Biomedical subjects
Publications and source records attributed to H K Yap.
A 9-year-old girl was diagnosed to have renal failure. However, her family has not been compliant with medical treatment and opted for traditional therapy instead. She was admitted in an ill state with fluid overload. What is the ECG diagnosis?
This study was undertaken to determine whether tailoring the dialysis prescription in Asian children on nightly intermittent peritoneal dialysis (NIPD), without adding high-dose therapy for cost-savings purposes, was able to achieve dialysis adequacy and improvement in nutrition. Eight children (age range: 5.5-20 years) on NIPD for a mean of 2.1 +/- 0.6 years, were studied at baseline and at 3 months and 9 months after their dialysis dose was tailored. Dialysis adequacy was measured by weekly Kt/Vurea and creatinine clearance (CCr). Fat-free mass (FFM) and percent body fat (%FAT) as measured by bioelectrical impedance, together with anthropometric measurements, serum total protein, and albumin, were used as indicators of nutrition. After the dialysis prescription was tailored, the mean weekly Kt/Vurea increased from 1.89 +/- 0.35 to 2.12 +/- 0.54 at 9 months, and total CCr increased from 36.4 +/- 11.51 L/1.73 m2 to 48.30 +/- 14.30 L/1.73 m2. The increase occurred despite a decline in residual renal function and was attributable to significant improvements in the peritoneal clearances of urea and creatinine (p < 0.05). The mid arm muscle circumference (MAMC) increased significantly (p = 0.006), while FFM increased from 25.68 +/- 7.92 kg to 26.95 +/- 9.83 kg, and %FAT decreased from 21.56% +/- 8.41% to 18.66% +/- 8.16%. The increase in FFM correlated significantly with a decrease in serum creatinine (r = -0.94, p = 0.005). In conclusion, tailoring the dialysis prescription in NIPD, without adding high-dose therapy, resulted in a trend of improvement in dialysis adequacy and some nutritional parameters.
The effect of growth hormone (GH) on subclinical disease activity in a 15-year-old boy with previously quiescent lupus nephritis and chronic renal failure is described. Institution of supraphysiological doses of GH resulted in a rise in erythrocyte sedimentation rate, decrease in serum complement, rise in anti-DNA antibody titers, and increase in T-cell activation markers, all of which improved following cessation of GH treatment.
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OBJECTIVE: To determine the efficacy and safety of oral desmopressin (DDAVP) treatment in Asian children with nocturnal enuresis. METHODOLOGY: This was a multicentre randomized placebo-controlled double-blind cross-over study. Patients were randomized to either active treatment with oral 400 mg DDAVP or placebo, with a 2-week medication-free period between the cross-over. Children with primary monosymptomatic nocturnal enuresis, aged between 7 and 18 years, with a minimum frequency of wetting of 6 nights or more during a 2-week observation period were recruited. Efficacy was measured by reduction in the average number of wet nights per week. RESULTS: Of the 37 children initially recruited, the outcomes for 34 children were included in the final cross-over analysis, as they had complete data for both the treatment periods. Statistical analysis by ANOVA showed that there was no significant difference between the medication-free period and the pretreatment period. However, the average number of wet nights per week for the DDAVP treatment period (2.5+/-2.7) was significantly lower than that of the placebo treatment period (4.5+/-2.1) (P < 0.0001). In terms of the safety profile, there was no significant change in bodyweight, blood pressure, serum sodium, serum osmolality, and urine osmolality following DDAVP treatment. CONCLUSION: Oral DDAVP is a safe and efficacious drug for the short-term treatment of children with primary nocturnal enuresis.
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Rapid advances in critical care technology and rising cost of medical care have spurred the development of outcome analysis including mortality risk prediction. The main objective of this study was to assess the risk factors contributing to mortality in our paediatric intensive care unit (PICU). This is a cohort study, consisting of consecutive admissions to the PICU from 1 January to 31 December 1997. The factors studied included multi-organ dysfunction syndrome (MODS), Pediatric Risk of Mortality III (PRISM III) scores in the first 24 hours (PRISM III-24), mechanical ventilation, renal replacement therapy, age, and diagnosis-related groups. Univariate and multivariate statistical methods were used. Univariate analysis showed that need for mechanical ventilation, renal replacement therapy, presence of MODS involving 3 or more organs and PRISM III-24 scores were significantly associated with outcome (P < 0.0005). Relative risk of mortality in the presence of MODS and PRISM III-24 scores > or = 8 were 11.3 (95% CI: 3.3 to 38.3) and 15.8 (95% CI: 2.0 to 127.8), respectively. Using Cox Proportional Hazards model, the relative risk of mortality for any new admission could be calculated by the equation RR = e0.1032 x P, where P = PRISM III-24 scores.
OBJECTIVES: To study the efficacy and safety of 1 year of growth hormone (GH) therapy in children with steroid-dependent nephrotic syndrome. STUDY DESIGN: A prospective pilot, open study in which GH (mean dose 0.32 mg/kg per week) was administered for 1 year to 8 children with steroid-dependent nephrotic syndrome requiring prednisolone (mean dose 0.46 mg/kg per day) to maintain remission. Steroid dependence was defined as recurrence of proteinuria within 2 weeks of discontinuation of prednisolone, or when the dose was lowered below a critical level. At entry, all patients had been steroid dependent for at least 1 year. Anthropometric and bone mineral density measurements after treatment were compared with 1-year pretreatment data. RESULTS: Pretreatment mean (+/-SD) chronologic age was 12.6 (+/-3.1) years, with a mean bone age of 9.1 (+/-2.0) years, with delayed puberty in five patients. The mean height velocity increased from 3.7 (+/-1.4) to 9.4 (+/-2.1) cm/yr after 1 year of treatment (p < 0.05). The mean height standard deviation score increased from -1.4 (+/-1.6) to -0.3 (+/-1.1), (p < 0.05). In the spine, the mean bone mineral density increased from 0.50 to 0.64 gm/cm2 (p < 0.05), and in the femoral neck, from 0.55 to 0.64 gm/cm2 (p < 0.05) after 1 year of treatment. Mean lean body mass increased from 58.1% to 62.6% (p < 0.01). There were no significant changes in creatinine clearance, fasting glucose, fasting insulin, or glycosylated hemoglobin levels. The mean bone age increased to 11.4 (+/-2.4) years, and pubertal stage advanced in 2 patients. CONCLUSIONS: One year of GH therapy is effective in improving the height standard deviation score, height velocity, bone mineral density, and lean body mass of children with steroid-dependent nephrotic syndrome. There were no significant adverse effects. However, the bone age accelerated at a greater pace than the height age, and further studies are required to define the role of GH therapy in steroid-dependent nephrotic syndrome.
Primary monosymptomatic nocturnal enuresis (PMNE) is often not openly discussed in Asian societies. We report the parental view of PMNE in Singapore, its impact on patients and their families and the traditional beliefs and its influence on subsequent management. A screening questionnaire was used in evaluating 30 children enrolled in a clinical trial on the use of oral Desmopressin for the treatment of PMNE. Primary monosymptomatic nocturnal enuresis was familial in 56.7% of patients. Fifty per cent of them were previously unevaluated. Earlier remedial attempts included bedtime fluid restriction and voiding (100%), incentive measures (43.3%), traditional practices (26.7%), punishment (20%), drugs (16.7%), psychotherapy (100%) and bladder training (3.3%). Perceived causes of PMNE were maturational delay (50%), deep sleep (50%), familial (43.3%), behavioural problems (43.3%) and excessive fluid intake (26.7%). Reasons for seeking treatment included restricted outdoor activities (90%), parental fatigue (86.7%), disrupted sleep for the household (46.7%) and fear of underlying pathology (26.7%). Perceived adverse effects on patients included social stigma (83.3%), disrupted sleep (33.3%) and impaired school performance (13.3%). Primary monosymptomatic nocturnal enuresis can thus be a chronic distressing problem in Asian communities.
A retrospective study of all children who had undergone renal transplantation at the National University Hospital was undertaken in order to investigate the types and frequency of infections in paediatric renal transplant recipients. A total of 13 children ranging in age from 3 to 17 years were transplanted over a 7-year period from 1989 to 1996. The mean follow-up period was 40.5 months. Ten patients (77%) had at least one episode of infection post-transplant, 70% of which occurred within the first 6 months post-transplant. These infections included urinary infections (8), disseminated cytomegalovirus (CMV) disease (4), Pneumocystis carinii pneumonia (1) and mycoplasma pneumonia (1). Urinary tract infections were significantly associated with the presence of ureteral stents. CMV disease was significantly associated with the use of mycophenolic acid in the early post-transplant period. Infection therefore continues to be a major cause of morbidity in paediatric renal transplant recipients.
Flow cytometric analysis of lymphocyte subsets were evaluated in 391 healthy Asian subjects ranging in age from birth to 40 years. Lymphocyte subsets were analysed using specific monoclonal antibodies: CD20 (B cells), CD3 and CD2 (T cells), CD16 and CD56+ (NK cells), CD4/CD3+ (helper-inducer T cells), CD8/ CD3+ (suppressor/cytotoxic T cells), HLA-DR expression on CD3 and CD25 (Tac) on CD3. The total white cell count, absolute lymphocyte counts, and B cell percentages peaked in infancy and declined steadily with age. Absolute counts of each subset, which were derived from absolute lymphocyte counts, also followed this trend. Increases with age were seen in the NK, T cell (CD2, CD3), and CD8 percentages. Males tended to have higher NK and CD8 percentages than females, and, conversely, females had higher CD3 and CD4 percentages than males. Comparison of our results with studies involving Caucasian subjects indicated higher NK percentages in our Asian population and lower CD4 absolute counts in the males of our population. These results indicate the presence of age, sex, and probable racial differences in lymphocyte subset expression. Our results may serve as reference standards for the Asian population.
UNLABELLED: The first live-attenuated Oka strain varicella vaccines needed to be stored at -20 degrees C. Reformulation of this vaccine by SmithKline Beecham Biologicals has provided a vaccine shelf life of up to 2 years when stored at +4 degrees C to +8 degrees C. In this study the immunogenicity and reactogenicity of two different production lots of this reformulated vaccine at two different titres each, which corresponded to the release and expected expiry titres, were evaluated. A double-blind randomised clinical trial was conducted in healthy children aged from 9 to 24 months. Immunogenicity was assessed by the measurement of varicella specific antibodies in paired serum samples taken before and from 35 to 63 days post vaccination. Reactogenicity was assessed by the evaluation of any untoward reactions occurring up to 42 days post vaccination. In order to assess protective efficacy, parents of these subjects were contacted approximately 6 months after completion of the trial. One hundred and ninety-one subjects were recruited into the study. Of the 181 initially seronegative subjects who completed the trial according to the protocol, 179 showed seroconversion (98.9%). Reactions to the vaccine were minor and observed in 46/191 (24%) of subjects. Rashes were present in 19, fever in 22, and both fever and rash in 5. Rashes were mainly maculo-papular in nature but were vesicular in 6. Febrile reactions were shortlived. After a 6-month follow up period, attenuated varicella with minor clinical symptoms was diagnosed in 6/52 vaccinees who had close contact with natural varicella (attack rate = 11.5%). CONCLUSION: This reformulated vaccine was well tolerated, highly immunogenic and provided protection against varicella. In increased stability allowing refrigerator storage makes it a good candidate for mass vaccination programmes.
Inflammatory response plays an important role in the pathogenesis of cerebral injury in bacterial meningitis. In this study, we evaluated the cytokine levels of interleukin 1-beta (IL1 beta), tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) in the cerebrospinal fluid (CSF), and determined their correlation with acute clinical complications and with changes in CSF biochemistry. Interleukin 6, TNF alpha and IL1 beta were present in 9/9, 3/9 and 4/9 patients, respectively. The CSFs with detectable TNF alpha or IL1 beta had higher levels of IL6 (p < 0.02), protein (NS) and lower glucose levels (p < 0.02), compared with those in which TNF alpha and IL1 beta were absent. Tumour necrosis factor alpha and IL1 beta levels also correlated with the presence of prolonged fever, fits, spasticity and death (logTNF alpha: r = 0.70, p < 0.05; logIL1 beta: r = 0.62, p = 0.08). The cytokine levels reflect the degree of inflammatory response and are positively correlated with the severity of acute clinical complications. Modulation of this inflammatory response in bacterial meningitis may improve its morbidity and mortality.
Restriction fragment length polymorphism (RFLP) of the T cell receptor beta-chain gene was studied in two groups of Chinese thyrotoxic patients, those with thyrotoxic hypokaleamic periodic paralysis (THPP) and those with Graves' Disease (GD). DNA digested with restriction enzymes Bgl II, Bam HI, Eco RI, Pvu II and Taq I were hybridized to a 770 bp TcR beta cDNA probe containing the joining (J) and constant (C) region segments. The TcR beta/Bgl II polymorphism of 9.2 kb and 10 kb fragments were observed in THPP, GD and normal controls. The genotype frequencies of this polymorphism, however, did not differ between patients (THPP or GD) and controls. These results, therefore, do not support the presence of an association between the TCR beta/Bgl II RFLP and THPP nor with GD susceptibility. Finally, restriction analysis of DNA from our patients and normal controls using enzymes Bam HI, Eco RI, Pvu II and Taq I with the T cell receptor beta-chain gene did not show polymorphisms, and were therefore not informative.
Two gene sequences specific for Mycobacterium tuberculosis were evaluated for the diagnosis of pulmonary tuberculous (PTB) in pleural fluid (PF), bronchoalveolar lavage fluid (BAL) and sputum (Sp). The 240 bp sequence (nts 460-700) coding for the MPB 64 protein coding gene and the 123 bp IS6110 insertion element present in multiple copies in the mycobacterial genome were amplified using the polymerase chain reaction. Fifty-nine clinical specimens were studied. The diagnosis of PTB was confirmed by positive M. tuberculosis cultures in 14 specimens, and by the presence of characteristic histological features of granuloma and Langerhan's giant cells on pleural biopsy in 3 PF specimens through cultures for M. tuberculosis were negative. The remaining 42 specimens were obtained from patient's with non-tuberculosis pulmonary infections or malignancy, and these served as negative controls. Our results showed that the IS6110 insertion element and MPB 64 gene sequence were detected in all 14 culture positive PTB cases, although detection of the latter sequence required both DNA amplification and oligonucleotide hybridization. There was however one false positive specimen with the MPB 64 detection protocol. More importantly, both the MPB 64 sequence and IS6110 insertion element protocols were unable to detect M. tuberculosis DNA in the 3 PF samples diagnosed by histological characteristics on pleural biopsy and culture negative. We conclude that DNA amplification for M. tuberculosis-specific sequences is a useful method for rapid diagnosis of PTB in culture positive specimens. However, the false negative results with TB culture negative cases of tuberculosis pleurisy, limits its usefulness for the diagnosis of tuberculous pleurisy.
Selective immunoglobulin deficiencies have been shown to be associated with atopic disease. In this study, serum immunoglobulin (Ig) G, A, M, E and IgG subclasses of 92 Asian asthmatic children were studied and compared with those of age-matched controls. The children, aged between 0.7 and 17.4 years (mean age 7.5 years), were recruited from the National University Hospital, Singapore. The serum Ig levels were measured by enzyme-linked immunosorbent assay, except for IgE which was measured by the fluorescent allergosorbent test. As expected, serum total IgE levels were markedly higher in the asthmatic children than in the controls (geometric mean = 513 units/ml and 164 units/ml, respectively; p < 0.0001). Serum IgM levels were also slightly higher in the asthmatic patients than in the controls (geometric mean = 1.74 and 1.51 milligrams, respectively; p < 0.04). Mean serum IgG and A and IgG subclasses (1-4) levels in the asthmatics did not differ significantly from those in the controls. However, four asthmatic children were found to have selective IgA deficiency (serum IgA < 0.08 milligrams). None of the patients was found to be IgG subclass-deficient.
Chronic granulomatous disease (CGD) is an uncommon disorder affecting neutrophil function, and is characterized by recurrent and severe pyogenic infections. Associated autoimmune disorders, in particular lupus-like disorders, are found in carriers of X-linked CGD and in patients with both the X-linked and the autosomal recessive (AR) forms of the disease. We describe a girl with the AR form of CGD and with rheumatoid factor-positive polyarthritis resembling juvenile rheumatoid arthritis. This association has been reported previously only in a single case report of a patient with probable CGD. The present report further substantiates the association between autoimmune phenomena and CGD.
DNA amplification of three Mycobacterium tuberculosis-specific DNA sequences by the polymerase chain reaction (PCR) were evaluated as a means for rapid diagnosis of tuberculous meningitis (TBM). The DNA sequences amplified were a 123 bp region of the IS6110 insertion elements which occur in multiple copies in the mycobacterial genome, a 240 bp region (nts 460-700) from the MPB 64 protein coding gene, and the 383 bp region of the 65 kDa heat shock protein (HSP) antigen. Twenty-seven cerebrospinal fluid (CSF) specimens were studied. Six were obtained from patients with TBM diagnosed by culture (4/6) or by the patients' response to anti-tuberculous therapy (2/6). The remaining 21 specimens were obtained from patients with febrile seizures (3/21), aseptic meningitis (3/21), septic meningitis (14/21), and cryptococcal meningitis (1/21), and these served as negative controls. Our results indicate that although the protocols involving the 3 DNA sequences were able to detect TB DNA in the 6 TBM specimens, the main drawback was their extreme sensitivity, thus giving rise to false positive results. In particular, the repeat copy sequence, IS6110, and the 65 kDa HSP gave unacceptably large numbers of false positive results (62% and 33%, respectively).