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J C Stevenson

Publications and source records attributed to J C Stevenson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Elevated serum lipoprotein(a) levels in young women with endometriosis.

Elevated serum lipoprotein(a) [Lp(a)] levels increase the risk of cardiovascular disease if levels of low-density lipoproteins (LDLs) are also high. The biological function of Lp(a) is unknown, but plasma levels may be elevated in inflammatory disease. Endometriosis is a common gynecologic disorder in which endometrial tissue is found outside of the lining of the uterine cavity. There is an immune component to this condition whereby the number of peritoneal macrophages is increased and the level of prostanoids and cytokines in peritoneal fluid is elevated. In the present study, we measured serum lipid, lipoprotein, and apolipoprotein levels in 29 women with endometriosis and in 29 matched healthy controls. Fasting serum triglyceride and apolipoprotein (apo) Al levels were higher in women with endometriosis (+28.1%, P < .001, and +12.3%, P < .01, respectively), but there were no significant differences in LDL or high-density lipoprotein (HDL) cholesterol levels. Serum Lp(a) levels were fivefold higher (P < .01) in the patients (median, 15.0 mg/dL; range, 0.05 to 60.0) than in controls (median, 3.1 mg/dL; range, 0.05 to 57.2). The distribution of apo(a) isoforms was similar in the two groups, but in women with endometriosis the individual apo(a) isoforms tended to be associated with higher serum Lp(a) levels. Endometriosis may represent a relatively common condition in which to investigate the role of Lp(a) in human metabolism.

Adult↗
PubMed1997

Physiological hyperinsulinemia is not associated with alterations in venous plasma levels of endothelin-1 in healthy individuals.

Elevations in circulating levels of both endothelin-1 (ET-1) and insulin are found in coronary heart disease and chronic heart failure. Although several studies have shown that insulin can stimulate ET-1 release from endothelial cell cultures, in vivo studies have yielded equivocal results. We sought to determine whether endogenous insulin at physiological concentrations leads to alterations in venous plasma ET-1 levels in healthy subjects. In addition, we investigated the effects of physiological and supraphysiological doses of insulin on the release of ET-1 from human umbilical vein endothelial cells (HUVECs) in vitro. In the in vitro experiment, ET-1 and insulin levels were measured during an intravenous glucose tolerance test (IVGTT) in 10 healthy subjects. In the in vitro experiment, HUVECs were incubated in the absence of serum and with different concentrations of insulin (25 pmol/L to 1 mumol/L) for 4 hours before measurement of secreted ET-1. The in vivo study showed no significant alterations in venous plasma ET-1 levels during IVGTTs (maximum plasma insulin, 616.9 +/- 147.0 pmol/L [mean +/- SEM]). In the in vitro experiment, increases in ET-1 release were observed under serum-free conditions at 100 pmol/L (physiological) and 1 mumol/L (supraphysiological) insulin (ET-1, 22.4% and 46.4% higher than control cultures, respectively, both P < .05). Our results show that insulin at physiological concentrations does not alter plasma ET-1 levels in healthy individuals, but does stimulate its secretion from vascular endothelial cells in vitro. This may have implications for the study of elevated ET-1 in hyperinsulinemic states.

Blood Glucose↗
PubMed1997

Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure.

OBJECTIVES: We attempted to assess insulin sensitivity in patients with chronic heart failure (CHF) and its relation to disease severity. BACKGROUND: Peripheral muscular changes influence the progression of heart failure. This effect may be due to chronic disturbances of insulin and glucose metabolism that affect the energy status of skeletal and myocardial muscle. METHODS: We investigated insulin sensitivity in 79 men-38 patients with CHF, 21 patients with angiographic evidence of coronary artery disease without CHF and 20 healthy control subjects-and assessed its relation to disease severity, etiology and hormonal status (all subjects had a similar age and body mass index). Insulin sensitivity was estimated by minimal modeling analysis of the glucose and insulin and profiles during a 0.5 g/kg body weight intravenous glucose tolerance test. RESULTS: Compared with control subjects, patients with CHF had similar mean fasting glucose but increased insulin levels (67 vs. 29 pmol/liter, p < 0.002) and a 58% reduced mean insulin sensitivity (2.01 vs. 4.84 min-1/pmol/ml x 10(5), p < 0.0001). Peak oxygen consumption (VO2) (r = 0.63), fasting triglycerides (r = -0.62) and age (r = -0.46, all p < 0.001) predicted insulin sensitivity independently. Rest norepinephrine and epinephrine levels, left ventricular ejection fraction and heart failure etiology were not related to insulin sensitivity. Patients with coronary artery disease but no CHF had an intermediate mean insulin sensitivity (3.30 min-1/pmol/ml x 10(5) [-32%, p = 0.042 vs. control subjects; +113%, p = 0.0023 vs. patients with CHF due to ischemic heart disease]). In multivariate analyses of all 79 subjects, age (p = 0.0006), triglycerides (p = 0.0023), fasting insulin (p = 0.0037) and the presence of CHF (p = 0.018) were independent predictors of impaired insulin sensitivity (adjusted joint R2 = 0.53, p < 0.0001). CONCLUSIONS: CHF is associated with marked insulin resistance, characterized by both fasting and stimulated hyperinsulinemia. Advanced heart failure (in terms of reduced peak VO2) is related to increased insulin resistance, but this is not directly mediated through ventricular dysfunction or increased catecholamine levels.

Blood Glucose↗
PubMed1997

Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure.

BACKGROUND: Elevated serum uric acid concentrations have been observed in clinical conditions associated with hypoxia. Since chronic heart failure is a state of impaired oxidative metabolism, we sought to determine whether serum uric acid concentrations correlate with measures of functional capacity and disease severity. METHODS: Fifty nine patients with a diagnosis of chronic heart failure due to coronary heart disease (n = 34) or idiopathic dilated cardiomyopathy (n = 25) and 20 healthy controls underwent assessment of functional capacity. Maximal oxygen uptake (MVO2) and regression slope relating to minute ventilation to carbon dioxide output (VE-VCO2) were measured during a maximal treadmill exercise test. Metabolic assessment consisted of measuring serum uric acid and fasting lipids, and insulin sensitivity, obtained by minimal modelling analysis of glucose and insulin responses during an intravenous glucose tolerance test. Clustering of indices of functional disease capacity and metabolic factors was explored using factor analysis and multivariate regression analysis. RESULTS: Compared to 20 healthy controls, patients with chronic heart failure had a 52% lower MVO2 (P < 0.001), 56.8% higher serum uric acid concentrations (P < 0.001) as well as a 60.5% lower insulin sensitivity (P < 0.001). Salient univariate correlations in the chronic heart failure group included serum uric acid concentrations with exercise time during the exercise test (r = -0.53), MVO2 (r = -0.50) (both P < 0.001), VE-VCO2 slope (r = 0.45), and NYHA functional class (r = 0.36) (both P < 0.01). In factor analysis of the chronic heart failure group, serum uric acid formed part of a principal cluster of metabolic variables which included MVO2 and VE-VCO2 slope. In multivariate regression analysis, serum uric acid concentrations emerged as a significant predictor of MVO2, exercise time (both P < 0.001,) VE-VCO2 slope and NYHA functional class (both P < 0.02), independent of diuretic dose, age, body mass index, serum creatinine, alcohol intake, plasma insulin levels, and insulin sensitivity index. CONCLUSIONS: There is an inverse relationship between serum uric acid concentrations and measures of functional capacity in patients with cardiac failure. The strong correlation between serum uric acid and MVO2 suggests that in chronic heart failure, serum uric acid concentrations reflect an impairment of oxidative metabolism.

Aged↗
PubMed1997

Hormone replacement therapy with dydrogesterone and 17 beta-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up.

OBJECTIVE: To assess serum lipid and lipoprotein concentrations and oral glucose tolerance in postmenopausal women treated with 17 beta-oestradiol (2 mg/day) and cyclical dydrogesterone (10 mg/day for 14 days per 28 day cycle). DESIGN: A 24 month prospective study of 29 women acting as their own controls. On-treatment samples were taken during the combined (oestrogen-progestogen) phase of therapy. SETTING: Metabolic research unit in London. POPULATION: Postmenopausal women with no previous exposure to hormone replacement therapy attending a menopause clinic in a London hospital. METHODS: Fasting serum sampling and oral glucose tolerance testing. MAIN OUTCOME MEASURES: Serum lipids and lipoprotein concentrations and plasma glucose, insulin and C-peptide responses to an oral glucose load. RESULTS: Restricting the analysis to the 17 women who completed the study, no effect was seen on serum triglyceride concentrations. There was a mean fall of 5.9% (95% CI 1.2 to -13.0) in concentrations of serum total cholesterol, reflecting the balance of a 10.7% fall (95% CI 4.3 to -25.8) in low density lipoprotein cholesterol concentrations and a 16.3% increase (95% CI 7.3 to -25.3) in those of high density lipoproteins. Fasting glucose concentrations and glucose tolerance test responses were unchanged. Fasting insulin concentrations fell substantially (-41.6%, 95% CI -23.4 to -59.8) with falls also being seen in insulin responses to glucose. Fasting C-peptide concentrations increased by 36.2% (95% CI 9.17 to 63.3), with no consistent effect on C-peptide responses to glucose. CONCLUSIONS: Dydrogesterone did not appear to oppose the potentially beneficial effects of oestradiol on insulin or either low or high density lipoproteins, making the combination with 17 beta-oestradiol a potentially useful option for postmenopausal women particularly those at risk of cardiovascular disease or diabetes mellitus.

Adult↗
PubMed1997

Relation between serum uric acid and lower limb blood flow in patients with chronic heart failure.

OBJECTIVE: To determine whether lower limb blood flow is related to serum uric acid concentrations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic treatment and insulin resistance. DESIGN: Lower limb blood flow was measured at rest and after maximum exercise followed by a five minute period of ischaemia (maximum blood flow) using strain gauge venous occlusion plethysmography. All patients underwent a metabolic assessment, which included an intravenous glucose tolerance test (IVGTT)-to obtain an index of insulin sensitivity- and measurement of serum uric acid. SETTING: University and hospital departments specialising in cardiology and metabolic medicine. SUBJECTS: 22 patients with chronic heart failure. RESULTS: Mean (SEM) resting and maximum blood flow values were 2.87 (0.23) and 24.00 (1.83) ml/100 ml/min, respectively. Patients in the upper tertile of serum uric acid had lower maximum blood flow than those in the lowest tertile (15.6 (2.2) v 31.0 (2.1) ml/100 ml/min, P = 0.003). Serum uric acid correlated with maximum blood flow (r = -0.86, P < 0.001), but not with resting blood flow. In stepwise regression analysis, uric acid emerged as the only predictor of maximum blood flow (standardised coefficient = -0.83 (P < 0.001), R2 = 0.68 (P < 0.001)), independently of diuretic dose, age, body mass index, plasma creatinine, fasting and IVGTT glucose and insulin, insulin sensitivity, maximum oxygen uptake and exercise time during the treadmill exercise test, and alcohol intake. CONCLUSIONS: There is a strong inverse relation between serum uric acid concentrations and maximum leg blood flow in patients with chronic heart failure. Further studies are needed to determine whether serum uric acid can be used as an index of vascular function in cardiovascular diseases.

Biomarkers↗
PubMed1997

17 beta-Oestradiol inhibits stimulated endothelin release in human vascular endothelial cells.

Oestrogen is believed to possess cardiovascular protective properties. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen for vascular smooth muscle cells. We have investigated release of ET-1 from human endothelial cells in response to 17 beta-oestradiol. Serum was found to stimulate significantly ET-1 release during the first 4 h of culture. 17 beta-Oestradiol significantly reduced ET-1 immunoreactivity in the media of treated cells by up to 49% of control values after 4 h. This effect was found to be inversely related to the dose of 17 beta-oestradiol. Significant dose-dependent increases in nitric oxide synthase expression were observed in response to oestrogen after 24 h but not after 4 h. Serum-free experiments demonstrated that low doses of oestrogen were able to inhibit thrombin-induced ET-1 release whilst supraphysiological levels did not. These results provide a further perspective on the ability of oestrogens to maintain vascular health.

Blood Physiological Phenomena↗
PubMed1997

Is there a menopausal metabolic syndrome?

Estradiol-17 beta has beneficial effects on a range of metabolic risk factors for coronary heart disease and the decline in estrogen concentrations at the menopause would be expected to have adverse effects. Review of the literature on effects of the menopause and of estradiol-17 beta provides evidence for the following changes occurring at or after the menopause: increased total cholesterol and triglycerides; decreased high density lipoprotein (HDL) and HDL subfraction 2; increased low density lipoprotein, particularly in the small, dense subfraction; increased lipoprotein (a); increased insulin resistance; decreased insulin secretion; decreased insulin elimination; increased android fat distribution; impaired vascular function; increased factor VII and fibrinogen, and reduced sex-hormone binding globulin. Many of these changes will themselves have adverse effects on other metabolic risk factors. This complex of inter-correlated adverse changes in metabolic risk factors justifies identification of a distinct menopausal metabolic syndrome which originates in estrogen deficiency and which could contribute to the increased risk of coronary heart disease seen in postmenopausal women. Estrogen replacement can diminish the expression of this syndrome.

Blood Glucose↗
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

Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis.

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.

Administration, Intranasal↗
PubMed1996

Mechanisms whereby oestrogens influence arterial health.

Coronary heart disease (CHD) is uncommon in premenopausal women compared with men of similar age, but its incidence increases after the menopause to reach that of men. There is now good population-based evidence that hormone replacement therapy (HRT) in postmenopausal women reduces the incidence of CHD, perhaps by up to 50%. Oestrogens have a beneficial effect on arterial health in many different ways. HRT may both reduce the risk of atheroma formation and improve arterial function. Depending on the formulation, HRT can lower LDL and triglycerides, and increase HDL. Oestrogen may also produce qualitative as well as quantitative improvements in lipoproteins. It can improve insulin resistance and hence carbohydrate metabolism, and may enhance fibrinolysis rather than coagulation. Thus these effects of HRT on risk factor for CHD will reduce the risk of atheroma development and progression. Oestrogen has direct effects on blood vessels and improves vascular function through various mechanisms including endothelium-dependent and calcium-dependent processes. HRT should therefore now be considered for use in postmenopausal women with established CHD risk.

Arteries↗
PubMed1996

Handling hormone replacement therapy: key issues for the prescriber.

OBJECTIVES: To examine the key considerations for physicians when prescribing hormone replacement therapy (HRT). METHODS: A review of the literature, including some unpublished data. RESULTS: As far as oral HRT is concerned, relatively large doses may have to be given because of the first-pass effect involving metabolism by the liver following absorption from the G1 tract. Alternatives include percutaneous gels, impregnated pessaries, subcutaneous implants and transdermal patches. The last of these offers the possibility of delivering oestrogen accurately in convenient form and many patients regard this as a more 'natural' way of treating the menopause. Provided equivalent doses of hormone are given, all these routes of administration are equally effective in preventing osteoporosis. The situation with respect to cardiovascular disease is more complex and different types of oestrogen or progestogen and different routes of administration can have different effects on metabolic risk factors. Certain oral HRT can adversely affect glucose tolerance and insulin metabolism while transdermal HRT has very little effect. CONCLUSIONS: The first issue for the physician is the choice of route of administration. To some extent this may depend on the patient's other clinical conditions such as raised triglycerides HRT. Patient preference is very important since this will affect compliance. One approach is to start with a fixed combination of oestrogen and progestogen which is usually easier for the patient to remember and use. Side-effects are usually due to the progestogen component. The variety of progestogens available in Europe means that switching to other combinations is not difficult if side effects occur. Patients satisfaction is the ultimate determinant.

Carbohydrate Metabolism↗
PubMed1996

Measuring body fat.

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Absorptiometry, Photon↗
PubMed1996

Metabolic effects of the menopause and oestrogen replacement.

There is little doubt that the metabolic disturbances seen following the loss of ovarian function are most important in the development of cardiovascular disease in women. The loss of hormones at the menopause appears to reduce both insulin secretion and elimination, but increasing insulin resistance thereafter brings about an increase in circulating insulin concentrations. Changes in lipids and lipoproteins are in an adverse direction, as are changes in body fat distribution, and changes in haemostatic factors would tend to favour coagulation rather than fibrinolysis. HRT with oestrogen appears to improve most of the metabolic abnormalities related to the menopause, but this is in part dependent on the type of oestrogen used and the route of administration. The addition of progestogen may influence the metabolic changes induced by oestrogens, and this will vary according to the type of the progestogen. Overall, the metabolic effects of any of the current HRT regimens would seem likely to be beneficial for CHD. Nevertheless, future HRT regimens should ideally be tailored to produce the most favourable changes in CHD metabolic risk factors, particularly in the case of the regimens which attempt to avoid cyclical bleeding.

Blood Coagulation↗
PubMed1996

Immunoglobulin haplotype frequencies in Anabaptist population samples: Kansas and Nebraska Mennonites and Indiana Amish.

Anabaptist history is a chronicle of repeated migrations, fissions, and fusions of various subgroups. The effects of these events should be evident in the population biology of the Anabaptist groups. No prior genetic studies have included the polymorphic and highly informative immunoglobulin markers. Here, 685 serum samples representing 1 Amish and 3 Mennonite community samples (7 congregations) were studied for immunoglobulin allotypes. The haplotypes IGHG*F B, IGHG*A,Z G, and IGHG*A,X,Z G range in frequency from 0.542 to 0.765, 0.123 to 0.290, and 0.075 to 0.170, respectively. IGK*1 frequencies range from 0.035 to 0.077. All frequencies are within expected ranges for central and western European population samples. There was considerable intergroup variability among the Anabaptist samples that was statistically significant (chi29 = 22.63, 0.005 < p < 0.01). Principal component analyses, including the immunoglobulin allotype frequencies and published data on ABO, MN, and Rhesus (Dd) markers, demonstrate that the Mennonite congregation samples with close historical ties group together and are distinct from the Amish and Meridian congregation samples.

Christianity↗