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Biomedical subjects

C Walton

Publications and source records attributed to C Walton.

At least 55 records · Page 3Linked to original sources
PubMed1996

Role of oral pamidronate in preventing bone loss in postmenopausal women.

We have performed a 2-year prospective double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen. One hundred and twenty-one such women (mean +/- SD age 57.6 +/- 3.4 years; mean +/- SD time since menopause 7.5 +/- 3.5 years) were randomized to receive either oral pamidronate (300 mg/day) for 4 weeks every 4 months (group A), oral pamidronate (150 mg/day) for 4 weeks every 2 months (group B) or identical placebo capsules (group C). Bone mineral density (BMD) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry. BMD at the lumbar spine (L2-4) increased significantly in groups A and B after 2 years of treatment (mean +/- SD 2.8 +/- 2.1% and 3.0 +/- 2.9% respectively, both p < 0.001) but decreased in the placebo group (-1.6 +/- 3.1%, p < 0.01). Identical results were seen for BMD at the femoral neck, which increased significantly in groups A and B after 2 years of treatment (1.2 +/- 2.3% and 1.3 +/- 2.9% respectively, both p < 0.05) but decreased in the placebo group (-1.9 +/- 3.9%, p < 0.05). There were significant differences over 2 years between the groups at all anatomical sites (lumbar spine, femoral neck and trochanteric region, all p < 0.001; Ward's triangle, p < 0.01). However, there were no significant differences between groups A and B, suggesting that the two treatment regimens were equally effective in conserving BMD. There were, however, marked differences in tolerability between the two treatment regimens: 13 women (34%) in group A withdrew from the study because of side-effects, but only 5 women (12%) in group B, which was comparable with placebo. These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women, and that the more frequent but lower dose regimen is well tolerated.

Absorptiometry, Photon↗
PubMed1996

Measuring body fat.

Explore the source record for details and available documents.

Absorptiometry, Photon↗
PubMed1996

11 beta-hydroxylase deficiency: management of a difficult case by laparoscopic bilateral adrenalectomy.

A 14-year-old girl presented with short stature and progressive virilization. She had not undergone the menarche. On investigation, she had elevated testosterone, androstenedione, dihydroepiandrosterone sulphate and 17 alpha-hydroxyprogesterone levels, which were all suppressed by overnight dexamethasone to within their normal ranges. An initial diagnosis of 21-hydroxylase deficiency was revised to 11 beta-hydroxylase deficiency after a tetracosactrin stimulation test, which showed only a modest rise in 17 alpha-hydroxyprogesterone level (from 92 nmol/l at baseline to 133 nmol/l at 60 minutes) and measurement of the basal 11-deoxycortisol, which was grossly elevated. Treatment with dexamethasone 0.5 mg nocte resulted in suppression of androgens in the daytime, but not in the evening, particularly androstenedione. Treatment with hydrocortisone 10 mg b.d. failed to suppress testosterone or androstenedione over a 24-hour period. Addition of cyproterone and oestrogen supplements had no effect and significant virilization persisted. Laparoscopic bilateral adrenalectomy was therefore performed as definitive treatment and resulted in remarkable clinical and biochemical improvement. This case illustrates difficulties in correct diagnosis, choice of appropriate steroid regimen and monitoring efficacy of treatment in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. More aggressive management with earlier bilateral adrenalectomy may be appropriate in selected cases.

Adolescent↗
PubMed1995

Relationships between insulin metabolism, serum lipid profile, body fat distribution and blood pressure in healthy men.

Insulin resistance and hyperinsulinaemia may be important in a cluster of coronary heart disease-related metabolic disturbances known as the insulin resistance syndrome. Whether the relationships between insulin and other features of the syndrome are independent of the amount and distribution of body fat is uncertain. We have investigated these relationships in 103 healthy males, using dual-energy X-ray absorptiometry to measure body fat directly. Volunteers underwent an intravenous glucose tolerance test (IVGTT), from which insulin sensitivity, secretion and elimination were determined by mathematical modelling analysis. Independently of adiposity and body fat distribution, serum triglyceride concentration was correlated with fasting C-peptide concentration and second-phase intravenous glucose tolerance test insulin concentration (r = 0.42, P < 0.001; r = 0.28, P < 0.05). High density lipoprotein subfraction 2 (HDL2) cholesterol was correlated with fasting C-peptide, first-phase IVGTT insulin concentration, and the hepatic insulin throughout index (r = -0.15 -0.20, -0. 20 respectively, all P < 0.05). The association of HDL2 cholesterol with the hepatic throughput index was additionally independent of serum triglyceride concentration (r = -0.18, P < 0.05). Our results suggest that relative hyperinsulinaemia leads to elevated triglyceride concentration, independently of body fat mass and distribution. Furthermore, the independent association of HDL2 cholesterol with hepatic insulin throughput confirms that hepatic insulin processing may may directly influence lipoprotein metabolism.

Absorptiometry, Photon↗
PubMed1995

Body fat distribution, rather than overall adiposity, influences serum lipids and lipoproteins in healthy men independently of age.

PURPOSE: We investigated the relationships between the amount and distribution of body fat and fasting serum lipids and lipoproteins to explore whether coronary artery disease (CAD) risk may be mediated through effects on the serum lipid profile. PATIENTS AND METHODS: We determined serum total cholesterol and triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and HDL subfractions 2 and 3 in 103 healthy men, aged 21 to 77 years (mean 48.7). The amount and distribution of fat were determined directly by dual energy X-ray absorptiometry. Adiposity was determined as the ratio between total body fat tissue and total body lean tissue, while fat distribution was taken as the ratio between the mass of fat tissue in the android (central) and gynoid (hip and thigh) regions. RESULTS: Univariate analysis showed both adiposity and fat distribution to be correlated with total serum cholesterol and triglyceride concentrations (adiposity r = .20, .21; both P < 0.05: fat distribution r = .25, .38; P < 0.05, P < 0.001, respectively). Fat distribution was also negatively correlated with HDL2 cholesterol (r = -.20, P < 0.05). In multiple linear regression analysis, neither age nor adiposity was significantly correlated with any serum lipid or lipoprotein concentration, while increasing android-to-gynoid ratio was independently associated with elevated total serum triglyceride (r = .40, P < 0.01) and decreased HDL2 (r = -.25, P < 0.05) concentrations. CONCLUSIONS: The association of both age and overall adiposity with the fasting serum lipid profile are mediated via their correlations with body fat distribution. In men, the distribution, rather than the amount, of body fat is related to adverse changes in serum lipids and lipoproteins, and hence potentially to increased CAD risk.

Absorptiometry, Photon↗
PubMed1995

Multiple cerebral haematomata and peripheral nerve palsies associated with a case of juvenile diabetic ketoacidosis.

A 15-year-old girl presented de novo in diabetic ketoacidosis having been comatose for 24 h (day 1). A CT scan and lumbar puncture performed on admission were normal and her conscious level slowly improved over several days. On day 7 she had central neurological signs of bilateral knee clonus and an extensor plantar response. In addition, she had developed lower motor neurological signs of an ulnar nerve palsy of the left forearm, and ulnar, median, and radial nerve palsies of the right forearm. Magnetic resonance imaging (MRI), performed on day 12, showed multiple small cerebral haematomata with appearances at least several days of age. The scattered lesions were localized particularly to the parieto-occipital region, with sparing of the basal ganglia and without cerebral oedema, a novel feature not previously described in juvenile ketoacidosis. Four months later there was minimal residual disability of her right arm. The clinical findings together with the MRI images suggested that the peripheral nerve and central lesions were temporally related, suggesting a common aetiology. However, it is likely that MRI showed cerebral lesions which may have been missed by the conventional CT scanning performed initially.

Adolescent↗
PubMed1995

The Medicare Transaction System Initiative.

The Health Care Financing Administration is developing a system that will effectively use information technology to reduce paperwork and streamline the processing of claims. This system, targeted to be up and running by late 1997, will usher in a new model of convenience for providers, payers, and clients.

Ambulatory Care Information Systems↗
PubMed1994

Associations between insulin sensitivity, and free fatty acid and triglyceride metabolism independent of uncomplicated obesity.

Insulin resistance is associated with hypertriglyceridemia and elevated free fatty acid (FFA) concentrations in obese and diabetic individuals, but it is unclear to what extent this relationship is independent of obesity and is present in healthy individuals. We studied 92 healthy middle-aged males selected from the top, middle, and lowest quintiles of the insulin sensitivity index (Si) determined in a group of 182 men using the minimal model of glucose disappearance. Plasma FFA, triglyceride, glucose, insulin, and C-peptide concentrations were measured during a 3-hour intravenous glucose tolerance test (IVGTT). The low-Si (most insulin-resistant) group had more central body fat distribution (subscapular/triceps skinfold thickness) and a higher median body mass index (BMI) of 26.8 (range, 21.1 to 41.1) kg.m-2 compared with the middle- and high-Si groups with BMIs of 24.9 (19.1 to 31.5) and 23.7 (18.8 to 33.2) kg.m-2 (P < .05). Relatively minor glucose intolerance in the low-Si group was no longer significant when central adiposity was accounted for. Glucose tolerance was maintained by increased insulin secretion, leading to IVGTT insulin responses twofold and fourfold higher in the middle- and low-Si groups, respectively, compared with the high-Si group (P < .01). Fasting FFA and triglyceride concentrations were increased in the low-Si group relative to the other groups independent of BMI or central adiposity (P < .01). During the IVGTT, FFA decreased to similar minimum concentrations in all three groups. Triglyceride concentrations during the IVGTT increased above their minimum levels, particularly in the low-Si group (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Insulin resistance, lipoproteins, body fat and hemostasis in nonobese men with angina and a normal or abnormal coronary angiogram.

OBJECTIVES: The aim of this study was to compare metabolic risk factors in men with anginal chest pain and a normal or abnormal coronary angiogram with those in healthy men. BACKGROUND: Risk factors for coronary heart disease, including lipoprotein abnormalities, hypertension and adiposity, may be metabolically interlinked, with insulin resistance and hyperinsulinemia being pivotal to these disturbances. METHODS: Glucose and insulin metabolism, lipids and lipoproteins, hemostasis, blood pressure and body fat distribution were measured in 77 nonobese middle-aged men who had anginal chest pain (39 with an abnormal coronary angiogram and 38 with no detectable angiographic abnormality) and were compared with those of 40 healthy men of similar age and body mass index. RESULTS: Patients with chest pain had higher insulin responses to an intravenous glucose challenge, lower insulin sensitivity, lower high density lipoprotein (HDL) and subfraction 2 cholesterol, lower apolipoprotein AI, higher triglycerides, greater android fat and higher systolic blood pressure at rest compared with levels in healthy control subjects (p < 0.05). Those with an abnormal coronary angiogram had lower tissue plasminogen activator levels, higher plasminogen activator inhibitor 1 levels and more android fat than did those with a normal angiogram (p < 0.05). Insulin sensitivity correlated positively with HDL (p < 0.05) and subfraction 2 (p < 0.001) cholesterol and negatively with triglycerides (p < 0.01), android fat proportion (p < 0.01) and systolic blood pressure (p < 0.05), whereas insulin response showed converse correlations. CONCLUSIONS: These findings provide new evidence of the central role of insulin resistance and hyperinsulinemia in the development of risk factors associated with coronary heart disease.

Adult↗
PubMed1994

Effects of different antihypertensive treatments on morphologic progression of diabetic nephropathy in uninephrectomized dogs.

We previously reported the renal hemodynamic effects of different antihypertensive regimens in uninephrectomized, alloxan-induced, diabetic (DM) beagle dogs following one year of treatment. Dogs were prospectively randomized to one of five groups (N = 26): nondiabetic controls, Group I; dogs with DM on no antihypertensive drugs, Group II; dogs on a converting enzyme inhibitor, lisinopril (L), Group III; dogs on a calcium antagonist, TA3090 (diltiazem-like), Group IV; and dogs on a combination of each drug, in reduced doses, Group V. The current paper extends our previous studies by describing the morphologic changes that occurred within each group of dogs studied. More than 100 glomeruli from the renal cortex of each dog were evaluated for increases in mesangial volume fraction (Vv), glomerulosclerosis (GS) and ateriolar hyalinosis. The interstitium was also evaluated for associated changes. Increases in Vv were attenuated in all treated groups (0.28 +/- 0.04, DM alone versus 0.16 +/- 0.05 L; 0.21 +/- 0.07, TA-3090; 0.19 +/- 0.06 micron 2/micron 2, L+TA 3090; P < 0.05) compared to untreated DM. An attenuated increase in Vv also correlated with a blunted rise in proteinuria in Groups III (r = 0.79) and V (r = 0.81) but not Group IV (r = 0.29). Development of focal GS was blunted in all treated groups; however, global GS was fourfold greater in Group IV compared to untreated DM. The degree of interstitial fibrosis also correlated with the degree of global GS. These data support the concept that both a converting enzyme inhibitor and heart rate lowering calcium antagonist attenuate morphologic progression of diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Assessment of insulin sensitivity in man: a comparison of minimal model- and euglycaemic clamp-derived measures in health and heart failure.

1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable. 2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease. 3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72-0.92 (P < 0.01-P < 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03-14.63 min-1/(pmol/l) x 10(-5)]. Patients with heart failure had the lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.

Adult↗
PubMed1994

Insulin resistance in chronic heart failure.

The objective of this study was to investigate the existence of abnormalities of insulin sensitivity in patients with chronic heart failure. Glucose metabolism and insulin resistance were assessed in 10 male patients with severe, chronic heart failure and in 10 matched control subjects. Glucose, insulin and C-peptide concentration profiles were measured following a 0.5 g.kg-1 intravenous glucose tolerance test. Insulin sensitivity (inversely related to insulin resistance) was estimated by minimal modelling analysis of the glucose and insulin profiles. Heart failure patients had similar mean fasting plasma glucose concentration to controls but a significantly greater mean fasting plasma insulin concentration (P = 0.002) and C-peptide concentration (P = 0.02). Plasma glucose response profile was similar in the two groups but the incremental plasma insulin response profile of the heart failure group was significantly greater (P = 0.004). Mean insulin sensitivity was 73% lower in the heart failure patients (P = 0.003). These findings show that patients with severe chronic heart failure are hyperinsulinaemic and insulin resistant compared with a matched health group. This insulin resistance and hyperinsulinaemia may contribute to the progressive deterioration in myocardial function and associated clinical features of fatigue and reduced exercise tolerance seen in heart failure. Interventions designed to overcome or reduce insulin resistance warrant further investigation.

Blood Glucose↗
PubMed1994

Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese men.

OBJECTIVE: To assess the features of the insulin resistance syndrome in patients presenting with cardiological syndrome X, who experience angina despite angiographically normal coronary arteries. PATIENTS AND METHODS: 14 Non-obese male patients with syndrome X and 38 symptom free, apparently healthy, male volunteers were studied. Insulin sensitivity (inversely related to insulin resistance) was measured by minimal modelling analysis of glucose and insulin concentrations during an intravenous glucose tolerance test. Serum lipids, lipoproteins, and apolipoproteins were also measured. RESULTS: Insulin sensitivity was 31% lower in the men with syndrome X (p < 0.05) and fasting insulin concentration was 30% higher (p < 0.05). The patient group also had 64% higher mean triglycerides (p < 0.001) and 20% lower mean high density lipoprotein cholesterol concentration (p < 0.01). Systolic blood pressure was also 10% higher in the syndrome X group (p < 0.01). There were no differences in total cholesterol, low density lipoprotein cholesterol or lipoprotein (a). CONCLUSION: These findings show that non-obese male patients with anginal chest pain but normal coronary arteries (syndrome X) are insulin resistant, hyperinsulinaemic, and have higher concentrations of triglycerides and lower high density lipoprotein cholesterol than healthy men. The insulin resistance syndrome may predispose to a spectrum of arterial disease capable of causing myocardial ischaemia.

Adult↗
PubMed1994

HRT mechanisms of action: carbohydrates.

Elevated insulin concentrations are frequently found in both men and women with coronary heart disease (CHD), and are likely to be due to insulin resistance. Hyperinsulinaemia may increase CHD risk by directly promoting atherogenesis, and insulin propeptides may also be important in this respect. However, increased insulin concentrations may adversely affect several other CHD risk factors, and it has been postulated that insulin resistance is a pivotal metabolic disturbance in a constellation of CHD risk factors. There is an association between hyperinsulinaemia and hypertension, although it is not known if this association is direct. Increased insulin concentrations are also associated with high triglycerides, low HDL or HDL2 concentrations, and increased small dense LDL. Obesity is also associated with insulin resistance, and it is the central or android body fat distribution which correlates with these metabolic disturbances. All these associated factors constitute a distinct syndrome--the insulin resistance syndrome--which is a frequent finding in patients with CHD, including microvascular angina. It is possible that the adverse associations of insulin resistance and dyslipidaemia are mediated through increased nonesterified fatty acid flux. Increased insulin levels are also associated with increases in the anti-fibrinolytic factor, plasminogen activator inhibitor-I (PAI-I). Whilst increased insulin levels are typically associated with insulin resistance, reduced hepatic insulin uptake may also be important. We now have techniques which can quantitate insulin secretion, hepatic uptake and release, elimination, and resistance. The menopause has appreciable effect on insulin and glucose metabolism. Estrogen and progesterone augment pancreatic insulin secretion, but the former reduces insulin resistance whilst the latter increases it.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1993

Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy.

Estrogen/progestin steroid combinations adversely affect glucose tolerance and insulin resistance, but their effects in combined hormone replacement therapy (HRT) have rarely been evaluated. We studied 61 untreated symptomatic postmenopausal women randomized to receive oral (conjugated equine estrogens, 0.625 mg/d continuous + levonorgestrel, 0.075 mg/d for 12 days of each 28-day cycle) or transdermal therapy (estradiol 17 beta, 0.05 mg/d continuous + norethindrone acetate, 0.25 mg/d for 14 days of each 28-day cycle). An untreated control group of 30 postmenopausal women not seeking HRT was also studied. Intravenous glucose tolerance tests (IVGTT) were performed at baseline and 3, 6, and 18 months later. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. There were no changes in glucose or insulin concentrations with transdermal therapy. Oral therapy caused a deterioration of glucose tolerance and an increased overall plasma insulin response, apparently due to a reduction in the immediate plasma insulin response to glucose. This may have resulted from increased hepatic insulin uptake, uncompensated for by an increase in first-phase pancreatic insulin secretion. Neither treatment caused significant insulin resistance compared with baseline, but with the oral treatment insulin resistance was greater during the combined phase compared with the estrogen-only phase. Thus the oral regimen affected both insulin delivery and insulin resistance. The transdermal regimen had relatively few effects on insulin metabolism.

Administration, Cutaneous↗
PubMed1993

Inactivation of human immunodeficiency virus by a medical waste disposal process using chlorine dioxide.

OBJECTIVE: To study the ability of a medical waste disposal process using chlorine dioxide to inactivate human immunodeficiency virus type 1 (HIV-1). DESIGN: Stock HIV-1 (HTLV-IIIB strain) was treated with chlorine dioxide under the following settings: cell culture medium alone, culture medium with 25% blood, culture medium with medical supplies treated by the Condor machine (Winfield Environmental Corp., Escondido, CA). MT-2 cells in 96-well tissue culture plates were inoculated with serial tenfold dilutions of treated and untreated HIV-1. Cytopathic effect was read on day five, and the TCID50 (50% tissue culture infectious dose) was calculated. RESULTS: Treatment of HIV-1 with chlorine dioxide in culture medium alone resulted in a 5.25 log10 reduction in TCID50. Treatment of HIV-1 with chlorine dioxide in the presence of 25% blood caused a 6.25 log10 reduction in HIV-1 infectivity. Treatment of HIV-1 with chlorine dioxide in the presence of medical supplies treated in the Condor machine resulted in a 4.75 log10 reduction in HIV infectivity. CONCLUSIONS: Chlorine dioxide inactivated HIV-1 in vitro. Chlorine dioxide inactivated HIV-1 in the presence of blood and in the presence of medical supplies under conditions that simulated the conditions existing in the Condor machine.

Blood↗
PubMed1993

The effects of the menopause on insulin sensitivity, secretion and elimination in non-obese, healthy women.

We have carried out intravenous glucose tolerance tests with measurement of plasma glucose, insulin and C-peptide concentrations on 66 premenopausal and 92 postmenopausal non-obese caucasian women. After adjustment for the effects of a number of possible confounding variables, including age and body mass index, there was little difference between pre and postmenopausal women in glucose and insulin concentrations either fasting or in response to intravenous glucose. Mathematical modelling analysis of the resultant plasma concentration profiles was used to obtain measures of insulin sensitivity, secretion and elimination, and non-insulin dependent glucose disposal. We found reciprocal differences in mean insulin sensitivity (increased by 50%) and non-insulin dependent glucose disposal (decreased by 30%). Plasma C-peptide response and pancreatic insulin secretion were markedly lower in the postmenopausal group (-35% and -51% respectively). However, the rate constant for insulin elimination was also lower in these women. As a result, intravenous glucose tolerance test plasma insulin concentrations were not significantly different between the two groups. We conclude that, despite the occurrence of little or no variation in plasma glucose and insulin concentrations, the menopause is associated with significant changes in insulin metabolism.

Adult↗