The Combined Use of Dickkopf-1 and Soluble Axl Improves Hepatocellular Carcinoma Diagnostic Efficacy in Hepatitis C Patients.

BACKGROUND: Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble Axl (sAxl) and their combined for early differentiating of HCC from premalignant benign liver diseases. METHODS: A total of 210 chronic hepatitis C (CHC) patients (55 fibrotic, 45 cirrhotic and 110 HCC) were enrolled. Both DKK1 and sAxl were tested using ELISA for all participants. RESULTS: HCC patients were accompanied by a significant increase (P<0.05) in DKK1 (5.38±2.05 ng/mL) and sAxl (178.02±49.39 ng/mL) compared to patients with fibrosis (2.16±0.6, 97.63±19.71 ng/mL, respectively) and cirrhosis (2.62±0.8, 121.84±34.66 ng/mL, respectively). Both DKK1 (AUC=0.852) and sAxl (AUC=0.882) had a good diagnostic accuracy in separating HCC from all non-HCC patients. Multiplying DKK1 with sAXL yielded values that significantly (P=0.0001) increased in patients who developed HCC (674.3 (434.2-1413.9)) versus fibrotic (204.9 (161.7-262)) and cirrhotic (254.4 (205.4-343.7)) patients. This model improves HCC diagnostic performances [AUC=0.921; sensitivity 90.9%, specificity 87%, PPV 88.5%, NPV 89.7% and efficiency 89.1%]. Elevated DKK1×sAxl values were associated with aggressive tumor features including multiple nodules, large size, Child-Pugh and BCLC late stages. CONCLUSIONS: combined use of DKK1×sAxl is simple and feasible HCC diagnostic model that could enhance HCC diagnostic accuracy and could replace AFP in follow up of patients with premalignant diseases.

Genetic and biochemical studies of hepatic carcinoma in the Egyptian population.

BACKGROUND: Hepatocellular carcinoma (HCC), a deadly malignancy of the liver, is considered the third leading reason behind cancer deaths. It is more frequent in men than in women of ages above 50. Liver disease, leading to liver cirrhosis (LC), is mostly caused by alcoholism abuse, reaction diseases of the liver, or viral hepatitis B or C infection. Interleukin-6 (IL-6) is considered an effective pro-inflammatory cytokine, which plays a crucial role in the host defense mechanism. Its level is higher in HCC patients than in LC cases, indicating that tumor cells increase the production of cytokines. The X-ray repair cross-complementing group 1 (XRCC1) gene is a major DNA repair gene. It acts as a scaffold of various activities that are concerned in the repairing method by interacting with components of base excision repair. This study aims to measure the serum concentrations of IL6 and C-reactive protein (CRP) and investigate whether XRCC1 Arg194Trp and Arg399Gln polymorphisms are related to HCC disease. MATERIALS AND METHODS: Whole-blood DNA was extracted from 123 HCC patients and 123 healthy volunteers. Tetra-primer amplification refractory mutation system was performed in the detection of XRCC1 Arg399Gln and Arg194Trp polymorphisms. RESULTS: Serum concentration levels of IL-6 and CRP are significantly higher in patients with HCC than in control subjects. The allelic and genotype frequency distributions of XRCC1 (Arg399Gln and Arg194Trp) are significantly increased in HCC cases compared to healthy volunteers. CONCLUSION: Arg/Gln, Arg/Trp, Gln/Gln, and Trp/Trp genotypes are associated with higher risk HCC than the Arg/Arg genotype.

Association of interferon gamma gene polymorphism and susceptibility to hepatitis C virus infection in Egyptian patients: A multicenter, family-based study.

BACKGROUND AND AIM: Polymorphisms in some genes may influence the persistence of hepatitis C virus (HCV) infection, clinical outcome, HCV replication, and liver damage. This study was conducted to investigate the role of the interferon gamma (IFN-γ) gene at (+874 T/A, -764 G/C, -179 C/A) single-nucleotide polymorphisms (SNPs) and its receptor (IFN-γR2) at (rs 2786067 A/C) SNP in the susceptibility of Egyptian families to HCV infection with high-resolution techniques. METHODS: In total, 517 Egyptian families, with 2246 subjects, were recruited to this study from the Upper and Lower Egypt governorates and were classified into three groups: 1034 patients with chronic hepatitis C virus, 108 subjects with spontaneous virus clearance (SVC), and 1104 subjects as a healthy control group. All subjects were genotyped for (+874 T/A, rs2430561, -764 G/C, rs2069707, -179 C/A, rs2069709, and rs 27860067, A/C) SNPs of the IFN-γ gene using the allelic discrimination real-time polymerase chain reaction technique and were confirmed using sequence-based typing. RESULTS: The carriage of T allele of (+874) IFN-γ is a risky allele and was significantly higher in chronic hepatitis C more than other two groups (odds ratio [OR]: 2.6646, P < 0.0002). On the other hand, the C allele of (-764, rs2069707) is a protective allele and was higher in SVC than the other two groups (OR: 0.2709, P < 0.0001). However, both (-179 C/A, rs 2069709) and (rs 27860067, A/C) SNPs are not polymorphic enough to be studied in the Egyptian population. CONCLUSIONS: HCV infection is associated with the T allele of (+874 rs2430561), while SVC of HCV is associated with the C allele of (-764, rs2069707) of the IFN-γ gene.

Diagnostic value of fibronectin discriminant score for predicting liver fibrosis stages in chronic hepatitis C virus patients.

BACKGROUND: Several noninvasive predictive models were developed to substitute liver biopsy for fibrosis assessment. AIM: To evaluate the diagnostic value of fibronectin which reflect extracellular matrix metabolism and standard liver functions tests which reflect alterations in hepatic functions. MATERIAL AND METHODS: Chronic hepatitis C (CHC) patients (n = 145) were evaluated using ROC curves and stepwise multivariate discriminant analysis (MDA) and was validated in 180 additional patients. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, albumin, complete blood count were estimated. Fibronectin concentration was determined using monoclonal antibody and ELISA. RESULTS: A novel index named fibronectin discriminant score (FDS) based on fibronectin, APRI and albumin was developed. FDS produced areas under ROC curves (AUC) of 0.91 for significant fibrosis and 0.81 for advanced fibrosis. The FDS correctly classified 79% of the significant liver fibrosis patients (F2-F4) with 87% sensitivity and 75% specificity. The relative risk [odds ratio (OR)] of having significant liver fibrosis using the cut-off values determined by ROC curve analyses were 6.1 for fibronectin, 4.9 for APRI, and 4.2 for albumin. FDS predicted liver fibrosis with an OR of 16.8 for significant fibrosis and 8.6 for advanced fibrosis. The FDS had similar AUC and OR in the validation group to the estimation group without statistically significant difference. CONCLUSION: FDS predicted liver fibrosis with high degree of accuracy, potentially decreasing the number of liver biopsy required.

Women's perception and experience of menopause: a community-based study in Alexandria, Egypt.

To determine symptoms, perceptions and practices after natural menopause by women aged 50-59 years, we conducted a cross-sectional study of 450 women from Alexandria. The most frequently recalled symptoms were tiredness (96.0%), headache (95.1%), hot flushes (90.7%), skin wrinkles (90.7%) and decreased sexual desire (89.1%). About 91% of women had never heard about hormone replacement therapy; 42.7% would expose their body to the sun; 12.4% were moderately active the year before menopause. Multiple regression analysis indicated that women's knowledge about menopause was related to marital status, education and employment status; practices were related to pattern of menopause, age of menopause and income.

Women's perception and experience of menopause: a community-based study in Alexandria, Egypt

To determine symptoms, perceptions and practices after natural menopause by women aged 50-59 years, we conducted a cross-sectional study of 450 women from Alexandria. The most frequently recalled symptoms were tiredness [96.0%], headache [95.1%], hot flushes [90.7%], skin wrinkles [90.7%] and decreased sexual desire [89.1%]. About 91% of women had never heard about hormone replacement therapy; 42.7% would expose their body to the sun; 12.4% were moderately active the year before menopause. Multiple regression analysis indicated that women's knowledge about menopause was related to marital status, education and employment status; practices were related to pattern of menopause, age of menopause and income

Hepatitis C virus infection in a community in the Nile Delta: risk factors for seropositivity.

The purpose of this study was to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti-HCV). One half of the village households were systematically selected, tested for anti-HCV, and interviewed: 973 of 3,999 (24.3%) subjects were anti-HCV-positive (reflecting prior HCV infection but not necessarily current liver disease), with nearly equal prevalence among males and females. Anti-HCV prevalence increased sharply with age among both males and females, from 9.3% in those 20 years of age and younger to >50% in those older than 35, suggesting a cohort effect with reduced transmission in recent years. Multivariate regression was used to estimate independent effects of risk factors on seropositivity. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age (P <.001); male gender (odds ratio [OR] = 2.5, 95% CI = 1.3-4.7); marriage (OR = 4.1, 2.4-6.9); anti-schistosomiasis injection treatment (OR = 2.0, 1.3-2.9); blood transfusion (OR = 1.8, 1.1-2.9), invasive medical procedure (surgery, catheterization, endoscopy, and/or dialysis) (OR = 1.5, 1.1-1.9); receipt of injections from "informal" health care provider (OR = 1.3, 1.0-1.6); and cesarean section or abortion (OR = 1.4, 1.0-1.9). Exposures not significantly related to anti-HCV positivity in adults included: history of, or active infection with, Schistosoma mansoni, sutures or abscess drainage, goza smoking in a group, and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti-HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti-HCV (OR = 1.7, 1.0-3.0). Prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated.

Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence.

This report describes a cross-sectional survey of the prevalence of antibodies to hepatitis C virus (anti-HCV) in a rural Egyptian community in the Nile Delta. One half of the village households were systematically selected and examined by questionnaire and testing sera for anti-HCV and HCV RNA. Blood samples were obtained from 3, 888 (75.4%) of 5,156 residents >/=5 years of age; an additional 111 samples were obtained from children younger than 5 years. Overall, 973 (24.3%) of 3,999 residents were anti-HCV-positive, and the age- and gender-adjusted seroprevalence was 23.7%. Anti-HCV prevalence increased sharply with age, from 9.3% in those 20 years of age and younger to >50% in those older than 35 years. Currently or previously married individuals were more likely to be seropositive than those never married, controlling for age (Mantel-Haenszel risk ratio = 1.8; 95% CI: 1.3, 2.6). Of the 905 anti-HCV-positive samples tested, 65% were also positive for HCV RNA. Active schistosomal infection was not associated with anti-HCV status; however, history of antischistosomal injection therapy (reported by 19% of anti-HCV positives) was a risk for anti-HCV (age-adjusted risk ratio = 1.3; 95% CI: 1.2, 1.5). This study, the largest community-based survey to date, supports earlier reports of high levels of anti-HCV among adults in rural areas of Egypt, although many of those who are seropositive will not have active liver disease. The large reservoir of HCV infection in the community provides an opportunity to investigate risk factors for transmission, the natural history of infection and effectiveness of preventive methodologies, and raises concern about the prospect of an increasing incidence of chronic liver disease in the coming decades.

Quality control for parasitologic data.

Accuracy of data is of paramount concern for all research. The task of providing objective assurances of accuracy of parasitologic data for a large, multi-center epidemiologic research project in Egypt (Epidemiology 1, 2, 3 [EPI 1, 2, 3]) presented a unique set of challenges undertaken jointly by the Ministry of Health's Qalyub Center for Field and Applied Research with technical assistance from Tulane University (New Orleans, LA). The EPI 1, 2, 3 project was part of large bilateral research program, the Schistosomiasis Research Project, undertaken jointly by the governments of Egypt and the United States. This paper describes the nature of the quality control system developed to accomplish this task, presents results and discusses the findings.

The epidemiology of schistosomiasis in Egypt: Qalyubia Governorate.

The primary objectives of this study, carried out in Qalyubia Governorate in Egypt (south-central Nile Delta), were to continue tracking historical trends of infection prevalence of Schistosoma mansoni and S. haematobium, determine whether satellites (ezbas) of mother villages differed significantly with respect to schistosomiasis transmission, and to asses schistosomiasis-induced morbidity on a population basis using ultrasonography. Our study revealed that S. haematobium has virtually disappeared from Qalyubia governorate, and that S. mansoni prevalence continues to decline slowly (17% in 1991 compared with 19% in 1990). The prevalence of intestinal schistosomiasis was actually higher in the mother villages than in the ezbas of the same villages, indicating that prevalence based on surveys of villages alone did not (at least for Qalyubia) cause underestimates of true prevalence. (A mother village is the large village in an area that includes hamlets or ezbas. In many areas, the infection rate in ezbas is significantly higher than in the larger central village.) Ultrasonographic studies revealed that less than 3% of the population had stage 2 or stage 3 periportal fibrosis, commonly associated with chronic schistosomiasis mansoni. This low level of morbidity was consistent with earlier data from Qalyubia, which also showed a low level of S. mansoni-induced morbidity in this governorate.

Prevalence of antibodies to hepatitis E in two rural Egyptian communities.

A population-based serosurvey in two rural Egyptian communities was used to assess age-specific prevalence of antibody to hepatitis E virus (anti-HEV). One community is in the Nile Delta (11,182 inhabitants; 3,997 participants) and the other in Upper Egypt (10,970 inhabitants; 6,029 participants). Samples were tested for anti-HEV with a commercial enzyme-linked immunoassay (ELISA) based on antigens derived from open reading frame (ORF)2 and ORF3. Although there was a clear difference in sensitivity among the lots of the commercial test used, it was still possible to determine the seroprevalence. The seroprevalence of anti-HEV exceeded 60% in the first decade of life, peaked at 76% in the second decade and remained above 60% until the eighth decade. Prevalence of this magnitude is among the highest reported in the world, with an age-specific pattern more similar to hyperendemic hepatitis A virus transmission than generally described. Lot-to-lot variation in the sensitivity of the commercial ELISA kit highlights a problem when comparing seroepidemiologic studies of different populations.

Is vernix caseosa a protective material to the newborn? A biochemical approach.

Twenty random samples of vernix caseosa were collected from immediately born neonates, in Jamahiriya Hospital, Benghazi. Biochemical studies of these samples revealed presence of lipids (62.5%), proteins (36%) and carbohydrate (1.5%). Also we could observe inhibition of staph. aureus and klebsiella growth on nutrient agar by this vernix. This observation could be explained either by its higher asparagine content or by its elevated lipid component. In addition tripalmitin was found to be the major lipid constituent, responsible for its hydrophobic property. So we recommend leaving this vernix layer on newborn skin until spontaneous drying.

Education and the professionals. Some aspects of innovation in medical education adopted by Ahfad University for Women.

PIP: This article describes the establishment in 1990 of a School of Medicine at Ahfad University for Women in Sudan. The school was premised on the view that women doctors would have a better opportunity to affect and improve women's health than men doctors. The curriculum is innovative and relies on a community orientation and a problem-solving approach. Medicine and health are taught in a holistic way. The new approach is rooted in the Alma Ata Declaration in 1978 of Health for All by the year 2000. The new method of delivery of medical care in the School of Medicine is based on the promotion of health through health education, prevention of disease, proper nutrition, provision of a safe water supply, attention to maternal/child health and family planning, and attention to the treatment of endemic diseases. In order to teach primary health care, medical schools must change their practices. Delivery of health care will have to be changed. New curriculum approaches emphasize learning objectives in each of the teaching modules and small group teaching. Integrated learning means the separate disciplines of medicine are taught as a whole multidisciplinary unit. Case management learning has the potential for increasing motivation and the ability to discover the knowledge needed to solve the problem. McMaster University relies on a problem-oriented approach to medical education that prepares the student for coping with changes in medical knowledge in the future. The challenge for educators is to create an efficient and comprehensive curriculum that will prepare a doctor for lifelong learning. Health settings have also changed to deemphasize sophisticated hospital settings in favor of community-based health centers. Ahfad University is the only one of its kind in Sudan. Medical education includes 6 years of schooling divided into 3 phases.^ieng

Knowledge and practices of pregnant women in relation to the intake of drugs during pregnancy.

The present study was done to assess Knowledge and practices of expectant women regarding drug intake during pregnancy. To achieve this aim, a simple random sample of 400 pregnant women during their last trimester of pregnancy were selected. A specially designed interview schedule was developed and used to collect the necessary data about the study subjects. The interview schedule consisted of four main parts to cover the following: 1. General characteristics of the sample. 2. Obstetrical characteristics of the sample 3. Knowledge about drug intake during pregnancy. 4. Practices of the study subjects in relation to drug intake during pregnancy. 5. Factors affecting their knowledge regarding drug intake during pregnancy. The main findings of the study were: 1. In general, the study sample lacked the essential knowledge regarding drug intake during pregnancy especially in relation to the risk time for taking drugs in which nearly one-fifth of the sample (19.5%) did not know that it is risky to take drugs during pregnancy without doctor's order. 2. Regarding the practices of the study subjects in relation to drug intake during pregnancy, it was observed that the majority of the sample (86%) took drugs without prescription such as vitamins and general tonics, antacids, analgesics, anti-emetics, sedatives and antibiotics to treat their minor or major complaints during pregnancy. 3. In this study, it was also found that certain factors seemed to affect women's knowledge regarding drug intake during pregnancy. It was more obvious to observe that nearly two-thirds (60.8%) of women whose age was less than 30 years were more likely to have inadequate and poor knowledge in this respect. It was observed that the majority (81.9%) of illiterate women were more likely to have inadequate and poor knowledge about drug intake during pregnancy. It was also found that nearly three-quarters (72.3%) of housewives were more likely to have poor and inadequate knowledge. It was also noticed that the majority (81.5%) of the primigravidae women were more likely to have poor and inadequate knowledge. It was also noted that the majority of women (87.1%) who had previous abortions were more likely to have poor and inadequate knowledge.

PIP: In Egypt, 400 randomly selected pregnant women attending prenatal clinics affiliated with El-Shatby Maternity Hospital, Dar El-Welada Hospital, Gamal Abdel Nasser Hospital, Boharram Bay Maternal and Child Health Center, and Bacous Maternal and Child Health Center were interviewed to determine their knowledge of and practices related to drug intake during pregnancy. 47.7% had adequate knowledge (i.e., 75% correct answers) of drug use during pregnancy. Only 14% did not use any drugs during pregnancy. The remaining 86% used drugs without a prescription. The most common drugs used were vitamins and tonics (78.8%), antacids (66.5%), analgesics (41.8%), and antiemetics (35.5%). The leading reasons for drug use included general weakness (78.8%), heart burn and indigestion (66.5%), headaches (41.8%), vomiting (35.5%), and cough and insomnia (27.5%). Factors associated with poor knowledge of drug use during pregnancy were: younger than 30, illiteracy, being a housewife, primigravidity, and history of abortion (p 0.05 for all factors). These findings indicate a need to inform pregnant women about the dangers of drug use during pregnancy, especially during the first 12 weeks of pregnancy. Nurses should play a key role in communicating these risks.

A study of a progestogen only oral contraceptive for lactating women in Khartoum, Sudan.

PIP: The acceptability and effectiveness of a progestogen-only oral contraceptive (OC), Ovrette, during lactation were investigated in 200 women recruited from a teaching hospital in Khartoum, Sudan. Ovrette contained 0.075 mg of norgestrel. 69 women (34.5%) had used OCs at some point prior to the index pregnancy. Serious complications (e.g., severe headache, chest pain, leg pain, abdominal pain, blurred vision) were reported by 8 respondents during the 12-month study period. Less serious side effects included dysmenorrhea (49 women), nausea (28 women), dizziness (38 women), vaginal discharge (86 women), headaches (78 women), and breast discomfort (21 women). Overall, 143 women (71.5%) experienced at least 1 side effect. Of the 21 women (10.5%) who discontinued Ovrette use before 12 months, 9 were motivated by menstrual problems and other side effects. The 12-month continuation rate was 89.1%. There were 2 pregnancies, only 1 of which represented method failure. These findings are consistent with previous studies indicating that use of progestin contraceptive agents is associated with more menstrual disturbances and pregnancies than combined OCs. Use of combined OCs is contraindicated during lactation, however.^ieng

Laparoscopic adhesiolysis for infertile patients with pelvic adhesive disease.

Thirty patients with secondary infertility were subjected to laparoscopic adhesiolysis during the period January 1986 to February 1987 at Al-Azhar Endoscopy and Microsurgery Unit. Second look laparoscopy (SLL) was performed after a period of 9-12 months. At laparoscopy, pelvic adhesive disease was staged according to the severity of the disease and compared with the finding at SLL. Five patients defaulted, three patients (12%) became pregnant and 22 patients underwent SLL. Ten patients (45.5%) showed no recurrence of adhesions. This study suggests that laparoscopy has a role in adhesiolysis of mild and moderate adhesions and SLL provides further opportunity to relyse reformed adhesions in some cases.

Further studies on the effect of niridazole on urinary and biliary excretion of copper.

Administration of niridazole to rats poisoned with copper caused a significant increase in both the urinary and biliary excretion of the metal. Although the urinary excretion of iron was increased by the drug, iron excretion was significantly decreased during the drug-induced excretion of copper after copper poisoning. Formation of a copper-niridazole chelate or chelates before excretion in the bile or urine may explain these findings. Polarity and molecular weights of the metal-drug chelates formed in vivo may be the directing forces not only in the selection of the metal for chelation, but also for its urinary or biliary excretion. The laboratory preparation of two copper-niridazole complexes lends support to these conclusions.

On the effects of ambilhar on mobilisation and biliary excretion of mercury.

The effect of administration of ambilhar to rats poisoned with mercury for two weeks were investigated. The results showed that administration of ambilhar to rats dosed with mercuric chloride, resulted in a significant increase in the faecal excretion of mercury. At the same time a significant decrease in the urinary output of the metal was found. Chelation of ambilhar with mercury to form a polar complex with a higher molecular weight could explain its biliary rather than its urinary excretion. The spectral studies of ambilhar and its two mercury complexes prepared in vitro support the possibility that stimulation of mercury excretion in bile results from the complexation of mercury by ambilhar in vivo.

Role of the thiazolyl sulphur of ambilhar as an electron donor in metal chelation.

Administration of ambilhar or its N-acetyl derivative to rabbits resulted in a significant increase in urinary iron excretion, due to chelation. Substitution of the sulphur of thiazole by nitrogen abolished its metal chelating power. In vitro three different iron chelates were obtained, containing one or two iron atoms per mole of drug. However, in vivo studies revealed the presence of an ambilhar iron complex in which 6 molecules of the drug were chelated with one iron atom. Reduction is an important factor in the process of metal chelation by the thiazole sulphur of the drug.