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Biomedical subjects

C S Cockram

Publications and source records attributed to C S Cockram.

At least 163 records · Page 9Linked to original sources

Analysis of a Chinese population suggests that the TNFB gene is not a susceptibility gene for Graves' disease.

Graves' disease is associated with different HLA genes in different races. The TNFB gene lies between the class I and class II HLA genes and has two alleles, TNFB*1 and TNFB*2. Studies in Caucasians have suggested that the TNFB gene might be a susceptibility gene for Graves' disease. To investigate further the role of TNFB in predisposition to Graves' disease, we determined whether the TNFB disease associations in the Chinese were similar to those in Caucasians. A total of 57 patients with Graves' disease (32 male) were studied. A TNFB gene fragment was amplified from genomic DNA by using the polymerase chain reaction and digested with Nco I to distinguish the TNFB alleles (TNFB*1 and TNFB*2). Genotype frequencies were compared with those in a racially matched group of 92 controls. TNFB*1 homozygosity occurred in 15 (26%) Graves' and 22 (24%) control subjects. TNFB*1/TNFB*2 heterozygosity occurred in 29 (51%) and 48 (52%) and TNFB*2 homozygosity in 13 (23%) and 22 (24%), respectively (NS). There were gender differences in the frequencies of TNFB*1 homozygosity (13 male [41%], 2 female [8%]). TNFB*1/TNFB*2 heterozygosity (13 male [41%], 16 female [64%]) (chi 2 = 7.3, p = 0.02), and TNFB*2 frequency (19 male [59%], 23 female [92%]; pc = 0.04) in Graves' patients. We conclude that the TNFB associations with Graves' disease in the Hong Kong Chinese differ between the genders and from those described in Caucasians. The TNFB gene is not a susceptibility gene for Graves' disease.

Asian People↗

Erythrocyte creatine levels in hyperthyroidism.

The mechanism by which erythrocyte mean corpuscular volume (MCV) is decreased in hyperthyroidism is not known. One possible mechanism is premature aging of erythrocytes in the circulation. Since erythrocyte creatine has been shown to be a good marker of cell senescence, we determined this in hyperthyroid patients and control subjects to examine whether the decrease in MCV is related to senescence. Erythrocyte creatine levels were similar in both hyperthyroid patients and controls, suggesting that premature senescence of erythrocytes does not account for the lower MCV in hyperthyroidism.

Adult↗

The HLA association with Graves' disease is sex-specific in Hong Kong Chinese subjects.

OBJECTIVE: Graves' disease is associated with different HLA genes in Caucasians and the Chinese, in whom the HLA associations may be stronger in males than females. Common HLA-associated susceptibility in both races may occur at the HLA-DQ loci. The aims of this study were to examine the HLA-A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis. DESIGN: HLA-A, B and DR types were determined by serological typing and DQA1 and DQB1 alleles by oligonucleotide probing of the respective enzymatically amplified gene. PATIENTS: Ninety-seven Chinese patients with Graves' disease (31 males with, 35 males without and 31 females without thyrotoxic periodic paralysis) and 105 racially matched healthy controls. MEASUREMENTS: Frequencies of HLA types/alleles at each locus were compared between patients and controls and between the Graves' subgroups using the chi 2-test. RESULTS: HLA-B46, DR9 and DQB1*0303 were associated with Graves' disease in males only; these associations were weaker in males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were protective, regardless of sex or the presence of thyrotoxic periodic paralysis. The positive HLA associations in the Hong Kong Chinese were distinct from those in Caucasians whereas the protective haplotype was similar to that described in Caucasians. CONCLUSIONS: These findings call in question the role of HLA genes in disease susceptibility but suggest a role for HLA in protection from Graves' disease.

Adult↗

Hyperinsulinaemia and Na+, K(+)-ATPase activity in thyrotoxic periodic paralysis.

OBJECTIVE: Thyrotoxic periodic paralysis (TPP) usually follows a heavy carbohydrate meal and this may be explained by hyperinsulinaemia stimulating Na+, K(+)-ATPase activity. To clarify this the effect of glucose load on serum insulin concentration and platelet Na+, K(+)-ATPase activity in thyrotoxic periodic paralysis (TPP) was examined. DESIGN: In all subjects a standard 75-g glucose tolerance test was done and blood samples were taken at 0, 1 and 2 hours. SUBJECTS: Twenty-five healthy controls (8 M and 17 F), 17 uncomplicated thyrotoxic patients (7 M and 10 F), 15 TPP patients who presented with paralysis and 4 TPP patients after treatment with antithyroid drugs. MEASUREMENTS: Plasma glucose was measured by the glucose oxidase method, serum insulin by radioimmunoassay and platelet Na+, K(+)-ATPase by the release of phosphate from ATP. RESULTS: TPP patients showed glucose intolerance (area under the curve (AUC) 16.5 +/- 4.4 (mean +/- SD) in TPP compared to 12.9 +/- 4.5 in controls (P < 0.01)) and hyperinsulinaemia (AUC 189.6 +/- 100.6 vs 98.5 +/- 53.4, P < 0.001). In uncomplicated thyrotoxicosis the results were similar to that in healthy controls. Platelet Na+, K(+)-ATPase were significantly higher in thyrotoxic patients compared to controls and in TPP patients were even higher. Ingestion of glucose increased platelet Na+, K(+)-ATPase in all groups. AUC for platelet Na+, K(+)-ATPase in TPP patients were significantly higher than in uncomplicated thyrotoxicosis (601 +/- 99.3 vs 482 +/- 109.4, P < 0.01) or healthy controls (320 +/- 107.3). In the 4 TPP patients studied after antithyroid treatment the results were similar to healthy controls. CONCLUSION: Patients with thyrotoxic periodic paralysis have hyperinsulinaemia and this is accompanied by higher Na+, K(+)-ATPase activity.

Adult↗

Unusual manifestations of craniofacial fibrous dysplasia: clinical, endocrinological and computed tomographic features.

Clinical, endocrinological and computed tomographic features of three patients with unusual manifestations or complications of craniofacial involvement of fibrous dysplasia are presented. One patient with polyostotic fibrous dysplasia presented in late pregnancy with acute onset of bilateral optic nerve compression and blindness secondary to a rapidly expanding mass of fibrous dysplasia tissue involving the sphenoid, pituitary and optic chiasm regions. A second patient with polyostotic fibrous dysplasia developed thyrotoxicosis and probable gigantism/acromegaly in keeping with a rare form of McCune-Albright syndrome. Extensive bony distortion of the skull and facial bones by fibrous dysplasia made clinical recognition of these complications more difficult. A third patient had monostotic fibrous dysplasia with marked sclerosis of the sphenoid bone on plain radiographs which mimicked appearances of a meningioma and resulted in a negative craniotomy as computed tomography was not yet available at the time of presentation. Each case demonstrated rare complications of craniofacial fibrous dysplasia and highlighted the wide spectrum of appearances in which it may manifest, often resulting in overlap and diagnostic confusion with other disease processes. The value of computed tomography in assessment is emphasized.

Adolescent↗

Hashimoto's thyroiditis, Sjogren's syndrome and orbital lymphoma.

A 69 year old Chinese housewife presented with periorbital puffiness, and dry eyes and mouth. Subsequent investigations confirmed the presence of Hashimoto's thyroiditis, Sjogren's syndrome and orbital lymphoma. This unusual combination is discussed with reference to previous publications.

Aged↗

The effects of enalapril and nifedipine on carbohydrate and lipid metabolism in NIDDM.

OBJECTIVE: To compare the effects of nifedipine and enalapril on carbohydrate and lipoprotein metabolism in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. RESEARCH DESIGN AND METHODS: A 12-week, double-blind, randomized study of plasma lipid levels and glycemic control in patients treated with nifedipine (n = 52) or enalapril (n = 50) was conducted. None of the patients were treated with insulin. Diet and dosages of oral hypoglycemic agents remained unchanged during the 12-week treatment period. RESULTS: Mean arterial pressure was reduced more by nifedipine than by enalapril (23.1 vs. 11.1 mmHg, P < 0.001). Similar reductions in body mass index and plasma triglycerides and increases in apolipoprotein A-I were seen with both treatments, but HbA1 was reduced more during treatment with enalapril than with nifedipine (0.49 vs. 0.20%, P = 0.035) and serum apolipoprotein B (apoB) also declined more with enalapril than with nifedipine (8.2 vs. 2.3 mg/dl, P = 0.009). CONCLUSIONS: Twelve weeks of treatment with enalapril in hypertensive NIDDM patients was associated with greater improvement in glycemic control and greater reduction in serum apoB concentration, although the reduction in blood pressure was less than with nifedipine. These changes in cardiovascular risk profile warrant investigation for a longer term.

Apolipoprotein A-I↗

Atrial natriuretic peptide and renin-angiotensin-aldosterone system in non-insulin-dependent diabetes mellitus.

A total of 78 Chinese patients with clinically uncomplicated non-insulin-dependent diabetes (NIDDM) who had plasma creatinine concentrations of < 150 mumol/l were studied. Antihypertensive treatment was discontinued for at least six weeks prior to measurements of routine biochemistry, proteinuria, plasma atrial natriuretic peptide (ANP) concentrations and components of the renin-angiotensin-aldosterone system (RAAS). BP was measured on three occasions during the six weeks period prior to these measurements. At the end of the six week period, a total of 33 patients had definite hypertension (supine BP > or = 160/95 mmHg). The hypertensive patients had significantly higher plasma sodium (mean +/- SD): 140.3 +/- 1.9 vs. 138.5 +/- 2.0 mmol/l, P < 0.001) and lower plasma potassium (3.8 +/- 0.5 vs. 4.2 +/- 0.5 mmol/l, P < 0.01) concentrations. These were associated with reduced plasma aldosterone (median (range): 297 (98-1145) vs. 448.5 (93-1330) pmol/l, P < 0.01) and renin concentrations (16.8 (7.4-71.8) vs. 23.5 (7.4-83.7) ng/l, P = 0.06). The hypertensive patients also had significantly higher plasma ANP concentrations (36.5 (20.5-125.1) vs. 23.2 (11.7-63.0) pg/ml, P < 0.001), serum angiotensin converting enzyme (ACE) activity (65 (26-140.9) vs. 47 (22-106) units/l, P < 0.001) and urinary albumin excretion (UAE) (35.4 (1.6-4800) vs. 7.8 (1.8-310.4) mg/day, P < 0.001). Glycaemic control and renal function were similar between the two groups. Mean arterial pressure (MAP) correlated positively with plasma ANP concentration (r = 0.53, P < 0.001) and serum ACE activity (r = 0.37, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A Chinese lady with Carney's complex.

A young Chinese lady with ACTH-independent Cushing's Syndrome was reported. Her clinical features was compatible with the recently described Carney's complex. Bilateral adrenalectomy was then performed. The diagnosis of bilateral pigmented nodular adrenocortical dysplasia was microscopically confirmed.

Adrenal Cortex↗

Herb-induced aconitine poisoning presenting as tetraplegia.

Both "chuanwu", the main root of Aconitum carmichaelii, and "caowu", the dried root of Aconitum kusnezoffii or other members of the Aconitum genus, have long been used in Oriental materia medica to treat rheumatism, arthritis, bruises, fractures and cardiac complaints. These herbs contain the highly toxic diterpene alkaloids aconitine, mesaconitine and hypaconitine. A case of aconitine poisoning due to chuanwu and caowu that is described presented as profound tetraplegia.

Aconitine↗

Binding of atrial and brain natriuretic peptides to cultured mouse astrocytes from different brain regions and effect on cyclic GMP production.

We prepared primary cultures of mouse astrocytes from the cerebral cortex, hypothalamus, and cerebellum to examine the possibility of regional disparity in binding of human atrial and porcine brain natriuretic peptides (hANP, pBNP) and their effect on cyclic guanosine monophosphate (cGMP) production. 125I-hANP and 125I-pBNP bound in a specific and saturable manner to all three regions. For both peptides, Scatchard analysis suggested a single population of binding sites on astrocytes from all three regions. No significant differences were observed in the maximal binding capacities (Bmax) or binding dissociation constants (KD) between the two peptides in the astrocyte preparations from different regions. ANP and BNP also evoked cGMP stimulation in a similar, dose-dependent fashion in astrocytes from all three regions, with maximal responses to both peptides reached at a concentration above 1 microM. While BNP elicited a greater maximal cGMP accumulation than ANP, no difference could be demonstrated in the cGMP responses to either peptide between brain regions. Thus we have been unable to demonstrate regional heterogeneity in the responsiveness of astrocytes to ANP and BNP.

1-Methyl-3-isobutylxanthine↗

The prevalence of diabetes mellitus and impaired glucose tolerance among Hong Kong Chinese adults of working age.

We studied 1513 employees (910 men and 603 women) from a public utility company and a regional hospital to document the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the Chinese working population of Hong Kong using a 75-g oral glucose tolerance test and World Health Organisation (1985) criteria. The overall prevalence of DM was 4.5 (95% confidence interval: 3.5-5.7%) and that of IGT 7.3 (6.0-8.6%). The prevalence of DM was 5.1 (3.7-6.5%) in men and 3.6 (2.1-5.1%) in women, while that of IGT was 7.4 (5.7-6.5%) in men and 7.1 (5.1-9.1%) in women. The truncated age-adjusted rate of DM for age 30-64 is 7.7% which is comparable to the age-adjusted prevalence rates among Chinese living in Singapore and Mauritius but in marked contrast to the low prevalence rate in Chinese living in Mainland China. Among the diabetic subjects, 38.2% had been previously diagnosed and 32% gave a family history affecting at least one first degree relative. Using polychotomous logistic regression analysis, the independent predictive factors for the development of DM include age (t = 7.31, P < 0.001), family history (t = 5.1, P < 0.001), waist hip ratio (t = 4.05, P < 0.001) and body mass index (t = 4.62, P < 0.001). Our data further confirm that Hong Kong Chinese have a moderate to high susceptibility to non-insulin-dependent diabetes (NIDDM) when exposed to sufficient environmental and lifestyle factors. The high prevalence of IGT indicates a potential for the prevalence of DM to continue to rise unless effective preventive measures are implemented.

Adolescent↗

Lithium-associated transient thyrotoxicosis in 4 Chinese women with autoimmune thyroiditis.

Four Chinese female patients who suffered from manic-depressive disorder and underlying autoimmune thyroiditis developed transient episodes of thyrotoxicosis during maintenance lithium therapy. Endocrinologically speaking, three of them had "Hashitoxicosis", while the other had silent lymphocytic thyroiditis. Albeit rare among Western patients, such lithium-associated thyroid dysfunctions appeared to be more likely to occur in Hong Kong Chinese. They seemed to involve multiple aetiological factors, such as autoimmune thyroid disease, the toxic and immunomodulatory roles of lithium and perhaps genetic and dietary factors. Because of their self-limiting nature, the importance of avoiding unnecessary and potentially deleterious antithyroid treatment is emphasised.

Adolescent↗

17 alpha-Hydroxylase deficiency with persistence of müllerian ducts in a genotypic male and paradoxical aldosterone secretion.

We report a case of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency in a Chinese genotypic male patient. Despite the male genotype, normal female external genitalia were present and with the introduction of cyclical oestrogen therapy withdrawal bleeding occurred, confirming the presence of functional endometrial tissue. We believe this to be the first report of persistent Mullerian duct structures in a genotypic male with 17 alpha-hydroxylase deficiency. It could be explained by either impaired secretion or impaired action of anti-Mullerian hormone. Further, contrary to the usual finding of suppressed aldosterone secretion, this patient had measurable levels of plasma aldosterone.

Adolescent↗

Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin-dependent diabetes mellitus (NIDDM).

A total of 412 Hong Kong Chinese diabetic patients were studied on at least two occasions 8-16 weeks apart. Although 28% were insulin-treated, only 3.6% had insulin-dependent diabetes (IDDM). In the remaining 397 patients with non-insulin-dependent diabetes (NIDDM), the mean (s.d.) body mass index (BMI) was 24.4 +/- 3.2 kg/m2 in females and 24.2 +/- 3.2 kg/m2 in males. Obesity was present in 17% of males (BMI > 27 kg/m2) and 40% of females (BMI > 25 kg/m2). Established hypertension was present in 49%. Abnormal albuminuria, defined as a mean urinary albumin/creatinine (UA/Cr) ratio greater than 5.4 mg/mmol based on two random spot urine samples, was present in 47%. On stepwise multiple regression analysis, UA/Cr ratio (R2 = 0.34, F = 65.4, P < 0.001) showed significant associations with systolic blood pressure (standardized regression coefficient beta = 0.40, P < 0.001), plasma creatinine concentration (beta = 0.27, P < 0.001) and glycosylated haemoglobin (beta = 0.20, P < 0.001). While the prevalence of hypertension increased with increasing severity of proteinuria, 40% of normoalbuminuric patients had hypertension. Among patients diagnosed before the age of 35 (n = 67), 52% were insulin-treated although only 10% were insulin-dependent. Among these NIDDM patients of young onset (n = 59), obesity was present in 25% of males and 56% of females. Overall, 18% of these patients had a blood pressure greater than 140/90 mmHg and 27% had abnormal albuminuria. In Hong Kong Chinese, diabetes mellitus is predominantly non-insulin-dependent even in the young. Obesity is more prevalent among females. Abnormal albuminuria is relatively common and is closely associated with hypertension and glycaemic control. In the light of increasing prevalence of diabetes among overseas Chinese, our findings may have important implications in the management of Chinese diabetic patients.

Adolescent↗

Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients.

OBJECTIVE: To compare the metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. RESEARCH DESIGN AND METHODS: After a 2-wk run-in period on dietary treatment alone, 12 Chinese normotensive patients with uncomplicated NIDDM were randomized to receive either metformin, or glibenclamide for 4 wk before being crossed-over to the alternative treatment for an additional 4 wk. Metabolic and hemodynamic index, including cardiac output estimation by impedance cardiography, were measured at baseline and at the end of each treatment period. RESULTS: Body mass index was reduced more with metformin than with glibenclamide, although glycemic control was similar with both drugs. Plasma total cholesterol concentration fell more with metformin (mean difference -0.65 mM, 95% confidence interval -0.96 to -0.32) than glibenclamide (mean difference -0.20 mM, 95% confidence interval -0.54-0.12) (P < 0.05). Compared with baseline values, erect diastolic blood pressure was reduced more by metformin (12.9% [95% confidence interval -21.5 to -4.4%]) than glibenclamide (-6.8% [95% confidence interval -14.9 to 1.2%]) (P < 0.001). The relative changes in the systemic vascular resistance index also differed between the two treatments (glibenclamide, 6.2 [-4.3 to 16.6%]; metformin, -1.2 [95% confidence interval -8.8-6.4%]) (P < 0.05)]. CONCLUSIONS: In normotensive NIDDM patients, treatment with metformin was associated with greater reductions in body weight, plasma total cholesterol concentration, and erect diastolic blood pressure, whereas the systemic vascular resistance index increased after treatment with glibenclamide. These findings merit long-term investigation.

Biomarkers↗

Serum lipid profile and its association with some cardiovascular risk factors in an urban Chinese population.

The lipid profile of a Chinese population, which has a lower prevalence of coronary heart disease compared with Caucasians, is studied to determine whether lipid-modifying disease prevention programs are necessary. The study population consisted of 910 men (mean age 36.7 +/- 9.2 yrs) and 603 women (mean age 38.6 +/- 9.1 yrs), who were employees of a public utility company and non-medical staff of a district hospital. Indices of obesity, fasting cholesterol (TC), and its various subfraction, triglycerides (TG), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B) concentrations were measured. Glucose tolerance was also estimated by measuring fasting and 2 h glucose after a 75 g oral glucose load. The lipid profile was similar to that of the North American population, with an overall prevalence of low density lipoprotein cholesterol (LDL-C) > or = 4.1 mmol/L of 21% and 11% in men and women respectively. Similar variations with age, sex, smoking and glucose tolerance compared with Caucasian populations were observed. The high prevalence of subjects with "undesirable" lipid values in this Chinese population, which at present has a coronary artery disease prevalence of one-eighth to one-quarter compared with that in Caucasians, suggests that the incidence of the disease may well rise in the future to pose a similar problem to that in Caucasian populations. Cut off values of lipids conferring increased cardiovascular risks need to be determined in this population, so that public health strategies may be formulated.

Adult↗

Blood coagulation abnormalities associated with envenoming by Trimeresurus albolabris in Hong Kong.

Snake bites in Hong Kong are most commonly due to Tr. albolabris (White-lipped pit viper, bamboo snake). We studied 21 cases of envenoming by Tr. albolabris prospectively in order to document the incidence and severity of associated coagulation abnormalities. Eighteen patients (86%) had increased blood concentrations of fibrin degradation products (FDP) ranging from 10-40 micrograms/l to greater than 200 micrograms/l (normal: less than 10 micrograms/l), the majority of whom also had detectable soluble fibrin monomers. Among these 21 patients, 10 had decreased blood concentrations of fibrinogen ranging from 0.3 kg/l to 1.9 g/l (normal: 2-4 gl/l). In 11 cases (52%), the euglobulin clot lysis time was shortened (less than 150 minutes) in association with elevated blood concentrations of FDP (n = 10) and decreased circulating fibrinogen levels (n = 8). Thrombocytopenia and/or prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and/or thrombin time (TT) were present in 10 patients (28%). Increased blood concentrations of FDP and decreased circulating fibrinogen levels were present in most of these cases. Envenoming by Tr. albolabris is therefore frequently associated with a coagulopathy compatible with increased fibrin/fibrinogenolysis. Measurement of blood concentrations of FDP is the most sensitive test for detecting the coagulopathy. There is, however, little correlation between the patterns of clinical manifestations and coagulation abnormalities although more severe clinical features were usually associated with high circulating FDP levels. Only one patient developed systemic bleeding but no fatality was observed. The coagulation abnormalities are usually correctable by replacement therapy. Further studies are required to study the mechanisms of this coagulopathy and its relationship with venom antigenaemia.

Adult↗