Length variation of a polyglutamine array in the gene encoding a small-conductance, calcium-activated potassium channel (hKCa3) and susceptibility to idiopathic generalized epilepsy

The present association study tested whether length variations of two adjacent polymorphic CAG repeats in the coding sequence of a small-conductance, calcium-activated potassium channel (hKCa3) confer susceptibility to common subtypes of idiopathic generalized epilepsy (IGE). We found no significant difference in the allelic length distribution of the CAG repeats between 290 healthy German controls and the entire sample of 126 German IGE patients (Wilcoxon rank-sum test, P = 0.44) or two subgroups, comprising either 78 patients with juvenile myoclonic epilepsy (Wilcoxon rank-sum test, P = 0.74) or 59 patients with idiopathic absence epilepsies (Wilcoxon rank-sum test, P = 0.44). Moreover, the allelic distribution in parents-child trios of 46 IGE offspring did not differ significantly between the transmitted and non-transmitted parental alleles (Wilcoxon rank-sum test, P = 0.48). Therefore, our association study provides no evidence that length variations of polyglutamine arrays in the N-terminus of the hKCa3 channel exert a frequent and relevant effect in the epileptogenesis of common subtypes of IGE.     

Antimicrobial sensitivities in urinary tract infections in men

Six-thousand-seven-hunderd and forty-nine positive urine cultures from a large metropolitan Veterans Administration hospital were analyzed with respect to the organisms isolated and their antimicrobial sensitivies. A predicted therapeutic efficacy index was calculated for each antimicrobial agent tested. Gram-negative pathogens accounted for 84% of the infections. Proteus infections outnumbered those due to strains ofEscherichia coli. Gentamycin was found to be the most effective antimicrobial agent.     

Heparin--examination of its antibacterial adsorption properties

One of the primary antibacterial defense mechanisms of the bladder is the action of the luminal mucopolysaccharide layer against adsorption of inoculated bacteria. Previous studies have shown that local instillation of the mucopolysaccharide heparin can prevent bacterial adsorption on the bladder mucosa denuded of this "antiadherence factor." To determine whether this action was due to the mucopolysaccharide composition of heparin, or rather to its anticoagulant property, protamine sulfate (a basic protein with anticoagulant properties) was tested for antiadsorptive efficacy. Protamine offered no protection against bacterial adherence in the rabbit model. It appears that heparin's protective effect is unrelated to its action as an anticoagulant.     

Differential gene expression in peripheral blood lymphocytes of cancer patients treated with whole body hyperthermia and chemotherapy: a pilot study.

PURPOSE: The effect of whole body hyperthermia (WBH) at 41.8-42 degrees C on the cellular immune system is still poorly investigated. The aim of this study was to identify genes that become upregulated in peripheral blood lymphocytes (PBLs) of cancer patients during a combined treatment with WBH and chemotherapy by generating complex arrays of cDNA. METHODS: PBLs were obtained from four patients with different malignancies treated with WBH and varying cytostatic schedules before treatment and immediately thereafter. After constructing subtracted cDNA libraries, clones were screened for cDNA induction by dot-blot and semi-quantitative RT-PCR (sq-RT-PCR). RESULTS: Among 192 clones, 39 cDNAs were significantly upregulated. Sequencing revealed three groups of genes for which upregulation of mRNA was confirmed by sq-RT-PCR. The first group consisted of genes encoding for various heat shock proteins (HSP 60, 90a, 90b, 105). Further sq-RT-PCR demonstrated differential expression of HSP27 and HSP70 as well. The second group (calcyclin-binding-protein, haemoglobin-beta-chain) comprised genes without pre-specified association to hyperthermia. The cDNA encoding macrophage-inflammatory-protein-1-beta was also observed and may be associated with the pre-described activation of lymphocyte sub-populations during WBH. CONCLUSION: Treatment with WBH and chemotherapy elicits significant short-term effects on the expression of a variety of genes responsible for cellular integrity, stimulation and migration of immune effector cells. Further investigation is warranted to more clearly define the role of those genes for the clinical effect of WBH.     

Spontane H?matomneigung und Hüftschmerzen bei einer 65-j?hrigen Patientin

The case of a 65-year-old woman with acquired hemophilia is reported. Acquired hemophilia is characterized by the development of inhibitors directed against coagulation factors. Impairment of plasmatic hemostasis leads to a severe bleeding tendency in individuals without a preexisting coagulation defect with considerable mortality. Pathophysiology, diagnostic work-up, and treatment are summarized and discussed.     

Quality assurance of sphincterotomy: A prospective single-centre survey

Quality assurance becomes an increasingly important part of clinical medicine and of the field of endoscopy. Endoscopic sphincterotomy is associated with a fairly high complication rate. We aimed to assess our quality of sphincterotomy for benchmarking by using a prospective electronic database registry, and to identify potential risk factors for post-interventional complications. Over 2 years, 471 sphincterotomies were performed in a single tertiary referral centre. Patient- and procedure-related variables were prospectively recorded with the support of a multi-centre international sphincterotomy registry. Multivariate analysis was performed. The overall post-interventional complication rate was 9.3%. Pancreatitis happened in 5.5%, bleeding in 2.1%, perforation in 1.3%, and cholangitis in 0.4%. In the multivariate analysis following variables remained highly significant and predictive for complications: ‘papilla only in lateral view’ (p=0.001), antiplatelet therapy (p=0.024), and opacification with contrast up to the pancreatic tail (p=0.001). The primary success rate of sphincterotomy was 95.1%. The rate of post-interventional pancreatitis did not differ significantly regardless of the presence of prophylactic pancreatic stent (p=0.56). The outcome of sphincterotomy in our centre matches with literature data. The extent of pancreatic duct opacification has an influence on the pancreatitis rate. Prevention of pancreatitis by inserting pancreatic stents is not confirmed.     

Right ventricular pacing is an independent predictor for ventricular tachycardia/ventricular fibrillation occurrence and heart failure events in patients with an implantable cardioverter-defibrillator

Aims: There is increasing evidence that right ventricular (RV) pacingmay have detrimental effects by increasing morbidity and mortalityfor heart failure in implantable cardioverter–defibrillator(ICD) patients. In this study we prospectively tested the hypothesisthat cumulative RV pacing increases ventricular tachycardia/ventricularfibrillation (VT/VF) occurrence (primary endpoint) and hospitalizationand mortality for heart failure (secondary endpoint) in a predominantlysecondary prophylactic ICD patient population. Methods and results: Two hundred and fifty patients were divided into two groupsaccording to the median of cumulative RV pacing (2 vs. >2%)and prospectively followed-up for occurrence of primary andsecondary endpoints for 18 ± 4 months. Established predictorsfor VT/VF occurrence and heart failure events such as age, leftventricular ejection fraction (EF), QRS duration, history ofatrial fibrillation, and NT-proBNP were collected at enrolment.Multivariate Cox regression analysis revealed that cumulativeRV pacing > 2% and EF < 40% were independent predictorsfor VT/VF occurrence and heart failure events. Kaplan–Meieranalysis showed that patients with >2% cumulative RV pacingmore frequently suffered from VT/VF occurrence and heart failurehospitalization. Conclusion: Cumulative RV pacing > 2% and EF < 40% are independentpredictors for VT/VF occurrence and mortality and hospitalizationfor heart failure in predominantly secondary prophylactic ICDpatients. Our data show that algorithms capable of reducingcumulative RV pacing should be used more frequently in clinicalpractice.     

Head-to-head comparison of B-type natriuretic peptide (BNP) and NT-proBNP in daily clinical practice

B-type natriuretic peptide (BNP; Abbott Diagnostics) and N-terminal proBNP (NT-proBNP, Roche Diagnostics) were compared in consecutive samples of 458 patients (mean age 60 years+/-16 years; 159 female, 299 male) sent for NT-proBNP measurement to investigate influences on both markers. BNP and NT-proBNP showed a close correlation with each other (r=0.89, p<0.0001). Using age- and gender-adjusted upper reference values the inter-rater agreement of both parameters was satisfactory (83%, Cohen's kappa coefficient=0.7). The combination of normal BNP and elevated NT-proBNP was significantly more frequent than vice versa (61 vs. 16 patients), and a calculated glomerular filtration rate<60 ml/min/1.73 m(2) was found in 39% of these patients. Multiple linear regression analysis revealed a significant influence of a reduced ejection fraction (<50%), renal dysfunction (calculated glomerular filtration rate<60 ml/min/1.73 m(2)), anemia, hypertension, age, and gender on both BNP and NT-proBNP. In conclusion, despite a close correlation and a satisfactory agreement between both markers in classification, frequent discrepancies in individual patients demonstrate that both markers are clinically not completely equivalent.