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Biomedical subjects

B A Khalid

Publications and source records attributed to B A Khalid.

At least 91 records · Page 5Linked to original sources

Adrenal histoplasmosis in Cushing's syndrome with bilateral adrenocortical nodular hyperplasia.

Adrenal histoplasmosis in Cushing's syndrome of adrenal origin is rare. A patient with Cushing's disease with bilateral nodular hyperplasia and histoplasmosis of both the adrenal glands is described. The diagnosis of histoplasmosis was only made post operatively as the constitutional manifestations, besides being partially masked by hypercortisolism also resemble those of tuberculosis.

Adrenal Gland Diseases↗

Prevalence of diabetes, hypertension and renal disease amongst railway workers in Malaysia.

A survey was done to determine the prevalence of diabetes mellitus, hypertension and renal disease, as well as extent of diabetic control, amongst the workers of Malaysian Railways. The prevalence of diabetes was high at 6.6%, with 3.8% of these being insulin dependent diabetes. The highest prevalence was in Indians (16.0%) followed by Chinese (4.9%) and Malays (3.0%). Using HbA1 measurements, diabetic control was poor in 70.6% of the diabetics. Hypertension was found in 37% and proteinuria in 35%. Renal impairment was present in 30% of the diabetics. This survey shows that diabetes, hypertension and renal disease are high amongst the railway workers in Malaysia.

Adult↗

Rhabdomyolysis associated with hypokalaemic periodic paralysis of renal tubular acidosis.

Two cases of hypokalaemia with serum potassium levels of 1.4 mmol/L and 1.9 mmol/L causing severe periodic paralysis since childhood are presented. There were associated with muscular aches and markedly raised muscle enzymes suggesting massive rhabdomyolysis. These abnormalities were due to renal tubular acidosis with markedly acidic arterial pH. The hypokalaemia and rhabdomyolysis responded to potassium and bicarbonate replacement. We postulate these patients had sporadic distal type of renal tubular acidosis and that the hypokalaemia and acidosis had caused the rhabdomyolysis.

Acidosis, Renal Tubular↗

Effects of Lugol's solution on thyroid function in normals and patients with untreated thyrotoxicosis.

Thirty-eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo-pituitary-thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay.

Adult↗

Clinical and endocrine profiles of 62 Malaysian women with polycystic ovary syndrome.

62 cases of polycystic ovary syndrome (PCO) were reviewed with regards to their clinical and endocrine features. The subgroup of patients with acanthosis nigricans (AN) was further studied in detail. The prevalence of the syndrome was significantly higher in the Indian (35.5% of cases). Obesity, AN, hirsutism, non-insulin dependent diabetes mellitus (NIDDM) and raised level of serum testosterone were present in 77.1%, 74%, 79%, 21% and 48% of the cases respectively. Patients with AN was associated with higher body mass index, serum testosterone level, and prevalence of hirsutism and NIDDM than patients without AN. These observations are in keeping with the hypothesis that hyperinsulinemia may be of importance in the pathogenesis of a sub-group of PCO associated with insulin resistant states.

Acanthosis Nigricans↗

Massive pericardial effusion in primary hypothyroidism.

A 44 year old lady with primary hypothyroidism presented with massive pericardial effusion without cardiac tamponade. Pericardial tap was done twice and the effusion resolved as the hypothyroid state improved. She remained hypertensive despite the euthyroid state. She was discharged well with L-thyroxine and anti-hypertensive therapy.

Adult↗

Hyperthyroid graves disease--a 5 year retrospective study.

The clinical, biochemical and immunological features of 180 patients with hyperthyroid Graves' disease managed at the Universiti Kebangsaan Malaysia (UKM) Endocrine Clinic from 1983 to 1987 were examined. The prevalence of the disease is highest in Chinese and lowest in Indians. The female: male ratio is 2.8:1. Hypokalaemic periodic paralysis and hypercalcaemia were present in 5.0% and 1.7% of the cases respectively. Pretibial myxoedema was extremely rare. Thyrotropin - binding inhibitory immunoglobulins, anti-thyroglobulin and anti-microsome antibodies were positive in 61.5%, 25.8% and 42.3% of the patients respectively. A eumetabolic state could be achieved in the majority of patients with antithyroid drugs alone. Definitive therapy with subtotal thyroidectomy or radioiodine were needed in 31.3% of cases.

Adolescent↗

Sporadic adult-onset hypophosphatemic osteomalacia--a report of two cases.

Two cases of sporadic adult onset hypophosphatemic osteomalacia are described. Both patients initially presented with intractable low backache and had lumbar laminectomies. In retrospect, they both had typical clinical and biochemical features of hypophosphatemic osteomalacia prior to surgery. Medical treatment resulted in rapid relief of symptoms in both patients.

Adult↗

Genital fibroblasts from normal individuals and patients with androgen insensitivity: demonstration of reduced or absent levels of a specific protein (Mr approximately 41K, pI approximately 6) in receptor negative cells.

Genital fibroblasts were obtained from normal individuals and from patients with a variety of syndromes of defective androgenization (complete androgen insensitivity, partial androgen insensitivity, microgenitalia, hypospadias, infertility). Cells were labelled with [35S]methionine, and patterns of protein synthesis compared by two-dimensional gel electrophoresis, with isoelectrofocusing electrophoresis gels or non-equilibrated pH gradient electrophoresis (NEPHGE) gels as the first dimension. A protein (mol. wt approximately 41K, pI approximately 6) was found on NEPHGE gels to be reduced or absent in fibroblasts in which androgen receptor levels were abnormal. The protein was unaltered by prior incubation with 1-100 nM dihydrotestosterone for 48 h, and was present in cells both from normal controls, and from patients with abnormal sexual differentiation showing normal androgen receptor levels. The coincidence of low or absent 41K with low or absent androgen receptors suggested the possibility that it may constitute a steroid-binding moiety of the androgen receptor. To test this possibility cytosols from normal foreskins or normal cultured fibroblasts were adsorbed with testosterone-sepharose affinity resin to remove androgen receptors. Cytosols so treated showed levels of 41K on NEPHGE indistinguishable from those in untreated cytosols, or in cytosols treated with underivatized sepharose. We therefore conclude that the 41K protein, while an accurate marker of the presence or absence of androgen receptors over a range of clinical disorders, is neither an androgen-induced protein nor an androgen-binding protein.

Androgens↗

The effect of corticosteroid pretreatment in vivo on the contraction of guinea-pig ileum and duodenum.

The effects of corticosteroid pretreatment on the contraction caused by acetylcholine or electrical stimulation of guinea-pig ileum and duodenum were studied. The acetylcholine dose-response curves for steroid pretreated ileum but not duodenum were significantly shifted to the right; evidence that pretreated ileum required higher dose of acetylcholine than normal to cause 50% maximal contraction. Naloxone enhanced the contraction of normal ileum caused by acetylcholine given at the dose of ED50, but not that of normal duodenum. The dose of morphine required to abolish electrically induced contraction was higher in steroid pretreated ileum than in normal ileum. Hence, corticosteroid pretreatment may affect intestinal contractility via opioidergic mechanisms which are found in the ileum but not in the duodenum.

Acetylcholine↗

The effects of naloxone, dexamethasone, deoxycorticosterone and 17-hydroxyprogesterone on blood pressure responses of normal and adrenalectomized rats during hypovolaemic shock.

The roles of, and interactions between, steroids and naloxone, an opioid antagonist, in the reversal of experimental hypotensive shock were studied in normal and adrenalectomized rats. In normal rats treated with dexamethasone or deoxycorticosterone or 17-hydroxyprogesterone the hypotension and shock caused by 1% bodyweight and 2% bodyweight haemorrhage could be substantially reversed by naloxone in a dose-related manner. In contrast, the reversal of hypotension by naloxone was markedly less in adrenalectomized rats. It is concluded that there is a co-ordinate release of pressor catecholamines and depressor enkephalins from adrenal glands in hypovolaemic shock. Eventually, the use of naloxone would be of much less value in the treatment of hypotension or shock in patients with Addison's disease.

17-alpha-Hydroxyprogesterone↗

Enzyme immunoassay for simultaneous measurement of autoantibodies against thyroglobulin and thyroid microsome in serum.

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.

Autoantibodies↗

Further evidence of the role of cyclic AMP as a mediator of the depressant effects of beta-adrenoceptor agonists and phosphodiesterase inhibitors on slow-contracting mammalian skeletal muscles.

The depressant effects of beta-adrenoceptor agonists and phosphodiesterase inhibitors on contractions of slow-contracting mammalian skeletal muscles are associated with increased muscular cyclic AMP levels. A strong correlation was found to exist between the percentage depression of contraction and the percentage increase in cyclic AMP level, irrespective of the drug used and regardless of the mechanism of cyclic AMP production. The results strongly support the mediatory role of cyclic AMP in the depressant effects of beta-adrenoceptor agonists and phosphodiesterase inhibitors on slow-contracting mammalian skeletal muscle contractions.

Adrenergic beta-Agonists↗

A common 43 K protein induced by glucocorticoids in a variety of cells and tissues.

We have investigated the domain of adrenal steroid action in a variety of mammalian cells and tissue by high resolution two-dimensional gel electrophoresis and autoradiography. Following in vivo or in vitro treatment with steroids, minced tissue or cells were pulsed with [35S]methionine, and they newly synthesized polypeptides compared with controls by visual inspection of partial protein maps. We have found a similar protein (Mr approximately 41-44K, pI approximately 6.3-6.5) to be consistently increased by dexamethasone in 3 rat tissues and 9 human, bovine and rat cell lines. The protein was constitutively synthesized in all targets; quantitative measurements on the magnitude of response show a 2-fold induction by dexamethasone in all systems, in vivo and in vitro. Glucocorticoid-specific hormones but not sex steroids increase the rate of synthesis; deoxycorticosterone has agonist or antagonist effects on 43K synthesis in different systems studied. Co-electrophoresis experiments indicated that 43K proteins co-migrate in at least 3 rat cell lines from tissues with diverse functions. The functional significance of this common glucocorticoid-induced protein is unknown; its ubiquity and electrophoretic properties suggest a highly conserved, common indicator of glucocorticoid action in diverse target cells and tissues, rather than a tissue-specific response.

Androstanols↗

A pituitary tumor producing high molecular weight adrenocorticotropin-related peptides: clinical and cell culture studies.

The tissue-specific processing of proopiomelanocortin (POMC), the precursor of ACTH, beta-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation. Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and beta-endorphin (ir-beta EP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-beta EP, corresponding to the elution positions of beta-lipotropin and beta-endorphin standards. Plasma ir-ACTH and ir-beta EP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-beta EP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.

Adenoma↗

Effects of steroids on fibroblasts: identification of glucocorticoid-regulated proteins by two-dimensional gel electrophoresis.

Fibroblasts cultured from normal human forearm or genital skin were exposed to dexamethasone (DM) 10(-9)-10(-7) M, deoxycorticosterone (DOC) 10(-6)M, or vehicle for 4-16 h and [35S]methionine-labelled proteins compared by two-dimensional gel electrophoresis. No effects on cell number or [35S]methionine incorporation were seen with either steroid, nor any effects of DOC on patterns of protein synthesis. In contrast, after 4 h incubation DM consistently (24/24 gels) caused increased abundance of a protein spot designated k (kappa; Mr approximately 41 000, pKi approximately 6.5). After 16 h steroid exposure, levels of protein kappa remained elevated; abundance of a second protein spot omega (omega; Mr approximately 42 000, pKi approximately 5.4) was consistently (8/8 gels) lower than in control fibroblasts. We interpret these data as evidence for glucocorticoid-specific effects on human skin fibroblasts, and that (within the pKi and molecular weight range studied) the observed changes in abundance of proteins kappa and omega constitute the human fibroblast glucocorticoid domain.

Child↗