Ser80Ile mutation and a concurrent Pro25Leu variant of the <Emphasis Type="Italic">VHL</Emphasis> gene in an extended Hungarian von Hippel-Lindau family

Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.     

Attempts to isolate virus from human trigeminal and facial ganglions

Herpes virus hominis type 1 was isolated from the trigeminal ganglion (ganglion semilunare, gasservian) in three out of 20 randomly selected autopsies. Two of the three patients had been treated with immunosuppressive or cytostatic agents. Clinical signs of herpes infection were not observed during the previous 6 months. No virus was isolated from the facial ganglion (geniculate ganglion) in the same 20 cases. The findings are discussed in relation to the viral etiology of acute peripheral facial palsy.     

Kidney recipients with allograft failure,transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.     

Evaluation of the quality of an injury surveillance system

The sensitivity, positive predictive value, and representativeness of the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) were assessed. Sensitivity was estimated at four centers in June through August 1992, by matching independently identified injuries with those in the CHIRPP database. The positive predictive value was determined by reviewing all "injuries" in the database (at Montreal Children's Hospital) that could not be matched. Representativeness was assessed by comparing missed with captured injuries (at Montreal Children's Hospital) on demographic, social, and clinical factors. Sensitivity ranged from 30% to 91%, and the positive predictive value was 99.9% (i.e., the frequency of false-positive capture was negligible). The representativeness study compared 277 missed injuries with 2,746 captured injuries. The groups were similar on age, sex, socioeconomic status, delay before presentation, month, and day of presentation. Injuries resulting in admissions, poisonings, and those presenting overnight were, however, more likely to be missed. The adjusted odds ratio of being missed by CHIRPP for admitted injuries (compared with those treated and released) was 13.07 (95% confidence interval 7.82-21.82); for poisonings (compared with all other injuries), it was 9.91 (95% confidence interval 5.39-18.20); and for injuries presenting overnight (compared with those presenting during the day or evening), it was 4.11 (95% confidence interval 3.11-5.44). These injuries were probably missed because of inadequate education of participants in the system. The authors conclude that CHIRPP data are of relatively high quality and may be used, with caution, for research and public health policy.