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Biomedical subjects

B A Khalid

Publications and source records attributed to B A Khalid.

At least 19 recordsLinked to original sources

Different starting times of alpha-tocopherol and gamma-tocotrienol supplementation and tumor marker enzyme activities in the rat chemically induced with cancer.

1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented continuously for 8 weeks in the diets of normal rats and rats chemically induced with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as well as placental glutathione S-transferase (PGST) and GGT activities histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The supplementation was started at three different times: simultaneously with DEN administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of plasma GGT activities and formation of PGST and GGT positive foci were attenuated significantly (P < 0.05) when alpha-T and gamma-T were supplemented simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after cancer induction did not affect plasma enzyme activities and formation of enzyme-positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30 mg/kg was found to be more effective in reducing the severity of hepatocarcinogenesis.

Alkaline Phosphatase

Opposite effects of sex steroids on 11 beta-hydroxysteroid dehydrogenase activity in the normal and adrenalectomized rat testis.

1. Sex steroids have been shown to regulate the biosynthesis of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 2. In vitro studies showed that oestradiol (E2) or testosterone (T) can interfere with the bioassay of enzyme activity, but not progesterone (P4). 3. For in vivo studies, the activity of 11 beta-HSD in the testis of normal and adrenalectomized (ADX) adult male Wistar rats was determined following a daily IM injection of sex steroids for 7 days. 4. The 11 beta-HSD activity was significantly reduced (P < 0.01) either by E2 or T in normal and ADX rats. The enzyme activity in normal rats given both T and E2 was even lower (P < 0.001) than when E2 was given alone. 5. P4 given to normal and ADX rats increased the enzyme activity higher than normal (P < 0.001). 6. The presence of corticosteroids influenced the effects of E2, but not of T and P4, on 11 beta-HSD activity. 7. E2 and T downregulate 11 beta-HSD activity, whereas P4 increased it. E2 did not act through lowering T level.

11-beta-Hydroxysteroid Dehydrogenases

Effects of iodine deficiency on insulin-like growth factor-I, insulin-like growth factor-binding protein-3 levels and height attainment in malnourished children.

OBJECTIVE: The expression and synthesis of IGF-I and IGFBP-3 have been shown to be regulated by hormones and nutrition. We study the effects of malnutrition and iodine deficiency on these growth factors and the height attainment of a group of children. DESIGN: We measured serum IGF-I and IGFBP-3 levels in a group of Malaysian aborigine children from three jungle settlements; Sinderut and Pos Lanai are known for iodine deficiency and endemic goitre, and Gombak is an iodine replete area with better socioeconomic status. PATIENTS: A total of 246 children were studied, 188 in the age group 4-10 years and 88 in the age group 11-15 years. MEASUREMENTS: All children were assessed anthropometrically and height standard deviation score (SDS) were calculated using the CDC Anthropometric Software package. Malnutrition was confirmed clinically and according to the WHO definition of malnutrition. IGF-I and IGFBP-3 were determined by radioimmunoassay, and T4 and TSH by immunoradiometric assay. RESULTS: Based on the height SDS, Sinderut and Pos Lanai children were significantly more malnourished and stunted than the Gombak children P = 0.0001). T4 levels were significantly lower (P = 0.0001) amongst the 4-10-years old Sinderut (81 +/- 2 nmol/l) than in Pos Lanai (101 +/- 3 nmol/l) or Gombak (123 +/- 3 nmol/l) children. Similar findings were also seen in the older children; mean T4 levels of those from Sinderut and Pos Lanai (83 +/- 3 and 88 +/- 4 nmol/l respectively), were low (P = 0.0001) compared to Gombak (118 +/- 3 nmol/l). Conversely, TSH levels in both age groups of Sinderut children were significantly elevated (P = 0.0001) (3.5 +/- 0.2 and 3.9 +/- 0.3 mU/l respectively) compared to age-matched groups from Pos Lanal (2.1 +/- 0.1 and 2.2 +/- 0.2 mU/l respectively) and Gombak (1.5 +/- 0.1 and 1.5 +/- 0.2 mU/l respectively). IGF-I and IGFBP-3 correlated significantly with the height SDS of the children, In both the 4-10 (r = 0.400, P = 0.0001 and r = 0.365, P = 0.0001 respectively) and 11-15 years age groups (r = 0.324, P = 0.002 and r = 0.533, P = 0.0001 respectively). Correlation between IGFBP-3 and T4 levels was more significant in the younger children (r = 0.412, P = 0.0001). Association between IGF-I and T4 levels was significant only in the 4-10 years age group (r = 0.237, P = 0.001). CONCLUSIONS: Varying duration and degree of exposure to malnutrition and iodine deficiency resulted in different mean levels of T4, TSH, IGF-I and IGFBP-3 in the three areas. The strong positive associations between IGF-I and IGFBP-3 levels and height SDS suggest that these biochemical measurements are indeed useful indicators of growth and nutritional status in children. The significant correlations between T4 and IGFBP-3 and IGF-1 suggests the importance of thyroid hormones in regulating the synthesis of these growth factors. The age-related increase of these growth factors even amongst malnourished, iodine deficient children implies that age-matched reference ranges are essential for proper evaluation of laboratory results.

Adolescent

The surgical treatment of adrenal diseases.

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

Adrenal Gland Diseases

How I do it: an improved temporal bone holder.

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.

Humans

Mineralocorticoid and glycyrrhizic acid block stress induced hypotension in rats.

1. The aim of this study was to investigate the effect of repeated exposure to stress on tail blood pressure (TBP) of normal as well as GCA (glycyrrhizic acid) and steroid treated rats. Male Sprague-Dawley rats (250 g) were exposed to ether vapour to achieve light anaesthesia prior to TBP recording. Rats were injected with either normal saline or naloxone prior to exposure to stress. Tail blood pressure was recorded daily for 2 weeks. 2. We found that ether stress caused a transient drop in TBP in control as well as in dexamethasone (DEX) treated rats. The stress-induced fall in blood pressure was reduced by naloxone in control rats but not in DEX treated rats. However the transient drop in TBP following stress was not seen in either GCA or deoxycorticosterone (DOC) treated rats. 3. We conclude that first, the reduction in TBP was due to the release of endogenous opioids caused by stress. Second, DOC may block the release of such endogenous opioids, preventing the drop in TBP in response to stress, while DEX did not. Third, GCA caused a similar mineralocorticoid effect on reversing stress induced hypotension.

Animals

Effects of glycyrrhizic acid on right atrial pressure and pulmonary vasculature in rats.

Glycyrrhizic acid (GCA) the active component of liquorice acts by inhibiting 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) which catalyses the reversible conversion of cortisol to cortisone. The aim of this study was to examine the effect of GCA on pulmonary arterial pressure. Male Sprague-Dawley rats (200g) received drinking water containing 0.1 mg/ml and 1.0 mg/ml GCA for 12 weeks. Tail blood pressure (BP) was recorded every three weeks and serum Na+ and K+ were measured at the beginning and the end of the experiment. Right atrial pressure (RAP) were measured at the end of 12 weeks just before the animals were sacrificed. Lung tissues were taken for histological examination using the elastic-van Gieson (EVG) staining method. There was a significant increase in tail BP in GCA treated rats compared to controls, for both dosages used. This was associated with an increase in serum Na+ and a decrease in K+ level. The mean RAP increased significantly from 2.69 +/- 0.23 mmHg to 4.47 +/- 0.32 mmHg (P < 0.001) in 0.1 mg/ml GCA treated rats and 6.86 +/- 0.54 mmHg (P < 0.0001) in rats receiving 1.0 mg/ml GCA in their drinking water. Histological examination showed increased thickness of pulmonary arterial wall (P < 0.0001). In conclusion GCA caused an increase in right atrial pressure as well as thickening of the pulmonary vessels suggesting pulmonary hypertension.

Administration, Oral

The prevalence of goitre in remote inland versus coastal areas.

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.

Female

Vitamin E, glutathione S-transferase and gamma-glutamyl transpeptidase activities in cultured hepatocytes of rats treated with carcinogens.

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.

2-Acetylaminofluorene

Effect of ovariectomy and sex hormones replacement on tumour marker enzymes under administration of chemical carcinogens in the rat.

The effect of ovariectomy and sex hormone/s replacement in female rats was investigated by the determination of the tumour marker enzymes gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP). This was compared to ovariectomized rats receiving sex hormone replacement and treated with carcinogen. Ovariectomy significantly increased the activity of plasma GGT. Plasma and microsomal ALP and microsomal GGT were unchanged. When replacements of estrogen (E), or progesterone (Prog), or combinations of both estrogen and progesterone were given to ovariectomized rats, the activity of plasma GGT was brought to the level of normal intact females. Treatment with carcinogen increased the PGGT activities in intact rats. In ovariectomized rats receiving carcinogen, the PGGT activities were significantly lower than in intact females and rats receiving both hormone replacement and carcinogen (p < 0.01). Carcinogen treatment in case of estrogen or progesterone replacement, either individually or in combination, showed GGT activities comparable to intact females receiving carcinogen. Both plasma and microsomal ALP were not affected by carcinogen administration. These results showed that ovariectomy reduced the severity of hepatocarcinogenesis while sex hormone replacement worsened the process.

Alkaline Phosphatase

Thyroid function and pubertal development in malnutrition.

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

Adolescent

The problem student on clinical rotations: a comparison of Malaysian and North American views.

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.

Clinical Clerkship

The effects of propranolol on skeletal muscle contraction, lipid peroxidation products and antioxidant activity in experimental hyperthyroidism.

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.

Animals

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

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

Adult

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

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

Adult

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

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

Adolescent

Fasting growth hormone levels in diabetes mellitus.

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).

Adolescent