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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 181 records · Page 10Linked to original sources

The effect of recombinant human insulin-like growth factor-I on chronic puromycin aminonucleoside nephropathy in rats.

We recently demonstrated that recombinant hGH exacerbates renal functional and structural injury in chronic puromycin aminonucleoside (PAN) nephropathy, an experimental model of glomerular disease. Therefore, we examined whether recombinant human (rh) IGF-I is a safer alternative for the treatment of growth failure in rats with chronic PAN nephropathy. The glomerulopathy was induced by seven serial injections of PAN over 12 wk. Experimental animals (n = 6) received rhIGF-I, 400 micrograms/d, whereas control rats (n = 6) received the vehicle. rhIGF-I improved weight gain by 14% (p < 0.05), without altering hematocrit or blood pressure in rats with renal disease. Urinary protein excretion was unaltered by rhIGF-I treatment in rats with chronic PAN nephropathy. After 12 wk, the inulin clearance was higher in rhIGF-I-treated rats, 0.48 +/- 0.08 versus 0.24 +/- 0.06 mL/min/100 g of body weight in untreated PAN nephropathy animals, p < 0.05. The improvement in GFR was not associated with enhanced glomerular hypertrophy or increased segmental glomerulosclerosis, tubulointerstitial injury, or renal cortical malondialdehyde content. In rats with PAN nephropathy, administration of rhIGF-I increased IGF-I and GH receptor gene expression, without altering the steady state level of IGF-I receptor mRNA. In normal rats with intact kidneys, rhIGF-I administration (n = 4) did not alter weight gain, blood pressure, proteinuria, GFR, glomerular planar area, renal cortical malondialdehyde content, or glomerular or tubulointerstitial damage, compared with untreated animals (n = 4). rhIGF-I treatment reduced the steady state renal IGF-I mRNA level but did not modify gene expression of the IGF-I or GH receptors. We conclude that: 1) administration of rhIGF-I improves growth and GFR in rats with chronic PAN nephropathy and 2) unlike rhGH, long-term use of rhIGF-I does not worsen renal functional and structural injury in this disease model.

Animals↗

Vitamin E ameliorates renal injury in an experimental model of immunoglobulin A nephropathy.

IgA nephropathy is one of the most common forms of glomerular disease. Nearly 25% of affected patients progress to end-stage renal disease over a 20-25-y follow-up period. IgA-containing immune complexes stimulate oxygen-free radical production by mesangial cells in vitro. The excessive oxidant stress may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal disease in an experimental model of incipient IgA nephropathy with mild kidney inflammation. IgA nephropathy was induced in male Lewis rats by oral immunization with 0.1% bovine gamma-globulin (BGG)-containing drinking water for 8 wk. At the completion of this period, animals received BGG, 1 mg/dose i.v., on three successive days. Experimental rats (n = 10) received a specially formulated diet containing 100 IU of vitamin E/kg of chow, whereas control animals (n = 10) were fed chow containing 30 IU of vitamin/kg of chow. The BGG immunization regimen induced mesangial IgA deposition in all rats. Vitamin E supplementation resulted in a nearly 5-fold increase in the serum vitamin E concentration. Vitamin E-treated rats gained more weight and had a lower incidence of hematuria, 20% versus 80% (p < 0.03). Moreover, proteinuria was decreased by 50%, and reduced renal plasma flow was restored to normal, compared with untreated rats with IgA nephropathy. Glomerular hypertrophy occurred in animals with IgA nephropathy, but less so in those receiving vitamin E supplementation. Renal cortical malondialdehyde content was reduced from 1.55 +/- 0.10 to 1.22 +/- 0.09 nmol/mg of protein (p < 0.01) in rats fed the vitamin E-enriched diet. Finally, renal transforming growth factor-beta 1 gene expression was reduced by 34% in rats with IgA nephropathy receiving vitamin E treatment (p < 0.05). We conclude that experimental IgA nephropathy is associated with increased renal oxidant injury. Dietary treatment with the antioxidant agent, vitamin E, attenuated renal functional and structural changes in this experimental glomerulopathy. These studies support the importance of clinical trials for the evaluation of the efficacy of antioxidant therapy in patients with IgA nephropathy.

Animals↗

Drug-induced disorders of glucose metabolism. Mechanisms and management.

Glucose homeostasis is maintained by a balance between the release and action of insulin, and the counterregulatory responses mediated principally by glucagon, catecholamines, growth hormone and cortisol. Hence, the effects of a drug on glucose metabolism may be mediated by any of these agents singly or in combination. Host factors, such as inherent glucoregulatory mechanisms, concurrent diseases, organ function and concomitant medications also increase the risk of drug-induced disturbances of glucose homeostasis in susceptible individuals. By far the most important agents causing hypoglycaemia are insulin and the sulphonylureas. Alcohol (ethanol), over-zealous glycaemic control, hypoglycaemic unawareness, detective counterregulation especially in insulin-dependent diabetes mellitus (IDDM), and renal and liver impairment are all important predisposing factors. Although antihyperglycaemic agents such as metformin and alpha-glucosidase inhibitors do not cause hypoglycaemia alone, they may enhance the hypoglycaemic effects of potent hypoglycaemic agents such as insulin and sulphonylureas. On the other hand, the potential hypoglycaemic effects of ACE inhibitors, alpha-blockers, lipid-lowering agents and recombinant human insulin-like growth factor demonstrated in experimental settings, are of potential therapeutic interest. Iatrogenic hypoglycaemia and intensive insulin treatment are associated with hypoglycaemic unawareness which may be obviated by meticulous avoidance of hypoglycaemia. Effective patient education remains an important preventive measure. Oral glucose is used to treat mild hypoglycaemic episodes while more severe episodes are treated by intravenous glucose or glucagon. Nasal glucagon and theophylline are other experimental measures to improve recovery from hypoglycaemia. In refractory hypoglycaemia due to hyperinsulinaemia such as during sulphonylurea overdosage or quinine treatment, the long-acting somatostatin, octreotide, may suppress insulin release and restore euglycaemia. Diuretics, beta-blockers, sympathomimetics, corticosteroids and sex hormones are commonly prescribed drugs which may have adverse effects on carbohydrate metabolism especially in patients with diabetes mellitus or those who are at risk of developing glucose intolerance. Pentamidine was frequently associated with dysglycaemia due to its pancreatic beta-cell cytotoxic effects but is now used less often to treat Pneumocystis carinii pneumonia in immunosuppressed patients. Despite the large number of anecdotal reports of drug-induced disturbances of glucose metabolism, many of the so-called adverse drug reactions were either idiosyncratic or coincidental. Nevertheless, they emphasise the complex nature of glucose homeostasis and its potential interactions with drugs, host factors and disease states. An understanding of these relationships may allow more critical interpretation of these clinical observations, better prediction of drug induced adverse effects on carbohydrate metabolism and the implementation of more rational therapy. Hence, the hypoglycaemic effects of a drug may be turned to a therapeutic advantage in patients with glucose intolerance. Similarly, the hyperglycaemic effect of a drug may help to treat refractory hypoglycaemia.

Adrenal Cortex Hormones↗

The metabolic syndrome in Hong Kong Chinese. The interrelationships among its components analyzed by structural equation modeling.

OBJECTIVE: To examine the pattern of the metabolic syndrome in Chinese and the causal relationships among its components, including aging, obesity, hyperglycemia, hypertension, hypertriglyceridemia, and hyperinsulinemia in these subjects. RESEARCH DESIGN AND METHODS: Based on a 75-g oral glucose tolerance test, the World Health Organization criteria were used for the diagnosis of glucose intolerance in a population-based study involving 1.513 Chinese subjects in two work sites. Demographic data including age, family history of diabetes, BMI, waist-to-hip ratio (WHR), and sitting blood pressure (BP) were documented. Fasting plasma glucose, triglyceride (TG) and insulin concentrations, and spot urinary albumin concentration (Ualb) were also measured. Structural equation modeling incorporating factor analysis and path analysis was performed to examine the causal relationships among these variables and their interactions. RESULTS: Subjects who were treated with antidiabetic and/or antihypertensive drugs or who had a plasma creatinine level > or = 150 mumol/l were excluded (n = 52). The prevalence of diabetes and impaired glucose tolerance (IGT) were 3.9% (n = 34) and 7.2% (n = 63) in men (n = 881) and 3.1% (n = 18) and 6.7% (n = 39) in women (n = 580), respectively. In both groups, glucose intolerance was associated with increasing age, higher BMI, WHR, BP, Ualb, serum TG, and insulin levels as well as higher prevalence rates of positive family history of diabetes. Structural equation modeling showed that age was a significant determinant for both BMI and WHR. Age and obesity accounted for most of the variance of BP, Ualb, plasma glucose, insulin and TG levels either directly or indirectly. Plasma glucose was determined by a positive family history of diabetes, age, and BMI while TG was dependent on BMI and WHR. Serum insulin was mainly determined by a positive family history of diabetes, obesity, plasma glucose, and TG levels. Apart from age and obesity, BP was also determined by serum insulin, both of which had causal effects on Ualb. CONCLUSIONS: This model emphasizes the centrality of aging and obesity as well as a positive family history of diabetes as major determinants of the components of the metabolic syndrome. These components in turn had causal effects upon one another. Apart from a familial tendency, a central neurohormonal mechanism may account for these abnormalities mediated primarily through obesity and in close association with aging.

Adult↗

Effects of uremia on growth in children.

Growth failure is a major complication of uremia in infancy and childhood. The influence of the primary renal disease leading to uremic growth retardation in children, the contributing factors leading to growth failure, such as metabolic acidosis, renal osteodystrophy, hyperparathyroidism, nutrition-endocrine and developmental disorders, are reviewed to update nephrologists on the complex issue of growth failure in children with uremia. The collaboration between endocrinologists and nephrologists in treating children with growth retardation is highlighted by a recently completed National Institutes of Health (NIH)-funded clinical trial on renal osteodystrophy plus the use of recombinant human growth hormone and insulin-like growth factor. Finally, this article concludes with a brief summary of an approach to reverse the effects of uremia on growth, including conservative nutritional management, treatment of anemia with erythropoietin, and selected aspects of growth and development after renal transplantation.

Acidosis↗

Growth in children with moderate renal insufficiency: measurement, evaluation, and treatment.

Essential in the treatment of children with chronic renal insufficiency (CRI) is the elimination of growth deficits. With the prospect of recombinant human growth hormone (rhGH) and other adjunct treatment, the appropriate measurement and assessment of growth retardation and growth recovery will document continued progress toward eliminating this disabling condition. Phases and determinants of growth at different ages are best described by growth velocity patterns. Nutritional, hormonal, and metabolic determinants interact throughout each phase of growth. Potential for growth loss and recovery is greatest during infancy and early childhood, as shown by the growth velocity index (GVI) of change in height standard deviation score (SDS) (deltaHt - SDS) divided by the growth velocity - SDS (GV - SDS) (GVI = deltaHT - SDS/GV - SDS). An appropriate target height based on potential from mid-parental heights should be set before intervention to establish goals for duration of treatment. Ultimate adult height is the only true measurement of outcome, although predictive formulas based on parental heights and bone age versus chronologic age (BA/CA) are mathematic tools to gauge the efficacy of ongoing regimes. True catch-up growth is defined as the full recovery of lost percentiles and cannot be assumed with an increase in growth velocity or incremental gain in Ht-SDS.

Adult↗

Waist circumference as a screening measurement for overweight or centrally obese Chinese.

The hypothesis that a single measurement, waist circumference, might be useful to identify people at health risk both from being overweight and from having central obesity was tested using data on 1513 subjects from a prevalence survey of diabetes mellitus in Hong Kong Chinese. It was found that a waist circumference > or = 94 cm for men and > or = 80 cm for women identified subjects with high BMI (> or = 25 kg/m2), and those with lower BMI but high WHR (> or = 0.95 for men, > or = 0.80 for women) with a sensitivity of < 31% and specificity of 100%. Decreasing the waist circumference cut-off to 85 cm for men and 75 cm for women increased the sensitivity to 79.2% in men and 56.4% in women. It was concluded that a single waist circumference measurement did not allow sensitive identification of people at health risk from being overweight or from having central obesity.

Adult↗

Urinary dopamine outputs do not rise in healthy Chinese subjects during gradually increasing oral sodium intake over 8 days.

1. All previous studies on the effects of changes in sodium intake on the renal dopamine (DA) response (increase in urinary DA output) have used sudden, large changes in oral sodium intake. The present study was designed to study the role of renal DA and the suppression of sympathetic nervous system activity in the natriuretic response to step-wise, gradual increases in sodium intake. 2. Seven healthy, male Chinese subjects (23-25 years) were studied. During the 12-day study period (day -3 to 8), subjects were given the same basic diet containing 1900 calories, 75 g protein, 20 mmol sodium and 45 mmol potassium. From days 1 to 8, subjects also received 'Slow sodium' tablets (Ciba-Geigy) equivalent to 50 mmol on day 1, 100 mmol on day 2, 150 mmol on day 3,200 mmol on day 4, 250 mmol on day 5, and 300 mmol on days 6 to 8. Body weight was recorded and blood pressure was measured after lying supine for 10 min in the morning before breakfast on entry and at the end of the low and high sodium intake periods. Urine was collected for 24 h on day -3 and from days 0 to 8 for the measurement of sodium, potassium, creatinine, free DA and free noradrenaline (NA). 3. After 4 days of sodium restriction, mean arterial pressure (mean +/- SEM) had decreased from 83.0 +/- 1.3 to 79.4 +/- 0.5 (P < 0.05) and body weight from 70.2 +/- 3.1 to 68.3 +/- 3.0 (P < 0.02). Following sodium loading, MAP and body weight did not change, but pulse rate had decreased from 64.1 +/- 2.8 to 57.4 +/- 2.6 (P < 0.02). 4. There was a 13-fold increase in sodium excretion (P < 0.02) by the last day of the high sodium intake period. There were no significant changes in urine volume and urinary excretion of potassium, creatinine and free DA throughout the high sodium intake period. In contrast, there was a 19.9-26.5% decrease in urine NA 4 and 6 days after the start of the increase in sodium intake. 5. Healthy Chinese subjects do not have a renal DA response to gradually increasing sodium intake over an 8-day period. Any tendency to hypervolaemia-related rises in blood pressure during the high sodium intake period may be partly offset by a reduction in sympathetic nervous system activity.

Adult↗

Ingestion of fluoride dentifrice by a group of mentally handicapped children during toothbrushing.

The purpose of this study was to determine the amount of fluoride dentifrice ingested by mentally handicapped children during toothbrushing. A group of 24 mentally handicapped children, aged between 3 and 12 years, were used in the study. There were encouraged to brush in their usual way with a sodium fluoride dentifrice from a preweighed tube. Rinsings and excess dentifrice were collected, and fluoride analyses were performed on the rinsings and controls. The amount of fluoride retained was in the range of 14 to 269 micrograms, with a mean of 87 micrograms, equivalent to a mean retention of 23.5% of dentifrice. This is similar to findings of studies of children of normal intelligence. Thus, fluoridated dentifrices should be used by mentally handicapped children, but, as with all young children, small amounts of dentifrice should be used, preferably under direct adult supervision.

Analysis of Variance↗

Human minisatellite loci composed of interspersed GGA-GGT triplet repeats.

We have isolated two tandemly repeated loci from human DNA which contain long blocks of GGA and GGT trinucleotide repeats. These two repeat unit types, together with other less common variants, are apparently irregularly interspersed along each repeat array. Genotyping methods have been developed for these highly polymorphic loci, including typing by polymerase chain reaction followed by Southern blot hybridization. Linkage analysis in Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees has been used to map the loci to chromosomes 15 and 22. In normal individuals, alleles at these loci can contain thousands of repeats, greatly exceeding repeat copy number at most trinucleotide and other simple repeat loci. No evidence for longer, higher-order repeats was observed among the limited number of repeats sequenced. These loci may represent a transitional state between simple repeat loci and some minisatellites.

Animals↗

The kidney in acid-base balance.

The practitioner's approach to the pediatric patient with metabolic acidosis begins with calculation of the serum anion gap, which allows the clinician to place the patient in one of two categories of acid-base disturbance: a normal anion gap acidosis or high anion gap acidosis. Likewise, the patient with metabolic alkalosis can be categorized by urinary chloride concentration and the response to chloride replenishment as either chloride-responsive or chloride-resistant. The disease states associated with each category are reviewed in this article.

Acid-Base Equilibrium↗

Insulin-like growth factor-I gene expression in the tibial epiphyseal growth plate of growth hormone-treated uremic rats.

To identify the molecular mechanisms involved in long bone growth of uremic animals, we evaluated the effects of recombinant human growth hormone (rhGH) supplementation on whole body growth, growth plate morphometrics, and insulin-like growth factor-I (IGF-I) gene expression in the tibial epiphyseal growth plates of uremic rats. Uremia was induced by a two-stage subtotal nephrectomy (Nx) of 30-day-old rats, followed by rhGH (N = 6) or saline (N = 6) treatment from day 56 to day 70 of age. Controls (N = 4) were sham decapsulated. Treatment with rhGH on Nx animals caused: (1) a significant increase in weight, (2) longitudinal growth similar to controls, and (3) increased total growth plate width predominantly due to an increase in hypertrophic zone width. rhGH increased IGF-I mRNA abundance in both zones, but the increase was greater in the proliferative zone. These changes were accompanied by concomitant alterations in IGF-I immunoreactivity. In uremic animals, therefore, rhGH treatment induces local IGF-I gene expression in the growth plate and increases the hypertrophic zone width but not the proliferative zone width. The latter suggests resistance to IGF-I action in that zone.

Animals↗

Transplantation for primary hyperoxaluria in the USA.

US data were sought for transplantation in primary hyperoxaluria (PH). The USRDS recorded 194 patients since 1974. By lifetable analysis, survival was better for transplanted than for non-transplanted patients (P < 0.001), even after trimming data for age < 55 and end-stage renal disease since 1985 (63 patients, 39 transplanted, 24 not transplanted). Transplant survival was longer for living related donor (21) vs cadaveric (17) transplants. Twenty-nine kidney transplants in 22 children were registered in NAPRTCS. Interview data with physicians showed that eight of 17 living related donor kidneys functioned well, three were borderline and six were lost. All six cadaver kidneys were lost. Four of six kidney-liver transplants functioned, and two died. United Network for Organ Sharing recorded 13 kidney-liver transplants in 11 patients. Six initially functioned well; two were retransplanted. Ultimately seven lived and four died. Overall, transplant is better than no transplant; cadaver donation results are poor; living related kidney donation can succeed; and kidney-liver transplant is still problematic in the US, and rarely follows appropriate investigation. Until more cooperative effort can be achieved, isolated kidney living related donor transplant is preferable, and does not preclude kidney-liver transplant later.

Adolescent↗

Is there a difference in dental caries between myopic and nonmyopic children?

A number of authors have reported that myopia is associated with high amounts of dental caries. Collagen is a major constituent of dentine and it is possible that the association between myopia and dental caries is a sign of a common collagen defect. Dental caries was quantified in an unselected sample of 9-year-old Hong Kong Chinese children, of whom 22 were subsequently classified as myopic and 80 as nonmyopic. Dental and refractive examinations were carried out independently of each other. No association was found between the presence of dental caries and the refractive state of the eye.

Child↗

Nephrosis in childhood.

Succinct aspects of clinical features, pathophysiology and prognosis of nephrotic syndrome in childhood, and indications for performing renal biopsy are enumerated in this review. Orthodox treatment of the nephrotic syndrome with more recent therapeutic approaches, and the role of diuretics, albumin infusions and immunizations in patients with the nephrotic syndrome are reviewed. The etiology of peritonitis, acute renal failure, and renal transplantation are re-examined to update nephrologists on the associated complications of this common childhood disease.

Child↗

Pulmonary infections in bone marrow transplantation: the Hong Kong experience.

The pattern of pulmonary infections in 59 consecutive bone marrow transplantations in Hong Kong was reviewed. Compared with published data from other marrow transplant units, we had a lower incidence of cytomegalovirus pneumonitis (1.7%) and a higher incidence of mycobacterial infections (5%). The latter is probably related to the high background prevalence of tuberculosis in the local population. Treatment with antituberculous drugs was effective.

Bacterial Infections↗