells
express functional TF, which may interact with rhFVIIa. It is the aim
of our study to investigate functional TF expression in human
endothelial cells in vitro in response to short and long term exposure
to rhFVIIa in the presence of an inflammatory stimulus.
Materials and methods: Human umbilical vein endothelial cells
(HUVEC) were incubated with pharmacologic concentrations of
rhFVIIa (3 and 15 mg/ml) short term (1 hour) or long term (20 hours) in
the absence or presence of TNFa (10–100 ng/ml). Tissue factor activity of adherent cells was analyzed using a FVII- and FX-dependent,
commercial coagulation assay using a FXa-specific substrate. Tissue
factor protein on the cell surface and in the whole cell were investigated by flow cytometry and Western blotting, respectively. TF gene
expression was analyzed by real time PCR. A mixture of TF-specific
antibodies that inhibit rhFVIIa binding was utilized to assess specificity.
Results: Basal expression of TF activity in HUVEC is at the limit of
detectability. TNFa induced an approximately 10-fold increase in TF
activity. rhVIIa induced a 15–30% reduction of TF activity in shortterm and 40–50% in long-term experiments. A dose-response effect
was observed in short-term but not in long-term experiments where
both doses inhibited TF expression to a similar extent. The TNFainduced increase of TF activity could be blocked by approximately
95% by antibodies known to block TF-rhFVIIa interaction.
Conclusions: In the presence of an inflammatory stimulus cultured
endothelial cells in vitro express tissue factor activity that can be
suppressed by specific antibodies. Pharmacologic doses of rhFVIIa
reduce functional TF activity thereby modulating endothelial thromboresistance. The mechanisms underlying this effect are under
current investigation.
Figure 1
Bleeding rate before and 30 min after rVIIa
P167
Figure 2
Packed RBC before and after rVIIa
Transfusion efficacy of ABO major-mismatched platelets
in children is inferior to ABO-identical platelets
Julmy F., Ammann R.A., Mansouri Taleghani B., Fontana S.,
Hirt A., Leibundgut K. (Bern)
Background: In contrast to transfusion of red blood cells, where
ABO-major compatibility is mandatory, this is not the case for
platelets.
Patients and methods: In a prospective study in thrombocytopenic
children we investigated the impact of providing either ABO-identical
or out-of-group single donor apheresis platelet concentrates (APCs)
by measuring the 1-hour percent platelet recovery (PPR1h). We
intended to prove the hypothesis, that there is a significant difference
in transfusion efficacy comparing ABO blood group identical with
ABO major-mismatched platelet transfusions. 400 APCs (median,
5/child, range, 1–68) were transfused to 50 children (29 girls, age
0.2–16.1 y). In case of major-mismatched transfusions from group A
donors, A antigen expression on platelet surface was measured by
flow cytometry in both the APC and in the recipient before and 1 hour
after transfusion. Linear mixed effect (LME) modeling was applied
for univariate and multivariate analyses. This parametrical method
accounts for the correlation among transfusions given to the same
patient.
Results: Transfusion efficacy of ABO major-mismatched APCs was
significantly inferior to ABO identical platelets as shown by univariate
LME analysis in table 1. Although transfusion efficacy was significantly influenced by other APC-related variables, major-mismatched
transfusions remained significantly inferior to identical ones also by
multivariate LME analysis (table 2). In case of major-mismatched
transfusions from A1 donors expressing A antigen on their platelets,
we showed by flow cytometry and fluorescent microscopy a rapid
clearance of these platelets from the circulation in group O and B
recipients. After major-mismatched transfusions of A2 platelets,
expressing no detectable A-antigen, and also after minor-mismatched
transfusions, the PPR1h did not differ from ABO-identical transfusions (median 36%, P = .58, and median 34%, P = .69, respectively).
POSTERS SSHé
POSTERS SGH
Conclusions: Major-mismatched platelet transfusions were significantly less efficient than ABO-identical transfusions. In children
requiring regular and continued platelet support, an ABO compatible
transfusion strategy should be the choice. In this context, transfusion
of major-mismatched A2 platelets was equivalent efficient as ABOidentical APCs, and this was also the case for minor-mismatched
(plasma incompatible) APCs, but in the latter there remains an inherent risk for hemolytic transfusion reactions.
Table 1
Forum Med Suisse 2008;8:(Suppl. 40)
74 S
P169
Erythrocyte storage in hypertonic (SAGM) or isotonic
(PAGGSM) conservation medium: Influence on cell properties
Zehnder L., Schulzki Th., Goede J.S., Hayes J., Reinhart W.H.
(Chur, Zürich, Davos)
Background and objectives: Red blood cell (RBC) storage for transfusion purposes leads to a time-dependent deterioration of cell properties (storage lesions). The aim of this study was to analyse the role of
either a hypertonic or isotonic additive preservation solution on such
parameters.
Materials and methods: RBC units were prepared from 20 blood
donors using either saline-adenin-glucose-mannitol (SAGM; 376
mosm/l) or phosphate-adenin-glucose-guanosin-saline-mannitol (PAGGSM; 285 mosm/l) as an additive solution. At the beginning (days 0–2)
and the end (days 42–44) of storage at 4 °C, RBC properties were
studied. The mean cellular volume (MCV) was calculated from the
microhematocrit, morphology was assessed on fixed RBCs, aggregability was tested by the sedimentation rate (ESR) in 3% dextran 70,
osmotic dependant RBC deformability by ektacytometry, and RBC
suspension viscosity with a Couette viscometer (Contraves LS-30).
Results: The MCV, measured in the native suspension by microhematocrit, increased from 87.6 ± 3.1 fl to 100.7 ± 4.3 fl in PAGGSM
and to 92.2 ± 2.5 fl in SAGM (p <0.001), after 42 days it was 95.8 ± 4.0
fl and 93.8 ± 3.9 fl, respectively. For both additives similar echinocytic
RBC shape transformations were observed after storage, and aggregability was decreased (ESR 44 ± 22 and 25 ± 17 mm/2h, p = 0.001).
Spontaneous hemolysis and osmotic fragility were less after storage in
PAGGSM than in SAGM. Ektacytometry showed a slight decrease of
osmotic dependant RBC deformability for both additives. After storage,
the viscosity of RBC units (Hct 61 ± 3%) and resuspensions of RBC in
fresh plasma (Hct 42 ± 2%) increased similarly.
Conclusions: The isotonic additive solution PAGGSM induced more
RBC swelling in the beginning and decreased spontaneous hemolysis
rate and osmotic fragility at the end of a 42-days storage than hypertonic SAGM. All other parameters such as echinocytosis, decreased
RBC deformability and aggregability and increased blood viscosity
were similar for both additive solutions and remain a major problem
of blood banking.
P170
Table 2
P168
WBC reduction of blood products may be associated with
a decreased incidence of allominunization
Koeppel R., Schanz U., Stussi G. (Zürich)
Alloimmunization to red blood cell (RBC) antigens is a common and
potentially serious clinical problem. It has been hypothesized that
white blood cell (WBC) reduction of blood products may reduce the
number of alloimmunizations. Therefore, we retrospectively analyzed
the the incidence of RBC antibodies (Ab) in the University hospital
Zürich over the last 33 years (1973–2006). RBC Ab were detected by
a 2 or 3 cell panel antibody screens (AS) and positive results were
further specified by additional RBC panels. During this time, a total of
378’785 AS were performed and 4097 patients had 5340 positive AS
(1.4%). The median age of the patients was 43 years (range 0–100)
and 66% were female. Antibodies were most commonly directed
against Rhesus (45%), Lewis (18%), and Kell (16%). The frequency
against Duffy, Kidd, Lutheran, MNS, and P blood group system was
below 10%. The most common Ab were anti-E (17%), anti-D (16%),
anti-K (16%), and anti-Lea (12%). Of the alloimmunized patients, 86%
had 1, 12% had 2 and 2% had 3 Ab. One patient had 10 alloantibodies. Females were more likely to have Ab against Rhesus and males
against Kell, Duffy, Lutheran, and P1. Since 1990, the number of
positive tests was increasing with a maximal incidence of 4.3%.
However, after 1999 the incidence of positive AS has decreased
rapidly to 1% coinciding with the introduction of general WBC reduction.
Globale Thrombusfestigkeit in vitro (Thromboelastometrie)
als Transfusionstrigger für die Thrombozytentransfusion bei
Patienten in Aplasie?
Schreiber A., Arber C., Buser A., Stern M., Marbet G.A., Gratwohl A.,
Tsakiris D.A. (Basel)
Thrombopenie ist eine obligate Nebenwirkung intensiver Chemotherapie. Zur Vorbeugung von Blutungskomplikationen werden bei aplastischen Patienten prophylaktische Thrombozytentransfusionen verabreicht. Der Richtwert für die Transfusionsindikation (5, 10 oder 20 G/L),
sog. «Transfusionstrigger», ist immer noch Diskussionspunkt. Zusätzliche Begleitfaktoren (Fieber, DIC, u.a.) werden dabei arbiträr berücksichtigt. Ein besserer Test als die Thrombozytenzahl wäre wertvoll. Die
Thromboelastometrie – eine Methode zur Evaluation der globalen
Hämostase im Vollblut – wird als möglicher Test diskutiert. Wir untersuchten, ob sie sensitiv genug ist, Veränderungen vor und nach prophylaktischen Thrombozytentransfusionen zu erfassen.
Methoden: Thromboelastometrie (RoTEM) wurde im Citrat-Vollblut
(0,11M, 1:9 v/v) vor und 1h nach Transfusion eines EinzelspenderThrombozytenkonzentrats bei 23 Patienten nach Stammzelltransplantation evaluiert (Alter 51 ± 15, 6F, 17M). Der Tranfusionseffekt wurde
mittels des “corrected count increment, CCI” nach 1h bewertet. CFT
(clot forming time) und MCF (maximal clot formation) wurden nach
Stimulation mit einem Phospholipid-Reagens für die extrinsische (ex)
oder intrinsische (in) Gerinnung erfasst. Zusätzlich wurde die prokoagulatorische Mikropartikelaktivität als Thrombingenerierung im Plasma
bestimmt (Zymuphen-Test).
Resultate: CFTex als Ausdruck schnellerer hämostatischer Reaktion
wird im individuellen Patienten signifikant kürzer unmittelbar nach
Transfusion (299 ± 217 vs 185 ± 120 s, p <0,001). MCFex, als Ausdruck
maximaler Gerinnselbildung steigt ebenfalls signifikant an (34 ± 7 vs
43 ± 6 mm, p <0,001). CFTin und MCFin verändern sich in der gleichen
Richtung. Die Veränderung am MCF bleibt sowohl bei adäquatem
(>7,5) wie auch bei ungenügendem CCI (<7,5) signifikant, wobei stärker
bei gutem CCI. Delta_MCF aber nicht Delta_CFT korreliert signifikant
mit CCI (Rho = 0,64, p <0,01). Die Mikropartikelaktivität im Plasma hat
sich nach der Transfusion durchschnittlich um 47% erhöht (p <0,01),
statistisch signifikant nur beim hohen CCI (vor 5 ± 8 nM, nach 9 ± 10
nM, p = 0,01).
Schlussfolgerung: Diese Daten zeigen, dass die in vitro Thrombusfestigkeit mit der Thrombozytenzahl und dem CCI korreliert. Dies dient
als Ausgangsbasis den Wert der Thromboelastometrie als Transfusionstrigger für die Thrombozytentransfusion in klinischen Studien zu untersuchen.
POSTERS SPSG
POSTERS SFGG
P171
Social Background and Delirium Syndrome as early markers
of prolonged hospital stays in older inpatients with dementia
Lang P.O., Hermann F.R. (Genève)
Objectives: To identify early markers of prolonged hospital stays in
elderly patients with dementia in acute hospitals.
Design: A prospective and multicentre study (9 hospitals in France).
Particpants: 468 medical inpatients with dementia at baseline and
hospitalized through an emergency department were considered.
Method: Data used in a logistic regression were obtained through a
CGA conducted in the first week of hospitalization. The center effect
was considered as a random effect. Prolonged hospital stay was
defined with a threshold adjusted for DRG according to the French
classification.
Results: Two-thirds of subjects in the cohort analyzed were women,
with a mean age of 86. Over 65% of subjects lived at home and 75%
reported that they had a caregiver. Formal and informal caregivers
were presents whatever the dependency level observed. Of the informal caregivers interviewed, 77% declared to feel severe burden.
Thirty-one stays (7%) were prolonged beyond the f-DRG-adjusted
limit. No demographic variables seemed to influence the length of
stay. In multifactorial analysis, a diagnosis of delirium syndrome in the
first week of hospitalization (odds ratio (OR) = 1.81) was identified as
an early marker of prolonged hospital stays. In addition, social background data seemed to have a predictive value. The disclosure of a
severe burden according to the Zarit’s Burden Inventory (OR = 1.24)
and, a bad social life in informal caregivers (OR = 0.92), corresponding with social score of the Duke’s Health Profile, were likewise
associated with prolonged stays. Dependence and cognitive impairment levels were not identified as risk factors.
Conclusion: The observed results suggest that, in a preventive
approach of prolonged hospital stays, interventions of multidisciplinary networks are needed. Already, before hospitalization, home
health care programs aimed at detecting crisis factors and establishing early prevention of crisis states may improve unfavourable medical and social condition and reduce unplanned hospitalization. In
hospital setting, a specialized ward dedicated to demented patients
with somatic diseases where management of BPSD and/or delirium
is delivered by cooperating geriatrician and psychiatrist in association
with an early social and psychological support appears to be an
interesting preventive approach to avoid prolonged hospital stays in
this population.
P172
Barriers to and facilitators of colorectal cancer screening
in the elderly: a systematic review
Guessous I., Dash C. (Lausanne, Atlanta)
Background: Although there have been many studies evaluating
factors related to CRC screening, little is known about the barriers to,
and facilitators of, CRC screening participation among the elderly.
Methods: We conducted a systematic literature search in Medline
(1995 to March 2007) and scanned reference lists of reviews to identify studies that reported barriers to or facilitators of CRC screening
uptake, compliance or adherence specifically for the elderly population (65 and older). We extracted information on study interventions,
baseline characteristics, and assessed whether barriers and facilitators were related to subjects, healthcare provider, policy or screening
tests.
Results: 74 studies met the eligibility criteria. The majority (65/74)
reported subject specific barriers/facilitators, 17 reported
barriers/facilitators related to healthcare providers, 26 reported policy
barriers/facilitators, and six reported screening test specific barriers.
Low level of education (13/65 citations), black race (9/65), low socioeconomic status (9/65), female gender (8/65), and lack of insurance
(8/65) were the most frequently reported barriers related to elderly.
Twelve studies reported co-morbidities and perceived health status
as “good” as barriers to CRC screening in the elderly. Being married
or living with partner was the most frequently reported facilitators
related to elderly (8/65). Having a family history of CRC and a positive
attitude towards screening were also reported as facilitators. Most
cited barriers related to healthcare provider were physician recommends/believes in stopping screening at a certain age (9/17) and lack
of screening recommendation by physician (8/17). Physician’s beliefs
about whether screening is beneficial, higher proportion of primary
care providers in county (vs. specialists) were reported as barriers as
well. Lack of health care insurance coverage (8/26), rural residence
Forum Med Suisse 2008;8:(Suppl. 40)
75 S
(5/26), and dual coverage with Medicare and Medicaid (3/26) were
the most frequent reported barriers related to finances, access and
policy, whereas 2001 Medicare coverage of colonoscopy (5/26) and
having a usual source of care (5/26) were consistently reported as a
facilitators.
Conclusions: Numerous subject, healthcare provider, policy and test
specific barriers to and facilitators of CRC screening in the elderly
were identified. They might be used to better tailor interventions to
increase CRC screening participation rates in the elderly.
P173
Stratégies pour bien vieillir. Le défi gérontagogique
Rapin C.H., Ruchat M. (Sion et Genève, Genève)
A l’ensemble des défis contemporains qu’entraîne l’allongement de
l’espérance de vie en bonne santé, les auteurs proposent d’ajouter le
«pari gérontagogique». Les concepts du «Bien vieillir» et de «Value
based medicine» (Rapin, 1999) se voient ici prolongés par celui de
«gérontagogie» définit comme l’art de bien conduire sa vieillesse.
Sous ce néologisme, les auteurs exposent leur hypothèse de la formation des aînées et des aînés comme un déterminant de bonne
santé. Ils s’appuient sur l’expérience d’un programme original de
formation transdisciplinaire, alliant notamment sciences médicales
et sciences de l’éducation. Cette formation nouvelle possède trois
caractéristiques essentielles: 1/ le travail en synergie des étudiantes
et étudiants de plusieurs générations, 2/ la recherche de solutions
aux problèmes de la vieillesse (solitude, manque d’autonomie, douleur, maltraitance, etc.) dans le respect des valeurs de tous les
acteurs du champ du vieillissement, et 3/le changement dans les
représentations et les pratiques sociales opéré par la formation. Cette
formation certificative est une des formes de l’«empowerment»
faisant partie des stratégies pour «Bien vieillir».
P174
Residents’ difficulties vis-à-vis end-of-life care
Luthy C., Cedraschi C., Pautex S., Rentsch D., Piguet V., Allaz A.F.
(Geneva)
Background: Residents in training are first-line physicians in hospital
settings and they are in the process of developing knowledge and
mastering clinical skills. They have to confront complex tasks calling
upon their personal background, their professional identity, their
relationships with the patients, and with the members of the multidisciplinary team.
Objective: In order to improve the clinical guidance of residents
faced with terminally ill hospitalized patients, we investigated the
difficulties perceived by internal medicine residents in end-of-life
care.
Methods: 24 consecutive first-year residents in internal medicine
were presented with the following question in a written form: “In your
experience, what are the difficulties and concerns you identify in the
management of a terminally ill patient hospitalised for end-of-life
care?”. A qualitative procedure was applied. The answers were
submitted to content analysis performed by three independent
researchers. Inter-rater agreement was high (kappa coefficient =
0.88); disagreements were solved by consensus.
Results: Physicians’ characteristics: female 37%; mean age 28 ± 2.2
years, mean duration of postgraduate training 2.5 ± 1.3 years. Total
number of answers: 82; the average number of responses/resident
was 3.3 ± 1.3. As 31 out of 82 answers included more than one category of difficulties/concerns regrouped into the same sentence, they
were split for analysis, yielding a total of 114 analyzed items. Eight
categories were obtained, encompassing the difficulties/concerns
expressed by the residents: provide adequate explanations; face
one’s limits/the limitations of medicine; decipher the queries; avoid
flight; manage provision of time; have sufficient theoretical knowledge; avoid false reassurance; and be able to help in spite of everything.
Conclusions: These results stress that residents identify the complexity of the dimensions of care in terminally ill patients early or very
early in their training. These junior residents’ responses point to the
right distance in-between getting involved and preserving oneself as
a dimension of major importance. Issues related to proximity with the
patient facing a terminal illness seem to be (at least) two-sided, inbetween avoidance or even flight – too far – and bonding or fusion –
too close.
POSTERS SPSG
POSTERS SFGG
P175
Lutter contre la sous-notification des effets indésirables
cutanés en gériatrie: un projet de pharmacovigilance proactive
Villaneau D., Trellu L., Plachta O., Vogt-Ferrier N. (Genève,
Swissmedic-Berne)
La pharmacovigilance suisse repose sur la notification spontanée
des effets indésirables médicamenteux à Swissmedic*. Postulant une
sous-notification des réactions cutanées induites par les médicaments (toxidermies) en gériatrie, nous avons instauré en 2007 une
recherche active des cas survenant dans un hôpital universitaire de
soins gériatriques aigus. De fait, en 2007, 60% des 50 déclarations
de pharmacovigilance provenant de cet hôpital ont concerné des
toxidermies.
Bilan: 5 réactions SEVERES: – 2 DRESS (Drug Rash with Eosinophilia
and Systemic Symptoms). Imputés: cyanocobalamine/picosulfate;
clopidogrel
– 2 érythèmes polymorphes, un buccal stoppé à un stade débutant
(polymédication), un périorbitaire lisinopril/métoprolol/penicilline
G/norfloxacine
– possible Pustulose Exanthématique Aiguë Généralisée (PEAG)
amoxicilline/ac.clavulanique)
Aucun érythème polymorphe majeur, ou Nécrolyse Epidermique
Toxique (NET) de type syndrome de Stevens-Johnson (SJS) ou Lyell
n’ont été signalés.
14 réactions BENIGNES:
– 11 exanthèmes maculo-papuleux allergiques. Imputés: antibiotiques 5/11
– 2 urticaires. Imputés: galantamine/picosulfate; gabapentine/galantamine
– 1 érythème pigmenté fixe: oxycodone
10 AUTRES types de réactions:
– 1 phototoxicité: co-trimoxazole
– 4 vasculites leucocytoclasiques confirmées par biopsie (purpura
vasculaire). Imputés: losartan/amoxicilline/enoxaparine; spironolactone; torasémide/fluoxétine/esoméprazole/enoxaparine;
co-trimoxazole
– 2 prurits simples. Imputés: buprénorphine; tamoxifène
– 1 érythrodermie fugace sous répaglinide/digoxine
– 2 importants hématomes aux sites d’injection d’enoxaparine
– 1 dermite de contact à un patch de fentanyl
Discussion: 87% des lettres de sortie mentionnaient ces évènements
cutanés ainsi que les médicaments imputés, témoignant d’une bonne
documentation des réactions en fin d’hospitalisation. Par contre, au
cours de leur séjour deux patients ont été réexposés (un lors d’un
transfert) aux molécules imputées lors de la 1ere toxidermie. Ceci
souligne la rigueur nécessaire dans le dossier patient pour de tels
évènements.
Conclusion: Une recherche active des cas de toxidermie en gériatrie
permet de lutter contre la banalisation de cette iatrogénie. La documentation immédiate des incidents dans le dossier de prescription
permettrait d’éviter des ré-expositions accidentelles.
* Swissmedic, Institut suisse des produits thérapeutiques.
P176
Prevention of adverse drug reactions in a geriatric nursing
home
Penasa U., Jäger M., Lutters M. (Baden)
Introduction: Older patients are more prone to adverse drug reactions than younger people because of polypharmacy, multimorbidities, renal dysfunction and increased sensitivity to side effects.
Underlying diseases like dementia or depression make diagnosis of
adverse drug reaction difficult.
Objectives: – prevent and detect medication related problems in a
nursing home, – in details: develop a table on relevant adverse drug
reactions of all drugs used in the nursing home including recommendations for control of laboratory parameters.
Methods: We focussed our research on cardiovascular, psychiatric
and respiratory drugs used in the nursing home. Relevant side
effects, recommended control parameters and pharmacokinetic data
(Q0, Vd, t1 ) were searched in the following manuals respectively inter⁄
net sites: 2– Arzneimittelkompendium der Schweiz 2007, – www.dosing.de, – Berthold H. Klinikleitfaden Arzneimitteltherapie 1999, Gustav
Fischer Verlag Stuttgart, – Therapie-Profile für die Kitteltasche 2003,
WVG Stuttgart. Based on these data we created a table with relevant
and frequent adverse drug reactions and recommendations for monitoring of side effects, especially laboratory parameters.
Forum Med Suisse 2008;8:(Suppl. 40)
76 S
Results/Discussion: Drugs eliminated mainly by the kidneys
(Q0 <0.5) were marked. Interactions were not considered because
there are so many and they don’t fit in a table.Instead, we provided
a table with substrates, inductor and inhibitors of cytochrome P450.
Information on frequency of laboratory controls was sparse, as well
as information on monitoring of rare but serious side effects like
hepatitis. Most drugs require a careful dose titration, for example
beta blockers, antidepressants, antipsychotic, antiepileptic, and antiParkinson drugs.
Conclusion: Many adverse drug reactions in elderly patients may be
avoided or early detected by carefully dosing, consideration of the
kidney function and regularly monitoring of known side effects.
P177
Prévalence, sévérité et étiologie des troubles cognitifs
en EMS
Joray S., Bourquin I., Ebbing K. (Lausanne)
Il existe peu de données épidémiologiques sur les troubles cognitifs
et les démences au sein de populations vivant en EMS (Etablissement Médico-Social). Selon notre expérience de médecins gériatre et
psychogériatre travaillant en EMS, les pathologies démentielles sont
extrêmement fréquentes et représentent le premier motif d’institutionnalisation.
Objectifs: évaluer au sein d’une population vivant en EMS, la prévalence des troubles cognitifs, leur sévérité et leur étiologie, ce de
manière systématique et sur une durée de 6 mois.
Population et méthodes: les personnes vivant dans un EMS de 79
lits gériatriques en ville de Lausanne ont été évaluées par un examen
clinique ciblé, comprenant un status neurologique, un status mental
ainsi qu’une évaluation psychiatrique lors d’antécédents psychiatriques. Une neuropsychologue a administré un MMSE (Mini Mental
Sate Examination) à chacun des résidents et établi une échelle CDR
(Clinical Dementia Rating) en fonction d’informations recueillies
auprès du personnel soignant. Tous les documents médicaux antérieurs en relation avec une problématique cognitive ont été recherchés, notamment les examens neuropsychologiques et neuroradiologiques. Sur la base de l’évaluation clinique et des examens
complémentaires, un diagnostic a été posé.
Résultats: au total 82 résidents ont été évalués sur une période de
6 mois. Leur âge moyen était de 85,8 ± 8,3 ans avec 78% de femmes. Le score MMSE moyen était de 12,7 ± 8,4. Plus de la moitié
(n = 43) présentait une démence sévère CDR 3, 13,4% (n = 11) une
démence modérée CDR 2 et 26,8% (n = 22) une démence légère
CDR 1. Parmi les 6 personnes avec un CDR à 0.5, seules 2 (2,4%)
étaient considérées sans trouble cognitif. Le diagnostic le plus fréquent est celui de probable maladie d’Alzheimer (n = 49, 59,6%), suivi
des démences vasculaires et mixtes (n = 14, 17,0%), des syndromes
Parkinson-démences, puis des étiologies psychiatriques, alcooliques
et finalement des causes rares.
Conclusion: sur l’ensemble d’une population vivant en long séjour
gériatrique, la presque totalité présente des troubles cognitifs. Pour
la plupart, un diagnostic de pathologie démentielle a été retenu, de
stade avancé dans la moitié des cas, le plus souvent une maladie
d’Alzheimer. Les démences de par leur fréquence et leur impact
fonctionnel sévère sont certainement le principal motif d’admission
en EMS.
SESSION INTERACTIVE DES POSTERS SPTC
INTERAKTIVE POSTERSESSION SKPT
Forum Med Suisse 2008;8:(Suppl. 40)
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P178
P180
Rôle du médicament dans les admissions aux soins intensifs
Besson M., Segala S., Chabert J., Piguet V., Chevrolet J.C.,
Dayer P., Desmeules J. (Genève)
Contexte: les effets indésirables médicamenteux (EIM) représentent
jusqu’à 6% des admissions hospitalières et sont évitables dans les
2/3 des cas. On ne dispose que d’une littérature ancienne et peu
étayée sur leur rôle dans les admissions aux soins intensifs (SI).
But: évaluer la part des EIM dans l’admission aux SI et leur caractère
évitable.
Méthode: étude pilote, prospective. Pendant 1 mois, les jours ouvrables, les admissions dans le service des SI aux Hôpitaux Universitaires de Genève ont été analysées. Les motifs de transferts, les données démographiques, médicales et médicamenteuses ont été
recueillies systématiquement. L’imputabilité de l’EIM dans l’admission
aux SI a été posée par une pharmacologue clinique. Celle-ci déterminait également le degré d’évitabilité.
Résultats: 174 admissions (2/3 des admissions totales) ont été analysées, sur lesquelles on dénombre 111 hommes (64%) et 101
patients (58%) de plus de 65 ans. Les patients provenaient de la
communauté (n = 102), des unités de soins (n = 32) et du post-opératoire (n = 34). Les EIM ont joué un rôle dans 20% des admissions
(34/174). 3 des ces 34 cas (9%) était des tentamen, dont l’imputabilité médicamenteuse était certaine. L’imputabilité de l’EIM était probable dans 20% des cas (7/34) et ces EIM évitables dans 40% des
cas (3/7). Pour les 18 cas restant (70%), l’imputabilité était possible.
Les principaux effets indésirables étaient cardiovasculaires et hémorragiques. Les médicaments les plus fréquemment en cause étaient
les [beta]-bloquants, les antiaggrégants plaquettaires et les corticoïdes. La polymédication (>3 médicaments), l’insuffisance rénale
(Clcréat <50 ml/min) et le sexe féminin sont retrouvés comme facteurs de risque d’être admis aux SI pour un EIM.
Conclusion: les EIM représentent une cause importante d’admission
aux SI et une partie d’entre eux sont évitables. Une étude de plus
grande envergure, avec évaluateurs indépendant, devrait permettre
de confirmer ces résultats, de préciser le coût humain mais aussi
financier de ces EIM et pour ceux qui sont évitables d’envisager des
stratégies de prévention.
Amélioration continue de la prescription en gériatrie
Vogt-Ferrier N., Parel Y., Villaneau D., Allali D., Gschwind L.,
Bouchoud Bertholet L., Ciubotariu M., Dayer P. (Genève)
Introduction: Les médicaments sont souvent source d’incidents
indésirables médicamenteux (IIM): effets indésirables, interactions
néfastes et problèmes liés à la prise en dehors des circonstances
prévues pour leur usage.
Objectif: Créer un outil d’assurance qualité pour identifier et quantifier les IIM. Fournir une image dynamique de la qualité de la prescription dans un hôpital gériatrique universitaire de soins aigus et définir
des priorités d’amélioration.
Méthode: La méthode, adaptée de protocoles éprouvés [1, 2],
repose sur une revue rétrospective d’un échantillon aléatoire de dossiers patients. On y recherche différents indicateurs, dont la présence
engendre une analyse plus fine afin d’identifier des IIM, un non-respect de recommandations de prescription ou d’administration.
Résultats: N = 50 dossiers, soit 11’811 doses de médicaments. 121
indicateurs d’IMM ont été détectés dont 78 (0,66 pour cent doses de
médicaments) étaient liés à un IIM (augmentation de la créatininémie
(15,4%), somnolence (10,3%)). Parmi les critères de non-conformité,
53 indicateurs ont été détectés dont 38 (0,32 %) étaient des prescriptions non conformes aux recommandations (IPP sans réelle nécessité
(42,1%)). Parmi les 43 indicateurs liés à l’administration détectés,
4 (0,03%) médicaments étaient utilisés sans respecter les modalités
d’administration (antibiotique iv alors que per os possible [100%]).
Discussion: L’analyse confirme la fréquente iatrogénie décrite en
gériatrie (3). Le nombre d’IIM relevé dans notre étude (0.66%) est plus
élevé que dans une autre étude similaire (0,2%) (4). Le protocole a été
modifié afin d’affiner les critères concernant l’insuffisance rénale
aiguë. Certains critères américains (2), avérés peu pertinents, ont été
remplacés.
Conclusion: Dynamique et modulable, cet outil peut s’adapter à tout
environnement, est facile d’emploi et permet une surveillance qualité
continue. Il procure de précieuses indications sur les mesures d’amélioration à implémenter pour éviter les pratiques de prescription risquées.
Références: 1. Griffin, FA, Resar RK. IHI Global Trigger Tool for
Measuring Adverse Events. 2007 (disponible sur www.IHI.org)
2. Fick DM, et al, Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Arch Intern Med 2003;
163:2716-2724 3. Bases de la thérapeutique médicamenteuse, 16e
éd., 2005, 274–277. 4. Cohen MM, and al. J Qual Saf Health Care.
2005 Jun;14(3):169–74.
P179
The characteristics and relationship between the effect size and
the odds ratio
Curtin F., Schulz P. (Genève)
Background: In clinical trials and meta-analyses, the status of
responder or non-responder to a treatment is generally derived from a
clinical variable measuring efficacy on a continuous scale. In trials
and meta-analyses, the measurement expressed on a continuous
scale is often evaluated by the effect size (difference of means
divided by a standard deviation), whereas the binary variable corresponding to the responder status is assessed by the odds ratio (OR).
Objective: The relationships between the effects size for continuous
outcome and the measure of association for the derived binary variables, the OR, are analysed.
Results: The mathematics describing the statistical metrics, OR and
effect size, are presented and their mathematical relationship is
analysed. The cut-off point on the continuous scale which determines
the responder status plays a role in the mathematical relationship
between OR and effect size. The impact of the location of the cut-off
point on the continuous scale is analysed: the location of the cut-off
point vis-à-vis the distributions of the continuous variables corresponding to the experimental and control treatments is essential.
According to the location of the cut-off point, the OR can be maximised. The OR is maximal if the cut-off is located at a point equidistant from the means of the two distributions of the variables representing experimental and control treatments outcomes. The
dependence of the OR on the magnitude of the effect size as well as
on the location of the cut-off point has important consequences on
the analysis of results of clinical trials: by changing the definition of
responders, i.e. by changing the location of the cut-off point, one can
obtain different results in terms of OR.
Conclusion: The responder status must be defined before the results
of the trial are analysed and, to ensure transparency, the results
obtained in treatments groups measured on the continuous scale
must be presented along the results obtained with the binary variable
responder/non-responder.
P181
Assessment of potential drug-drug interactions at hospital
discharge
Bertoli R., Caronzolo D., Bissig M., Waldispühl B., Lozano Becerra
J.C., Odorico M., Pons M., Bernasconi E. (Lugano, Bellinzona)
Background: About 5% of all adverse drug reactions in hospitals are
caused by drug-drug interactions, the majority of which are avoidable. Up to 10% of all hospitalized patients have at least one adverse
drug reaction after discharge. Change of medication during hospital
stay and lack of therapeutic care after discharge are among the most
important risk factors for drug related problems. For the patients it is
therefore of great importance that discharge medication has the
lowest risk of potential drug-drug interactions and that doctors are
aware of possible, preventable, drug-related complications.
Aim: Evaluation of the prevalence of potential drug-drug interactions
and assessment of their clinical relevance in patient’s discharge medication in the medical ward of a community teaching hospital. The
clinically relevant information was reported to the treating physicians.
Methods: Prospective study of medication from 51 patients (200 at
the end of the study) at discharge from a medical ward. Prescribed
drugs were analysed for interactions using a commercially available
software (Pharmavista®). Two clinical pharmacists and a physician
assessed the clinical relevance of detected interactions, eliminated
those which were considered clinically not relevant and elaborated
recommendations for those considered clinically relevant.
Results: The mean age of the 51 patients studied so far (19 men,
32 women) was 68 years. At discharge, patients took an average of
7 different drugs. 67% of patients had at least one potential drugdrug interaction. In total, 105 potential drug-drug interactions were
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identified: 62 (59%) of minor severity, 34 (32%) of moderate severity
and 4 (4%) of major severity. Oral anticoagulation and acetylsalicylic
acid were the most frequently implicated drugs. 66% of the overall
detected interactions were considered clinical relevant and resulted
in a warning to the treating physician.
Conclusions: A computerised drug-drug interaction programme
(detection) together with clinical pharmacological experience (interpretation/evaluation) can be useful for decreasing the number of
potential harmful drug combinations. This approach may lead to an
improvement in the quality of prescription, preventing possible risks
and thus contributing to the patient’s safety.
P182
Tödliche Intoxikation mit Eibennadeln (Taxus baccata)
bei einer 44-jährigen Patientin
Berthold P., Mattes H., Stürer A., Neuhaus M., Plattner T.,
Brunner H.R., Beer H.J. (Baden, Zürich, Bern)
Hintergrund: Seit dem Altertum wird die Eibe zu Mord, Selbstmord
und Abtreibung missbraucht. Als immergrüner Nadelbaum wächst die
Eibe langsam, wird bis 1000 Jahre alt und 15 m hoch. Nadeln, Rinde
und Samen sind stark giftig, die roten Früchte nicht. Sie enthält ein
Alkaloidgemisch: Taxin B (30–40%), Taxin A (1,3%), Taxol,
Biflavonoide und cyanogene Glycoside. Taxin B ist kardiotoxisch,
hemmt den Na- und Ca-Transport in die Myokardzellen. Niedrige
Konzentrationen sind positiv ino- und chronotrop, höhere bewirken
einen AV-Block bis zur Asystolie. Taxin A ist auch hochdosiert
bradykardisierend. Taxol ist ein Mitosehemmer.
Fallbeschreibung: Eine 44-jährige Pat., wegen Depression in Psychiatrie hospitalisiert, nahm nach Selbststudium über Eibenintoxikationen im Internet eine Handvoll Eibennadeln in suizidaler Absicht ein.
Nach 2 h traten Schwindel, Nausea/Vomitus und eine progrediente
Bewusstseinstrübung sowie Kreislaufinstabilität auf, gefolgt von
wechselnder Vigilanz, Sehstörungen und Hypotonie. Im EKG polymorphe Breitkomplextachykardien, rasch wechselnd mit extremer
Bradykardie bis 20/Min. Nach Einlage einer Magensonde kam es
erneut zu Bradykardie und Kammerflimmern, welches zunächst erfolgreich defibrilliert wurde. Nach Intubation, Gabe von Mg und Noradrenalin Kreislaufstabilisierung, die Pupillen waren mydriatisch und
reaktionslos. Im Echo fand sich eine völlig asynchrone Herzaktion.
Nach erfolgter Magenspülung trat erneut eine Bradykardie auf,
gefolgt von einer Kammertachykardie, die trotz Defibrillation persistierte, in ein Kammerflimmern und dann in eine Asystolie überging,
die auf externes und internes Pacing refraktär war. Die Reanimation
wurde daraufhin (61⁄2 h nach Eintritt) abgebrochen.
Diskussion: 50–100 g Eibennadeln gelten als tödlich. Nach
Aufnahme zerkleinerter Eibennadeln treten Symptome wesentlich
schneller auf. Wichtig ist die primäre Giftelimination (Aktivkohle,
Magenspülung, evtl. Gastrokopie), eine spezifische Therapie ist nicht
bekannt. Es wurden Fälle mit massiv erhöhtem Digitalisspiegel
beschrieben (Kreuzreaktivität), anekdotisch war die Therapie mit
Digitalis-spez. AK erfolgreich (der Digitalisspiegel unserer Pat. war
<0,26 nmol/l). In einem weiteren Fall war eine Therapie mit Lidocain
erfolgreich.
Schlussfolgerung: Die Eibenintoxikation verläuft leider auch heute
noch meist tödlich, da eine spezifische Therapie nicht existiert und
die Giftelimination oft zu spät kommt.
Abb. 1
EKG bei Eintritt
Forum Med Suisse 2008;8:(Suppl. 40)
78 S
P183
Measurement of free plasma levels of antiretroviral drugs
using a new ultrafiltration method circumventing the loss by
adsorption reveals high interindividual variability in free fractions
Fayet A., Buclin T., Telenti A., Biollaz J., Decosterd L.A. (Lausanne)
Background: Total plasma levels are used for Therapeutic Drug
Monitoring of antiretroviral drugs, whereas unbound concentrations
are expected to exert antiviral activity. The determination of free drug
levels in plasma can be performed by ultrafiltration, a technique
flawed however by the irreversible adsorption of many drugs onto the
membrane filters and plastic components. This results in spuriously
low levels and underestimated free fractions. We report a new procedure for the accurate measurement of unbound plasma levels of
antiretroviral drugs by ultrafiltration.
Methods: During in vitro experiments, plasma spiked with antiretroviral drugs were placed in pre-washed Centrifree ultrafiltration tubes,
and centrifuged at 2000 g. The ultrafiltrate was collected in four fractions (0–8, 8–16, 16–24 and 24–30 minutes), diluted 1:1 with MeOH
without delay, and analysed by LC-MS/MS.
Results: Free drug levels in the early 0-8 min ultrafiltrate fraction were
very low and highly variable, and gave free fractions substantially
lower than the mean value in the late three fractions (8–16,16–24 and
24–30 minutes) for lopinavir (mean: 0.89 vs 2.01%, p <0.01), nelfinavir
(0.091 vs 0.52%, p <0.01), saquinavir (0.98 vs 2.73%, p <0.01),
tipranavir (0.014 vs 0.072%, p <0.01) and efavirenz (0.28 vs 1.17%,
p <0.01). In the two last fractions, the ultrafiltrate levels remained
constant, indicating a saturable initial drug adsorption without further
influence on the accuracy of free drug level determination beyond
16 min of ultrafiltration. The adsorption phenomenon was modest for
indinavir, amprenavir and ritonavir and unnoticeable for atazanavir
and nevirapine. Applied to patients’ plasma, the procedure reveals
a substantial inter-individual variability in the free fraction for many
antiretroviral drugs.
Conclusions: The change in procedure for the determination of free
antiretroviral drug levels enables to circumvent drug loss due to early
adsorption on ultrafiltration membrane. Measurement of free drug
levels is thus made easier in special situations (pregnancy, haemodilution, protein level changes, liver/kidney insufficiency etc.).
P184
Low-dose Valganciclovir is efficacious and safe for
prophylaxis of cytomegalovirus infection in kidney
transplantation
Perrottet N., Manuel O., Venetz J.P., Lamoth F., Decosterd L.A.,
Buclin T., Biollaz J., Meylan P., Pascual P. (Lausanne, Edmonton)
Background: Optimal valganciclovir (VGC) dosage and duration for
cytomegalovirus (CMV) prophylaxis in kidney transplant recipients
remains controversial. This study aimed to determine GCV blood
levels and efficacy/safety observed under low-dose oral VGC in kidney transplant recipients. Secondly, to quantify the variability of GCV
blood levels, and its potential clinical impact.
Methods: In this prospective study, each patient at risk for CMV
undergoing kidney transplantation received low-dose VGC (450 mg
qd) prophylaxis for 3 months, unless GFR was below 40 mL/min, in
which case the dose was adapted to 450 mg every other day. GCV
levels, at trough (Ctrough) and at peak (C3h) were measured monthly
and CMV viremia was assessed during and after prophylaxis using
real time quantitative Polymerase Chain Reaction. Adverse effects
were recorded on each GCV sampling. Patients were followed up to
one year after transplantation.
Results: 38 kidney recipients (19 D+/R+, 11 D+/R-, 8 D-/R+) received
3-month VGC prophylaxis. Most patients (mean GFR of 59 mL/min)
received 450 mg qd but the dose was reduced to 450 mg every other
day in 6 patients with mean GFR of 22 mL/min. Average GCV C3h
and Ctrough (regressed at 24 h or 48 h) were 3.9 mg/L (CV 33%,
range: 1.3–8.2) and 0.4 mg/L (CV 111%, range 0.1–3.3). Population
pharmacokinetic analysis showed a fair dispersion of the parameters
mainly influenced by renal function. Despite this variability, patients
remained aviremic during VGC prophylaxis. Neutropenia and thrombocytopenia (grade 2-4) were reported in 4% and 3% of patients
respectively. During follow-up, asymptomatic CMV viremia was
reported in 25% patients. One year after transplantation, 12%
patients (all D+/R-) had developed a CMV disease, which was treated
with a therapeutic 6-week course of oral VGC.
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Conclusion: Average GCV blood levels after oral administration of
low-dose VGC in kidney transplant recipients were comparable to
those previously reported with oral GCV prophylaxis, efficacious and
well tolerated. Thus, a 3-month course of low-dose VGC is appropriate for the renal function of most kidney transplant recipients.
P185
Disposition of oral valganciclovir during continuous renal
replacement therapy in two lung transplant recipients
Perrottet N., Robatel C., Meylan P., Pascual P., Venetz J.P., Aubert
J.D., Berger M., Decosterd L.A., Biollaz J., Buclin T. (Lausanne)
Background: Oral valganciclovir (VGC) is hydrolysed into active
ganciclovir (GCV) which is eliminated in the kidney by filtration and
secretion. VGC dosage has to be adapted in renal failure with continuous renal replacement therapy (CRRT), a condition sometimes
encountered early after solid organ transplantation. This investigation
aimed to determine whether VGC 450 mg every 48 hours provides
appropriate GCV exposure for cytomegalovirus (CMV) prophylaxis
during CRRT.
Methods: GCV pharmacokinetics were extensively studied during
CRRT in two lung transplant recipients with acute renal failure receiving VGC 450 mg every 48 hours trough a nasogastric tube. In vitro
experiments using blank whole blood spiked with GCV further investigated exchanges between plasma and erythrocytes.
Results: GCV disposition was characterised by an area under the
curve (AUC) of 98.0 and 55.4 mg·h/L, resulting in trough concentrations of 0.7 and 0.2 mg/L, an apparent total body clearance of 3.3
and 5.8 L/h, a terminal half-life of 16.9 and 14.1 h, and an apparent
volume of distribution of 60.3 and 104.9 L. The observed sieving
coefficient (filtrate/plasma) was 1.05 and 0.96, and the hemofiltration
clearance 3.3 and 3.1 L/h, respectively. High sieving values could be
explained by an efflux of GCV from erythrocytes. In vitro experiments
confirmed that erythrocytes are loaded with significant GCV amount
and release it quickly into plasma, thus contributing to the apparent
efficacy of hemofiltration.
Conclusion: These results indicate that a VGC dosage of 450 mg
every 48 hours was adequate for CMV prophylaxis during CRRT,
providing GCV levels similar to those reported using 900 mg qd in
transplant recipients with normal renal function.
P186
Preliminary results: Topical retinoids during the first
trimester of pregnancy
Panchaud A., Csajka C., Rousso Ph., Rothuizen L., Buclin Th., and
the European Network of Teratogen Information Services E.N.T.I.S.
(Lausanne, various places)
Background: While retinoids given orally are strong human teratogens, their topical use has not been formally prohibited during pregnancy, considering their very low absorption. However, isolated
observations suggest a potential association with characteristic
retinoid embryopathy. Epidemiological data are still scant to confidently confirm or rule out this risk.
Method: The Swiss Teratogen Information Service (STIS) carried out
a collaborative observational study to evaluate the rate of congenital
malformations following first trimester exposure to topical retinoids.
Data prospectively recorded by the ENTIS members between 1992
and 2006 were collected using a standard questionnaire.
Results: Data were obtained on 248 pregnant women (age 30.5 ±
4.0, range 21–42) exposed to topical retinoids (11 lost to follow-up).
110/227 were known as primigravid, 136/226 as primiparous, 11/184
as reporting tobacco use, 23/174 alcohol use. 199 exposures
occurred during the critical period for retinoid embryopathy (week 2
to 5) and 233 during the first trimester (mean week of call 10 ± 6,
range 0–35). Exposures were to six different retinoids (adapalene 28,
retinoic acid 12, tretinoin 148, isotretinoin 54, motretinide 1, tazaroten
1, combined 4). Congenital abnormalities were observed in 8 of 194
newborns known for first trimester exposure (prevalence 4.1%, CI95
1.3–6.9): congenital cerebral cysts with autism, bilateral polycystic
kidneys with early termination, hemangiomas, angiomas, unilateral
cataract, unilateral microphtalmia, cleft soft palate, and poly-malformation (ventricular septal defect, pulmonary valve stenosis, aorctic
coarctation, undescended testes). Another 8 newborns presented
minor variants: 2 ankyloglossia, 2 external ear misshape, hypermetropia, naevus, metatarsus varus. Further comparisons with a
matched control group of unexposed pregnancies are underway.
Forum Med Suisse 2008;8:(Suppl. 40)
79 S
Conclusions: The calculated confidence interval for the prevalence of
abnormalities in this population encompasses the rate of anomalies
(2–4%) reported in the general population. This study is sufficiently
powered to exclude with fair certainty an effect of the order of a doubling or more of baseline risk. However, a small increase in congenital
abnormalities cannot be ruled out. Concretely, these results bring
reassuring elements in case of fortuitous exposure to topical
retinoids. However, they can certainly not be recommended for use
during pregnancy, as their risk/benefit ratio remains questionable.
P187
Delayed neurologic sequelae after acute carbon monoxide
poisoning
Ruggieri F., Al-Haj Husain N., Kupferschmidt H., Joos B., Fischler M.
(Zürich)
Case report: After being accidentally exposed to a residential fire for
30–40 minutes a 21-year-old woman was intubated because of coma
and poor oxygen saturation (SaO2 80%). On admission she was
mechanically ventilated with 100% O2, the temperature was 37.4 °C,
the heart rate 110/min, blood pressure 120/70 mm Hg and SaO2
98%. The first arterial blood gas revealed: pH 7.1, pCO2 6.3 kPa, pO2
7.0 kPa, COHb 20%, O2Hb 64%, lactate 10.7 mmol/L. Troponine and
ECG were normal. She then was transferred to the ICU. Hyperbaric
oxygen (HBO) was not administered. After extubation on day 7 she
progressively developed psychosis, parkinsonism, choreoathetosis in
the upper limbs, mutism, central blindness, urinary and fecal incontinence suggesting delayed neurologic sequelae (DNS) secondary to
carbon monoxide poisoning. MRI of the brain performed on day 14
revealed high-signal-intensity lesions on T2-weighted images in the
caudate nucleus and putamen, posterior periventricular white matter
and parieto-occipital cortex bilaterally, which showed gadolinumenhancement on T1-weighted images. The lesions were consistent
with encephalopathy by CO poisoning with bilateral striatal involvement and cortical laminar necrosis. She was started on amantadine
4 x 200 mg/d with improvement of her parkinsonism. She gradually
regained neurological and neuropsychological function after 4 months
rehabilitation.
Conclusion: Carbon monoxide binds to haemoglobin (COHb) with
nearly 240 times the affinity of oxygen. Poisoning results mainly in
cardiac and neurological damage. Delayed neuropsychiatric syndrome (DES) is characterized by amnesia, personality changes,
movement disorders, focal deficits and develops in up to 40% of
patients with significant CO exposure. It can occur insidiously days
or even several weeks after apparent recovery and being discharged
home (lucid intervals). The exact mechanisms by which CO produces
these toxic effects are not yet well understood and the development
of DNS correlates poorly with COHb levels. Pulse oximetry is unreliable because it overestimates SaO2 in the presence of COHb. Mainstay of therapy remains 100% O2 via high-flow mask and supportive
care. Hyperbaric oxygen (HBO) accelerates dissociation of CO from
hemoglobin and may prevent DNS, however the evidence is not
convincing. The use of HBO should be considered in coma, cardiac
dysfunction, severe acidosis (pH <7.1) and COHb >25% (in pregnancy >20%).
P188
In vitro study of P-glycoprotein interaction with naloxone
and naltrexone
Kanaan M., Daali Y., Dayer P., Desmeules J. (Genève)
Background: The poor oral bioavailability of the opioid antagonist
naloxone (NA) (<1%) as compared with that of naltrexone (NX) (up
to 40%) seems to be related to a weaker intestinal absorption rate
rather than a more extensive first pass metabolism. This could be
attributed to a greater interaction of naloxone with the efflux drug
transporter P-glycoprotein (P-gp) as compared with that of naltrexone.
Aim: We studied the involvement of P-gp in the transepithelial transport of the two opioid antagonists, using a human in vitro Caco-2 cell
monolayers model.
Methods: Transmission electron microscopy (TEM), transepithelial
electrical resistance (TEER), [3H]-mannitol permeability, Western blot
analysis and bidirectional transport of rhodamine 123 have been
performed to assess the integrity of the Caco-2 model. The bidirectional transport of NA and NX (1, 10, 50 and 100 microM) across the
SESSION INTERACTIVE DES POSTERS SPTC
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monolayers was investigated at physiological pH (7.4/7.4) in the
presence and absence of the specific P-gP inhibitor elacridar
(GF1210918) (4 microM). Analytical quantification was achieved using
high performance liquid chromatography.
Results: NA and NX showed no statistically significant differential
transport rates between the basolateral-to-apical (B-A) and apical-tobasolateral (A-B) directions and neither the influx nor the efflux were
affected by the P-gp inhibitor.
Conclusion: NA and NX are not P-gp substrates. The differential
intestinal absorption of the two opioid antagonists is P-gp independent and seems not to be related to a differential interaction with an
intestinal transporter.
P189
Micro-cocktail validation for CYP3A and CYP2D6
assessment using a low dose of midazolam (0.075 mg)
and dextromethorphan (2.5 mg)
Daali Y., Samer C., Eap C., Rebsamen M., Rossier M., Dayer P.,
Desmeules J. (Genève, Lausanne)
Background/Aim: Cocktail approach is generally preferred to individual administration of probes in order to characterize the activity of
multiple enzymes. However, cocktail strategy has several drawbacks
such as drug-drug interactions, tolerability and toxicity. Hence, there
is a need to develop cocktails using low doses of probes. Our aim
was to investigate whether the simultaneous oral administration of
microdoses of midazolam (MDZ) and dextromethorphan (DEM) can
be used to assess the simultaneous activities of CYP3A and
CYP2D6.
Methods: As part of a 5 arm randomized cross-over control trial on
the analgesic efficacy of oxycodone, ten healthy young non-smoking
males received the following combinations of drugs: Quinidine (Q)+
ketoconazole (K) or Q+placebo (P) or K+P or P+P. In all cases MDZ
(0.075 mg) and DEM (2.5 mg) were administrated 1 hour after Q, K or
P. CYP2D6 and CYP3A activities were determined after urine collection during 8 hours (ratio DEM/DOR), and a blood sample (EDTA) after
30 min (ratio 1-OH-MDZ/MDZ). DEM and DOR analysis was performed using LC-fluorescence. MDZ and 1-OH-MDZ determination
was performed using GC-MS. Allele’s variants of CYP2D6 were
detected using the AmpliChipTMCYP450 (Roche).
Results: CYP2D6 genotype predicted 1 poor (PM), 1 intermediate
(IM), 7 extensive (EM) and 2 ultra rapid (UM) metabolizers. A good
correlation was obtained between the predicted and the measured
phenotypes except for 1 EM phenotyped as UM. Two duplications for
alleles *41/*41xN and *1/*2xN were detected and the two volunteers
were phenotyped as UM. A potent inhibition of CYP2D6 or CYP3A4
was obtained when Q or K were used. Mean metabolic ratio
DEM/DOR in P and K groups were 0.015 (±0.028) and 0.015 (±0.019).
It significantly increased in Q and QK groups (0.668 (±0.676) and
0.743 (±1.038)). Mean 1-OH-MDZ/MDZ in P, Q were 2.73 (±1.05) and
2.55 (±1.40) while it significantly decreased in K and QK groups (0.11
(±0.05), 0.10 (±0.05)). Moreover, there were no statistically significant
differences between QK and K sessions for CYP3A and between QK
and Q for CYP2D6 which indicate that there is no interaction between
the two metabolic pathways.
Conclusion: Simultaneous assessment of CYP3A and CYP2D6 activities can be obtained by low oral doses (micro-cocktail) of MDZ and
DEM. Specific inhibitors such as Q or K modulates selectively
CYP2D6 or CYP3A activities.
P190
Kidney-related adverse drug reactions: results of a
pharmacovigilance program in hospitalized patients
Zuliani E., Bertoli R., Cerny A. (Lugano)
Background: The standard classification of terms based on organ
systems (CIOMS) does not account for ADRs in which the kidney is
involved as a cause of an ADR. Hence we developed a new pathophysiologic classification of kidney-related ADRs and then applied it
to the information in a pharmacovigilance database.
Methods: We retrospectively studied all cases of ADRs who have
been submitted to the regional pharmacovigilance center by the
internal medicine department of the Civico Hospital in Lugano
between 01/2002 to 12/2005. We defined as kidney target any case in
which the drug had a direct pharmacological effect on the kidney and
this effect was responsible for the ADR. We classified as kidney
Forum Med Suisse 2008;8:(Suppl. 40)
80 S
cofactor the cases where the primary effect was not at the level of the
kidney. We used standard statistical analysis tools.
Results: Among the 70 patients with kidney-related ADRs we identified 66% target and 34% cofactor cases. Electrolyte disorders were
the most frequent type of kidney target ADR (85%), followed by AKI
(48%). 96% of the cofactor cases had a GFR <60 ml/min/1.73 m2.
The patient with a kidney-target ADR tended to be an old woman,
with AKI and/or an electrolyte disturbance, with ACEI/ARBs or diuretics causing the ADR. The patient with kidney-cofactor ADR tended to
be an old man, with major hemorrhage or hypoglycemia from accumulation of a LMW heparin or a sulfonylurea, respectively. Using a
definition of AKI based on a predetermined stepwise increase in
serum creatinine, we identified 22 patients with drug-related AKI.
When applying the RIFLE criteria to these patients, 18% did not
qualify as AKI. None of these patients, as well as none of the patients
that fell into the RIFLE renal “risk” category, needed renal replacement therapy. Since there were only 2 deaths related to drug-induced
AKI, we could not draw any conclusions on the capacity of the RIFLE
approach of predicting mortality.
Discussion: We analyzed the kidney-related ADRs by adopting a
new patho-physiologic classification. Using the WHO classification
for ADRs based on organ systems, some of the kidney-related ADRs
would fall under other categories. We also took into consideration the
cases in which the kidney had a major contribution to the development of ADRs, which allows to have a better estimate of the real
burden of kidney-related ADRs. In spite of the low number of
patients, there seemed to be a relationship between the RIFLE classification and the need for renal replacement therapy, whereas we
could not find a clearcut relationship between this classification and
outcome. Establishing the applicability of the RIFLE criteria to other
patient populations, such as the population with drug-induced AKI,
may prove useful.
P191
Catechol-methyl-transferase polymorphisms and pain
sensitivity in fibromyalgia
Chabert J.*, Rebsamen M., Cedraschi C., Besson M., Matthey A.,
Chiappe A., Piguet V., Rossier M., Dayer P., Desmeules J. (Genève)
Background and aims: Fibromyalgia (FM) is a chronic musculoskeletal pain condition. We previously demonstrated a state of central
sensitization in FM using selective neurophysiological quantitative
sensory testing (Nociceptive Flexion Reflex (NFR)). Some polymorphisms affecting the gene encoding catechol-O-methyltransferase
(COMT) are associated with a reduction in the enzyme activity that
influences pain regulation and anxiety and may participate in chronic
painful diseases. Our aim was to evaluate the relation between COMT
polymorphisms and quantitative sensory testing using NFR in FM as
compared to a match control population.
Methods: 198 patients and 99 controls were included. The FM
patients were asked to stop their centrally-acting analgesic treatment
if they had one. 137 were classified as able to stop medication (ASM)
and 61 as unable to stop medication (USM). Patients and controls
were assessed for COMT genotype focused on 4 single nucleotide
polymorphisms determined by TaqMan PCR: rs6269, rs4633, rs4818,
and rs4680. Evaluation of pain thresholds was performed using the
NFR.
Results: Most subjects were middle-aged females, with a 10 year
mean duration of symptoms. Clinical measures indicated moderate
to severe pain in both groups of FM. Psychosocial and functional
aspects were severely affected in FM, USM group displaying worse
results. Almost half of the ASM group was previously on central acting analgesics (antidepressant, opioid or anticonvulsivant medications) as compared to nearly all USM patients (p <0.001). For COMT
genotype, 3 major haplotypes were identified: ATCA (49%), GCGG
(40%), ACCG (8%), that accounted for 97% of the seven detected.
Those 3 haplotypes have been previously associated with different
pain sensitivity levels: low (LPS), average (APS), or high (HPS) respectively. Six combinations of these 3 haplotypes were present. The
number of LPS/LPS was significantly decreased in the USM group
(4.9%) vs the ASM group (18.2%, p = 0.003) or controls (21.2%,
p = 0.007). In ASM patients, a state of central sensitization was
present in the majority of FM (71%) and the NFR of the LPS/LPS
was significantly better compared to the others haplotypes (median
24.3 vs 21.3 p <0.05).
Conclusion: COMT polymorphisms seems to be associated with the
severity of neurophysiological and psychosocial consequences of FM
and could contribute to account for a subgroup of FM patients prone
to severe consequences of the disease.
Supported by the SNSF (NRP53–4049-405340-104645/1)
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Forum Med Suisse 2008;8:(Suppl. 40)
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