Immunostaining of p53 protein in ovarian carcinoma: correlation with histopathological data and clinical outcome

Objective: The objective of this study was to analyze the incidence of immunohistochemically detectable p53 protein accumulation in epithelial ovarian carcinomas and to correlate these data with the clinical outcome so as to clarify further the role of p53 mutations in prognosis with these patients.Methods: Tumor tissues from 179 patients with epithelial ovarian carcinoma were used for immuno-histochemical analysis with monoclonal antibody DO1 and BP 53-12-1 on formalin-fixed, paraffin-embedded tissue.Results: A total of 78 cases (44%) showed positive nuclear p53 staining. The p53-positive cases were found in all histological types of epithelial ovarian tumors. p53 staining was found in tumors of all stages with a higher percentage of positive cases in stage IV ovarian carcinomas (not significant). Poorly differentiated carcinomas showed a significantly higher percentage of p53 protein expression than did highly differentiated tumors (P=0.0002). Clinical follow-up of up to 14 years (median 25 months) showed a slightly but not significantly shortened disease-free and overall survival time for patients with p53-positive epithelial ovarian carcinomas.Conclusions: We conclude from our data that p53 expression in ovarian carcinoma is associated with poor differentiation but not with the disease being in an advanced stage. There was a tendency for shortened disease-free and overall survival for patients with p53-positive tumors.     

Decreased ATP-sensitive K(+) current density during chronic human atrial fibrillation

Chronic atrial fibrillation (AF) is associated with shortening of action potential duration (APD), which involves modified activity of atrial ion currents. However, little is known about the activity of ATP-sensitive K(+) channels (I(K,ATP)) during chronic AF. An AF-related increase in the activity of I(K,ATP) would reduce APD and could contribute to initiation and/or perpetuation of AF. Here, we studied the activity of I(K,ATP) in atrial myocytes from patients with sinus rhythm (SR) and chronic AF. Human atrial myocytes were isolated from atrial tissue obtained from patients undergoing open-heart surgery. Inward rectifier currents were measured with the whole-cell patch-clamp technique by applying a depolarizing ramp pulse (1245 ms) from -100 to +40 mV (0.5 Hz). I(K,ATP) was activated with the I(K,ATP) channel opener rilmakalim. The inward rectifier I(K1) and I(K,ATP) were identified by their sensitivity to 1 mM Ba(2+). Density of I(K1) did not differ between cells from patients with AF (at -100 mV: -14.8 +/- 1.3 pA/pF, n = 38/10 (cells/patients)) and SR (-13.8 +/- 1.5 pA/pF, n = 33/16). In both types of cells, rilmakalim stimulated I(K,ATP) (defined as rilmakalim-inducible current) in a concentration-dependent manner (0.3-10 microM). However, maximum activation of I(K,ATP) with 10 microM rilmakalim was smaller in AF than in SR cells (at -100 mV: -5.3 +/- 0.8 pA/pF, n = 22/7 vs. -11.2 +/- 2.9 pA/pF, n = 19/9; at +40 mV: +9.6 +/- 2.1 pA/pF, n = 22/7 vs. +23.7 +/- 3.4 pA/pF, n = 19/9 for AF and SR, respectively; P < 0.05). Only aortic valve disease and pulmonary hypertension were found to be independent contributors to I(K,ATP) current density. We provide evidence that chronic AF is associated with a downregulation of ATP-sensitive K(+) currents. These changes may provide an additional molecular mechanism for electrical remodeling in chronic AF.     

Examining Mediators of the Relationship Between Community Mobilization and HIV Incidence Among Young South African Women Participating in the HPTN 068 Study Cohort

AIDS and Behavior - We previously demonstrated that village community mobilization (CM) was associated with reduced HIV incidence among adolescent girls and young women (AGYW) in South Africa....     

Chronic cyclooxygenase-2 inhibition does not alter blood pressure and kidney function in renovascular hypertensive rats

BACKGROUND: It has been shown that the macula densa participates in the regulation of increased renin expression in two-kidney one-clip (2K1C) renovascular hypertension. Prostaglandins might be one of the mediators of macula densa function, because the cyclooxygenase-2 (COX-2), one of the rate-limiting enzymes of the prostaglandin pathway, is upregulated in 2K1C renovascular hypertensive rats. We tested the effect of chronic COX-2 inhibition on blood pressure, urinary aldosterone excretion and kidney morphology, as well as kidney function. METHODS: Four groups were established: two groups of 2K1C renovascular hypertensive rats treated with the specific COX-2 inhibitor Celecoxib (cele) (15 mg/kg per day) or placebo immediately after operation, and two sham-operated control groups fed with Celecoxib or placebo. RESULTS: Long-term COX-2 inhibition in 2K1C renovascular hypertensive rats did not alter blood pressure at any point of time. Urinary aldosterone excretion was elevated by clipping the renal artery (2K1C, 8.1 +/- 1.9, versus controls, 3.6 +/- 0.5 ng/24 h; P = 0.05) but was not influenced by treatment with Celecoxib. Also, Celecoxib treatment did not alter glomerular filtration rate (GFR), serum sodium, serum creatinine, serum urea or proteinuria in 2K1C renovascular hypertensive rats. Interstitial fibrosis of the left clipped kidney was markedly reduced (2K1C, 6.19 +/- 0.83% versus 2K1C + cele 3.00 +/- 0.68% of total area; P = 0.012), whereas the interstitial fibrosis of the non-clipped kidney or the glomerulosclerosis of both kidneys were not affected by Celecoxib treatment. CONCLUSIONS: Celecoxib reduces the interstitial fibrosis of the clipped kidney. Blood pressure, urinary aldosterone excretion or whole kidney function were not affected in renal hypertensive rats.     

Why HIV Infections Have Increased Among Men Who Have Sex with Men and What to Do About It: Findings from California Focus Groups

A resurgence of sexual risk taking, STDs, and HIV incidence has been reported among men who have sex with men (MSM) in several countries. We asked 113 MSM in 12 focus groups conducted in five California cities to identify factors leading to increased risk taking and assess prevention messages to reduce risk in this population. Participants perceived that HIV risk taking has increased because (1) HIV is not the threat it once was due to more effective therapies, (2) MSM communicate less about HIV, and social support for being safe has decreased, and (3) community norms have shifted such that unsafe sex is more acceptable. The prevention messages ranked most likely to motivate risk reduction encouraged individuals to seek social support from friends. Themes ranked least likely to succeed were those that described the negative consequences of HIV or reinforced existing safer sex messages.     

Unexpected results found in larvae samples from two postmortem forensic cases

Forensic Toxicology - In forensics, entomological specimens can be used as additional/alternative matrices to detect xenobiotics when human specimens are limited in their application. Despite some...     

Electrocardiographic gated (99m)Tc-sestamibi SPECT immediately after primary percutaneous coronary intervention characterizes reperfusion success

Following an acute myocardial infarction, the size of the infarct and the resulting left ventricular volume and function are important predictors of mortality. Identifying patients with impaired tissue level perfusion after percutaneous coronary intervention (PCI) for myocardial infarction therefore could have prognostic implications. To obtain combined measures of left ventricular perfusion, volumes and function we applied a gated myocardial perfusion imaging by (99m)Tc-sestamibi single photon emission computerized tomography to 19 patients immediately after revascularization by PCI and repeated this after 3 months. The results of the acute myocardial perfusion imaging significantly correlated to final infarct size, left ventricular volumes and function 3 months later. It is concluded that the method holds the potential for risk stratifying patients immediately after revascularization for acute myocardial infarction.     

A modified single-loop reconstruction after pancreaticoduodenectomy reduces severity of postoperative pancreatic fistula in high-risk patients

Background

Double-loop (DL) reconstruction after pancreaticoduodenectomy (PD), diverting pancreatic from biliary secretions, has been reported to reduce rates and severity of postoperative pancreatic fistula (POPF) compared to single loop (SL) reconstruction at the price of prolonged operative duration. This study investigated the feasibility of a new reconstruction method combining the advantages of DL with the simplicity of SL in patients with high-risk pancreas.

The effect of hepatectomy on glucose homeostasis in pig and in man.

BACKGROUND/AIMS: The liver is regarded the most important source of glucose production and it is common practice to administer glucose during human liver transplantations to avoid hypoglycaemia. The purpose of this study was to evaluate the importance of extra-hepatic contribution (kidney, gut and muscle) to the glucose homeostasis in the anhepatic pig and in man during the anhepatic phase of human liver transplantations. METHODS: Blood glucose and lactate were monitored in the anhepatic phase in 46 patients undergoing liver transplantation. Arterial-venous differences of lactate, glucose, glycerol, alanine and free fatty acids were measured over kidney, gut and hind leg in 18 pigs made anhepatic. RESULTS: Blood glucose did not change significantly and blood lactate increased only marginally during the anhepatic phase of human orthotopic liver transplantation. In the anhepatic pig, however, blood glucose decreased with a halflife of about 26 min and blood lactate increased. Kidney gluconeogenesis was 0.116+/-0.016 mmol min(-1). Fifty percent of kidney glucose output could be accounted for by lactate- and glycerol uptake. CONCLUSIONS: The results show that in humans extra hepatic gluconeogenesis is sufficient to maintain normal blood glucose in the anhepatic phase of orthotopic liver transplantation, while in the pig this was not the case.