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.     

Characteristics of very poor outcome schizophrenia

The authors compared 21 "Kraepelinian" schizophrenic patients who had been ill and dependent on others for the past 5 years with 76 chronic schizophrenic patients in remission or with exacerbations requiring hospitalization. The Kraepelinian patients met the criteria for schizophrenia by more diagnostic systems than the exacerbated patients, were less responsive to haloperidol, had more severe negative symptoms, and had similarly severe positive symptoms. They had cerebral ventricles that were more asymmetrical and a greater family history of schizophrenia spectrum disorders than the other chronic patients. These data suggest that patients with 5 years of illness and complete dependency on others may represent a subgroup of schizophrenia.     

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.     

Comparison of the AMPA Antagonist Action of New 2,3-Benzodiazepines in Vitro and Their Neuroprotective Effects in Vivo

PURPOSE: AMPA receptor-mediated excitotoxicity is thought to be a critical process in diseases accompanied by neuronal cell loss following a hypoxic/anoxic state of the central nervous system. It has been suggested that blockade of AMPA receptors might result in significant protection of neurons against cellular damage. For testing the hypothesis, in vitro efficacy and in vivo neuroprotective action of new 2,3-benzodiazepine (2,3BDZ) AMPA antagonists have been compared. METHODS: 2.3BDZs were tested on kainate-evoked whole-cell currents in cultured neurons as well as on population spikes (PS) in rat hippocampal slices. Data were correlated with those obtained from the spreading depression (SD) experiments in chicken retina. Compounds were also examined in the gerbil bilateral carotid occlusion model (BCO), where percentage decrease of ischemia-related hypermotility (HM), impaired spatial memory (SA), and hypoxia-induced hippocampal CA1 neuronal cell death (CA1) were evaluated. RESULTS: Certain structural modifications of classical 2,3BDZs resulted in increased in vitro activity and improved in vivo efficacy. In particular, the halogen-substituted compounds EGIS-9879 and EGIS-9883 showed the highest neuroprotective efficacy (84% and 47% protection in CA1, 71% and 82% decrease in HM, respectively; 4 x 5 mg/kg i.p.) in BCO. PS and SD were correlated to the decrease of neuronal loss in the CA1 area. Lack of significant correlation was found between PS and CA1 (r = 0.437, p = 0.079) or SD and CA1 (r = 0.380, p = 0.146). CONCLUSIONS: Several new 2.3BDZ AMPA receptor antagonists have been synthesized at EGIS Pharmaceuticals characterized by remarkable in vitro and corresponding in vivo neuroprotective properties.     

Labiaplasty of the labia minora: patients' indications for pursuing surgery

IntroductionLimited information is available regarding patients’ indication for seeking labiaplasty of the labia minora.AimThe aim of this article is to investigate a patient's indications for seeking labiaplasty of the labia minora.MethodsThis is a retrospective review of the medical records of all patients undergoing labiaplasty at our clinic over a 27-month period.Main Outcome MeasuresIndications for surgery were assessed using standardized questionnaires during the patients’ initial history and physical. Patients were divided into three groups as based on the questionnaire, including: Group I—patients seeking the procedure strictly for aesthetic reasons; Group II—patients seeking the procedure strictly for functional impairment (i.e., pain and discomfort); and Group III—patients who feel they are having the surgery for both aesthetic and functional reasons. Patients undergoing the surgery for aesthetic reasons were also asked whether this was strictly a personal decision or was influenced by either another man or woman whether a friend, spouse, or partner.ResultsThe review revealed 131 patients had undergone a labia reduction surgery: Group I—those who received labia reduction surgery for strictly aesthetic reasons equaled 37% (49/131); Group II—those seeking the surgery strictly for functional impairment equaled 32% (42/131); and Group III—those seeking the surgery for both functional and aesthetic reasons equaled 31% (40/131).ConclusionThe majority of patients undergoing reduction of the labia minora do so for functional reasons with minimal outside influences affecting their decision for treatment. Miklos JR, and Moore RD. Labiaplasty of the labia minora: Patients's indications for pursuing surgery.     

Right Ventricular Involvement of an Aggressive Malignant Peripheral Nerve Sheath Tumor

We present a case of a 58-year-old woman who had a painful right thigh mass for a few months. A transthoracic echocardiogram revealed no evidence of an intracardiac mass. She had a whole-body positron emission tomography/computed tomography scan two months later that revealed masses in her right lower extremity and a mass in her right ventricle that had not been initially reported. She had been initially diagnosed with an undifferentiated pleomorphic sarcoma, but this diagnosis was changed to a malignant peripheral nerve sheath tumor with repeat pathology. She was subsequently hospitalized. An echocardiogram showed a mass covering 80% of her right ventricle (RV). Serial cardiac magnetic resonance imaging revealed a 9.4 × 5.6 cm RV mass with vascular and avascular portions and inflow and outflow tract obstruction. Computed tomography showed no other metastases. Due to a delay in diagnosis and a decline in left ventricular ejection fraction, the patient could not undergo palliative chemotherapy or radiotherapy