Biomedical subjects
Publications and source records attributed to H B Wong.
The frequency of deletional alpha-thalassaemia in a Javanese population sample (n = 103) was investigated at three restriction sites of the alpha-globin gene (BamHI, BglII and RsaI). The overall gene frequency of alpha+ deletional thalassaemia was found to be very low (0.03). Leftward (-alpha 4.2) and rightward (-alpha 3.7) deletions and triplicated genes were present in equal frequency (0.015 and 0.005, respectively).
Molecular and non-molecular techniques have been utilized for the detection and characterisation of alpha- and beta-thalassaemia genes. Non-molecular techniques example, haematological indices and haemoglobin electrophoresis allow samples to be screened rapidly without the use of radionuclides but these techniques are unable to detect mutations at the gene level. Molecular analysis of alpha- and beta-globin genes either by Southern Blotting and radionuclides or DNA amplification using the polymerase chain reaction (PCR) allows detection of specific mutations and have enabled prenatal diagnosis of the thalassaemias.
The diagnosis of bacterial meningitis can be difficult nowadays when antibiotics are freely used in infants and children with fever due to infection, so that a positive smear or culture may be difficult to achieve. In areas where sophisticated methods of diagnosis may be hard to come by, the simple procedure of simultaneously estimating the blood and cerebrospinal fluid (CSF) glucose levels may be helpful in distinguishing bacterial meningitis from viral meningitis. 74 proven cases of bacterial meningitis and aseptic meningitis were investigated prior to treatment. There were 36 cases of bacterial meningitis and 38 cases of aseptic meningitis. The CSF glucose/plasma glucose ratio was calculated for each patient. The cases were divided into two groups; Group A with CSF glucose/plasma glucose ratio of (0.38-2.0) and Group B with CSF glucose/plasma glucose ratio of (0.1-0.35). In Group A, two out of 59 cases died while in Group B, nine out of 15 died (p < 0.01). 44 out of 59 in Group A recovered fully while only two out of 15 in Group B were cured (p < 0.01). It was also found that 54.2% in Group A were admitted in deep coma compared with 86.7% in Group B (p < 0.05) and 25.4% in Group A were admitted with seizures while 66.7% in Group B had convulsion (p < 0.01). Hence, a low CSF glucose/plasma glucose ratio was associated with a poor outcome. The mechanisms responsible for these findings are discussed especially with reference to the blood-brain barrier (BBB).(ABSTRACT TRUNCATED AT 250 WORDS)
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The incidence of structural renal tract abnormalities in 109 children with documented congenital heart disease (CHD) was studied using real-time sonography. In these children, 11.9% had associated urologic anomalies, which included hydronephrosis, duplication, ectopia, agenesis, and dysplasia of kidneys. Children with associated extracardiac anomalies had a significantly higher incidence of renal tract anomalies (39.1%) compared to those with isolated CHD (4.7%). Therefore, sonographic screening of the renal tract should be performed routinely in patients with CHD, especially in those with multiple congenital defects.
Two hundred and eighteen patients with acute gastro-enteritis (GE) and 67 controls (patients admitted during the period of study for illness other than (GE) were included in this study. Their stool samples were subjected to the following tests to detect the presence of rotavirus: enzyme-linked immunosorbent assay (ELISA), latex agglutination and electron microscopy. Samples positive by any one or more of the above methods were considered positive for rotavirus and were subjected to polyacrylamide gel electrophoresis of viral RNA. Rotavirus was detected in 59 (27.1%) of the 218 GE samples and four (6%) of the control samples. ELISA was the most sensitive test and could detect viral antigen long after the other methods failed to do so.
A series of Chinese newborns of consecutive normal vaginal deliveries were investigated for the distribution of serum transferrin subtypes by polyacrylamide gel iso-electric focusing at pH 3.5-9.5. Newborns whose mothers had a history of previous spontaneous abortion (n = 189) had a significantly higher frequency of the C2 variant and the C2 gene compared to those (n = 864) without a history of spontaneous abortion. There was no significant difference in the frequency of transferrin alleles between newborns with normal and low birth weight (n = 147).
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A case of eosinophilic meningitis in a young boy from Indonesia is reported. Clinically, he had a subacute meningitis with eosinophilic pleocytosis in the cerebrospinal fluid. The clinical and laboratory findings strongly suggest Angiostrongylus cantonensis as the aetiologic agent although the parasite was not found. The other most likely causes in the region are also considered and the life-cycle of Angiostrongylus cantonensis and the epidemiology of its infection are briefly reviewed.
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A new method using enzymatically amplified DNA sequences for the prenatal diagnosis of alpha-thalassaemia was evaluated. DNA from a foetus at risk for alpha(0)-thalassaemia was analysed to detect the presence of alpha-globin genes. The procedure involved amplification of a 136-base-pair (bp) region of the alpha-globin gene complex between the psi alpha and alpha 2 region. Amplification was performed using a pair of oligonucleotide primers and a heat stable DNA polymerase which allowed repeated cycles of DNA synthesis at 72 degrees C. A 136 bp product was detected by gel electrophoresis indicating the foetus was not positive for Bart's hydrops foetalis. The result was confirmed using the gene mapping technique. Prenatal diagnosis of alpha-thalassaemia by DNA amplification offers two advantages over the gene mapping technique since radionucleotides are not used and results can be obtained in 3 days.
Forty-eight children with suspected isolated pulmonary valvar stenosis were evaluated clinically and echocardiographically between January 1987 and December 1988. Fourteen patients with significant transpulmonary peak systolic pressure gradient greater than 30 mmHg on continuous-wave Doppler interrogation were subjected to right heart catheterisation. Percutaneous transluminal balloon valvuloplasty was performed in 11 of these patients with peak systolic pressure gradient than 40 mmHg across the pulmonary valve at cardiac catheterisation. Satisfactory reduction of systolic right ventricular pressure (110 +/- 43 to 46 +/- 17 mmHg, p less than 0.001) and peak systolic pressure gradient across pulmonary valve (92 +/- 44 to 27 +/- 16 mmHg, p less than 0.001), were achieved in all cases. The reduction of peak systolic pressure gradient (64 +/- 37 mmHg, range = 29-158 mmHg), was positively correlated with the initial right ventricular systolic pressure (r = 0.92, p less than 0.0002). There was no significant complication in this series and all patients were discharged the day after the procedure. Percutaneous transluminal balloon valvuloplasty is effective and safe. It should be the treatment of choice for significant valvar pulmonary stenosis in children.
This study describes the occurrence of anaemia (haemoglobin level below 12.5 g/dl) amongst National Service (NS) Registrants in Singapore. A total of 32,320 subjects were screened and the prevalence of anaemia was 0.51%. The Indians had the highest prevalence compared to the other races. The commonest cause of anaemia was haemoglobinopathy. Though alpha-thalassaemia is the commonest form of haemoglobinopathy in Singapore, we found that beta-thalassaemia was the commonest form of haemoglobinopathy in anaemic subjects. In the Chinese and Malay races, the commonest cause of anaemia was haemoglobinopathy. For the Indian and Other races, it was iron deficiency. Of all the subjects with haemoglobinopathy, 86.2% did not have a family history of anaemia. Iron deficiency occurred in about a third of the anaemic subjects. The prevalence was highest in the low income groups and the Indian and Other races. But with higher standards of living, blood loss may be a more important cause for iron deficiency than poor nutrition.
The HLA-A, -B antigens in 159 Chinese patients with Graves' disease were compared with those of 330 controls. The HLA-DR antigens of the patients were also studied in 100 normals. Analysis of the increased prevalence of Bw46, according to the sex and age of onset of disease of the patients, showed that the strong association of Bw46 resided with male patients (n = 58), Pc = 0.0000052, RR = 4.2. Although the frequency of Bw46 was also increased in female patients (n = 101), it was statistically not significant. For the DR9 antigens, the strong association with male patients was also observed, viz. Pc = 0.019, RR = 3.2. Males also had higher risks of Graves' disease if they had homozygous Bw46 at presentation. Further analysis by age of onset of disease revealed the segregation of significant association with Bw46 for the males at 1-19 yr, Pc = 0.0011, RR = 17.5 HLA associations (Bw46 and DR9) with Graves' disease in Chinese are observed primarily in males, especially those whose known ages of onset of the disease are between 1-19 yr (Bw46).
First-trimester prenatal diagnosis by DNA analysis was carried out for seven pregnancies at risk for homozygous alpha 0-thalassaemia. Transabdominal placental biopsy was carried out at 10-12 weeks' gestation. The presence of alpha-globin genes in the fetal DNA was determined by restriction endonuclease mapping and hybridization with cloned alpha-globin probe. Homozygous alpha 0-thalassaemia was detected in two fetuses and the pregnancies were interrupted. Alpha 0-thalassaemia in both cases was confirmed by electrophoresis of the umbilical cord blood where only haemoglobin Bart's was detected. The remaining five fetuses were diagnosed as normal or as possessing alpha-thalassaemia-1 trait and the pregnancies are being carried to term. The use of DNA analysis in prenatal diagnosis of fetuses at risk for homozygous alpha 0-thalassaemia enables detection of the haemoglobinopathy at 10 weeks' gestation.
Fetal abnormalities may be strongly inherited e.g. in the Mendelian diseases. Some of the abnormalities are due to detectable chromosome anomalies, while the majority of fetal abnormalities arise as a result of the interaction of polygenes and environmental factors. The process of fetal abnormality diagnosis depends on a careful taking of the history and its evaluation. The clinical examination of the fetus by real time ultrasound, if relevant and finally special investigations which are to some extent invasive such as chorionic villus sampling, amniocentesis and fetal blood sampling. The fetal tissue so obtained may be assessed for their genetic structure by DNA recombinant methods, or the disease may be diagnosed by analysis of the genic products. The commoner hereditary diseases probing fetal abnormalities in S.E. Asia are described and the diagnosis of these diseases discussed. Fetal diagnosis, at the moment, is still labour intensive and costly and must be applied in a discriminate fashion.
The history of postgraduate medical education in Singapore is described culminating in the award of the local higher qualification - the master of Medicine, equivalent to the higher qualifications awarded by the Royal Colleges in UK and Australasia. Initially, in 1971, the M.Med. in Internal Medicine, Paediatrics, Obstetrics and Gynaecology and Surgery and the M.Sc. in Public Health and Occupational Medicine were awarded and since then, the M.Med. in Anaesthesia and Psychiatry were also awarded. At present, the courses leading to the Examinations are well attended not only by local postgraduates but also by doctors from overseas. The number of postgraduates certified over the various period in Singapore is documented.