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Biomedical subjects

C S Cockram

Publications and source records attributed to C S Cockram.

At least 127 records · Page 7Linked to original sources
PubMed1997

Fasting plasma glucose as a screening test for diabetes and its relationship with cardiovascular risk factors in Hong Kong Chinese.

OBJECTIVE: To evaluate the use of fasting plasma glucose (FPG) in the diagnosis of diabetes and the relationship between FPG and various cardiovascular risk factors in a community-based Hong Kong Chinese population. RESEARCH DESIGN AND METHODS: The results of 1,470 oral glucose tolerance tests from a prevalence survey for glucose intolerance and lipid abnormality in a Hong Kong Chinese working population were examined. Our previous report showed that an FPG of 5.7 mmol/l corresponded to a 2-h plasma glucose (PG) of 11.1 mmol/l, and we used this value as a cutoff value and examined the relationship between FPG and various cardiovascular risk factors in nondiabetic subjects. RESULTS: An FPG cutoff value of 7.8 mmol/l gave a sensitivity of 20.0% and a specificity of 100% in the diagnosis of diabetes (defined as 2-h PG > or = 11.1 mmol/l). We divided the non-diabetic subjects (FPG < 7.8 mmol/l and 2-h PG < 11.1 mmol/l) into two groups: subjects with FPG < 5.7 mmol/l and those with FPG > or = 5.7 mmol/l and < 7.8 mmol/l. Subjects in the latter group were older, had higher blood pressure, BMI, waist-to-hip ratio, 2-h PG, fasting and 2-h insulin, fasting serum triglyceride, VLDL cholesterol, apolipoprotein B, and urinary albumin concentrations, as well as lower plasma HDL cholesterol and HDL2 cholesterol concentrations. CONCLUSIONS: These findings suggest that an FPG cutoff value of 7.8 mmol/l, as recommended by the World Health Organization, was too high when applied to Chinese populations. As in the case of hyperlipidemia, plasma glucose concentration should be viewed as a continuum in terms of its relationship with cardiovascular risk.

Adult↗
PubMed1997

Dexfenfluramine in obese Chinese NIDDM patients. A placebo-controlled investigation of the effects on body weight, glycemic control, and cardiovascular risk factors.

OBJECTIVE: To investigate the safety, efficacy, and metabolic effects of dexfenfluramine in obese Chinese NIDDM patients. RESEARCH DESIGN AND METHODS: Thirty-two patients, mean (+/- SD) body weight 76.2 +/- 8.5 kg with corresponding BMI 31.1 +/- 2.1 kg/m2, were randomized into a two-phase study, after a 2-week single-blind run-in period on placebo. Phase 1 was a randomized 3-month double-blind placebo-controlled trial during which either dexfenfluramine or placebo was added to the existing treatment regimens of diet plus or minus sulfonylureas without metformin. Phase 2 was a further 3-month single-blind trial during which the placebo group was given dexfenfluramine without patients' knowledge of changing to active medication, while the active group continued with dexfenfluramine. Body weight, glycemic control, blood pressure, lipids, and quality of life were assessed before and at 3 and 6 months after randomization. A total of 27 patients were also followed for an additional period of 6-12 months (215 +/- 53 days) after dexfenfluramine treatment was withdrawn. RESULTS: During the run-in period, both groups were comparable for all parameters measured. At 3 months, mean changes in BMI were -1.2 +/- 1.0 kg/m2 (dexfenfluramine) vs. -0.1 +/- 0.5 kg/m2 (placebo) (P < 0.001). The mean changes in fasting plasma glucose were -1.14 +/- 0.99 vs. 0.51 +/- 1.34 mmol/l (dexfenfluramine vs. placebo, P = 0.004). HbA(1c) also significantly improved in the dexfenfluramine group (-0.80 +/- 0.53 vs. 0.25 +/- 0.64%, P < 0.001). During the 3-month single-blind dexfenfluramine treatment in the ex-placebo group, there were similar improvements in body weight and glycemic indexes. After cessation of dexfenfluramine therapy at 6 months, significant increases in body weight and glycemic indexes, almost back to the baseline, were observed for both groups. CONCLUSIONS: Dexfenfluramine aids weight loss and improves glycemic control in obese Chinese NIDDM patients over a 3- to 6-month period. These effects are emphasized after withdrawal of treatment and further support the longer-term use of dexfenfluramine for chronic complicated obesity.

Adult↗
PubMed1997

Clozapine: a mimicry of phaeochromocytoma.

OBJECTIVE: To report a case of clozapine-induced hypertension with raised urinary catecholamines. CLINICAL PICTURE: A 27-year-old man fulfilling DSM-III-R criteria for catatonic schizophrenia was treated with clozapine. He later developed both hypertension and raised urinary catecholamines which mimicked phaeochromocytoma. TREATMENT: Clozapine was withdrawn. OUTCOME: Both blood pressure and urinary catecholamines normalised. CONCLUSIONS: Clozapine may induce sympathetic hyperactivity.

Adult↗
PubMed1997

Acromegaly in a woman presenting with diabetic ketoacidosis and insulin resistance.

A 22-year-old Chinese woman presented with typical features of diabetic ketoacidosis. There was a family history of diabetes but she was not obese. Plasma glucose and bicarbonate levels were 27.0 mmol/l and 5 mmol/l, respectively. Significant insulin resistance was noticed: she needed up to 15 units of insulin per hour. She required up to 120 units daily for her diabetic control even after her acidosis had subsided. She was then noticed to have the clinical features of acromegaly. The diagnosis was confirmed, and a cranial CT scan confirmed the presence of a pituitary macroadenoma. She underwent uneventful trans-sphenoidal resection of the tumour and her insulin requirement gradually lessened. Acromegaly should be considered in the differential diagnosis of unexplained insulin resistance.

Acromegaly↗
PubMed1996

Endothelin-3 attenuates the cyclic GMP responses to C-type natriuretic peptide in cultured mouse astrocytes.

The effect of endothelin-3 (ET-3) on cyclic GMP (cGMP) responses to C-type natriuretic peptide (CNP) was studied in primary cultures of mouse astrocytes. Attenuation of CNP-stimulated cGMP formation by ET-3 was time-dependent, with maximum inhibition achieved at 30 min of preincubation. ET-3 suppressed cGMP production in response to 10 nM CNP in a dose-dependent fashion, with an IC50 of 0.04 nM and a maximal inhibitory concentration of 1 microM, which led to a 66% reduction of the cGMP increment from 45.0 +/- 4.2 pmol/mg protein to 15.4 +/- 2.6 pmol/mg protein. ET-1, ET-2, and ET-3 were equipotent in suppressing the CNP-induced cGMP response, suggesting that this effect was mediated by ETB receptors. Staurosporine, Ro 31-8220, calcium-free medium, nifedipine, verapamil, lanthanum, thapsigargin, BAPTA, W7, calmidazolium, U-73122, neomycin, quinacrine, wortmannin, herbimycin-A, okadaic acid, and sodium orthovanadate failed to block the effect of ET-3. Cycloheximide (100 microM), however, partially but significantly reversed the inhibitory effect of ET-3 on CNP-induced cGMP from 48.2 to 73.3% of the control value. The results support the premise that ET-3 and CNP interact within the central nervous system. The data also suggest that cGMP accumulation in mouse astrocytes is mediated by activation of certain kinases through as yet undefined mechanisms and not by protein kinase C, increased intracellular calcium, or other second messenger pathways such as phospholipases A2, C, D, tyrosine kinase, or protein phosphatases.

Adenosine Diphosphate Ribose↗
PubMed1996

Adrenomedullin, a novel vasoactive hormone, binds to mouse astrocytes and stimulates cyclic AMP production.

We have examined the effects of adrenomedullin (AM), a novel hypotensive peptide first isolated from human pheochromocytoma, on receptor binding and cyclic AMP (cAMP) generation in primary cultures of mouse astrocytes. Competition binding studies showed that rat adrenomedullin (rAM) displaced the specific binding of [125I]rAM in a dose-dependent manner, with an estimated IC50 of 33 nM. Rat calcitonin gene-related peptide (rCGRP), which interacts with AM receptors in some vascular tissues, did not produce significant displacement of [125I]rAM at concentrations up to 3.3 microM. rAM stimulated cAMP production in mouse astrocytes in a dose-dependent manner, with an EC50 of 74 nM and a maximal stimulatory concentration of 1 microM. CGRP8-37, a CGRP receptor antagonist, failed to inhibit the cAMP response to rAM, although it attenuated CGRP-stimulated cAMP production. These data indicate that cultured mouse astrocytes possess specific AM receptors which are coupled to adenylate cyclase but do not interact with CGRP. AM may function as a neuropeptide and may play a role in the central regulation of blood pressure and body fluid balance.

Adrenomedullin↗
PubMed1996

Identification of C-type natriuretic peptide gene transcripts in glial cells.

C-type natriuretic peptide (CNP), a third member of the natriuretic peptide family, is found throughout the central nervous system (CNS), particularly in those regions involved in neuroendocrine regulation. Astrocytes, which have important physiological roles in normal neuronal functioning, express receptors of CNP. Using reverse transcription-polymerase chain reaction (RT-PCR), followed by hybridization with a digoxigenin-labelled cDNA probe, we have demonstrated the expression of CNP gene transcripts in both cultured mouse astrocytes and rat C6 glioma cells, with the former expressing the gene at a considerably higher level than the latter. Our data raise the possibility that CNP may act in autocrine and/or paracrine fashion in glial cell physiology and neuromodulate communication between glial cells and neurones.

Animals↗
PubMed1996

Albuminuria, insulin resistance and dyslipidaemia in Chinese patients with non-insulin-dependent diabetes (NIDDM).

In order to examine relationships between albuminuria, insulin resistance, and dyslipidaemia in non-insulin-dependent diabetes (NIDDM), we studied 164 Chinese patients (68 men, 96 women), treated with diet or oral hypoglycaemic agents, on three occasions during a 6-week period. Antihypertensive treatment, if previously prescribed, was withdrawn for at least 2 weeks before the study period. Insulin resistance was calculated from simultaneous fasting plasma glucose and insulin concentrations using the homeostasis model assessment (HOMA) method. Based on two of three 24 h urinary collections, 87 (53%) patients had normoalbuminuria, 46 (28%) microalbuminuria, and 31 (19%) macroalbuminuria. Despite similar glycaemic control, patients with abnormal albuminuria had higher mean arterial pressure, fasting plasma total cholesterol, triglyceride and serum apo B concentrations and were more insulin resistant than normoalbuminuric patients. Albuminuria correlated with mean arterial pressure (r = 0.31, p < 0.001), triglyceride (r = 0.36, p < 0.001), total cholesterol (r = 0.28, p = 0.001), apolipoprotein B (apo B) (r = 0.25, p = 0.003), and insulin resistance (r = 0.25, p < 0.002). These close associations may contribute to the increased cardiovascular risk in Chinese NIDDM patients with abnormal albuminuria.

Albuminuria↗
PubMed1996

Pancreatic beta cell function and antibodies to glutamic acid decarboxylase (anti-GAD) in Chinese patients with clinical diagnosis of insulin-dependent diabetes mellitus.

Antibodies to glutamic acid decarboxylase (anti-GAD) and pancreatic beta cell secretory function were measured in 39 consecutive Chinese patients with a clinical diagnosis of insulin-dependent diabetes mellitus (IDDM) (19 males, mean +/- SD age. 37 +/- 15 years; body mass index (BMI), 22 +/- 4 kg/m2; mean duration of disease, 6.7 +/- 5.6 years). IDDM was defined on the basis of acute symptoms with heavy ketonuria (> 3+) or ketoacidosis at diagnosis, or requirement for continuous insulin treatment within one year of diagnosis. Insulin deficiency was defined as a post-glucagon stimulated plasma C-peptide concentration < or = 0.6 nmol/l. Overall, anti-GAD antibodies were positive (> 18 units) in 23% (n = 9) of these patients. Of the 39 patients, 29 (74%) were insulin deficient and 10 (26%) were non-insulin deficient. Anti-GAD antibodies were positive in 31% of the insulin-deficient patients but in none of the non-insulin-deficient group. Insulin deficiency and anti-GAD positivity were associated with younger age, earlier age of clinical onset and lower BMI. There were independent negative relationships between levels of anti-GAD antibodies and blood pressure and a positive relationship between insulin dosage and albuminuria. This study emphasises the difficulty in differentiating clinically between IDDM and NIDDM in Chinese patients. Despite the acute presentation, these patients had variable pancreatic beta cell secretory function. The varying duration of disease may partly explain the low prevalence of positive anti-GAD antibodies in these patients, but seems unlikely to explain fully the difference from Caucasian IDDM patients.

Adult↗
PubMed1996

Binding of CNP-22 and CNP-53 to cultured mouse astrocytes and effects on cyclic GMP.

We examined the binding characteristics of the two endogenous forms of C-type natriuretic peptide (CNP-22 and CNP-53) and their effects on cyclic GMP (cGMP) accumulation in primary cultures of mouse astrocytes. CNP-22 and CNP-53 competitively inhibited the specific binding of [125I][Tyr0]CNP, with an IC50 value of 32 and 37 pM, respectively. They also induced cGMP production in a dose-dependent and similar fashion, with an EC50 of 32 nM and maximal cGMP responses of 189.6 +/- 21.6 pmol/mg protein for CNP-22, and 170.3 +/- 18.7 pmol/mg protein for CNP-53, respectively. The effect of CNP-53 could not be explained by conversion to CNP-22, because HPLC analysis did not show significant proteolytic conversion by astrocytes during the incubation. Our results suggest that CNP-53 could, in concert with other natriuretic peptides, have a neuromodulatory function and thereby contribute to the central regulation of hemodynamic and fluid homeostasis.

Animals↗
PubMed1996

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry.

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell-mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ-specific autoimmune disease.

Abatacept↗
PubMed1996

Diastolic dysfunction and natriuretic peptides in systolic heart failure. Higher ANP and BNP levels are associated with the restrictive filling pattern.

BACKGROUND: Left ventricular diastolic dysfunction is common in patients with systolic heart failure and the restrictive type of filling pattern appears to be associated with increased cardiac mortality. Both artrial and brain (or ventricular) natriuretic peptides are also proven markers of the severity of heart failure. The aim of this study was to determine in a large cohort of patients with systolic heart failure whether diastolic abnormalities, and in particular the restrictive filling pattern of transmitral flow velocity, correlate with plasma atrial and brain natriuretic peptide levels. METHODS: Sixty-eight consecutive patients with symptomatic systolic heart failure (ejection fraction < 0.5) underwent two-dimensional Doppler echocardiography of left ventricular systolic and diastolic function, together with measurement of atrial and brain natriuretic peptides. RESULTS: The restrictive filling pattern was present in 62%, the abnormal relaxation pattern in 31% and only 7% were normal. Atrial and brain natriuretic peptide (ANP/BNP) levels were significantly higher in the restrictive compared to the abnormal relaxation group (ANP: 202.2 +/- 31.7 vs 102.5 +/- 22.1 pg.ml-1, P = 0.012; BNP: 277.8 +/- 27.7 vs 162.4 +/- 21.9 pg.ml-1, P = 0.002). In addition, a restrictive filling pattern was associated with lower ejection fractions (P = 0.026), higher pulmonary artery systolic pressure (P < 0.001), larger left atrial size (P = 0.044), and were more likely to be in New York Heart Association class III or IV than those with an abnormal relaxation pattern (P = 0.007). Both atrial and brain natriuretic peptides correlated inversely with ejection fraction (P < 0.001), fractional shortening (P < 0.001), and positively with pulmonary artery pressure (P = 0.004 and 0.001 respectively). There were no significant correlations between single diastolic parameters and atrial or brain natriuretic peptide levels for the total patient group except between mitral peak A wave velocity and brain natriuretic peptides (r = -0.3, P = 0.01). For those with abnormal relaxation pattern mitral, valve E-wave deceleration time correlated significantly with both atrial and brain natriuretic peptide levels (P < 0.01). CONCLUSIONS: This study confirms that the restrictive filling pattern of transmitral flow velocity is a marker of more severe heart failure, as indicated by its association with higher atrial and brain natriuretic peptide levels, lower ejection fraction and higher pulmonary artery pressure. Thus, this easily obtained Doppler-derived marker of diastolic dysfunction is useful for identifying those patients with more severe heart failure.

Aged↗
PubMed1996

Thyrotoxic periodic paralysis in a Chinese population.

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium < or = 3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+/- SEM) plasma potassium on admission was 2.17 +/- 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis does not exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.

Adult↗
PubMed1996

Thyrotoxicosis and renal tubular acidosis presenting as hypokalaemic paralysis.

A 34-yr-old Chinese woman presented with hypokalaemic periodic paralysis. She had a goitre and was biochemically thyrotoxic. However, she also had urinary potassium loss with a metabolic acidosis and reduced ability to acidify her urine. The co-existence of distal renal tubular acidosis (RTA) was confirmed. There was no evidence of xerostomia or xerophthalmia, although anti-Ro antibody and rheumatoid factor were positive. Paralytic attacks did not recur after the thyrotoxicosis was controlled with radioactive iodine. Possible pathogenic mechanisms for the association of these disorders are discussed. Female patients presenting with thyrotoxic periodic paralysis (TPP) should be thoroughly investigated for possible additional precipitating factors in view of the strong male predominance of TPP, particularly when there are atypical metabolic features.

Acidosis, Renal Tubular↗
PubMed1996

Serum bilirubin and cardiovascular risk factors in a Chinese population.

BACKGROUND: Many risk factors for cardiovascular disease (CVD) have been identified. Recently an association between low concentration of serum bilirubin and increased risk of CVD has been reported. However, information on this topic remains scarce. METHODS: We examined the relationships between serum bilirubin and CVD risk factors in 1508 Hong Kong Chinese. We divided the subjects into four quartiles based on serum bilirubin concentrations. Cardiovascular risk factors studied include age, sex, smoking, obesity glycaemic status and lipid indices. RESULTS: Decreasing serum bilirubin concentration was associated with older age, increased prevalence of smoking, higher body mass index and systolic blood pressure, increased glycated haemoglobin, fasting and 2 h insulin, triglyceride, very-low-density lipoprotein and apolipoprotein B concentrations, and lower high-density lipoprotein concentration. Women had lower bilirubin concentrations than men. After adjustment for age, sex, smoking and insulin levels as covariates, the associations between serum bilirubin concentration and glycated haemoglobin, triglyceride, high-density lipoprotein and very-low-density lipoprotein persisted. The prevalence rates of abnormal glucose tolerance (impaired glucose tolerance or diabetes) were similar amongst the four quartiles of bilirubin concentrations. However, the mean bilirubin concentration was significantly lower in subjects with abnormal glucose tolerance (9.3 +/- 3.5 mumol/l, n = 178) than in normal subjects (10.1 +/- 5.2 mumol/l, n = 1330, P = 0.039). When analysed as a continuous variable by age-adjusted partial correlation coefficients, serum bilirubin concentration was inversely correlated with fasting insulin, triglyceride, very-low-density lipoprotein and glycated haemoglobin level. CONCLUSIONS: There were close associations between low serum bilirubin concentration and increased CVD risk factors. Subjects with abnormal glucose tolerance also had lower serum bilirubin concentration than normal subjects. Some of these associations (body mass index, systolic blood pressure) could be explained by differences in insulin level. These relationships between bilirubin and CVD risk factors require further clarification, although abnormal intermediary metabolism and antioxidant deficiency may be possible linking factors.

Adult↗