Serum creatine kinase: an adjunct biochemical index of subclinical thyrotoxicosis?
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Biomarkers↗
Biomedical subjects
B A Khalid
Publications and source records attributed to B A Khalid.
An improved instrument mounting arm.
Although some form of commercial instrument mounting arm is available, a paucity of information in the literature may cause problems in selecting the most appropriate model for an ENT department wishing to trial their invention for use in the clinic or operating theatre. The instrument mounting arm described here is based on existing designs used by hobbyists and model makers for many years but the main benefit of this innovation is its multi-purpose use in the operating theatre and cost effectiveness since it is made of aluminum alloy. It is compact, stable and easily adjustable and can incorporate an endoscope holder or an operating end piece to mount various ENT instruments that offers considerable advantages to the unassisted operator.
Endoscopes↗
Differential regulation of the oxidative 11beta-hydroxysteroid dehydrogenase activity in testis and liver.
11Beta-hydroxysteroid dehydrogenase (11beta-HSD) Type I enzyme is found in testis and liver. In Leydig cell cultures, 11beta-HSD activity is reported to be primarily oxidative while another report concluded that is primarily reductive. Hepatic 11beta-HSD preferentially catalyzes reduction and the reaction direction is unaffected by the external factors. Recent analysis of testicular 11beta-HSD revealed two kinetically distinct components. In the present study, various steroid hormones or glycyrrhizic acid (GCA), given for 1 week, or thyroxine given for 5 weeks to normal intact rats had different effects on the 11beta-HSD oxidative activity in testis and liver. Deoxycorticosterone, dexamethasone, progesterone, thyroxine, and clomiphene citrate increased testicular 11beta-HSD oxidative activity, but decreased hepatic enzyme activity except for deoxycorticosterone (unchanged). Corticosterone and testosterone decreased 11beta-HSD oxidative activity in testis but not that of liver (which was unchanged). Estradiol, GCA and adrenalectomy lowered oxidative activity of 11beta-HSD in testis and liver, but the degrees of reduction were different. The in vivo effects of glucocorticoids too were different, even in the same organ. Dexamethasone, a pure glucocorticoid, has greater affinity for glucocorticoid receptors (GR) than corticosterone. The direct effects of dexamethasone via GR in increasing testicular 11beta-HSD oxidative activity may override its indirect effects. Possibly, the reverse occurs with corticosterone treatment, as it has both glucocorticoid and mineralocorticoid effects. Because both organs have Type I isoenzyme, the difference in 11beta-HSD oxidative activities of these two organs could be attributable to the presence of an additional isozyme in testis or differences in tissue-specific regulatory mechanisms.
11-beta-Hydroxysteroid Dehydrogenases↗
Sociodemographic determinants of glycaemic control in young diabetic patients in peninsular Malaysia.
Recent studies have shown that good glycaemic control can prevent the development of diabetic complications in type 1 and type 2 diabetes. We wished to observe the glycaemic control in patients from different centres in Peninsular Malaysia and the factors that determine it. We recruited 926 patients with diabetes diagnosed before age 40 years from seven different centres, with proportionate representation from the three main ethnic groups. Clinical history and physical examination were done and blood taken for HbA1c and fasting glucose. The overall glycaemic control was poor with geometric mean HbA1c of 8.6% whilst 61.1% of the patients had HbA1c greater than 8%. Glycaemic control in patients with type 2 diabetes varied between various centres and ethnic groups, with the best control obtained in Chinese patients. Significant predictors of HbA1c in both type 1 and type 2 diabetes include access to nurse educators, ethnic background and WHR. In type 2 diabetes, use of insulin was a significant predictor, while in type 1 diabetes, household income was a significant predictor. Socioeconomic status did not have a significant effect in type 2 diabetes. There were no significant differences in the glycaemic control in patients with different educational status. In conclusion, glycaemic control in big hospitals in Malaysia was poor, and was closely related to the availability of diabetes care facilities and ethnic group, rather than socioeconomic status.
Adult↗
Palm vitamin E is comparable to alpha-tocopherol in maintaining bone mineral density in ovariectomised female rats.
Vitamin E has been shown to affect bone metabolism. In this study we determined the effects of palm vitamin E and alpha-tocopherol on bone metabolism. Sprague-Dawley female rats fed with normal rat chow were divided into 4 groups and supplemented with either palm vitamin E 30 mg/kg rat weight, palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight. One group was not supplemented. Half of these rats were ovariectomised before supplementation was given for 10 months. As expected, bone mineral density of the ovariectomised rats fed on normal rat chow diet was lower compared to the intact rats. However, these changes were not seen in the supplemented group of rats. Both intact and ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight had a lower bone calcium content in both femoral and vertebral bones whilst rats fed palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight were able to maintain bone calcium content. Alkaline phosphatase activity was elevated in ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight and alpha-tocopherol 30 mg/kg rat weight compared to the intact rats. Alpha-tocopherol also reduced the activity of tartrate-resistant acid phosphatase post-ovariectomy. These findings indicate that both palm vitamin E and alpha-tocopherol maintained bone mineral density in ovariectomised rats but caused conflicting effects on bone calcium content. Further study is needed in order to determine the mechanisms involved.
Acid Phosphatase↗
In vivo effects of stress, ACTH and corticosterone on testicular 11beta-hydroxysteroid dehydrogenase oxidative activity in rats and the possible mechanism of actions.
The effects of stress and corticosterone on testicular 11beta-hydroxysteroid dehydrogenase (11beta-HSD) oxidative activity have been controversial, whilst that of adrenocorticotrophic hormone (ACTH) have not been investigated before. Hence, the aim of the present study was to determine the in vivo effects of stress due to injection and sham operation, ACTH and corticosterone on testicular and hepatic 11beta-HSD oxidative activity and plasma testosterone levels in normal and adrenalectomized (ADX) rats and their possible mechanism of actions. Adrenalectomy reduced both testicular 11beta-HSD oxidative activity and plasma testosterone levels. The effects of injection and sham operation significantly increased plasma corticosterone levels with decreased testicular 11beta-HSD oxidative activity and plasma testosterone levels in normal but not in ADX rats. Likewise. ACTH or corticosterone treatment for 7 days decreased both testicular 11beta-HSD oxidative activity in a dose dependent manner and plasma testosterone levels in normal rats; but the values in ADX rats remained unchanged. However, none of the above values were significantly lower than that of the ADX levels. Corticosterone seems to maintain testicular 11beta-HSD oxidative activity within the range between normal and ADX rats. These changes are not attributable to diurnal rhythms, as the time of sacrifice has been fixed between 8:30 and 10:30 am. In the liver, no significant change in 11beta-HSD oxidative activity was observed with sham operation, ACTH or corticosterone treatment; but adrenalectomy significantly decreased it. In conclusion, in the intact normal rats, stress, ACTH or corticosterone modulates testicular (but not hepatic) 11beta-HSD oxidative activity indirectly through the adrenal glands and the physiological level of corticosterone is ideal for normal reproductive functions.
11-beta-Hydroxysteroid Dehydrogenases↗
Research misconduct.
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Clinical Trials as Topic↗
Autoimmune markers in young Malaysian patients with type 1 diabetes mellitus.
This study determined the prevalence and significance of autoantibodies to GAD65 (GAD Ab), insulin (IAA), tyrosine-like phosphatase (IA2) and islet-cell (ICA) in a group of 213 young Malaysian Type 1 diabetics, diagnosed before the age of 40 years. Venous blood was taken at fasting, and at 6 minutes post-glucagon (1 mg i.v.). IAA was detected in 47.4%, GAD Ab in 33.8%, IA2 in 8.9% and ICA in 1.4% of the subjects. When based on post-glucagon C-peptide level of 600 pmol/L, 172 (80.7%) patients had inadequate pancreatic reserve, while the remainder 41(19.3%) showed normal response. The autoantibodies, either alone or in combination, were detectable in both groups of patients; higher prevalence in those with poor or no beta-cell function (73.3% versus 46.3%, p = 0.0001). Although the prevalence of GAD Ab was highest in newly diagnosed patients (< 5 years), unlike IA2 and ICA, the marker remained detectable in 24-25% of those patients with long-standing disease. Nineteen patients could probably belong to the "latent autoimmune diabetes in adults (LADA)" subset, where pancreatic reserve was adequate but patients had detectable autoantibodies and insulin-requiring. On the other hand, 68 of the 213 patients (32%) were seronegative, but presented with near or total beta-cell destruction. Thus, as has also been suggested by others, there is indeed etiological differences between the Asian and the Caucasian Type 1 diabetics, and, there is also the possibility that other, but unknown autoantigens are involved in causing the pancreatic damage.
Adolescent↗
Prevalence of glutamic acid decarboxylase antibodies amongst young Malaysian diabetics.
This study determined the prevalence of glutamic acid decarboxylase antibodies (GAD Ab) in a group of 926 young Malaysian diabetics of three ethnic groups, Malay, Chinese, and Indian. Patients were clinically diagnosed to be Type 1 or Type 2 before the age of 40 years. The overall GAD Ab positivity was 17.4% (161/926), significantly higher in the Type 1 than the Type 2 diabetics (35.5%, 116/329 vs. 7.5%, 45/597, P=0.0001). Compared to GAD Ab negative patients, seropositive diabetics were diagnosed at younger age (21.2+/-0.9 vs. 27.4+/-0.3 y, P=0.0001), had lower fasting (289+/-27.4 vs. 640+/-17.6 pmol/l, P=0.0001) and post-glucagon C-peptide levels (527+/-51.8 vs. 1030+/-28.9 pmol/l, P=0.0001). There were no racial differences in the prevalence of GAD Ab; of the total Type 1, 30.8, 36.4, and 39.4% were Malay, Chinese, and Indian diabetics, respectively and of the total Type 2, 8.8, 8.2, and 4.4% were Malay, Chinese, and Indian diabetics respectively. There was a curvilinear relationship between GAD Ab and the post-glucagon C-peptide levels, suggesting that GAD Ab do play a role in the beta-cells destruction and could be an important immune marker for the LADA group. This study reconfirmed previous reports that the autoimmune mechanisms in the Type 1 Asian diabetics are indeed different from the Caucasians, and further investigations should be carried out to explain the differences.
Adolescent↗
Systolic hypertension and duration of diabetes mellitus are important determinants of retinopathy and microalbuminuria in young diabetics.
This cross-sectional study looked at the prevalence of microalbuminuria and retinopathy in a cohort of 926 young, Type 1 and Type 2 diabetes mellitus (DM) patients, and determined the factors which were associated with these microvascular complications. The prevalence of microalbuminuria, defined as the albumin:creatinine ratio > or = 2.5 (for males) or > or = 3.5 mg/mmol (for females), was 13.4% in Type 1 DM, 69.5% in insulin-requiring Type 2 DM and 16% in Type 2 DM treated only with oral hypoglycemic agents. Compared to those with normal renal functions, these patients were older (P < or = 0.01), had significantly elevated blood pressures (P < 0.01 or P = 0.0001), and in the case of Type 1 DM, with a higher body mass index (P = 0.0001) and waist-hip ratio (P < 0.01). The prevalence of diabetic retinopathy in Type 1 DM was found to increase with the duration of diabetes, from 1.4% in the newly-onset (< 5 years), to 9.9% in those with 5-10 years disease, to 35% among patients with more than 10 years of diabetes (P < 0.0001). In this study, it was also observed that 10% of the Type 2 DM patients already had retinopathy within 5 years of diagnosis, and the prevalence increased significantly to 42.9% (P < 0.0001) among patients who had been diabetics for more than 10 years. Stepwise multiple regression analysis showed that besides the disease duration, systolic blood pressure was the most common and significant determinant for both microalbuminuria and retinopathy in both types of DM, thus implying that in order to reduce the risk of microvascular complications in diabetes mellitus, systolic and not just the diastolic blood pressure, should be effectively controlled.
Adult↗
Palm vitamin E improves bone metabolism and survival rate in thyrotoxic rats.
The effects of vitamin E derived from palm oil on bone turnover in thyrotoxic rats were studied. Palm vitamin E reduced bone resorption to a greater extent than bone formation in thyrotoxic rats, suggesting a net reduction in bone loss. The action of palm vitamin E is probably due to its antioxidant properties. Survival rates were also significantly increased in thyrotoxic rats given palm vitamin E, suggesting the role of free radicals in the overall morbidity and mortality in thyrotoxicosis.
Analysis of Variance↗
Novel effects of deoxycorticosterone on testicular 11beta-hydroxysteroid dehydrogenase activity and plasma testosterone levels in normal and adrenalectomized rats.
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.
11-beta-Hydroxysteroid Dehydrogenases↗
Naloxone and vitamin E block stress-induced reduction of locomotor activity and elevation of plasma corticosterone.
Normal rats, on being repetitively stressed by being restrained in a tight container for two hours, had higher levels of plasma corticosterone compared to pre stress values. These rats also reacted to the stress by a behavioral response in which there was marked decrease in locomotor activity assessed by the open field test (pre stress: 71.3 +/- 2.6 squares crossed versus post stress: 14.3 +/- 2.5 squares crossed) by counting the number of squares entered by the rat over 5 minutes. By the 6th to 7th exposures to the repetitive stress, the rats adapted to the stress and had normal plasma corticosterone levels and locomotor activity scores comparable to the pre stress values. These responses to stress were completely blocked by the administration of 0.32 microg/100 g BW of naloxone i.p at 10 minutes prior to the stress. In rats fed with rat chow supplemented with 90 mg/kg rat chow or 150 mg/kg rat chow of vitamin E, there was significant reduction of the plasma corticosterone levels and improvement in the locomotor activity. Stress thus caused opioid mediated increase in plasma corticosterone and reduction in locomotor activity which could be blocked by naloxone. These stress responses probably also involved generation of oxygen free radicals which were scavenged by the vitamin E, thus reducing the effects of repetitive stress on locomotor activity and serum corticosterone levels.
Animals↗
Congenital hypothyroid screening using cord blood TSH.
BACKGROUND: Clinical diagnosis of congenital hypothyroidism (CH) is difficult at birth without neonatal screening. In line with the priorities of the national health services in Malaysia towards preventive medicine, early diagnosis and treatment of CH is emphasised. We conducted a pilot study at Kuala Lumpur's Maternity Hospital between April 1995 and November 1995 to estimate the incidence of CH and also evaluated the problems associated with large-scale neonatal screening using a commercial TSH kit on cord bloodspots. PATIENTS: A total of 11,000 newborns were screened using cord blood spots taken at birth. RESULTS: Two hundred and fifty newborns (2.27%) hand cord TSH > 20 mlU/L and had to be recalled for re-evaluation. Of these, 4 had cord TSH of > 100 mlU/L; three were confirmed to have congenital hypothyroidism and one had transient hyperthyrotropinaemia. Our study estimated the incidence of CH to be one in 3,666 live births in Kuala Lumpur, Malaysia. Clinical features of hypothyroidism are subtle during the early weeks of life. However, prolonged neonatal jaundice (3/3), widely opened posterior fontanelle (3/3) and dry skin (3/3) were the common features in all our cases by 2-6 weeks of life. CONCLUSION: This study suffered a high dropout rate. Twenty-six percent of the patients were not traceable after discharge and 48% did not respond to our recall. We stress the importance of public education and awareness in contributing to the cost-effectiveness of the screening program.
Congenital Hypothyroidism↗
Effects of glycyrrhizic acid and steroid treatment on corticotropin releasing factor and beta-endorphin containing neurons of the hypothalamus of the rat.
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.
Animals↗
Markers of ventricular tachyarrythmias in patients with acromegaly.
INTRODUCTION: Sudden cardiac death is a known complication of acromegaly. Little is known of the exact mechanism leading to sudden cardiac death in these patients. Ventricular tachyarrhythmias may be an important cause. If this is so, clinical markers of ventricular tachyarrhythmias may be more common in this group of patients. The presence of these markers allow better risk stratification among acromegalic patients. METHODS: We performed signal averaged electrocardiography and analysed 12 lead electrocardiography for QT dispersion on 17 acromegaly patients who attended the UKM endocrine clinic within a period of 5 months and compared them with similar age matched controls. Signal averaged electrocardiogram was performed using Marquette Mac 12/15 ECG analyser and QT intervals were measured manually from 12 lead ECG tracings. Late potential positivity was defined by the standard Breithardt criteria. QT dispersion was defined as the longest minus the shortest QT interval from all 12 lead tracings. Echocariography was done to assess left ventricular hypertrophy in patients and controls. RESULTS: Late potential positivity was found to be more common in acromegaly patients compared with controls (chi-square, p < 0.05, n = 34) and QT dispersion was also found to be significantly higher in the acromegaly group compared with control s (mean +/- SE QT dispersion respectively 121.0 +/- 8.6 ms vs 86.2 +/- 7.0 ms, t-test, p < 0.05, n = 34). Left ventricular hypertrophy was present in five acromegaly patients and two in the control group. CONCLUSION: Acromegaly patients have a higher incidence of late potential positivity and higher QT dispersion compared with age matched controls. These findings might explain the increase susceptibility of these patients to sudden cardiac deaths from ventricular tachyarrhythmias.
Acromegaly↗
Regeneration of adrenal cortical tissue after adrenal autotransplantation.
This study tested the possibility of adrenal autotransplantation in rats. Since the cortex and the medulla of the adrenal gland were from different origin embryologically, either whole adrenal glands (ADR), or capsule and cortex (CAP) or medulla (MED) were autotransplanted in the subcutaneous tissue. The functions of regenerated adrenal nodules were tested by measuring plasma corticosterone levels every fortnight. At the end of 9 weeks the rats were exposed to hypovolemic shock followed by naloxone injection to reverse the shock response. Results showed that rats transplanted with either cortex or whole adrenal started secreting corticosterone at 5 weeks post-transplantation (107.73 +/- 21.98 ng/ml, 126.04 +/- 48.41 ng/ml, respectively). Corticosterone levels increased to the value which were not significantly different from control by 9 weeks post-transplantation. However, rats transplanted with adrenal medulla showed very low corticosterone levels. Nine weeks post-transplantation, the mean blood pressure (MBP) of the CAP group was 135 +/- 13 mmHg and was not significantly different from sham-operated controls, whereas MBP of MED group was significantly lower than sham-operated animals (99 +/- 11 mmHg versus 141 +/- 9 mmHg). The MBP of the ADR group was also lower compared to sham-operated controls (112 +/- 17 mmHg P < 0.05). The MBP of the adrenal group was not statistically significant compared to the CAP group. After 1% body weight haemorrhage, the MBP decreased significantly in ADR (45 +/- 5 mmHg, P < 0.05) and MED group (36 +/- 9 mmHg, P < 0.001) compared to sham-operated rats (78 +/- 11 mmHg) but not in the CAP (56 +/- 9 mmHg). It was concluded that autotransplanted whole adrenal or adrenocortical tissues survived subcutaneously and produced sufficient corticosterone to alleviate haemorrhagic shock. Adrenal medullary tissue failed to regenerate subcutaneously and the presence of adrenal medullary tissue may suppressed the growth of transplanted adrenal gland.
Adrenal Cortex↗
Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves' disease.
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.
Adult↗