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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 235 records · Page 13Linked to original sources

Therapeutics of X-linked hypophosphatemic rickets.

X-linked hypophosphatemia, the most common form of familial rickets, is conventionally treated with 1,25-dihydroxyvitamin D3 (5-50 ng/kg per day) plus phosphate supplementation (70-100 mg/kg per day). However, nephrocalcinosis is noted in many children treated with this therapy. Whether to treat or not and whether such treatment should be continued into adulthood or in pregnancy are unsettled questions. This article reviews these controversies and provides current recommendations.

Calcitriol↗

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↗

Expression of insulin-like growth factor-1 in uremic rats: growth hormone resistance and nutritional intake.

This study was designed to test the hypothesis that induction of insulin-like growth factor-1 (IGF-1) is reduced in the uremic rat liver, which would help to explain the purported growth hormone resistance noted in uremia. IGF-1 mRNA, in the steady state and after acute induction by two doses of 100 micrograms/100 g body wt recombinant human growth hormone (rhGH), was quantitated by solution hybridization in total liver RNA, extracted by the guanidine thiocyanate/cesium chloride gradient method. Eighteen Sprague-Dawley rats weighing 100 to 102 g were randomly divided into three groups: sham-operated control rats (control group); 5/6 nephrectomized rats (uremic group); and sham-operated controls with dietary intake matching that of the uremic rats (pair-fed group). The results showed that the steady state liver IGF-1 mRNA was 1.7 arbitrary densitometry units (ADU) in the uremic animals, and was lower than the value of 3.2 ADU in the control animals (P < 0.05). After the acute administration of rhGH, the liver IGF-1 mRNA of control, uremic and pair-fed groups showed mean increases of 154% (P < 0.05), 124% (not significant, NS) and 117% (NS), respectively. The lack of IGF-1 induction in the uremic group supported the concept of growth hormone resistance in uremia. In addition, a similar lack of induction was observed in the pair-fed group, whose food intake was 65% that of the control animals. This indicated that the lack of IGF-1 induction was at least partially due to the reduced food intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alterations in the neuroendocrine control of growth hormone secretion in the uremic rat.

Chronic renal insufficiency (CRI) is associated with growth failure in children and laboratory rats and is considered to be due, in part, to co-existent malnutrition. Alterations in hypothalamic control of growth hormone (GH) secretion have been suggested in uremic patients. We sought to determine whether factors unique to CRI play a role in this disturbance of GH regulation. Using in situ hybridization histochemistry, we compared messenger RNA (mRNA) levels for the hypothalamic neurohormones GH-releasing hormone (GHRH) and somatostatin (SRIH) in three groups: rats with CRI induced by 5/6 nephrectomy (NPX, N = 4); sham-operated, ad libitum fed rats (SAL, N = 5); and sham-operated, pair-fed rats (SPF, N = 5). We also measured plasma GH at 10 minute intervals for a six hour period via intra-atrial cannulae. The NPX group had significantly lower hypothalamic GHRH mRNA concentrations than both other groups; in addition, these levels were significantly lower in the SPF than in the SAL group. Concentrations of hypothalamic SRIH mRNA did not differ significantly among the three experimental groups. Six-hour mean plasma GH concentrations were significantly lower in the SPF (18.3 +/- 1.8 micrograms/liter) than in either the SAL (27.0 +/- 3.3 micrograms/liter) or the NPX groups (36.8 +/- 7.2 micrograms/liter); the difference in the mean plasma GH levels in the NPX vs. the SAL group did not attain statistical significance. This study provides evidence for an effect of CRI on the neuroendocrine control of GH secretion not related to caloric intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Studies of alteration of hepatic cholesterol metabolism in puromycin-induced nephrotic syndrome in rats.

Hypercholesterolemia frequently accompanies the nephrotic syndrome, but the mechanism responsible for elevation of plasma cholesterol is poorly understood. Specifically, the contribution of abnormal hepatic cholesterol metabolism to elevated concentrations of serum cholesterol has never been studied in depth. The objective of the present study was to define the alteration of hepatic cholesterol metabolism in puromycin induced nephrotic syndrome in rats. Studies involved measurements of specific activities of four enzymes participating in the maintenance of hepatic cholesterol metabolism: HMG-CoA-reductase, the rate limiting enzyme of cholesterol synthesis; cholesterol 7 alpha-hydroxylase, the rate limiting enzyme in bile acid synthesis; acyl CoA: cholesterol acyltransferase, the enzyme responsible for esterification of cholesterol; and cholesterol ester hydrolase (CEH), an enzyme which hydrolyzes cholesterol. Multiple injections of puromycin resulted in a production of nephrotic syndrome with massive proteinuria, hypoalbuminemia, hypercholesterolemia, ascites and edema. HMG-CoA-reductase (nmol/hr/mg protein) and cholesterol 7 alpha-hydroxylase activities (nmol/hr/mg protein) in rats with nephrotic syndrome were not statistically significant as compared to control rats (4.0 +/- 0.7 and 2.0 +/- 0.6 vs. 3.3 +/- 0.4 and 1.6 +/- 0.2), respectively. Our results also demonstrate, for the first time, that the normal diurnal rhythm in HMG-CoA reductase activity is no longer present in the nephrotic animals. The activities in the nephrotics in the day was 4.0 nmol/hr/mg and at night, 3.9 nmol/hr/day, compared to the control values of 3.3 nmol/hr/mg in the day and 6.9 nmol/hr/mg at night. ACAT activities were 428 +/- 78 versus 302 +/- 64 pmol/min/mg/protein (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of metabolic acidosis on the expression of insulin-like growth factor and growth hormone receptor.

To further our understanding of the growth failure in metabolic acidosis, we examined the insulin-like growth factor (IGF-I and IGF-II), the IGF binding protein-3 (IGFBP-3), and the hepatic IGF mRNA and growth hormone receptor mRNA in control, pair-fed and acidotic rats. The rats in the last group were made acidotic by using ammonium chloride (1.5%) as their sole fluid intake for eight days. Metabolic acidosis was confirmed by a blood pH of 7.11 +/- 0.10 (mean +/- SD). The mean starting weights for all rats were 167.1 +/- 3.4 grams. Growth impairment was observed in the acidotic rats after one week of ammonium chloride intake. The body weights of the acidotic rats compared to those of the control rats were 155.5 +/- 18.9 g versus 222.8 +/- 9.7 g, P < 0.001; the pair-fed rats weighed 156.8 +/- 19.6 grams. All rats were bled and sacrificed on day 8. Sera and tissue were analyzed with the following results: compared to the ad libitum controls, the same IGF-I concentrations were significantly decreased in the acidotic animals (P < 0.02) as well as pair-fed controls (P < 0.005). The serum IGF-II and IGF-binding protein-3 concentrations were unchanged by acidosis or food restriction. The hepatic IGF-I mRNA was significantly reduced by acidosis (P < 0.01) and pair-feeding (P < 0.01). Compared to control, the mean hepatic IGF mRNA in acidosis was significantly lower (P < 0.01). However, there was no significant difference between the acidotic and the pair-fed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

Effects of ultraviolet radiation on contact lens parameters.

Ultraviolet (UV) radiation has been proposed as an alternative method for contact lens disinfection. In order for UV radiation to be considered a viable contact lens disinfection method, its effects on lens polymers and parameters must be minimal. To evaluate this, soft contact lenses from each of the four FDA categories, soft lenses with handling tints, and rigid gas permeable (RGP) lenses were exposed to UV radiation in a controlled laboratory setting and their parameters measured. After 20 h of UV exposure, we found statistically significant changes in at least one parameter for each lens type evaluated. Most of these changes were small and within the error of measurement and, therefore, were not considered clinically significant. However, the group 2 soft lenses showed an increase in all four measured parameters--power, center thickness, diameter, and water content. These changes may have an impact on lens fitting characteristics and performance. Other than these changes for group 2 soft lenses, 20 h of UV exposure appeared to have little clinical effect on the contact lenses evaluated. This suggests that UV radiation may prove to be a feasible alternative method of disinfection for most types of contact lenses.

Contact Lenses, Hydrophilic↗

An insert earphone system for delivery of spectrally shaped signals for physiological studies.

Acoustic signals arriving at the eardrum in free-space carry directionally dependent temporal and spectral information resulting from the acoustical effects of the body, head, and external ear as well as from differences in the length of the sound path to each ear. Through analysis of the responses of single auditory neurons, the acoustical and neural mechanisms by which sounds in free-space are localized are being studied. The approach involves simulation of free-field signals at the two eardrums of a cat via earphones and a study of the neuronal responses to such a virtual acoustic space. This approach makes it possible to manipulate different stimulus parameters independently in order to examine their role in determining the spatial characteristics of neuronal response. This report describes an insert earphone system designed for the delivery of such simulated signals which are broadband transients having complex spectra that mimic the acoustic transfer function of the external ear for frequency components up to 30 kHz or more.

Acoustic Stimulation↗

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 acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation.

To test the hypothesis that growth retardation in nonanion gap acidosis may be associated with impairment of growth hormone (GH) secretory patterns, we examined GH secretion in rats made acidotic with ammonium chloride ingestion. Considerable growth retardation was demonstrated in pair-fed and acidotic rats after 1 wk of ammonium chloride ingestion compared with control. With stable metabolic acidosis sustained on the 8th day of experiment, pulsatile secretion of GH was evaluated by blood samples drawn every 10 min for 6 h. Using deconvolution analysis to quantitate in vivo GH secretory rates, we found significant inhibition of pulsatile GH secretion in acidotic rats. Changes in amplitude of GH pulses and mean mass of GH pulses correlated with changes in body weight. These studies showed that chronic metabolic acidosis causes growth impairment, reduced food efficiency, and amplitude-specific inhibition of pulsatile secretion of GH. We propose that this GH axis suppression, whether mediated by decreased nutrients or not, contributes significantly to growth failure in children with renal tubular acidosis. Because a similar degree of inhibition of GH secretion was seen in pair-fed rats, we infer that insufficient calorie intake in metabolic acidosis may contribute to disruption of normal GH secretion patterns. These changes in GH secretion were specific, because acidotic rats were different from pair-fed controls in that they showed no change in either half-life of GH in circulation or in pulse frequency. Such observations offer a rationale for more detailed clinical investigations into the impact of metabolic acidosis on physiological regulation of pulsatile GH secretion in humans.

Acid-Base Equilibrium↗

Glucocorticoid-induced changes in the quantity and secretory capacity of individual rat somatotropes.

Chronic glucocorticoid treatment is complicated by growth failure. The study presented here was designed to investigate the effect of cortisone on growth hormone (GH) secretion by individual pituitary cells in young male rats. Beginning at 37 days of age, animals were injected sc with cortisone acetate (CORT; 5.0 mg/rat per day) or the same volume of saline (SAL) for 8 days. At 45 days of age, the body weights of the CORT animals (134.5 +/- 5.5 g) were significantly less (P < 0.0005) than those of SAL controls (179.3 +/- 4.2 g). The secretory capacity of dispersed pituitary cells was assessed by the reverse hemolytic plaque assay. Cells were exposed to six concentrations of GH-releasing hormone (GHRH) ranging from 0.01 to 3.0 nM. CORT treatment significantly decreased the absolute number of somatotropes per pituitary gland (CORT, 1.23 +/- 0.03 x 10(6); SAL, 1.57 +/- 0.09 x 10(6); P = 0.025). Conversely, the mean plaque areas were significantly greater for CORT animals at all concentrations of GHRH tested, indicating that the amount of GH secreted by individual somatotropes was significantly increased by CORT. It was concluded that the paradoxical increase in the in vitro GHRH responsiveness, which is commonly observed after glucocorticoid treatment, was due to an increase in the capacity of fewer individual somatotropes to secrete GH.

Animals↗

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↗

Trends in asthma therapy in Hong Kong, 1987-1992.

To audit the clinical practice in drug treatment of bronchial asthma in Hong Kong, two questionnaire surveys were conducted in 1987 and 1992. The questionnaire was adapted from the 1984 European Audit. The response rate was 40% (248 of 615 mailings) in 1987 and 32% (207 of 652 mailings) in 1992. A total of 86% and 87% of responders were general practitioners (GP), respectively, and the others were chest physicians (CP). For treatment of acute severe asthma in adults, parenteral aminophylline was the first drug used by GP in 1987, whereas inhaled beta-agonist was used in 1992. Parenteral steroid was more often used by both GP and CP in 1992. In children, inhaled beta-agonist was always the first choice and parenteral steroid ranked higher in 1992, overtaking parenteral aminophylline. For maintenance therapy of chronic asthma in adults, inhaled beta-agonist ranked first in both surveys. Inhaled steroid has become much more popular with GP, ranking second in 1992, overtaking oral bronchodilators. With CP, inhaled steroid was already ranking second in 1987, and it was used as the first drug, as frequently as inhaled beta-agonist, in 1992. In children, in 1987, inhaled beta-agonist was the first drug of choice, and prophylactic drugs ranked lower than oral bronchodilators with both GP and CP. In 1992, cromoglycate and inhaled steroids were much more often used, so much so that among CP, inhaled steroid ranked first, just ahead of inhaled beta-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Disease profiles in Chinese in Hong Kong: an analysis of the primary diagnoses in 561 acute hospital medical admissions.

Little is known about the disease profiles in Chinese living in an urbanized community like Hong Kong. Accordingly, the discharge summaries of 561 acute hospital medical admissions were reviewed and the primary diagnoses (the main reason for admission or the most important clinical problem) were coded according to the International Classification of Diseases. Our data indicate that cardiovascular diseases are the most important cause of acute medical admissions and mortality and that gastrointestinal hemorrhage is very common amongst the Chinese in Hong Kong.

Adult↗

Clinical features and hospital management of bites by the white-lipped green pit viper (Trimeresurus albolabris).

The clinical features and hospital management of 31 patients who were bitten by the white-lipped green pit viper (Trimeresurus albolabris) in Hong Kong are reviewed. The cardinal features in these patients were local pain and swelling and mild coagulation abnormalities. Hospital management should include prophylaxis against tetanus, analgesics and measures to reduce local effects such as elevation of the limb. The benefits of the use of prophylactic antibiotics remain to be established. Severe coagulation disturbances were uncommon and responded to fresh frozen plasma and platelet transfusion.

Adolescent↗