1: Med Teach. 2009 Apr;31(4):e162-8.
Is a web-based concordance test feasible to assess therapeutic decision-making
skills in a French context?
Sibert L, Giorgi R, Dahamna B, Doucet J, Charlin B, Darmoni SJ.
Department of Urology, Rouen University, Rouen, France. louis.sibert@chu-rouen.fr
BACKGROUND: At the end of undergraduate medical curriculum, a written
simulation-based examination is used in France to assess therapeutic
decision-making skills and to rank students for the purpose of matching their
training specialties. However, this examination based on a single assessment
method remains a subject of debate. AIM: To study the feasibility of a web-based
Concordance test for therapeutic decision-making assessment. METHODS: A 12
clinical-case Concordance test was developed based on objectives for the
undergraduate training program. The test was administered on line to candidates
with different levels of clinical experience. Fifteen therapeutic teachers
constituted the reference panel. Data analysis included analysis of variance,
post-hoc test, and Cronbach's alpha. RESULTS: One hundred and seventy
participants (113 students, 34 residents, 23 physicians) fully completed the
free-access test on line with no technical problems. Differences between the mean
scores for groups were significant (p < 0.001). Significant differences occurred
between fourth year students and residents (p < 0.001), fourth year students and
physicians (p = 0.001). No difference was found between residents and physicians.
Reliability coefficient was 0.67. CONCLUSION: A web-based Concordance test in the
field of therapeutic decision-making was considered feasible in a French learning
environment. Further research is warranted to determine its usefulness as a part
of the National Examination.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 19404888 [PubMed - in process]
2: Eur J Gastroenterol Hepatol. 2009 Apr 28. [Epub ahead of print]
Jaundice revealing a k light chain myeloma because of liver light chain deposits.
Montialoux H, Savoye G, Savoye-Collet C, Ramirez S, François A, Lerebours E,
Goria O.
Departments of aHepatogastroenterology bRadiology cHistopathology, Rouen
University Hospital, France.
We report the case of a 77-year-old man referred for jaundice and diagnosed with
intrahepatic light chain deposit as primary manifestation of a kappa light chain
multiple myeloma. Jaundice is a very rare way of presentation for myeloma. In our
observation, diagnosis was made by liver biopsy, which found light chain deposits
infiltrating perisinusoidal spaces. We discuss jaundice's possible mechanisms in
myeloma.
PMID: 19404208 [PubMed - as supplied by publisher]
3: Rheumatology (Oxford). 2009 Apr 24. [Epub ahead of print]
Paradoxical adverse events of anti-tumour necrosis factor therapy for
spondyloarthropathies: a retrospective study.
Fouache D, Goëb V, Massy-Guillemant N, Avenel G, Bacquet-Deschryver H,
Kozyreff-Meurice M, Ménard JF, Muraine M, Savoye G, Loët XL, Tharasse C, Vittecoq
O.
Department of Pharmacy, University of Medicine-Pharmacy, Department of
Rheumatology, Rouen University Hospital and Inserm U905 (IFRMP 23), Institute for
Biomedical Research, University of Rouen, Department of Pharmacovigilance,
Department of Biostatistics, Department of Ophthalmology and Department of
Hepatogastroenterology, Rouen University Hospital, Rouen, France.
Objectives. Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior
uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF
drugs. This retrospective study aimed to describe the different PAEs that have
occurred in a population of SpA patients treated with anti-TNF drugs, and to
determine whether they are drug specific. Methods. Since 2000, we have followed
296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis,
12 Crohn's disease) and 77 psoriatic arthritis] treated with at least one
anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients
treated only with conventional DMARDs who served as controls. Considering the
cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset
PAEs in exposed patients were calculated. Results. Respective cumulative exposure
times were 287, 290 and 62 patient-years for infliximab, etanercept and
adalimumab. We observed the following PAEs: five psoriasis (three under
infliximab and one with etanercept or adalimumab), three AAU (1/100
patient-years, all under etanercept) and four IBD (three under etanercept and one
under infliximab). There was no significant association among any of these PAEs
and a specific anti-TNF agent; nor significant difference in the overall PAEs
among patients receiving anti-TNF drugs or controls (P = 0.303), the latter
experiencing two psoriasis and three AAU. Conclusions. Undesirable side
effects-IBD, AAU and psoriasis-may appear with anti-TNF drugs. Even if they are,
a priori, paradoxical, no evidence supports any PAEs to be anti-TNF
agent-specific in SpA.
PMID: 19395543 [PubMed - as supplied by publisher]
4: Encephale. 2009 Apr;35(2):173-5. Epub 2008 Aug 19.
[Chlorpromazine-induced agranulocytosis: A case report.]
[Article in French]
Stephan F, Podlipski MA, Kerleau JM, Petit M, Guillin O.
Service universitaire de psychiatrie, centre hospitalier du Rouvray, 4, rue
Paul-Eluard, 76300 Sotteville-lès-Rouen, France.
CASE REPORT: We report the case of a 50-year-old man, treated with chlorpromazine
for schizophrenia, who developed an agranulocytosis. Three mechanisms of
drugs-induced agranulocytosis have been reported: toxic, genetic and immune.
Phenothiazines are responsible for drug-induced agranulocytosis. This patient had
been treated with first and second generation antipsychotic drugs during his life
and had already been exposed to chlorpromazine or other phenotiazines without any
signs of toxicity. However, two months after the introduction of chlorpromazine
he presented an agranulocytosis (leukocytes 1.4G/L and neutrophils 0.2G/L). After
discontinuation of chlorpromazine, blood count returned to normal. The role of
chlorpromazine in inducing toxic agranulocytosis was based on: (i) normal blood
count before the introduction of chlorpromazine; (ii) occurrence of
agranulocytosis within the first weeks of chlorpromazine treatment; (iii) normal
bone marrow and blood count after discontinuation of chlorpromazine; (iv)
chlorpromazine was the only new drug prescribed to this patient at the time the
agranulocytosis occurred. Risk factors for toxic agranulocytosis in this patient
were: old age, association of phenothiazine with other drugs known to be able to
induce agranulocytosis, and past history of use of high doses of chlorpromazine.
DISCUSSION: This case report highlights the risk of chlorpromazine in inducing
agranulocytosis, a risk underestimated in regard of the clozapine risk to induce
agranulocytosis or neutropenia. For this reason, it seems reasonable to recommend
performing a blood count before introduction of phenothiazine in patients with
risk factors for toxic drug-induced agranulocytosis (old age, female, receiving
other drugs with a high potential to induce agranulocytosis and having received
high doses of phenothiazine for a long time).
Publication Types:
English Abstract
PMID: 19393387 [PubMed - in process]
5: J Clin Endocrinol Metab. 2009 Apr 21. [Epub ahead of print]
The paradoxical increase in cortisol secretion induced by dexamethasone in
primary pigmented nodular adrenocortical disease involves a glucocorticoid
receptor-mediated effect of dexamethasone on protein kinase A catalytic subunits.
Louiset E, Stratakis CA, Perraudin V, Griffin KJ, Libé R, Cabrol S, Fève B, Young
J, Groussin L, Bertherat J, Lefebvre H.
INSERM U413, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and
Neuroendocrine Communication (E.L., V.P., H.L.), University of Rouen, Mont Saint
Aignan, 76821, France; Section on Endocrinology and Genetics, Program in
Developmental Endocrinology and Genetics (C.A.S., K.J.G.), National Institute of
Child Health & Human Development, Bethesda, Maryland 20892; Department of
Endocrinology (R.L., L.G., J.B.), CHU Cochin & Institut Cochin, INSERM U567, CNRS
UMR8104, IFR 116, Université Paris V-René Descartes, 75014 Paris, France;
Department of Pediatric Endocrinology (S.C.), University Paris
VI-Pierre-et-Marie-Curie, Hospital Trousseau, 75571 Paris, France; Department of
Endocrinology (B.F., J.Y.), University Paris-Sud 11, Hospital Bicêtre, 94275 Le
Kremlin Bicêtre, France; Department of Endocrinology (H.L.), University Hospital
of Rouen, Institute for Biomedical Research, University of Rouen, 76031Rouen,
France.
Context: Primary pigmented nodular adrenocortical disease (PPNAD) results in most
cases from mutations of the protein kinase A (PKA) regulatory subunit 1A
(PRKAR1A) gene. Patients with PPNAD exhibit a paradoxical increase in cortisol
secretion in response to dexamethasone. Objective: To investigate the mechanism
of the action of dexamethasone on adrenocortical cells removed from patients with
PPNAD and a transgenic model of PPNAD (Tg(tTA/X2AS) mice). Design & Setting: In
vitro study performed in an academic research laboratory. Patients: Eleven
patients with histologically proven PPNAD were included in the study.
Intervention: Cultured PPNAD cells were incubated with dexamethasone in the
presence of various modulators of the cAMP/PKA pathway and the glucocorticoid
receptor (GR) antagonist RU486. Main outcome measure: Cortisol and corticosterone
were measured by radioimmunological assays in cell culture supernatants. Results:
Dexamethasone stimulated in vitro cortisol secretion from PPNAD tissues in six
patients. The stimulatory effect of dexamethasone on cortisol release was not
reduced by the adenylyl cyclase inhibitor SQ22536 nor potentiated by the
phosphodiesterase inhibitor IMBX and the cAMP analog 8Br-cAMP. Conversely, the
PKA inhibitor H89 and RU486 inhibited the cortisol response to dexamethasone.
Dexamethasone had no effect on cortisol production from normal human
adrenocortical cells but stimulated corticosteroidogenesis in the presence of
RU486. Similarly, dexamethasone failed to influence corticosterone release by
adrenocortical cells removed from Tg(tTA/X2AS) mice but stimulated
corticosteroidogenesis in the presence of RU 486. Conclusions: These results
indicate that, in human PPNAD tissues, dexamethasone paradoxically stimulates
cortisol release through a GR-mediated effect on PKA catalytic subunits.
PMID: 19383776 [PubMed - as supplied by publisher]
6: J Occup Rehabil. 2009 Apr 21. [Epub ahead of print]
Precision and Recall of Search Strategies for Identifying Studies on
Return-To-Work in Medline.
Gehanno JF, Rollin L, Le Jean T, Louvel A, Darmoni S, Shaw W.
Institute of Occupational Health, Rouen University Hospital, 1 rue de Germont,
76000, Rouen, France, jean-francois.gehanno@chu-rouen.fr.
Introduction The purpose of this study was to report on the qualities of various
search strategies and keywords to find return to work (RTW) studies in the
Medline bibliographic database. Methods We searched Medline for articles on RTW
published in 2003, using multiple search strings, and hand searched 16 major
periodicals of rehabilitation or occupational medicine. Among the retrieved
articles, those considered to be relevant, were pooled in a Gold Standard
Database. From this database, we identified candidate text words or MeSH terms
for search strategies using a word frequency analysis of the abstracts and a
MEDLINE categorization algorithm. According to the frequency of identified terms,
searches were run for each term independently and in combination. We computed
Recall, Precision, and number needed to read (NNR = 1/Precision) of each keyword
or combination of keywords. Results Among the 8,073 articles examined, 314 (3.9%)
were considered relevant and included in the Gold Standard Database. The search
strings ("Rehabilitation, Vocational" [MeSH]), ("Return to work"[All]) and ("Back
to work"[All]) had Recall/Precision ratio of 30.46/19.11, 59.55/87.38 and
3.18/90.91%, respectively. Their combination with the Boolean operator OR yielded
to a Recall/Precision ratio of 73.89/58.44% and a NNR of 1.7. For the end user
requiring comprehensive literature search, the best string was ("Return to work"
OR "Back to work" OR "Rehabilitation, vocational"[MeSH] OR
"rehabilitation"[Subheading]), with a Recall of 88.22% and a NNR of 18.
Conclusions No single MeSH term is available to help the physician to identify
relevant studies on RTW in Medline. Locating these types of studies requires the
use of various MeSH and non-MeSH terms in combination to obtain a satisfactory
Recall. Nevertheless, enhancing the Recall of search strategies may lead to lower
Precision, and higher NNR, although with a non linear trend. This factor must be
taken into consideration by the end user in order to improve the
cost-effectiveness ratio of the search in Medline.
PMID: 19381789 [PubMed - as supplied by publisher]
7: Gynecol Obstet Fertil. 2009 Apr 17. [Epub ahead of print]
[Against labor induction after previous cesarean delivery.]
[Article in French]
Ricbourg-Schneider A, Marpeau L.
Service de gynécologie-obstétrique, CHU Charles-Nicolle, 1, rue de Germont, 76000
Rouen, France.
PMID: 19376739 [PubMed - as supplied by publisher]
8: Glia. 2009 Apr 16. [Epub ahead of print]
Elastin-derived peptides: Matrikines critical for glioblastoma cell
aggressiveness in a 3-D system.
Coquerel B, Poyer F, Torossian F, Dulong V, Bellon G, Dubus I, Reber A, Vannier
JP.
Groupe de Recherche, Micro-Environnement et Renouvellement Cellulaire Intégré,
MERCI UPRES EA3829, Faculté de Médecine et Pharmacie, Université de Rouen, 76183
Rouen Cedex, France.
In the most common primary brain tumors, malignant glioma cells invade the
extracellular matrix (ECM) and proliferate rapidly in the cerebral tissue, which
is mainly composed of hyaluronan (HA) along with the elastin present in the
basement membrane of blood vessels. To determine the role of ECM components in
the invasive capacity of glioma cell lines, we developed a 3-D cell-culture
system, based on a hydrogel in which HA can be coreticulated with kappa-elastin
(HA-kappaE). Using this system, the invasiveness of cells from four glioma cell
lines was dramatically increased by the presence of kappaE and a related,
specific peptide (VGVAPG)(3). In addition, MMP-2 secretion increased and MMP-12
synthesis occurred. Extracellular injections of kappaE or (VGVAPG)(3) provoked a
pronounced and dose-dependent increase in [Ca(2+)](i). kappaE significantly
enhanced the expression of the genes encoding elastin-receptor and tropoelastin.
We propose the existence of a positive feedback loop in which degradation of
elastin generates fragments that stimulate synthesis of tropoelastin followed by
further degradation as well as migration and proliferation of the very cells
responsible for degradation. All steps in this ECM-based loop could be blocked by
the addition of either of the EBP antagonists, lactose, and V-14 peptide,
suggesting that the loop itself should be considered as a new therapeutic target.
(c) 2009 Wiley-Liss, Inc.
PMID: 19373935 [PubMed - as supplied by publisher]
9: Gynecol Obstet Fertil. 2009 Apr;37(4):353-7. Epub 2009 Apr 14.
[Suburethral sling procedures for stress urinary incontinence.]
[Article in French]
Sergent F, Gay-Crosier G, Marpeau L.
Clinique gynécologique et obstétricale, hôpital Charles-Nicolle, CHU de Rouen, 1,
rue de Germont, 76031 Rouen, France; Université de Rouen, 22, boulevard Gambetta,
76183 Rouen, France.
The rational of the surgical treatment of female stress urinary incontinence has
changed over the past few years. The techniques of colposuspension have been
replaced by the suburethral slings, retropubic initially with the TVT, recreating
a backboard between the urethra and the vaginal anterior wall. Nevertheless with
overall cure rates of 69% to 88%, in periods beyond 5 years, the colposuspension
still remains the reference (high-grade scientific evidence). Based on
observational studies (low quality scientific evidence), with generally a short
follow-up, the results of the TVT appear similar. More recently, the suburethral
transobturator tape (TOT) was introduced to reduce the complications of the TVT.
It is thus difficult to currently have an objective idea of the effectiveness of
the TOT compared to the TVT, even if the first impressions, with respect to the
TOT, are rather favourable. Furthermore the TOT technique itself and the
biomaterials used, have continued to evolve. In fact, if the complications of
these two kinds of suburethral slings are different: bladder perforation for the
TVT, prosthetic erosion for the TOT, in contrast, in the future, their
indications could be different. Therefore the TVT appears more effective in
presence of intrinsic sphincter deficiency with urethral hypermobility.
Publication Types:
English Abstract
PMID: 19369107 [PubMed - in process]
10: J Cereb Blood Flow Metab. 2009 Apr 15. [Epub ahead of print]
Newborn- and adult-derived brain microvascular endothelial cells show age-related
differences in phenotype and glutamate-evoked protease release.
Legros H, Launay S, Roussel BD, Marcou-Labarre A, Calbo S, Catteau J, Leroux P,
Boyer O, Ali C, Marret S, Vivien D, Laudenbach V.
EA 4309 Neovasc Microvascular Endothelium and Neonatal Brain Lesions, IHURBM,
IFRMP 23, School of Medicine and Pharmacy, University of Rouen, Rouen, France.
Few data are available on the involvement of brain microvascular endothelial
cells (BMECs) in excitotoxic neonatal brain lesions. Therefore, we developed an
original approach for investigating mouse-derived BMECs in vitro. We hypothesized
that newborn and adult BMEC cultures would show age-related differences in
phenotype and sensitivity to glutamate. Expression of the monocarboxylate
transporter, MCT1, was higher in neonatal than in adult BMECs, whereas expression
of the glucose transporter, GLUT1, was higher in adult than in neonatal BMECs
that overexpressed the N-methyl-D-aspartate receptor NR1 subunit (NMDAR1)
compared with adult BMECs. The ability of neonatal and adult BMECs to be
activated by glutamate was confirmed through intracellular calcium ([Ca(2+)](i))
recording. The glutamate-induced [Ca(2+)](i) increase was blocked by the
selective NMDAR antagonist, MK-801. Significant glutamate-evoked
concentration-dependent release of tissue-type plasminogen activator (t-PA) and
matrix metalloproteinases (MMPs) activities was found in supernatants of
neonatal, but not in adult BMECs. The glutamate-mediated release of t-PA, MMP-2,
and MMP-9 proteolytic activities in neonatal BMECs was blocked by MK-801.
Conceivably, this protease release from neonatal BMECs may participate in
neonatal brain lesions.Journal of Cerebral Blood Flow & Metabolism advance
online publication, 15 April 2009; doi:10.1038/jcbfm.2009.39.
PMID: 19367295 [PubMed - as supplied by publisher]
11: Br J Cancer. 2009 Apr 21;100(8):1330-5.
TP53 mutations predict disease control in metastatic colorectal cancer treated
with cetuximab-based chemotherapy.
Oden-Gangloff A, Di Fiore F, Bibeau F, Lamy A, Bougeard G, Charbonnier F,
Blanchard F, Tougeron D, Ychou M, Boissière F, Le Pessot F, Sabourin JC, Tuech
JJ, Michel P, Frebourg T.
Inserm U614, Faculty of Medicine, Institute for Biomedical Research, University
of Rouen, Rouen, France.
Recent studies have suggested that activation of the EGFR pathway leads to
malignant transformation only if the p53 protein is inactivated. Therefore, we
evaluated the impact of TP53 mutations on cetuximab-based chemotherapy (CT)
sensitivity in combination with KRAS mutations that have been associated with
cetuximab resistance. KRAS and TP53 status were assessed in tumours from 64
metastatic colorectal cancer patients treated with cetuximab-based CT and
correlated to clinical response using the Fisher's exact test. Times to
progression (TTPs) according to gene status were calculated using the
Kaplan-Meier method and compared with log-rank test. TP53 mutations were found in
41 patients and were significantly associated with controlled disease (CD), as
defined as complete response, partial response or stable disease (P=0.037) and
higher TTP (20 vs 12 weeks, P=0.004). Remarkably, in the subgroup of 46 patients
without KRAS mutation, but not in patients with KRAS mutation, TP53 mutations
were also associated with CD (P=0.008) and higher TTP (24 vs 12 weeks, P=0.0007).
This study suggests that TP53 mutations are predictive of cetuximab sensitivity,
particularly in patients without KRAS mutation, and that TP53 genotyping could
have a clinical interest to select patients who should benefit from
cetuximab-based CT.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 19367287 [PubMed - in process]
12: Ann Pathol. 2009 Apr;29(2):134-7. Epub 2009 Mar 19.
[Cystic adenomatoid tumor of the uterus.]
[Article in French]
Leaha C, Opris I, Macé P, Resch B, Sabourin JC.
Service de pathologie, pavillon Jacques-Delarue, hôpital Charles-Nicolle, 1, rue
de Germont, 76031 Rouen cedex, France.
Adenomatoid tumors are benign neoplasms of mesothelial origin, which involve the
feminine and masculine genital tracts. They are more generally casually
discovered. Our study presents an adenomatoid tumour, of cystic shape, which
enables discussion of the histogenesis of this tumour and enlightenment of
differential diagnoses which can at times result in an incorrect malignant
diagnosis.
Publication Types:
English Abstract
PMID: 19364588 [PubMed - in process]
13: Ann Fr Anesth Reanim. 2009 Apr;28(4):384-7. Epub 2009 Apr 9.
[Acute respiratory distress subordinate to a morphine overdose during a frail
elderly patient controlled analgesia]
[Article in French]
Ades A, Compère V, Abriou C, Baert O, Fourdrinier V, Dureuil B.
Département d'anesthésie-réanimation et Samu, CHU Charles-Nicolle, 1, rue de
Germont, 76031 Rouen cedex, France.
We describe a case-report of an 85-year-male patient with a patient-controlled
analgesia (PCA) after a total hip arthroplasty. Four hours after surgery, acute
respiratory distress secondary to a morphine overdose occurred, requiring an
antagonisation with naloxone. Morphine overdose during a PCA was always caused by
a wrong use of the pump. In this case-report, no mistake of programming or
administration's use was found. Too important morphine's doses managed in
comparison with the patient's age and his renal failure could explain this
morphine's accumulation and the respiratory distress. This observation reminds us
the obligation to determine the optimal posology in accordance with the rate of
glomerular filtration estimated by Cockcroft and Gault formula for patients using
a PCA.
Publication Types:
English Abstract
PMID: 19361945 [PubMed - in process]
14: Gynecol Obstet Fertil. 2009 Apr;37(4):358-62. Epub 2009 Apr 7.
[Against the systematic use of segmental resection in colorectal endometriosis:
Do not replace the pain by unpleasant digestive symptoms!]
[Article in French]
Roman H, Bourdel N.
Clinique gynécologique et obstétricale, CHU Charles-Nicolle, 1, rue de Germont,
76031 Rouen cedex, France.
PMID: 19356966 [PubMed - in process]
15: Prenat Diagn. 2009 Apr 7. [Epub ahead of print]
Gastroschisis and absence of the septum pellucidum: an accidental association?
Brasseur-Daudruy M, Treguier C, Bruneau B, Bach-Segura P, Eurin D, Verspyck E.
Department of Pediatric Radiology, Rouen University Hospital, Rouen, France.
PMID: 19353618 [PubMed - as supplied by publisher]
16: Gynecol Obstet Fertil. 2009 Apr;37(4):313-20. Epub 2009 Apr 5.
[Laser assisted hatching: Rouen University Hospital outcomes.]
[Article in French]
Blessmann-Roset J, Rives N, Clavier B, Milazzo JP, Mazurier S, Mousset-Siméon N,
Macé B.
EA 4308 << spermatogenèse et qualité du gamète male >>, laboratoire de biologie
de la reproduction, CECOS, CHU Charles-Nicolle, 1, rue de Germont, 76031 Rouen
cedex, France.
OBJECTIVE: Despite technical progress in In Vitro Fertilisation (IVF) procedure,
embryo implantation rate remains low. Assisted hatching has been proposed to
facilitate natural embryo hatching and implantation. PATIENTS AND METHODS: Our
study has evaluated whether laser assisted hatching improves implantation,
pregnancy and live birth rates in different cases. We studied retrospectively 143
IVF cycles concerning more than 38 years old women, 166 IVF cycles after two
previous implantation failures and 180 frozen-thawed embryo transfers. RESULTS:
Population characteristics were comparable in hatched and control groups.
Implantation, pregnancy and live birth rates in women more than 38 years old were
comparable with or without assisted hatching. Concerning repeated implantation
failures, even if implantation, pregnancy and live birth rates were higher in
assisted hatching group (FIV or ICSI), the differences were not significant.
After frozen-thawed embryo transfers, implantation rate was significantly better
with assisted hatching (19.14% vs 8.84% [p=0.02]). DISCUSSION AND CONCLUSION:
Assisted hatching improves embryo implantation rate after frozen-thawed embryo
transfer.
Publication Types:
English Abstract
PMID: 19346148 [PubMed - in process]
17: Gastroenterol Clin Biol. 2009 Apr;33(4):280-4. Epub 2009 Apr 3.
[Clinical case: perioperative chemotherapy of gastric cancer: for whom? which
risks?]
[Article in French]
Michel P.
Service d'hépato-gastroentérologie et nutrition, unité d'oncologie digestive,
hôpital Charles-Nicolle, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex,
France.
PMID: 19345537 [PubMed - in process]
18: Leukemia. 2009 Apr 2. [Epub ahead of print]
Vasculogenic mimicry of acute leukemic bone marrow stromal cells.
Mirshahi P, Rafii A, Vincent L, Berthaut A, Varin R, Kalantar G, Marzac C,
Calandini OA, Marie JP, Soria C, Soria J, Mirshahi M.
[1] 1Department of Onco Haematology, UMRS 872, CNRS, E: 18, INSERM, Université
Paris VI, Paris, France [2] 2Department of Onco Haematology, Groupe de recherches
MERCI, Faculté de Médecine et Pharmacie, Rouen, France.
Angiogenesis is thought to be involved in the development of acute leukemia (AL).
We investigated whether bone marrow stromal cells (BMSCs) derived from stem cells
might be responsible for the increase in microvascular density (MVD), and
compared 13 bone marrow samples from AL patients with 23 samples from patients in
complete remission (controls). We demonstrated that AL-derived BMSC secreted more
insulin growth factor-1 (IGF-1) and SDF-1alpha than controls. In addition, in
contrast to normal adherent BMSCs, adherent BMSCs derived from CD133+/CD34+ stem
cells from AL patients were able to form capillary-like structures ('vasculogenic
mimicry') on Matrigel. The increase in vasculogenic mimicry occurred through PI3
kinase and rho GTPase pathway as inhibitors of these signaling pathways
(wortmannin and GGTI-298, respectively) were able to reduce or prevent capillary
tube formation. In normal BMSC, addition of exogenous IGF-1 generated
capillary-like tubes through the same pathway as observed spontaneously in
AL-derived BMSC. The involvement of IGF-1 in the mimicry process was confirmed by
the addition of a neutralizing antibody against IGF-1R or a IGF-1R pathway
inhibitor (picropodophyllin). In conclusion, AL-derived BMSC present functional
abnormalities that may explain the increase in MVD in the bone marrow of AL
patients.Leukemia advance online publication, 2 April 2009;
doi:10.1038/leu.2009.10.
PMID: 19340002 [PubMed - as supplied by publisher]
19: Anesth Analg. 2009 Apr;108(4):1326-30.
Bacterial colonization after tunneling in 402 perineural catheters: a prospective
study.
Compère V, Legrand JF, Guitard PG, Azougagh K, Baert O, Ouennich A, Fourdrinier
V, Frebourg N, Dureuil B.
Department of Anesthesia and Intensive Care, Rouen University Hospital, 1 rue de
Germont, 76031 Rouen, France. vincent.compere@chu-rouen.fr
BACKGROUND: Bacterial colonization of peripheral nerve catheters is frequent,
although infection is relatively rare. With central venous catheters, the
tunneling of the catheter into the subcutaneous tissue significantly decreases
catheter colonization and catheter-related sepsis. We evaluated the incidence of
bacterial colonization in adult patients with tunnelized perineural nerve
catheters. METHODS: Peripheral nerve catheters placed under sterile conditions
for postoperative analgesia were evaluated prospectively. After removal, they
were analyzed for colonization. Quantitative culture was used as described by
Brun-Buisson for intravascular catheters. The site of insertion was monitored
daily for any signs of infection. RESULTS: Four-hundred-two patients were
included in the study during a 2-yr period. The mean duration of peripheral nerve
catheters was 48 h (47-50.4). Positive culture occurred in 25 catheters,
indicating that the incidence of colonization was 6.22% (3.8-8.5). The
microbiological analysis of the catheter tip cultures revealed coagulase-negative
staphylococci in 72%. Twenty-two catheters of 25 catheters each had one
microorganism, and for three catheters, two microorganisms were identified. No
infection was found in any patient. CONCLUSION: The incidence of perineural
catheter colonization is low with subcutaneous tunneling. Controlled randomized
studies are warranted to determine whether this procedure decreases the risk for
infection.
PMID: 19299807 [PubMed - indexed for MEDLINE]
20: Hum Mutat. 2009 Apr;30(4):E591-602.
Partial deletion of the MAPT gene: a novel mechanism of FTDP-17.
Rovelet-Lecrux A, Lecourtois M, Thomas-Anterion C, Le Ber I, Brice A, Frebourg T,
Hannequin D, Campion D.
Inserm U614, Faculty of medicine, 76183, Rouen, France.
A heterozygous genomic deletion removing exons 6 to 9 of the microtubule
associated protein tau (MAPT) gene, predicting to result into a truncated protein
lacking the first microtubule binding domain, was detected in a patient with
frontotemporal dementia (FTD). Cell culture experiments showed that the truncated
tau isoforms had a dramatic decrease in the normal binding to microtubules but
acquired the ability to bind microtubule associated protein-1B (MAP-1B). This
indicates that this tauopathy likely results both from a loss of function
mechanism and from a deleterious gain of function by which cytoplasmic deleted
forms of tau sequester another MAP. Both mechanisms could contribute to impair
microtubule dynamics. (c) 2009 Wiley-Liss, Inc.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 19263483 [PubMed - in process]
21: FEBS J. 2009 Apr;276(7):1826-44. Epub 2009 Feb 23.
Control of mammalian gene expression by amino acids, especially glutamine.
Brasse-Lagnel C, Lavoinne A, Husson A.
Appareil Digestif, Environnement et Nutrition, EA 4311, Université de Rouen,
France.
Molecular data rapidly accumulating on the regulation of gene expression by amino
acids in mammalian cells highlight the large variety of mechanisms that are
involved. Transcription factors, such as the basic-leucine zipper factors,
activating transcription factors and CCAAT/enhancer-binding protein, as well as
specific regulatory sequences, such as amino acid response element and
nutrient-sensing response element, have been shown to mediate the inhibitory
effect of some amino acids. Moreover, amino acids exert a wide range of effects
via the activation of different signalling pathways and various transcription
factors, and a number of cis elements distinct from amino acid response
element/nutrient-sensing response element sequences were shown to respond to
changes in amino acid concentration. Particular attention has been paid to the
effects of glutamine, the most abundant amino acid, which at appropriate
concentrations enhances a great number of cell functions via the activation of
various transcription factors. The glutamine-responsive genes and the
transcription factors involved correspond tightly to the specific effects of the
amino acid in the inflammatory response, cell proliferation, differentiation and
survival, and metabolic functions. Indeed, in addition to the major role played
by nuclear factor-kappaB in the anti-inflammatory action of glutamine, the
stimulatory role of activating protein-1 and the inhibitory role of C/EBP
homology binding protein in growth-promotion, and the role of c-myc in cell
survival, many other transcription factors are also involved in the action of
glutamine to regulate apoptosis and intermediary metabolism in different cell
types and tissues. The signalling pathways leading to the activation of
transcription factors suggest that several kinases are involved, particularly
mitogen-activated protein kinases. In most cases, however, the precise pathways
from the entrance of the amino acid into the cell to the activation of gene
transcription remain elusive.
Publication Types:
Review
PMID: 19250320 [PubMed - indexed for MEDLINE]
22: Int J Obstet Anesth. 2009 Apr;18(2):142-9. Epub 2009 Feb 4.
Anaesthesia mode for caesarean section and mortality in very preterm infants: an
epidemiologic study in the EPIPAGE cohort.
Laudenbach V, Mercier FJ, Rozé JC, Larroque B, Ancel PY, Kaminski M, Bréart G,
Diemunsch P, Subtil D, Lejus C, Fresson J, Arnaud C, Rachet B, Burguet A,
Cambonie G; Epipage Study Group.
Collaborators: Larroque B, Ancel PY, Blondel B, Bréart G, Dehan M, Garel M,
Kaminski M, Maillard F, du Mazaubrun C, Missy P, Supernant K, Durand M, Matis J,
Messer J, Treisser A, Burguet A, Abraham-Lerat L, Menget A, Roth P, Schaal JP,
Thiriez G, Lévêque C, Marret S, Marpeau L, Boulot P, Picaud JC, Donadio AM,
Ledésert B, André, Fresson J, Boutroy JL, Hascoët JM, Arnaud C, Bourdet-Loubère
S, Grandjean H, Rolland M, Leignel C, Lequien P, Pierrat V, Puech F, Subtil D,
Truffert P, Boog G, Le Mauff E, Rouger-Bureau V, Rozé JC, Ancel PY, Bréart G,
Kaminski M, du Mazaubrun C, Dehan M, Zupan V, Vodovar M, Voyer M.
Department of Neonatology and Pediatric Intensive Care, Rouen Institute for
Biomedical Research, University of Rouen, Rouen, France.
vincent.laudenbach@chu-rouen.fr
BACKGROUND: Little is known about the influence of anaesthesia for caesarean
section on outcome in very preterm infants. METHODS: A prospective,
population-based, cohort study (the EPIPAGE cohort) included all births before 33
weeks in nine French regions in 1997. Of 2360 infants live-born between 27 and 32
weeks, 1338 were delivered by caesarean section with general anaesthesia (n=711,
53.1%), spinal anaesthesia (n=419, 31.3%), or epidural anaesthesia (n=208,
15.6%). Neonatal mortality was compared among these three groups using bi-
(according to gestational age and to anaesthetic technique) and multivariate
analyses. RESULTS: Neonatal mortality was 10.1% with general anaesthesia, 12.2%
with spinal anaesthesia and 7.7% with epidural anaesthesia. After adjustment for
gestational age and characteristics of pregnancy, delivery and neonate, spinal
anaesthesia was associated with a higher risk of neonatal death than general
anaesthesia (adjusted odds ratio, 1.7; 95% confidence interval 1.1 to 2.6).
CONCLUSION: In this population-based study, spinal anaesthesia was associated
with an increased risk of neonatal mortality in very preterm infants compared to
general anaesthesia (and epidural anaesthesia), independently from gestational
age and characteristics of the pregnancies, deliveries and neonates. Although
this multivariate analysis does not prove a causal relationship, the results
suggest it could exist, particularly if maternal haemodynamics are poorly
controlled. With recent significant change in the conduct of spinal anaesthesia,
further studies are needed to investigate potential harmful effects of
anaesthesia on very preterm infants delivered by caesarean section.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 19195873 [PubMed - in process]
23: Rev Med Interne. 2009 Apr;30(4):307-10. Epub 2009 Feb 4.
[Drug-associated tendon disorders: After fluoroquinolones ... here are statins!]
[Article in French]
Marie I, Noblet C.
Département de médecine interne, CHU de Rouen, 147, avenue du Marechal-Juin,
76031 Rouen cedex, France.
PMID: 19195746 [PubMed - in process]
24: Clin Vaccine Immunol. 2009 Apr;16(4):484-7. Epub 2009 Jan 28.
Prevalence of anti-varicella-zoster virus antibodies in French infants under 15
months of age.
Pinquier D, Gagneur A, Balu L, Brissaud O, Gras Le Guen C, Hau-Rainsard I, Mory
O, Picherot G, De Pontual L, Stephan JL, Maple P, Breuer J, Aubert M, Caulin E,
Sana C, Pradat P, Soubeyrand B, Reinert P.
Hôpital Charles Nicolle, Pôle Mère-Femme-Enfant, Centre Hospitalier Universitaire
Rouen, France. didier.pinquier@chu-rouen.fr
Varicella is a widespread disease of childhood resulting from primary infection
with varicella-zoster virus (VZV). The objective of this study was to determine
the kinetics of the decline of maternal anti-VZV antibodies in French infants
between birth and the age of 15 months in order to estimate the duration of
passively acquired maternal anti-VZV immunoglobulin G (IgG). This prospective
multicenter study was conducted between October 2005 and January 2007 in the
pediatric wards and/or pediatric emergency units of seven French hospitals
scattered throughout the country. The level of anti-VZV IgG antibodies in serum
was measured by a time-resolved fluorescence immunoassay (TRFIA) (the threshold
considered positive is 150 mIU/ml). A total of 345 infants were included.
Seventy-seven percent of mothers reported a history of varicella. A rapid decline
in the prevalence of anti-VZV antibodies was observed during the first few months
of life, with the mean antibody titer decreasing from 536 mIU/ml at birth and
through 1 month to below the 150-mIU/ml threshold at 3 to 4 months. The half-life
of passively acquired maternal immunoglobulins was around 6 weeks. Based on a
large number of subjects, this study clearly demonstrated, for the first time in
France, high levels of passively acquired maternal antibodies during the neonatal
period, and it allowed us to estimate the duration of passively acquired maternal
anti-VZV IgG in French infants. After 4 to 5 months, infants had very low levels
of maternal anti-VZV IgG, below the 150-mIU/ml cutoff of the VZV IgG TRFIA.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 19176690 [PubMed - in process]
25: Neurogastroenterol Motil. 2009 Apr;21(4):411-9. Epub 2008 Dec 18.
Does magnetic stimulation of sacral nerve roots modify colonic motility? Results
of a randomized double-blind sham-controlled study.
Gallas S, Gourcerol G, Ducrotté P, Mosni G, Menard JF, Michot F, Leroi AM.
Digestive Tract Research Group EA3234/IFRMP23, Rouen University Hospital,
University of Rouen, Rouen, France.
Although sacral nerve root stimulation (SNS) can result in a symptomatic
improvement of faecal incontinence, the mechanism of action remains unknown. The
aim of this study was to assess whether short-term magnetic SNS can inhibit
pharmacologically induced propulsive colonic contractions. Twelve healthy
volunteers (median age: 43.5 years old) were studied on two separate occasions
and randomized into either active (15 Hz, 100% output intensity for 5 s min(-1)
for 30 min) or sham rapid rate lumbosacral magnetic stimulation (rLSMS).
Colorectal motility was recorded with a manometric catheter located at the most
proximal transducer in the left colon and the most distal, in the rectum. Colonic
contractions were provoked by instilling Bisacodyl. The effects of rLSMS on
colonic, sigmoid and rectal contractions were monitored and recorded after
Bisacodyl instillation. The appearance of high-amplitude contractions propagated
or not (HAC/HAPC) provoked by Bisacodyl instillation was significantly delayed
during active compared to sham stimulation (P = 0.03). There was no difference in
the characteristics of HAC/HAPC (i.e. frequency, amplitude, duration, velocity of
propagation) or the motility index with active or sham stimulation. The
perception of urgency tended to be decreased with rLSMS following Bisacodyl
instillation. The catheter was expulsed within a median of 16.5 min (range 8-39)
after Bisacodyl administration during active stimulation compared to 14 min
(range 5-40) during sham stimulation (P = 0.03). This study suggests that rLSMS
could delay the appearance of the first Bisacodyl-induced colonic contractions.
PMID: 19126187 [PubMed - in process]
26: Int Urogynecol J Pelvic Floor Dysfunct. 2009 Apr;20(4):393-9. Epub 2008 Dec
17.
Female sexual function following surgery for stress urinary incontinence:
tension-free vaginal versus transobturator tape procedure.
Sentilhes L, Berthier A, Loisel C, Descamps P, Marpeau L, Grise P.
Department of Gynecology, Rouen University Hospital, Rouen, France.
loicsentilhes@hotmail.com
The aim of this study was to compare sexual function outcome following
tension-free vaginal (TVT) versus transobturator tape (TOT) for stress urinary
incontinence (SUI). All women who underwent TVT or TOT procedures for SUI with no
concomitant prolapse repair between January 2002 and July 2007 were sent a
retrospective pre-post questionnaire. Eighty-one and 64 women were sexually
active before and after TVT and TOT procedures, respectively. Sexual function
outcome did not differ pre- and postoperatively for the TVT and TOT groups, and
postoperatively between the two groups. Responders reported an improvement of
intercourse satisfaction in 23 (29.5%) and 21 (32.9%) cases, whereas 14 (17.3%)
and eight (12.5%) complained of sexual function deterioration after TVT and TOT
procedure, respectively (p = 0.43). This study suggests that anti-incontinence
surgery can have a positive and negative outcome on sexual function, with no
significant differences between the TVT and TOT procedures.
PMID: 19089306 [PubMed - in process]
27: Gut. 2009 Apr;58(4):586-93. Epub 2008 Nov 18.
Dietary modulation of peroxisome proliferator-activated receptor gamma.
Marion-Letellier R, Déchelotte P, Iacucci M, Ghosh S.
Appareil Digestif Environnement Nutrition (ADEN EA 4311), Faculté de
Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les
Peptides (IFR23), 22, boulevard Gambetta, 76183 Rouen cedex, France.
marion_rachel@hotmail.com
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear
receptor that regulates intestinal inflammation. PPAR gamma is highly expressed
in the colon and can be activated by various dietary ligands. A number of fatty
acids such as polyunsaturated fatty acids or eicosanoids are considered as
endogenous PPAR gamma activators. Nevertheless, other nutrients such as
glutamine, spicy food or flavonoids are also able to activate PPAR gamma. As PPAR
gamma plays a key role in bacterial induced inflammation, anti-inflammatory
properties of probiotics may be mediated through PPAR gamma. The aims of the
present review are to discuss of the potential roles of dietary compounds in
modulating intestinal inflammation through PPAR gamma.
Publication Types:
Review
PMID: 19017686 [PubMed - indexed for MEDLINE]
28: Indian J Med Sci. 2009 Mar;63(3):89-91.
Clinical interest of autoantibodies directed against citrullinated peptides in
Indian patients with rheumatoid arthritis.
Goeb V.
Rheumatology Department, Rouen University Hospital, Rouen, France.
goebvince@yahoo.fr.
PMID: 19359775 [PubMed - in process]
29: Curr Opin Rheumatol. 2009 May;21(3):244-50.
Costimulation blockade in rheumatic diseases: where we are?
Goëb V, Buch MH, Vital EM, Emery P.
Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine,
University of Leeds, Leeds LS7 4SA, UK.
PURPOSE OF REVIEW: To describe the mechanisms of action of abatacept (CTLA4-Ig)
and summarize the evidence of its efficacy and safety in rheumatoid arthritis
(RA) and other rheumatic diseases such as juvenile idiopathic arthritis (JIA).
RECENT FINDINGS: Several studies have demonstrated the clinical efficacy (disease
activity, quality of life, prevention of structural damage) of abatacept in
patients with RA who have failed to respond to standard disease-modifying
antirheumatic drugs (DMARDs) and antitumour necrosis factor-alpha biologic
agents. Selective modulation of T-cell costimulation may also be an alternative
therapy for children with JIA who are resitant to conventional DMARDs or
biologics. SUMMARY: T-cell activation is critical to the onset and maintenance of
RA. Abatacept (CTLA4-Ig), the first selective T-cell costimulation modulator has
shown to be effective in RA and JIA. Recent 2-year data from the 'AIM' trial
suggests an increased and sustained effect of blocking of T cell signalling on
the inhibition of RA structural damage progression over time. Abatacept's safety
profile in combination with DMARDs also seems to be favourable but should be
avoided in combination with other biologics.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 19342956 [PubMed - in process]