Rapid screening for glucose-6-phosphate dehydrogenase deficiency and haemoglobin polymorphisms in Africa by a simple high-throughput SSOP-ELISA method.
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BACKGROUND: Mutations in the haemoglobin beta-globin (HbB) and glucose-6-phosphate dehydrogenase (G6PD) genes cause widespread human genetic disorders such as sickle cell diseases and G6PD deficiency. In sub-Saharan Africa, a few predominant polymorphic variants of each gene account for a majority of these deficiencies. Examining at a larger scale the clinical importance of these independent genetic disorders, their possible association with malaria pathogenesis and innate resistance, and their relevance for antimalarial drug treatment, would be easier if an accurate screening method with limited costs was available. METHODS: A simple and rapid technique was developed to detect the most prominent single nucleotide polymorphisms (SNPs) in the HbB and G6PD genes. The method is able to detect the different haemoglobin polymorphisms A, S, C and E, as well as G6PD polymorphisms B, A and A- based on PCR-amplification followed by a hybridization step using sequence-specific oligonucleotide probes (SSOPs) specific for the SNP variants and quantified by ELISA. RESULTS: The SSOP-ELISA method was found to be specific, and compared well to the commonly used PCR-RFLP technique. Identical results were obtained in 98% (haemoglobin) and 95% (G6PD) of the tested 90 field samples from a high-transmission area in Tanzania, which were used to validate the new technique. CONCLUSION: The simplicity and accuracy of the new methodology makes it suitable for application in settings where resources are limited. It would serve as a valuable tool for research purposes by monitoring genotype frequencies in relation to disease epidemiology. (+info)
Glucose-6-phosphate dehydrogenase deficiency decreases vascular superoxide and atherosclerotic lesions in apolipoprotein E(-/-) mice.
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OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway that is a major source of cellular NADPH. The purpose of this study was to examine whether G6PD deficiency affects vascular oxidants and atherosclerosis in high-fat fed apolipoprotein (apo) E(-/-) mice. METHODS AND RESULTS: G6PD-mutant mice whose G6PD activity was 20% of normal were crossbred with apoE(-/-) mice. Among male apoE(-/-) mice that were fed a western-type diet for 11 weeks, G6PD wild-type (E-WT), and G6PD hemizygous (E-Hemi) mice were compared. Basal blood pressure was significantly higher in E-Hemi. However, superoxide anion release, nitrotyrosine, vascular cell adhesion molecule (VCAM)-1, and inducible nitric oxide synthase immunohistochemical staining were less in E-Hemi compared with E-WT aorta. Serum cholesterol level was lower in E-Hemi, but aortic lesion area was decreased in E-Hemi even after adjusting for serum cholesterol. CONCLUSIONS: Lower NADPH production in G6PD deficiency may result in lower NADPH oxidase-derived superoxide anion, and thus lower aortic lesion growth. The association of higher blood pressure with lower serum cholesterol levels in this mouse model is indicative of the complex effects that G6PD deficiency may have on vascular disease. (+info)
The role of the G6PD AEth376G/968C allele in glucose-6-phosphate dehydrogenase deficiency in the seerer population of Senegal.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in tropical Sub-Saharan countries. The allele most frequently associated with G6PD deficiency in this a region is G6PD 376G/202A. Here, we show that, the prevalence of G6PD deficiency is 12% in the Sereer ethnic group from Senegal ant that the 376G/968C genotype is predominant; the frequency of the 376G/202A genotype is very low in this ethnic group. (+info)
Management of neonatal hyperbilirubinemia: pediatricians' practices and educational needs.
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BACKGROUND: Early detection and treatment of neonatal hyperbilirubinemia is important in the prevention of bilirubin-induced encephalopathy. In this study, we evaluated the New Jersey pediatricians' practices and beliefs regarding the management of neonatal hyperbilirubinemia and their compliance with the recommendations made by the American Academy of Pediatrics (AAP) in 1994. METHODS: A survey questionnaire was mailed to a random sample of 800 pediatricians selected from a list of 1623 New Jersey Fellows of the AAP initially in October 2003 and then in February 2004 for the non-respondents. In addition to the physicians' demographic characteristics, the questionnaire addressed various aspects of neonatal hyperbilirubinemia management including the diagnosis, treatment, and follow up as well as the pediatricians' beliefs regarding the significance of risk factors in the development of severe hyperbilirubinemia. RESULTS: The adjusted response rate of 49.1% (n = 356) was calculated from the 725 eligible respondents. Overall, the practicing pediatricians reported high utilization (77.9%) of the cephalocaudal progression of jaundice and low utilization (16.1%) of transcutaneous bilirubinometry for the quantification of the severity of jaundice. Most of the respondents (87.4%) identified jaundice as an indicator for serum bilirubin (TSB) testing prior to the neonate's discharge from hospital, whereas post-discharge, only 57.7% felt that a TSB was indicated (P < 0.01). If the neonate's age was under 72 hours, less than one-third of the respondents reported initiation of phototherapy at TSB levels lower than the treatment parameters recommended by the AAP in 1994, whereas if the infant was more than 72 hours old, almost 60% were initiating phototherapy at TSB lower than the 1994 AAP guidelines. Most respondents did not regard neonatal jaundice noted after discharge and gestational ages 37-38 weeks as being significant in the development of severe hyperbilirubinemia. However, the majority did recognize the importance of jaundice presenting within the first 24 hours and Rh/ABO incompatibility. CONCLUSION: The pediatricians' practices regarding the low utilization of laboratory diagnosis for the quantification of jaundice after discharge and underestimation of risk factors that contribute to the development of severe hyperbilirubinemia are associated with initiation of phototherapy at lower than AAP recommended treatment parameters and recognition of neonatal hyperbilirubinemia as an important public health concern. (+info)
Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system.
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A cytotoxic effect of human neutrophils on mammalian tumor cells is demonstrated. Cytotoxicity depends on the presence of intact neutrophils, phagocytosable particles, and a halide cofactor and is inhibited by azide, cyanide, and catalase. Neutrophils from patients with myeloperoxidase (MPO) deficiency or defective H1O2 production are not cytotoxic, but activity is resotred by addition of purified MPO or H2O2 respectively. The findings support a mechanism involving the phagocytosis-induced extracellular release of MPO and H2O2 and their reation with a halide cofactor to damage the target cells. (+info)
Audit of birth defects in 34,109 deliveries in a tertiary referral center.
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The objective of the study is to determine the proportion and different types of birth defects among the children born in Hospital Kuala Lumpur. A cross-sectional study was conducted for a period of 18 months where all consecutively born infants, dead or alive were included. There were total of 34,109 births recorded during this period. The proportion of birth defects in Hospital Kuala Lumpur was 3.1% (n = 1056). The commonest involved were the hematology system, (157.7 per 10,000 births), the central nervous system, genitourinary system and chromosomal anomalies. The proportion was significantly higher in males and in the Chinese (p < 0.001). The commonest abnormalities are Glucose 6 Phosphate Deficiency (157.7/10000), Down's syndrome (12.6/10000), thalassaemia (8.8/10000), cleft lip and/or palate (7.6/10000) and anencephaly (7.3/10000). Neural tube defect is common and ranked second after G6PD deficiency. There is a need for a birth defect registry to assess the extent of the problem in Malaysia. (+info)
Acute massive haemolysis in children with glucose-6-phosphate dehydrogenase deficiency.
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We report seven consecutive episodes of acute massive haemolysis accompanied by symptomatic anaemia and gross haemoglobinuria in six boys with glucose-6-phosphate dehydrogenase deficiency seen in a regional hospital during a 12-year period. They presented at a mean age of 5.5 years (range, 1.5-11.3 years) with trough haemoglobin levels between 35 and 84 g/L. Two children developed transient renal impairment. Five children required erythrocyte transfusion, of whom one underwent exchange transfusion during the oliguric phase. Three patients required intensive care but all recovered from the haemolysis. The probable precipitating factors included consumption of fava beans (n=2), exposure to mothballs (n=1), treatment with herbal medicine or intramuscular injection of unknown nature (n=3), and upper respiratory tract infection (n=1). Although uncommon, acute massive haemolysis remains a life-threatening complication in children with glucose-6-phosphate dehydrogenase deficiency. Improvement in patient education and public health measures is suggested. (+info)
Does familiarity breed acceptance? The influence of policy on physicians' attitudes toward newborn screening programs.
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OBJECTIVE: As newborn screening (NBS) programs expand to include conditions that challenge traditional public health criteria, little is known about what influences physicians' attitudes toward screening. We examined the effect of state policy and perceived state policy on pediatricians' attitudes toward screening. METHODS: Six hundred pediatricians from the American Academy of Pediatrics who practiced in Wisconsin, Colorado, Florida, or Illinois were queried about (1) testing high-risk infants and (2) universal NBS for cystic fibrosis (CF), glucose-6-phosphate dehydrogenase deficiency (G6PD), and type 1 diabetes. RESULTS: A total of 225 (41%) of 548 eligible pediatricians returned 223 surveys with usable data. The majority were supportive of NBS for CF (n = 188 [84%]) and G6PD (n = 130 [58%]), whereas only 25% (n = 55) supported type 1 diabetes screening. Pediatricians who lived in states that screen for a condition were more likely to support screening than those who lived in states that did not (CF: 117 of 119 [98%] vs 71 of 89 [80%]; type 1 diabetes: 32 of 88 [36%] vs 23 of 109 [21%]). Physicians also were more likely to support NBS when they believed that it was offered in their state versus when they believed that it was not (CF: 117 of 119 [98%] vs 52 of 65 [80%]; G6PD: 28 of 32 [88%] vs 75 of 108 [69%]; type 1 diabetes: 7 of 14 [50%] vs 25 of 102 [25%]). CONCLUSIONS: Most pediatricians are supportive of NBS for CF and G6PD but not type 1 diabetes. Pediatricians who live in states that screen or believe that their states screen are more likely to support screening. (+info)