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Biomedical subjects

R Ames

Publications and source records attributed to R Ames.

16 recordsLinked to original sources

Calcium supplementation does not affect CRP levels in postmenopausal women--a randomized controlled trial.

INTRODUCTION: Epidemiological studies suggest that calcium supplementation may decrease the risk of cardiovascular disease. METHODS: Since the inflammatory marker C-reactive protein (CRP) is a risk factor for cardiovascular disease, and CRP production is potentially responsive to parathyroid hormone, we measured high-sensitivity CRP at baseline and 12 months in a subset of healthy postmenopausal women participating in a randomized controlled trial of the effects of 1 g of calcium daily on the incidence of fractures. RESULTS: At baseline, we found that CRP correlated positively with indices of body weight and fat and with bone mineral density (BMD) at the total body and total hip sites, but the associations between CRP and BMD were lost after adjustment for body weight. There were consistent associations between levels of CRP and markers of the metabolic syndrome (fat mass, plasma triglycerides, fasting glucose). CONCLUSION: After 1 year of calcium supplementation, there was no difference between the groups in levels of CRP. We conclude that levels of CRP correlate with anthropometric and biochemical features of insulin resistance, but that they are neither predictive of BMD nor affected by 1 g of calcium supplementation in healthy postmenopausal women.

Aged↗

Determinants of sex hormone-binding globulin in normal postmenopausal women.

OBJECTIVE: To examine the factors influencing the levels of sex hormone-binding globulin (SHBG) in normal postmenopausal women by assessing the relationship between SHBG and measured anthropometric, metabolic and hormonal variables. DESIGN: Cross-sectional, observational study. SUBJECTS AND METHODS: Seventy normal postmenopausal women aged 47-71 years (mean 58 years), participated in the study. Information was collected on medical, reproductive and smoking history, alcohol use, dietary intake and physical activity. Body composition measurements using dual-energy absorptiometry, and analyses of biochemical and hormonal indices were performed. RESULTS: Bivariate correlation coefficients indicated that SHBG was inversely related to body weight (r = - 0.44), fat mass (r = - 0.35), and abdominal obesity (r = - 0.42). It was also inversely related to the glucose and insulin levels during an oral glucose tolerance test (- 0.24 < r < - 0.40), serum oestradiol (r = - 0.26), and physical activity (r = - 0.24). Multiple regression analysis indicated that significant independent correlates of SHBG concentration were fat mass, physical activity, alcohol intake, serum oestradiol, and insulin-like growth factor-1, all having a negative impact on SHBG. CONCLUSIONS: From these observed associations, it is concluded that maintenance of body weight, moderate alcohol consumption, and physical activity will tend to reduce SHBG concentrations in postmenopausal women, thereby increasing the levels of free oestradiol. This mechanism could mediate the beneficial effects of these factors in preventing the development of osteoporosis and cardiovascular disease.

Aged↗

Hyperlipidemia of diuretic therapy.

Hyperlipidemia is a widely acknowledged side effect of thiazide diuretic therapy, but it is often dismissed as a short-term effect of high-dose therapy. Large clinical trials usually show no lipid change during late follow-up. These large trials use intention-to-treat analysis which masks the lipid effect. On-treatment analysis regularly reveals the persistence of hyperlipidemia during 4-5 years of treatment. Studies of low-dose thiazide therapy give conflicting results. Meta-analysis of these studies reveals hyperlipidemia of a milder degree than with high-dose thiazide treatment. However, a trade-off of effects is apparent because systolic blood pressure is lowered less well with low doses. Thus, thiazide effects on blood pressure and lipids are dose-dependent. Similar meta-analysis of indapamide 2.5 mg daily shows no adverse lipid effect and a lowering of blood pressure equivalent to 50 mg of hydrochlorothiazide. Regarding clinical events, low-dose thiazide treatment exerts primary prevention of coronary heart disease but provides less benefit against stroke and congestive heart failure than does high-dose therapy. Thus, an evidence-based therapeutic strategy for further reducing cardiovascular risk is as follows: initiate antihypertensive therapy with low-dose diuretics. Add beta-blockers and dihydropyridine-type calcium channel blockers for further antihypertensive effect, if needed. Hypertension resistant to a 3-drug regimen should be treated with high-dose thiazides. Lipids should be monitored at each step and treated with diet and statin drugs to maintain lipid goals. Risk factor control is an old concept that has yet to be effectively implemented.

Adrenergic beta-Antagonists↗

A view of death and dying among the Chinese and Japanese.

The practices of medicine around the world have been fused into that of faith and religion. In serving our patients' need to accept death, physicians must also be sensitive to this underlying basic human concern as they prepare for this final journey. The Chinese and Japanese, reflecting their belief in Buddhism, perceive death as a natural part and an extension of life itself.

Attitude to Death↗

Bone mineral density of the proximal femur and lumbar spine in glucocorticoid-treated asthmatic patients.

The importance of the proximal femur as a site of osteoporotic fractures, the development of techniques for bone mineral density (BMD) measurement at this site and the apparent selectivity of the osteopenic effects of glucocorticoids have focused attention on the assessment of proximal femoral BMD in steroid-treated subjects. We have, therefore, measured BMD (Lunar DPX) in the lumbar spine and proximal femur of 31 asthmatic patients receiving long-term glucocorticoid therapy (mean +/- SEM dose 16 +/- 1 mg prednisone/day, mean duration 10 +/- 2 years). BMD values expressed as the percentage of normal age- and sex-appropriate mean values, after weight adjustment, were as follows: lumbar spine 80 +/- 2%, femoral neck 83 +/- 2%, Ward's triangle 78 +/- 3% and trochanter 86 +/- 2%. All these values were significantly less than control (p less than 0.0001) and the decrement in BMD was more marked in Ward's triangle than at the other two femoral sites (p less than 0.05). In all regions BMD was unrelated to dose or duration of steroid treatment. It is concluded that there are reductions in the BMD of the lumbar spine and proximal femur in glucocorticoid-treated asthmatics, probably reflecting the mixed cortical/trabecular make-up of both regions.

Adult↗

Relationships between upper-arm anthropometry and soft-tissue composition in postmenopausal women.

The value of upper-arm anthropometry as a measure of lean- and fat-tissue masses in 140 normal postmenopausal white women was assessed by studying the relationships of these measures to total and regional fat, and lean masses measured by dual-energy x-ray absorptiometry. Midarm circumference (MAC) was highly correlated with total and regional fat masses (r = 0.85-0.89, P less than 0.0001) but less so with lean-tissue masses (r = 0.26-0.34). Triceps-skinfold thickness was also correlated with fat masses (r = 0.70-0.74, P less than 0.0001) but not with lean mass (r = 0.02-0.09). The derived index, arm muscle area (AMA), was less closely correlated with fat mass than was MAC (r = 0.59-0.61), but its correlation with lean-tissue mass was comparable to that for MAC (r = 0.37-0.43). Multiple-regression analysis confirmed that the anthropometric indices were more closely correlated with fat than with lean mass. It is concluded that all these indices are useful measures of fat mass but that none, including AMA, is a specific index of lean-tissue mass in normal postmenopausal women.

Adipose Tissue↗

Determinants of total body and regional bone mineral density in normal postmenopausal women--a key role for fat mass.

In order to determine which clinical, anthropometric, dietary, and biochemical variables are independent predictors of total and regional bone mineral density (BMD) in normal postmenopausal women, a cross-sectional study of 140 normal postmenopausal women has been carried out. Subjects were white, aged 45-71 yr (mean 58 yr), and had no history of disorders or medication use likely to influence bone or calcium metabolism. Multiple regression analysis was used to derive models for total and regional BMD in terms of the other variables measured. The analysis indicated that total body BMD was positively related to fat mass (P less than 0.0001), serum estrone (P = 0.0095) and age at menopause (P = 0.0165), and negatively related to age (P less than 0.0001), 24-h urine calcium (P = 0.0002), sex hormone-binding globulin (P = 0.0003), and serum alkaline phosphatase activity (P = 0.0029) (R2 = 0.61). Similar relationships were found in the subregions of the total body scans and in the lumbar spine and proximal femur, with insulin-like growth factor-1, parity, and age at menarche also being related to BMD at at least two of these sites. Lean body mass was not an independent correlate of BMD at any site once fat mass was taken into account. Muscle strength, physical activity, alcohol intake, and dietary intakes of calcium, sodium and protein did not emerge as significant predictors of BMD in this homogeneous group of postmenopausal women. We conclude that total body fat is the most significant predictor of BMD throughout the skeleton and this relationship is not explicable in terms of either estrone production in fat tissue or the dependence of skeletal load-bearing on fat mass. The mechanism underlying this relationship is an important question to be addressed in bone biology.

Aged↗

Bone density in women receiving depot medroxyprogesterone acetate for contraception.

OBJECTIVE: To determine if the use of the injectable contraceptive depot medroxyprogesterone (DMPA), which reduces ovarian oestrogen production, is associated with changes in bone density. DESIGN: Population study. DMPA users were compared with two control groups selected from larger population studies and individually matched for several putative determinants of bone density (age, race, body mass index, and years of oestrogen deficiency). Controls and DMPA users were matched without prior knowledge of their bone density measurements. SETTING: Teaching hospital and community family planning clinics. SUBJECTS: 30 current users of DMPA with a minimum five years' previous use, 30 premenopausal controls, and 30 postmenopausal controls. MAIN OUTCOME MEASURE: Lumbar spine and femoral neck bone mineral density assessed by dual energy x ray absorptiometry. RESULTS: Compared with premenopausal controls matched for age, race, and body mass index, DMPA users had significantly reduced bone density in the lumbar spine (mean difference 7.5% (95% confidence interval 1.9% to 13.1%), p = 0.002) and in the femoral neck (6.6%, (0.8% to 12.3%), p = 0.007). Compared with postmenopausal controls matched for body mass index and duration of oestrogen deficiency, DMPA users had greater bone density in the lumbar spine (8.9% (4.3% to 13.5%), p = 0.001), but in the femoral neck the difference in bone density was less (4.0% (-0.4% to 8.5%), p = 0.04). CONCLUSIONS: Women using DMPA have bone density values intermediate between those of normal premenopausal and postmenopausal controls; thus, the degree of oestrogen deficiency induced by DMPA may have an adverse effect on bone density.

Absorptiometry, Photon↗

The influence of osteophytes and aortic calcification on spinal mineral density in postmenopausal women.

The assessment of vertebral bone mineral density (BMD) in the anterio-posterior projection has become widely used in the management and prevention of osteoporosis. Recently, it has been demonstrated that the presence of spinal osteophytes has a major impact on measured BMD in men, thus casting doubt on the value of these BMD measurements. We have assessed the impact of osteophytic and aortic calcification on spinal and femoral BMD measurements in 130 normal postmenopausal women, aged 45-71 yr. Lateral lumbar spine radiographs were obtained in all subjects and graded separately (0-3) for osteophytes and aortic calcification. Both forms of calcification increased with age, and BMD of all sites was correlated positively with body weight and negatively with age. The correlation coefficients between BMD and calcification scores were nonsignificant. Multiple regression analysis, including weight, age, and calcification scores, demonstrated a small but significant effect of osteophyte score on lumbar BMD (partial r2 = 0.04; P = 0.012) and a similar trend for Ward's triangle and the trochanteric region (partial r2 = 0.02; P less than 0.06). The aortic calcification score remained nonsignificant. It is concluded that the influence of spinal osteophytes on lumbar BMD in postmenopausal women is substantially less than that in men and is, therefore, unlikely to interfere with BMD estimation in most subjects. The relationship between proximal femoral BMD and osteophyte score suggests a real relationship between skeletal density and degenerative joint disease, as has been demonstrated by others.

Aged↗

Effects of aminobisphosphonate infusion on biochemical indices of bone metabolism in rheumatoid arthritis.

In a phase 1 study, seven patients with classical rheumatoid arthritis were treated with intravenous 3-amino-1-hydroxypropylidene-1-1-bisphosphonate (APD). Following this treatment, bone resorption as measured by fasting urine calcium/creatinine and hydroxyproline/creatinine ratios, was reduced. This was sustained for 6 months in only three patients. Elevations of these ratios often coincided with flares of active arthritis in the remaining four patients. Bone turnover as measured by serum osteocalcin levels was reduced in all patients but serum alkaline phosphatase levels remained unchanged. There was no consistent improvement in clinical indices of disease activity.

Adult↗

Aminobisphosphonate inhibition of interleukin-1-induced bone resorption in mouse calvariae.

Interleukin-1 (IL-1) is probably an important lymphokine mediator of inflammation and bone resorption. IL-1 derived from mononuclear cells, a melanoma cell line (MM96 cells), and recombinant human IL-1 (rHuIL-1 beta) increased in vitro bone resorption, as measured by the release of 45Ca from cultured mouse calvariae. The 50% maximum active resorption was observed with 0.125 ng/ml or approximately 10(-11) M rHuIL-1 beta. The resorptive action of IL-1 was not entirely dependent on prostaglandin mediation, since its effect was evident when prostaglandin synthesis was inhibited in the cultures by indomethacin. IL-1-induced resorption has been shown to be inhibited by 10(-5) M 3-amino-1-hydroxypropylidene-1-1-bisphosphonate (APD). This inhibition was partially reversed by increasing doses of IL-1. In vitro toxicity studies showed that at concentrations of 10(-4) M, APD inhibited the growth of cultured MM96, murine myelomonocytic P388D1, and rat osteosarcoma UMR 106 cells, but not other mast and lymphoid cell lines. These in vitro observations may have relevance to the use of APD in bone and joint diseases in which inflammation and bone resorption are prominent.

Animals↗

Effects of diuretic drugs on the lipid profile.

Thiazide-type diuretic drugs modify the lipoprotein profile when used in the short term treatment of hypertension. Total cholesterol increases by 6 to 7% on average because of raised concentrations of low density or very low density lipoprotein cholesterol or both. High density lipoprotein cholesterol does not change. Spironolactone has a lesser effect on lipids than do thiazides. In contrast, the methylindoline compound, indapamide, a diuretic with vasodilator activity, has produced no adverse effects on lipids or lipoproteins. Long term data on thiazide monotherapy are sparse but suggest a persistence of the lipid effect for as long as 6 years of treatment. The clinical impact of these lipid changes is unclear. Although clinical trials have proved the benefit of lowering cholesterol on the incidence of coronary heart disease, the clinical significance of these diuretic-induced increases is unknown. A clinical trial will be required to resolve the issue by comparing antihypertensive drugs with and without adverse effects on the lipid profile. Because coronary heart disease is the most common complication of mild hypertension, and as diuretic-based regimens have not succeeded in curbing it, resolution of this concern is important.

Benzothiadiazines↗

Detection of a surface antigen on NIH3T3 cells transfected with a human leukemia oncogene.

This study was conducted to examine the cell surface changes associated with oncogene induced transformation. Using the transfection technique the DNA of a human acute lymphocytic leukemia (ALL) was used to transform murine NIH3T3 cells. Balb/c mice were immunized with these transfectants and their immune splenocytes were used to produce a monoclonal antibody (17-9H3). Antibody 17-9H3 was demonstrated to bind to the cell membranes of transfectants and leukemia cells but not normal 3T3 cells in an enzyme linked immunosorbent assay. Fresh human leukemias, cultured leukemia lines and normal hemopoietic cells were examined with immunoperoxidase staining techniques to determine the specificity of 17-9H3. Our data suggest that the antigen associated with a human acute lymphocytic leukemia oncogene is ubiquitous, distributed among both neoplastic and normal hemopoietic cells. Among fresh human leukemias the antigen appears to be present primarily on fresh null ALLs and chronic myelogenous leukemia (CML) in blast crisis. This antigen was also found to be expressed by the majority of cultured T-cell lines tested.

Animals↗