Effect of cold storage on the haemostatic cascade systems

This study dealt with the effect of citrate phosphate dextrose adenine (CPDA) whole blood stored at 4 degrees C for 5 weeks and fresh frozen plasma at -30 degrees C for 12 months on coagulation, fibrinolytic and kallikrein system activation. Stored whole blood showed a significant decrease in ATIII activity by the second week with a significant decrease in thrombin-antithrombin complex by the fourth week. alpha 2-antiplasmin and plasminogen decreased significantly by the first and second week, respectively, accompanied by a significant increase in D-dimer level by the fourth week. A significant decrease in C1-inhibitor activity occurred by the first week associated with a significant increase in kallikrein activity by the third week. However, all measured parameters were minimally affected in fresh frozen plasma. Therefore, fresh frozen plasma supplemented with packed RBCs are preferred to whole blood stored over 3 weeks especially in patients with proteolytic enzyme system activation.     

The association of HLA class II DR B1 alleles with HCV infection in Egyptian children

Background and study aimsHuman leucocyte antigens (HLA) class II appear to play an important role in the individual’s immune response to viral infection. The aim of this study is to assess the relationship between HLA class II antigens with the clinical, laboratory and histopathological state of the liver in Egyptian children and adolescents with chronic hepatitis C virus (HCV) infection.Patients and methodsThe study included 46 chronically infected HCV children and adolescents without – hepatitis B virus (HBV) nor human immunodeficiency virus – (HIV). Their mean age was 10.4 ± 4.23 years (3–17). HLA-DRB typing was done by polymerase chain reaction (PCR) for the patients and 20 control subjects. Biochemical and haematological parameters were assessed as well as a liver biopsy was taken from the included patients.ResultsThe most frequent alleles demonstrated among patients were DRB1103, DRB1104 and DRB1113 (45.6%, 39.1% and 26.1%), respectively. Analysis of DRB1 frequencies between patients and control revealed that DRB1*15 is significantly reduced among patients when compared with the control group (p < 0.01). Patients possessing the allele DRB1*03 had significantly reduced platelet count (p = 0.03), and this allele was presented to a greater extent in patients with minimal grade of inflammation. Patients with DRB1*04 had significantly low serum albumin (p = 0.04) and patients with DRB1*13 had significantly high serum aspartate aminotransferase (AST) levels (p = 0.05).ConclusionIn Egyptian HCV-infected children, special HLA patterns were found; HLA DRB1*03 was present in nearly half of the patients, while the frequency of HLA DRB1*15 was significantly reduced among the cases in comparison to the control subjects.     

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.     

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.