Growth hormone/insulin-like growth factor-1 axis: a possible non-nutritional factor for growth retardation in children with cerebral palsy.

OBJECTIVE: To assess growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis as a possible non-nutritional factor for growth retardation in children with cerebral palsy (CP). METHODS: A case-control study was conducted at a tertiary university hospital. Thirty children with CP (seven children with normal growth [CP-N] and 23 with retarded growth [CP-R]), 30 children with protein energy malnutrition (PEM), and 30 healthy children (REF group) underwent an assessment of growth parameters, serum IGF-1, basal GH, and peak GH after stimulation with insulin. RESULTS: PEM patients had higher basal GH levels than CP-N, CP-R and REF groups (p = 0.026, p < 0.001, and p < 0.001 respectively). After insulin stimulation, CP-N, CP-R, and PEM patients had lower GH levels compared to the REF group (p = 0.04, p = 0.007, and p = 0.036 respectively). IGF-1 levels were lower in CP-R group compared to CP-N and REF groups (p = 0.037 and p < 0.001 respectively), and in PEM group compared to CP-N and REF groups (p < 0.001 and p < 0.001 respectively). CONCLUSIONS: CP-R patients failed to demonstrate the same high basal GH response as PEM patients, and responded inadequately to the insulin stimulation test, but they had IGF-1 levels comparable to those of PEM patients. On the other hand, CP-N patients behaved as controls regarding their basal GH and IGF-1 levels, but failed to respond adequately to the insulin stimulation test. The PEM group presented high basal GH and low IGF-1 levels. These findings suggest that non-nutritional factors contribute to growth retardation in CP children.

Eixo hormônio de crescimento/fator de crescimento semelhante à insulina-1: um possível fator não nutricional para o retardo de crescimento em crianças com paralisia cerebral / Growth hormone/insulin-like growth factor-1 axis: a possible non-nutritional factor for growth retardation in children with cerebral palsy

OBJETIVO: Avaliar o eixo hormônio de crescimento (GH)/fator de crescimento semelhante à insulina 1 (IGF-1) como possível fator não nutricional para o retardo de crescimento em crianças com paralisia cerebral (PC). MÉTODOS: Um estudo caso-controle foi realizado em um hospital universitário terciário. Trinta crianças com PC [sete crianças com crescimento normal (PC-N) e 23 com retardo de crescimento (PC-R)], 30 crianças com desnutrição proteico-energética (DPE), e 30 crianças sadias (grupo REF) tiveram avaliados seus parâmetros de crescimento, IGF-1 sérico, GH basal, e pico de GH após estímulo com insulina. RESULTADOS: Os pacientes com DPE apresentaram níveis basais mais elevados de GH do que os grupos PC-N, PC-R e REF (p = 0,026, p < 0,001 e p = 0,001, respectivamente). Após estímulo com insulina, os grupos PC-N, PC-R e DPE apresentaram níveis menores de GH se comparados ao grupo REF (p = 0,04, p = 0,007, p = 0,036, respectivamente). O nível de IGF-1 foi menor no grupo PC-R se comparado aos grupos PC-N e REF (p = 0,037 e p < 0,001, respectivamente), e no grupo DPE se comparado aos grupos PC-N e REF (p < 0,001 e p < 0,001, respectivamente). CONCLUSÕES: Os pacientes com PC-R não demonstraram a mesma resposta basal elevada do GH apresentada pelos pacientes com DPE, e responderam de forma inadequada ao estímulo com insulina, mas apresentaram níveis de IGF-1 comparáveis aos dos pacientes com DPE. Por outro lado, os pacientes com PC-N tiveram comportamento semelhante ao dos controles com relação aos níveis basais de GH e IGF-1, mas não responderam adequadamente ao estímulo com insulina. O grupo DPE apresentou GH basal elevado e IGF-1 baixo. Esses achados sugerem que fatores não nutricionais contribuem para o retardo de crescimento em crianças com PC.

OBJECTIVE: To assess growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis as a possible non-nutritional factor for growth retardation in children with cerebral palsy (CP). METHODS: A case-control study was conducted at a tertiary university hospital. Thirty children with CP (seven children with normal growth [CP-N] and 23 with retarded growth [CP-R]), 30 children with protein energy malnutrition (PEM), and 30 healthy children (REF group) underwent an assessment of growth parameters, serum IGF-1, basal GH, and peak GH after stimulation with insulin. RESULTS: PEM patients had higher basal GH levels than CP-N, CP-R and REF groups (p = 0.026, p < 0.001, and p < 0.001 respectively). After insulin stimulation, CP-N, CP-R, and PEM patients had lower GH levels compared to the REF group (p = 0.04, p = 0.007, and p = 0.036 respectively). IGF-1 levels were lower in CP-R group compared to CP-N and REF groups (p = 0.037 and p < 0.001 respectively), and in PEM group compared to CP-N and REF groups (p < 0.001 and p < 0.001 respectively). CONCLUSIONS: CP-R patients failed to demonstrate the same high basal GH response as PEM patients, and responded inadequately to the insulin stimulation test, but they had IGF-1 levels comparable to those of PEM patients. On the other hand, CP-N patients behaved as controls regarding their basal GH and IGF-1 levels, but failed to respond adequately to the insulin stimulation test. The PEM group presented high basal GH and low IGF-1 levels. These findings suggest that non-nutritional factors contribute to growth retardation in CP children.

Bilateral Wilms' tumor: Mansoura multi-centers 15 years experience.

PURPOSE: Bilateral Wilms' tumor (WT) is a challenge. Aggressive surgical resection is needed to prevent recurrence. We revised the clinico-epidemiological criteria of bilateral WT patients in our locality and relation to outcome. SUBJECTS AND METHODS: 462 WT patients were registered in three medical centers at Mansoura, Egypt. Twenty five patients had bilateral WT whose medical records were revised for all clinico-epidemiologic data plus treatment details, toxicity, and outcome. RESULTS: The mean age was 34.5 months; 64% of cases were female. Abdominal mass was the commonest presentation (72%). Congenital anomalies were reported in two cases (one case showed hemihypertrophy and the other showed aniridia). About 60% had favorable pathology. Nineteen cases had synchronous bilateral WT (76%) and the remaining (six cases) had metachronous tumors. For the synchronous cases, the response rate to preoperative chemotherapy was 79% and nephron sparing surgery for the least involved kidney was possible in all. Survival rate was 74%. Metachronous tumor management included nephrectomy followed by chemotherapy for the initially diagnosed tumors. However, nephron sparing surgery of the contralateral tumors following preoperative chemotherapy was possible in two cases and the survival rate was 33%. No renal failure or any therapy-related complications were reported. CONCLUSIONS: Bilateral WT is predominantly synchronous with favorable histology, with female predilection and possibly congenital anomalies. Preoperative chemotherapy followed by nephron sparing surgery has a favorable outcome with preserved renal function especially in patients with synchronous WT. Response to preoperative chemotherapy had a statistically significant prognostic impact.

Glucosidase acid beta gene mutations in Egyptian children with Gaucher disease and relation to disease phenotypes.

INTRODUCTION: More than 200 mutations have been found in patients with Gaucher disease (GD) and some mutations usually have a high frequency in certain populations. Genotype/phenotype correlation in patients with GD has not been established. This study was designed to determine underlying mutations in Egyptian children with GD and to assess their relation to disease phenotypes. METHODS: This study comprised 17 patients with GD and 10 healthy controls. Thirteen patients were type 1 GD, 2 type 2, and 2 type 3. DNA was extracted from peripheral blood leukocytes. Exons 9 and 10 were amplified by polymerase chain reaction, and deoxyribonucleic acid sequencing was done with an ABI 310 genetic analyzer. RESULTS: Wild type allele was detected in 95% (19/20) and a normal variant in 5% (1/20) of controls. L444P allele was encountered in 50% (13/26) of the alleles in type 1 patients, H451P in 7.7% (2/26) and recombinant alleles (RecNcil, RecNcil + M450L, RecFs, RecFs + M450L) in 34.6% (9/26). L444P and Rec alleles each occurred in 50% (2/4) of type 2 and 3 patients. A new mutation was seen in this study {g.7336A>C, (M450L)} and 2 mutant alleles were not determined. Type 1 GD patients had L444P/L444P genotype (23.1%) and Rec alleles/L444P (53.8%), while type 2 and 3 GD patients had Rec alleles/L444P genotypes (100%) with a poor phenotype/genotype correlation. CONCLUSIONS: L444P and Rec alleles are common in the studied patients. Novel mutations are continuously detected, adding to the expanding panel of GD mutations. No significant genotype-phenotype association was observed.

Nosocomial infections and fever of unknown origin in pediatric hematology/oncology unit: a retrospective annual study.

BACKGROUND: pediatric hematology/oncology patients are faced with an increased risk of nosocomial infections (NIs) that vary in different populations and different institutions with considerable morbidity and mortality. This study was undertaken to assess the frequency and patterns of NIs in 1564 pediatric patients and to determine the prevalence of causative organisms and their antimicrobial sensitivity. METHODS: a retrospective analysis was made in the patients admitted between January 2007 and January 2008 to the pediatric hematoloy/oncology unit of Mansoura University, Egypt. The 1564 patients showed 2084 admissions and 27 092 inpatient days. The Centers for Disease Control and Prevention criteria were used as a standard definition for NI. RESULTS: the overall rate of NIs in all patients and neutropenic patients was 8.6 and 25.3 per 1000 patient-days respectively. The frequent sites of NIs were blood stream (42.7%), the respiratory system (25.3%), the urinary system (22.2%) and the central nervous system (9.8%), whereas nosocomial fever of unknown origin constituted 52.9% of cases. The incidence of NIs was significantly higher during neutropenic days (P<0.001). Gram-positive organisms represented 64.5% of pathogens (Staphylococci 71.5%, Streptococci 16%, and pneumococci 7%), and Gram-negative organisms represented 30% (E. coli 48.6%, Klebsiella 15.7%, Pseudomonas 35.7%, and C. albicans 5.5%). Positive cultures were more frequent in summer (July to September). Susceptibility of isolated organisms was relatively low (cefoperazone/sulbactam 49.9%, amikacin 35.9%, imipenem/cilastin 34.4%, cefoperazone 33.6%, and vancomycin 36.5%). Methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci represented 30%, 45% and 75% of isolated S. aureus, Gram-negative organisms and Enterococci, respectively. CONCLUSIONS: blood stream infection and fever of unknown origin are the most common nosocomial infections in pediatric hematology/oncology patients with a higher risk during neutropenic days. Isolated organisms are multi-drug resistant, predominantly Gram-positive pathogens with a high incidence of methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci organisms.

Reverse hybridization StripAssay detection of beta-thalassemia mutations in northeast Egypt.

AIM: beta-Thalassemias are widely distributed in Mediterranean and Middle Eastern countries. Reverse hybridization StripAssay method is reported to be rapid, simple, reproducible and less expensive. The aim of this study is to evaluate reverse hybridization StripAssay method for detection of beta-thalassemia mutations in Egyptian children. SUBJECTS AND METHODS: Forty children with beta-thalassemia major with mean age of 10.33+/-4.75 years were recruited consecutively from outpatient Hematology Clinic of Mansoura University Children's Hospital. Mutation analysis was performed by the beta-Globin StripAssay MED. RESULTS: The most frequent mutant alleles detected were; IVS 1.110, IVS 1.1 and IVS 1.6 accounting for 33.75, 27.5 and 18.75% respectively. The detection rate of the used method in our population was 90%. CONCLUSION: beta-globin StripAssay is a fast, easy-to-perform and reliable method for genetic screening of beta-thalassemia patients in Egypt. IVS 1.110, IVS 1.1 and IVS 1.6 are the most frequent mutant alleles with poor phenotype/genotype correlation.

Endothelin-1 and leptin as markers of intrauterine growth restriction.

OBJECTIVE: To explore the role of endothelin-1 (ET-1) and leptin in intrauterine growth restriction (IUGR) among preeclamptic and non-pre-eclamptic women. METHODS: Forty three patients with a pregnancy complicated by IUGR, 23 cases with severe pre-eclampsia and 20 cases of non-pre-eclamptic were enrolled. Control group comprised 15 cases with uncomplicated pregnancy. Blood samples from umbilical artery and maternal venous blood were collected at the time of delivery for analysis of ET-1 and leptin levels. Mode of delivery, birth weight and Apgar score were also recorded. RESULTS: The mean maternal and fetal ET-1 level was significantly higher in pregnancies complicated by IUGR than in control group. The mean maternal leptin level was significantly higher in pre-eclamptic patients when compared to non-preeclamptic and control groups. Mean fetal leptin level was significantly lower in patients compared to control; however, when fetal leptin corrected to fetal weight, it was insignificantly different in the both groups. E-mail: m. alhaggar@yahoo.co.uk. CONCLUSION: Maternal plasma ET-1 and leptin correlate with the degree of fetal growth restriction originating from deterioration of placental function. Maternal plasma leptin and ET-1 levels may reflect deterioration in fetal growth.

Parvovirus B19 infection in pediatric oncology patients: diagnostic value of clinical and serologic parameters compared with nested PCR.

BACKGROUND: Oncology patients are at particular risk for parvovirus B19 infection, which may cause severe, persistent, usually nonspecific illness in this group. AIM: This study was designed to assess the prevalence and impact of parvovirus B19 in pediatric oncology patients receiving chemotherapy, and to define the optimal diagnostic tests in such patients. SUBJECTS AND METHODS: Fifty-nine children under chemotherapy (39 with acute lymphocytic leukemia and 20 with solid tumors) with mean age of 4.96+/-1.94 years, in addition to 30 healthy children of matched age and sex, were enrolled in this study. Clinical and laboratory data were collected by examination and from patients' records. Specific parvovirus B19 immunoglobulin (Ig) M and IgG antibodies were assessed by enzyme-linked immunosorbent assay, and parvovirus DNA was detected by nested polymerase chain reaction (PCR) for all patients and controls. RESULTS: Parvovirus DNA was detected in 16 (27.1%), IgM in 3 (5.1%), and IgG in 36 (61%) patients. IgM had sensitivity, specificity, and accuracy of 18.75%, 100%, and 77.9%, respectively, whereas those of IgG were 81.25%, 53.4%, and 61%, respectively. PCR-positive patients had significantly higher frequency of unexplained anemia, red blood cell transfusions, and longer hospital stay than PCR-negative patients (P<0.001). Multiple linear regression analysis showed that unexplained anemia and multiple red blood cell transfusions were the most important variables that can predict PCR positivity. CONCLUSIONS: Parvovirus B19 is not an uncommon problem in pediatric oncology patients who exhibited weak antibody response and nonspecific clinical features. Screening of these patients with PCR rather than serology is recommended when infection is suspected.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: unusual clinical associations and novel claudin16 mutation in an Egyptian family.

BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder that eventually progresses to renal failure, depending upon the extent of nephrocalcinosis. Its basic pathogenesis is impaired tubular resorption of magnesium and calcium in the thick ascending limb of the loop of Henle (TAL) due to a genetic defect in paracellin-1 (a tight junction protein expressed in TAL). Mutations of the claudin16 gene (CLDN16), formerly called paracellin-1 gene (PCLN-1), have been linked to FHHNC. METHODS: An extended Egyptian family with more than one member affection by nephrocalcionsis was included and thoroughly investigated in the current study after giving informed consent. Thorough history was taken for polyuria, polydipsia and hypocalcemia symptoms, as well as clinical examination with stress on anthropometric measurements and radiological evaluation for kidneys and bones. Laboratory workup for the differential diagnosis of nephrocalcinosis was done: complete urinalysis, including urinary calcium excretion, urine pH and electrolytes, arterial blood gas (ABG), serum electrolytes (sodium, potassium, calcium, magnesium and phosphorous), renal function tests as well as parathyroid and gonadotropin-sex hormone assay. DNA extraction from peripheral blood leukocytes was done followed by amplification using primers previously described, purification and finally sequencing to analyze each exon of the CLDN16 gene. RESULTS: Two sibs for a consanguineous couple were affected by nephrocalcinosis and showed persistent hypocalcemia, hypercalciuria, nephrocalcinosis with persistently alkaline urine and ocular manifestations in the form of congenital cataracts, high myopia and retinal abnormalities. The elder sib showed genitourinary abnormalities in the form of hypospadias and cryptorchidism. These two sibs had a homozygous two-base deletion in exon 1 of the CLDN16 gene (C. 233_234 del GG; Ins C), causing a frame shift mutation (Arg55 fs); however, their parents were heterozygote carriers for that mutation. CONCLUSION: The above-mentioned clinical data in the two affected sibs together with the family history of end-stage renal disease associated with nephrocalcinosis and high myopia suggested a diagnosis of FHHNC, which was confirmed for the first time in an Egyptian family by a novel mutation in exon 1 of the CLDN16 gene. Genitourinary associations with FHHNC have not yet been reported in the literature. Here, we will try to highlight the principles of mutation detection based on sequencing with the use of the online NCBI databases, statistics and other search tools.

Evaluation of myrrh (Mirazid) therapy in fascioliasis and intestinal schistosomiasis in children: immunological and parasitological study.

A total of 21 children with fascioliasis (8 males and 13 females) with mean age of 10.4 years, 8 children with schistosomiasis mansoni (6 males and 2 females) with mean age of 11.37 years were treated with Myrrh (Mirazid) which is an oleo-gum resin from the stem of Commiphora molmol tree (Family Burseraceae). Also, ten healthly cross matched children were utilized as controls. Diagnosis was based on the detection of Fasciola hepatica or Schistosoma mansoni eggs in stool by Kato-Katz technique. Mirazid was given as 10 mg/kg/d an hour before breakfast for 3 consecutive days in schistosomiasis and for 6 days in fascioliasis. Clinical evaluation and stool analysis were done initially and at 2, 4 and 12 weeks post treatment to evaluate cure. Rectal snip was done for responding schistosomiasis cases to confirm recovery. Automated complete blood count with manual assessment of eosinophils, serum total IgE (enzyme immunoassay) and in vitro cytokines assay (IL-1 beta, IL-4, IL-5) by ELISA were performed for all subjects before treatment and repeated 12 weeks only for patients after therapy. Parasitologic cure was 90.9% in fascioliasis and 100% in schistosomiasis at 4 weeks post treatment. After a second dose Fasciola patients who remained positive were cured. Total IgE was significantly higher in Fasciola and Schistosoma patients before treatment compared to control (p < 0.001; 0.005 respectively) and decreased significantly with therapy (p = 0.001; 0.036). IL-1beta was higher in both patient groups than control (p < 0.001; 0.003) and decreased significantly 12 weeks after therapy to control level (p < 0.001; 0.017). IL-5 was high before treatment in both groups (p = 0.041; 0.027) and decreased significantly after 12 weeks after therapy (p = 0.005; 0.012). IL-4 did not differ from control before therapy (p = 0.58; 0.79) but increased significantly after treatment in both patient groups (p = 0.04; 0.02). It is concluded that Mirazid is an effective fasciolicidal and schistosomicidal drug. IL-1beta and IL5 were high in fascioliasis and schistosomiasis, but decreased with therapy denoting immunopathogenesis. The depressed IL-4 production may be a parasite immune evasion or host regulatory mechanism and cytokines levels may be criteria of cure.