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Biomedical subjects

T T Tan

Publications and source records attributed to T T Tan.

At least 19 recordsLinked to original sources

Plasma renin and aldosterone in thyroid diseases.

The effect of thyroid hormones on the renin-angiotensin-aldosterone system has not been fully resolved. Highly specific immunoassays for measurement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultrasensitive TSH enables a direct and more accurate measurement of these hormones. We investigated the relationship between plasma renin, aldosterone and thyroid hormones in the basal state and after intravenous frusemide. This is a cross-sectional study involving 37 patients with thyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH levels, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11 with hypothyroidism. Basal plasma renin was significantly higher in thyrotoxicosis (63.4 +/- 9.8 microU/ml, mean +/- SEM) compared to euthyroid (32.7 +/- 4.4 microU/ml) and hypothyroid (26.7 +/- 9.8 microU/ml). Basal plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 microU/ml) was significantly higher than hypothyroid (p = 0.02). Basal plasma aldosterones were not significantly different except for suppressed TSH (157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were significantly increased in all groups. Plasma renin was highly correlated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), fT4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correlated poorly to serum aldosterone (r = 0.212, p < 0.03). This study clearly showed that regulation of renin was mainly influenced by fT3, and that aldosterone response to frusemide was blunted in thyrotoxicosis despite normal electrolytes.

Aldosterone

The surgical treatment of adrenal diseases.

Between January 1978 to December 1993, 130 cases of adrenal diseases were diagnosed and surgically treated at the National University of Malaysia. They were 58 cases (44.6%) of Conn's syndrome, 40 cases (30.7%) of Cushing's syndrome, 20 cases (15.3%) of phaeochromocytoma and 12 cases (9.2%) of adrenocortical carcinoma (ACC). The commonest cause of Conn's syndrome was an adenoma (96.5%) which affected the left gland four times more than the right gland. Cushing's syndrome was caused by adrenocortical adenoma (32.5%), diffuse bilateral adrenal hyperplasia (40.0%), pigmented macronodular hyperplasia (20.0%) and adrenal carcinoma (7.5%). Twenty-five percent of the phaeochromocytomas were extraadrenal in origin arising mainly from the abdominal sympathetic chain. More than 50% of ACCs were non-functioning tumours. Fifty percent of the patients with ACC had inoperable tumours. The prognosis was poor even with adjuvant chemoradiotherapy. The main surgical approach was the anterior transabdominal route. There was no operative mortality or morbidity in all operated cases.

Adrenal Gland Diseases

State of mutational alterations of p53 and retinoblastoma susceptibility genes in papillomavirus-negative small cell cervical carcinomas.

Genetic aberrations were examined to assess the possible roles that p53 and retinoblastoma susceptibility genes might have played in the development of small cell cervical carcinomas. Cervical cancer tissues from 12 patients with small cell cervical carcinoma that were free of human papillomavirus were analyzed. The presence of mutational alterations were examined by polymerase chain reaction-single-strand conformation polymorphism and by direct DNA sequencing. None of 12 small cell cervical carcinomas were found to contain mutations in regions of p53 and retinoblastoma susceptibility genes that were functionally important and where most mutations, in human tumors have been found. Furthermore, there was no evidence indicative of loss of heterozygosity of chromosome region 17p13 (in which p53 is located) in these tumors. These data seem to suggest that whereas mutant type of p53 and retinoblastoma susceptibility genes may exhibit "oncogenic" function in many human tumors, mutational inactivation of these genes may not be an important feature in the carcinogenic development of human papillomavirus-negative small cell cervical carcinomas.

Base Sequence

Multiple endocrine neoplasia type 1 (MEN1) in two Asian families.

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disease characterized by neoplasia of the parathyroid glands, anterior pituitary and endocrine pancreas, is rarely reported in Asian populations. The MEN1 gene, mapped to chromosome 11q13 but yet to be cloned, has been found to be homogeneous in Caucasian populations through linkage analysis. Here, two previously unreported Asian kindreds with MEN1 are described; linkage analysis using microsatellite polymorphic markers in the MEN1 region was carried out. The first kindred, of Mongolian-Chinese origin, is a multigeneration family with over 150 living members, eight of whom are affected to date. The second kindred is of Chinese origin consisting of four affected members. Linkage to chromosome 11q13 was confirmed in both kindreds, supporting evidence for genetic homogeneity. A recombination in the larger kindred localizes the gene distal to marker D11S956, consistent with its placement from previous studies. We also show that it is feasible to use these markers for predictive testing, as four gene carriers were detected in 13 family members with unknown disease status in the first kindred.

Adult

ANF(1-28) is a potent suppressor of pro-opiomelanocortin (POMC) mRNA but a weak inhibitor of beta EP-LI release from AtT-20 cells.

Controversies remain whether atrial natriuretic factor (ANF) may play a role in modulating the release of POMC derived peptides from pituitary corticotrophs. Employing AtT-20 mouse pituitary tumour cells, we report here the effects of rat ANF(1-28) and sodium nitroprusside (SNP), both of which augment cellular levels of cGMP through activating particulate and soluble guanylyl cyclases respectively, on the expression of POMC mRNA abundance. Furthermore, the cellular contents and secretion of (beta endorphin-like immunoreactivity) beta EP-LI from these cultures were also examined. Whereas the abundance of POMC mRNA was found to be markedly suppressed following 4h of incubation with rANP(1-28) (0.01 to 1 microM), SNP (0.1 to 10 microM) and dibutyryl-cGMP (1 to 100 microM) in a dose related manner, only a modest reduction in the release and cell contents of beta EP-LI was found in some of these cultures. It is also of interest to note that in all the cases examined, the inhibitory effect was associated with a significant suppression of cAMP levels in the cultures. Taken together, our present findings suggest that ANF may play a more important role in suppressing the production than the release of POMC related peptides from AtT-20 cells. Thus, it raises the possibility that hypothalamic ANF may likewise modulate the function of the pituitary-adrenal axis through exerting a greater effect on inhibiting the production than the secretion of pituitary ACTH.

Animals

Thyroid function and pubertal development in malnutrition.

Thyroid function and pubertal development of aborigines (Orang Asli) and Malays at different socioeconomic strata were assessed among 1136 subjects aged 7 years and above. Anthropometric measurements, goitre and pubertal staging were done. Serum thyroxine (T4), triiodothyronine (T3) and growth hormone were measured using radioimmunoassays (RIA) and serum thyroid stimulating hormone (TSH) by immunoradiometric assays (IRMA). It was found that serum T3 in children was significantly higher in Malays from rural areas, girls and children aged less than 13 years. However, in adults, T3 was significantly associated with anthropometric indices. On the contrary, serum T4 levels were higher among children from urban areas. In adults, serum T4 levels were significantly related to nutritional status and they increased according to the levels of social development, being lowest in remote areas and highest in urban areas. However, serum TSH levels were significantly higher in Orang Asli at all ages and among malnourished children. By using multiple regression, apart from age, gender and ethnicity, nutritional status was a significant predictor for T3 levels in children and adults. Presence of goitre was an important factor which determined the T4 levels in children and adults after controlling for other factors. It was also a predictor for TSH levels in children but not in adults. Fasting serum growth hormone (GH) levels were significantly higher among less privileged groups and decreased according to social development. Serum growth hormone was negatively correlated with anthropometric indices and had a significant association with malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

31,781 cases of non-surgical female sterilisation with quinacrine pellets in Vietnam.

The quinacrine method of non-surgical female sterilisation involves transcervical intrauterine insertion of 252 mg quinacrine as pellets during the proliferative phase of the menstrual cycle; the drug causes inflammation and fibrosis of the proximal fallopian tube. We have carried out a field trial of 31,781 cases in twenty-four provinces of Vietnam from Jan 2, 1989, until October, 1992. There were 818 pregnancies after the procedure, of which 80 were carried to term. Some women received only one dose of quinacrine; the majority received two doses with an interval of one month. Cumulative life-table pregnancy rates per 100 women at 1 year (for studies of at least 50 cases followed for 12 months) were 2.63 (SE 0.17) among 9461 women who received two doses and 5.15 (0.48) among 2225 who received only one dose. Failure rates (pregnancies) were strongly affected by the skill of the doctor or midwife. There were no deaths and only 8 serious complications were reported (0.03%); by contrast, in a similar series of women undergoing surgical sterilisation, 30 deaths and between 540 and 1812 serious complications would be expected. All reported side-effects were minor and of short duration. There were 19 ectopic pregnancies and the incidence was 0.89 per 1000 woman-years of use. There was one birth defect (anencephaly), in a fetus conceived 2.5 months after quinacrine insertions; however, we believe it is not related to the procedure. An estimated 242 maternal deaths will be averted by these 31,781 sterilizations. This method is safe and acceptably effective for female sterilisation.

Adult

Primary infertility in a phenotypic male with 46XX chromosomal constitution.

The case of a 32 year old male with normal male adrenarchal hair pattern, bilateral gynaecomastia, a small phallus, hypospadias and bilateral poorly developed testes presenting with primary infertility secondary to azoospermia and a pelvic cyst is described. Repeated chromosomal analysis showed 46XX chromosomal constitution. Laparotomy revealed a simple cyst between the urinary bladder and the rectum. XX male syndrome is a rare cause of male infertility. The majority of cases is due to interchange of a fragment of the short arm of the Y chromosome containing the region that encodes the testes determining factor with the X chromosome. The presence of a simple cyst in the anatomical location of the uterus to our knowledge has not been reported in the literature.

Adult

Prevalence of NIDDM and impaired glucose tolerance in aborigines and Malays in Malaysia and their relationship to sociodemographic, health, and nutritional factors.

OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in different ethnic groups living in the same physical environment and to find their relationship to nutritional status and dietary intake. RESEARCH DESIGN AND METHODS: The study was conducted among Malays and Orang Asli in six rural and urban locations in Malaysia. OGTTs were performed on 706 adult subjects > or = 18 yr of age. WHO criteria were used for diagnosing diabetes mellitus and IGT. RESULTS: The overall prevalence of diabetes mellitus and IGT among Orang Asli was 0.3 and 4.4% compared with 4.7 and 11.3%, respectively, among Malays. This increased prevalence of glucose intolerance among Malays was associated with higher levels of social development. Among rural Malays, the crude prevalence of diabetes in a traditional village was 2.8% and in the land scheme was 6.7%, whereas urban Malays had a prevalence of 8.2%. In contrast, the prevalence of IGT (10.5-14.8%) was higher among rural Malays, compared with 9.6% among urban Malays. Ethnic group, > or = 40 yr of age, an income > M$250, fewer daily activity, and obesity were associated with a higher prevalence of diabetes. CONCLUSIONS: Diabetes mellitus and IGT, which were more common among Malays than Orang Asli, were associated with more affluent life-styles and modernization.

Adult

Usefulness and limitations of thyrotropin measurements as a first-line test for follow-up of Graves' patients.

We evaluated the usefulness of sensitive thyrotrophin hormone (TSH) measurements in determining the thyroid status in the follow-up of Graves' patients undergoing medical treatment with thionamides. Out of a total of 186 serum samples tested, TSH levels were suppressed in 123 (66.1%), normal in 32 (17.2%) and elevated in 31 (16.7%) cases. Total T4, or T3 or both were elevated only in 97 (74.8%) cases of TSH-suppressed patients, indicating that TSH is less discriminatory as a first-line test for patients under treatment due to the hypothalamic-pituitary lag period. No comparisons with free T4 or free T3 were done in this study. Both total T4 (120 +/- 28 nmol/l) and TBII (23 +/- 21%) levels were significantly greater (p < 0.02) in the euthyroid group with suppressed TSH. This may suggest that persistence of a thyrotoxic state may still be present.

Adolescent

Effect of gender and age on fasting serum growth hormone levels in normal subjects.

Fasting growth hormone (GH) level is an important reference level in dynamic tests of GH secretion. Other studies have demonstrated sex and age variation in the rate of GH secretion. We analysed fasting serum samples from 377 normal subjects (193 males and 184 females, age range 6 to 81 years old), using our in-house enzyme immunoassay. We found sex differences in fasting GH levels to be only significant in the prepubertal children (Tanner stage I), being higher in girls than in age-matched boys (p < 0.05). Both sexes showed age-dependent changes in fasting GH levels (p < 0.001); highest levels were achieved at puberty and subsequently declined with advancing age. Hence, the physiological sex difference and age-dependency in GH secretion can also be demonstrated in single fasting samples.

Adolescent

Low incidence of hypercalcaemia in tuberculosis in Malaysia.

In this study we examined the incidence of hypercalcaemia among patients with tuberculosis in Malaysia. Serum calcium concentration and other calcium metabolism parameters were studied in 43 newly diagnosed tuberculous patients from the Kuala Lumpur General Hospital and the National Tuberculosis Centre. Forty-four patients admitted to the medical wards of the General Hospital, Kuala Lumpur were recruited as controls. The incidence of hypercalcaemia was found to be only 1/43 (2.3%). There was no significant difference between the mean serum calcium and other calcium metabolism parameters between the patients and the controls. Despite earlier reported incidences of 30-50%, this study showed that hypercalcaemia in tuberculosis is uncommon in Malaysia.

Adult

Thyroid hormones and autoantibodies in pregnant patients with thyroid diseases.

Serum concentrations of thyroid stimulating hormone (TSH) and thyroid autoantibodies in pregnant patients with thyroid disease at various stages of pregnancy were determined by in-house ELISAs. In normal pregnancy, serum TSH levels were significantly elevated (p < 0.05) from 13 weeks of gestation. The normal reference ranges for TSH for the second (0.6-5.0 mIU/l) and third trimester (0.6-5.6 mIU/l) were significantly higher (p < 0.05; p < 0.01 respectively) compared to 0.4-4.5 mIU/l for the first trimester. In pregnant thyroid patients, serum TSH levels correlated highly (p < 0.001) to T4 (r = 0.740), FT4I (r = 0.683) and MicAb (microsomal antibodies) (r = 0.825) but weaker (p < 0.01) to T3 (r = -0.512), FT3I (r = 0.520) and TgAb (thyroglobulin antibodies) (r = 0.618). Thus, measurement of TSH with the highly sensitive ELISA (enzyme linked immunosorbent assay) would form a useful first line test for thyroid dysfunction in pregnancy while measurement of thyroid autoantibodies would aid in the diagnosis of autoimmune hypothyroidism.

Adult

Serum thyroid stimulating hormone (TSH) in malnutrition: preliminary results.

This is a report of a cross sectional study involving 3 groups of children, moderately malnourished (BMI < 15), mildly malnourished (BMI 15-18) and well nourished (BMI > 18) to determine the differences in hormonal and biochemical parameters between the groups. The children were of age range from 7-17 years old. The children were from the same area with exposure to the same food, drinking water and environment. There were significant differences in the nutritional indices between the three groups. No differences were observed in levels of triiodothyronine (T3), thyroxine (T4) and T3:T4 ratio. Significant difference however was found in the TSH levels using highly sensitive IRMA TSH assays. Moderately malnourished children had higher TSH levels (p < 0.05) compared to mildly malnourished and well-nourished children. No difference was found between the mildly malnourished and well-nourished groups. There were no significant differences in serum cortisols done at similar times, fasting growth hormone and calcium. Serum alanine transminase (ALT) however was higher in moderately malnourished than in well-nourished children. Thus using highly sensitive IRMA TSH assays, we were able to detect differences in TSH levels even though T3, T4 and T3:T4 ratio, cortisol, growth hormone and calcium were normal, implying in moderately malnourished children, a higher TSH drive to maintain euthyroid state.

Adolescent

Primary hyperparathyroidism--a surgical review of 12 cases.

Twelve cases of primary hyperparathyroidism operated by the Universiti Kebangsaan Malaysia Surgical Team from 1978 to 1989 were reviewed. There was a preponderance of Indian females in this series. The majority of the cases presented late and with complications. Renal calculi and bone disease were the commonest complications noted. Of the 12 patients, 9 had single parathyroid adenoma of which 4 were ectopically located, and 2 had hyperplasia of the parathyroids. These were all successfully operated. The remaining patient had 2 failed neck explorations. Failure at initial exploration was due to ectopic location of the glands. Meticulous surgical technique, knowledge of the anatomical variations of location of the parathyroid glands and availability of frozen section facility are essential for successful outcome.

Adenoma

Hypercalcemia in a patient with tuberculous mediastinal lymphadenopathy.

We describe the case of a 48 year old Indian female with hypercalcemia due to tuberculosis. She presented with symptoms of hypercalcemia and chest radiographs showed bilateral hilar lymphadenopathy with normal lung fields. The diagnosis of tuberculosis was made histologically from biopsy of the enlarged hilar nodes. Her hypercalcemia resolved following one month of anti-tuberculous treatment. The prevalence of hypercalcemia in tuberculosis has been reported to be high in western series. There is, however, a paucity of local data on the subject. The presence of 1-alpha-hydroxylase-like activity in pulmonary alveolar macrophages with resulting increased formation of active vitamin D metabolites is the postulated mechanism of tuberculosis associated hypercalcemia.

Female