Magd A. Kotb

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

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.

Hepatitis C virus infection in Egyptian children: single centre experience

Summary.  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 Childrens 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.

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia

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 Childrens 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.

Liver Glycogenoses: Are they a Possible Cause of Polyneuropathy? A Cross-sectional Study

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.

Pulmonary hypertension and cardiac hypertrophy in children recipients of orthotopic living related liver transplantation

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Improving the Recognition of Heart Murmur

Diagnosis of congenital cardiac defects is challenging, with some being diagnosed during pregnancy while others are diagnosed after birth or later on during childhood. Prompt diagnosis allows early intervention and best prognosis. Contemporary diagnosis relies upon the history, clinical examination, pulse oximetery, chest X-ray, electrocardiogram (ECG), echocardiography (ECHO), computed tomography (CT) and cardiac catheterization. These diagnostic modalities reliable upon recording electrical activity or sound waves or upon radiation. Yet, congenital heart diseases are still liable to misdiagnosis because of level of operator expertise and other multiple factors. In an attempt to minimize effect of operator expertise this paper built a classification model for heart murmur recognition using Hidden Markov Model (HMM). This paper used Mel Frequency Cepestral coefficient (MFCC) as a feature and 13 MFCC coefficients. The machine learning model built by studying 1069 different heart sounds covering normal heart sounds, ventricular septal defect (VSD), mitral regurgitation (MR), aortic stenosis (AS), aortic regurgitation (AR), patent ductus arteriosus (PDA), pulmonary regurgitation (PR), and pulmonary stenosis (PS). MFCC feature used to extract feature matrix for each type of heart sounds after separation according to amplitude threshold. The frequency of normal heart sound (range= 1Hz to 139Hz) was specific without overlap with any of the studied defects (ranged= 156-556Hz). The frequency ranges for each of these defects was typical without overlap according to examined heart area (aortic, pulmonary, tricuspid and mitral area). The overall correct classification rate (CCR) using this model was 96% and sensitivity 98%. This model has great potential for prompt screening and specific defect detection. Effect of cardiac contractility, cardiomegaly or cardiac electrical activity on this novel detection system needs to be verified in future works.

Pilot study of classic galactosemia: Neurodevelopmental impact and other complications urge neonatal screening in Egypt

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Pediatric Online Evidence-Based Medicine Assignment Is a Novel Effective Enjoyable Undergraduate Medical Teaching Tool: A SQUIRE Compliant Study.

Abstract Evidence-based medicine (EBM) is delivered through a didactic, blended learning, and mixed models. Students are supposed to construct an answerable question in PICO (patient, intervention, comparison, and outcome) framework, acquire evidence through search of literature, appraise evidence, apply it to the clinical case scenario, and assess the evidence in relation to clinical context. Yet these teaching models have limitations especially those related to group work, for example, handling uncooperative students, students who fail to contribute, students who domineer, students who have personal conflict, their impact upon progress of their groups, and inconsistent individual acquisition of required skills. At Pediatrics Department, Faculty of Medicine, Cairo University, we designed a novel undergraduate pediatric EBM assignment online system to overcome shortcomings of previous didactic method and aimed to assess its effectiveness by prospective follow-up during academic years 2012 to 2013 and 2013 to 2014. The novel web-based online interactive system was tailored to provide sequential single and group assignments for each student. Single assignment addressed a specific case scenario question, while group assignment was teamwork that addressed different questions of same case scenario. Assignment comprised scholar content and skills. We objectively analyzed students’ performance by criterion-based assessment and subjectively by anonymous student questionnaire. A total of 2879 were enrolled in 5th year Pediatrics Course consecutively, of them 2779 (96.5%) logged in and 2554 (88.7%) submitted their work. They were randomly assigned to 292 groups. A total of 2277 (89.15%) achieved ≥80% of total mark (4/5), of them 717 (28.1%) achieved a full mark. A total of 2178 (85.27%) and 2359 (92.36%) made evidence-based conclusions and recommendations in single and group assignment, respectively (P < 0.001). A total of 1102 (43.1%) answered student questionnaire, of them 898 (81.48%) found e-educational experience satisfactory, 175 (15.88%) disagreed, and 29 (2.6%) could not decide. A total of 964 (87.47%) found single assignment educational, 913 (82.84%) found group assignment educational, and 794 (72.3%) enjoyed it. Web-based online interactive undergraduate EBM assignment was found effective in teaching medical students and assured individual student acquisition of concepts and skills of pediatric EMB. It was effective in mass education, data collection, and storage essential for system and student assessment.

Erratum: 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 (2004) vol. 83 (712-715))

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