Analysis of the mononuclear inflammatory cell infiltrate in the cirrhotic, dysplastic nodules and hepatocellular carcinomas in patients with chronic hepatitis C infection

BACKGROUND: Hepatocarcinogenesis is a multistep process entailing the transitions from normal liver --> chronic hepatitis and cirrhotic nodules (CH/CNs) --> dysplastic nodules (DNs) --> hepatocellular carcinomas (HCCs). We hypothesized that hepatocarcinogeneis on top of chronic hepatitis C (CH-C) is associated with alterations in the mononuclear inflammatory cell infiltrate (MICs) in response to altered antigenicity of the damaged hepatocytes. MATERIALS AND METHODS: A total of 19 hepatic resection specimens entailing the entire continuum of the lesional steps of the hepatocarcinogenesis (on top of CH-C) were evaluated for MICs using immunohistological methods and mouse monoclonal antibodies (CD3, CD20, CD68 and T-cell intracellular associated antigen, TIA-1). RESULTS: HCCs were: 1) overrepresented in elderly males (56.1 +/- 2.0 years, with male to female ratio of 1.8:1), and 2) more common in the right than in left lobe (1.1:1) The transitions from normal liver to the subsequent lesional steps (CH-C/CNs, DNs and HCCs) was associated with statistically significantly (p < 0.000) increased density of: tumor infiltrating lymphocytes (9.5 +/- 0.2 vs. 87.1 +/- 1.3 vs. 73.6 +/- 1.6 vs. 72.1 +/- 3.5), CD20+ B cells (4.4 +/- 0.2 vs. 35.0 +/- 2.9 vs.11.3 +/- 1.8 vs. 11.3 +/- 1.6), CD68+ macrophages (1.4 +/- 0.1 vs. 9.5 +/- 1.8 vs. 22.3 +/- 1.6 vs. 18.8 +/- 2.0), CD3+ cells (5.4 +/- 0.1 vs. 87.0 +/- 1.3 vs. 62.2 +/- 1.3 vs. 61.0 +/- 3.4) and TIA-1(+) cytototoxic T cells (0.4 +/- 0.1 vs. 11.6 +/- 2.0 vs. 24.9 +/- 1.2 vs. 30.5 +/- 1.6). CONCLUSIONS: Increased MICs during hepatocarcinogeneis (on top of CH-C) may reflect change in the antigenicity of the damaged hepatocytes. Although both B (humoral response) and T (cell mediated immunity) lymphocytes were involved, the later were the most numerous immunocytes. A considerable fraction of these T cells was TIA-1(+) cells suggesting their cytotoxic potential.     

Variable omeprazole kinetics in healthy Jordanian adults

OBJECTIVES: The objective of this study was to examine the pharmacokinetics of orally administered omeprazole in healthy adult Jordanian men. METHOD: Plasma concentrations of omeprazole were measured over a 12 h period after administration of a single oral dose of 40 mg omeprazole (Losec), AstraZeneca, UK). Subjects were healthy adult Jordanian men age 18-38 (24 +/- 4, mean +/- SD). The pharmacokinetic parameters were derived from the plasma concentration-time profiles for AUC(0-t), AUC(0-inf), C(max), t(max), t(1/2e) and K(e). RESULTS: The pharmacokinetic of omeprazole were scattered over a wide range. The median AUC(0-inf) was 784.86 +/- 1182.88 (ng.h/ml), and the median C(max) was 521 +/- 354 (ng/ml) (median +/- SD). In general, most subjects showed normal distribution (approximately 90%). Some subjects (10%) did show very high AUC and C(max) compared with the reported AUC and C(max) levels. These subjects had higher half-lives and lower rates of elimination. CONCLUSION: Significant difference in the pharmacokinetics of omeprazole after a single dose administration was noted. Approximately 10% of the study group showed very high omeprazole plasma levels and AUCs. Differences in the pharmacokinetics might be due to differences in the genetic make-up of subjects.     

The role of optical coherence tomography in multiple sclerosis: expert panel consensus

Optic neuritis (ON), a common manifestation of multiple sclerosis (MS), often occurs as the initial manifestation of central nervous system demyelination or develops during the course of this disease. Since the retinal nerve fiber layer (RNFL) is composed only of unmyelinated axons, measuring RNFL thickness represents a viable method of monitoring axonal loss in these patients. Optical coherence tomography (OCT) is a noninvasive, noncontact, accurate, and reproducible technique that quantitates the thickness of the peripapillary RNFL, fovea, and macula. Because of its potential role in defining axonal loss in ON and in assessing longitudinal changes in the RNFL before and after MS treatment, a multidisciplinary expert panel was charged with the following tasks: assess the current capabilities of OCT; review the current data about OCT, ON, and MS; and determine whether OCT could be a primary or secondary outcome measure in future MS clinical trials. The panel concluded that: [1] OCT is valid and reproducible; [2] OCT has yielded some important limited data concerning cross-sectional studies with ON and MS; [3] more studies are required to correlate OCT results with other measures of MS disease activity; [4] after correlation with these other measures and upon agreement of standardized technical and statistical methods, OCT may evolve into a important primary or secondary outcome metric for MS clinical trials and patient care.     

A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.     

Does loss of hormonal receptors influence the pathophysiological characteristics of the HER-2 breast cancer phenotype?

Background

Some breast carcinomas (BC) of the HER-2 type respond poorly to endocrine therapy, indicating that hormonal receptor (HR) status possibly impacts the biological criteria of this tumor class. The aim of this study was to compare the clinicopathological characteristics of HR-positive and HR-negative tumors occurring in HER-2 and non-HER-2 BC.

Facets of career satisfaction for women physicians in the United States: a systematic review

Women make up a growing proportion of the physician workforce, and their career satisfaction may affect their health. The authors hypothesized that many facets adversely affecting career satisfaction in women physicians were extrinsic, therefore, preventable or modifiable. The authors conducted a systematic review of the literature in English published through February 2010 to examine facets of career satisfaction of U.S. women physicians. The authors used the women physician AND job satisfaction OR career satisfaction Medical Subject Headings (MeSH) terms, and reviewed bibliographies of key articles to ensure inclusion of relevant studies. The authors used the "Strengthening the Reporting of Observation Studies in Epidemiology" quality tool. Of an initial 1,000 studies, only 30 met the inclusion criteria. Facets reported most frequently to influence career satisfaction for women physicians were income/prestige, practice characteristics, and personal/family characteristics. Overall, career satisfaction for women and men physicians was 73.4% (range = 56.4% to 90%) and 73.2% (range = 59% to 90%), respectively. When compared with men, women physicians were more concerned with perceived lack of time for relationships with patients, colleagues, and family; less satisfied with mentoring relationships and support from all sources; and less satisfied with career-advancement opportunities, recognition, and salary. Career satisfaction can affect health, as well as health and safety of patients. Many factors adversely affecting career satisfaction for women physicians are extrinsic and, therefore, modifiable.