Endogenous estradiol in elderly individuals: cognitive and noncognitive associations.

OBJECTIVE: To investigate an association between endogenous estradiol (E(2)) levels and cognition and behavior in elderly individuals. PATIENTS: We studied 135 community-based men and women aged 52 to 85 years in urban Bangkok, Thailand; 72 had dementia and 63 did not. MATERIALS AND METHODS: Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria after appropriate investigations. Blood samples for assay were collected in the morning after 6 hours of fasting. Levels of E(2) were measured by radioimmunoassay (double antibody technique). The Thai version of the Mini-Mental State Examination was used to assess cognition; the Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms; and the Functional Assessment Questionnaire was used to assess instrumental activities of daily living. RESULTS: There was no correlation between age and level of E(2) in either men or women. Individuals with lower estrogen levels had more behavioral disturbances (men: r = -0.467, n = 45; P =.001; women: r = -0.384, n = 90; P<.001) and worse cognition (men: r = 0.316, n = 45; P =.03; women: r = 0.243, n = 90; P =.02) and function (men: r = -0.417, n = 45; P =.004; women: r = -0.437, n = 90; P<.001). The threshold level of endogenous E(2) in elderly individuals for the risk of developing dementia was less than 15 pg/mL (<55 pmol/L) in men and less than 1 pg/mL (<4 pmol/L) in women. CONCLUSION: Lower E(2) levels are correlated with poor cognitive, behavioral, and functional status in older individuals.

Risk factors for dementia and impaired cognitive status in Thai elderly.

OBJECTIVE: To examine the association of physical and biochemical risk factors for dementia and cognitive status in an urban population based Thai elderly. MATERIAL AND METHOD: This study was part of an integrated health research project from 1997 to 1999. Subjects were 550 elders who lived in a community within 10 km from Siriraj Hospital, Bangkok, Thailand. They were 55 years and older. Thai mental state examination (TMSE) was applied to all subjects as the screening test for dementia. Those who scored less than or equal to 24 out of 30 were categorised as having cognitive impairment or suspected of having dementia, and they were then examined in detail for the diagnosis of dementia using the DSM IV criteria. Blood pressure and body weight were recorded. Blood was drawn for biochemical and haematological analysis including the serology for syphilis and thyroid function test as the basic screening investigation for dementia. Descriptive data, expressed as the mean, standard deviation, Pearson Chi square and ANOVA tests were analysed with SPSS 9.0 in the study. RESULTS: Of 550 subjects, 261 (47.45%) were classified as the normal subjects group, 49 (8.91%) as the cognitively impaired group, and 240 (43.82%) as the dementia group. 377 subjects (68.55%) were female and the distribution of females in each subgroup ranged from 63.3-75.5 per cent. The mean age in the normal group was 67.47 +/- 6.05 years, the cognitively impaired group was 70.14 years and the dementia group was 69.63 +/- 9.21 years. Systolic blood pressure (BP), diastolic BP, serum cholesterol, SGOT, GGT, serum albumin, haemoglobin, MCHC, neutrophil counts and weight were statistically significant factors that were associated with cognitive status. Both systolic and diastolic BP were high in the higher cognitive status group. Serum albumin, serum cholesterol levels and body weight were also higher in the high cognitive status group. CONCLUSION: This study demonstrated an association between nutritional status and cognitive status in Thai elderly. Poorer nutritional factor in lower cognitive function individuals might explain a lower of both systolic and diastolic BP in the dementia subjects compared to the healthy subjects.

Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight.

OBJECTIVE: Hyperthyroidism in pregnancy occurs with a prevalence of 0.05--0.2% and has been shown to affect neonatal outcomes. Fetal weight increases markedly during the third trimester of pregnancy. This retrospective study was performed to examine the effect of maternal hyperthyroidism during late pregnancy on neonatal birth weight (NBW). DESIGN: Medical and obstetric records of 293 pregnant women with present and past history of hyperthyroidism were retrospectively reviewed. PATIENTS: There were 188 records of 181 patients with adequate data for inclusion in the analysis. The patients were divided into two groups according to the maternal thyroid function during the third trimester of pregnancy: hyperthyroidism (HT; 35 cases) and euthyroidism (ET; 153 cases). MEASUREMENTS: Maternal thyroid function tests were periodically evaluated before and during the third trimester of pregnancy. Neonatal thyroid function tests and birth weight of the newborn infants were also assessed. RESULTS: There was no significant difference of maternal age between HT and ET groups mean +/- SD (27.6 +/- 5.5 vs. 29.2 +/- 5.4 years). The NBW of the HT group was not significantly different from that of the ET group (2880 +/- 590 vs. 3019 +/- 426 g). However, the prevalence of infants with low birth weight (LBW) defined as NBW of lower than 2500 g in HT group was 22.9% which was significantly higher than the 9.8% in the ET group (P = 0.039, OR = 2.7, 95%CI = 1.1--7.1) and 9.7% of infants born to healthy mothers at Siriraj Hospital (control group) between 1991 and 1995 (P = 0.01, OR = 2.7, 95%CI = 1.3--6.1). The 90% CI for the true difference between the prevalence of LBW infants born to ET and HT mothers was 0.7--25.4. There was no significant difference in the prevalence of LBW infants in ET and control groups. Multiple logistic regression analyses showed that maternal hyperthyroidism during the third trimester of pregnancy was an independent factor associated with increased prevalence of LBW infants (P = 0.037, OR = 4.1, 95%CI = 1.1--15.0). CONCLUSIONS: Maternal hyperthyroidism during the third trimester of pregnancy independently increases the risk of low birth weight by 4.1-fold. Appropriate management of hyperthyroidism throughout pregnancy is essential in the prevention of this undesirable neonatal outcome.

Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism.

OBJECTIVE: Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease. SUBJECTS: Seventy-one patients with newly diagnosed Graves' disease were studied. METHODS AND MEASUREMENTS: Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the MMI group but not in the PTU group. CONCLUSIONS: During 12-weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.

Regional patterns in the incidence of aplastic anemia in Thailand. The Aplastic Anemia Study Group.

The annual incidence of aplastic anemia has been determined in a rigorous and standardized epidemiologic study conducted in Thailand. A total of 374 cases were identified over a period of 3-6 years in three geographically defined and distinct regions of the country; Bangkok, Khonkaen in the northeast, and Songkla in the south. The incidence was 3.9 cases per million persons in Bangkok, 3.0 per million in Songkla, and 5.0 per million in Khonkaen. These rates are as high or higher than in any region of Europe or Israel as reported in the International Agranulocytosis and Aplastic Anemia Study, in which the methods and case definition were the same. Rates were stable over the course of the study. There were marked differences in incidence between northern and southern rural regions of Thailand, and among Bangkok suburbs. These differences, together with an unusual peak in the incidence among young people in Bangkok, suggest the possibility of occupational and environmental factors in the etiology of aplastic anemia.

Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Aplastic Anemia Study Group.

Agranulocytosis, a syndrome characterized by a marked reduction in circulating granulocytes, is strongly associated with medical drug use in Europe and the United States. Unregulated use of common pharmaceutical agents in developing countries has been suspected of causing large numbers of cases of agranulocytosis and deaths, especially among children. To elucidate the incidence and etiology of agranulocytosis in Thailand, a population-based case-control study of symptomatic agranulocytosis that resulted in hospital admission was conducted in Bangkok from 1990 to 1994. An attempt was also made to study the disease in Khonkaen (in northeastern Thailand) and Songkla (in southern Thailand), but there were insufficient cases in the latter regions, and the analysis was confined to subjects from Bangkok. In that region, the overall incidence of agranulocytosis was 0.8 per million per year; there were no deaths. As expected, the incidence was higher in females (0.9 per million), and it increased with age (4.3 per million beyond age 60). Among 25 cases and 529 controls the relative risk estimate for a combined category of all suspect drugs was 9.2 (95% confidence interval = 3.9-21), and the proportion of cases that could be attributed to drug use was 68%. For individual drugs and drug classes the data were sparse; within these limitations, the strongest association appeared to be with antithyroid drugs. One case and three controls were exposed to dipyrone, a drug known to cause agranulocytosis; with such scanty data the risk could not be evaluated. Exposure to pesticides or solvents was not associated with an increased risk. This is the first formal epidemiologic study of agranulocytosis in a developing country. As in the West, most cases are attributable to medical drug use. However, the incidence of agranulocytosis in Bangkok, and apparently, in Thailand as a whole, is unusually low, and the disease does not pose a public health risk.

Evaluation of the new fasting plasma glucose cutpoint of 7.0 mmol/l in detection of diabetes mellitus in the Thai population.

To determine whether a fasting plasma glucose (FPG) cutpoint of 7.0 mmol/l can be appropriately used for detection of diabetes mellitus (DM) in the Thai population, different FPG cutpoints were evaluated for their efficacy in the diagnosis of DM. A plasma glucose level of > or = 11.1 mmol/l at 2 h after a 75-g oral glucose tolerance test (OGTT) was used as the gold standard criterion for diagnosis of DM. OGTT was performed in 496 subjects who were at risk of developing diabetes. They were 120 males and 376 females, 14-76 years old (mean +/- S.D. = 45.0 +/- 12.2 years). Plasma glucose level was determined in NaF preserved plasma using the glucose oxidase method. Diagnosis of DM was made in 22.8% of cases by the gold standard criterion as compared to 4.2% by using FPG values of > or = 7.8 mmol/l. The sensitivity of the FPG cutpoint of 7.8 mmol/l was 18.6%. Diagnosis of DM using FPG > or = 7.0 mmol/l improved the sensitivity to 33.6% with a positive predictive value of 100% and highest Youden's index of 0.836. The receiver operating characteristic curve of FPG revealed the best cutpoint to lie between 5.6-6.0 mmol/l. A FPG cutpoint of < 6.0 mmol/l over-estimated the prevalence of diabetes. DM and impaired glucose tolerance were noted in 65.6 and 29.5% of the subjects who had FPG values between 6.0 and 6.9 mmol/l, respectively. We conclude that FPG cutpoint of 7.0 mmol/l is applicable to a high risk Thai population for detection of DM. OGTT is recommended for definitive determination of glucose tolerance status in those individuals with FPG values between 6.0 and 6.9 mmol/l.

Behavior in self-care of the foot and foot ulcers in Thai non-insulin dependent diabetes mellitus.

A cross sectional study was conducted to examine behavior in self-care of the foot and foot ulcers in Thai non-insulin dependent diabetic patients. Fifty-five patients with foot ulcers (ulcer group; 42 females and 13 males) and 110 patients without foot ulcers (control group; 83 females and 27 males) were evaluated for self foot-care behavior using a questionnaire consisting of questions about foot inspection, foot cleaning, nail-care, and the use of footwear which possessed a total score of 20. The results showed that a mean total self foot-care score of the ulcer group was significantly lower than that of the control group (14.50 +/- 3.35 vs 15.74 +/- 2.31; p < 0.01). The patients with foot ulcers had lower mean scores in all of the four self foot-care categories than did those without foot ulcers. However, only the difference in foot cleaning score was statistically significant (7.35 +/- 0.21 vs 7.88 +/- 0.11; p < 0.05). A univariate analysis has shown that the risk of developing foot ulcers was significantly associated with a total self foot-care score of less than 15 with an odd ratio of 2.6 and a 95 per cent confidence interval of 1.3-5.6. Regarding the behavior in self foot ulcer-care, 45.5 per cent of the diabetic patients with foot ulcers had neglected them and 54.5 per cent had inappropriately cared for their ulcers. In conclusion, Thai non-insulin dependent diabetic patients with foot ulcers understood less about self foot-care practice than did those without foot ulcers. Incorrect self foot-care behavior particularly foot cleaning is associated with an increased risk of foot ulceration. In addition, diabetic patients should be advised about the correct self-care of their feet and foot ulcers in order to prevent foot ulceration and its complications.

Low drug attributability of aplastic anemia in Thailand. The Aplastic Anemia Study Group.

From 1989 to 1994, a population-based, case-control study of aplastic anemia was conducted in Thailand, including the regions of Bangkok, Khonkaen in the northeast, and Songkla in the south. An annual incidence in Bangkok of 3.7 cases per million population, about twice as high as in Western countries, has been reported. To evaluate the etiologic role of drugs, 253 subjects were compared with 1,174 hospital controls. With multivariate adjustment for confounding, a significant association was identified for exposure 2 to 6 months before admission to thiazide diuretics (relative risk estimate 7.7; 1.5 to 40). There were crude associations with sulfonamides (relative risk estimate, 7.9; P = 0.004) and mebendazole (6.3; P = 0.03) (there were insufficient data for multivariate adjustment). Excess risks for the three drugs were in the range of 9 to 12 cases per million users. There was no significant association with chloramphenicol, although the multivariate relative-risk estimate was elevated (2.7; 0.7 to 10). Other drugs that have been reported to increase the risk of aplastic anemia, such as nonsteroidal anti-inflammatory drugs and anticonvulsants, were not commonly used. There were no associations with commonly used drugs, including benzodiazepines, antihistamines, oral contraceptives, and herbal preparations. For all associated drugs, the overall etiologic fraction (the proportion of cases attributable to an exposure) was 5%, compared with 25% in Europe and Israel. Drugs are uncommon causes of aplastic anemia in Thailand, and their use does not explain the relatively high incidence of the disease in that country.

Use of household pesticides and the risk of aplastic anaemia in Thailand. The Aplastic Anemia Study Group.

BACKGROUND: Aplastic anaemia is a severe blood dyscrasia that is more common in Thailand than in Western countries. Its a etiology remains poorly understood. METHODS: A case-control study was conducted in Bangkok and two rural regions of Thailand. The effect of household pesticides was evaluated among 253 incident cases of aplastic anaemia and 1174 hospital controls. RESULTS: A total of 54% of the cases and 61% of the controls were exposed 1-6 months previously. For most individual household pesticides and for groups classified according to chemical type (organophosphates, pyrethrins, and organochlorines), the relative risk (RR) estimates approximated 1.0; upper 95% confidence limits were below 2.0 for many comparisons. A significant association was observed for exposure to combination products containing dichlorvos and propoxur, with an overall RR estimate of 1.7 (95% confidence interval [CI]: 1.1-2.6); the estimate for regular use was 1.6 (95% CI: 0.9-2.9). CONCLUSIONS: The absence of a higher risk for the regular use of dichlorvos/propoxur reduces the credibility of the apparent association, which could well have been an artefact of multiple comparisons. We conclude that most household pesticides used in Thailand do not appear to increase the risk of aplastic anaemia.

Efficacy of using basal plasma adrenocorticotropic hormone-radioimmunoassay (ACTH-RIA) level in the identification of the cause of Cushing's syndrome.

Basal (8.00 a.m.) plasma ACTH-radioimmunoassay (ACTH-RIA) levels were studied in 32 cases of endogenous Cushing's syndrome (17 Cushing's disease, 13 adrenocortical tumors, and 2 ectopic ACTH syndrome) and 11 normal volunteers. There were overlaps in the ranges of plasma ACTH-RIA levels among patients with Cushing's disease, adrenocortical tumors, and normal volunteers but not ectopic ACTH syndrome. By using different plasma ACTH-RIA levels as cut-off points in differentiating ACTH-dependent from ACTH-independent Cushing's syndrome, the level of 30 pg/ml had the highest diagnostic efficacy with a 94.7 per cent sensitivity, a 84.6 per cent specificity and a 90.6 per cent diagnostic accuracy.

Antitriiodothyronine antibody in patient with Hashimoto's thyroiditis.

We described a 44-year-old female patient with a history of goiter for 2 months. Physical examination revealed a diffusely enlarged thyroid gland weighing 40 g firm to hard in consistency. She was clinically euthyroid and had neither ophthalmopathy nor dermopathy. Serum thyroid hormone levels revealed total T4 (RIA) of 4.8 micrograms/dL (normal, 4-11 micrograms/dL), total T3 (RIA) of above 600 ng/dL (70-175 ng/dL), and TSH (IRMA) of 54 mU/L (0.3-6 mU/L). Antithyroglobulin and antiperoxidase antibody titers were 1:5,120 and 1:409,260, respectively. Because of the discrepancy between the patient's clinical status and laboratory values, assay for thyroid hormone autoantibodies (THAA) was done and subsequently demonstrated antitriiodothyronine antibody with percentage of precipitation by polyethylene of 98.4 per cent (normal range, 3.06 +/- 8.58%). In conclusion, THAA should be suspected in patients whose clinical status is incoherent with the thyroid function test.

Factors associated with diabetic foot ulceration in Thailand: a case-control study.

A case-control study was conducted to determine factors involved in foot ulceration in Thai non-insulin-dependent (Type 2) diabetic patients. Fifty-five patients with foot ulcers (42 females and 13 males) and 110 patients without foot ulcers (83 females and 27 males) were evaluated for 26 factors possibly associated with foot ulceration. The results showed that diabetic patients with foot ulcers had significantly lower diabetic knowledge and foot-care practice scores; poorer glycaemic control, renal function, and visual function, and higher prevalence of retinopathy and peripheral neuropathy than diabetic patients without foot ulcers, whereas there were no differences in peripheral vascular status between both groups, each having a low prevalence. Multiple logistic regression analyses indicated that the risk of developing foot ulcers was associated with only three factors which were peripheral nerve status as determined by somatosensory evoked potentials (OR = 1.67; 95% CI 0.31 -8.97), visual acuity (OR = 0.223 per unit decrease in decimal visual acuity; 95% CI = 0.005, 0.39) and fasting plasma glucose level (OR = 1.01 per mmol l-1 increase; 95% CI = 1.00, 1.02). We conclude that peripheral neuropathy, visual impairment, and poor glycaemic control, but not peripheral vascular insufficiency, are the major independent risk factors associated with foot ulceration in Thai diabetic patients.

Primary thyroid carcinoma and thyrotoxicosis.

A 60-year-old man noticed rapid enlargement of a long-standing thyroid goitre, with dysphagia and difficulty in breathing. Thyrotoxicosis was diagnosed. Chest X-ray revealed multiple pulmonary metastases. He underwent near-total thyroidectomy. The histopathology revealed an undifferentiated thyroid carcinoma with some areas of papillary carcinoma and its follicular variant. Postoperative 131I total body scan showed residual thyroid tissue in the neck and one functioning metastasis in the right rib, posteriorly. The patient's condition deteriorated rapidly and he died from pneumonia. The autopsy showed widespread metastases of undifferentiated thyroid carcinoma. Only the right rib contained the follicular variant of papillary carcinoma.

A study of cell-mediated immune response to pancreatic antigens in patients with fibrocalculous pancreatic diabetes.

In order to investigate whether there was any association between autoimmunity to pancreatic antigens with FCPD as well as IDDM, cell-mediated immune response to pancreatic antigens was studied by lymphoproliferation assay in 7 FCPD, 17 IDDM, 33 NIDDM patients and 102 normal controls. Optimal pancreatic antigen concentrations used were 100, 150 and 200 micrograms/ml. Positive results were considered for each concentration of antigens tested, at stimulation index (SI) > (mean +/- 2 SD) SI obtained from normal age-matched controls with the use of the corresponding concentration of antigen. The one who gave positive result with any of these optimal antigen concentrations was considered to be the responder to pancreatic antigens. With this criterion, the responders were found to be 3/7 (42.9%) FCPD, 6/17 (35.3%) IDDM and 6/33 (18.2%) NIDDM patients; while there were 11 of all 102 (10.8%) normal controls.

Nocturnal 8 mg dexamethasone suppression test: a practical and accurate test for identification of the cause of endogenous Cushing's syndrome.

The efficacy of a nocturnal 8 mg dexamethasone suppression test (nocturnal DST) was compared with that of the standard high-dose dexamethasone suppression test (standard DST) in identifying the cause of endogenous Cushing's syndrome in 10 proven cases with Cushing's disease, 20 with adrenal tumours, and one with ectopic ACTH syndrome. The nocturnal test compared serum cortisol concentration at 8 am before and after administration of a single dose of 8 mg dexamethasone at 11 pm. Suppression of serum cortisol level to < 50% of the baseline value indicated a diagnosis of Cushing's disease, while a lack of suppression below that limit indicated one of the other two causes of Cushing's syndrome: glucocorticoid-secreting adrenal tumour or ectopic ACTH syndrome. The nocturnal DST had a sensitivity of 90%, a specificity of 100%, an accuracy of 96.8%, a positive predictive value of 100%, and a negative predictive value of 95.5%. These values are comparable to the efficacy of the standard DST in distinguishing Cushing's disease from glucocorticoid-secreting adrenocortical tumour or ectopic ACTH syndrome. Furthermore, this rapid test does not require hospitalisation or urine collection like the standard DST. The nocturnal 8 mg dexamethasone suppression test is practical, fairly reliable, and an effective alternative with which to identify the cause of endogenous Cushing's syndrome.

Effects of alpha-glucosidase inhibitor (acarbose) combined with sulfonylurea or sulfonylurea and metformin in treatment of non-insulin-dependent diabetes mellitus.

The effects of alpha-glucosidase inhibitor (acarbose) were studied in 36 patients with non-insulin-dependent diabetes mellitus (NIDDM), aged 34-67 years with a mean duration of diabetes of 8.8 +/- 0.9 years. They were poorly controlled with diet plus sulfonylurea alone or plus sulfonylurea combined with metformin drugs. Acarbose, 100 mg three times daily, was additionally given to these patients for six months. Results showed small but significant decreases (P < 0.001) in postprandial blood glucose level. Glycosylated hemoglobin level was lowered significantly (P < 0.001) and was normalised (level of < 8%) in 17 per cent of the patients. Fasting serum triglycerides level decreased significantly (P < 0.01), whereas, no significant changes in serum total cholesterol and HDL cholesterol levels were seen. Body weight also decreased significantly (P < 0.001) at the end of acarbose trial. Flatulence was the major side effect of acarbose found in 42 per cent of the patients but it was well-tolerated and may be transient and self-limited. We concluded that the addition of acarbose to the therapeutic regimens of diet therapy plus sulfonylurea or plus sulfonylurea combined with metformin drugs led to significant improvement of glycemic control. Acarbose may be a safe and valuable adjunct to diet and sulfonylurea and metformin treatments in obese, poorly-controlled patients with NIDDM.

An association of aplastic anaemia in Thailand with low socioeconomic status. Aplastic Anemia Study Group.

The relationship of socioeconomic status to the risk of aplastic anaemia was evaluated in a case-control study conducted in Bangkok and two rural regions of Thailand (Khonkaen and Songkla). Among 152 cases and 921 controls there were significant trends of increasing risk with decreasing years of education (P = 0.01) and total household income (P = 0.0001), after control for confounding. The relative risk estimate for those with monthly incomes of < 1500 baht (about $60 U.S.) was 3.9 (95% confidence interval 2.1-7.3) compared to those with monthly incomes of at least 5000 baht (about $200). The pattern of increasing risk with decreasing income was observed in all three regions, with significant trends in Bangkok (P = 0.004) and Khonkaen (P = 0.003). This finding may partly explain the high incidence of aplastic anaemia in Thailand. Low socioeconomic status may be a surrogate for one or more environmental factors that could cause aplastic anaemia, such as infectious pathogens or toxic exposures.

Differing frequency of autoantibodies to glutamic acid decarboxylase among Koreans, Thais, and Australians with diabetes mellitus.

The wide racial-geographic differences in the incidence and prevalence of insulin-dependent diabetes mellitus (IDDM) between Europids and Asian populations prompted us to compare frequencies of positivity of autoantibody to glutamic acid decarboxylase (GAD). The patients with IDDM included 41 Koreans, 30 Thais, and 45 Australian Europids; the Koreans included 14 cases regarded as atypical IDDM by reason of a delayed requirement for insulin treatment. Autoantibodies were measured by radioimmunoprecipitation using iodinated purified porcine brain GAD. The frequency of positive tests for anti-GAD of 30% (8/27) for Koreans and 51% (20/39) for Thais was significantly lower than the 84% (38/45) for Australian Europids, even after stratifying by age of onset. Correspondingly, the mean levels of anti-GAD among seropositive cases were significantly lower for Koreans than for Australian Europids. In contrast to Thais and Australians, more than half the Koreans were diagnosed at age > 20 years, but there was no significant difference in positivity for anti-GAD between those over or under the age of 20 at diagnosis. The different frequency of positivity in tests for anti-GAD among Koreans, Thais, and Australian Europids with IDDM suggests that there is a greater etiologic heterogeneity of IDDM among Asian than Europid populations, in whom autoimmune destruction of pancreatic islets predominates.

HLA class II polymorphism in Thai insulin-dependent diabetes mellitus.

Fifty-seven Thai IDDM patients were studied for HLA class I by LCT and HLA class II by LCT and PCR-RFLP. It was found that DRB1*0301, DR3, DQB1*0201, DRB3*0202, DQA1*0501 and DQ2 were significantly increased with R.R. = 10.0, 6.6, 4.2, 3.7, 3.5 and 3.2 and Pc < 0.005, 0.001, 0.01, 0.005, 0.01 and 0.005, respectively. In contrast, DQA1*0101, DRB3*0301, DR5 and DQ1 were significantly decreased with R.R. = 0.2, 0.2, 0.3 and 0.5 and Pc < 0.01, 0.05, 0.01 and 0.05, respectively. The primary factor for IDDM susceptibility is probably DRB1. The homozygous Asp57/Asp57 DQB1 genotype appears to determine resistance to IDDM while Arg52-DQA1, non-Asp57-DQB1 haplotype confers susceptibility to IDDM. The common haplotypes in Thai IDDM cases were DRB1*0301, DRB3*0202, DQA1*0501, DQB1*0201, DPB1*0401 and DRB1*0405, DQA1*0301, DQB1*0402 (or 0401 or 0302), DPB1*0401 (or 0301 or 1501). The less common haplotypes were DRB1*0406, DQA1*0301, DPB1*0302, DPB1*0501 and DRB1*1202, DRB1*0301, DQA1*0601, DQB1*0301, DPB1*0501. DR3 was increased in both gender groups with early onset (< 10 years) regardless of a family history of DM. However, DR3/DR4 genotype was increased only in female patients with a family history of DM and early onset. In conclusion, DRB1, DRB3, DQA1 and DQB1, but not DPB1 are involved in the occurrence of IDDM. The cooperation of HLA class II and X-chromosome may contribute to the development of IDDM in addition to other factors such as other genetic (chromosomes 11, 19, 14, 7), immunologic and environmental factors which require further study.