John stevenson - Academia.edu (original) (raw)
Papers by John stevenson
Osteoporosis in Clinical Practice, 2004
Drugs, 1988
The pathogenic mechanisms causing malignant hypercalcaemia are primarily increased bone calcium m... more The pathogenic mechanisms causing malignant hypercalcaemia are primarily increased bone calcium mobilisation and renal calcium retention. In some reticuloendothelial malignancies, enhanced intestinal calcium absorption may also play a role. Malignant hypercalcaemia is a life-threatening condition, and there are many patients with malignancy in whom suppression of this complication is most desirable. In such cases, successful management of the hypercalcaemia will enable the overall treatment aims, such as tumour removal or ablation, to be achieved. Acute treatment involves the rapid lowering of serum calcium from potentially fatal concentrations, and comprises the use of intravenous rehydration, calcitonin and diphosphonates. In the longer term, other measures may be introduced to maintain and control the calcium concentration while specific antitumour therapy is instituted.
Drugs, 1981
Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. A major physiologic... more Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. A major physiological function of the hormone appears to be the protection of the skeleton against resorption in humans. It thus opposes the resorptive actions of parathyroid hormone and 1,25 dihydroxyvitamin D. This action is utilised pharmacologically in order to treat diseases where increased bone resorption is a major component. The efficacy of calcitonin in the treatment of Paget's disease of bone is well established, especially as it is currently the most effective agent in the treatment of the osteolytic form of the disease. In other bone diseases where resorption of bone is a component it is likely to be worthy of a trial of therapy. There are also sound theoretical reasons why calcitonin may be of benefit in the treatment of certain osteoporoses, especially in combination with other agents. Most recent studies would seem to support his view. A disadvantage of calcitonin therapy is that the hormone has to be administered parenterally, although future developments may obviate this. It is, however, a form of retreatment which is free of any long term serious side effects, and calcitonin now has a definite place in the management of specific bone and calcium disorders.
Surgical Endocrinology, 1993
New Techniques in Metabolic Bone Disease, 1990
British Medical Journal, 1982
Surgical Endocrinology, 1993
Atherosclerosis, 1993
Sex hormone deficiency is associated with increased coronary heart disease (CHD) risk in women. W... more Sex hormone deficiency is associated with increased coronary heart disease (CHD) risk in women. We measured fasting serum lipids and lipoprotein concentrations in a group of 542 healthy non-obese pre- and postmenopausal women (aged 18-70 years). Ageing was associated with increased concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein subfraction 3 (HDL3) cholesterol and triglycerides, and decreased concentrations of high density lipoprotein subfraction 2 (HDL2) cholesterol. Body mass index (BMI) was related positively to concentrations of total and LDL cholesterol. Postmenopausal women had significantly higher concentrations of total cholesterol (P < 0.001), triglycerides (P < 0.005), LDL cholesterol (P < 0.001) and high density lipoprotein subfraction 3 (HDL3) cholesterol (P < 0.001), whilst those of HDL and HDL2 cholesterol were significantly lower (P < 0.001). These differences were independent of age, BMI and other potential confounding variables. We conclude that the menopause is associated with potentially adverse changes in lipids and lipoproteins, independent of any effects of ageing. These changes may in part explain the increased incidence of coronary heart disease seen in postmenopausal women.
Hormone Research, 1989
The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 prem... more The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.
American Journal of Medicine, 1995
purpose: We investigated the relationships between the amount and distribution of body fat and fa... more 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 MEIHODS: We determined serum total cholesterol and triglyceride, low-density lipoprotein cholesterol, highdensity 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.
We investigated sex-and menopause-related differences in body composition and regional fat distri... more We investigated sex-and menopause-related differences in body composition and regional fat distribution,
Calcified Tissue International, 1993
A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the ... more A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed “stiffness.” Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P P P P
British Medical Journal, 1988
In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insul... more In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors. Seventy-four men [age, 48.4Ϯ1.3 years (meanϮSEM); body mass index (BMI), 25.6Ϯ0.3 kg/m 2 ] who were free of coronary heart disease and diabetes underwent anthropometric measurements (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness ratios, measurement of fasting plasma leptin, and an intravenous glucose tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin concentrations were correlated with BMI (rϭ0.57, PϽ0.001), S:T (rϭ0.34, Pϭ0.003), S:B (rϭ0.37, PϽ0.001), systolic and diastolic blood pressures (both rϭ0.24, Pϭ0.044), fasting triglycerides (rϭ0.31, Pϭ0.007), serum uric acid (rϭ0.35, Pϭ0.003), fasting glucose (rϭ0.32, Pϭ0.003) and insulin (rϭ0.33, Pϭ0.004), and IVGTT insulin (rϭ0.63, PϽ0.001). A negative correlation was observed between leptin and insulin sensitivity (rϭϪ0.32, Pϭ0.006). No significant correlations emerged between plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI (standardized coefficient [SC] ϭ0.40, Pϭ0.001), fasting insulin (SCϭ0.23, Pϭ0.036), and IVGTT insulin (SCϭ0.51, PϽ0.001) emerged as independent predictors of plasma leptin concentrations (R 2 ϭ0.56, PϽ0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SCϭ0.56, PϽ0.001, R 2 ϭ0.45, PϽ0.001).
Journal of The American College of Cardiology, 1997
Objectives. We attempted to assess insulin sensitivity in patients with chronic heart failure (CH... more 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 × 105, 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 × 105 [−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.
The Obstetrician & Gynaecologist, 2005
Osteoporosis in Clinical Practice, 2004
Drugs, 1988
The pathogenic mechanisms causing malignant hypercalcaemia are primarily increased bone calcium m... more The pathogenic mechanisms causing malignant hypercalcaemia are primarily increased bone calcium mobilisation and renal calcium retention. In some reticuloendothelial malignancies, enhanced intestinal calcium absorption may also play a role. Malignant hypercalcaemia is a life-threatening condition, and there are many patients with malignancy in whom suppression of this complication is most desirable. In such cases, successful management of the hypercalcaemia will enable the overall treatment aims, such as tumour removal or ablation, to be achieved. Acute treatment involves the rapid lowering of serum calcium from potentially fatal concentrations, and comprises the use of intravenous rehydration, calcitonin and diphosphonates. In the longer term, other measures may be introduced to maintain and control the calcium concentration while specific antitumour therapy is instituted.
Drugs, 1981
Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. A major physiologic... more Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. A major physiological function of the hormone appears to be the protection of the skeleton against resorption in humans. It thus opposes the resorptive actions of parathyroid hormone and 1,25 dihydroxyvitamin D. This action is utilised pharmacologically in order to treat diseases where increased bone resorption is a major component. The efficacy of calcitonin in the treatment of Paget's disease of bone is well established, especially as it is currently the most effective agent in the treatment of the osteolytic form of the disease. In other bone diseases where resorption of bone is a component it is likely to be worthy of a trial of therapy. There are also sound theoretical reasons why calcitonin may be of benefit in the treatment of certain osteoporoses, especially in combination with other agents. Most recent studies would seem to support his view. A disadvantage of calcitonin therapy is that the hormone has to be administered parenterally, although future developments may obviate this. It is, however, a form of retreatment which is free of any long term serious side effects, and calcitonin now has a definite place in the management of specific bone and calcium disorders.
Surgical Endocrinology, 1993
New Techniques in Metabolic Bone Disease, 1990
British Medical Journal, 1982
Surgical Endocrinology, 1993
Atherosclerosis, 1993
Sex hormone deficiency is associated with increased coronary heart disease (CHD) risk in women. W... more Sex hormone deficiency is associated with increased coronary heart disease (CHD) risk in women. We measured fasting serum lipids and lipoprotein concentrations in a group of 542 healthy non-obese pre- and postmenopausal women (aged 18-70 years). Ageing was associated with increased concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein subfraction 3 (HDL3) cholesterol and triglycerides, and decreased concentrations of high density lipoprotein subfraction 2 (HDL2) cholesterol. Body mass index (BMI) was related positively to concentrations of total and LDL cholesterol. Postmenopausal women had significantly higher concentrations of total cholesterol (P < 0.001), triglycerides (P < 0.005), LDL cholesterol (P < 0.001) and high density lipoprotein subfraction 3 (HDL3) cholesterol (P < 0.001), whilst those of HDL and HDL2 cholesterol were significantly lower (P < 0.001). These differences were independent of age, BMI and other potential confounding variables. We conclude that the menopause is associated with potentially adverse changes in lipids and lipoproteins, independent of any effects of ageing. These changes may in part explain the increased incidence of coronary heart disease seen in postmenopausal women.
Hormone Research, 1989
The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 prem... more The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.
American Journal of Medicine, 1995
purpose: We investigated the relationships between the amount and distribution of body fat and fa... more 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 MEIHODS: We determined serum total cholesterol and triglyceride, low-density lipoprotein cholesterol, highdensity 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.
We investigated sex-and menopause-related differences in body composition and regional fat distri... more We investigated sex-and menopause-related differences in body composition and regional fat distribution,
Calcified Tissue International, 1993
A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the ... more A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed “stiffness.” Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P P P P
British Medical Journal, 1988
In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insul... more In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors. Seventy-four men [age, 48.4Ϯ1.3 years (meanϮSEM); body mass index (BMI), 25.6Ϯ0.3 kg/m 2 ] who were free of coronary heart disease and diabetes underwent anthropometric measurements (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness ratios, measurement of fasting plasma leptin, and an intravenous glucose tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin concentrations were correlated with BMI (rϭ0.57, PϽ0.001), S:T (rϭ0.34, Pϭ0.003), S:B (rϭ0.37, PϽ0.001), systolic and diastolic blood pressures (both rϭ0.24, Pϭ0.044), fasting triglycerides (rϭ0.31, Pϭ0.007), serum uric acid (rϭ0.35, Pϭ0.003), fasting glucose (rϭ0.32, Pϭ0.003) and insulin (rϭ0.33, Pϭ0.004), and IVGTT insulin (rϭ0.63, PϽ0.001). A negative correlation was observed between leptin and insulin sensitivity (rϭϪ0.32, Pϭ0.006). No significant correlations emerged between plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI (standardized coefficient [SC] ϭ0.40, Pϭ0.001), fasting insulin (SCϭ0.23, Pϭ0.036), and IVGTT insulin (SCϭ0.51, PϽ0.001) emerged as independent predictors of plasma leptin concentrations (R 2 ϭ0.56, PϽ0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SCϭ0.56, PϽ0.001, R 2 ϭ0.45, PϽ0.001).
Journal of The American College of Cardiology, 1997
Objectives. We attempted to assess insulin sensitivity in patients with chronic heart failure (CH... more 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 × 105, 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 × 105 [−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.
The Obstetrician & Gynaecologist, 2005