Genetic polymorphisms of interleukin 6 and interleukin 10 in Egyptian patients with systemic lupus eythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Cytokine gene polymorphisms play an important role in SLE. Thus, this study aimed to investigate the associations between interleukin 6 (IL-6) and interleukin 10 (IL-10) promoter single-nucleotide polymorphisms (SNPs) and their susceptibility to SLE and the implications for plasma levels. We genotyped IL-6-174G/C (rs1800795) using mutagenically separated polymerase chain reaction (MS-PCR) and IL-10-1082G/A (rs1800896) and -819C/T (rs1800871) using sequence specific primer polymerase chain reaction (SSP-PCR) in 100 Egyptian patients and 119 controls. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). There was significant increase in the frequency of IL-6 (-174) GG genotype (P < 0.05) and G allele (P < 0.01) compared to controls. A significant increase in the distribution of IL-10 (-1082G/A) GG (P < 0.05) and AA (P < 0.05) genotypes and a significant reduction in the frequency of GA genotype (P < 0.05) was found in SLE patients. The mean serum concentration of IL-6 (P < 0.001) and IL-10 (P < 0.001) was significantly elevated in SLE patients compared to healthy controls. There was no significant association of the most common clinical findings and IL-6 and IL-10 gene polymorphisms in SLE patients. In conclusion, our preliminary study indicated that both GG genotype and G allele of IL-6 (-174G/C) could be considered as risk factors for SLE. In addition, the polymorphisms at IL-10 (-1082 G/G and AA) may play a role in SLE susceptibility in Egyptian patients. Larger prospective studies are needed to confirm our findings.

(18)FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response.

To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070). In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8), respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3 (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7) to 31.9 (+/-52.7) cm(3) (P=0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer.

Vitamin C enhances chemosensitization of esophageal cancer cells in vitro.

Chemotherapy is increasingly utilised in multimodal protocols to try and improve outcomes. Cisplatin and 5-fluorouracil (5-Fu) are the mainstay of chemotherapeutic regimens, and an understanding of sensitivity and resistance of esophageal cancer to these agents is of considerable clinical importance. Antioxidants may modulate the response to chemotherapy, and in this study we examined the effect of vitamin C on 5-Fu and cisplatin cytotoxicity and related pathways in the esophageal cancer cell lines OE33 and SKGT-4. The antiproliferative effect of antitumor agents was measured by the MTT assay, and the transcription factors NF-kappaB and AP-1 pathways were assessed by electrophoretic mobility gel shift assay. 5-Fu and cisplatin demonstrated marked morphological changes and decreased cell proliferation. A combination of vitamin C with 5-Fu or cisplatin exerted a significantly enhanced cytotoxic effect compared to both drugs individually. Treatment of esophageal cancer cells with 5-Fu and cisplatin induced NF-kappaB and AP-1 activation. Pretreatment with vitamin C inhibited 5-Fu or cisplatin induced NF-kappaB nuclear translocation and DNA binding activity, but vitamin C had no effect on IkappaB-alpha protein levels. Vitamin C also inhibited 5-Fu- and cisplatin-induced AP-1 activation. Our data demonstrate that vitamin C enhances the antitumor activity of 5-Fu and cisplatin, in part by inhibiting translocation of NF-kappaB and AP-1, and sensitizes cancer cells to drug-induced cell death. The data suggest that vitamin C supplementation may improve the efficacy of chemotherapy for esophageal cancer.

Surface properties and microporosity of polyhydroxybutyrate under scanning electron microscopy.

This study was designed to investigate the surface properties especially surface porosity of polyhydroxybutyrate (PHB) using scanning electron microscopy. PHB granules were sprinkled on the double-sided sticky tape attached on a SEM aluminium stub and sputtered with gold(10nm thickness) in a Polaron SC515 Coater, following which the samples were placed into the SEM specimen chamber for viewing and recording. Scanning electron micrographs with different magnification of PHB surface revealed multiple pores with different sizes.

Biocompatibility test of polyhydroxybutyrate on human cell line.

The human fibroblast MRC-5 cells incubated with PHB granules (TM) added at a final concentration of 4 mg/ml showed a time-course pattern of survival. The percentages of dead cells obtained were at the rate of 3.8% after 7 days, respectively. When the MRC-5 cells grown in different material, using the test concentration of 4 mg/ml PCM, they were found to show a similar time-course increasing pattern of death as that obtained with PHB. However, the death was noted in the cells incubated for 7 days, the death rates obtained was 40.54% respectively.

Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation.

Esophageal adenocarcinoma arising on a background of Barrett's esophagus is increasing in incidence. A molecular understanding of both the progression of Barrett's esophagus and the factors determining the response of adenocarcinoma to neoadjuvant therapy is required, and this study focused on the role of proteins regulated by the bcl-2 family of genes, which are important regulators of programmed cell death (apoptosis). In total, 48 patients (36 men, 12 women) with Barrett's adenocarcinoma were studied. All patients received preoperative chemoradiotherapy followed by surgery. Bcl-2, bax and bcl-x protein expression were detected by standard avidin-biotin peroxidase method. Bcl-2, bax and bcl-x expression were detected in 84%, 80%, and 76%, respectively, of normal squamous mucosa. An increasing degree of dysplasia in Barrett's mucosa both before and after chemoradiotherapy was significantly associated with a reduction of bcl-2 expression (P = 0.03 and 0.009, respectively). Bcl-2 expression was significantly associated with tumor differentiation (P = 0.03) and a trend towards earlier T stage (P = 0.08), but not with nodal status. Pre-therapeutic bcl-2, bax and bcl-x protein expression (27%, 75%, and 87.5%, respectively) were not associated with tumor response or resistance to therapy. Bcl-2-positive patients had a significantly improved survival compared with bcl-2-negative tumors. A significant reduction of bcl-2 expression is associated with the progression of Barrett's mucosa to adenocarcinoma. Bcl-2 expression was associated with improved survival. Preoperative chemoradiotherapy induces expression of bax and bcl-x protein. The pretreatment expression of bcl-2 and related proteins did not predict response or resistance to neoadjuvant chemoradiotherapy, suggesting that regulators of apoptosis alone do not determine the response of Barrett's adenocarcinoma to neoadjuvant therapy.

Planning cancer prevention strategies based on epidemiologic characteristics: an Egyptian example.

BACKGROUND AND METHODS: We describe the epidemiology, cancer prevention strategies, and educational messages to be learned from four characteristic cancers in Egypt: urinary bladder, liver, lung, and early-onset colorectal cancers. RESULTS: For bladder cancer, effective and convenient treatment of schistosomiasis, using social marketing and mass media in public and medical education has contributed dramatically to primary prevention of bladder cancer in Egypt. For liver cancer, educating hospital administrators to remove structural barriers to good practice may help the control of hepatitis transmission and related liver cancer. For lung cancer, the 50-year American experience for controlling tobacco smoking, beginning with physicians, could be very effective in Egypt and other countries with increasing smoking rates in the young so as to avert the expected epidemics of lung cancer. For colorectal cancer, more attention to physician and public education about the importance of interviewing colorectal cancer patients about a family history of cancer and the screening of at-risk families could be very effective in early detection of colorectal cancer. CONCLUSION: Countries with similar cancer epidemiology experience should make use of successful cancer prevention and education strategies that could be translated from the Egyptian experience.

Studies on heterologous resistance between schistosomiasis mansoni and fascioliasis.

S. mansoni and F. gigantica GSTs were purified from adult worm homogenates by affinity chromatography. Assessment of both SmGST and FgGST as candidate vaccines was done by comparing vaccinated mice groups challenged with S. mansoni cercariae with control ones in terms of worm load, tissue egg number viability and maturity, and the survival rate of the animals. SmGST 5 ug vaccination generally appeared to confer best protection against homologous challenge followed by FgGST 5 ug while vaccination with both antigens using low doses (2 ug) appeared to have no specific role in decreasing worm load but had significant effects on egg production.

Postoperative hepatic catabolic stress response in patients with cirrhosis and chronic hepatitis.

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.

Cancer mortality in Menofeia, Egypt: comparison with US mortality rates.

OBJECTIVES: In developing countries where cancer registries are unavailable, mortality statistics from death certification may be a practical source of cancer statistics. We aimed at describing the cancer mortality in Egypt and comparing it to that in the US. METHODS: We used the mandatory and routinely available mortality records of Menofeia province in the Nile Delta region of Egypt, which is typical of the rest of Egypt. We determined cancer mortality rates, and compared them with the Surveillance, Epidemiology, and End Results (SEER) mortality rates of the US. RESULTS: Bladder and liver cancers were the two most common causes of cancer mortality in Menofeia, Egypt. When adjusted for age the Egyptian rates were much higher than the US rates (9.5/100,000 and 8.4/100,000 for bladder and liver cancer, respectively, compared with 2.3/100,000 and 2.5/100,000 for the same cancers from SEER data). We also observed that age-specific rates for early-onset colorectal cancer under age 40 and premenopausal breast cancer were higher in Egypt than in the US. CONCLUSION: This study confirms our earlier observations about the higher proportion of early-onset colorectal cancer in Egypt, and opens the door for future studies to investigate familial clustering of cancer in Egypt.

Reduced expression of mismatch repair genes in colorectal cancer patients in Egypt.

An Egyptian hospital-based pilot case-control study was conducted to investigate the relationship between the expression level of mismatch repair (MMR) genes and the risk of colorectal cancer. The relative expression of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in patients than controls, but only the difference in hPMS2 expression was statistically significant (p<0. 01). Although 50% of the cases had chemotherapy or radiotherapy within the last six months before the blood was drawn, their gene expression was not statistically different from those who had not undergone such therapies. After adjustment for age and sex, the odds ratios (OR) calculated from a logistical regression model, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04 to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be unique in the Egyptian population. Further studies with newly diagnosed patients before they begin therapy will provide more convincing data about the role of MMR gene expression in the etiology of colorectal cancers in Egypt.

Human chronic fascioliasis: hepatitis B and C among infected cases.

Sera from one hundred and fifty three chronic Fasciola cases were screened for the presence of HB markers (HBsAg, anti HBc and anti HBs) and anti HCV using ELISA technique. Quantitative stool examination and estimation of liver enzymes (AST-ALT-bilirubin) levels of the study population were performed. HBsAg was present in 5 (3.3%), anti HBs in 13 (8.5%), HBexposed (HBex) in 44 (28.8%) and anti HCV in 13 (8.5%) of examined sera. HBV and HCV markers were significantly higher among older age groups. Concerning familial aggregation of hepatitis markers, 7 (15.9%) of the 44 HBex cases had two individuals per family who had evidence of exposure to HBV. No significant change in Fasciola GMEC and liver function tests have been noticed.

Knowledge of, attitudes toward, and barriers to cancer control and screening among primary care physicians in Egypt: the need for postgraduate medical education.

METHODS: The authors surveyed 177 primary care physicians in Menofeia, in the Nile Delta area of Egypt, to test their knowledge of, attitudes toward, and perceived barriers to cancer control and screening. RESULTS: The physicians viewed cigarette smoking and radiation exposure as the most important cancer risk factors, followed by occupation, family history, and sun exposure. The majority of the physicians saw diet as contributing little or nothing to cancer risk. Most of the physicians lacked knowledge about early cancer detection and screening. Junior practitioners, in particular, reported a lack of information about liver cancer and hepatitis viruses despite the prevalence of these viruses in the country. Large proportions of mid-career and senior primary care physicians who had no postgraduate education cited lack of knowledge and not being familiar with an approach to cancer prevention as reasons for not performing screening activities. CONCLUSION: The importance of smoking, diet, and early detection of common cancer types should receive more attention in the undergraduate medical curriculum of Egypt. Health and medical education authorities in Egypt should authorize more postgraduate education opportunities for senior primary care physicians, aimed at increasing their knowledge of prevention and improving their attitudes toward primary cancer prevention and screening.

High prevalence of hepatitis C in Egyptian patients with chronic liver disease.

The highest prevalence rates of hepatitis C virus infection in the world have been recently reported among Egyptian blood donors and frequent recipients of transfusions and other blood products. This is the first report, however, demonstrating hepatitis C as the most frequent association with chronic liver disease in Egypt. Of 1023 patients referred to the Liver Institute in Menoufia governorate for evaluation of chronic liver disease, 752 (73.5%) had antibodies to hepatitis C compared with 168 (16.4%) with hepatitis B surface antigen. Hepatitis C antibody was more common in patients with active schistosomiasis and patients without hepatitis B surface antigenaemia. Of 100 patients having liver biopsies, histological findings consistent with chronic viral hepatitis or its complications were found in 89 and antibody to hepatitis C was present in 75 (84.3%) of these patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma. These data pointing to the importance of hepatitis C as a cause of chronic liver disease in Egypt emphasise the necessity of studies delineating its routes of transmission in this country.

Hepatitis C virus-polymerase chain reaction of routinely processed liver biopsies.

The aim of the study was to evaluate the specificity and sensitivity of detection of hepatitis C virus (HCV)-RNA in formalin-fixed paraffin-embedded (FFPE) liver biopsies by polymerase chain reaction (PCR). Routinely processed FFPE diagnostic needle liver biopsies as well as stored serum samples from 43 patients with liver disease were tested for HCV-RNA by reverse transcription-nested PCR using the same sets of primers and following strict anticontamination measures. Twenty-nine cases were positive and 14 were negative for serum HCV-RNA. Tissue HCV-RNA was detected in 17 out of the 29 serum HCV-RNA-positive cases but not in any of the 14 serum HCV-RNA-negative cases. Compared to serum-PCR, tissue-PCR was 100% specific, 58.6% sensitive, and 72% efficient. HCV-RNA was detected more frequently in biopsies stored for less than 1 year, than in those stored for more than 1 year (P = 0.046). In biopsies stored for up to 1 year detection of HCV-RNA by PCR was 81.8% sensitive and 90.9% efficient. Short (< 0.5 cm) liver biopsies were as sufficient for nucleic acid extraction and amplification as long (> 0.5 cm) ones. It is concluded that following strict anticontamination measures, HCV-RNA detection by PCR in routinely fixed, processed, and stored diagnostic liver biopsies provides a valuable adjunct to diagnosis of HCV infection. In this study, this option was free from contamination problems, even though routine batch histological processing schedules were used.

Mother-to-child transmission of hepatitis B virus in a semirural population in Egypt.

A follow-up study for one year was made on 35 babies born to HBsAg positive mothers in a semirural population in Egypt. Five of 21 babies (24%) showed HBsAg in the umbilical cord blood and remained positive throughout the observation period. At 3 months, eight of 37 babies (23%) were HBsAg + ve. At 6 months, 13 of 35 babies (37%) were HBsAg + ve and they were also still found positive at 12 months. None of 30 babies born to HBsAg-ve mothers developed antigenaemia throughout the observation period. Factors which significantly contributed to transmission were maternal educational level, family socio-economic standard, family residence, maternal e/anti-e status, and maternal schistosomal infestation. Factors which did not significantly affect transmission were maternal age, maternal parasitic non-schistosomal infestations, maternal transaminases level, order of the child in the family, and type of child feeding. Of particular note, four of five babies (80%) born to HBsAg + ve mothers who as well had schistosomiasis were HBsAg + ve throughout the observation period.

Rapid adaptation of pituitary responsiveness to TRH in the post-surgical state. The role of free T3.

In eight clinically and biochemically euthyroid patients undergoing routine major non-thyroidal surgery preoperative and daily postoperative serum concentrations of total and free thyroid hormones were measured. Thyrotrophin-releasing hormone (TRH) tests were performed preoperatively and on the first 3 postoperative days. There was a significant fall in mean serum total and free triiodothyronine (T3) concentrations on the postoperative days and mean reverse T3 concentrations rose reciprocally. There was no significant change in mean basal thyroid-stimulating hormone (TSH) values, but there was a significant increase in the mean TSH-response to TRH on the first postoperative day. The mean TSH response than declined sequentially until day 3 while mean free T3 concentrations remained significantly depressed. Mean serum free thyroxine(T4)concentrations remained normal during the study. Intrapituitary conversion of T4 to T3 or other down regulatory mechanisms could explain this rapid adaptation of the pituitary axis.

The accuracy and standardization of TBG kits.

Three kits for measurement of serum thyroxine-binding globulin (TBG) were compared with a reference radioimmunoassay in forty-three normal euthyroid subjects. The Corning Immophase kit gave similar results to those with the reference method with satisfactory precision and accuracy. The Behringwerke AG RIA-gnost kit gave results with adequate but lower correlation with the reference method (r = 0.80) than that of the Corning kit trial (r = 0.92). The mean value was significantly greater than the reference method mean, indicating that the Behringwerke kit was inaccurately standardized. The CEA-Sorin TBG kit (Eurotope services) gave results with a poor correlation against the reference method (r = 0.59). The mean value was also significantly greater than the reference mean indicating that this kit is both inaccurately standardized and less precise than the other two. It is stressed that TBG-kits need to be periodically standardized against reference methods in the absence of properly validated primary standards in all batches.

A method for the preparation of human thyroxine-binding globulin; its importance in the establishment of an accurate and specific radioimmunoassay.

Pure thyroxine-binding globulin (TBG) is required in radioimmunoassay to prepare monospecific antisera, [125I]TBG and as primary standard. Homogeneous TBG was prepared by a three-stage affinity chromatography procedure; it could not be dissociated into subunits and its molecular weight by SDS polyacrylamide gel electrophoresis was 59 000. The amino acid composition was in agreement with two earlier reports. The secondary structure determined by circular dichroism in the far U.V. showed it to contain 24% each of alpha-helix and beta-pleated sheet. Serum TBG was determined by a 24-h radioimmunoassay using polyethyleneglycol to separate bound and free TBG. Serum TBG (mg/l, mean +/- S.D.) was: normal men 15.3 +/- 2.11 (n = 34), normal women 18.4 +/- 2.72 (n = 32) (P less than 0.005), in women on oral oestrogens 24.0 +/- 5.0 (n = 23), in normal pregnancy 38.6 +/- 3.0 (n =37), in cord blood 21.7 +/- 3.5 (n = 25) (P less than 0.001) and in euthyroid subjects aged over 60 years 17.8 +/- 4.5 (P n.s.). In women with thyroid disease TBG was reduced in hyperthyroidism: 15.5 +/- 2.5 (n = 28) and elevated in hypothyroidism: 21.0 +/- 4.0 (n = 25). Wider use in TBG-assay of non-denatured TBG of proven composition and structure should decrease the scatter in reference ranges and improve its value as a routine thyroid function test as both a primary measurement and as the T4 : TBG ratio.