Although some form of temporal bone holder is in use in virtually all ENT postgraduate teaching departments, a paucity of information in the literature may cause problems in selecting the most appropriate model to those responsible for equipping temporal bone laboratories. The bone holder which we describe is based on existing designs but incorporates a built-in irrigation system which offers considerable advantages to the unassisted operator.
A filter method for collection and storage of capillary blood spots for glycated haemoglobin (gHb) has been developed. Glass fibre filters (GFB) impregnated with 0.8 M boric acid were used to collect and store capillary blood. Haemoglobin from the dried blood spots was eluted into water and determined by Drabkin's method, while gHb in the eluates was determined by the microcolorimetric method. The intraassay coefficients of variation (CVs) were 4.5, 4.5 and 3.1% at 882, 1101 and 1704 pmol HMF/mg Hb, respectively. The corresponding inter-assay CVs were 8.6, 8.6 and 6.3%, respectively. A total of 63 paired capillary and venous blood samples were measured by both the direct and GFB method. The GFB method showed excellent correlation with the direct method (r = 0.948 and r = 0.994) after 7 and 14 days' storage at room temperature. The GFB method will enable prior collection and postage of blood samples by patients.
A combined enzyme immunoassay (micro-ELISA) technique was established for measuring autoantibodies against thyroglobulin and thyroid microsome, involving the immuno-dot blot technique. Thyroglobulin and thyroid microsome antigens (1 g/L each) prepared from normal thyroids were spotted separately onto nitrocellulose membrane filter discs. Results by this method and those by immunofluorescence correlated well. The percentages of confirmed positives were 30% and 48% and the negatives were 58% and 46% (n = 50) for thyroglobulin and microsome, respectively. Testing these samples by gelatin agglutination gave a high percentage of false positives (up to 20%, n = 128) and hemagglutination testing yielded a high percentage of false negatives (up to 20%, n = 45). The titer of autoantibodies by the micro-ELISA technique was greater than by agglutination. This technique is highly specific and sensitive.
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.
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.
The atherogenic potential of soybean oil (Sb) and palm oil (PO) was compared by measuring lipid profile, lipid peroxidation (LP) and activity of the antioxidant enzyme glutathione peroxidase (GSHPx) in rat sera and liver and heart homogenates. Male Rattus norwegicus rats were fed a basal diet, or basal diet fortified with 20% weight/ weight Sb or PO for 4 or 9 months. There was no difference in high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio between the two groups, but triglyceride concentrations were higher in the PO fed rats compared to the Sb fed rats, although the difference diminished after 9 months. No differences in serum LP and GSHPx activity were seen between the two groups. In the liver and heart, LP was lower in PO after 4 months feeding, but the reverse was seen after 9 months. Liver and heart GSHPx activity was higher in the PO group after both treatment periods. In conclusion, both PO and Sb fed rats appeared comparable in their lipid profile, but the PO food had a temporary beneficial effect on the LP process in liver and heart. GSHPx activity however did not correlate well with LP in liver and heart, suggesting involvement of other antioxidants.
The effects of castration with/ without testosterone replacement in male rats, and ovarectomy with oestrogen replacement in female rats, on serum lipids were studied. Simultaneous feeding with diets fortified with 20% weight/ weight (w/ w) soybean oil (Sb) or palm oil (P0) were done to determine the influence of these oils on serum lipids in castrated and sex hormone replaced rats. Two month old male and female Rattus norwegicus rats were given the above treatment for 4 months, and their sera assayed for lipid profile. Castration increased HDL-cholesterol (HDLchol) and total cholesterol (Tchol) concentrations. Testosterone or oestrogen replacement in male and female rats respectively increased HDLchol and decreased LDL-cholesterol (LDLchol) concentrations. Testosterone replacement also decreased Tchol concentration back to noncastrated levels, and reduced serum triglycerides (TG) to lower than non-castrated levels. Addition of Sb or P0 to the diet increased the LDLchol in the testosterone or oestrogen replaced male and female rats, but there was no difference between the two groups. P0 raised serum TG of the testosterone replaced group compared to control and Sb groups. In conclusion, testosterone and oestrogen were found to have favourable effects on serum lipids. Sb and P0 did not differ in their effects on lipoprotein cholesterol and Tchol, but P0 raised serum TG as compared to Sb.
The effects of long-term administration of tocotrienol on hepatocarcinogenesis in rats induced by diethyl nitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated by the determination of plasma and liver gamma-glutamyl transpeptidase (GGT), cytosolic glutathione reductase (GSSG-Rx), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). Twenty-eight male Rattus norwegicus rats (120-160g) were divided according to treatments into four groups: control group, tocotrienol - supplemented diet group (30mg/kg food), DEN/AAF-treated group and DEN/AAF treated plus tocotrienol-supplemented-diet group (30mg/kg food). The rats were sacrificed after nine months. The results obtained indicated no difference in the morphology and histology of the livers of control and tocotrienol-treated rats. Greyish-white neoplastic nodules (two per liver) were found in all the DEN/ AAF treated rats (n-10) whereas only one nodule was found in one of the carcinogen treated rats receiving tocotrienol supplementation (n-6). Histological examination showed obvious cellular damage for both the DEN/AAF-treated rats and the tocotrienol-supplemented rats but were less severe in the latter. Treatment with DEN/AAF caused increases in GGT, GSH-Px, GST and GSSG-Rx activities when compared to controls. These increases were also observed when tocotrienol was supplemented with DEN/AAF but the increases were less when compared to the rats receiving DEN/AAF only.
A study to determine the prevalence of goitre and abnormal thyroid status during pregnancy in Malaysian women was conducted. Two hundred and three women (Malay = 85, Chinese = 47 and Indian = 71) in the third trimester and with no known thyroid disease were studied. There was a marked racial disparity in the prevalence of goitre: Indian 61%, Malay 28% and Chinese 29% (p = 0.001). The serum thyrotropic hormone (TSH) was significantly higher in Indians (median: 1.36 uIU/ml) compared to Malays (1.14 uIU/ml, p = 0.009). The serum albumin was also significantly lower in Indians (mean +/- sd; 36.12 +/- 3.9 mmol/l) compared to Malays (39.3 +/- 4.8 mmol/l) or Chinese (39.1 +/- 5.2) (p < 0.001). Thyroid antibody was detected in 14.6% of these women with no significant racial difference in its prevalence. Three women were found to be thyrotoxic but none were hypothyroid. This study found a high prevalence of goitre among the pregnant Indian women, probably related to the protein malnutrition state. The high prevalence of positive thyroid antibody in our population indicates that a high percentage of women are at risk of developing postpartum thyroiditis.
Fasting serum growth hormone (GH) levels of different groups of diabetic patients were measured and compared to age-matched normal subjects. Insulin-dependent diabetes mellitus (IDDM) children (aged 12-17 years) were found to have significantly lower fasting GH levels than age-matched normal children (p < 0.001). In the adult age groups of 18-44 and 45-76 years, the IDDM patients showed increased fasting GH levels compared to age-matched normal subjects (p < 0.06 and p < 0.001 respectively) and non-insulin-dependent diabetes mellitus (NIDDM) patients (p < 0.05 and p < 0.001 respectively). The fasting GH levels of IDDM patients of the age group 18-44 years also showed significant correlations with glycated haemoglobin (r = 0.510, p = 0.002) and fasting blood sugar levels (r = 0.571, p = 0.01).
Hypercholesterolemia causes endothelial dysfunction, an early feature of atherosclerosis, leading to increased production of adhesion molecules and cytokines. The aim of this study was to investigate the effects of three months of treatment with low dose atorvastatin on serum levels of adhesion molecules, interleukin-6 (IL-6) and highly sensitive C-reactive protein (hs-CRP) in patients with non-familial hypercholesterolemia. Fifty-five patients with non-familial hypercholesterolemia were randomized to treatment with atorvastatin 10 mg/day or placebo for 3 months. Soluble intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, IL-6 and hs-CRP levels were measured to assess the inflammatory activity of the endothelium. There was a significant reduction in ICAM-1 at 2 weeks (p<0.0001) with further reduction at 3 months (p<0.0001). At 3 months, there were significant reductions in VCAM-1 (p<0.02), IL-6 (p<0.0001) and hs-CRP (p<0.01), but an increase in E-selectin levels (p<0.002). Treatment with statin was an independent determinant of change in ICAM-1 (p<0.05) and IL-6 levels (p<0.05) after correcting for anthropometric indices, blood pressure and lipid profile. Low-dose atorvastatin treatment leads to reduction in proinflammatory markers of endothelial function, suggesting an attenuation of endothelial activation and improvement in endothelial function, independent of lipid lowering. This may lead to a reduction in the progression of atherosclerosis.
Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.
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.
The objective of this study was to elucidate influencing factors of HbA1C in various health care settings. The glycaemic control was suboptimal in all settings. Multivariate analysis confirmed three factors were significant in HbA1C outcome; insulin (p=0.000), medication (p=0.043) and ethnicity (p=0.000).
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.
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 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.
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.
Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing neurons are shown to be present in the hypothalamus and both neurons are found at the paraventricular nucleus (PVN). Steroid hormones have been found to alter the plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD) which is needed for the inactivation of the steroid pathway, so therefore would cause changes to these neurons. The aim of this study was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the PVN of the hypothalamus. Rats were given either DM, DOC or GCA and adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats were transfused transcardially before sacrifice and the brain were dissected for immunohistochemical analysis. We found that immunostaining of the CRF containing neurons demonstrate a reduction in the number of positive neurons in DM treated rats. DOC and GCA treated rats showed the same result as in DM rats but the reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in the number of beta EP containing neurons but naloxone increased the number of beta EP containing neurons markedly. In conclusion, GCA and DOC have similar effects on CRF and beta EP containing neurons at the PVN.
The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) protects the testis from the inhibitory effects of corticosterone on testosterone (T) production. The objectives of the present studies were to determine the effects of deoxycorticosterone (DOC) and its mechanism of actions on testicular 11beta-HSD activity and plasma T levels after 7 days of treatment. The results revealed that at the end of 7 days treatment, DOC significantly increased testicular 11beta-HSD activity and plasma T levels in normal rats. However, the time course showed that high plasma T levels lowered 11beta-HSD activity on day 14 and by 21 days both the levels normalized. In adrenalectomized (ADX) rats, only the enzyme activity increased significantly but not plasma T levels. Spironolactone, a competitive inhibitor of mineralocorticoid receptor (MR), did not change testicular 11beta-HSD activity in both normal and DOC treated rats suggesting that DOC did not act through MR in increasing 11beta-HSD activity. On the other hand, spironolactone significantly decreased plasma T levels in DOC treated rats. Progesterone (P), a competitive inhibitor of glucocorticoid receptors (GR) or corticosterone significantly suppressed testicular enzyme activity and plasma T levels in DOC treated normal rats. Carbenoxolone which is an inhibitor of 11beta-HSD activity significantly depressed testicular 11beta-HSD activity and plasma T levels in DOC treated normal rats. This paper suggests that DOC increased testicular 11beta-HSD activity through GR; whilst increase in plasma T levels required functioning adrenal glands. The testicular 11beta-HSD is one of the regulators of T levels and vice versa.