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1: Hum Mutat. 2006 Aug 28;27(10):1063 [Epub ahead of print] Biological effects of four PSEN1 gene mutations causing Alzheimer disease with spastic paraparesis and cotton wool plaques. Dumanchin C, Tournier I, Martin C, Didic M, Belliard S, Carlander B, Rouhart F, Duyckaerts C, Pellissier JF, Latouche JB, Hannequin D, Frebourg T, Tosi M, Campion D. Inserm U614, IFRMP, Faculte de Medecine, Rouen, France. We describe the biological consequences on PSEN1 exons 8 or 9 splicing and Abeta peptides production of four PSEN1 mutations associated with a phenotypic variant of Alzheimer disease, which includes cotton wool plaques and spastic paraparesis (CWP/SP). Two of these mutations (c.869-22_869-23ins18 and c.871A>C, p.T291P) are novel mutations located in intron 8 and exon 9, respectively. The c.869-22_869-23ins18 mutation caused exon 9 skipping whereas the c.871A>C (p.T291P) mutation showed only a modest effect on exon 9 skipping. The previously reported E280G and P264L mutations, located in exon 8, had no effect on mRNA splicing. Infection of cells with mutant T291P, E280G, or P264L cDNAs caused a variable increase in secreted Abeta42. We conclude that none of the previously proposed mechanisms, i.e. exceptionally large increases in secreted Abeta42 levels or loss of PSEN1 exons 8 or 9, provides complete explanation of the CWP/SP phenotype. (c) 2006 Wiley-Liss, Inc. PMID: 16941492 [PubMed - as supplied by publisher] 2: J Radiol. 2006 Sep;87(9):1007. [Continuing Medical Education: apply for FEPUR accreditation!] [Article in French] Dacher J. President de la FEPUR, Federation de Radiodiagnostic et Imagerie Medicale, CHU de Rouen, 1 rue de Germont, F-76031 Rouen Cedex. PMID: 16936623 [PubMed - in process] 3: Adv Cardiol. 2006;43:97-105. Heart rate slowing for myocardial dysfunction/heart failure. Mulder P, Thuillez C. INSERM U644, Faculte de Medecine et de Pharmacie, Rouen, France. Heart failure is a major health problem, and is one of the few cardiovascular diseases that increased its prevalence over the last decade. Increased heart rate, generally observed in patients with heart failure, is involved in the deterioration of cardiac pump function. However, the effects of 'pure' heart rate reduction on the progression of heart failure are unknown. In a rat model of heart failure, ivabradine, a blocker of I(f) channels reduces dosedependently heart rate without modification of blood pressure. This heart rate reduction is associated with an improvement in cardiac function. After chronic administration, this improvement of cardiac function persists after ivabradine withdrawal, revealing an improvement in intrinsic myocardial function. This beneficial effect could be explained by direct effects of heart rate reduction induced by ivabradine, i.e. improved myocardial oxygen supply to demand ratio, and/or myocardial tissular effects induced by chronic decrease in heart rate such, i.e. decreased extracellular collagen accumulation, increased myocardial microcirculation. In conclusion, 'pure' chronic heart rate reduction can be beneficial in heart failure. PMID: 16936475 [PubMed - in process] 4: Ann Cardiol Angeiol (Paris). 2006 Aug;55(4):199-203. [Immediate results and clinical follow-up of patients treated with drug eluting stents implantation in routine clinical practice] [Article in French] Vochelet F, Tron C, Eltchaninoff H, Sebagh L, Tavildari A, Cribier A. Service de cardiologie, hopital Charles-Nicolle, 1, rue de Germont, 76000 Rouen, France. Multiple recent randomized studies have demonstrated the superiority of drug eluting stents (DES) compared to bare stents for reduction of restenosis rates after angioplasty. We sought to study if the results obtained in these studies with highly selected patients could be translated to patients treated in routine clinical practice. To this end, we retrospectively reviewed hospital charts of 134 consecutive patients treated in our center with 202 DES implantation between November 2002 and January 2004. Thirty nine % of patients had diabetes and 59% had multivessel disease. Coronary lesions were often complex (type B2: 24%, type C: 35%). Mean percent diameter stenosis was 68 +/- 13% with a reference artery diameter of 2.62 +/- 0.5 mm. One patient (0.75%) died in-hospital from cardiogenic shock. At a mean follow-up of 12 +/- 2.6 months, 7 patients (5.3%) died, including 2 extracardiac deaths. Recurrent chest pain occurred in 16 patients (12%), with only 3 (2.3%) in-stent restenosis. Major adverse cardiac event rate was 8.2%. This study confirms that in a non-selected population, the rate of subsequent revascularization after DES implantation is very low. It can be hoped that the indications of implantations will progressively spread with a lowered cost of these DES. PMID: 16922169 [PubMed - in process] 5: Arterioscler Thromb Vasc Biol. 2006 Aug 17; [Epub ahead of print] Direct and Indirect Effects of Alloantibodies Link Neointimal and Medial Remodeling in Graft Arteriosclerosis. Thaunat O, Louedec L, Jianping D, Bellier F, Groyer E, Delignat S, Gaston AT, Caligiuri G, Joly E, Plissonnier D, Michel JB, Nicoletti A. Universite Pierre et Marie Curie-Paris6, INSERM UMRS 681, Centre de recherche des Cordeliers, Paris; INSERM U698 and Universite Denis Diderot, Hopital Xavier Bichat, Paris; INSERM U563, IFR Claude de Preval, Toulouse; and Department of Vascular Surgery, Hopital Universitaire de Rouen, France. OBJECTIVE: Chronic vascular rejection, the main cause of allograft failure, is characterized by the destruction of smooth muscle cells (SMCs) in the media concomitantly with the proliferation of SMCs in the adjacent neointima. We hypothesized that alloantibodies might be responsible for these 2 opposite but coordinated events. METHODS AND RESULTS: We used the rat aortic interposition model of chronic vascular rejection. During the rejection process, a neointima composed of proliferating SMCs from the recipient developed, whereas the SMCs in the media, all of donor origin, underwent apoptosis. Alloantibody deposition was detected only in the media. Using in vitro cultures experiments, we observed that alloantibody binding to donor SMCs exerts (1) a rapid upregulation of the transcription of growth factors genes, followed by (2) the induction of apoptosis after 24 hours. The transient production of growth factors by donor SMCs in response to the binding of alloantibodies induced the proliferation of recipient SMCs in culture supernatant transfer experiments. Additional data suggest that among the repertoire of alloantibodies, those directed against myosin heavy chain I might carry the remodeling effect. CONCLUSIONS: Our data suggest that during chronic vascular rejection, alloantibody binding to donor medial SMCs is a crucial event that links neointimal and medial remodeling. PMID: 16917106 [PubMed - as supplied by publisher] 6: Crit Care Med. 2006 Aug 15; [Epub ahead of print] Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: The PNEUMOREA prospective multicenter study* Auburtin M, Wolff M, Charpentier J, Varon E, Le Tulzo Y, Girault C, Mohammedi I, Renard B, Mourvillier B, Bruneel F, Ricard JD, Timsit JF. From the Service de Reanimation Medicale et des Maladies Infectieuses, Hopital Bichat-Claude-Bernard (MA, MW, BM, J-FT), AP-HP, Paris; Service de Reanimation Medicale, Hopital Cochin (JC), AP-HP, Paris; Centre National de Reference des Pneumocoques, Hopital Europeen Georges-Pompidou (EV), AP-HP, Paris; Service de Maladies Infectieuses et Reanimation Medicale, Hopital Pontchaillou (YLT), Rennes; Service de Reanimation Medicale, Hopital Charles-Nicolle (CG), Rouen; Service de Reanimation Medicale, Hopital Edouard-Herriot (IM), Lyon; Service de Reanimation Medicale, Hotel-Dieu (BR), Nantes; Service de Reanimation Medicale, Hopital Andre-Mignot (FB), Le Chesnay; Service de Reanimation Medicale, Hopital Louis-Mourier (J-DR), AP-HP, Paris; and Groupe d'Epidemiologie, INSERM U578, and Service de Reanimation Medicale, Hopital Albert Michalon (J-FT), Grenoble, France. OBJECTIVE:: To identify factors associated with mortality and morbidity among adults admitted to intensive care units (ICUs) for pneumococcal meningitis, particularly the impact of delayed antibiotic administration. DESIGN:: We conducted a prospective, multicenter, observational study of 156 consecutive adults hospitalized for pneumococcal meningitis. We analyzed parameters associated with 3-month survival. SETTING:: Fifty-six medical and medical-surgical ICUs in France. INTERVENTION:: None. RESULTS:: Of the 148 strains isolated, 56 (38%) were nonsusceptible to penicillin G. At 3 months after ICU admission, the mortality rate was 33% (51/156), and 34% of survivors (36/105) had neurologic sequelae. Multivariate analysis identified three variables as independently associated with 3-month mortality: Simplified Acute Physiology Score II (odds ration [OR], 1.12; 95% confidence interval [CI], 1.072-1.153; p = .002); isolation of a nonsusceptible strain (OR, 6.83; 95% CI, 2.94-20.8; p < 10), and an interval of >3 hrs between hospital admission and administration of antibiotics (OR, 14.12; 95% CI, 3.93-50.9; p < 10). In contrast, a cerebrospinal fluid leukocyte count >10 cells/muL had a protective effect (OR, 0.30; 95% CI, 0.10-0.944; p = 0.04). CONCLUSIONS:: Independent of severity at the time of ICU admission, isolation of penicillin-nonsusceptible strains and a delay in antibiotic treatment following admission were predictors of mortality among patients with pneumococcal meningitis. PMID: 16915106 [PubMed - as supplied by publisher] 7: J Clin Forensic Med. 2006 Aug 14; [Epub ahead of print] Sudden death from a "broken heart" in a young woman. Clarot F, Vaz E, Vicomte C, Gricourt C, Papin F, Proust B. Rouen University Hospital, Department of Forensic Medicine, CHU Rouen-Charles, Nicolle-Rouen 76031, France. A case of ruptured myocardial infarct in a young woman with no previous medical history is presented, as well as a review of the literature and forensic aspects are discussed. PMID: 16914361 [PubMed - as supplied by publisher] 8: J Am Geriatr Soc. 2006 Aug;54(8):1225-30. Clinical presentation of hypernatremia in elderly patients: a case control study. Chassagne P, Druesne L, Capet C, Menard JF, Bercoff E. Geriatrics Department, CHU Rouen, Rouen, France. philippe.chassagne@chu-rouen.fr OBJECTIVES: To assess early clinical signs and their prognostic value in elderly patients with hypernatremia. DESIGN: Prospective, case control study of 150 patients with hypernatremia matched to 300 controls. SETTING: Multicenter study including seven short- and long-term geriatric care facilities. MEASUREMENTS: Clinical assessment of hydration status at bedside, such as abnormal skin turgor or dry oral mucosa. Secondary outcome measures: 30-day mortality rate and clinical indicators (assessed at the peak of natremia) associated with mortality. RESULTS: Patients and controls were comparable in terms of drugs and underlying diseases, except for history of dementia, which was more frequent in patients than in controls. Patients were significantly more likely than controls to have low blood pressure, tachycardia, dry oral mucosa, abnormal skin turgor, and recent change of consciousness. Only three clinical findings were found in at least 60% of patients with hypernatremia: orthostatic blood pressure and abnormal subclavicular and forearm skin turgor. The latter two signs were significantly more frequent in patients with hypernatremia. Four other signs (tachycardia, abnormal subclavicular skin turgor, dry oral mucosa, and recent change of consciousness) had a specificity of greater than 79%. Using logistic regression, four signs were significantly and independently associated with hypernatremia: abnormal subclavicular and thigh skin turgor, dry oral mucosa, and recent change of consciousness. The mortality rate was 41.5% and was significantly higher in patients with hypernatremia. The status of consciousness when hypernatremia was diagnosed was the single prognostic indicator associated with mortality (odds ratio=2.3, 95% confidence interval=1.01-5.2). CONCLUSION: Most of the classical signs of dehydration are irregularly present in patients with hypernatremia. Caregivers should carefully screen any variations in consciousness, because they may reveal severe hypernatremia. PMID: 16913989 [PubMed - in process] 9: Graefes Arch Clin Exp Ophthalmol. 2006 Aug 10; [Epub ahead of print] Impact of new lamellar techniques of keratoplasty on eye bank activity. Muraine M, Toubeau D, Gueudry J, Brasseur G. Department of Ophthalmology, Hopital Charles Nicolle, Boulevard Gambetta, 76031 Cedex, Rouen, France, Marc.Muraine@chu-rouen.fr. BACKGROUND: Deep anterior lamellar keratoplasty (DALK) has become an increasingly popular alternative to penetrating keratoplasty in patients with stromal corneal pathologies. The main advantages of DALK are: prevention of long-term endothelial loss, elimination of allograft reaction and short topical steroid treatment with lower risks of glaucoma, cataract and infection. Because this technique enables surgeons to use corneal grafts with low endothelial density, the aim of this paper was to determine whether this type of innovation has had a significant impact on eye bank activity. METHODS: We reviewed our corneal graft activity over a 40-month period and assessed the proportion of deep lamellar and penetrating keratoplasties. During the same period, we also evaluated our eye bank activity and recorded the utilisation of grafts with endothelium abnormalities, which were only suitable for lamellar techniques. RESULTS: Deep lamellar keratoplasty represented 29.8% (85 out of 285) of corneal transplantations. Forty-eight percent of all corneas stored at the local eye bank were unsuitable for penetrating keratoplasty; 36.6% of those were not suitable for endothelial deficiencies. Among these, 72.7% were used for DALK and 27.3% were rejected. This permitted a 24.5% increase in corneal grafting activity. In contrast, Descemet's membrane was removed at the time of surgery in 12% of corneas with healthy endothelium, which was used for deep lamellar keratoplasty. CONCLUSIONS: Deep anterior lamellar keratoplasty development and close collaboration between eye banks and surgeons can induce a significant increase in corneal grafting. This could be a partial solution in countries confronted with corneal graft shortages. PMID: 16900356 [PubMed - as supplied by publisher] 10: Rheumatology (Oxford). 2006 Aug 9; [Epub ahead of print] Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are unable to predict their responses to infliximab. Lequerre T, Jouen F, Brazier M, Clayssens S, Klemmer N, Menard JF, Mejjad O, Daragon A, Tron F, Le Loet X, Vittecoq O. Rheumatology Department, Rouen University Hospital, Rouen, France; Inserm U519, IFR 23, Faculte de Medecine, Rouen, France. Objectives. To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients' responses to infliximab. Methods. A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software. Results. Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab. Conclusion. The search for soluble markers in RA patients' sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis. PMID: 16899502 [PubMed - as supplied by publisher] 11: Intensive Care Med. 2006 Aug 1; [Epub ahead of print] Effects of vertical positioning on gas exchange and lung volumes in acute respiratory distress syndrome. Richard JC, Maggiore SM, Mancebo J, Lemaire F, Jonson B, Brochard L. Medical Intensive Care Unit, UPRES EA 38 30, Rouen University Hospital Charles Nicolle, 1 rue de Germont, 76031, Rouen, France, Jean-Christophe.Richard@chu-rouen.fr. OBJECTIVE: Supine position may contribute to the loss of aerated lung volume in patients with acute respiratory distress syndrome (ARDS). We hypothesized that verticalization increases lung volume and improves gas exchange by reducing the pressure surrounding lung bases. DESIGN AND SETTING: Prospective observational physiological study in a medical ICU. SUBJECTS AND INTERVENTION: In 16 patients with ARDS we measured arterial blood gases, pressure-volume curves of the respiratory system recorded from positive-end expiratory pressure (PEEP), and changes in lung volume in supine and vertical positions (trunk elevated at 45 degrees and legs down at 45 degrees ). MEASUREMENTS AND RESULTS: Vertical positioning increased PaO(2) significantly from 94[Symbol: see text]+/-[Symbol: see text]33 to 142[Symbol: see text]+/-[Symbol: see text]49[Symbol: see text]mmHg, with an increase higher than 40% in 11 responders. The volume at 20[Symbol: see text]cmH(2)O measured on the PV curve from PEEP increased using the vertical position only in responders (233[Symbol: see text]+/-[Symbol: see text]146 vs. -8[Symbol: see text]+/-[Symbol: see text]91[Symbol: see text]ml in nonresponders); this change was correlated to oxygenation change (rho[Symbol: see text]=[Symbol: see text]0.55). End-expiratory lung volume variation from supine to vertical and 1[Symbol: see text]h later back to supine, measured in 12 patients showed a significant increase during the 1-h upright period in responders (n[Symbol: see text]=[Symbol: see text]7) but not in nonresponders (n[Symbol: see text]=[Symbol: see text]5; 215[Symbol: see text]+/-[Symbol: see text]220 vs. 10[Symbol: see text]+/-[Symbol: see text]22[Symbol: see text]ml), suggesting a time-dependent recruitment. CONCLUSIONS: Vertical positioning is a simple technique that may improve oxygenation and lung recruitment in ARDS patients. PMID: 16896856 [PubMed - as supplied by publisher] 12: Nephrol Ther. 2005 Dec;1(6):323-4. [Boredom once arose from uniformity.] [Article in French] Godin M, Canaud B. Nephrologie, CHU de Rouen, Hopital de Bois-Guillaume, 76031 Rouen cedex, France. Publication Types: Editorial PMID: 16895702 [PubMed - in process] 13: Proteomics. 2006 Aug 7;6(17):4829-4837 [Epub ahead of print] Proteomic analysis of the autoantibody response following immunization with a single autoantigen. Mouquet H, Drouot L, Charlionnet R, Arnoult C, Bonnet-Bayeux F, Thomas M, Leprince J, Joly P, Tron F, Gilbert D. Inserm, U519 and IFR23, Faculte de Medecine et de Pharmacie, Rouen, France. In most autoimmune diseases, the autoantibody response is directed against several antigens of the target organ whose identification is crucial for understanding the physiopathological process. Thus, technologies allowing a characterization of the whole autoantibody pattern of both human and experimental autoimmune diseases are required. Here we have used immunoproteomic analysis of human epidermal extracts to characterize the diversity of the anti-desmosome antibody response induced in normal mice immunized with desmoglein 1, the major autoantigen of pemphigus foliaceus, an autoimmune blistering skin disease. In particular, this analysis enables us to characterize the binding properties of anti-desmosome mAbs derived from these mice and to show that the autoantibody response induced upon immunization with a single autoantigen targets different epidermal autoantigens with a pattern similar to that observed in certain variety of human pemphigus. PMID: 16892487 [PubMed - as supplied by publisher] 14: Ann Fr Anesth Reanim. 2006 Aug 4; [Epub ahead of print] [Interest of D-lactate as a colic hypoperfusion marker during aortic abdominal aneurysm surgery.] [Article in French] Collange O, Veber B, Tamion F, Lavoine A, Plissonnier D, Dureuil B. Departement d'anesthesie-reanimation, hopital Charles-Nicolle, CHU de Rouen, 76031 Rouen, France; Inserm E9920, faculte de medecine pharmacie de Rouen, France. OBJECTIVE: D-lactate is the dextogyre form of the lactate usually measured in intensive care. Its bacterial origin should make it a marker of translocation during gut ischemia. The aim was to test D-lactate as a postoperative marker of colic hypoperfusion measured during aortic surgery. STUDY DESIGN: Prospective observational cohort study. PATIENTS AND MEASUREMENTS: Patients operated for abdominal aortic aneurysm. Two groups were stratified on inferior mesenteric arterial residual pressure (IMArP) measured during the surgery: Colic hypoperfusion during surgery (CHs) group: patients with an IMArP<40 mmHg. Control Group: patients with an IMArP>/=40 mmHg. Baseline data such as age, duration of aortic clamping and severity score (IGS II) were collected. The D-lactate was measured in postoperative at admission time in ICU and then daily. D-lactate(max) defined the maximum value of D-lactate for one patient. MAIN RESULTS: Twenty-nine patients were included, 23 in the control group and 6 in the CHs group. Groups were comparable at baseline. D-lactate(max) was significantly higher in the CHs group (median: 0.13 mmol/l; min-max: 0.03-0.9 mmol/l) than in the control group (0.03; 0-0.26 mmol/l, p=0.007). CONCLUSION: D-lactate could be postoperative marker of colic hypoperfusion measured during surgery for abdominal aortic aneurysm. PMID: 16891085 [PubMed - as supplied by publisher] 15: J Hosp Infect. 2006 Aug 4; [Epub ahead of print] Alcohol-based hand rub: influence of healthcare workers' knowledge and perception on declared use. Tavolacci MP, Merle V, Pitrou I, Thillard D, Serra V, Czernichow P; the Alcohol-based Hand Rub Commission of Infection Control Committee. Department of Epidemiology and Public Health, Rouen University Hospital, Rouen, France; Commission of Infection Control Committee, Rouen University Hospital, Rouen, France. Handrubbing with alcohol-based hand rub (AHR) is a validated alternative to handwashing. The aims of this study were to compare knowledge and declared use of AHR between different categories of healthcare worker (HCW), and to assess factors associated with the use of AHR. A standardized questionnaire was sent to all HCWs in a tertiary care university hospital. The following data were collected for each HCW: job title (physician, nurse, nursing assistant or other), sources of information about AHR; knowledge and perception of AHR and declared use of AHR in daily practice instead of unmedicated or antiseptic soap. Of 5238 questionnaires, 1811 were returned. Physicians had better knowledge about AHR than other HCWs. HCWs' knowledge of AHR efficacy and skin tolerance were independently associated with the use of AHR instead of unmedicated or antiseptic soap. The declared use of AHR differed according to professional category. PMID: 16891041 [PubMed - as supplied by publisher] 16: Nephrol Ther. 2006 Jul;2(3):136-139. Epub 2006 May 19. [Cutaneous infection due to Mycobacterium chelonae in a hemodialysed patient.] [Article in French] Drouineau O, Rivault O, Le Roy F, Martin-Passos E, Young P, Godin M. Service de nephrologie hemodialyse transplantation renale, hopital de Bois-Guillaume, CHU de Rouen, 147, avenue Marechal-Juin, 76230 Bois-Guillaume, France. We report a case of a hemodialysed patient who developed a cutaneous Mycobacterium chelonae infection. This infection was only localised on the left upper limb, downstream from the arteriovenous fistula. M. chelonae is an unusual human pathogen, which is present in soil, dust, and stagnant water. Various factors, especially immunosuppression can favour this sort of infection in humans. Because of the ubiquity of the mycobacterium, the source of the inoculation sometimes remains unknown. However, a great number of cases are related to nosocomial infections. The preferential localizations are cutaneous, ocular, and pulmonary. Some cases of cutaneous infections due to M. chelonae, or caused by other atypical mycobacterium, are described in renal transplantation, peritoneal dialysis and hemodialysis. In the case we describe here, the source of contamination was not identified. The outcome was favourable with clarithromycin. This treatment is still continued because of a reappearance of the lesions when treatment was discontinued. PMID: 16890138 [PubMed - as supplied by publisher] 17: J Radiol. 2006 Jul-Aug;87(7-8):973-5. [What is your diagnosis?] [Article in French] Creuze N, Lachkar S, Bertrand D, Etienne M, Savoye-Collet C, Caron F, Dacher JN. Departement d'imagerie medicale, Service de maladies infectieuses et tropicales, CHU Charles Nicolle, Rouen, France. PMID: 16888592 [PubMed - in process] 18: Gastroenterol Clin Biol. 2006 Jun-Jul;30(6-7):845-51. Impact of radiation schedule and chemotherapy duration in definitive chemoradiotherapy regimen for esophageal cancer. Di Fiore F, Lecleire S, Galais MP, Rigal O, Vie B, David I, Hamidou H, Paillot B, Jacob JH, Michel P. Digestive Oncology Unit, Hepatogastroenterology Department, Rouen University Hospital- Charles Nicolle, Rouen. eliottdf@hotmail.com Impact of radiotherapy (RT) schedule on local response and duration of the 5-fluorouracil/cisplatin (5 FU/CDDP) chemotherapy (CT) on m are still questioning in chemoradiotherapy (CRT) regimen in esophageal carcinoma.AIM: Evaluate two RT schedules and two different CT durations by a retrospective comparison of the CRT regimens used by two centres between 1994 and 2000. METHODS: In centre I (regimen I), patients received 2 CT concomitantly to a continuous RT (50 Gy/25 fractions/5 weeks). In centre II (regimen II), patients received 6 CT, 3 were concomitant to a split course RT (20 Gy/10 fractions x 3 courses) and 3 CT were delivered after CRT. RESULTS: A total of 129 patients were included, 74 in centre I and 55 in centre II respectively. Main patient characteristics were similar between the two groups. Clinical complete response to CRT was significantly more frequent in regimen I (83.8% vs 65.4%; P=0.02). The median overall survival (OS) was 20 months in regimen I and 22 months in regimen II (NS). During follow-up, responder patients to CRT in regimen II experienced significant fewer metastasis (51.6% vs 27.8%; P=0.03) with a trend to an increased 5-year survival (19.4% vs 11.3%) and OS (26.5 vs 21.0 months) (NS). Grade 3-4 toxicities were not different. CONCLUSION: Clinical complete response to CRT was significantly more frequent with a continuous RT whereas additional CT after CRT significantly reduced metastasis occurrence. CRT regimen in esophageal carcinoma may be more effective using a continuous RT schedule and additional CT courses after CRT completion. PMID: 16885868 [PubMed - in process] 19: J Fr Ophtalmol. 2006 Apr;29(4):398-403. [Intraocular fluids analysis for etiologic diagnosis of presumed infectious uveitis.] [Article in French] Vasseneix C, Bodaghi B, Muraine M, Favennec L, Brasseur G. Service d'Ophtalmologie, CHU Charles Nicolle, Rouen. PURPOSE: To study the etiologic distribution of patients with presumed infectious uveitis who underwent ocular fluid analysis. PATIENTS AND METHODS: We retrospectively analyzed vitreous and or aqueous humor samples of patients with presumed infectious uveitis, referred to the department of Ophthalmology of the University Hospital of Rouen, France, between January 1997 and June 2004. We excluded patients with postsurgical or endogenous endophthalmitis. We noted clinical features and intraocular sample analysis methods for each pathogen. RESULTS: The study included 42 patients, 24 men and 18 women, aged between 6 and 79 years (mean, 39.5 years). Uveitis was unilateral in 88% of cases and bilateral in 12%. Posterior uveitis was predominant (52%), followed by panuveitis (24%), anterior (14%), and intermediate uveitis (10%). Aqueous humor and vitreous analysis confirmed etiological diagnosis for 13 of 41 patients (31%) and three of six cases (50%), respectively. Inflammation was controlled or stabilized in all cases. The most pejorative visual outcome was observed for candidiasis and viral retinitis. Positivity of intraocular samples was variable, depending on the suspected pathogen, with results similar to those reported in other studies. DISCUSSION: Atypical features in potential infectious uveitis justify ocular paracentesis or vitrectomy, which are more efficient since molecular biological tools have become available. Sensitivity of aqueous humor analysis is high for posterior uveitis and suspicion of viral retinitis. New molecular variants applied to ocular samples will improve the etiological diagnosis of infectious uveitis, particularly for pathogens that are difficult to culture, such as fungi and bacteria. PMID: 16885806 [PubMed - in process] 20: J Intern Med. 2006 Aug;260(2):164-7. Intravenous immunoglobulin-associated cranial pachymeningitis. Marie I, Herve F, Lahaxe L, Robaday S, Gerardin E, Levesque H. Department of Internal Medicine, Rouen University Hospital, Rouen Cedex, France. isabelle.marie@chu-rouen.fr To date, intravenous immunoglobulin (IvIg) has more often been considered as a safe medication. However, with the wider use of IvIg, severe side effects have also been reported to occur in IvIg-treated patients, notably aseptic meningitis. Other neurological complications have more rarely been described in patients receiving IvIg therapy, e.g. stroke or acute encephalopathy. We recently observed a case which is of particular interest, as the patient with steroid-refractory polyarteritis nodosa developed cranial pachymeningitis related to IvIg therapy. To our knowledge, this is the first reported case of cranial pachymeningitis complicating IvIg therapy. Our findings emphasize the importance of recognizing IvIg-related neurological complications in IvIg-treated patients. As cranial pachymeningitis is a fibrosing process, both recognition and management at an early stage are required to prevent definite neurological impairment in patients. Publication Types: Case Reports Review PMID: 16882281 [PubMed - indexed for MEDLINE] 21: Int J Occup Med Environ Health. 2006;19(1):81-2. Polyhexamethylenebiguanide hydrochloride exposure and erythema multiforme in a physician. Gehanno JF, Priot AE, Balguerie X, Caillard JF. Department of Occupational Medicine, Rouen University Hospital Charles Nicolle, Rouen, France. A 52-year-old woman physician developed recurrent erythema multiforme. Occupational and environmental exposure assessment suggested a disinfectant containing polyhexamethylenebiguanide hydrochloride (PHMB), Phagosept. Elimination of the product was followed by disappearance of symptomatology. Literature search revealed cases of sensitization and anaphylaxis due to contact with PHMB, but to our knowledge, this is the first report on PHMB-induced erythema multiforme. Publication Types: Case Reports PMID: 16881604 [PubMed - indexed for MEDLINE] 22: J Neurosci Res. 2006 Jul 28; [Epub ahead of print] Inhibition of proteasome and Shaggy/Glycogen synthase kinase-3beta kinase prevents clearance of phosphorylated tau in Drosophila. Blard O, Frebourg T, Campion D, Lecourtois M. Faculty of Medicine, ISERM, U614, Rouen, France. Tauopathies, including Alzheimer's disease (AD), are a group of neurodegenerative disorders characterized by the presence of intraneuronal filamentous inclusions of abnormally phosphorylated tau protein. In AD brains, it has been shown that the level of abnormally phosphorylated tau is higher than in age-matched control brains, suggesting that abnormally phosphorylated tau is resistant to degradation. By using a Drosophila model of tauopathy, we studied the relationship between tau phosphorylation and degradation. We showed that in vivo reduction of proteasome activity results in an accumulation of high-molecular-weight forms of hyperphosphorylated tau. We also found that glycogen synthase kinase (GSK)-3beta-mediated hyperphosphorylated forms of tau are degradable by the proteasomal machinery. Unexpectedly, GSK-3beta inactivation resulted in a very large accumulation of high-molecular-weight species consisting of hyperphosphorylated tau, suggesting that, depending on the kinase(s) involved, tau phosphorylation state affects its degradation differently. We thus propose a model for tauopathies in which, depending on toxic challenges (e.g., oxidative stress, exposure to amyloid peptide, etc.), abnormal phosphorylation of tau by kinases distinct from GSK-3beta leads to progressive accumulation of hyperphosphorylated tau oligomers that are resistant to degradation. (c) 2006 Wiley-Liss, Inc. PMID: 16878320 [PubMed - as supplied by publisher]
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