Clinical and Genetic Spectrum of Bartter Syndrome Type 3.

Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1-41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.

Conflict of Interest Policies at French Medical Schools: Starting from the Bottom.

BACKGROUND: Medical faculties have a role in ensuring that their students are protected from undue commercial influence during their training, and are educated about professional-industry interactions. In North America, many medical faculties have introduced more stringent conflict of interest (COI) policies during the last decade. We asked whether similar steps had been taken in France. We hypothesized that such policies may have been introduced following a 2009-2010 drug safety scandal (benfluorex, Mediator) in which COIs in medicine received prominent press attention. METHODS: We searched the websites of all 37 French Faculties of Medicine in May 2015 for COI policies and curriculum, using standardized keyword searches. We also surveyed all deans of medicine on institutional COI policies and curriculum, based on criteria developed in similar US and Canadian surveys. Personal contacts were also consulted. We calculated a summary score per faculty based on 13 criteria. [range 0-26; higher scores denoting stronger policies]. RESULTS: In total, we found that 9/37 (24%) of French medical schools had either introduced related curriculum or implemented a COI-related policy. Of these, only 1 (2.5%) had restrictive policies for any category. No official COI policies were found at any of the schools. However, at 2 (5%), informal policies were reported. The maximum score per faculty was 5/26, with 28 (76%) scoring 0. CONCLUSION: This is the first survey in France to examine COI policies at medical faculties. We found little evidence that protection of medical students from undue commercial influence is a priority, either through institutional policies or education. This is despite national transparency legislation on industry financing of health professionals and limits on gifts. The French National Medical Students Association (ANEMF) has called for more attention to COI in medical education; our results strongly support such a call.

Unusual presentation of primary toxoplasmosis infection in a kidney-transplant patient complicated by an acute left-ventricular failure.

Although primary toxoplasmosis is a rare event following kidney transplantation, it can be life threatening. This report describes this complication. The patient presented with high-grade fever, haemolytic anaemia and haemophagocytic-syndrome-related pancytopaenia. Toxoplasma gondii diagnosis was ascertained by blood and bone-marrow PCR assays. After 6 weeks with Clindamycin plus pyrimethamine therapies and despite negativation of T. gondii blood PCR assay, the patient developed left-ventricular failure. After adding sulfamethoxazole/ trimethoprim, ramipril, digoxine, bisoprolol and spironolactone, he progressively recovered. Anti-T. gondii therapy was continued for 6 months. Four years later he received a third kidney allograft: at that time anti-T. gondii antibodies had become negative. The outcome was uneventful despite immunosuppression but with inclusion of sulfamethoxazole/trimethoprim prophylaxis. More than 3 years after the third kidney transplantation the patient has had no toxoplasmosis reactivation. This case report highlights that T. gondii can be the cause of myocarditis in a renal transplant recipient.

Vertigo after renal transplantation: a sign of paucisymptomatic cryptococcal meningitis.

We report what is to our knowledge the first case of severe isolated vertigo that developed after renal transplantation and was a manifestation of cryptococcal meningitis. Treatment with antifungal therapy resulted in the complete resolution of vertiginous symptoms. Immunosuppressed patients with an opportunistic infection of the central nervous system can present with extremely tenuous features of infection and atypical neurologic signs.

Induction therapy with either anti-CD25 monoclonal antibodies or rabbit antithymocyte globulins in liver transplantation for hepatitis C.

BACKGROUND: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). The aim of our sequential study was to assess the safety and efficacy of induction therapy using either rabbit antithymocyte globulins (RATG) or anti-CD25 monoclonal antibodies. METHODS: From January 2000 to January 2003, 31 patients underwent OLT for HCV-related ESLD, and survived more than 1 month post-transplantation. Up to July 2001, induction relied on RATG (Thymoglobulins; Sangstat, Lyon, France) which was given for a median of 5 d, i.e. a total dose of 406 +/- 45 mg (n = 16; group I). Thereafter, induction was based on either basiliximab or dacluzimab (n = 15; group II). Steroids and tacrolimus (from day 1 onwards) were given as maintenance therapy. The primary end-points were at 6 months post-transplantation. RESULTS: Patient and graft survivals were excellent and similar in both groups. The acute rejection rate was 37.5% in group I and 20% in group II (p = ns). The rates of serious bacterial and fungal infections as well as cytomegalovirus infections were similar in both groups. Even if the overall pattern of post-transplant liver enzymes did not differ between the two groups, the rate of HCV recurrence tended to be higher in group II (80%) compared with group I (56.25%; p = ns) patients. Both induction therapies were clinically and biologically well tolerated. CONCLUSION: RATG induction therapy is as efficient and as safe as induction with anti-CD25 monoclonal antibodies.