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Childhood thyrotoxicosis is not an uncommon illness, but there is a considerable relapse rate in these patients on medical treatment. An attempt is made in this study to identify those markers that are predictive of a tendency to relapse in childhood thyrotoxicosis. A total of 32 patients with Graves disease were included in the study. Several features were correlated with a tendency to relapse. Of these features, sex, family history, and antibody status were not significantly correlated to relapse. However, of 17 patients with goiter size two times normal or larger, 16 relapsed in comparison with seven relapses of 15 patients with goiter size less than two times normal (p = 0.0039). Of eight patients without ophthalmopathy, only two relapsed, while 21 patients of 24 patients with ophthalmopathy, relapsed (p = 0.002). Of 13 patients with serum thyroxine levels below 20 mcg/dl, six relapsed; of the 19 patients with serum thyroxine levels above 20 mcg/dl, 17 relapsed (p = 0.039). Among 24 patients with a previous relapse, only one achieved a remission with a second course of treatment. The remaining 23 patients had recurrent relapses. Hence it was found that goiter size, presence of ophthalmopathy, total thyroxine levels, and a previous relapse correlated significantly with a further relapse.

Fifty-nine children with steroid-responsive nephrotic syndrome (SRNS), ages ranging from two to 18 years, were studied to determine the incidence of atopy, using both clinical and immunological parameters. Children with SRNS were found to have a significantly higher incidence of atopy both in themselves (z = 2.51, p less than 0.05) and their first-degree relatives (z = 2.34, p less than 0.05). The proportion of children with raised serum IgE levels (60%) and the geometric mean (631 U/ml) in SRNS children were significantly higher than control values, 14.5% and 136 U/ml, respectively (p less than 0.0001). Intra-group comparison showed that children with multiple relapses (more than two relapses) had higher incidence of skin test positivity to house dust mite (p less than 0.01) and to two or more antigens (p less than 0.05). Our data would suggest that atopy may be a predisposing factor in local children with SRNS.

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).

A 10 year retrospective analysis of the clinical features and survival of 24 Singapore children with systemic lupus erythematosus was made. The female to male sex ratio was 11:1. The median age at diagnosis was 9.3 years (range: 3.5-17.6 years), and the median duration of follow-up was 3.6 years (range: 3 months-10 years). The common modes of presentation were prolonged fever and malar rash (both 46%). Renal involvement (71%) was frequent. There were six deaths, three from chronic renal failure, two from infection, and one from carditis. The overall survival at 5 years was 0.800 (s.e.m. = 0.090), and at 10 years 0.698 (s.e.m. = 0.103). The survival for lupus nephritis was 0.727 at 5 years (s.e.m. = 0.116), and 0.586 at 10 years (s.e.m. = 0.130). Although the 5 year survival rate is comparable with other series, there were more deaths after the first 5 years, and morbidity from the disease as well as from therapy was considerable.

Blood glucose and serum immunoreactive insulin levels were measured following an oral glucose load in 20 unrelated children with multiple transfused thalassaemia. Results suggest that even though overt diabetes and glucose intolerance are uncommon before the age of 13 years, the presence of insulin resistance is evident, especially in those who have been splenectomized.

The factors influencing the development of electroencephalographic (EEG) abnormalities and hypertensive encephalopathy were studied in 31 children with acute glomerulonephritis and hypertension. Based on the degree of background slowing on the EEG, they were divided into 2 groups: group 1 had a percent EEG power for frequencies 1-4 Hz of less than or equal to 6.45 (upper 95th percentile confidence limit in 31 age- and sex-matched controls), while group 2 had values greater than 6.45. Six of 16 children in group 2 developed grand mal convulsions and had prolonged changes in the level of consciousness. There were no significant differences between the mean levels of peak blood pressures (systolic, diastolic and mean), degree of fluid overload, and fractional sodium excretion in the 2 groups. However, group 2 had significantly higher mean blood urea and creatinine levels (p less than 0.02 and p less than 0.03 respectively). These findings suggest that hypertension alone does not predict the subsequent development of EEG abnormalities and hypertensive encephalopathy. The concomitant presence of azotaemia may render the child more susceptible to cerebral autoregulatory dysfunction, resulting in hypertensive encephalopathy.

We studied the distribution of HLA-A, B, and DR and MT1, MT2, MT3 genotypes in all 20 Chinese children with insulin-dependent diabetes mellitus (IDDM) attending the four government pediatric units in Singapore. We found an increase in HLA BW22 but the corrected probability value was not statistically significant. AW33 and B17 were observed in 50% and 55% of IDDM children, respectively, compared with 11% and 13% of normal controls, respectively. The values for AW33 were as follows: corrected P = 0.00094 and relative risk (RR) = 8.17; for B17 they were corrected P = 0.001 and RR = 7.55. In addition, the frequency of DR3 was 50% in IDDM children compared with 14% of normal controls (corrected P = 0.0019, RR = 6.20). AW33, B17, and DR3 are in linkage disequilibrium in our normal Chinese population. All ten patients who were positive for DR3 also had B17. The frequency of DR4 was not increased, and there were no protection IDDM related antigens found. These differences compared with the results in Western populations may contribute to the relative rarity of IDDM among Chinese children.

A retrospective analysis of the clinical features and outcome of 39 Chinese children with Kawasaki syndrome was made. The mean age of onset was 2.7 years (range: 0.2-13 years). The male:female ratio was 2.9:1. One child presented with nephrotic syndrome. This renal manifestation has not been described in Kawasaki disease. Ten (32%) out of 31 patients were found to have coronary aneurysms by cross-sectional echocardiography. The only significant risk factor detected in this group of patients was anaemia (P less than 0.007). There was one (2.5%) death from acute myocardial infarction and the rest of the patients were clinically well with a mean follow-up period of 1 year (mean: 5-40 days). This study indicates that there is a high incidence of coronary aneurysm complicating Kawasaki syndrome in Chinese comparable with that reported in Japanese children.

Renal manifestations in Kawasaki disease are rare, and nephrotic syndrome in this disorder has not been described previously. We report a 3 month old infant with Kawasaki disease, presenting with nephrotic syndrome which responded to steroid therapy. The patient, however, developed coronary aneurysms and died of acute myocardial infarction.

We studied the distribution of HLA-DR and MT1, MT2, MT3 genotypes in 23 Chinese children with insulin-dependent diabetes mellitus (IDDM). The frequency of DR3 was 48% in IDDM children compared to 14% of normal controls (corrected p = 0.0098, RR = 5.70). The frequency of DR4 was not increased. These differences when compared with the results of Western populations may contribute to the relative rarity of IDDM among Chinese children.

Nineteen children with insulin-dependent diabetes mellitus were assessed for microangiopathic complications in the University Department of Paediatrics, Singapore. Of 17 who underwent nerve conduction studies, all showed impaired nerve conduction velocities, with more sensory than motor nerve involvement. The extent of neuropathy was significantly correlated with the duration of disease. Of five children who showed significant proteinuria, two had impaired creatinine clearance, two had cataract formation, and two retinopathy, in one background and in one proliferative. Our study showed a high prevalence of microangiopathic complications in these diabetic children and it is hoped that improved blood glucose control, with the aid of home blood glucose monitoring, may minimize or arrest the microangiopathic complications.

The distinguishing feature of the allergic person is his or her elevation of serum IgE. This propensity to develop a sustained IgE response is determined genetically. The biologic effects of IgE are mediated via Fc receptors (Fc epsilon R) present on mast cells and basophils (Fc epsilon R type 1) and subpopulations of monocytes, macrophages, eosinophils, and platelets (Fc epsilon R type 2). Interaction of allergen with IgE on these cells results in receptor "bridging" and the release of histamine and other inflammatory mediators. Fc epsilon R type 2 on lymphocytes and monocytes are upregulated in atopic disease and may play a role in the allergic inflammatory reaction. The activation of B cells to synthesize IgE requires several stages (see Fig. 2). T cells play an important role in the regulation of IgE synthesis. In vitro activation of resting B cells to synthesize IgE requires direct cellular interaction with T cells or the presence of IL4 for activation. The latter effect is inhibited by alpha-interferon. Preactivated B cells are influenced in an isotype-specific manner by T-cell-derived IgE binding factors (IgE-BF), which may act as IgE-potentiating or IgE-suppressive factors, depending on their degree of glycosylation. The regulation of IgE synthesis is an important area of investigation. It provides us with an understanding of the basis of the human allergic response and ultimately may provide the basis for novel strategies in the treatment of allergic diseases.

HLA in 12 unrelated Chinese paediatric patients with insulin dependent diabetes mellitus (IDDM) were found to have an increased frequency of BW22, B17 and AW33. BW22 was observed in 5/12 (41.7%) of IDDM patients compared to 40/330 normal unrelated Chinese controls (p less than 0.005, rr = 5.2). AW33 and B17 were observed in 6/12 (50.0%) and 7/12 (58.3%) of IDDM patients respectively, compared to 36/330 and 46/330 in the normal controls respectively (AW33: corrected p less than 0.0026, RR = 8.2, B17: corrected p less than 0.0026, rr = 8.6). HLA B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of this study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states.

Singaporean Chinese IDDM was significantly associated with AW33, BW58, DR3 and DR4. AW33, BW58 and DR3 being in strong linkage disequilibrium among the Chinese, were associated most strongly with IDDM whose onset was less than or equal to 10 years. The strength of this association showed a significant inverse relationship with age of onset. The frequency of DR4 was significantly elevated on in the 11-20 year IDDM group. The importance of DR3 in Chinese IDDM was also reflected in the observations of joint occurrences of DR antigens. In the less than or equal to 10 years subgroup, the significant association were either DR3/DRW9, DR3/DR4 or DR3/BLANK. In the 11-20 years subgroup, DR4 appeared to be more important and DR4/DR3 and DR4/BLANK were strongly associated with IDDM in this subgroup.

Nineteen children with insulin-dependent diabetes mellitus in the University Department of Paediatrics were assessed for complications of diabetes. 36.8% showed marked growth stunting, and half of the patients who attained puberty had a delayed onset of puberty. 42% showed limited joint mobility. Almost all the patients developed hypertrophic lipodystrophy while only 5 patients developed reversible lipoatrophy. Abnormal nerve conduction velocities were found in all 17 patients tested, with more of sensory nerve involvement. A significant correlation was found between duration of disease and the extent of neuropathy. Evidence of nephropathy was found in 5 patients, 2 of whom showed impaired renal function. One patient had background retinopathy, another had proliferative retinopathy and 2 patients developed cataracts. The high prevalence of microangiopathic complications in these children is probably related to their previous poor diabetic control and it is hoped that with home blood glucose monitoring to improve their control, these complications may be arrested or minimized.