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A
Aziz, M., A. El-Hadad, and M. A. Kotb, "Polymorphisms of glutathione S transferase gene and CYP1A1 associated with childhood acute lymphoblastic leukemia.", Egypt Journal of Laboratory Medicine , vol. 17, issue 1,2, pp. 193-202, 2005.
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EE Habib EE, M. S. M. El-Minawi, and M. A. Kotb, "Late effects and audiologic findings of childhood acute lymphblastic leukemia and lymphoma survivors treated by chemotherapy with or without cranial irradiation. ", Scientific Medical Journal , vol. 18, issue 2, pp. 14-27, 2006.
El-Karaksy, H., N. El-Koofy, M. El-Hawary, A. Mostafa, M. Aziz, M. El-Shabrawi, N. A. Mohsen, M. Kotb, M. El-Raziky, M. A. El-Sonoon, et al., "Prevalence of factor V Leiden mutation and other hereditary thrombophilic factors in Egyptian children with portal vein thrombosis: results of a single-center case-control study.", Annals of hematology, vol. 83, issue 11, pp. 712-5, 2004 Nov. Abstract

No identifiable cause can be found in more than half of the cases of portal vein thrombosis (PVT). Our aim was to assess the prevalence of factor V Leiden mutation and other thrombophilic factors as risk factors in the development of PVT in the pediatric age group. From March 2001 to January 2002, 40 children with PVT were enrolled in the study, in addition to 20 age-matched and sex-matched controls. Protein C, protein S, antithrombin III, and activated protein C resistance (APCR) were assayed. Molecular study of factor II and factor V mutations was carried out. Of the patients, 25 had detectable hereditary thrombophilia (62.5%), 12 had factor V Leiden mutation (30%), 11 had protein C deficiency (27.5%), 6 had factor II mutation (15%), 1 had antithrombin III deficiency (2.5%), and none had protein S deficiency. Five children had concurrence of more than one defect. Factor V Leiden mutation is the most common hereditary thrombophilia associated with PVT and the relative risk of factor V Leiden mutation, as a cause of PVT, was six times more than in controls (odds ratio=6). Concurrence of more than one hereditary thrombophilic factor was seen in 12.5% of our patients. Circumstantial risk factors (neonatal sepsis, umbilical sepsis, umbilical catheterization) were not more significantly prevalent among patients with hereditary thrombophilia than among those with no detectable abnormalities in anticoagulation.

El-Karaksy, H., M. El-Shabrawi, N. Mohsen, M. Kotb, N. El-Koofy, and N. El-Deeb, "Capillaria philippinensis: a cause of fatal diarrhea in one of two infected Egyptian sisters.", Journal of tropical pediatrics, vol. 50, issue 1, pp. 57-60, 2004 Feb. Abstract

Capillaria philippinensis is an emerging infection in Egypt. Reports in children are scarce. We report here two sisters with C. philippinensis infection, aged 8 and 12 years. Their father was a fisherman and they had a habit of picking small pieces of uncooked fish to eat while their mother prepared their meals. They came from El-Menia governorate, which lies in the northern part of Upper Egypt. Most reported cases from Egypt come from this governorate and nearby areas. Both sisters had persistent profuse watery diarrhea of 12 months' duration. Their weights were below the 5th percentile for age. Both were hypoalbuminemic, but only the younger had pedal edema. Both had hypokalemia and hyponatremia. During the course of their illness they were repeatedly admitted to different hospitals and received intravenous fluids, but the correct diagnosis was not reached. Diagnosis was made by stool examination at our hospital when eggs and larvae were detected in stool samples. Although a diagnosis was promptly made, the older sister who suffered from pneumonia and septic shock unfortunately died a few days after admission. The younger sister was treated successfully with albendazole 200 mg twice daily. Diarrhea abated, pedal edema disappeared, and she started to gain weight.

El-Raziky, M. S., M. El-Hawary, N. El-Koofy, S Okasha, M Isa, M. Kotb, K. Salama, G. Esmat, M. El-Raziky, A. M. Abouzied, and H. El-Karaksy, "Hepatitis C virus infection in Egyptian children: single centre experience.", Journal of viral hepatitis, vol. 11, issue 5, pp. 471-6, 2004 Sep. Abstract

The outcome of hepatitis C virus (HCV) infection acquired in childhood is uncertain because of the diversity of the epidemiological and clinical features of infection and disease. The aim of this study was to determine the outcome of HCV infection in 105 Egyptian children who tested positive for HCV antibody (anti-HCV). The data of 105 anti-HCV-positive children presenting to the Pediatric Hepatology Unit, Cairo University Children's Hospital, between 1995 and 2002, were retrospectively analysed for risk factors. Seventy-four children with available polymerase chain reaction results were further analysed clinically, serologically and histologically. The age range was 1.3-22 years, with a mean of 11.2 +/- 4.9 years. History of blood transfusion was found in 81 children (77%). HCV RNA was detected in 58.1% of 74 children. Persistently elevated alanine aminotransferase (ALT) levels were present in 40 patients (54.1%). Hepatitis B virus markers (HBsAg and/or anti-HBc) were detected in 18 patients (24.3%). Twenty-six of the 43 HCV RNA-positive children underwent a diagnostic liver biopsy that showed chronic hepatitis in 19 patients (73.1%), cirrhosis in one case only (3.8%), and normal biopsy findings in seven children (26.9%). Blood transfusion remains a major risk of HCV transmission among Egyptian children. HCV infection is not always benign in the childhood period. ALT levels remain elevated in half of the children and histological abnormalities are detected in three quarters of HCV RNA-positive cases.

El-Shabrawi", "M. H. F., H. M. El-karaksy, S. H. Okasha, H. M. El-Sayed, M. A. Kotb, A. M. Hassan, and A. - M. Ibrahim, "Pulmonary Function Testing in Children with Chronic Liver Disease", Alexandria Journal of Pediatrics, Volume 16, Number 2, , vol. 16, issue 2, pp. 405-409, 2002. pulmonary_function_testing_in_children_with_chronic_liver_disease2002_16_2_405.pdf
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Habib, E. E., M. Aziz, and M. Kotb, "Genetic polymorphism of folate and methionine metabolizing enzymes and their susceptibility to malignant lymphoma.", Journal of the Egyptian National Cancer Institute, vol. 17, issue 3, pp. 184-92, 2005 Sep. Abstract

BACKGROUND: Folate and methionine metabolism is involved in DNA synthesis and methylation. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylene-tetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms MTHFR 677 C-->T and MTHFR 1298 A-->C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5, 10- methylene-tetrahydrofolate and results in a reduced incidence of DNA double strand breakage. The MS 2756 A-->G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA.

PATIENTS AND METHODS: To test this hypothesis, genetic polymorphisms in the folate metabolic pathway were investigated using the DNA from a case-control study on 31 patients having malignant lymphoma from the Oncology Outpatient Clinic of the New Children's Hospital, Cairo University and 30 controls who were actually normal children attending for vaccination to the same hospital.

RESULTS: We found that there is a higher susceptibility with the MTHFR 677CC and MTHFR 1298 AA genotypes (OR=4.3, 95% CI 1.12-16). When those harbor at least one variant allele in either polymorphism of MTHFR they were defined as reference. For the MS 2756 AG genotype polymorphism there was also a higher susceptibility to developing malignant lymphoma (OR=2.6; 95% CI 1.1- 6.4).

CONCLUSION: Results suggest that folate and methionine metabolism may play an important role in the pathogenesis of malignant lymphoma. Further studies to confirm this association and detailed biologic mechanisms are now required.

HOSNI, H. N., M. M. Kamel, M. A. Kotb, and M. GHEITH, "Histopathological Study of Upper Gastrointestinal Tract for Helicobacter Pylori and Giardiasis in Egyptian Children", Med. J. Cairo Univ., vol. 80, issue 1, pp. 283-291, 2012.
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Kotb, M. A., Abd El Satar I, Badr AM, A. N, Ismail HA, Hamza AF, and A. E. K. H. M, "Pulmonary Hypertension and Cardiac Hypertrophy in Children Recipients of Orthotopic Living Related Liver Transplantation", Journal of Advanced Research, vol. 8, pp. 663-668, 2017. pulmonary_hypertension_post_liver_transplant_.pdf
Kotb, M. A., E. M. Hawary, S Okasha, M Isa, and M. Aziz, "Protein C, protein S, antithrombin III and factor V Leiden (Q506) mutation in veno-occlusive disease in Egyptian children", Alexandria Journal of Pediatrics , vol. 17, issue 2, pp. 501-504, 2003.
Kotb, M. A., A. El Henawy, S. Talaat, M. Aziz, G. H. El Tagy, M. M. El Barbary, and W. Mostafa, "Immune-mediated liver injury: prognostic value of CD4+, CD8+, and CD68+ in infants with extrahepatic biliary atresia.", Journal of pediatric surgery, vol. 40, issue 8, pp. 1252-7, 2005 Aug. Abstract

BACKGROUND: Hepatic fibrosis and cirrhosis develop progressively in extrahepatic biliary atresia (EHBA) despite timely surgical intervention.

PURPOSE: The aim of the study was to define CD4+ helper T lymphocytes, cytotoxic CD8+ T lymphocytes, and CD68+ (macrophages) infiltration of portal tracts and lobules and hepatic fibrosis as possible predictive measures of outcome of infants having EHBA.

METHODS: The outcome of 32 infants with EHBA was correlated to their percutaneous biopsy and postportoenterostomy core liver tissue infiltration by CD4+, CD68+, and CD8+ cells and to the degree of detected fibrosis.

RESULTS: Portoenterostomy cores were heavily infiltrated by CD4+, CD8+, and CD68+, compared with the preoperative liver biopsy (P = .008, .004, and .017, respectively). Infants having favorable outcome had more macrophage infiltration in portoenterostomy core compared with those having an unfavorable outcome (25.66 +/- 29.77 per HPF compared with 11.62 +/- 4.58, P = .000). Mean CD4+/CD8+ ratio was 1.54 +/- 1.37 in those who died within 18 months postoperatively and 0.733 +/- 0.48 in others (P = .021).

CONCLUSION: Immune-mediated destruction of portal tracts is an integral part of pathogenesis of EHBA.

Kotb, M. A., H. N. Elmahdy, F. E. Mostafa, E. M. Falaki, C. W. Shaker, M. A. Refaey, and K. W. Y. Rjoob, "Improving the Recognition of Heart Murmur", International Journal of Advanced Computer Science and Applications, vol. 7, issue 7, pp. 283-287, 2016.
Kotb, M. A., A. Idrees, W. N. Lotfi, G. Taha, and M. Aziz, "Elevated levels of interleukin 18 in children with acute and chronic liver disease: Further evidence of T-cell- mediated liver injury.", Alexandria Journal of Pediatrics, vol. 16, issue 2, pp. 327-332, 2002.
Kotb, M. A., "Ursodeoxycholic acid in neonatal hepatitis and infantile paucity of intrahepatic bile ducts: review of a historical cohort.", Digestive diseases and sciences, vol. 54, issue 10, pp. 2231-41, 2009 Oct. Abstract

We retrospectively reviewed the role of ursodeoxycholic acid in infants having nonsurgical cholestasis attending the Hepatology Clinic, New Children Hospital, Cairo University, Egypt, from 1985 until 2005. Files of 496 infants with neonatal hepatitis and 97 with intrahepatic bile duct paucity were included; of them 241 (48.6%) and 52 (46.4%) received 20-40 mg/kg/day ursodeoxycholic acid for 319.2 +/- 506.9 days and 480.3 +/- 583.3 days, respectively. The outcome of infants with neonatal hepatitis with intake of ursodeoxycholic acid and those without was: 108 (44.8%) and 179 (70.2%) successful (P = 0.000), 11 (4.6%) and 13 (5.1%) improved (P = 0. 474), 112 (46.5%) and 61 (23.9%) suffered failed outcome (P = 0.000), and 10 (4.1%) and 2 (0.78%) died (P = 0.014), respectively. Likelihood of successful outcome with ursodeoxycholic acid intake was 0.345 (P = 0.000), and that of deterioration was 2.76 (P = 0.000). For those having intrahepatic bile duct paucity likelihood of successful outcome with ursodeoxycholic acid intake was 0.418 (P = 0.040) and that of deterioration was 2.64 (P = 0.028). Ursodeoxycholic acid failed in management of this cohort of infants with nonsurgical cholestasis.

Kotb, M. A., "Aflatoxins in Infants with Extrahepatic Biliary Atresia", Med. J. Cairo Univ., vol. 83, issue March 1, pp. 207-210,, 2015. Aflatoxins in Infants with Extrahepatic Biliary Atresia
Kotb, M. A., D. Mosallam, C. W. S. Basanti, S. T. M. El Sorogy, A. M. Badr, H. E. H. Abd El Baky, and I. H. Draz, "Ursodeoxycholic acid use is associated with significant risk of morbidity and mortality in infants with cholestasis: A strobe compliant study.", Medicine, vol. 99, issue 7, pp. e18730, 2020. Abstract

The off-label use of medications is a "right" for pediatricians, owing to lack of enough safety and effectiveness drug trials in pediatric age group. Pediatricians have to rely on their personal judicial use of medications in children.We studied off-label use of ursodeoxycholic acid (UDCA) retrospectively during 2005 to 2015 among those who attended the Pediatic Hepatology Unit, Cairo University.We analyzed data of 779 neonates and infants with cholestasis. 15% dropped out. Males comprised 374 (56.5%). Cholestasis was due to surgical causes in 129 (19.5%), neonatal hepatitis in 445 (67.2%), and paucity of intrahepatic bile ducts in 88 (13.3%). Three hundred sixty (54.4%) received UDCA (15-30 mg/kg/d), and 302 (45.6%) did not. Both groups were matched as regards causes and severity of cholestasis. Those who received UDCA had worse outcome (P < .001), and more complications (P < .001). A total of 73.1% (221) achieved cure without UDCA compared to only 45.8% (165) of those on UDCA (P < .001).UDCA is not effective and not safe in Egyptian neonates and infants with cholestasis. UDCA use compromises chance of cure, and is associated with serious morbidity, progression of disease, and death. UDCA off-label use mortality was absolutely preventable. Off- label use of UDCA in neonates and children should be utterly prohibited. Information of use of off-label medications, effectiveness, and safety, should be recorded, analyzed, and made available within context of Off-label Use Registry Studies with informed consent of parents.

Kotb, M. A., S. Hamad, and Moussa S, "Pericentric inversion of chromosome 15 [inv(15) (q12p11.20)] in children with conduct disorder.", The Egyptian Journal of Psychiatry , vol. 23, issue 2, pp. 165-178, 2000.
Kotb, M. A., L. Mansour, and R. A. Shamma, "Screening for galactosemia: is there a place for it?", International Journal of General Medicine, vol. 12, pp. 193–205, 2019. 23-may-2019-ijgm-180706-screening-for-galactosemia-is-there-a-place-for-it-.pdf
Kotb, M. A., E. M. Hawary, S Mansour S, W. Lotfi, S. Shaker, S Okasha, M Isa, M Aziz M, and S. Talaat, "Protein C activity, protein S, antithrombin III, factor V leiden (Q506) mutation and methylene tetrahydrofolate reductase 677-T polymorphism in children with hepatic veno-occlusive disease.", Alexandria Journal of Pediatrics , vol. 21, issue 3, pp. 451-455, 2007.
Kotb, M. A., M. Kamal, S. Mansour, E. M. Hawary, W. N. Lotfi, H. Hamdi, M. M. E. Barbary, S. Kaddah, W. Mostafa, and A. Kotb, "Progression of disease in extrahepatic biliary atresia is associated with reduced total hepatic blood flow: descriptive results of a prospective pilot study ", Alexandria Journal of Pediatrics , vol. 20, issue 1, pp. 63-68, 2006.
Kotb, M. A., O. Afify, E. M. Hawary, and S Okasha, M Isa, "EEG changes in liver glycogenoses: a crosssectional study.", Alexandria Journal of Pediatrics , vol. 18, issue 1, pp. 61-65, 2004.
Kotb, M. A., "EXTRAHEPATIC BILIARY ATRESIA; KOTB DISEASE IS POTENTIALLY PREVENTABLE", Excellence in Pediatrics Conference, London, UK, December, 2015.
Kotb, M. A., "Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia.", Journal of pediatric surgery, vol. 43, issue 7, pp. 1321-7, 2008 Jul. Abstract

BACKGROUND: Ursodeoxycholic acid is a bile acid that was found to increase bile flow, protect hepatocytes, and dissolve gallstones.

PURPOSE: The objective of this study is to review ursodeoxycholic acid in infants and children with extrahepatic biliary atresia.

METHODS: We used a statistical analysis of data of records of infants and children having extrahepatic biliary atresia who underwent Kasai portoenterostomy and attended Hepatology Clinic, New Children's Hospital, Cairo University, Egypt, from May 1985 until June 2005.

RESULTS: Of 141 infants with extrahepatic biliary atresia, 108 received ursodeoxycholic acid for mean duration +/- SD of 252.6 +/- 544.9 days in a dosage of 20 mg/kg per day. The outcome of infants who did not receive ursodeoxycholic acid and those who did was the following: 8 (24.2%) and 11 (10.18%) had a successful outcome (P = .043), 0 (0%) and 7 (6.4%) improved (P = .148), 25 (75.7%) and 84 (77.7%) had a failed outcome (P = .489), and none vs 5 died (4.6%) (P = .135), respectively. The predictors of successful outcomes were age less than 65 days at portoenterostomy (P = .008) and absence of ursodeoxycholic acid intake (P = .04) with a likelihood of a successful outcome that was 2.8, that associated with ursodeoxycholic acid intake.

CONCLUSION: In this cohort of infants with extrahepatic biliary atresia, ursodeoxycholic acid was not shown to be effective, and its use was associated with a plethora of hepatic and extrahepatic complications.

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