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Biomedical subjects

R Swaminathan

Publications and source records attributed to R Swaminathan.

At least 19 recordsLinked to original sources

Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis.

OBJECTIVES: To compare the efficacy, safety, and tolerance of enalapril and nifedipine in hypertensive patients with non-insulin dependent diabetes. DESIGN: One year double blind follow up of patients randomly allocated to either enalapril or nifedipine with matching placebos for the alternative drug. SETTING: Metabolic Investigation Unit, Hong Kong. SUBJECTS: 102 patients were randomised: 52 to nifedipine and 50 to enalapril. At baseline 44 patients had normoalbuminuria, 36 microalbuminuria, and 22 macroalbuminuria. MAIN OUTCOME MEASURES: Blood pressure, albuminuria, and parameters of renal function and glycaemic control. RESULTS: In patients who completed one year's treatment the median dose required by the nifedipine group (n = 49) was 60 mg/day; seven (14%) required additional diuretics. Of 41 patients given enalapril, 37 required the maximum dose (40 mg/day) and 27 (76%) required diuretics. At one year mean arterial blood pressures were similar in both groups. Albuminuria fell by 54% in the enalapril group and 11% in the nifedipine group (p = 0.006). Fractional albumin clearance ratio fell by 47% in the enalapril group and increased by 3% in the nifedipine group (p = 0.009). Creatinine clearance fell similarly in both groups but plasma creatinine concentration was increased by 20% in the enalapril group versus 8% in the nifedipine group (p = 0.001). CONCLUSION: Patients taking enalapril often required diuretics to control blood pressure. Enalapril reduced proteinuria significantly more than nifedipine in the microalbuminuric and macroalbuminuric patients but increased plasma creatinine concentrations. Longer follow up is required to clarify the importance of enalapril's antiproteinuric effect.

Albuminuria

The inter-relationships between albuminuria, plasma albumin concentration and indices of glycaemic control in non-insulin-dependent diabetes mellitus.

We studied the relationship between albuminuria (measured as albumin/creatinine ratio (alb/Cr) in a random urine sample) and measures of glycaemic control (fructosamine, HbA1 and glucose) in 470 patients with non-insulin-dependent diabetes mellitus (NIDDM). Albumin excretion was in the microalbuminuric range (alb/Cr ratio > 5.4-40.3) in 112 (23.8%) and in the macroalbuminuric range (alb/Cr ratio > 40.3 mg/mmol) in 89 patients (18.9%). Fourteen percent (n = 67) of patients had a normal plasma HbA1 (< or = 8.5%) while 27% (n = 127) had a normal plasma fructosamine concentration (< or = 2.2 mmol/l). Using stepwise multiple regression analysis, plasma fructosamine concentration was found to be independently and negatively associated with urine albumin/creatinine ratio (B = 0.24, P < 0.006) in the macroalbuminuric group. Further analysis of the relationship between plasma albumin concentration and indices of glycaemic control showed that plasma albumin concentration correlated negatively with random plasma glucose concentration in the normoalbuminuric patients (r = -0.16, P = 0.008) but not in microalbuminuric or macroalbuminuric groups. HbA1 was not correlated with plasma albumin concentration. Our results indicate that albuminuria has an effect on the plasma fructosamine concentration which is independent of plasma albumin concentration.

Adult

Serum intact parathyroid hormone levels in elderly Chinese females with hip fracture.

Serum intact parathyroid hormone (PTH), 25 hydroxyvitamin D(25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), albumin, and ionized calcium were measured in 61 Chinese female patients with hip fracture and 61 control subjects. Hip fracture patients had low albumin, ionized calcium, and 250HD levels. Serum PTH and 1,25(OH)2D values were not different between the two groups. We conclude that although 250HD level in hip fracture patients is low, there is no evidence of secondary hyperparathyroidism, suggesting that the low 250HD levels may be a secondary phenomenon in response to the fracture.

Aged

The effects of calcium supplementation and exercise on bone density in elderly Chinese women.

A randomized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly. Fifty Chinese women, aged 62-92 years, living in a hostel for the elderly in Hong Kong were randomized to enter one of four treatment groups: (I) calcium supplementation of 800 mg (as calcium lactate gluconate) daily; (II) load-bearing exercise four times a week plus a daily placebo tablet; (III) calcium supplementation daily and load-bearing exercise four times a week; (IV) a placebo tablet daily. The interventions went on for 10 months. The bone mineral density (BMD) was measured at three sites in the hip (femoral neck, Ward's triangle and intertrochanteric area) and the L2-4 level of the spine. The percentage change in BMD in 10 months was used as the main outcome measurement. The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention. The BMD at Ward's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement (p less than 0.05), but there was no significant change at the spine and femoral neck. Exercise had no effect on bone loss at any site. However, the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck (p less than 0.05), but not at the other sites. The parathyroid hormone levels fell significantly in subjects on calcium supplements (p less than 0.01). Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day. It was effective in reducing bone loss at the hip, and there may be interaction effects with exercise in maintaining bone density.

Aged

A rapid assay for the measurement of Na+,K(+)-ATPase inhibitors.

A rapid and automated assay for inhibitors of Na+, K(+)-ATPase was developed by determining the amount of inorganic phosphorus (Pi) released by Na+,K(+)-ATPase in a centrifugal analyzer. This method avoids long incubation, strong acids and centrifugation as in the conventional manual method. The coefficients of variation of intra- and inter-assay at ouabain concentration 0.5 mumol/L were 1.0 and 1.4%, respectively. The method is quick, reproducible and easy compared with current techniques.

Animals

Stimulation of the Na+,K(+)-ATPase activity of K562 human erythroleukemia cells by triiodothyronine.

The effect of triiodothyronine (T3) on Na+,K(+)-ATPase activity of K562 human erythroleukemic cell was studied to understand why the erythrocyte sodium pump activity is decreased in hyperthyroidism. Na+,K(+)-ATPase activity of K562 cell lysates was assayed by measuring the release of inorganic phosphate (Pi) from ATP. Na+,K(+)-ATPase activity of K562 cell grown in the presence of T3 for 48 hours was significantly higher than that of control (0.98 +/- 0.05 mumol Pi h-1 mg protein-1 vs 0.82 +/- 0.10 mumol Pi h-1 mg protein-1, p < 0.05). The Na+,K(+)-ATPase activity could be stimulated in a time- and concentration-dependent manner; maximum stimulatory effect of T3 was seen at a concentration of 10(-7) mol/L. When an inducer [cytosine-beta-D-arabino-furanoside (ARA-C)] was added to the culture medium, the K562 cells showed signs of differentiation and synthesised haemoglobin. At the same time, the Na+,K(+)-ATPase activity remained high. We conclude that T3 stimulates Na+,K(+)-ATPase activity of K562 cells and in the presence of T3 during differentiation, the enzyme activity remains high.

Cell Differentiation

Microalbuminuria and other cardiovascular risk factors in nondiabetic subjects.

The association between urinary albumin:creatinine ratio and other cardiovascular risk factors such as age, blood pressure, obesity, glycemic indices, insulin and lipid profile was examined in a population in a Chinese community consisting of 795 men (mean age 35.8 +/- 8.8 yr) and 538 women (mean age 37.9 +/- 8.9 yr) with a normal glucose tolerance defined by WHO criteria. Men with a urinary albumin:creatinine ratio above the 90th percentile had higher systolic and diastolic blood pressures, fasting plasma glucose, 2-h glucose after a 75 g oral glucose load, and fasting serum insulin. Women with high urinary albumin:creatinine values had higher systolic and diastolic blood pressures, body mass index, waist-hip ratio, fasting insulin and triglycerides. Multivariate analysis showed that only systolic blood pressure and fasting glucose in men, and diastolic blood pressure and fasting insulin in women, independently contributed to urinary albumin:creatinine. When the effect of blood pressure was eliminated by excluding subjects with systolic blood pressure > 140 and diastolic > 90 mm Hg, only fasting insulin was associated with urinary albumin:creatinine in women. No associations were found for men. We conclude that microalbuminuria may be a marker for cardiovascular disease only because of its association with blood pressure in men, while in women, there is an additional independent association with fasting serum insulin.

Adult

Atrial natriuretic peptide and urinary dopamine output in non-insulin-dependent diabetes mellitus.

1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion < or = 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion > or = 300 mg/day). 2. The supine systolic blood pressure (mean +/- SD) was higher in patients with abnormal albuminuria (group 1: 140.9 +/- 27.4 mmHg; group 2: 158.1 +/- 26.4 mmHg; group 3: 166.7 +/- 23.9 mmHg; F = 13.1, P < 0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9-37.1) pg/ml; group 2: 39.1 (34.2-44.6) pg/ml; group 3: 50 (38.6-54.7) pg/ml; F = 4.24, P < 0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2-1437.0) nmol/day; group 2: 1142.3 (975.9-1337.2) nmol/day; group 3: 982.7 (775.7-1245) nmol/day; F = 3.10, P < 0.05, analysis of variance].(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor

Age-related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of bone metabolism in Chinese women.

OBJECTIVE: To study the age-related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of calcium metabolism in Chinese women who habitually have a low calcium intake. DESIGN: Cross-sectional study. SUBJECTS: One hundred and fifty-six healthy Chinese women aged 20-83 years. None were on any medication or vitamin supplements. Subjects over the age of 60 years were all living in a hostel; younger subjects were nurses or subjects attending a family clinic for minor illnesses. MEASUREMENTS: Fasting blood and urine samples were collected for biochemical measurements and calcium absorption was measured using 45Ca by the method of Marshall and Nordin. Bone density was measured by dual energy X-ray densitometry (Norland X R20 X-ray bone densitometer) at the left hip and lumbar spine. Serum parathyroid hormone was measured by a chemiluminometric assay. RESULTS: Plasma ionized calcium concentration, alkaline phosphatase, bicarbonate, plasma creatinine and serum B2 microglobulin were significantly higher in the elderly than in the young, whereas plasma phosphate and the anion gap were higher in the young. Urinary excretion of calcium, phosphate and hydroxyproline were all higher in older women. Plasma parathyroid hormone concentration was positively correlated with age even after taking into account the decline in renal function (as indicated by the rise in B2 microglobulin (r = 0.506, P less than 0.001). Serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were not lower in the older women. Fractional calcium absorption from an oral load of radiolabelled calcium was significantly lower in the older women and 37% of the older women were below the 2.5 percentile found in the younger women. Bone density measured by dual energy X-ray densitometry was also significantly lower in the elderly. CONCLUSION: In Chinese women there is an increase in PTH and a decrease in calcium absorption with age in spite of the presence of normal vitamin D metabolites.

Absorption

Prediction of mortality in patients in acute medical wards using basic laboratory and anthropometric data.

The value of anthropometric and biochemical indices in predicting short-term mortality among patients in general medical wards was assessed in 294 patients admitted consecutively to a district hospital over a one month period. Using a stepwise logistic regression model and supported by the linear discriminant analysis method, mortality within 3 months could be predicted with sensitivity of 83% and specificity of 84% using the following variables: sex, functional ability, urea, total protein, alkaline phosphatase and albumin-adjusted calcium. Addition of anthropometric values and biochemical nutritional indices did little to improve the accuracy of the prediction, contrary to previous findings among surgical patients and elderly residents of long-term care institutions.

Activities of Daily Living

The contribution of steroids to digoxin-like immunoreactivity in cord blood.

Samples of cord serum from 29 healthy neonates were analysed for digoxin-like immunoreactive substance (DLIS), cortisol, 17 beta-oestradiol, progesterone, dehydroepiandrosterone-sulphate (DHEAS), 17 alpha-hydroxyprogesterone (17OHP), androstenedione, oestriol and ouabain-like activity (OLA; by inhibition of Na+, K+ATPase activity). The mean serum concentration of DLIS was 0.91 (SD = 0.19) nmol/L and the mean OLA was 26.1 (SD = 11.5) nmol/L. There was no correlation between DLIS and OLA. DLIS correlated significantly with oestriol (r = 0.521), progesterone (r = 0.534) and 17OHP (r = 0.43). Stepwise multiple regression analysis showed that 17 beta-oestradiol, progesterone and androstenedione contributed to DLIS and the intercept was 0.64 (SD = 0.127). The concentrations of steroids (17 beta-oestradiol, progesterone, androstenedione) required to displace digoxin by 50% in the digoxin immunoassay and inhibit Na+,K+ATPase in the OLA assay were 10(3)-10(4)-fold higher than those found in cord serum. We conclude that the contribution of these steroids to DLIS is small and that DLIS and OLA measure different compounds.

Cross Reactions

Interrelationships between urinary sodium, calcium, hydroxyproline and serum PTH in healthy subjects.

The effect of sodium intake on the excretion of calcium, hydroxyproline (OHP) and serum parathyroid hormone (PTH) was examined. When seven healthy males increased their sodium intake by 200 mmol/day, excretion of calcium increased by 1.70 mmol/day and that of OHP by 27%. Serum PTH, however, did not increase significantly. In a cross-sectional study of 334 healthy female subjects there were strong positive correlations between fasting urinary sodium/creatinine (Na/Cr) and calcium/creatinine (Ca/Cr) ratios (r = 0.573) and between Na/Cr and urinary OHP/Cr ratios (r = 0.246). Serum PTH was negatively correlated with Na/Cr ratio (r = -0.161). We conclude that an increase in dietary sodium causes calciuria and an increase in hydroxyproline excretion. The results do not support the hypothesis that this is mediated by PTH.

Adult

Assessment of glucose tolerance test criteria for diagnosis of diabetes in Chinese subjects.

OBJECTIVE: To examine and compare WHO diagnostic criteria for diabetes mellitus. RESEARCH DESIGN AND METHOD: The relationship between FPG and 2-h glucose are examined in 680 OGTTs with a quadratic regression model and ROC analysis. Simultaneous measurements of HbA1 and fructosamine are also compared with multiple linear regression. RESULTS: Two hundred eighteen subjects (32%) had 2-h glucose greater than or equal to 11.1 mM, of which only 86 had FPG greater than or equal to 7.8 mM. Only 2 subjects had FPG greater than 7.8 mM and 2-h glucose less than 7.8 mM. Of subjects with 2-h glucose less than 7.8 mM (n = 332), only 9 had FPG greater than 6.0 mM. From the quadratic model, the predicted FPG corresponding to 2-h glucose = 11.1 mM was 5.7 mM, whereas the predicted 2-h glucose corresponding to FPG = 7.8 mM was 15.2 mM. ROC analysis showed that, with 2-h glucose greater than or equal to 11.1 mM as indicating diabetes, an FPG of 5.6 mM gave an intersect for sensitivity and specificity of 87%. HbA1 and fructosamine correlated more closely with 2-h glucose and area under the OGTT curve than with FPG. CONCLUSIONS: Given that a 2-h glucose cutoff of 11.1 mM can be justified from other studies, our results suggest that the FPG cutoff of 7.8 mM when used for screening purposes should be reduced. At a suggested value of 7.0 mM, specificity remains 98.5%, whereas sensitivity increases to 57%.

China

Influence of obesity on plasma fructosamine concentration.

The influence of obesity on plasma fructosamine concentration was studied in 68 diabetic and 1335 nondiabetic subjects from a Chinese community. Obese nondiabetic men (body mass index > 25 kg/m2) had lower fructosamine concentrations than nonobese nondiabetic men (body mass index < or = 25 kg/m2); the pattern was similar for diabetic women. Stepwise multiple-regression analysis showed that, apart from known factors (total protein, albumin, and indices of glycemic control), fructosamine was also associated with body mass index and plasma fasting triglycerides. However, the contribution of these were small except in diabetic women. We conclude that the effect of obesity on fructosamine is small.

Adult

Blood pressure and urinary cations in a Chinese population.

The prevalence of hypertension and the relationship between blood pressure, age, body mass index (BMI) and urinary cations from casual urine specimens were examined in 1,513 Chinese employees of a public utility company and non-medical personnel of a district hospital. The prevalence of hypertension, defined as systolic blood pressure greater than or equal to 140 or a diastolic blood pressure greater than or equal to 90 mmHg, or a past history of hypertension, was 17% in men and 5% in women. After excluding subjects who were on antihypertensive medication, age, body mass index, and urinary sodium/potassium ratio were independently and positively associated with blood pressure, while urinary potassium/creatinine ratio was inversely related to blood pressure. No association with urinary sodium or sodium/creatinine ratio was found. Higher mean blood pressure in men was accompanied by lower urinary potassium/creatinine and potassium concentration and higher sodium/potassium ratio, even though men had the same mean BMI when compared with women. A difference in potassium intake between the sexes may partly account for this finding. We conclude that in this Chinese population, whose dietary intake is more influenced by the West compared with Chinese in the Peoples' Republic of China, age and BMI are important determinants of blood pressure, together with potassium intake as reflected by urinary potassium excretion. No association of blood pressure with sodium excretion was demonstrated.

Adolescent

Association between insulin and blood pressure in a community population with normal glucose tolerance.

The purpose of this study was to examine the relationship between insulin and BP in patients with normal glucose tolerance. The associations between systolic and diastolic BP, age, body mass index, waist/hip ratio, fasting glucose, insulin, fructosamine, glycosylated haemoglobin, lipid profile, and glucose and insulin two hours after 75 g oral glucose were examined in 1,520 employees of a public utility company and non-medical staff of a district hospital. Patients with impaired glucose tolerance or diabetes mellitus (using WHO criteria) were excluded. In men (mean age 35.6 +/- 8.7 years, n = 769), both systolic and diastolic BP were positively associated with age, body mass index, waist/hip ratio, fasting and 2h glucose and insulin, triglycerides and apolipoprotein B, and were negatively associated with glucose/insulin ration, and high density lipoprotein and cholesterol and its subfractions. However, in multivariate analysis only body mass index, age, fasting glucose and insulin were independent predictors of systolic BP, while only body mass index and age predicted diastolic BP. In women, age, glycosylated haemoglobin, 2h glucose/insulin ratio, 2h glucose, fructosamine and triglycerides were predictors of systolic BP. Fasting or 2h insulin, and glucose/insulin ratios did not predict diastolic BP. The results are compatible with the hypothesis that systolic hypertension may reflect a hyper-insulinaemic state even in those with normal glucose tolerance, independent of age and obesity. The association between plasma lipids and blood pressure is probably mediated by insulin and obesity.

Adult

D-mannose as a preservative of glucose in blood samples.

We studied the changes in blood glucose concentration in blood samples collected in heparinized specimen tubes containing no other preservative, or containing NaF, D-mannose, or a combination of NaF and D-mannose. Blood concentration in samples taken into NaF decreased by 0.40 mmol/L in the first 2 h; thereafter, there was no change. In samples collected into mannose there was a small but significant decrease in blood glucose concentration with time. When samples containing mannose were analyzed immediately after collection, the concentration of glucose was higher than in later analyses, probably because of an exchange of intracellular glucose for extracellular mannose. When a combination of NaF and mannose was used, the blood glucose concentration was relatively stable but slightly higher than nonpreserved samples for the next 24 h. However, samples containing mannose were unsuitable for electrolyte analysis. We conclude that a combination of D-mannose and NaF may be a better preservative for blood glucose than either compound alone.

Adult