Metabolic syndrome and cardiometabolic risk factors among indigenous Malaysians.

OBJECTIVES: This study was undertaken to investigate the occurrence of metabolic syndrome (MetS) and cardiovascular disease (CVD) risk in Orang Asli (OA), the indigenous people of Peninsular Malaysia. OA consist of Negrito, Proto-Malay, and Senoi groups who collectively comprise only 0.76% of the population of Peninsular Malaysia. Owing to the challenges in accessing their remote villages, these groups are often excluded in larger government health surveys. Although tropical diseases were scourges in the past, with rapid national development, many OA communities have been gradually urbanized. We believe an epidemiological transition is occurring and non-communicable diseases are on the rise. STUDY DESIGN: A retrospective cross-sectional study. METHODS: Indigenous Malaysians (n = 629) from three major groups (Negrito, Proto-Malay, and Senoi) were recruited, after ethics approval and informed consent. Body mass index (BMI), body weight, height, waist circumference, and systolic and diastolic blood pressure were measured, and participants were examined for acanthosis nigricans. Venous blood samples were used for measurements of fasting blood sugar, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Insulin resistance was estimated using a surrogate measurement TG/HDL-C. The ratios of TC to HDL-C, and of LDL-C to HDL-C were determined. MetS was accessed according to the Joint Interim Statement of the IDF Tsak Force on Epidemiology and Prevention. RESULTS: MetS affected 29.57% of the OA population investigated and was significantly more prevalent (P < 0.05) in women than in men (35.25% vs 21.95%, P < 0.001). MetS prevalence was the highest among the Proto-Malays (39.56%), followed by Negritos (26.35%) and Senois (11.26%). The most prevalent risk factor among the Negritos with MetS was low HDL-C (95.35%), whereas central obesity was the most common risk factor among the Proto-Malays (82.91%). In contrast, hypertension was the commonest risk factor among the Senois with MetS (94.44%). Elevated TG/HDL-C ratios resulted in the highest risk for MetS among the OA population (relative risk [RR] = 7.01, 95% confidence interval [CI] = 3.58-13.72). The risk was almost four-fold among those with high TG (RR = 3.89, 95% CI = 3.08-4.91) and three-fold among those with BMI obesity (RR = 3.37, 95% CI = 2.61-4.36) and central obesity (RR = 2.99, 95% CI = 2.48-3.61). CONCLUSIONS: This may well be the first comprehensive report about MetS in OA indigenous communities in Malaysia. We have shown that rapidly urbanized OA communities had significant prevalence of MetS and associated cardiometabolic risk factors. Major contributory factors may include changes from previous hunter-gatherer lifestyles and subsistence diets to more urbanized lifestyles and easier access to high calorie foods.

The SAD-MEN questionnaire: a new and reliable questionnaire for assessing sexual dysfunction in Asians with diabetes.

AIM: The aim of this study is to construct a new tool for the assessment of sexual dysfunction among men with diabetes that is valid and reliable across different ethnicities, languages and socio-economic backgrounds in South East Asia. METHODS: Focus group interviews were conducted to determine the construct of the questionnaire. Content and face validity were assessed by a panel of experts. A pilot study was conducted to validate the Sexual Dysfunction in Asian Men with Diabetes (SAD-MEN) questionnaire in English and Malay. The International Index of Erectile Function-5 (IIEF-5) was used for comparison. Construct validity was assessed using exploratory factor analysis, reliability was determined using Cronbach's α (> 0.700), and test-retest reliability using Spearman's rank correlation coefficient. RESULTS: The SAD-MEN questionnaire yielded moderate face and content validity, with high reliability as shown by Cronbach's α values of 0.949 for sexual performance and 0.775 for sexual desire for the English version. The Malay language questionnaire had a Cronbach's α value of 0.945 for sexual performance and 0.750 for sexual desire. Test-retest reliability using Spearman's test gave correlation coefficients of r = 0.853, P = 0.000 for the English language questionnaire and r = 0.908, P = 0.000 for the Malay language questionnaire. CONCLUSION: The SAD-MEN questionnaire is a valid and reliable tool by which to assess sexual dysfunction in English- and Malay-speaking Malaysian and South East Asian men with diabetes.

Development and validation of the Asian Diabetes Quality of Life (AsianDQOL) Questionnaire.

AIM: To construct a type-2 diabetes specific quality of life (QOL) tool for Asian populations that is valid and reliable across different ethnicities, languages, and socio-economic backgrounds. METHODS: A focus group determined the domains affecting QOL in consultation with an expert group. A pilot study was conducted to validate the Asian Diabetes QOL (AsianDQOL) in English, Malay and Chinese-Mandarin. The World Health Organization Brief Quality of Life Questionnaire (WHOQOL-BREF) was used for comparison. Exploratory factor analysis (EFA), reliability analysis (RA) using Cronbach's alpha, test-retest reliability, and confirmatory factor analysis (CFA) using structural equation modeling (SEM) was undertaken using the statistical software IBM SPSS Statistics version 20. RESULTS: EFA with eigenvalues (>1) and factor loadings ≥0.3 for English and Malay language demonstrated 21 items (5 components). CFA (English version) confirmed the model (CMIN 201.08, p-value 0.071, GFI 0.88, RMSEA 0.036, CFI 0.978). CFA (Malay version) confirmed the 5-factor model (CMIN 189.39, p-value 0.085, GFI 0.937, RMSEA 0.025, CFI 0.987). The Cronbach's alpha scores (English version) were 0.917, 0.818, 0.816, 0.749 and 0.719, respectively. The Malay version scored 0.833, 0.819, 0.816, 0.775, 0.673, respectively, whilst the Chinese/Mandarin version scored 0.890, 0.719, 0.826, 0.862 and 0.759, respectively. Test-retest reliability showed Pearson correlation of 0.600 (English version), 0.700 (Malay version) and 0.500 (Chinese-Mandarin version). A scoring system was generated based on the 25th, 50th and 75th centiles for all the three languages. CONCLUSION: The AsianDQOL is a valid, reliable and stable tool for assessing QOL in multi-ethnic and multi-lingual T2DM Asian populations.

Diabetes quality of life perception in a multiethnic population.

AIM: The aim of this study was to determine ethnic differences and predictors of the perception of quality of life (QOL) in a multiethnic Malaysian population with type 2 diabetes. METHODS: A population-based cross-sectional study was done in three different states in Malaysia. The Asian Diabetes Quality of Life (AsianDQOL) tool specific for type 2 diabetes is the primary outcome tool. One-way analysis of covariance was undertaken to examine ethnic differences on the total and component AsianDQOL scores controlling for important covariates. Stepwise multiple linear regression models were used for selecting predictors for the AsianDQOL score with stratification for ethnicity and language. RESULTS: A total of 647 subjects (338 Malays, 160 Chinese and 149 Indians) were recruited. Chinese scored significantly lower (78.1 ± 11.6) on the AsianDQOL (total) score compared to Malays (81.4 ± 9.0) and Indians (81.5 ± 9.2) (F = 3.060, p = 0.049, η (2) = 0.02). Likewise, Chinese scored significantly lower (21.0 ± 4.3) on the AsianDQOL (diet) score compared to Malays (22.8 ± 3.6) and Indians (22.5 ± 3.7) (F = 4.96, p = 0.008, η (2) = 0.04). The main predictors of AsianDQOL (total) score for the English language group of different ethnicities were sexual dysfunction (-4.5), having visual problems (-3.7), female (-2.8) and glycemic control (-1.6). Sexual dysfunction was negatively correlated with QOL in Malay, Chinese ethnic group and Indian ethnic groups. CONCLUSION: The perception of AsianDQOL is different across ethnic groups and languages spoken. Significant differences in the English-speaking group and the non-English-speaking group are detected within the same ethnicity. Sexual dysfunction severely impacts AsianDQOL in a multiethnic Asian population and remains an important determinant regardless of ethnicity and language.

Prevalence of diabetes in Malaysia and usefulness of HbA1c as a diagnostic criterion.

AIM: The prevalence of diabetes mellitus among Malaysians aged ≥ 30 years of age has increased by more than twofold over a 20-year period. This study aimed to determine the current status and to evaluate the diagnostic usefulness of the HbA(1c) cut-off point of 48 mmol/mol (6.5%). METHODS: Using a two-stage stratified sampling design, participants aged ≥ 18 years were recruited from five zones selected to represent Malaysia. An oral glucose tolerance test was performed on all those not known to have diabetes. RESULTS: A total of 4341 subjects were recruited. By World Health Organization criteria, the prevalence of diabetes mellitus was 22.9%; of that percentage, 10.8% was known diabetes and 12.1% was newly diagnosed diabetes. Diabetes was most prevalent amongst Indians (37.9%) and Malays (23.8%). Prevalence of new diabetes mellitus was only 5.5% (95% CI 4.9-6.3) when based on the HbA(1c) diagnostic criteria of 48 mmol/mol (6.5%) and, although the cut-off point was highly specific (98.1%), it was less sensitive (36.7%) compared with 45 mmol/mol (6.3%), which showed the optimal sum of sensitivity (42.5%) and specificity (97.4%) in identifying new diabetes mellitus. CONCLUSION: This study recorded an overall diabetes prevalence of 22.6%, almost a twofold increase from 11.6% reported in 2006. This was likely attributable to the higher prevalence of new diabetes (12.1%) diagnosed following an oral glucose tolerance test. An HbA(1c) of 45 mmol/mol (6.3%) was found to be a better predictive cut-off point for detecting new diabetes in our multi-ethnic population.

Predictors of ischaemic heart disease in a Malaysian population with the metabolic syndrome.

AIMS: Cardiovascular disease is the foremost cause of mortality in Malaysia but little is known about the prevalence of the metabolic syndrome and its associations with other known cardiovascular risk markers. We undertook a population-based study to examine these. METHODS: For the study, 4341 subjects were selected using a multistage stratified sampling method. Subjects were interviewed for personal and past medical history. Biomedical markers and anthropometric indices were measured. The metabolic syndrome was defined using the harmonized criteria. The associations between the metabolic syndrome and cardiovascular risk markers, including high-sensitivity C-reactive protein, microalbuminuria and HbA(1c) were examined. RESULTS: The prevalence of the metabolic syndrome was 42.5%. Subjects with the metabolic syndrome are significantly more likely to have higher BMI (> 25 kg/m(2)), HbA(1c) [≥ 42 mmol/mol (6.0%)], LDL (≥ 2.6 mmol/l), elevated albumin:creatinine ratio (> 2.5 µg/mmol creatinine for men, 3.5 µg/mmol creatinine for women) and high-sensitivity C-reactive protein (> 3 mg/l); odds ratio 5.48, 6.14, 1.44, 3.68 and 1.84, respectively, P < 0.001. The presence of an elevated albumin:creatinine ratio and high-sensitivity C-reactive protein are strong predictors for the presence of a higher number of positive criteria of the metabolic syndrome. HbA(1c) > 48 mmol/mol (6.5%) is associated with increased relative risk of elevated albumin:creatinine ratio, high-sensitivity C-reactive protein and LDL (relative risk 3.10, 2.46 and 1.65 respectively, P < 0.001). CONCLUSIONS: We confirmed the high prevalence of the metabolic syndrome in Malaysia. Our study revealed a strong relationship between risk markers of elevated BMI, HbA(1c), LDL, albumin:creatinine ratio and high-sensitivity C-reactive protein with the presence of the metabolic syndrome, putting them at a statistically high risk for cardiovascular mortality.

HLA-DQ A1, -DQB1 and -DRB1 gene polymorphism--in Malay type 1 diabetes mellitus patients and their use for risk prediction.

HLA-DQA1, -DQB1, and -DRB1 gene polymorphism were analyzed to study type 1 DM susceptibility in Malay patients from Southeast Asia (Malaysia and Singapore). Patients showed significant increases in the occurrence of DQA1*0501 (50.7% vs. 20.4%; RR = 3.97; Pc < 0.01), DQB1*0201 (48% vs. 19.1%; RR = 3.86; Pc < 0.05), and DRB1*0301 (38.7 vs. 6.8%; RR = 8.36; 95% Pc < 0.05). Conversely, significant decreases were noted in the occurrence of DQA1*0601 (14.7% vs. 35.2%; RR = 0.33; Pc = 0.008) and DQB1*0601 (4% vs. 23.5%; RR = 0.16; Pc < 0.05) in type 1 DM patients. Using a logistic regression model, we derived a risk prediction model for type 1 DM in our indigenous Malay population based on the identified HLA genotypes. The RR for type 1 DM increases by a factor of 5.68 for every unit increase in the number of DRB1*0301 allele (P < 0.001), and decreases by a factor of 0.18 per unit increase in the number of DQB1*0601 allele (P < 0.001). After adjusting for these two HLA genotypes, DQA1*0501, DQB1*0201 and DQA1*0601 were not statistically significant as risk predictors. The lower incidence of type 1 DM in the Malay population may be contributed by the genotypic combinations of DR and DQ genes as well as the linkage disequilibria between susceptible and protective alleles.

The effects of short-term, rapid glycemic control on the peroneal nerve function and serum VCAM-1 and AGE in type 2 diabetic patients in Malaysia.

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.

Islet autoimmunity status in Asians with young-onset diabetes (12-40 years): association with clinical characteristics, beta cell function and cardio-metabolic risk factors.

In this paper, the islet autoimmunity status and relation to clinical characteristics, beta cell function and cardio-metabolic risk factors in young-onset Asian diabetic patients are evaluated at baseline. The study population consisted of 912 patients (from China, India, Malaysia and Singapore) with age 12-40 years and diabetes duration <12 months. Autoantibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase (IA-2A), beta cell function and cardio-metabolic risk parameters were assessed. Among our young patient cohort, 105 (11.5%) patients were GADA and/or IA-2A positives (Ab +ve). Ab +ve patients were younger, leaner, had more severe hyperglycaemia and lower beta cell function. The frequency of metabolic syndrome was significantly lower in Ab +ve patients (27%) compared to Ab -ve patients (54%). However, a substantial proportion of patients in both groups of patients had atherogenic dyslipidaemia, hypertension and albuminuria (micro or macro). In our study cohort, only one in 10 Asian youth with new-onset diabetes had evidence of islet autoimmunity. At least 60% of Ab +ve and 50% of Ab -ve patients demonstrated classical features of type 1 and type 2 diabetes respectively. Regardless of autoimmunity status, the cardio-metabolic risk factors, in particular atherogenic dyslipidaemia, hypertension and albuminuria were common in our patients with young-onset diabetes.

ACTH producing pulmonary carcinoid and pituitary macroadenoma: a fortuitous association?

We report a case of a 45 year-old man who presented initially with a non-functioning pituitary macroadenoma. A routine chest radiography done preoperatively revealed a right lung nodule which was confirmed by computed tomography (CT) of the thorax. Transfrontal hypophysectomy was performed while a conservative approach was taken for the lung nodule. Four years later, he presented acutely with adrenocorticotrophic hormone (ACTH) dependent Cushing's syndrome which resolved following a right lobectomy. Histological examination revealed an atypical carcinoid. To our knowledge, this is the first reported case of an ectopic ACTH secreting pulmonary carcinoid found in association with a non-functioning pituitary macroadenoma.

Prevalence of insulin resistance in schizophrenia in HUKM.

This is a cross-sectional study to determine the prevalence of insulin resistance and its associated factors in Hospital UKM patients with schizophrenia using the Homeostatic Model Assessment (HOMA) model. Fasting glucose and insulin from 85 patients were obtained. Fasting glucose revealed 15% of the patients were diabetic, while another 15% had impaired fasting glucose. Using the HOMA model, 68% of the patients had insulin resistance. Univariate analyses found BMI (p < 0.001) and waist circumference (p < 0.001) to be associated with insulin resistance. The statistical significance disappeared after multivariate analyses. All patients with schizophrenia should be screened and managed as a group at high risk for development of diabetes with emphasis on body weight management.

An open label comparative study of glimepiride versus repaglinide in type 2 diabetes mellitus Muslim subjects during the month of Ramadan.

This study was conducted to compare the treatment efficacy between a prandial glucose regulator, repaglinide and a new sulphonylurea, glimepiride in Muslim Type 2 diabetic patients who practice Ramadan fasting. Forty-one patients, previously treated with a sulphonylurea or metformin, were divided to receive either repaglinide (n=20, preprandially three-times daily) or glimepiride (n=21, preprandially once daily) 3 months before the month of Ramadan. During Ramadan, patients modified their eating pattern to two meals daily, and the triple doses of repaglinide were redistributed to two preprandial doses. Four point blood glucose monitoring were performed weekly during the month of Ramadan and the subsequent month. Measurements of the 4-point blood glucose were significantly lower in the glimepiride group compared to the repaglinide group both during and after Ramadan. The glycaemic excursion was better in the morning for the repaglinide group and better in the afternoon and evening for the glimepiride group during the Ramadan period. There was no statistically significant difference in the incidence of hypoglycaemia between the two groups during and after Ramadan. There was no difference in the glycaemic excursion post-Ramadan. The longer duration of action of glimepiride may offer an advantage over repaglinide during the 13.5 hours of fast in Ramadan for diabetic patients.

Syndrome of inappropriate antidiuretic hormone caused by continuous lumbar spinal fluid drainage after transphenoidal surgery.

A 53-year-old acromegalic woman had cerebrospinal fluid rhinorrhoea following transphenoidal surgery for a pituitary microadenoma. A continuous lumbar spinal fluid drainage catheter was inserted and on the sixth postoperative day, she developed hyponatremia with features of syndrome of inappropriate antidiuretic hormone (SIADH) requiring hypertonic saline administration. Over-drainage is potentially hazardous and close biochemical monitoring is required. To our knowledge, this is the first reported case of SIADH caused by continuous lumbar drainage in an adult.

Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control.

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.

Masking of central diabetes insipidus and hypogonadotrophic hypogonadism by germ cell tumour in suprasellar--pineal region.

A patient with beta hCG-secreting germ cell carcinoma of the pineal and suprasellar regions presented with hydrocephalus, Parinaud's syndrome, hypopituitarism and polyuria. Central diabetes insipidus was strongly suspected although the water deprivation test was not diagnostic. The polyuria however, responded to ADH analogue when the hypothyroidism and hypocortisolism were treated. Pubertal development was evident and serum testosterone was normal despite the low FSH/LH, suggesting hCG stimulation of Leydig cells. This case illustrates that a beta hCG-germ cell tumour of the suprasellar region causing hypopituitarism can mask the presence of central diabetes insipidus and hypogonadotrophic hypogonadism.

Use of the denaturing gradient gel electrophoresis (DGGE) method for mutational screening of patients with familial hypercholesterolaemia (FH) and Familial defective apolipoprotein B100 (FDB).

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.

Microalbuminuria prevalence study in hypertensive type 2 diabetic patients in Malaysia.

Microalbuminuria is the earliest indicator of diabetic kidney disease and generalised vascular endothelial dysfunction. The Microalbuminuria Prevalence (MAP) Study was carried out to assess the prevalence of macroalbuminuria, microalbuminuria and normoalbuminuria in Asian hypertensive patients with type 2 diabetes on usual care. This paper presents a subanalysis of data from patients in Malaysia. In 733 analysed patients, the prevalence of macroalbuminuria and microalbuminuria was 15.7% and 39.7%, respectively. The high prevalence of diabetic nephropathy in these high-risk patients is a cause for concern, and the Malaysian Health Care system should be prepared for a pandemic of end-stage renal disease due to diabetic nephropathy.

The role of endoscopic endonasal approach to pituitary tumours: HUKM experience.

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.

A comparison between tocopherol and tocotrienol effects on gastric parameters in rats exposed to stress.

Rats exposed to stress developed various changes in the gastrointestinal tract and hormones. The present study was designed to compare the impact of tocopherol and tocotrienol on changes that influence gastric and hormonal parameters important in maintaining gastric mucosal integrity in rats exposed to restrain stress. These include gastric acidity, gastric tissue content of parameters such as malondialdehyde, prostaglandin (PGE(2)), serum levels of gastrin and glucagon-like peptide-1 (GLP-1). Sixty male Sprague-Dawley rats (200-250 g) were randomly divided into three equal sized groups, a control group which received a normal rat diet (RC) and two treatment groups each receiving a vitamin deficient diet with oral supplementation of either tocopherol (TF) or tocotrienol (TT) at 60 mg/kg body weight. Blood samples were taken from half the number of rats (non-stressed group) after a treatment period of 28 days before they were killed. The remaining half was subjected to experimental restraint-stress, at 2 hours daily for 4 consecutive days (stressed groups), on the fourth day, blood samples were taken and the rats killed. The findings showed that the gastric acid concentration and serum gastrin level in stressed rats were significantly (P<0.05) reduced compared to the non-stressed rats in the control and TF groups. However, the gastric acidity and gastrin levels in the TT group were comparable in stressed and non-stressed rats. These findings suggest that tocotrienol is able to preserve the gastric acidity and serum gastrin level which are usually altered in stressed conditions. The PGE(2) content and the plasma GLP-1 level were, however, comparable in all stressed and non-stressed groups indicating that these parameters were not altered in stress and that supplementation with TF or TT had no effect on the gastric PGE2 content or the GLP-1 level. The malondialdehyde, an indicator of lipid peroxidation was higher from gastric tissues in the stressed groups compared to the non-stressed groups. These findings implicated that free radicals may play a role in the development of gastric injury in stress and supplementation with either TF or TT was able to reduce the lipid peroxidation levels compared to the control rats. We conclude that both tocopherol and tocotrienol are comparable in their gastro-protective ability against damage by free radicals generated in stress conditions, but only tocotrienol has the ability to block the stress-induced changes in the gastric acidity and gastrin level.