Schizophrénie, diabète et nouveaux neuroleptiques [Schizophrenia, diabetes and new neuroleptics].

Diabetes mellitus occurs more frequently in schizophrenic patients. The use of a novel antipsychotic drug seems to be concomitant to a further increase in imbalance of blood glucose homeostasis. Such cases have already been reported in the literature indicating that diabetes mellitus might be a real side effect of this novel class of neuroleptics. In conclusion, it seems that schizophrenic patients under such treatment would greatly benefit from a closer clinical and biological follow up regarding glucose metabolism. Further randomised studies would be needed.

Lymphome et grossesse: quelle prise en charge [Management of lymphoma and pregnancy]

With an incidence of 1/6000 pregnancies, per-partum lymphoma is a rare but not an exceptional event, which gynaecologists and family physicians can be confronted in the course of their career The diagnosis, without a peripheral adenopathy, can be challenging because symptoms, such as fatigue or dyspnoea, can easily be attributed to the pregnancy. Although the therapeutic management is complex, because it involves the mother and her embryos, it can be optimal in the majority of cases. The multidisciplinary management, with modern diagnostic and therapeutic approaches, greatly improved the prognosis of these young women. Today, it generally allows the safekeeping of the baby with an outcome for the mother identical to the one observed in the population at large.

Pathogenesis of arenavirus hemorrhagic fevers.

Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments.

Rôle de l'EGFR dans le cancer pulmonaire non à petites cellules [The role of EGFR in non-small cell lung carcinoma]

EGFR receptor is expressed on most of the non small cell lung carcinoma (NSCLC) cells. Its relative importance in oncogenesis and tumour progression seems to greatly vary among NSCLC. Two molecules targeting differently EGFR are currently used for the treatment of metastatic NSCLC. cetuximab, a monoclonal antibody directed against the extracellular domain of the receptor, leads to a moderate survival benefit when associated with standard first-line chemotherapy. Erlotinib, a small EGFR tyrosine-kinase inhibitor molecule is used in 2nd or 3rd treatment line. Predictive factors for efficiency of these new treatments are subjects of intense research, in order to allow a better selection of the patients who could benefit from such a strategy.

Management of hepatitis C virus (HCV) infection in drug substitution programs.

BACKGROUND: In Switzerland, intravenous drug use (IDU) accounts for 80% of newly acquired hepatitis C virus (HCV) infections. Early HCV treatment has the potential to interrupt the transmission chain and reduce morbidity/mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programs are often insufficiently screened and treated. OBJECTIVE/METHODS: With the aim to improve HCV management in IDUs, we conducted a cross sectional chart review in three opioid substitution programs in St. Gallen (125 methadone and 71 heroin recipients). Results were compared with another heroin substitution program in Bern (202 patients) and SCCS/SHCS data. RESULTS: Among the methadone/heroin recipients in St. Gallen, diagnostic workup of HCV was better than expected: HCV/HIV-status was unknown in only 1% (2/196), HCV RNA was not performed in 9% (13/146) of anti-HCV-positives and the genotype missing in 15% (12/78) of HCV RNA-positives. In those without spontaneous clearance (two thirds), HCV treatment uptake was 23% (21/91) (HIV-: 29% (20/68), HIV+: 4% (1/23)), which was lower than in methadone/heroin recipients and particularly non-IDUs within the SCCS/SHCS, but higher than in the, mainly psychiatrically focussed, heroin substitution program in Bern (8%). Sustained virological response (SVR) rates were comparable in all settings (overall: 50%, genotype 1: 35-40%, genotype 3: two thirds). In St. Gallen, the median delay from the estimated date of infection (IDU start) to first diagnosis was 10 years and to treatment was another 7.5 years. CONCLUSIONS: Future efforts need to focus on earlier HCV diagnosis and improvement of treatment uptake among patients in drug substitution programs, particularly if patients are HIV-co-infected. New potent drugs might facilitate the decision to initiate treatment.

Durability and outcome of initial antiretroviral treatments received during 2000--2005 by patients in the Swiss HIV Cohort Study.

BACKGROUND: Little is known about time trends, predictors, and consequences of changes made to antiretroviral therapy (ART) regimens early after patients initially start treatment. METHODS: We compared the incidence of, reasons for, and predictors of treatment change within 1 year after starting combination ART (cART), as well as virological and immunological outcomes at 1 year, among 1866 patients from the Swiss HIV Cohort Study who initiated cART during 2000--2001, 2002--2003, or 2004--2005. RESULTS: The durability of initial regimens did not improve over time (P = .15): 48.8% of 625 patients during 2000--2001, 43.8% of 607 during 2002--2003, and 44.3% of 634 during 2004--2005 changed cART within 1 year; reasons for change included intolerance (51.1% of all patients), patient wish (15.4%), physician decision (14.8%), and virological failure (7.1%). An increased probability of treatment change was associated with larger CD4+ cell counts, larger human immunodeficiency virus type 1 (HIV-1) RNA loads, and receipt of regimens that contained stavudine or indinavir/ritonavir, but a decreased probability was associated with receipt of regimens that contained tenofovir. Treatment discontinuation was associated with larger CD4+ cell counts, current use of injection drugs, and receipt of regimens that contained nevirapine. One-year outcomes improved between 2000--2001 and 2004--2005: 84.5% and 92.7% of patients, respectively, reached HIV-1 RNA loads of <50 copies/mL and achieved median increases in CD4+ cell counts of 157.5 and 197.5 cells/microL, respectively (P < .001 for all comparisons). CONCLUSIONS: Virological and immunological outcomes of initial treatments improved between 2000--2001 and 2004--2005, irrespective of uniformly high rates of early changes in treatment across the 3 study intervals.

Complementary effects of adenosine and angiotensin II in hypoxemia-induced renal dysfunction in the rabbit.

The acute renal effects of hypoxemia and the ability of the co-administration of an angiotensin converting enzyme inhibitor (perindoprilat) and an adenosine receptor antagonist (theophylline) to prevent these effects were assessed in anesthetized and mechanically-ventilated rabbits. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by the clearances of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (-12 +/- 2%), GFR (-16 +/- 3%) and RBF (-12 +/- 3%) with a concomitant increase in renal vascular resistance (RVR) (+ 18 +/- 5%), without changes in filtration fraction (FF) (-4 +/- 2%). These results suggest the occurrence of both pre- and postglomerular vasoconstriction during the hypoxemic stress. In 7 rabbits pretreated with intravenous perindoprilat (20 microg/kg), the hypoxemia-induced changes in RBF and RVR were prevented. FF decreased significantly (-18 +/- 2%), while the drop in GFR was partially blunted. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction by perindoprilat. In 7 additional rabbits, co-administration of perindoprilat and theophylline (1 mg/kg) completely prevented the hypoxemia-induced changes in RBF (+ 11 +/- 3%) and GFR (+ 2 +/- 3%), while RVR decreased significantly (-14 +/- 3%). Since adenosine and angiotensin II were both shown to participate, at least in part, in the renal changes induced by hypoxemia, the beneficial effects of perindoprilat and theophylline in this model could be mediated by complementary actions of angiotensin II and adenosine on the renal vasculature.

Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients.

PURPOSE: Thirty to forty percent of patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis develop intra-abdominal invasive candidiasis (IC). A corrected Candida colonization index (CCI) > or =0.4 is a powerful predictor of IC. Fluconazole prevents intra-abdominal IC in this setting, but azole-resistant Candida species are emerging. The aim of this study was to explore the efficacy and safety of caspofungin for prevention of intra-abdominal IC in high-risk surgical patients. METHODS: Prospective non-comparative single-center study in consecutive adult surgical patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis. Preventive caspofungin therapy (70 mg, then 50 mg/day) was given until resolution of the surgical condition. Candida colonization index and CCI, occurrence of intra-abdominal IC and adverse events were monitored. RESULTS: Nineteen patients were studied: 16 (84%) had recurrent gastrointestinal perforation/anastomotic leakage and 3 (16%) acute necrotizing pancreatitis. The median duration of preventive caspofungin therapy was 16 days (range 4-46). The colonization index decreased significantly during study therapy, and the CCI remained <0.4 in all patients. Caspofungin was successful for prevention of intra-abdominal IC in 18/19 patients (95%, 1 breakthrough IC 5 days after inclusion). No drug-related adverse event requiring caspofungin discontinuation occurred. CONCLUSION: Caspofungin may be efficacious and safe for prevention of intra-abdominal candidiasis in high-risk surgical patients. This needs to be further investigated in randomized trials.

Utilité du dosage de la CRP dans le diagnostic, le pronostic et le suivi de la pneumonie acquise dans la communauté [Role of C-reactive protein in the diagnosis, prognosis and follow-up of community-acquired pneumonia].

Community-acquired pneumonia (CAP) is a major clinical problem in terms of morbidity, mortality, and use of hospital resources. It is well recognized that a delay in making the diagnosis and instituting appropriate antibiotic treatment is associated with an increased mortality. C-reactive protein may be helpful in the management of patients with CAP. CRP is widely used in the management of CAP, including diagnosis, prognosis and follow-up. But its usefulness is not known. The aim of this systematic review was to evaluate the usefulness of CRP in the diagnosis, prognosis and follow-up of CAP.

Evaluation of the new photosensitizer Stakel (WST-11) for photodynamic choroidal vessel occlusion in rabbit and rat eyes.

PURPOSE: To evaluate the photodynamic potential of a new hydrosoluble photosensitizer (WST-11, Stakel; Steba Biotech, Toussus-Le-Noble, France), for use in occlusion of normal choroidal vessels in the rabbit eye and CNV (choroidal neovascularization) in the rat eye. METHODS: Occlusive and nonocclusive parameters of Stakel and verteporfin photodynamic therapy (PDT) were investigated in pigmented rabbits. Eyes were followed by fluorescein angiography (FA) and histology at various intervals after PDT. RESULTS: When occlusive parameters (fluence of 50 J/cm(2), 5 mg/kg drug dose and DLI [distance to light illumination] of 1 minute) were used, Stakel PDT was efficient immediately after treatment without associated structural damage of the RPE and retina overlying the treated choroid in the rabbit eye. Two days later, total occlusion of the choriocapillaries was seen in 100% of the treated eyes, along with accompanying histologic structural changes in the overlying retina. When the occlusive parameters (fluence, 100 J/cm2; drug dose, 12 mg/m2; and DLI, 5 minutes) of verteporfin PDT were used, occlusion of the choriocapillaries was observed in 89% of the treated eyes. Histology performed immediately after treatment demonstrated structural damage of the overlying retina and RPE layer. Weaker, nonocclusive Stakel PDT parameters (25 J/cm2, 5 mg/kg, and DLI of 10 minutes) did not induce choriocapillary occlusion or retinal lesions on FA or histology. Weaker, nonocclusive verteporfin PDT parameters (10 J/cm2, 0.2 mg/kg, and DLI of 5 minutes) did not induce choriocapillary occlusion. However, histology of these eyes showed the presence of damage in the retinal and choroidal tissues. Moreover, preliminary results indicate that selective CNV occlusion can be achieved with Stakel PDT in the rat eye. CONCLUSIONS: Unlike verteporfin PDT, Stakel PDT does not cause direct damage to the RPE cell layer or retina. These observations indicate that Stakel PDT may have a high potential for beneficial therapeutic outcomes in treatment of AMD.

Réplication cérébrale du VIH malgré une thérapie antirétrovirale efficace: impact clinique et prise en charge [Intracerebral HIV replication despite an efficient antiretroviral treatment: clinical impact and management].

Various neurological and neuropsychological manifestations are still relatively frequently reported in HIV infected patients in the highly active antiretroviral therapy era. A fraction of them could be related to HIV replication in the central nervous system (CNS) despite adequate peripheral viral suppression. This hypothesis is supported by numerous reports of detectable HIV RNA in the cerebrospinal fluid in the context of a low or undetectable viremia in association with neurological or neuropsychological complaints. In addition, some antiviral molecules may not achieve adequate levels in the CNS, thus potentially favoring intracerebral HIV replication and even antiretroviral resistance. Neurologic manifestations in the presence of CNS HIV replication often decrease after antiretroviral treatment CNS penetration optimization.

Septic arthritis of the pubic symphysis caused by Streptococcus mitis.

Septic arthritis of the pubic symphisis is distinguished from osteitis pubis by positive cultures. The symptoms, physical examination and laboratory findings of these two conditions are comparable. We present a case of 57-year-old woman with septic arthritis of pubic symphisis caused by Streptococcus mitis, a commensal oral flora that belongs to viridans group streptococci, which normally reside in the oral cavity, the gastrointestinal and the urogenital tract.

Diarrhées infectieuses [Infectious diarrhea].

Traveler's diarrhea is generally a benign condition which resolves spontaneously in 48 h. Information on dietary hygiene, severity of symptoms and dehydration, as well as their management, is essential. Chemoprophylaxis and antibiotic treatment are not recommended, except in very specific situations. The incidence of chronic diarrhea in HIV-positive patients has dramatically decreased since the introduction of HAART. In the absence of any correlation with the initiation of HAART, a stepwise diagnostic workup is indicated (bacteriological cultures and microscopic examination of fecal samples followed by ileocolonoscopy and gastroduodenoscopy). Specific treatment of any pathogens identified, and HAART in the case of microsporidiasis or cryptosporidiosis, constitute the mainstay of therapeutic management of chronic diarrhea in these patients.

Determinants of methicillin-susceptible Staphylococcus aureus native bone and joint infection treatment failure: a retrospective cohort study.

BACKGROUND: Although methicillin-susceptible Staphylococcus aureus (MSSA) native bone and joint infection (BJI) constitutes the more frequent clinical entity of BJI, prognostic studies mostly focused on methicillin-resistant S. aureus prosthetic joint infection. We aimed to assess the determinants of native MSSA BJI outcomes. METHODS: Retrospective cohort study (2001-2011) of patients admitted in a reference hospital centre for native MSSA BJI. Treatment failure determinants were assessed using Kaplan-Meier curves and binary logistic regression. RESULTS: Sixty-six patients (42 males [63.6%]; median age 61.2 years; interquartile range [IQR] 45.9-71.9) presented an acute (n = 38; 57.6%) or chronic (n = 28; 42.4%) native MSSA arthritis (n = 15; 22.7%), osteomyelitis (n = 19; 28.8%) or spondylodiscitis (n = 32; 48.5%), considered as "difficult-to-treat" in 61 cases (92.4%). All received a prolonged (27.1 weeks; IQR, 16.9-36.1) combined antimicrobial therapy, after surgical management in 37 cases (56.1%). Sixteen treatment failures (24.2%) were observed during a median follow-up period of 63.3 weeks (IQR, 44.7-103.1), including 13 persisting infections, 1 relapse after treatment disruption, and 2 super-infections. Independent determinants of treatment failure were the existence of a sinus tract (odds ratio [OR], 5.300; 95% confidence interval [CI], 1.166-24.103) and a prolonged delay to infectious disease specialist referral (OR, 1.134; 95% CI 1.013-1.271). CONCLUSIONS: The important treatment failure rate pinpointed the difficulty of cure encountered in complicated native MSSA BJI. An early infectious disease specialist referral is essential, especially in debilitated patients or in presence of sinus tract.