Interleukin-1beta increases urine flow rate and inhibits protein expression of Na(+)/K(+)-ATPase in the rat jejunum and kidney.

The effect of interleukin-1beta (IL-1beta) on urine flow rates and Na(+)/K(+)-ATPase activity and expression was studied in rat intestinal and renal epithelia. The cytokine produced a significant diuretic effect and increased urine flow rate by around 10-fold compared with the control. This effect was considered to be secondary to the well-documented natriuretic effect of the cytokine described in the literature. On the other hand, we have shown previously that IL-1beta inhibits glucose absorption from the jejunum. As sodium excretion and glucose absorption are both dependent on Na(+)/K(+)-ATPase activity, the effect of the cytokine on the renal and intestinal pump was investigated. IL-1beta inhibited, in a dose-dependent manner, the activity of Na(+)/K(+)-ATPase in villus and crypt jejunal cells and in medullary and cortical kidney cells. Western blot analysis revealed a decrease in the protein expression of the enzyme, which was confirmed by the radiolabeled ouabain binding assay. The results suggest that the diuretic and natriuretic effect of IL-1beta and its inhibitory effect on glucose absorption are all due to downregulation of the Na(+)/K(+) pump in the kidney and jejunum.     

Observer variation in the histopathological classification of thymoma: correlation with prognosis.

AIMS--To assess the ability of three histopathologists, experienced in thoracic surgical reporting, consistently to classify thymomas as cortical, medullary, or mixed pattern tumours. METHODS--Three histopathologists classified 74 thymomas (none frank carcinomas) as of either cortical, medullary, or mixed pattern, on two separate occasions. Kappa statistics were used to assess inter- and intra-observer agreement. Tumour type was compared with surgical stage as a predictor of biological behaviour. RESULTS--Inter- and intra-observer agreement were only moderate (kappa 0.48 and 0.52, respectively). For only 26 of 74 tumours could a categorisation be consistently agreed on. Follow up information was obtained for 73 cases, with a mean follow up period of five years. The prognoses for those 26 of 74 cases appeared to be at variance from previously reported studies, and showed internal inconsistency, with the mixed pattern category showing a worse survival than the cortical category. For the group as a whole, however, stage at presentation was related to survival, with an overall five year survival of 78% (100% for stage I, 84% for stage II, 27% for stage III and 0% for stage IV). CONCLUSIONS--The classification of thymomas into cortical, medullary, or mixed pattern tumours is difficult to apply. Surgical stage remains a better guide to prognosis.     

Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibodies to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human pro-bombesin

Several recent studies have confirmed the endocrine nature of small cell carcinoma of the lung. In extra-pulmonary sites, small cell 'undifferentiated' carcinomas have classical morphological features similar to their pulmonary counterpart. We therefore investigated, using immunocytochemistry, the possibility that the non-pulmonary neoplasms may also be endocrine in nature. Sections of 29 small cell carcinomas from oesophagus, stomach, larynx, colon and urinary bladder were immunostained using antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), cytokeratin, leucocyte common antigen and peptides including bombesin, the C-flanking peptide of human probombesin, adrenocorticotrophic hormone, neurotensin, calcitonin and pancreatic polypeptide. All the tumours showed immunoreactivity for at least one of the two general endocrine markers PGP 9.5 and NSE. Twenty-three of the 29 cases were immunoreactive for PGP 9.5, 27 for NSE. All were positive for cytokeratin and negative for leucocyte common antigen. Of the regulatory peptides, immunoreactivity was obtained with antisera to bombesin (one case), the C-flanking peptide of human pro-bombesin (14 cases), adrenocorticotrophic hormone (one case) and calcitonin (three cases). No PGP 9.5-, NSE- or peptide-like immunoreactivity was detected in 25 control tumours from similar sites, including lymphomas and poorly differentiated tumours. These results suggest that non-pulmonary small cell carcinoma has an endocrine character.     

Dose-intensive therapy for extensive-stage small cell lung cancer and extrapulmonary small cell carcinoma: long-term outcome.

Treatment for extensive-stage small cell lung cancer (ES SCLC) or extrapulmonary small cell carcinoma (EPSC) is typically palliative. We set out to determine progression-free survival (PFS) and overall long-term survival of ES SCLC and EPSC patients, physiologically aged < or = 60 years, responding to first-line chemotherapy followed by high-dose combination alkylating agents with hematologic stem cell support. Patients in first-line chemotherapy response underwent stem cell collection (marrow, peripheral blood progenitor cells, or both) followed by high-dose therapy with 1 of 2 regimens: CBP (cyclophosphamide, cisplatin, and carmustine) or ICE (ifosfamide, carboplatin, and etoposide) with or without etanidazole. Involved-field radiotherapy was given to selected patients with oligometastatic disease distributed in sites allowing for reasonable radiation ports, and prophylactic cranial radiotherapy was given upon recovery to patients in complete response (CR) or near-CR. A total of 36 patients were treated. Of 29 patients with ES SCLC, 6 (21%) had achieved CR, 18 near-CR, and 5 partial response prior to high-dose therapy. Of 7 patients with EPSC, 3 (43%) had achieved CR, 3 had achieved near-CR, and 1 had progression of disease prior to high-dose therapy. Thirteen ES SCLC patients received high-dose CBP. Of the remaining 23 patients with SCLC or EPSC, 17 were treated with ICE and 6 with ICE plus etanidazole, a hypoxic cell sensitizer. Treatment-related mortality was 11% (4 of 36 patients). For all patients, the median event-free survival (EFS) was 5 months. The 2- and 5-year survivals after intensification were 12% (95% confidence interval [CI], 5%-31%) and 9% (95% CI, 3%-27%), respectively. Of the 30 patients in or near CR prior to high-dose therapy, 5 remain continuously progression-free (2 ES SCLC, 3 EPSC) for a median of 55 months (range, 1-96 months) after high-dose therapy. By multivariate analysis, factors associated with more favorable EFS were the use of a more aggressive induction regimen (ICE), and the EPSC histology. These factors were also associated with more favorable overall survival. Other factors associated with more favorable overall survival were the use of short induction therapy (< or = 4 cycles) and younger age (<50 years). Except for high-dose ICE with etanidazole, the use of high-dose systemic therapy in ES SCLC and EPSC was associated with low treatment-related morbidity and mortality over the past 5 years. Late complications were infrequent, and most patients returned to full-time work and activity, barring disease recurrence. Nonetheless, few patients with ES SCLC have progression-free long-term survival. We conclude that high-dose therapy is not indicated as an approach for ES SCLC, except as part of an investigative trial. Conversely, 3 of the 7 patients with EPSC remain relapse-free (range, 1-96 months), warranting further phase II evaluation of this approach in this population.     

Application of an aldrin and dieldrin ELISA to the detection of pesticides in eggs

This paper details the results obtained when a number of egg samples, collected in Egypt from different races of chicken were analyzed for the presence of the organochlorine insecticides aldrin and dieldrin. A simple ELISA was used for the detection and quantification of aldrin and dieldrin. The test was modified for application in this high protein system. Pesticide was detected in 83–352% (14/17) of the samples at levels ranging from 0.006 to 0.7 ppm (0.006 to 0.7 μg ml^‐1). People eating eggs containing these amounts of pesticides which are above the World Health Organisation average daily intake levels would be at increased risk.     

Axon-myelin sheath relations of oligodendrocyte unit phenotypes in the adult rat anterior medullary velum

Axon-oligodendrocyte relations of Rip-immunolabelled and dye-injected oligodendrocyte units are characterised in the adult rat anterior medullary velum (AMV). Each oligodendrocyte unit comprised the oligodendrocyte cell body, processes and the internodal myelin segments they support. Oligodendrocyte units corresponded to classically described type I/II or type III/IV unit phenotypes which respectively myelinated discrete populations of small and large diameter axons, delineated by a myelinated fire diameter of 2-4 microns (diameter of the axon plus its myelin sheath). Within units, mean fibre diameter was directly related to mean internodal length and inversely related to the number of myelin sheaths in the unit. The relationship between fibre diameter and internodal length was retained in units which myelinated axons of different diameters, indicating that axon diameter was an important determinant of the longitudinal dimensions of myelin sheaths. We also show that type III/IV units maintained a far greater volume of myelin than type I/II units. It was concluded that type I/II and III/IV oligodendrocytes represent two functionally and morphologically distinct phenotypes whose distribution densities were determined by the diameter and spatial dispersion of axons.     

HbA1c over 8.5% is not predictive of increased infection rate following penile prosthesis implant surgery in diabetic patients with erectile dysfunction

Diabetes mellitus is associated with increased risk of erectile dysfunction. Penile prosthesis implantation is an efficient therapeutic option for erectile dysfunction, but not without risk, as infection remains a prominent concern. This study investigates diabetes mellitus as a risk factor for penile prosthesis implantation infection and the relationship between haemoglobinA1c levels and infection rates. All diabetic patients with erectile dysfunction who underwent penile prosthesis implantation surgery between January 2012 and November 2019 at Hamad Medical Corporation, Qatar, were included in this retrospective observational study. A total of 599 diabetic patients with erectile dysfunction had penile prosthesis implantation. Mean age was 59.69 ± 31.19. Penile prosthesis implantation infection rate was 0.83% (5/599), while the mean haemoglobinA1c level was 7.58 ± 1.45 mmol/l (range: 4.1–12.6). A comparison between diabetic patients with penile prosthesis implantation infection and those without infection revealed no significant difference in the level of haemoglobinA1c between the two groups with mean haemoglobinA1c in patients with infected implants 7.14 and 7.59 for noninfected (p = 0.491). Limitations include retrospective single-centre design and low-infection rates reducing sample number. Penile prosthesis implantation infection rate in a large series of diabetic patients was low with no significant association between haemoglobinA1c level and penile prosthesis implantation infection observed.     

Endocrine contribution to the sexual dysfunction in patients with advanced chronic kidney disease and the role of hyperprolactinemia

In this study, we investigated the prevalence of sexual dysfunction among males with advanced chronic kidney disease and the effect of treating hyperprolactinemia among these patients. In this prospective study, patients were assessed with history, physical examination, hormonal assessment, and two questionnaires, IIEF and AIPE. Patients with hyperprolactinemia received treatment with cabergoline 0.5 mg once per week for 6 months and were re-evaluated. A total of 102 patients were included in this study, 75 (73.53%) were on hemodialysis, 13 (12.75%) on peritoneal dialysis and 14 (13.73%) on medical treatment alone. Ninety (88.24%) patients had premature ejaculation, 85 (83.33%) had anything from mild-to-moderate-to-severe erectile dysfunction. The incidence of hypogonadism and hyperprolactinemia was 34.4%. Patients treated with cabergoline (n = 26) showed a significant increase in LH levels (p = .003) and a significant decrease in prolactin levels (p = .003). Testosterone levels and the incidence of erectile dysfunction or premature ejaculation did not improve significantly. There is a high incidence of sexual dysfunction among patients. Treatment of hyperprolactinemia is effective in correcting prolactin levels, but does not improve erectile dysfunction or premature ejaculation. Therefore, treating hyperprolactinemia is not an overall effective treatment for erectile dysfunction in these patients.     

Long-Term Outcomes of Everolimus Therapy in De Novo Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundRisk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of everolimus (EVR) in minimizing this risk when combined with a reduced CnI dose.BackgroundTo systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post-liver transplantation.MethodsWe searched MEDLINE, Scopus, and the Cochrane Library for randomized controlled trials comparing EVR- and CnI-based regimens post-liver transplantation. Assessment of studies and data extraction were undertaken independently.ResultsEight studies were selected, describing 769 patients. Cockcroft-Gault GFR was higher at one (P = .05), 3, and 5 years (P = .030) in patients on EVR compared to those receiving CnI therapy. The composite endpoint of efficacy failure was similar between the 2 arms after 1, 3, and 5 years of study. More patients discontinued EVR due to adverse effects in 1 year; however, no difference was noted after 3 or 5 years. A higher rates of proteinuria, peripheral edema, and incisional hernia occurred in patients on EVR.ConclusionsThe analysis confirms noninferiority of EVR and reduced CnI combination. Combination regimen resulted in better renal function compared to standard CnI therapy.