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Biomedical subjects

C C Chow

Publications and source records attributed to C C Chow.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

Autoimmune polyglandular syndrome and primary biliary cirrhosis.

Liver involvement in autoimmune polyglandular syndrome (APS) in the form of chronic active hepatitis has been well described. However, to our knowledge, primary biliary cirrhosis in APS has not been reported. Here we report the case of a 27-year-old man who presented with classical insulin-dependent diabetes mellitus and subsequently developed Hashimoto's thyroiditis, hypogonadism, and primary biliary cirrhosis. The latter diagnosis was confirmed by a cholestatic pattern of liver enzymes, positive anti-mitochondrial antibody, normal cholangiogram, and characteristic liver biopsy findings. Primary biliary cirrhosis should probably be regarded as a possible, though uncommon, component of APS.

Adult↗

Stochastic resonance without tuning.

Stochastic resonance (SR) is a phenomenon wherein the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular, non-zero level of noise. SR has been proposed as a means for improving signal detection in a wide variety of systems, including superconducting quantum interference devices, and may be used in some natural systems such as sensory neurons. But for SR to be effective in a single-unit system (such as a sensory neuron or a single ion channel), the optimal intensity of the noise must be adjusted as the nature of the signal to be detected changes. This has been thought to impose a limitation on the practical and natural uses of SR. Here we show that the ability of a summing network of excitable units to detect a range of weak (sub-threshold) signals (either periodic or aperiodic) can be optimized by a fixed level of noise, irrespective of the nature of the input signal. We also show that this noise does not significantly degrade the ability of the network to detect suprathreshold signals. Thus, large nonlinear networks do not suffer from the limitations of SR in single units, and might be able to use a single noise level, such as that provided by the intrinsic noise of the individual components, to enhance the system's sensitivity to weak inputs. This suggests a functional role for neuronal noise in sensory systems.

Models, Neurological↗

Vascular complications of pancreatic transplantation: MR evaluation.

PURPOSE: To determine the value of magnetic resonance (MR) angiography and MR imaging with dynamic gadopentetate dimeglumine-enhanced gradient-echo (Gd-GRE) sequences in detection of vascular complications of pancreatic transplantation. MATERIALS AND METHODS: Three radiologists evaluated findings of 32 MR examinations in 20 adult patients who underwent pancreatic transplantation. The images were obtained with a surface coil and T1-weighted and T2-weighted fast spin-echo sequences, Gd-GRE sequences, and MR angiography. Vascular abnormality was confirmed at surgery or biopsy, and vascular patency with clinical correlation. RESULTS: Absence of flow was found in six of 32 studies (19%): acute vascular thrombosis of the vascular pedicle and/or branch vessels in four studies (three patients) and chronic pancreatic rejection in two studies (one patient). Gd-GRE images helped identify infarction in two patients. The sensitivity of MR angiography for detection of acute vascular compromise was 100%, and the specificity was 93%. CONCLUSION: MR angiography and MR imaging with Gd-GRE sequences allow detection of vascular complications of pancreatic transplantation.

Adult↗

Euthyroid sick syndrome in pulmonary tuberculosis before and after treatment.

Alterations of circulating thyroid hormones are frequently present in chronic nonthyroidal illnesses and may predict prognosis. Pulmonary tuberculosis, a common treatable debilitating disease, may provide a useful model for detailed evaluation of changes of thyroid hormones in relation to subsequent recovery or mortality. Over a period of 12 months, we performed a prospective study of 40 consecutive Chinese patients aged over 50 years and admitted with newly diagnosed pulmonary tuberculosis. Blood samples were drawn for serial thyroid function tests [free thyroxine (T4), free triiodothyronine (T3) and thyroid-stimulating hormone] before treatment and at 1, 2 and 4 months afterwards. Mortality was determined up to 12 months of follow-up. The euthyroid sick syndrome occurred in 63% of patients at presentation. Twelve of 25 euthyroid sick patients died as compared to one of 15 patients with normal baseline thyroid function tests (P < 0.02). Among euthyroid sick patients, those who died had significantly lower free T3 concentration at presentation than those who survived (P < 0.05). An undetectable free T3 concentration at presentation was associated with a subsequent mortality of 75% (9 of 12). Of the survivors, all patients demonstrated a significant rise in serum free T4 concentrations following treatment, which was apparent by 1 month. These data suggest that an undetectable free T3 concentration at presentation reflects severity of illness and predicts a subsequent high mortality.

Aged↗

Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients.

OBJECTIVES: Optimal insulin regimens for non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patients receiving insulin either alone or in combination with their previous oral hypoglycemic agents (OHAs). RESEARCH DESIGN AND METHODS: Fifty-three Chinese patients with NIDDM (mean age 53.9 +/- 12.6 years, duration of diabetes 9.0 +/- 4.9 years, body wt 60.4 +/- 13.3 kg with corresponding body mass index 24.2 +/- 4.3 kg/m2, receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA failure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice-daily insulin (insulin group). Insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) < 7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemic control, and quality of life were assessed before and at 3 and 6 months after stabilization. RESULTS: Both groups showed similar improvement of glycemic control. For the combination group, FPG decreased from 13.5 +/- 2.7 to 8.9 +/- 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 +/- 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 +/- 3.6 to 7.5 +/-3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 +/- 3.5 mmol/l at 6 months (P < 0.0001). No significant differences were observed between the groups. Similarly, both groups had significant improvement of fructosamine and glycosylated hemoglobin (HbA1c). Fructosamine fell from a mean of 458 to 365 mumol/l at 3 months (P < 0.0001) and to 371 mumol/l at 6 months (P < 0.0001) and from 484 to 325 mumol/l at 3 months (P < 0.0001) and to 350 mumol/l at 6 months (P < 0.0001) for the combination and insulin groups, respectively. HbA1c decreased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 months (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 months (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements were very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs 57.2 U/day, P < 0>0001). Both groups gained weight. However, for the combination group, weight gain was 1.6 +/- 1.8 kg at 3 months and 2.1 +/- 2.5% kg at 6 months (both P < 0.0001 vs baseline), whereas for the insulin group, weight gain was 3.5 +/- 4.3 and 5.2 +/- 4.1 kg, respectively (both P < 0.0001 vs baseline). Weight gain was significantly greater in the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 +/- 1.0 to 1.4 +/- 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 +/ 0.7 mmol/l at 6 months [P < 0.02] but not in the combination group. No changes were observed in total and high-density lipoprotein cholesterol. No severe hypoglycemic reactions were recorded in either group. Mild reactions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority of patients (82.7%) wanted to continue insulin beyond 6 months, irrespective of the treatment group. CONCLUSIONS: In NIDDM patients with secondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin replacement.

Analysis of Variance↗

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↗

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↗