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Impact of CD34 subsets on engraftment kinetics in allogeneic peripheral blood stem cell transplantation.

Research Abstract
Our objective was to evaluate, probably for the first time, the impact of CD34 subsets on engraftment kinetics in allogeneic PBSC transplantation (PBSCT). PBSC graft components were analyzed in 62 cases for the absolute count/kg of total CD34+ and the following subsets: DR- and +, CD71+/-, CD38+/-, CD33+/- and CD61+/-. Time to ANC >0.5 and >1 x 10(9)/l and platelets >20 and >50 x 10(9)/l was reported. The median value for each parameter was used to discriminate rapid from slow engraftment. Four parameters showed significant predictive power of early neutrophil engraftment, namely CD34+ /DR- (P = 0.002), CD34+/38- (P = 0.02), CD34+/CD61- (P = 0.04) and total CD34+ cell dose (P = 0.04). Four parameters showed significant predictive power of early platelet engraftment, namely CD34+/CD61+ (P = 0.02), CD34+ /CD38- and total CD34+ cell dose (P = 0.04) and CD34+ /CD71- (P = 0.05). Comparing patients who received > to those who received the threshold dose(s), only CD34+ /CD38- lost its significance for neutrophil engraftment; and only CD34+ /CD61+ retained its significance for platelet engraftment (P = 0.03); furthermore, the former group required significantly fewer platelet transfusions (P = 0.018). We concluded that in allogeneic PBSCT, the best predictor of early neutrophil engraftment is the absolute CD34+ /DR- and for early platelet engraftment is the absolute CD34+ /CD61+ cell dose.
Research Authors
Kamel AM, El-Sharkawy N, Mahmoud HK, Khalaf MR, El Haddad A, Fahmy O, El Fattah RA, Sayed D.

Research Department
Research Journal
Bone Marrow Transplant.
Research Member
Research Pages
pp. 129 - 36
Research Rank
2
Research Vol
Vol. 35 - No. 2
Research Year
2005

Associations of pesticides, HCV, HBV, and hepatocellular carcinoma in Egypt.

Research Abstract
The rate of hepatocellular carcinoma (HCC) is increasing in Egypt where the major risk factors are chronic infections with hepatitis B and C viruses (HBV and HCV). A major segment of the population is employed in agriculture, raising the possibility that exposure to pesticides is an additional risk factor for HCC. The objective of this study is to investigate pesticides as environmental risk factors for HCC while taking into account viral risk factors. We conducted a case-control study of 236 subjects with confirmed HCC recruited from the National Cancer Institute, Cairo University, Egypt, and 236 controls matched on sex, age group and urban-rural status recruited from orthopedic department, Cairo University Hospital, Egypt. Patients who agreed to participate signed a consent form, answered a questionnaire and gave a blood sample for hepatitis virus testing. The manuals of the Ministry of Agriculture for approved use and type of pesticides since 1965 were linked to the questionnaire data for types of crops and pests that the subject had to combat, to attribute specific pesticides that were used by each subject. Subjects also reported duration of the exposure (years). Case-control comparisons in these data were stratified by sex, age group, and urban vs. rural residence. Data were analyzed using unconditional logistic regression models adjusting for age, HCV RNA, and current hepatitis B infection. Among rural males, the adjusted odds ratio (OR) for organophosphorus compounds was 2.7 (95% CI = 1.3-5.3) and for carbamates it was 2.9 (95% CI = 1.4-5.8). No statistically significant associations between HCC and pesticides were observed for urban males or for females. As expected, the strongest risk factors for HCC in this study were HCV RNA (OR = 16-17) and current HBV infection (OR = 27-28). This study therefore suggests that exposures to organophophorus and carbamate pesticides are additive risk factors to current HCV and HBV infection among rural males. Future investigation should address the possible hepatocarcinogenicity of pesticides using biomarkers of exposure and other techniques to better estimate dose-response relationships.
Research Authors
Ezzat S, Abdel-Hamid M, Eissa SA, Mokhtar N, Labib NA, El-Ghorory L, Mikhail NN, Abdel-Hamid A, Hifnawy T, Strickland GT, Loffredo CA.

Research Journal
Int J Hyg Environ Health.
Research Member
Nabiel Nazmi Hanna Mikhail
Research Pages
pp. 329 - 339
Research Rank
2
Research Vol
Vol. 208 - No. 5
Research Year
2005

Prevalence of and risk factors for hepatitis C in rural pregnant Egyptian women.

Research Abstract
Prevalence and risk factors for hepatitis C virus (HCV) infection were studied in 2,587 pregnant women from three rural Egyptian villages in the Nile Delta being admitted to a prospective cohort study of maternal-infant transmission; 408 (15.8%) had antibodies to HCV (anti-HCV) and 279 (10.8%) also had HCV-RNA. Fewer than 1% gave a history of jaundice or liver disease. Risk factors for anti-HCV included increasing age, low socioeconomic status and a history of blood transfusion or injection therapy for schistosomiasis. Sub-analyses after stratification of subjects by village revealed risks associated with specific venues for medical care, having a previous delivery attended by a traditional birth assistant (TBA), receiving medical care in a temporary clinic located in a mosque, overnight admission to a private doctor's clinic, and circumcision by a TBA or a 'health barber'. Our results suggest HCV causes very little detected illness in young adult Egyptian women and some sources of HCV transmission in rural Egypt in the past were associated with the provision of medical care and varied by location. Prevention should be focused on providing appropriate resources and health education should be given to formal and informal health care providers and should be sufficiently broad to adjust for local variations in exposures.
Research Authors
Stoszek SK, Abdel-Hamid M, Narooz S, El Daly M, Saleh DA, Mikhail N, Kassem E, Hawash Y, El Kafrawy S, Said A, El Batanony M, Shebl FM, Sayed M, Sharaf S, Fix AD, Strickland GT.

Research Journal
Trans R Soc Trop Med Hyg.
Research Member
Nabiel Nazmi Hanna Mikhail
Research Pages
pp. 102 - 107
Research Rank
1
Research Vol
Vol. 100 - No. 2
Research Year
2006

High prevalence of hepatitis E antibodies in pregnant Egyptian women.

Research Abstract
The epidemiology of hepatitis E virus (HEV), an enterically-transmitted cause of acute viral hepatitis (AVH), is not fully understood. During outbreaks on the Indian subcontinent and elsewhere, HEV causes severe AVH with mortality rates around 20% during pregnancy. In Egypt, where prevalence of HEV antibodies (anti-HEV) in rural communities is very high, severe HEV-caused AVH in pregnant women has not been reported. This study examined a cohort of 2,428 pregnant women in the Nile Delta to assess prevalence of, and risk factors for, anti-HEV and correlated these with history of liver disease. Anti-HEV prevalence was 84.3%. Several risk factors associated with anti-HEV included older age, many siblings, not using soap to wash produce and frequent contact with cats. History of jaundice and liver disease was rare and not increased in those having anti-HEV. Our results confirm Egypt's high HEV endemicity and show that almost all women of childbearing age in these communities had prior HEV exposures without a history of liver disease. Reasons for the lack of clinical hepatitis remain unclear but could be the result of early childhood HEV exposures, producing long-lasting immunity and/or modify subsequent responses to exposure. Alternatively, the predominant HEV strain(s) in Egypt are less virulent than those in South Asia.
Research Authors
Stoszek SK, Abdel-Hamid M, Saleh DA, El Kafrawy S, Narooz S, Hawash Y, Shebl FM, El Daly M, Said A, Kassem E, Mikhail N, Engle RE, Sayed M, Sharaf S, Fix AD, Emerson SU, Purcell RH, Strickland GT.
Research Journal
Trans R Soc Trop Med Hyg.
Research Member
Nabiel Nazmi Hanna Mikhail
Research Pages
pp. 95 -101
Research Rank
1
Research Vol
Vol. 100 - No. 2
Research Year
2006

Hepatitis E antibody seroconversion without disease in highly endemic rural Egyptian communities.

Research Abstract
Hepatitis E virus (HEV) is enterically transmitted and causes self-limiting acute viral hepatitis (AVH) primarily in less developed countries. A prospective cohort study to assess incidence of, and risk factors for, seroconversion to HEV (anti-HEV) was conducted in two Egyptian villages with a 67.7% anti-HEV prevalence. Nine hundred and nineteen villagers who were initially anti-HEV-negative were followed for 10.7 months. Thirty-four (3.7%) had strong anti-HEV serologic responses at follow-up giving an estimated anti-HEV incidence of 41.6/1,000 person-years. No significant associations were found between anti-HEV seroincidence and demographic and socioeconomic factors, source of water, household plumbing or sanitation, hand and vegetable washing, ownership of animals, jaundice and many other variables. None of the seroconverting subjects gave a history compatible with AVH during the interval. We hypothesize that both zoonotic and anthroponotic transmission of avirulent (possibly genotype-3) HEV is occurring extensively in these rural villages. An alternative explanation for the lack of morbidity among anti-HEV incident cases could be initial asymptomatic infections occur during early childhood with subsequent antibody titer boosting without illness upon re-exposure to the virus.
Research Authors
Stoszek SK, Engle RE, Abdel-Hamid M, Mikhail N, Abdel-Aziz F, Medhat A, Fix AD, Emerson SU, Purcell RH, Strickland GT
Research Journal
Trans R Soc Trop Med Hyg.
Research Member
Nabiel Nazmi Hanna Mikhail
Research Pages
pp. 89 - 94
Research Rank
1
Research Vol
Vol. 100 - No. 2
Research Year
2006

Active surveillance for acute viral hepatitis in rural villages in the Nile Delta.

Research Abstract
BACKGROUND: Acute viral hepatitis is less frequent in Egypt than serum antibody levels suggest. Because acute viral hepatitis has a wide clinical spectrum, we tested the hypothesis that many cases are undetected because of mild illness caused by initial, early-childhood exposure to hepatitis viruses. METHODS: During active case detection among 20,000 inhabitants of rural villages in Egypt, we screened 1715 symptomatic patients for serum alanine aminotransferase (ALT) levels. Viral hepatitis markers were tested in 47 subjects who had ALT levels that were least twice the normal level. RESULTS: Of the 47 individuals tested, 4 children aged 3-5 years had immunoglobulin M (IgM) antibodies to hepatitis A virus (anti-HAV IgM). One also had a possible false-positive result to a test for IgM antibodies to hepatitis E virus. None had serological evidence of acute hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. However, 33 of the remaining 43 had active HCV infection, having both antibodies to HCV (anti-HCV) and HCV RNA. Four others anti-HCV without HCV RNA, and 2 others had seroconversion to anti-HCV during follow-up. Two patients who were positive for hepatitis B surface antigen had chronic HBV infection. Only 3 with elevated ALT levels had no evidence of acute or chronic infections with known hepatitis viruses. Immunoglobulin G antibodies to hepatitis E virus was detected in 40 patients. CONCLUSION: Active surveillance covering approximately 50,000 person-years detected only 4 cases of acute HAV infection. Almost all persons with mild symptoms and elevated ALT levels had serological evidence of chronic viral hepatitis, most often associated with HCV. Many of these cases were probably "flare-ups" of HCV infection or incidental illness in patients with chronic HCV infection, but some could have been caused by difficult-to-confirm initial HCV infections. Although serological evidence for exposures was highly prevalent, hepatitis viruses seldom caused acute viral hepatitis in these communities.
Research Authors
Meky FA, Stoszek SK, Abdel-Hamid M, Selim S, Abdel-Wahab A, Mikhail N, El-Kafrawy S, El-Daly M, Abdel-Aziz F, Sharaf S, Mohamed MK, Engle RE, Emerson SU, Purcell RH, Fix AD, Strickland GT.

Research Journal
Clin Infect Dis.
Research Member
Nabiel Nazmi Hanna Mikhail
Research Pages
pp. 628 - 633
Research Rank
2
Research Vol
Vol. 1;42 - No. 5
Research Year
2006

Transmission of hepatitis C virus between parents and children.

Research Abstract
Egyptian children with infected parents are at high risk of infection with hepatitis C (HCV). Analysis of data collected during surveys of rural communities show children whose parents had antibodies to HCV (anti-HCV) were at higher risk for having anti-HCV than children whose parents did not. The association was greater with mothers than fathers and when the parent had HCV RNA. For instance, 87 (14%) of 612 children had anti-HCV whose mothers had HCV RNA compared with 28 (7%) of 401 whose mothers only had anti-HCV and 79 (2.6%) of 3,086 whose mothers were seronegative. These associations persisted after controlling for age, parenteral exposures, and serologic status of the other parent. Sequencing isolates from 13 families with parent(s) and children having HCV RNA showed 10 of 18 had genetically similar viruses. These findings suggest Egyptian children are at high risk of being infected with HCV by their parents and identification of the transmission routes would allow for preventive measures.
Research Authors
Mohamed MK, Magder LS, Abdel-Hamid M, El-Daly M, Mikhail NN, Abdel-Aziz F, Medhat A, Thiers V, Strickland GT.

Research Journal
Am J Trop Med Hyg.
Research Member
Nabiel Nazmi Hanna Mikhail
Research Pages
pp. 16 - 20
Research Rank
2
Research Vol
Vol. 75 - No. 1
Research Year
2006

Association between the HER2 expression and histological differentiation in Wilms tumor.

Research Abstract
Human epidermal growth factor receptors (HER) play a critical role in the branching morphogenesis of renal tubules. In the current study, we analyzed the expression of HER2 in Wilms tumor and assessed the role of this gene in the tumorgenesis of Wilms tumor. During the period from 1960 to 2005, 40 patients with Wilms tumor were treated in our department. Twenty-four of those patients (except those with clear cell sarcoma of the kidney and malignant rhabdoid tumor of the kidney) were collected and assessed. The histological component of each Wilms tumor was divided into three categories (epithelial, blastemal, and mesenchymal) and the extent of HER2 protein expression was analyzed immunohistochemically. The normal kidney tissue accompanied with 12 cases of Wilms tumor was also examined. In the normal kidney, HER2 showed a strong immunoreactivity in the cell membranes of the collecting tubules and in the endothelial cells. Of 24 cases, 15 cases showed an epithelial component, while 24 cases had a blastemal component and 21 cases had a mesenchymal component, respectively. Among the 15 specimens with epithelial cell differentiation, eight (53.3%) showed HER2 immunoreactive epithelial cells. HER2 immunoreactive blastemal cells were present in 11 (45.8%) of 24 specimens with blastemal cells. On the other hand, only 3 (14.3%) of 21 specimens containing mesenchymal cells showed HER2 immunoreactivity. These results suggest that the extent of HER2 expression is associated with epithelial differentiation in Wilms tumor. These histological findings may therefore help to explain the development of Wilms tumor from the standpoint of histological differentiation.
Research Authors
Salem M, Kinoshita Y, Tajiri T, Souzaki R, Tatsuta K, Higashi M, Izaki T, Kohashi K, Tsuneyoshi M, Taguchi T.

Research Department
Research Journal
Pediatr Surg Int.
Research Pages
pp. 891 - 896
Research Rank
1
Research Vol
Vol. 22 - No. 11
Research Year
2006

Glomerular expression and elevated serum Bcl-2 and Fas proteins in lupus nephritis: preliminary findings.

Research Abstract
Programmed cell death (apoptosis) is involved in glomerular injuries leading to glomerulonephritis. Bcl-2 and Fas are proteins that promote cell survival and death, respectively. This study tests the hypothesis that lupus nephritis is associated with alterations of Bcl-2 and Fas protein expression. Thirty-six patients with lupus nephritis and 10 controls (normal individuals) were included in this study. Bcl-2 and Fas positive cells were examined in kidney biopsies by immunohistochemistry. Bcl-2 and Fas serum levels were evaluated by enzyme-linked immunosorbent assay (ELISA). In the glomeruli of normal kidneys, Bcl-2 and Fas proteins were completely absent. In lupus nephritis patients, glomerular expression of Bcl-2 and Fas was seen in mesangial cells (1.3 +/- 0.1 and 2.0 +/- 0.1 for Bcl-2 and Fas, respectively). Similarly, a statistically significantly higher Bcl-2 (217.1 +/- 85.9) and Fas (767.9 +/- 271) serum levels were found in lupus patients compared to controls (148.6 +/- 87, 550.3 +/- 91 for Bcl-2 and Fas, P 0.05). A direct correlation between serum Bcl-2 and Fas and chronicity index was also found. Compared to normal controls, lupus nephritis is associated with glomerular expression and elevated serum levels of Bcl-2 and Fas proteins. These findings suggest possible roles for Bcl-2 and Fas in glomerular injury during evolution of lupus nephritis. The diagnostic, prognostic and therapeutic ramifications of our findings are open to further investigation.
Research Authors
Fathi NA, Hussein MR, Hassan HI, Mosad E, Galal H, Afifi NA.

Research Department
Research Journal
Clin Exp Immunol.
Research Member
Research Pages
pp. 339 - 343
Research Rank
2
Research Vol
Vol. 146 - No. 2
Research Year
2006

Prospective study of cross-infection from upper-GI endoscopy in a hepatitis C-prevalent population.

Research Abstract
BACKGROUND: A high prevalence of hepatitis C (HCV) in the Egyptian Nile Delta increases the demand for upper-GI endoscopy (UGIE) and the risk of cross-infection with this virus. OBJECTIVE: To assess the potential for UGIE to transmit HCV when endoscopes are reprocessed according to current international standards. DESIGN: A prospective cohort study to detect the incidence of HCV and hepatitis B cross-infections. SETTING: The endoscopic unit of the National Liver Institute, a hospital for patients with chronic liver disease. PATIENTS: A total of 859, including 149 of 249 patients (60%) at risk (HCV-antibody negative) retested 3 to 10 months after UGIE with endoscopes previously used on HCV carriers. INTERVENTIONS: Nurses were trained to process endoscopes according to American Society for Gastrointestinal Endoscopy guidelines, and procedures were observed and recorded. MAIN OUTCOME MEASUREMENTS: Seroconversions were determined by using enzyme immunoassays for anti-HCV; reverse transcriptase-polymerase chain reaction was used to detect HCV-ribonucleic acid (RNA). RESULTS: Four patients, initially negative, tested positive for anti-HCV after UGIE. However, 2 of these had HCV-RNA in their baseline blood sample, and the other 2 did not have HCV-RNA in their follow-up sample. LIMITATIONS: Very-high prevalence of anti-HCV in subjects reduced the proportion at risk of infection, and follow-up was difficult. CONCLUSIONS: There were no cases of proven transmission of HCV when endoscopes were reprocessed by using currently accepted standards. This negative study is encouraging, because patients undergoing UGIE in the Nile Delta of Egypt where HCV-caused liver disease is so pervasive would be at maximum risk of HCV cross-infection from UGIE.
Research Authors
Mikhail NN, Lewis DL, Omar N, Taha H, El-Badawy A, Abdel-Mawgoud N, Abdel-Hamid M, Strickland GT.

Research Journal
Gastrointest Endosc.
Research Member
Nabiel Nazmi Hanna Mikhail
Research Pages
pp. 584 - 588
Research Rank
2
Research Vol
Vol. 65 - No. 4
Research Year
2007
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