Endothelin Converting Enzyme-1 Expression in Endometrial Adenocarcinomas

Endothelin-1 (ET-1) is a potent mitogen in various precursor tumor cells, including endometrial adenocarcinoma. It is proposed that ET-1 produced by endometrial adenocarcinoma may participate in the angiogenesis of this carcinoma in vivo. Endothelin converting enzyme-1 (ECE-1) is the key enzyme that synthesizes ET-1. In this study, we tried to demonstrate the expression of ECE-1 in endometrial carcinomas. Deparaffinized tissue sections from patients with endometrial adenocarcinoma were analyzed by immunohistochemistry for the presence of ECE-1. Our study showed that the expression of ECE-1 was markedly increased in 9 of 15 (60%) well-differentiated endometrial adenocarcinomas; in contrast, only 2 out of 10 (20%) control specimens showed a mild labeling. With new selective inhibitory molecules emerging, research is currently evaluating the possible inhibition of ECE-1 as an alternative approach for the treatment of endometrial as well as other carcinomas.     

The impact of visceral fat on multiple risk factors and carotid atherosclerosis in chronic haemodialysis patients.

Sir, We read with much interest the original article by Yamauchiet al. [1] reporting the importance of visceral fat (VF) incarotid atherosclerosis, lipid abnormalities and hyperinsulinaemiain maintenance haemodialysis patients. In their study, the patientswere separated into three groups according to VF content, andthree groups were compared for well known atherosclerotic     

The cost-effectiveness of treating chronic hepatitis B patients in a median endemic and middle income country

Background/aims

Chronic hepatitis B (CHB) infection is a serious public health problem due to its potential liver disease sequelae and highly expensive medical costs such as the need for liver transplantation. The aim of this study was to quantify the burden of active CHB in terms of mortality and morbidity, the eligibility of antiviral treatment and to assess various treatment scenarios and possible salvage combinations for cost-effectiveness.

Methods

A population cohort from a large data base of chronic hepatitis B patients was constructed and stratified according to 10-year age groups, the prevalence of HBsAg, HBV DNA level, ALT level, HBeAg status and the presence of cirrhosis. An age-specific Markov model for disease progression and cost-effectiveness analysis was constructed and calibrated for the specific population setting.

Results

Of about 3.2 million estimated HBsAg carriers, 25?% are eligible for treatment. If the active cohort remains untreated, 31?% will die due to liver related complications. Within a 20-year period, 11?% will have developed decompensated cirrhosis, 12?% liver cancer and 6?% will need liver transplantation. Quality adjusted life years (QALYs) for the no treatment scenario ranged from 9.3 to 14.0. For scenarios with antiviral treatment, QALYs ranged from 9.9 to 14.5 for lamivudine, 13.0–17.5 for salvage therapy, and 16.6–19.0 for the third generation drugs entecavir and tenofovir.

Conclusion

In a country with considerable amount of active CHB patients, monotherapy with a highly potent third generation drug has the most health-gain, and is cost-effective in both HBeAg-positive and negative in all stages of liver disease.     

Observer Variability of the Breast Imaging Reporting and Data System (BI-RADS) Lexicon for Mammography

AIM: We aimed to determine the inter- and intra-observer variabilities between breast radiologists and a general radiologist in categorizing mammographic lesions using the Breast Imaging Reporting and Data System (BI-RADS), and to evaluate the effects of the histopathologic results on the variability. METHODS: Mammograms from 142 women who underwent biopsy were evaluated. 3 breast radiologists (2 with >10 years experience and 1 with 1 year experience) and 1 general radiologist retrospectively reviewed mammograms twice within an 8-week interval. Inter- and intra-observer variabilities were assessed with Cohen's kappa statistic, and the positive predictive value for final assessments was calculated. RESULTS: The intra-observer variability for mass and calcification assessments was moderate to almost perfect (kappa values: 0.41-1) for breast imagers and was fair to substantial for the general radiologist (kappa values: 0.21-0.8). Inter-observer agreement between the breast imagers was higher than between the breast and general radiologists. There was no apparent difference in agreement between observers for malignant and benign subgroups. CONCLUSIONS: The differences in intra- and inter-observer agreement between the breast imagers and the general radiologist affirm the utility of the BI-RADS lexicon. The histopathologic results of the lesions do not affect the agreement. BI-RADS is a simple and adequate tool for assessing mammograms, even after only 1 year of training.     

Hyaluronan based heparin free coated open and closed extracorporeal circuits for high risk coronary revascularization

This prospective randomized study compares the inflammatory response and fibrinolytic activation of fully coated/uncoated and open/closed extracorporeal circuits (ECC) in high risk patients. Over a 2-month period, 48 patients with EuroSCOREs 6 or greater undergoing coronary revascularization were prospectively randomized to one of the four perfusion protocols: Group 1: Closed and totally hyaluronan based heparin free coated (Vision HFO-GBS-HF, Gish Biomedical, Rancho Santa Margarita, CA) ECC with a soft-shell coated venous reservoir (SVR11S2-HFC, Gish Biomedical) and a hard-shell cardiotomy (CAPVRF44, Gish Biomedical) (n = 12); Group 2: Closed and totally uncoated identical ECC with soft-shell uncoated venous reservoir and a hard-shell cardiotomy (n = 12); Group 3: Open, totally hyaluronan based heparin free coated ECC (n = 12); and Group 4: Control-open, uncoated ECC (n = 12). Blood samples were collected at T1: Baseline; T2: 15 minutes after cardiopulmonary bypass (CPB) initiation; T3: before cessation of CPB; T4: 15 minutes after protamine reversal, and T5: in the intensive care unit. Serum IL-6 levels were significantly lower at T2 in all study groups, at T3 for coated groups, and T4 for closed+coated group (p < .05 versus control). Creatine kinase M-band (MB) levels in coronary sinus blood demonstrated well preserved myocardium after CPB in both coated groups versus Control (p < .05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups versus control at T2, for both coated groups at T3 and only for closed + coated group at T4 (p < .05). Postoperative hemorrhage (mL) was 510 +/- 40 in closed + coated and 536 +/- 40 in open + coated groups (control: 784 +/- 48, p < .05). No significant differences in thrombin-antithrombin complex and free plasma hemoglobin were observed. Desorbed protein amount on ECC (mg/dL) was 1.7 +/- .01 in closed+coated, 2.01 +/- .01 in open+coated, and 3.3 +/- .015 in control groups (p < or = .05). Use of a closed and completely heparin free coated ECC may reduce neutrophil degradation, cytokine release characterized by improved clinical outcomes including reduced blood loss, reduced requirement for inotropes, and reduced atrial fibrillation.     

A novel approach for small sample size family-based association studies: sequential tests

In this paper, we propose a sequential probability ratio test (SPRT) to overcome the problem of limited samples in studies related to complex genetic diseases. The results of this novel approach are compared with the ones obtained from the traditional transmission disequilibrium test (TDT) on simulated data. Although TDT classifies single-nucleotide polymorphisms (SNPs) to only two groups (SNPs associated with the disease and the others), SPRT has the flexibility of assigning SNPs to a third group, that is, those for which we do not have enough evidence and should keep sampling. It is shown that SPRT results in smaller ratios of false positives and negatives, as well as better accuracy and sensitivity values for classifying SNPs when compared with TDT. By using SPRT, data with small sample size become usable for an accurate association analysis.