Is male fertility associated with type 2 diabetes mellitus?

Objective  

The aim of this study was to determine the prevalence of infertility in Qatari men with Diabetes Mellitus (T2DM) and to examine the association between T2DM and infertility.     

Long-term graft outcome in patients with chronic allograft nephropathy after immunosuppression modifications

Background/aim  This retrospective study was conducted to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy (CAN). Methods  One-hundred and seventy-four cyclosporin (CsA)-treated renal transplant recipients were studied. Patients were included if they had a biopsy-proven CAN (mild to moderate) with serum creatinine ≤3.5 mg/dL. Patient treatment was switched to either: (A) MMF/reduced dose CsA (MMF for azathioprine (Aza); n = 132); or (B) Aza/Tac for CsA (n = 42). Patient records were checked for graft function and survival, and for co-morbidities after conversion. Results  Mean follow-up before conversion was 52.2 ± 31.1 and 47.9 ± 27.4 months for groups A and B, respectively. There was significant deterioration of graft function in group B after five years (P < 0.5). Ten-year actuarial graft survival was 38% in group A and 19% in group B (P = 0.04). Nine patients (five patients and four patients in groups A and B, respectively) started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P = 0.05), but a significantly higher incidence of diabetes mellitus (P = 0.04).There was no significant change or difference in blood pressure between groups. Conclusions  Our results suggest that in patients with CAN and deteriorating allograft function, CsA minimization and addition of MMF achieved favorable efficacies in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.     

Does posttransplant anemia at 6 months affect long-term outcome of live-donor kidney transplantation? A single-center experience

Background/Aims  Posttransplantation anemia (PTA) frequently occurs. We aimed to assess the prevalence of anemia at 6 months of transplantation in patients under different protocols of immunosuppression, and to determine the impact of anemia on long-term patient and graft survival. Methods  We included 832 renal transplant recipients who were categorized at 6 months according to hemoglobin (Hb) level into two groups: the first group, with Hb >13 g/dl in males and >12 g/dl in females (group I, 385 cases); and the second group, with Hb <13 g/dl in males and <12 g/dl in females (group II, 447 cases). We compared the two groups regarding posttransplant complications as well as patient and graft survival. Results  Although there was no significant difference between the two groups regarding acute rejection episodes, chronic allograft nephropathy was significantly higher in the anemic group. Other posttransplant medical complications were comparable in both groups. Graft survival was significantly higher in the nonanemic group. However, no difference in patient survival was detected. Conclusion  From this study, we can conclude that prevalence of PTA is high, especially in females and those receiving calcineurine inhibitors (CNI) and mycophenolate mofetil (MMF), and that it was associated with poorer graft outcome but with no effect on patient survival.     

Changes in chromatin phenotype predict the response to hormonal deprivation therapy in patients with prostate cancer

OBJECTIVE

To assess the value of studying chromatin organization using high‐resolution digital image analysis to predict the response to hormonal‐deprivation therapy (HDT) in patients with prostate cancer, using pretreatment prostate tissues.

MATERIALS AND METHODS

A tissue microarray (TMA) was constructed using pretreatment paraffin‐embedded tissues from transurethral resection of the prostate (TURP) samples (48 patients, 96 cores). None of the patients had received any treatment for prostate cancer before TURP. The patients’ medical records for 5 years after treatment were assessed; patients were divided, based on their prostatic specific antigen (PSA) levels after treatment, into those optimally responsive to HDT (14) and those resistant to HDT (34). The latter were further subclassified based on their nadir PSA level. Imaging comprised a calibrated digital image‐analysis system with software for densitometric and texture analysis, the latter being assessed on manually segmented nuclei (≥30 nuclei/core).

RESULTS

Most of the measured digital texture features assessing chromatin density and distribution were significantly different between the prognostic groups (P = 0.001). In the training set, 12 of 14 HDT‐responsive and 23 (68%) of HDT‐resistant patients were accurately predicted. However, all HDT‐resistant patients with a nadir PSA level of >5 ng/mL were accurately predicted. The overall classification sensitivity was 47%, specificity 94% with a positive predictive value of 85%. However, the sensitivity was 100% between patients optimally responsive to HDT and those poorly responsive with a nadir PSA level of >5 ng/mL.

CONCLUSION

Quantitative image analysis of chromatin phenotype showed promising value in predicting before treatment the response to HDT in patients diagnosed with prostatic adenocarcinoma. However, further work using larger data sets is required before adapting the technique in routine clinical practice.     

Antagonist-induced increase in 5-HT1A-receptor expression in adult rat hippocampus and cortex

Many receptor antagonists function as reverse agonists on the signaling transduction pathway, but little is known about the action of these drugs on the regulation of receptor expression. Serotonin 1A (5-HT1A) receptor expression in 5-HT and serum-free fetal hippocampal cultures is increased in the presence of a specific 5-HT1A-receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635). To study the plasticity of postsynaptic 5-HT1A receptors in the presence of antagonist in vivo, adult Sprague Dawley rats were injected i.p. either once or twice daily with a dose of WAY 100635 (3 mg/kg) over a period of 3 days. The 5-HT1A receptor expression was detected by immunocytochemistry and light microscopy, and the receptor immunoreactivity (IR) in hippocampus subregions was quantitatively assessed by using a comparative computer-assisted morphometric analysis. Following the daily injections of WAY 100635, a significant increase in 5-HT1A receptor labeling in hippocampal neurons was recorded. This marked increase in 5-HT1A receptor expression, which occurred within 4 h after a single injection of WAY 100635, is evident on the somata membrane and dendritic processes of hippocampal and cortex layer V neurons. By contrast, no increase in 5-HT1A receptor-IR was observed after multiple daily injections at a low dose (1 mg/kg) of WAY 100635. Our study shows that a single or multiple daily injections of WAY 100635 can result in an increase in 5-HT1A receptor-IR. This increase in labeling is consistent with an enhanced expression of the receptor protein. The action of this "inverse agonist" may have clinical importance in disorders such as depression, epilepsy, and Alzheimer's disease in which 5-HT1A receptor levels are deficient.