1: J Invest Dermatol. 2009 Jan 29. [Epub ahead of print]
A Comparison of Two Regimens of Topical Corticosteroids in the Treatment of
Patients with Bullous Pemphigoid: A Multicenter Randomized Study.
Joly P, Roujeau JC, Benichou J, Delaporte E, D'Incan M, Dreno B, Bedane C, Sparsa
A, Gorin I, Picard C, Tancrede-Bohin E, Sassolas B, Lok C, Guillaume JC, Doutre
MS, Richard MA, Caux F, Prost C, Plantin P, Chosidow O, Pauwels C, Maillard H,
Saiag P, Descamps V, Chevrant-Breton J, Dereure O, Hellot MF, Esteve E, Bernard
P.
1Department of Dermatology, INSERM U901, University of Rouen, Rouen, France.
Superpotent topical corticosteroids (CS) have been demonstrated to improve
bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen
using lower doses of topical CS and a shorter duration could improve the outcome
of BP patients even more. Three-hundred and twelve BP patients were included in a
multicenter randomized controlled trial and stratified depending on the extent of
BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to
the standard regimen (clobetasol propionate cream, 40 g per day initially, with
CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS
tapering over 4 months. A noninferior rate of BP control was obtained with the
mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%;
P=0.005). Event-free survival, that is, the combined outcome of deaths and
life-threatening adverse events did not differ between the two treatment groups
(P=0.77). However, upon adjusting through the Cox model for age and Karnofsky
score, a strong beneficial effect of the mild regimen was observed in patients
with moderate BP, with an almost twofold decrease in the risk of death or
life-threatening adverse events relative to the standard regimen (hazard
ratio=0.54; 95% confidence interval, 0.30-0.97; P=0.039). This mild regimen
allows a 70% reduction of the cumulative doses of CS and improves BP patients'
outcome.Journal of Investigative Dermatology advance online publication, 29
January 2009; doi:10.1038/jid.2008.412.
PMID: 19177141 [PubMed - as supplied by publisher]
2: Clin Vaccine Immunol. 2009 Jan 28. [Epub ahead of print]
Prevalence of anti-Varicella-Zoster virus antibodies in French infants below 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; CHU Brest, France; Hôpital Jean Verdier, Bondy, France; CHU
Bordeaux, France; Hôpital Mère-Enfant, Centre d'Investigation Clinique
Pédiatrique, CHU Nantes, France; CHI Créteil, France; CHU Nord, Saint-Etienne,
France; Centre for Infections, Health Protection Agency, London, UK; Institute of
Cell and Molecular Science, Queen Mary University, London, UK; Sanofi Pasteur
MSD, Lyon, France; Service d'Hepatogastroentérologie, Hotel-Dieu, Hospices Civils
de Lyon, France; IFR62 Lyon-Est, Université Claude Bernard Lyon 1, France; INSERM
U871, Lyon, France.
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 decline of maternal varicella antibodies between 0 and 15 months
of age in French infants in order to estimate the duration of passively acquired
maternal VZV IgG. This prospective multicentre study was conducted between
October 2005 and January 2007 in paediatric wards and/or paediatric emergency
units of seven French hospitals scattered throughout the country. The level of
anti-VZV IgG antibodies in serum was measured by the Time-Resolved Fluorescence
Immunoassay (TRFIA) technique (threshold 150 mIU/ml: considered as protective).
345 infants were included. Seventy-seven percent of mothers reported a history of
varicella. A rapid decline of the prevalence of anti-VZV antibodies was observed
during the first few months of life with the mean antibody titre decreasing from
536 mIU/mL in the [0-1[ month group to below the 150 mIU/mL threshold at already
3-4 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 allowed to estimate the
duration of passively acquired maternal VZV IgG in French infants. After 4-5
months, infants had very low levels of maternal VZV IgG below the negative (150
mIU/ml) cut off of the VZV IgG TRFIA.
PMID: 19176690 [PubMed - as supplied by publisher]
3: Mov Disord. 2009 Jan 23;24(2):286-289. [Epub ahead of print]
Microsubthalamotomy effect at day 3: Screening for determinants.
Maltête D, Chastan N, Derrey S, Debono B, Gérardin E, Lefaucheur R, Mihout B,
Hannequin D.
Department of Neurology, Rouen University Hospital, Rouen, France.
A microsubthalamotomy (mSTN) effect has been frequently reported after
implantation that improves Parkinson's motor disability. It is usually believed
that mSTN effect reflects the post-traumatic tissue reaction within the STN.
However, it has never, to our knowledge, been reported whether pre and
intraoperative factors could predict this mSTN effect. Preoperative clinical
characteristics, that is, age, disease duration, Mattis Dementia Rating Scale
score, levodopa responsiveness, severity of motor fluctuations and dyskinesia,
and intraoperative parameters, that is, the number of tracks, distance of typical
STN neuronal activity recorded along all microelectrodes, and along the
definitive electrodes, were assessed in 40 consecutive PD patients submitted for
STN stimulation. Multiple stepwise regression analysis showed that only the
number of tracks used for microelectrodes recordings was predictor of the
contralateral mSTN effect (F (4,73) = 1.83, P = 0.02). This result suggests that
the contralateral mSTN depends on the tissue changes along the entirety of
surgical trajectories affecting both STN and its adjacent structures. (c) 2008
Movement Disorder Society.
PMID: 19170190 [PubMed - as supplied by publisher]
4: J Clin Oncol. 2009 Jan 21. [Epub ahead of print]
Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa Polymorphisms and KRAS Mutations on the
Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With
Cetuximab Plus Irinotecan.
Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M, Blanchard F, Lamy A,
Penault-Llorca F, Frébourg T, Michel P, Sabourin JC, Boissière-Michot F.
Departments of Pathology, Biology, Biostatistics, and Oncology, Centre Régional
de Lutte Contre le Cancer Val d'Aurelle-Paul Lamarque, Montpellier; Digestive
Oncology Unit, Department of Gastroenterology, Rouen University Hospital; Inserm
U614, Faculty of Medicine; Department of Pathology, Rouen University Hospital;
and the Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France.
PURPOSE: The antiepidermal growth factor receptor antibody cetuximab shows
activity in irinotecan-refractory metastatic colorectal cancer (mCRC), mainly in
wild-type KRAS tumors. Cetuximab may also exert antitumor effects through
antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibody Fc portion
interacts with Fc receptors (FcgammaRs) expressed by immune cells. ADCC is
influenced by FcgammaRIIa-H131R and FcgammaRIIIa-V158F polymorphisms that are
clinically relevant in follicular lymphoma and metastatic breast cancer treated
with rituximab and trastuzumab, respectively. We investigated the association of
FcgammaR polymorphisms and KRAS mutation with the outcome of
irinotecan-refractory mCRC patients treated with cetuximab plus irinotecan.
PATIENTS AND METHODS: Tumor and normal tissues from 69 patients were screened for
KRAS mutations using a sensitive multiplex assay and genotyped for FcgammaRIIa
and FcgammaRIIIa polymorphisms by direct sequencing and multiplex allele-specific
polymerase chain reaction, respectively. The results were correlated with
response and progression-free survival (PFS). RESULTS: KRAS mutations were
associated with lower response rate (4% v 27% in nonmutated patients; P = .021)
and shorter PFS (3.0 v 5.3 months; P = .021). Patients with FcgammaRIIa-131H/H
and/or FcgammaIIIa-158V/V genotypes had longer PFS than 131R and 158F carriers
(5.5 v 3.0 months; P = .005). The difference remained significant for
mutated-KRAS patients. By multivariate analysis, KRAS mutation and FcgammaR
combined status were independent risk factors for PFS. CONCLUSION: Combined
FcgammaRIIa/FcgammaRIIIa polymorphisms are prognostic factors for disease
progression in mCRC patients treated with cetuximab plus irinotecan. As these
polymorphisms are also clinically relevant in mutated-KRAS mCRC, an important
role of ADCC in cetuximab efficacy is presumed.
PMID: 19164213 [PubMed - as supplied by publisher]
5: J Hosp Infect. 2009 Jan 20. [Epub ahead of print]
Aerial dispersal of meticillin-resistant Staphylococcus aureus in hospital rooms
by infected or colonised patients.
Gehanno JF, Louvel A, Nouvellon M, Caillard JF, Pestel-Caron M.
Department of Occupational Medicine, Rouen University Hospital, Rouen, France.
The aim of this study was to assess to what extent patients with
meticillin-resistant Staphylococcus aureus (MRSA) at respiratory sites shed
viable MRSA into the air of hospital rooms. We also evaluated whether the
distance from the patient could influence the level of contamination. Air
sampling was performed directly onto MRSA-selective agar in 24 hospital rooms
containing patients with MRSA colonization or infection of the respiratory tract.
Samplings were performed in duplicate at 0.5, 1 and 2-3m from the patients'
heads. Clinical and environmental isolates were compared using antimicrobial
resistance patterns and pulsed-field gel electrophoresis. MRSA strains were
isolated from 21 out of 24 rooms, in quantities varying from between 1 and
78cfu/m(3). In each of the 21 rooms, at least one of the environmental isolates
was identical to a clinical isolate from the patient in that room. There was no
significant difference in MRSA counts between the distance from the patient's
head and the sampler. This study demonstrates that most patients with MRSA
infection or colonisation of the respiratory tract shed viable MRSA into the air
of their room. The results emphasise the need to study MRSA in air in more detail
in order to improve infection control recommendations.
PMID: 19162372 [PubMed - as supplied by publisher]
6: Pathol Biol (Paris). 2009 Jan 19. [Epub ahead of print]
[Efficacy of a multidisciplinary team for preventing hospital acquired invasive
aspergillosis: A five years experience.]
[Article in French]
Etancelin P, Silly S, Merle V, Bonmarchand G, Richard JC, Vannier JP, Nouvellon
M.
Laboratoire d'hygiène hospitalière, institut de biologie clinique, CHU de Rouen,
1, rue de Germont, 76031 Rouen, France.
Invasive hospital-acquired aspergillosis (IA) is responsible for lethal
outbreaks. In 2002, an interdisciplinary team was created in the teaching
hospital of Rouen in order to organize the surveillance of construction sites by
the implementation of environmental measures of prevention. The aim of our study
was to estimate the efficiency of these measures using an indirect indicator,
reflecting the incidence of the cases of invasive nosocomial aspergillosis (AI):
the consumption of antifungals. From the nominative prescriptions established, we
studied the medical files about 210 patients to track down the number of IA cases
in intensive care unit (ICUI) and in pediatric hematology-oncology units between
2002 and 2006. The incidence of the cases was put in parallel with the various
periods of level 5-risk works during these five years. The relative risk of
appearance of the disease was calculated. In pediatric haematology-oncology unit,
35 cases were diagnosed on 99 medical files which have been studied and in ICU 19
cases were classified on 93 studied files. The follow-up of the incidence in both
units stake in parallel with the periods of level 5-risk works does not show
increase of the number of cases. The calculated relative risk indicates the same
result: the level 5-risk works are not a factor facilitating the appearance of
invasive aspergillosis cases. This study shows the importance of the
environmental measures of prevention during the periods of works within services
for risk. The coordination of the actors within an interdisciplinary cell seems
thus essential for the prevention of AIN.
PMID: 19157722 [PubMed - as supplied by publisher]
7: J Hosp Infect. 2009 Jan 13. [Epub ahead of print]
Influence of infection control report cards on patients' choice of hospital:
pilot survey.
Merle V, Germain JM, Tavolacci MP, Brocard C, Chefson C, Cyvoct C, Edouard S,
Guet L, Martin E, Czernichow P.
Department of Epidemiology and Public Health, Rouen University Hospital, Rouen,
France.
The impact on patients' attitudes of quality report cards on infection control in
hospitals has never previously been studied. In 2006, the French government
implemented a mandatory report card on infection control activity (ICALIN) in all
hospitals. This approach was aimed at encouraging professionals to change their
routine practices in case they should lose patients due to a low ICALIN score.
Our objective was to assess what impact ICALIN could have on patients' attitude
as regards hospital choice. We performed a survey of patients and visitors in 14
randomly selected hospitals of various ICALIN scores. A convenience sample of 381
patients and visitors completed an anonymous questionnaire on ICALIN, their
reasons for choosing a hospital and attitude in the event of a low ICALIN score.
Factors associated with interest in ICALIN and impact of ICALIN on hospital
choice were assessed by logistic regression. Our results showed that 77% of
participants were interested in ICALIN. ICALIN was ranked sixth as a reason for
choosing a hospital. In the case of a low ICALIN, 24.1% of participants would
refuse admission and 54.9% would seek advice from their general practitioner.
Sociodemographic factors had no influence on patients' attitude. In conclusion,
our survey suggests that patients take note of poor performance on infection
control report cards. As most patients rely on their general practitioner to
interpret these report cards, there is a definite need for further communication
with general practitioners on this issue.
PMID: 19147258 [PubMed - as supplied by publisher]
8: World J Gastroenterol. 2009 Jan 21;15(3):300-9.
Transient and etiology-related transcription regulation in cirrhosis prior to
hepatocellular carcinoma occurrence.
Caillot F, Derambure C, Bioulac-Sage P, Francois A, Scotte M, Goria O, Hiron M,
Daveau M, Salier JP.
Inserm Unite 905, Faculte de Medecine-Pharmacie, 22 Bvd Gambetta, 76183 Rouen
cedex, France. frederique.caillot@etu.univ-rouen.fr.
AIM: To search for transcription dysregulation that could (1) differentiate
hepatocellular carcinoma (HCC)-free from HCC-related cirrhosis (2) differentiate
HCC-free cirrhosis related to HCV from that related to alcohol intake. METHODS:
Using microarray analysis, we compared transcript levels in HCC-free cirrhosis
(alcoholism: 7; hepatitis C: 7), HCC-associated cirrhosis (alcoholism: 10;
hepatitis C: 10) and eight control livers. The identified transcripts were
validated by qRT-PCR in an independent cohort of 45 samples (20 HCC-free
cirrhosis; 15 HCC-associated cirrhosis and 10 control livers). We also confirmed
our results by immunohistochemistry. RESULTS: In HCC-free livers, we identified
70 transcripts which differentiated between alcoholic-related cirrhosis,
HCV-related cirrhosis and control livers. They mainly corresponded to
down-regulation. Dysregulation of Signal Transduction and Activator of
Transcription-3 (STAT-3) was found along with related changes in STAT-3 targets
which occurred in an etiology-dependent fashion in HCC-free cirrhosis. In
contrast, in HCC, such transcription dysregulations were not observed.
CONCLUSION: We report that transcriptional dysregulations exist in HCC-free
cirrhosis, are transiently observed prior to detectable HCC onset and may be
appear like markers from cirrhosis to HCC transition.
PMID: 19140229 [PubMed - in process]
9: Thromb Haemost. 2009 Jan;101(1):212-4.
Haplotypic or genotypic combinations of three protein Z polymorphisms influence
protein Z plasma level.
Le Cam-Duchez V, Barbay V, Bal Dit Sollier C, Drouet L, Coudert M, Soria C, Borg
JY.
Unité Fonctionnelle d'Hémostase Vasculaire, Hématologie Biologique, CHU de Rouen
- Hôpital Charles Nicolle, 1, rue de Germont, 76031 Rouen Cedex, France. E-mail:
Veronique.Le-Cam-Duchez@chu-rouen.fr.
PMID: 19132212 [PubMed - in process]
10: Crit Care Med. 2009 Jan;37(1):124-31.
Interface strategy during noninvasive positive pressure ventilation for
hypercapnic acute respiratory failure.
Girault C, Briel A, Benichou J, Hellot MF, Dachraoui F, Tamion F, Bonmarchand G.
Department of Medical Intensive Care, Rouen University Hospital, Rouen, France.
Christophe.Girault@chu-rouen.fr
OBJECTIVE: To assess the influence of initial mask choice on the clinical
effectiveness and tolerance of noninvasive positive pressure ventilation (NIPPV)
in the management of hypercapnic acute respiratory failure. DESIGN: A prospective
randomized controlled clinical study. SETTING: A medical intensive care unit at a
university hospital. INTERVENTION: Randomization between two NIPPV interfaces.
PATIENTS: Initial mask choice was randomized between two standard masks: face
(NIPPVf group) and nasal (NIPPVn group). The main end point was mask failure
(i.e., mask change and/or intubation). Secondary end points were tolerance of
NIPPV, change in respiratory parameters during the first 3 days, and patient
outcome. Results were analyzed on an intent to treat basis. A per protocol
analysis was also conducted. MAIN RESULTS: Ninety patients with underlying
chronic lung disease were included, 46 in the NIPPVf group and 44 in the NIPPVn
group. The overall success rate of NIPPV was 83%. Mask failure occurred
significantly more often in the NIPPVn group (32/44 vs. 9/46; p < 0.0001), mainly
because of the need for mask change (32/44 vs. 0/46; p < 0.0001) because of the
occurrence of major buccal air-leaks in 94% of cases. Improvement in respiratory
parameters was similar in the two groups. Whereas air-leaks were more frequent in
the NIPPVn group (p < 0.05), respiratory comfort was assessed as lower and
complications more frequent by the staff in the NIPPVf group from day 2 (p <
0.05). CONCLUSIONS: A face mask should be the first-line strategy in the initial
management of hypercapnic acute respiratory failure with NIPPV. However, if NIPPV
has to be prolonged, switching to a nasal mask may improve comfort by reducing
face mask complications.
PMID: 19050635 [PubMed - in process]
11: FEMS Microbiol Lett. 2009 Jan;290(1):105-13. Epub 2008 Nov 13.
Characterization of AtlL, a bifunctional autolysin of Staphylococcus lugdunensis
with N-acetylglucosaminidase and N-acetylmuramoyl-l-alanine amidase activities.
Bourgeois I, Camiade E, Biswas R, Courtin P, Gibert L, Götz F, Chapot-Chartier
MP, Pons JL, Pestel-Caron M.
Groupe de Recherche sur les Antimicrobiens et les Microorganismes, Rouen
University Hospital, Rouen, France.
The nucleotide sequence of atlL, a gene encoding a putative Staphylococcus
lugdunensis peptidoglycan hydrolase, was determined using degenerate consensus
PCR and genome walking. This 3837-bp gene encodes a protein, AtlL, that appears
as a putative bifunctional autolysin with a 29-amino acid putative signal peptide
and two enzymatic putative centres (N-acetylmuramoyl-l-alanine amidase and
N-acetylglucosaminidase) interconnected with three imperfect repeated sequences
displaying glycine-tryptophan motifs. In order to determine whether both lytic
domains were functional, and verify their exact enzymatic activities, gene
fragments harbouring both putative domains, AM (N-acetylmuramoyl-l-alanine
amidase enzymatic centre plus two repeated sequences) and GL
(N-acetylglucosaminidase enzymatic centre plus one repeated sequence), were
isolated, subcloned, and expressed in Escherichia coli. Purified recombinant AM
and GL protein truncations exhibited cell wall lytic activity in zymograms
performed with cell walls of Micrococcus lysodeikticus, Bacillus subtilis, and S.
lugdunensis. AtlL is expressed during the whole growth, with an overexpression in
the early-exponential stage. Liquid chromatography-mass spectrometry analysis of
muropeptides generated by digestion of B. subtilis cell walls demonstrated the
hydrolytic bond specificities and confirmed both of the acetyl domains'
activities as predicted by sequence homology data. AtlL is the first autolysin
described in S. lugdunensis, with a bifunctional enzymatic activity involved in
peptidoglycan hydrolysis.
PMID: 19025571 [PubMed - indexed for MEDLINE]
12: Am J Physiol Endocrinol Metab. 2009 Jan;296(1):E182-90. Epub 2008 Nov 4.
Methotrexate induces intestinal mucositis and alters gut protein metabolism
independently of reduced food intake.
Boukhettala N, Leblond J, Claeyssens S, Faure M, Le Pessot F, Bôle-Feysot C,
Hassan A, Mettraux C, Vuichoud J, Lavoinne A, Breuillé D, Déchelotte P, Coëffier
M.
ADEN EA4311, Institute for Biomedical Research, IFRMP23, 22 Boulevard Gambetta
76183 Rouen Cedex 1, France.
One of the main secondary toxic side effects of antimitotic agents used to treat
cancer patients is intestinal mucositis. This one is characterized by compromised
digestive and absorptive functions, barrier integrity, and immune competence. At
the same time, food intake is decreased, which may induce intestinal damages per
se. The aim of the study was to characterize which alterations are specific to
methotrexate, independently of the anorexic effect of the drug. Male
Sprague-Dawley rats received subcutaneously saline solution as control group or
2.5 mg/kg of methotrexate during 3 days (D0-D2). Methotrexate-treated rats were
compared with ad libitum and pair-fed controls. Histological examinations and
specific markers of the immune and nonimmune gut barrier function were assessed
at D4 or D7. Compared with ad libitum and pair-fed controls, methotrexate induced
at D4 villus atrophy associated with epithelial necrosis. Mucosal protein
synthesis rate and mucin contents of methotrexate treated rats were reduced. At
the same time, cathepsin D proteolytic activity was increased compared with ad
libitum and pair-fed controls, whereas calpain activity was increased when
compared with the only pair-fed controls. These intestinal lesions were
associated with various metabolic disturbances such as increased TNF-alpha level
and inflammation score in the jejunum but also disturbances of amino acid
concentrations in the duodenum and plasma. At D7, these alterations were
partially or completely normalized. In addition to the consequences of a low food
intake, methotrexate further impairs different biological processes leading to a
dramatic loss of gut homeostasis. Targeted nutritional management of chemotherapy
receiving patients should be set up to prevent or limit such alterations.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 18984853 [PubMed - in process]
13: Hum Reprod. 2009 Jan;24(1):37-44. Epub 2008 Oct 22.
Fertility preservation in adolescent males: experience over 22 years at Rouen
University Hospital.
Menon S, Rives N, Mousset-Siméon N, Sibert L, Vannier JP, Mazurier S, Massé L,
Duchesne V, Macé B.
Laboratoire de Biologie de la Reproduction-CECOS, Groupe de recherche EA 4308
'Spermatogenesis and Male Gamete Quality, Rouen University Hospital, 76031 Rouen
cedex, France.
BACKGROUND: Sperm banking is a suitable procedure to prevent infertility after
cancer therapy in male adolescents. We evaluated the feasibility of semen
preservation in 156 adolescents aged between 13 and 20 years and then we assessed
fertility outcome after treatment. METHODS: Age, urogenital history, indications
for cryopreservation, histological diagnosis and semen parameters were recorded.
Fertility status after treatment was assessed by a questionnaire addressed to
those patients who had utilized sperm storage. Post-treatment semen analysis was
performed for 22 patients. RESULTS: Cryopreservation was possible in 88.5% of
cases. Azoospermia was detected in 2.6% of the patients at the time of diagnosis.
Malignant disease accounted for 84% of our male adolescents. In this type of
disease, semen parameters were significantly altered only among patients with
metastatic malignant bone tumour. After treatment, nine patients presented
azoospermia, five patients achieved pregnancy spontaneously, two achieved it
after assisted reproductive technique using fresh ejaculated spermatozoa and one
following sperm donation. Three failed with cryopreserved sperm. CONCLUSIONS:
Semen cryopreservation is possible for most adolescents and, regardless of
disease type, may be a means of preserving fertility prior to gonadotoxic
treatment that might impair the spermatogenesis process.
PMID: 18945713 [PubMed - in process]
14: J Neurosurg. 2009 Jan;110(1):19-29.
Quality of life and brain damage after microsurgical clip occlusion or
endovascular coil embolization for ruptured anterior communicating artery
aneurysms: neuropsychological assessment.
Proust F, Martinaud O, Gérardin E, Derrey S, Levèque S, Bioux S, Tollard E,
Clavier E, Langlois O, Godefroy O, Hannequin D, Fréger P.
1 Departments of Neurosurgery,, 2 Neuroradiology, and, 3 Neurology, Rouen
University Hospital, Rouen; and, 4 Department of Neurology, Amiens University
Hospital, Amiens, France.
Object For anterior communicating artery (ACoA) aneurysms, endovascular coil
embolization constitutes a safe alternative therapeutic procedure to
microsurgical clip occlusion. The authors' aim in this study was to evaluate the
quality of life (QOL), cognitive function, and brain structure damage after the
treatment of ruptured ACoA aneurysms in a group of patients who underwent
microsurgical clipping (36 patients) compared with a reference group who
underwent endovascular coiling (14 patients). Methods At 14 months posttreatment
all patients underwent evaluations by independent observers. These observers
evaluated global efficacy, executive functions using a frontal assessment battery
of tests (Trail making test, Stroop tasks, dual task of Baddeley, verbal fluency,
and Wisconsin Card Sorting test), behavior dysexecutive syndrome (the Inventaire
du Syndrome Dysexécutif Comportemental questionnaire [ISDC]), and QOL by using
the Reintegration To Normal Living Index. Brain damage was analyzed using MR
imaging. Results In the microsurgical clipping and endovascular coiling groups,
the distribution on the modified Rankin Scale (p = 0.19) and mean QOL score (85.4
vs 83.4, respectively) were similar. Moreover, the proportion of executive
dysfunctions (19.4 vs 28.6%, respectively) and the mean score on the ISDC
questionnaire (8.9 vs 8.5, respectively) were not significant, but verbal memory
was more altered in the microsurgical clipping group (p = 0.055). Magnetic
resonance imaging revealed that the incidence of local encephalomalacia and the
median number of lesions per patient increased significantly in the microsurgical
clipping group (p = 0.003). Conclusions In the 2 groups, no significant
difference was observed regarding QOL, executive functions, and behavior. Despite
the significant decrease in verbal memory after microsurgical clipping, the
interdisciplinary approach remains a safe and useful strategy.
PMID: 18928356 [PubMed - in process]
15: Psychoneuroendocrinology. 2009 Jan;34(1):140-9. Epub 2008 Oct 8.
Regulation of feeding and anxiety by alpha-MSH reactive autoantibodies.
Sinno MH, Rego JC, Coëffier M, Bole-Feysot C, Ducrotté P, Gilbert D, Tron F,
Costentin J, Hökfelt T, Déchelotte P, Fetissov SO.
Digestive System & Nutrition Laboratory (ADEN EA4311), Institute of Biomedical
Research, Rouen University & Hospital, IFR23, 76183 Rouen, France.
alpha-Melanocyte-stimulating hormone (alpha-MSH) is a stress-related neuropeptide
involved in the regulation of motivated behavior, appetite and emotion including
stimulation of satiety and anxiety. Although autoantibodies (autoAbs) reactive
with alpha-MSH have been identified in human subjects and in rats, it remained
unknown if these autoAbs are involved in the regulation of feeding and anxiety
and if their production is related to stress. Here we show that repeated exposure
of rats to anxiolytic mild stress by handling increases the levels and affinity
of alpha-MSH reactive IgG autoAbs and that these changes are associated with
adaptive feeding and anxiety responses during exposure of rats to a strong stress
by food restriction. Importantly, an increase in affinity of alpha-MSH reactive
autoAbs was associated with changes of their functional roles from stimulation to
inhibition of alpha-MSH-mediated behavioural responses, suggesting that these
autoAbs can be a carrier or a neutralizing molecule of alpha-MSH peptide,
respectively. Using a model of passive transfer into the brain, we show that
alpha-MSH autoAbs affinity purified from blood of rats exposed to repeated mild
stress, but not from control rats, are able to increase acutely food intake,
suppress anxiety and modify gene expression of hypothalamic neuropeptides in
naïve rats. These data provide the first evidence that autoAbs reactive with
alpha-MSH are involved in the physiological regulation of feeding and mood,
supporting a further role of the immune system in the control of motivated
behavior and adaptation to stress.
PMID: 18842346 [PubMed - in process]
16: Rev Med Interne. 2009 Jan;30(1):53-7. Epub 2008 Oct 4.
[Uncommon manifestation revealing sarcoidosis.]
[Article in French]
Armengol G, Bernet J, Lahaxe L, Lévesque H, Marie I.
Département de médecine interne, CHU de Rouen-Boisguillaume, 147, avenue du
Maréchal-Juin, 76031 Rouen cedex, France.
INTRODUCTION: Bilateral hilar lymphadenopathy, with or without lung parenchymal
infiltrates, is the most common radiographic finding in patients with
sarcoidosis. Atypical pulmonary findings have been uncommonly reported and
include multiple large lung nodules, cavitation, lobar collapse, pleural
effusions or pneumothorax. OBSERVATION: We report a 21-year-old non caucasian
patient who presented with pulmonary nodular infiltration and sinonasal
involvement revealing sarcoidosis. Thoracic and sinus computed tomographic scan
showed both multiple excavated large lung nodules and micronodules, hilar
lymphadenopathy and sinus thickening. Laboratory studies disclosed elevated
angiotensin converting enzyme serum level (120UI/L). Outcome was favorable after
institution of corticosteroids (at an initial dose of prednisone of 1mg/kg/day);
at eight-month-follow-up, the patient was asymptomatic, while receiving
prednisone 22.5mg/day. CONCLUSION: In patients exhibiting unusual pulmonary
manifestations, diagnosis of sarcoidosis relies on compatible clinical signs,
evidence of non-caseating granulomas, and exclusion of underlying conditions
including infections, malignancy and other granulomatous diseases (Wegener
disease, pneumoconiosis).
Publication Types:
English Abstract
PMID: 18835653 [PubMed - in process]
17: Neuropsychopharmacology. 2009 Jan;34(2):424-35. Epub 2008 Jun 4.
Pituitary adenylate cyclase-activating polypeptide inhibits food intake in mice
through activation of the hypothalamic melanocortin system.
Mounien L, Do Rego JC, Bizet P, Boutelet I, Gourcerol G, Fournier A, Brabet P,
Costentin J, Vaudry H, Jégou S.
INSERM U 413, Laboratory of Cellular and Molecular Neuroendocrinology, University
of Rouen, Mont-Saint-Aignan, France.
Pituitary adenylate cyclase-activating polypeptide (PACAP) and the
proopiomelanocortin (POMC)-derived peptide, alpha-melanocyte-stimulating hormone
(alpha-MSH), exert anorexigenic activities. While alpha-MSH is known to inhibit
food intake and stimulate catabolism via activation of the central
melanocortin-receptor MC4-R, little is known regarding the mechanism by which
PACAP inhibits food consumption. We have recently found that, in the arcuate
nucleus of the hypothalamus, a high proportion of POMC neurons express PACAP
receptors. This observation led us to investigate whether PACAP may inhibit food
intake through a POMC-dependent mechanism. In mice deprived of food for 18 h,
intracerebroventricular administration of PACAP significantly reduced food intake
after 30 min, and this effect was reversed by the PACAP antagonist PACAP6-38. In
contrast, vasoactive intestinal polypeptide did not affect feeding behavior.
Pretreatment with the MC3-R/MC4-R antagonist SHU9119 significantly reduced the
effect of PACAP on food consumption. Central administration of PACAP induced
c-Fos mRNA expression and increased the proportion of POMC neuron-expressing
c-Fos mRNA in the arcuate nucleus. Furthermore, PACAP provoked an increase in
POMC and MC4-R mRNA expression in the hypothalamus, while MC3-R mRNA level was
not affected. POMC mRNA level in the arcuate nucleus of PACAP-specific receptor
(PAC1-R) knock-out mice was reduced as compared with wild-type animals. Finally,
i.c.v. injection of PACAP provoked a significant increase in plasma glucose
level. Altogether, these results indicate that PACAP, acting through PAC1-R, may
inhibit food intake via a melanocortin-dependent pathway. These data also suggest
a central action of PACAP in the control of glucose metabolism.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 18536705 [PubMed - in process]
18: Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 5;150B(1):148-50.
No pathogenic rearrangement within the DISC 1 gene in psychosis.
Legallic S, Bou J, Haouzir S, Allio G, Demily C, Petit M, Frebourg T, Thibaut F,
Campion D.
INSERM U, IFRMP, Rouen, France.
A translocation disrupting the DISC 1 gene segregates with schizophrenia and
related psychiatric disorders in a large Scottish family. Mutation screening of
this gene by routine PCR-based methods has remained largely negative. We sought
to detect rearrangements affecting DISC 1 in 347 individuals meeting the DSM3R
criteria for schizophrenia or schizoaffective disorder, 70 subjects with bipolar
disorder and 377 psychiatrically healthy controls, but failed to detect any
pathological rearrangement. 2008 Wiley-Liss, Inc.
PMID: 18395819 [PubMed - in process]
