Population study of Aymara Amerindians for the PCR-DNA polymorphisms HUMTH01, HUMVWA31A, D3S1358, D8S1179, D18S51, D19S253, YNZ22 and HLA-DQα

Allele and genotype frequencies for eight DNA polymorphisms (HUMTH01, HUMVWA31A, D3S1358, D8S1179, D18S51, D19S253, YNZ22 and HLA-DQalpha) were determined in a population sample of Aymara Indians from Bolivia using PCR. No deviations of the observed allelic frequencies from Hardy-Weinberg equilibrium were found for all the systems studied. Significant differences in the allele frequencies were found between the Aymara and Quechua populations only for HUMVWA31A, which suggests a certain degree of genetic differentiation between the two populations.     

Chemically Accessible Hsp90 Inhibitor That Does Not Induce a Heat Shock Response

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Stimulation of serotonin1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats

RATIONALE: Changes in serotonin(1B) (5-HT(1B)) receptor function appear to modify the reinforcing properties of cocaine, but the direction of this effect is not completely clear. Pharmacological stimulation of 5-HT(1B) enhanced the rewarding properties of self-administered cocaine while attenuating the threshold-reducing effect of cocaine in the intracerebral brain stimulation procedure. OBJECTIVE: The present study investigates how pharmacological modification of 5-HT(1B) receptor-mediated neurotransmission influence cocaine motivational properties in the conditioned place preference paradigm in rats. METHODS: In separate groups of rats the motivational properties of CP 94,253, a selective 5-HT(1B) agonist, or GR 127935, a 5-HT(1B/D) receptor partial agonist, given alone or in combination, were determined. To evaluate their influence on cocaine-induced place conditioning, CP 94,253, that was found to be aversive, was given every day before each conditioning session, while GR 127935, which given alone had no effect, was administered only before cocaine conditioning sessions. RESULTS: CP 94,253, injected IP at 2.5 and 10 (but not 0.5) mg/kg produced place aversion in the place conditioning paradigm. The aversive effect of 2.5 mg/kg CP 94,253 was completely reversed by 10 mg/kg SC GR 127935. Given before every conditioning session, CP 94,253 did not modify place conditioning by four injections of 10 mg/kg cocaine but at 2.5 mg/kg it potentiated a sub-threshold dose of cocaine. The place preference caused by these two drugs was completely reversed by 10 mg/kg GR 127935. The antagonism by GR 127935 of CP 94,253's effects was shown not to be due to the induction of state-dependent effects. CONCLUSION: The results suggest that stimulation of 5-HT(1B) receptors causes place aversion, and enhances the effect of low doses of cocaine in the conditioned place preference paradigm.     

Clinical Outcomes of Kidney Transplantation in Patients With Biopsy-Proven Glomerulonephritis

Background

The clinical outcomes after kidney transplantation (KT) according to the types of glomerulonephritis (GN) as the cause of end-stage renal disease (ESRD) are various, but there are not many studies on this.

Amelioration of streptozotocin-induced diabetes in rats: effect of islet isografts on plasma lipids and other metabolic abnormalities.

Administration of streptozotocin in rats results in many metabolic abnormalities, including hyperlipidemia. Plasma triglycerides, cholesterol, insulin, and glucose levels were compared in normal rats, in rats with streptozotocin-induced diabetes, and in streptozotocin-injected rats ameliorated of diabetes 1 mo later by transplantation of adult or neonatal islets to the liver or the lung. Mean plasma glucose levels were 98 ± 4 mg/dl in normal rats, 504 ± 36 mg/dl in untreated diabetic rats, and 139 ± 18, 146 ± 9, and 117 ± 19 mg/dl in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the glucose levels in the recipients of intraportal islets were significantly higher than in normal rats. Mean plasma insulin levels were 23 ± 4 μU/ml in normal rats, 12 ± 5 μU/ml in diabetic rats, and 46 ± 14, 84 ± 25, and 30 ± 5 μU/ml in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the insulin levels in the recipients of intraportal islets were also significantly higher than those in normal rats. Mean plasma triglyceride levels were 35 ± 3 mg/dl in normal rats, 280 ± 72 mg/dl in diabetic rats, and 49 ± 9, 58 ± 8, and 70 ± 4 mg/dl in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the levels in recipients of neonatal islets were significantly higher than those in normal rats. Mean plasma cholesterol levels were 122 ± 10 mg/dl in normal rats, 88 ± 13 mg/dl in diabetic rats, and 105 ± 10, 166 ± 19, and 114 ± 18 mg/dl in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the levels were significantly higher than normal only for the group receiving neonatal islet tissue via the portal vein. Islet transplantation ameliorated diabetes, but mild hyperglycemia persisted even though plasma insulin levels were elevated above normal in recipients of intraportal islets. In addition, plasma triglyceride levels remained slightly elevated after transplantation of neonatal islets, and cholesterol levels were elevated in the group with the highest insulin levels. Possible mechanisms to explain the abnormalities after islet transplantation are discussed. The results indicate the difficulty in restoring completely normal metabolism by ectopic islet transplantation in diabetic recipients.     

Emergency psychiatry training: the new old problem

Unevenness in emergency psychiatry training is still an issue as borne out by a recent literature review. An emergency setting in a general hospital is described with its attendant problem areas for psychiatric residents' function and learning. An adaptable curriculum is reported that takes into account limits of time, finances, and faculty.     

Randomized double-blind placebo-controlled multicenter evaluation of efficacy and dose finding of midodrine hydrochloride in women with mild to moderate stress urinary incontinence: a phase II study

Midodrine is a potent and selective ₁-receptor agonist and its potential to increase urethral closure pressure could be useful in the treatment of female stress incontinence. The aim of this randomized double-blind placebo-controlled multicenter study was to evaluate the efficacy and safety of midodrine for the treatment of stress urinary incontinence. The primary criterion of efficacy was the maximum urethral closure pressure at rest. Voiding diaries, symptom and incontinence questionnaires and patient/investigator global assessment were also used to evaluate its efficacy. After 4 weeks of treatment no significant changes in MUCP were found. The global assessment by the patient and investigator did indicate that patients on active treatment had a more positive assessment than the placebo group. In conclusion, midodrine did not cause significant improvements in urodynamic parameters, but there were subjective improvements in some of the patients in the treated groups. Furthermore midodrine was well tolerated.Editorial Comment: The authors present a controlled trial of midodrine hydrochloride in women with genuine stress incontinence. Although the primary efficacy criterion chosen was maximum urethral pressure at rest, a number of other evaluations were performed, including voiding diaries, subjective symptom questionnaires, and patient/investigator global assessment of therapeutic response. The study finds no change in urethra closure pressure at rest when taking the medication, although both patient and investigator global assessments indicate a significant therapeutic response. The study is ambitious, well accounted for in the report, and the results critically assessed by the authors. Although the results are equivocal as to the efficacy of midodrine hydrochloride in treating stress urinary incontinence, the study clearly presents and discusses the difficulties met in evaluating the pharmacological treatment of incontinence.     

Long-term Clinical Significance of Tacrolimus Trough Level at the Early Period After Kidney Transplantation

BackgroundThe stable immunosuppressant level at the early period after kidney transplantation (KT) is one of the most important factors for the prognosis of KT. However, the extent of immunosuppression varies according to the policies of each KT center. We investigated the relationship between the clinical outcome and tacrolimus trough level (TTL) at the early post-transplant period.Materials and MethodsWe retrospectively analyzed medical records of patients who underwent KT between July 2007 and June 2016. We investigated TTLs at 3 months after KT. We evaluated the incidence of biopsy-proven acute rejection (BPAR), cytomegalovirus infection, and graft survival according to the TTLs.ResultsA total of 426 patients who received KT during the study period were enrolled. The mean age of KT recipients was 46.3 ± 11.5 years, and 55.5% of patients were men. The incidence of BPAR within 1 year after KT was significantly higher when TTLs at 3 months were less than 4.0 ng/mL (P = .020). Death-censored graft survival rates were significantly lower in KT recipients with BPAR and TTL less than 4.0 ng/mL (P < .001, P < .001, respectively). In multivariate analysis, BPAR and TTL less than 4.0 ng/mL at 3 months after KT were independent risk factors for graft failure.ConclusionBPAR and TTL less than 4.0 ng/mL at 3 months after KT are important risk factors for allograft failure. Therefore, TTL should be kept at least 4.0 ng/mL or more at 3 months after KT to reduce the incidence of BPAR within 1 year after KT.     

Comparison of Different Treatment Modalities Outcomes in Clinically Node-positive Bladder Cancer: Analysis of a Population-based Cancer Registry

IntroductionPatients with clinically node-positive bladder cancer were historically considered to have uniformly poor prognosis and were frequently treated with palliative chemotherapy (CHT) only. Although retrospective data show that long-term survival with combined treatment (surgery + CHT) is possible in one-third of these patients, consensus on a treatment algorithm is still lacking. The aim of the study is to compare the efficacy of different treatment modalities based on data from a population-based cancer registry.Patients and MethodsThe study comprises 661 patients identified from the Czech National Cancer Registry (1996-2015) with cTanyN1-3M0 bladder cancer; 195 were treated with CHT alone, 234 underwent radical cystectomy alone (RC), and 232 received a combination of RC and perioperative CHT (RC + CHT). Multivariate Cox proportional hazard regression analyses were used to evaluate the effectiveness of various treatments.ResultsThe 5-year OS for CHT alone, RC alone, and RC + CHT were 21.7% (95% confidence interval [CI], 15.4%-28.0%), 12.1% (95% CI, 7.4%-16.7%), and 25.4% (95% CI, 18.9%-31.9%), respectively (P < .001). The median survivals were 17, 10, and 23 months, respectively. In multivariate analysis, age > 60 years (hazard ratio, 1.29; 95% CI, 1.06-1.56; P = .011) and clinical stage cT3-4 (hazard ratio, 1.39; 95% CI, 1.12-1.71; P = .002) were negative predictors of survival. When compared with CHT, RC + CHT reduced the risk of overall mortality by 21% (P = .044).ConclusionApproximately one-quarter of clinically node-positive patients may achieve long-term survival with combined treatment integrating RC and perioperative CHT. The overall survival of patients is significantly improved with a multimodal approach in comparison to CHT alone.