Exposition au VIH, à l'hépatite B et C au cabinet médical et à l'hôpital. Prévention et prophylaxie postexpositionnelle [Exposure to HIV, hepatitis B and C in office practice and hospital. Prevention and post-exposure prophylaxis]

Suite à un accident exposant à du sang (piqûre; coupure), provenant d'un patient infecté, le risque d'infection par VIH est d'environ 0,3% et par le virus de l'hépatite C (VHC) d'environ 0,5%. Chez les personnes vaccinées avec une réponse immunitaire adéquate (titre d'anticorps HBs >100 mUI/ml), aucune infection professionnelle par hépatite B n'a été reconnue en Suisse. La plupart des infections par VIH et VHB peuvent être prévenues par un traitement d'urgence et une prophylaxie postexpositionnelle (PEP). Il n'y a actuellement aucune prophylaxie postexpositionnelle pour le VHC. En cas de transmission de VHC, un traitement rapide par peginterféron et ribavirine est à envisager. Chaque hôpital et cabinet médical doivent mettre sur pied un système pour assurer une prise en charge optimale et en urgence des blessures par piqûres ou coupures. Lors de blessures accidentelles avec du sang de patients séropositifs pour le VIH et dans des situations complexes, il est recommandé de consulter un médecin du personnel ou un infectiologue expérimenté. The risk of infection after an occupational needle stick injury with blood from an infected source patient is approximately 0.3% for HIV and 0.5% for hepatitis C virus (HCV). In Switzerland no cases of occupational HBV infection have been recorded in fully vaccinated persons with a documented adequate vaccine response (HBsantibody titer >100 mIU/mL). Most occupational HIV und HBV infections can be prevented by appropriate emergency measures and post-exposure prophylaxis (PEP). No HCV-PEP is currently available. Early therapy with peginterferon and ribavirin should be considered in cases of occupational HCV seroconversion. Every hospital and office practice should establish a system for 24 h/24 h emergency management of occupational needle stick injuries. In the setting of an HIV-seropositive source patient and in complex situations, early consultation with a specialist in occupational medicine or infectious diseases should be considered.

Neurologie [News in neurology 2013].

In 2013, perampanel is approved as an add-on treatment for generalised and focal seizures in pharmaco-resistant epilepsy. New anticoagulants are superior to antivitamin K in stroke secondary prevention in case of atrial fibrillation. DBS remains a valid therapeutic option for advanced Parkinson's disease. Intranasal ketamine seems to reduce the intensity of severe migraine aura. High concentrations of topic capsaicin improve post-herpetic neuralgia. In Alzheimer's disease, statins might deteriorate cognitive functions. Oral immuno-modifing treatments for relapsing remitting multiple sclerosis have shown to slow cerebral atrophy progression at two years.

Post-collisional Neogene magmatism of the Mediterranean Maghreb margin: a consequence of slab breakoff

A 1 200 km-long linear magmatic belt extends along the Mediterranean coast the Maghreb from Eastern Tunisia to Morocco. This belt is mainly composed of Langan calc-alkaline metaluminous to peraluminous granitoids and associated andesites/cites Central and Eastern Algeria. In Tunisia and Oranie/Western Morocco, calc alkaline activity started later (during the Serravallian) and was followed by the placement of alkali basalts and basanites since the Tortonian to the Pliocene and, in me places, the Pleistocene. Available data on the tectonic setting, petrology, age and biochemistry of this belt show that most of its striking features, e.g. (1) very low magma production rate, subduction-related geochemical imprint, extensive crustal contamination the calc-alkaline magmatism and (2) progressive magmatic change from calc-alkaline alkaline, are consistent with magma generation during a slab breakoff process as proposed Carminati et al, in 1998. The magmatism associated with this breakoff started in Central Eastern Algeria at 16 Ma, then propagated eastwards and westwards, The upward of asthenospheric enriched plume-type mantle through the tear in the downgoing first triggered melting of the overlying lithospheric mantle which had been metasomatised during a previous subduction period. Heat supply from this uprising asthenosphere may have warmed up the continental crust and made its involvement in assimilation processes easier. As the asthenosphere ascended through the `window' in the slab, partial melting occurred at the uprising boundary between asthenosphere and lithosphere, generating basalts with transitional characteristics between those of calc-alkaline and alkaline basalts. As the asthhenospheric upwelling proceeded partial:melting then occurred in the sole asthenospheric mantle, producing alkali basalts. (C) 2000 Academie des sciences Editions scientifiques et medicales Elsevier SAS.

Specific inhibition of the JNK pathway promotes locomotor recovery and neuroprotection after mouse spinal cord injury.

Limiting the development of secondary damage represents one of the major goals of neuroprotective therapies after spinal cord injury. Here, we demonstrate that specific JNK inhibition via a single intraperitoneal injection of the cell permeable peptide D-JNKI1 6h after lesion improves locomotor recovery assessed by both the footprint and the BMS tests up to 4 months post-injury in mice. JNK inhibition prevents c-jun phosphorylation and caspase-3 cleavage, has neuroprotective effects and results in an increased sparing of white matter at the lesion site. Lastly, D-JNKI1 treated animals show a lower increase of erythrocyte extravasation and blood brain barrier permeability, thus indicating protection of the vascular system. In total, these results clearly point out JNK inhibition as a promising neuroprotective strategy for preventing the evolution of secondary damage after spinal cord injury.

Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients.

Epstein-Barr virus (EBV) contributes to the pathogenesis of post-transplant lymphoproliferative disease (PTLD) in more than 70% of cases. EBV DNAemia surveillance has been reported to assist in the prevention and treatment of PTLD in hematopoietic stem-cell transplantation (HSCT) recipients. Derived from experience in HSCT and taking into account that PCR-based EBV monitoring techniques are currently available in most solid organ transplant (SOT) centres, there is a great interest in EBV surveillance and prevention of PTLD in SOT recipients. In the present document we have tried to address from a practical perspective different important topics regarding the prevention and management of EBV-related PTLD in SOT. To this end, available information on SOT was analysed and combined with potentially useful data from HSCT and expert observations. The document is therefore structured according to different specific questions, each of them culminating in a consensus opinion of the panel of European experts, grading the answers according to internationally recognized levels of evidence. The addressed issues were grouped under the following topics. (i) Timing and epidemiological data of PTLD. Prophylaxis guided by clinical risk factors of early and late PTLD in SOT. (ii) Relationship of EBV DNAemia load monitoring and the development of PTLD in solid organ transplant recipients. (iii) Monitoring of EBV DNAemia after SOT. Which population should be monitored? What is the optimal timing of the monitoring? (iv) Management of SOT recipients with persistent and/or increasing EBV DNAemia.

Cryptic diversity among Western Palearctic tree frogs: postglacial range expansion, range limits, and secondary contacts of three European tree frog lineages (Hyla arborea group).

We characterize divergence times, intraspecific diversity and distributions for recently recognized lineages within the Hyla arborea species group, based on mitochondrial and nuclear sequences from 160 localities spanning its whole distribution. Lineages of H. arborea, H. orientalis, H. molleri have at least Pliocene age, supporting species level divergence. The genetically uniform Iberian H. molleri, although largely isolated by the Pyrenees, is parapatric to H. arborea, with evidence for successful hybridization in a small Aquitanian corridor (southwestern France), where the distribution also overlaps with H. meridionalis. The genetically uniform H. arborea, spread from Crete to Brittany, exhibits molecular signatures of a postglacial range expansion. It meets different mtDNA clades of H. orientalis in NE-Greece, along the Carpathians, and in Poland along the Vistula River (there including hybridization). The East-European H. orientalis is strongly structured genetically. Five geographic mitochondrial clades are recognized, with a molecular signature of postglacial range expansions for the clade that reached the most northern latitudes. Hybridization with H. savignyi is suggested in southwestern Turkey. Thus, cryptic diversity in these Pliocene Hyla lineages covers three extremes: a genetically poor, quasi-Iberian endemic (H. molleri), a more uniform species distributed from the Balkans to Western Europe (H. arborea), and a well-structured Asia Minor-Eastern European species (H. orientalis).

Salvage Regimen With Autologous Stem Cell Transplantation With Or Without Rituximab Maintenance For Relapsed Diffuse Large B-Cell Lymphoma (Dlbcl): Coral Final Report

Times Cited: 0 References: 0 Citation MapAbstract : Background: Chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard treatment for relapsed DLBCL. No study has compared salvage therapies and evaluated maintenance post ASCT.Methods: DLBCL CD 20+ in first relapse or pts refractory after first therapy were randomized between R ICE (rituximab, ifosfamide, etoposide, carboplatinum) or R DHAP (rituximab dexamethasone cytarabine cisplatinum). Responding patients received BEAM and ASCT then randomized between observation or maintenance with rituximab every 2 m for 1 yr (Gisselbrecht J Clin Oncol; 2010).Results: Analysis was made on 477 pts (R ICE: 243 pts; R DHAP: 234 pts): 255 relapses >12m, 213 refractory/early relapses; 306 pts had prior rituximab; secondary(s) IPI 0-1: 281 pts; s IPI 2-3:181pts. There was no difference in response rate between R ICE 63.6% and R DHAP 64.3%. There was no difference between R ICE and R DHAP at 4 yrs for EFS (26% vs 37% p=0.2) and OS (43% vs 51%, p=0.3). Factors affecting 4 yrs EFS, PFS and OS were: prior treatment with rituximab; early relapse< 12 m; s IPI 2-3. ASCT was performed in 255 pts and 242 randomized for maintenance: 122 pts rituximab (R), 120 pts observation (O). Distribution between R/O arms were respectively: median age 54 /53 yrs, Male 76/83; female 46/37; secondary IPI 0-1: 84/81; sIPI 2-3: 36/36. 89/76 relapses >12m., 33/41 refractory/early relapses. Median follow up was 44 m with 111 events. 4 yrs EFS was 52.8 % (CI 46-59) with 63% (CI 56-69) OS. There was no difference in EFS, PFS and OS between R and O arms. In multivariate analysis, sIPI2-3 significantly affected EFS, PFS, OS (p=0.0004). Women (83pts) had a better 4 yrs EFS 63% than male (159pts) 37% (p=0.01). The difference was only in the R arm (p=0.004). Gender was an independent prognostic factor in the R arm. Toxicity was mild with 12% SAE versus 4% for R /O respectively.Conclusions: There was no difference between R ICE and R DHAP and between post ASCT maintenance with R or O. Women did significantly better after ASCT with rituximab. Early relapses to upfront rituximab-based chemotherapy have a poor prognosis.

A non-invasive assessment of hepatic glycogen kinetics and post-absorptive gluconeogenesis in man.

A novel approach to the study of hepatic glycogen kinetics and fractional gluconeogenesis in vivo is described. Ten healthy female subjects were fed an iso-caloric diet containing 55% carbohydrate energy with a 13C abundance of 1.083 atom percent for a 3-day baseline period; then, a diet of similar composition, but providing carbohydrate with a 13C abundance of 1.093 atom percent was started and continued for 5 days. Resting respiratory gas exchanges, urinary nitrogen excretion, breath 13CO2 and plasma 13C glucose were measured every morning in the fasting state. The enrichment in 13C of hepatic glycogen was calculated from these measured data. 13C glycogen enrichment increased after switching to a 13C enriched carbohydrate diet, and was identical to the 13C enrichment of dietary carbohydrates after 3 days. The time required to renew 50% of hepatic glycogen, as determined from the kinetics of 13C glycogen enrichment, was 18.9 +/- 3.6 h. Fractional gluconeogenesis, as determined from the difference between the enrichments of glucose oxidized originating from hepatic glycogen and plasma glucose 13C was 50.8 +/- 5.3%. This non-invasive method will allow the study of hepatic glycogen metabolism in insulin-resistant patients.

Prise en charge du syndrome post-thrombotique [Management of post-thrombotic syndrome].

Post-thrombotic syndrome (PTS) is the most frequent chronic complication of deep vein thrombosis with an estimated prevalence of 30-50%. PTS is a significant cause of disability, especially when complicated by venous ulcers. Therefore, it has important socio-economic consequences for both the patient and the health care system. Aim of this review is to resume state of the art literature on the management of PTS.

Anti-CD154 mAb and rapamycin induce T regulatory cell mediated tolerance in rat-to-mouse islet transplantation.

BACKGROUND: Anti-CD154 (MR1) monoclonal antibody (mAb) and rapamycin (RAPA) treatment both improve survival of rat-to-mouse islet xenograft. The present study investigated the effect of combined RAPA/MR1 treatment on rat-to-mouse islet xenograft survival and analyzed the role of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Treg) in the induction and maintenance of the ensuing tolerance. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice were treated with MR1/RAPA and received additional monoclonal anti-IL2 mAb or anti CD25 mAb either early (0-28 d) or late (100-128 d) post-transplantation. Treg were characterised in the blood, spleen, draining lymph nodes and within the graft of tolerant and rejecting mice by flow cytometry and immunohistochemistry. Fourteen days of RAPA/MR1 combination therapy allowed indefinite islet graft survival in >80% of the mice. Additional administration of anti-IL-2 mAb or depleting anti-CD25 mAb at the time of transplantation resulted in rejection (100% and 89% respectively), whereas administration at 100 days post transplantation lead to lower rejection rates (25% and 40% respectively). Tolerant mice showed an increase of Treg within the graft and in draining lymph nodes early post transplantation, whereas 100 days post transplantation no significant increase of Treg was observed. Rejecting mice showed a transient increase of Treg in the xenograft and secondary lymphoid organs, which disappeared within 7 days after rejection. CONCLUSIONS/SIGNIFICANCES: These results suggest a critical role for Treg in the induction phase of tolerance early after islet xenotransplantation. These encouraging data support the need of developing further Treg therapy for overcoming the species barrier in xenotransplantation.

Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome.

PURPOSE: Whereas gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain are common in children suffering from the so-called post-diarrheal form (D+) of hemolytic uremic syndrome (HUS), more serious gastrointestinal complications are rare. We tried to define factors predictive of the severity of gastrointestinal complications post D+ HUS. METHODS: We reviewed the files of all children admitted to our hospital for D+ HUS between 1988 and 2000. We retained those cases with gastrointestinal complications and analyzed the consequences of these complications on the evolution of the children's conditions. RESULTS: Sixty-five children with D+ HUS were admitted to our hospital during this period. Sixteen children developed gastrointestinal complications involving one or more digestive organs: necrosis of the colon or ileum, hemorrhagic colitis, pancreatitis, transient diabetes, hepatic cytolysis and cholestasis, peritonitis and prolapse of the rectum. One child died. CONCLUSION: Gastrointestinal complications of D+ HUS are rare, but they can be lethal, and early surgery may sometimes prove necessary. However, we were not able to demonstrate a correlation between the severity of the gastrointestinal manifestations and the clinical or biological signs accompanying D+ HUS.

Sudden death: ethical and legal problems of post-mortem forensic genetic testing for hereditary cardiac diseases.

Hereditary non-structural diseases such as catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT, and the Brugada syndrome as well as structural disease such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) cause a significant percentage of sudden cardiac deaths in the young. In these cases, genetic testing can be useful and does not require proxy consent if it is carried out at the request of judicial authorities as part of a forensic death investigation. Mutations in several genes are implicated in arrhythmic syndromes, including SCN5A, KCNQ1, KCNH2, RyR2, and genes causing HCM. If the victim's test is positive, this information is important for relatives who might be themselves at risk of carrying the disease-causing mutation. There is no consensus about how professionals should proceed in this context. This article discusses the ethical and legal arguments in favour of and against three options: genetic testing of the deceased victim only; counselling of relatives before testing the victim; counselling restricted to relatives of victims who tested positive for mutations of serious and preventable diseases. Legal cases are mentioned that pertain to the duty of geneticists and other physicians to warn relatives. Although the claim for a legal duty is tenuous, recent publications and guidelines suggest that geneticists and others involved in the multidisciplinary approach of sudden death (SD) cases may, nevertheless, have an ethical duty to inform relatives of SD victims. Several practical problems remain pertaining to the costs of testing, the counselling and to the need to obtain permission of judicial authorities.