This study was done to determine the anthropometric measurement patterns of Malay children from wealthy families in Malaysia and to make a comparison with NCHS reference population. A population of 900 children aged between 3-12 years old from Taman Tun Dr Ismail, Kuala Lumpur (TDI), were examined but only 871 of them were eligible for the study. Weight, height, mid-arm circumference and skin fold thickness were measured. The increment pattern of anthropometric measurements of TDI children was quite similar to NCHS except for having a lower median weight for age and height for age. There was prepubescent increase in skin folds thickness in both sexes, followed by a midpubescent decrease and a late pubescent increase. The study indicated that Malay children from a wealthy background have growth rates comparable to children in the West, hence NCHS percentile charts are suitable as a reference for comparing the nutritional status of Malay children in Malaysia.
1. The effects of alpha-tocopherol and gamma-tocotrienol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) activities in cultured hepatocytes prepared from rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated. 2. Both the alpha-tocopherol and gamma-tocotrienol treated hepatocytes showed significantly higher (P < 0.05) GST activities than untreated hepatocytes prepared from the carcinogen treated rats in the first 3 days of culture. Treatment with alpha-tocopherol and gamma-tocotrienol generally resulted in a tendency to increase the GST activities above that in the untreated hepatocytes. 3. Treatment with high doses (125-250 microM) of alpha-tocopherol and low doses (12.5-25 microM) of gamma-tocotrienol generally resulted in a significant reduction in gamma-GT activities at 1-3 days. gamma-GT activities are reduced as the dose of alpha-tocopherol and gamma-tocotrienol are increased.
It has been shown that lipid peroxidation product levels in the soleus muscles of rats fed palm olein were lower than in the soleus muscles of rats fed soya bean oil. A study was carried out to test our hypothesis that the lower level of lipid peroxidation products in the soleus muscle of palm olein-fed rats is due, at least partly, to the higher amount of vitamin E in their soleus muscles. Experimentally induced hyperthyroid rats were fed either ground rat chow or ground rat chow mixed with palm olein oil or soya bean oil for a period of 8 weeks. Euthyroid rats fed ground rat chow for a similar period served as controls. At the end of the 8-week period, the rats were sacrificed and the α-tocopherol and tocotrienol levels in their soleus muscles were measured using high pressure liquid chromatography. It was found that the levels of α-tocopherol (23.682 ± 0.363), α-tocotrienol (1.974 ± 0.040) and γ-tocotrienol (1.418 ± 0.054) in μg/g tissue wet weight in the soleus muscles of hyperthyroid rats fed palm olein oil were statistically significantly higher than those found in the soleus muscles of hyperthyroid rats fed soya bean oil, which were 14.299 ± 0.378, 0.053 ± 0.053 and 0.184 ± 0.120μg/g tissue wet weight, respectively. The result shows that the increased level of a-tocopherol and tocotrienols found in the soleus muscles of hyperthyroid rats fed palm olein oil is responsible, at least partly, for the lower amount of lipid peroxidation products in these muscles compared with the soleus muscles of hyperthyroid rats fed soya bean oil in our earlier study.
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.
Since conventional radioimmunoassays (RIA) for measurement of 17-hydroxyprogesterone (17-OHP) in serum samples require a laborious solvent extraction step, a direct and rapid in-house RIA was developed for early diagnosis and management of congenital adrenal hyperplasia (CAH). In-house rabbit anti-17-OHP antiserum, tritium labelled 17-OHP and dextran-coated charcoal were used in assay buffer with low pH 5.1 and preheated serum samples. Both inter- and intra-assay CVs were < 10% and the sensitivity was 1.2 nmol/l or 12 fmol/tube. Results from the direct assay correlated well with values from an extraction assay, r = 0.88 in samples from CAH patients, r = 0.85 in adults and children, 0.69 and 0.40 in term and preterm neonates respectively, 0.66 and 0.63 in luteal phase and third trimester pregnancy; p < 0.001 in all groups except p < 0.05 in preterm neonates. However, results from the direct assay were two to three times higher in serum samples from CAH patients, normal adults and children, but were five to seven times higher in pregnancy and term neonates and thirty times higher in preterm neonates. The markedly elevated levels measured by the direct assay are probably due to cross-reactivities with water-soluble steroid metabolites such as 17-hydroxypregnenolone sulphate and dehydroepiandrosterone sulphate (DHEAS). Although the direct assay is only useful as a screening test for preterm babies, it can be used for both diagnosis and monitoring of treatment of CAH in all other age groups.
Familial hypercholesterolaemia (FH) and Familial defective apolipoprotein B100 (FDB) are autosomal dominant inherited diseases of lipid metabolism caused by mutations in the low density lipoprotein (LDL) receptor and apolipoprotein B 100 genes. FH is clinically characterised by elevated concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), presence of xanthomata and premature atherosclerosis. Both conditions are associated with coronary artery disease but may be clinically indistinguishable. Seventy-two (72) FH patients were diagnosed based on the Simon Broome's criteria. Mutational screening was performed by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE). Positive mutations were subjected to DNA sequencing for confirmation of the mutation. We successfully amplified all exons in the LDL receptor and apo B100 genes. DGGE was performed in all exons of the LDL receptor (except for exons 4-3', 18 and promoter region) and apo B100 genes. We have identified four different mutations in the LDL receptor gene but no mutation was detected in the apo B 100 gene. The apo B100 gene mutation was not detected on DGGE screening as sequencing was not performed for negative cases on DGGE technique. To our knowledge, the C234S mutation (exon 5) is a novel mutation worldwide. The D69N mutation (exon 3) has been reported locally while the R385W (exon 9) and R716G (exon 15) mutations have not been reported locally. However, only 4 mutations have been identified among 14/72 patients (19.4%) in 39 FH families. Specificity (1-false positive) of this technique was 44.7% based on the fact that 42/76 (55.3%) samples with band shifts showed normal DNA sequencing results. A more sensitive method needs to be addressed in future studies in order to fully characterise the LDLR and apo B100 genes such as denaturing high performance liquid chromatography. In conclusion, we have developed the DNA analysis for FH patients using PCR-DGGE technique. DNA analysis plays an important role to characterise the type of mutations and forms an adjunct to clinical diagnosis.
This cross-sectional study compared serum lipoprotein (a) [Lp(a)] concentrations in type 1 and type 2 diabetic subjects and examined the determinants of Lp(a) concentrations in both types of diabetes. Serum Lp(a) was measured in 26 type 1 and 107 type 2 diabetic patients and 126 non-diabetic controls. HbA(1c), fasting lipids and urinary albumin were also assayed. Lp(a) concentrations were higher in both type 1 and type 2 diabetic patients compared with controls (P<0.0001 and P<0.0001, respectively), and were higher in type 1 than type 2 diabetic patients (P<0.05). Waist-hip ratio (WHR) was an independent determinant of Lp(a) concentrations in both type 1 and type 2 diabetes.
This study determined the effects of palm vitamin E (TRF) diet on the levels of blood glucose, glycated hemoglobin (gHb), serum advanced glycosylation end-products (AGE) and malondialdehyde (MDA) of diabetic Sprague-Dawley rats. The rats received either control (normal rat chow), TRF diet (normal chow fortified with TRF at 1 g/kg) or Vitamin C diet (vitamin E-deficient but contained vitamin C at 45 g/kg). The animals were maintained on the respective diet for 4 weeks, made diabetic with streptozotocin (STZ), then followed-up for a further 8 weeks. At week-4, mean serum AGE levels of rats given TRF diet (0.7 +/- 0.3 units/ml) were significantly lower than those of control or Vitamin C diet rats (p pounds 0.03). The levels increased after STZ and became comparable to the other groups. At week 12, blood glucose (20.9 +/- 6.9 mM) and gHb (10.0 +/- 1.6%) of rats on TRF diet remained significantly low compared to that of control or Vitamin C diet rats (p pounds 0.03). MDA however, was not affected and remained comparable between groups throughout the study. This study showed that TRF may be a useful antioxidant; effectively prevented increase in AGE in normal rats, and caused decrease in blood glucose and gHb in diabetic rats. Further studies are needed to elucidate the mechanisms of action of TRF.
1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.
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.
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)
Thyroid eye disease is autoimmune in nature and associated with Graves' Disease. Autoantibodies to the 64 kDa antigen in thyroid membranes cross-react to the 64 kDa proteins in human eye muscle membranes. Antibody dependent cell mediated cytotoxicity against eye muscle cells are also found in patients with thyroid eye disease. The purpose of this paper is to review the treatment available and to share the authors' experience using cyclosporin A. In the majority of cases, thyroid eye disease is mild, manifest only as bilateral or unilateral proptosis, with/without grittiness of the eyes. This is usually treated conservatively with eye drops. If proptosis is more severe and there is incomplete closure of eyelids, epiphora and conjunctival injection, then lateral tarrsorrhaphy is usually effective, combined with use of eye pads and eye drops. The problem of diplopia can be treated conservatively with special lenses, or with surgical correction of tethered muscles. However when proptosis is severe, with raised intraocular pressure, severe chemosis and danger of blindness, then the choice of therapy is controversial: rapid decompression by surgical means or use of high doses of prednisolone. Most prefer prednisolone therapy initially, surgical decompression if it fails. Various other methods have been tried, aimed at the immunological nature of the disease, namely plasmapheresis, radiotherapy and immunosuppressive drugs such as cyclosporin, with variable success. Our experience with cyclosporin had been mixed and inconclusive.
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.
In order to study the effect of levothyroxine in the treatment of endemic goitre, a longitudinal study was conducted among the Aborigines in Lanai Post and Sinderut Post, situated in an iodine-deficient area located in the district of Kuala Lipis, Pahang. All subjects in the treatment group (Lanai Post) were given 100 µg of levothyroxine per day and were followed for 1 1/2 years. A total of 311 subjects were examined at baseline, 323 on the first, 256 on the second, 239 on the third and 184 on the fourth visit following levothyroxine supplementation. Goitre prevalence, thyroid hormones, thyroid volume, nutritional status, urinary iodine levels, arterial blood pressure and mental performance were determined. Following the intervention, goitre prevalence was significantly reduced in the treatment group (baseline 42.8% vs final visit 13.0%, p<0.0001); however, no significant difference was noted in the control group. Total T4 levels were increased in the treatment group (p<0.0001), while a significant reduction was noted in the control group (p<0.0001). Thyroid-stimulating hormone levels increased significantly in the treatment group following 1 year of intervention, while no significant changes were observed in the control group. As for the thyroid volume, both groups showed a significant increment following the intervention (p<0.0001). With respect to the nutritional status, the treatment group showed a significant increase in body weight following the intervention (p<0.05). In addition, the mid-arm circumference and body mass index also increased after 1 year of intervention. However, the control group showed a reduction in the waist-hip ratio (p<0.0001). Although there was no statistical difference in the waist-hip ratio in the treatment group, there has been a significant reduction observed after 1 year of intervention. At 1 year, a reduction in skinfold thickness was noted in the treatment group while only the triceps and subscapular were increased in the control group. The body fat was decreased in the treatment group following 1 year of intervention (p<0.0001). No particular trend was noted in the urinary iodine excretion in the treatment group, but surprisingly, the levels were increased in the control group (p<0.0001). A significant increase in both systolic and diastolic blood pressures was observed in the treatment group following 1 year of intervention, but the controls showed a reduction in the systolic blood pressure (p<0.0001). Both groups showed a remarkable increase in mental performance, with a more pronounced effect in the treatment group (p<0.05). The correction of iodine deficiency by levothyroxine supplementation has a short-term beneficial effect in reducing the prevalence of goitre and improving the mental ability among the Aborigines in endemic areas; however, proper monitoring and close supervision are needed to maintain compliance.
Surgery for pituitary tumours at our institution was performed by rhinosurgical route by combined procedure by otolaryngologist and neurosurgeons. A retrospective review of case records of patients who had endonasal endoscopic transphenoidal approach for pituitary tumours from September 1998 to December 2004 was performed. A total of 81 trans-sphenoidal surgeries were performed during this study period. Only 68 case records with adequate information were available for review, 56 patients were included in the study and 12 were excluded. There were 24 males (42%) and 32 females (58%). The ethnic distribution, were 29 Malays, 24 Chinese, 2 Indian and 1 others. The age ranged from 16 years to 76 years, with a mean of 46 years. The majority of our patients presented with visual symptoms (38), headache (28), menstrual cycle disturbance or impotence (14) and acromegalic features (16). Forty patients had macroadenoma (71%) and 16 had microadenomas (29%). Thirty-six patients out of 40 macro-adenomas had suprasellar extensions (90%). Only eleven patients had lumbar drain inserted prior to commencement of the surgery and the majority of these were macroadenomas. The common complications encountered were diabetes insipidus (4), cerebrospinal fluid leak (2), meningitis (3), epistaxis (2), septal perforation (2), intercavernous sinus haemorrhage (3) and anterior pituitary insufficiency (2). Our study reveals that endonasal trans-sphenoidal approach is a safe and effective method of management of pituitary adenomas.
The purpose of this study is to explore the types of problem students that clinical teachers encounter in clinical settings. A questionnaire developed by the Association of American Medical Colleges that lists a variety of types of problem students was completed by 466 clinicians at the University of Washington School of Medicine (UWSOM) and 98 Malaysian clinicians from Universiti Kebangsaan Malaysia (UKM) and Universiti Sains Malaysia (USM). In addition, 120 medical students from UKM completed a slightly modified version of this questionnaire. Both the faculty and student questionnaires asked the respondent to identify the frequency of a given problem type. The faculty was also asked to estimate how difficult it was to evaluate a specific problem. In general, there was strong agreement among the North American and Malaysian faculty on the frequency and difficulty of the 24 types of problem students listed. There were some notable differences, such as Malaysian teachers perceiving the "shy" student more frequently than their North American counterparts who rated the student with deficits in knowledge more frequently. However, the overall similarity in the rankings suggest that clinical teachers face similar types of problems, independent of cultural differences and institutional differences.
The study was conducted to compare the prevalence of goitre among Malays and Aborigines in remote inland rural areas to those in coastal areas. All subjects were examined thoroughly by an experienced endocrinologist for the presence of goitre. The overall goitre prevalence in coastal areas was 6.3%; 6.0% (4/67) of Aborigines and 6.7% (4/60) of Malays were affected. However, in remote inland areas, the prevalence of goitre was almost 5 times higher compared to coastal areas. The prevalence of goitre was 30.7% in Baling; 30.2% (19/63) Aborigines and 30.8% (92/299) Malays were affected. Iodine deficiency is the most likely cause for the high prevalence of goitre in the remote inland areas.
1. The effects of thyroxine treatment on soleus and extensor digitorum longus (EDL) muscle contractions and their cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels were examined in anaesthetized cats. 2. Thyroxine treatment decreased the tension of incomplete tetanic contractions of the soleus as well as the EDL muscles. The effect on tension of these muscles was not associated with an increase in the cyclic AMP level of the muscle as is the case with a beta 2-adrenoceptor agonist effect. 3. The results do not support the involvement of cyclic AMP in the tension depressant effect of thyroxine on contractions of skeletal muscle. 4. It is suggested that the muscle weakness and tremor observed in thyrotoxicosis and during administration of beta 2-adrenoceptor agonists are mediated by different mechanisms.
BACKGROUND: The role of endothelial injury and circulating adhesion molecule in the development and progression of diabetic peripheral neuropathy in the long-term has been established previously.
AIMS: To study the effects of short-term glycemic control using insulin and oral hypoglycemic agent therapy (OHA) on the peroneal nerve function and vascular cell adhesion molecule-1 (VCAM-1) and advanced glycation endproducts (AGE) levels in type 2 diabetic patients.
SETTINGS AND DESIGN: A randomized controlled study involving poorly controlled (HbA1c, 7.5%-11%) type 2 diabetic patients attending the endocrinology outpatient center in a tertiary hospital in Kuala Lumpur.
MATERIALS AND METHODS: Twenty-nine patients were randomized to receive insulin (n=15) or OHA (n=14) for 8 weeks. The glycemic variables (HbA1c, fasting plasma glucose [FPG], fructosamine), VCAM-1, serum AGE and the peroneal motor conduction velocity (PMCV) were measured at baseline and at 4-week intervals.
STATISTICAL ANALYSIS USED: Paired 't' test or Kruskal Wallis test; and the unpaired 't' test or Mann-Whitney U test were used for within-group and between-group analyses, respectively. Correlation was analyzed using Spearman's correlation coefficient.
RESULTS: Within-group analysis showed significant progressive improvement in HbA1c at weeks 4 and 8 in the insulin group. The PMCV improved significantly in both groups by week 8, and by week 4 (P = 0.01) in the insulin group. PMCV correlated negatively with VCAM-1 (P = 0.031) and AGE (P = 0.009) at week 8.
CONCLUSION: Aggressive glycemic control with insulin improves the peroneal nerve function within 4 weeks. Improvement in the serum VCAM-1 and AGE levels correlated significantly with improvement in peroneal nerve conduction velocity only in the insulin group.
Study site: Tertiary endocrinology outpatient center in Kuala Lumpur, Malaysia
1. The mean levels of lipid peroxidation products, namely conjugated diene and malonaldehyde, were increased in the soleus muscles of hyperthyroid cats, while the mean glutathione peroxidase activity was decreased. No corresponding similar changes were noted in the fast extensor digitorum longus muscles and serum. 2. Propranolol administration prevented the increase in conjugated diene level in the soleus muscles of hyperthyroid cat but not the malonaldehyde level. It also prevented the reduction in glutathione peroxidase activity in the slow oxidative soleus muscles of hyperthyroid cats. 3. Maximal twitch tension, subtetanic tension and maximum tetanic tension of soleus and EDL muscles were reduced in hyperthyroid cats. Propranolol administration for 5 weeks to hyperthyroid cats did not prevent the reduction in tension of contractions of these muscles. 4. It is suggested that lipid peroxidation might not be responsible for the myopathy in hyperthyroidism and propranolol administration does not improve skeletal muscle function in hyperthyroid animals.