Publications

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1999
Mohsen, N. A., M. A. Kotb, Abd El Fattah MM, and I. HA, "Interaction of tumor necrosis factor alpha and nitric oxide in pediatric chronic liver diseases", The Arab Journal of Laboratory Medicine, vol. 25, issue 1, pp. 97-106, 1999.
2000
Kotb, M. A., and M. Aziz, "Antineutrophil cytoplasmic antibodies and other antibodies in neonatal hepatitis and extrahepatic biliary atresia.", Scientific Medical Journal , vol. 12, issue 3, pp. 41-51, 2000.
Kotb, M. A., N. El-Koofy, W. N. Lotfi, and M. Kamal, "Doppler assessed haemodynamic changes in infants and children suffering cholestasis.", The Gazette of Egyptian Pediatric Association , vol. 48, issue 3, pp. 345-356, 2000.
Kotb, M. A., Mahmould A, Moussa S, and A. HH., "Fragile X syndrome and other cytogenetic abnormalities presenting by poor school performance in boys with no dysmorphic features.", The Gazette of Egyptian Pediatric Association , vol. 48, issue 2, pp. 157-175, 2000.
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.
2001
Kotb, M. A., A. Kotb, M. F. Sheba, N. M. El Koofy, H. M. El-Karaksy, M. K. Abdel-Kahlik, A. Abdalla, M. E. El-Regal, R. Warda, H. Mostafa, et al., "Evaluation of the triangular cord sign in the diagnosis of biliary atresia.", Pediatrics, vol. 108, issue 2, pp. 416-20, 2001 Aug. Abstract

BACKGROUND: Infantile cholestasis continues to represent a diagnostic challenge. It is very important to diagnose surgically correctable disorders, such as biliary atresia, in a timely manner to prevent progressive damage to the liver. It has been recently suggested that the triangular cord (TC) sign is a simple and useful tool in the diagnosis of biliary atresia.

METHODS: We prospectively studied 65 infants presenting with conjugated hyperbilirubinemia (age range: 32-161 days). All patients underwent ultrasonographic examination with a 7.0-MHz transducer (Acuson, Mountain View, CA). The TC was defined as a triangular, or tubular, echogenic density seen immediately cranial to the portal vein bifurcation.

RESULTS: The TC sign was identified in 25 infants, and all of them had histologic features suggestive of biliary atresia; the diagnosis was confirmed at surgery by gross morphology of hepatobiliary system, and liver biopsy, with or without intraoperative cholangiogram. Among the 40 patients who did not have the TC sign, 6 had paucity of the intrahepatic bile ducts. Three had alph-1-antitrypsin deficiency, and 31 had neonatal hepatitis. None of the 40 patients who did not have the TC sign developed acholic stools. Seven patients with biliary atresia were followed by ultrasonographic examination for 6 months after the Kasai procedure. The TC sign disappeared in all patients after the surgery; however, the TC sign reappeared in 3 patients who developed progressive cholestasis after the procedure.

CONCLUSION: The TC sign is a simple, timesaving, and reliable diagnostic tool in the evaluation of infants with infantile cholestasis. The TC sign may also prove to be helpful in following patients after hepatoportoenterostomy. We suggest a new diagnostic strategy for patients suspected to have biliary atresia. When the TC sign is visualized, the patient should undergo intraoperative cholangiogram to confirm the diagnosis of biliary atresia, reserving percutaneous liver biopsy for those patients in whom the TC sign could not be detected.

2002
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.
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
2003
Kotb, M. A., and N. Sabry, "Depression and body image in children with chronic liver disease. A cross-sectional study", Current Psychiatry , vol. 10, issue 2, pp. 168-181, 2003.
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.
Lotfi, W. N., M. A. Kotb, M. M. Said, and F. M. Mahmoud, "The role of intravenous immunoglobulins in children with recent onset dilated cardiomyopathy. ", The Egyptian Heart Journal, vol. 55, issue 2, pp. 379-385, 2003.
2004
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.
Sidhom, I., H. Hussein, M. Kotb, G. Anwar, S. Aboulnaga, M. Amin, E. Ebeid, and H. Ahmed, "Multidisciplinary Approach to Wilms' Tumor: 10 Years Experience of NCI, Egypt", Journal of Clinical Oncology, vol. 22, issue (14_suppl), pp. 544-8544, 2004.
Kotb, M. A., H. K. Abdallah, and A. Kotb, "Liver glycogenoses: are they a possible cause of polyneuropathy? A cross-sectional study.", Journal of tropical pediatrics, vol. 50, issue 4, pp. 196-202, 2004 Aug. Abstract

We encountered two children suffering from liver glycogenoses (GSD) over a period of 5 years (1992-1997) who presented with a demyelinating peripheral neuropathy diagnosed by electromyography (EMG) and nerve conduction studies (NCV). The aim of the study was to evaluate the involvement of muscle and motor nerve in children suffering from liver glycogenoses. In a cross-sectional study, 22 children suffering from liver GSD (with no current neurological symptoms) and 20 age- and sex- matched clinically free children (control group) underwent creatine phospho-kinase (CPK), EMG, and NCV studies. Abnormal EMG and/or NCV studies were found in 11 children. Six (27.27 per cent) were found to have axonopathy, three (13.63 per cent) demyelinating polyneuropathy, and two (9.1 per cent) had mixed axonal and demyelinating neuropathy. Two children with axonopathy had GSD type VI, another had GSD type IV, and three had GSD of undiagnosed type. Three of those having a demyelinating polyneuropathy had GSD type III, another had GSD type IV, and the last had GSD of undiagnosed type. None were found to have a cardiomyopathy or a myopathy on EMG. This is the first report of neuropathy associated with GSD types III, IV, and VI in children. It might be discovered by EMG and/or NCV studies in a clinically, neurologically normal child suffering from GSD, or present as an acute polyneuropathy.

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-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-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.

2005
Kotb, M. A., E. M. Razky, H. M. E. Karaksy, M. S. E. Razky, S Okasha, M Isa, R. Hussein, E. N. Dessouky, M. M. E. Barbary, E. H. Tantawy, and W. Mostafa, "Evaluation of TC sign by 3 dimensional sonography in extrahepatic biliary atresia: A prospective study. ", The Medical Journal of Cairo University, vol. 78, issue 4 suppl, pp. 103-106, 2005.
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.
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., M. Sheba, N. El Koofy, S. Mansour, H. M. E. Karaksy, N. M. Dessouki, W. Mostafa, M. El Barbary, H. E. El-Tantawy, and S. Kaddah, "Post-portoenterostomy triangular cord sign prognostic value in biliary atresia: a prospective study.", The British journal of radiology, vol. 78, issue 934, pp. 884-7, 2005 Oct. Abstract

The triangular cord sign (TC sign) is a sensitive and specific tool in prompt diagnosis of extrahepatic biliary atresia. The objective of this study is to evaluate post-operative TC sign presence in outcome prediction of infants with biliary atresia after Kasai hepato-portoenterostomy 27 infants and children with biliary atresia underwent 122 ultrasound examinations using both 5 MHz and 7 MHz convex linear transducers in 33 months follow up. For all infants TC sign identification was included pre-operatively, ultrasound was done 2 weeks post-operatively then bimonthly for 3 months, monthly for 2 months and every 3 months thereafter. 14 (53.8%) had post-operative TC sign. Once post-operatively positive, it remained positive throughout the study. It did not reappear in an initially post-operatively TC sign negative infant. Those having post-operative TC sign had statistically worse outcomes (0 became anicteric, 2 improved, 7 had progressive disease and 6 died) than those with a negative TC sign (p = 0.04) (3 became anicteric, 5 improved, 2 progressed and 1 died). Presence of TC sign post-operatively correlated with measure of removal of all fibrous cone at porta-hepatis during portoenterostomy (p = 0.026). Post-portoenterostomy TC sign is associated with more morbidity and mortality; and reflects inadequate surgical technique.

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.

2006
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.
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.