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Biomedical subjects

R Lindsay

Publications and source records attributed to R Lindsay.

At least 163 records · Page 9Linked to original sources
PubMed1990

Estrogen treatment of patients with established postmenopausal osteoporosis.

We conducted a controlled study of the effects of oral estrogen therapy in postmenopausal women with established postmenopausal osteoporosis. Bone mass was measured in the lumbar vertebrae and hip using dual photon absorptiometry. Both estrogen-treated women and the control group received calcium supplements to bring total intake to approximately 1500 mg/day. For those women with an intact uterus in the estrogen wing of the study, a progestin was added to the therapy for 12-14 days each calendar month. The number of years from menopause was 14.6 +/- 0.9 in the estrogen-treated group and 13.7 +/- 1.1 in the calcium-treated group. Estrogen treatment was associated with increased vertebral bone mass by dual photon absorptiometry during the 2 years of the study (+10.6%; P less than .01). There was also an increase in bone density at the femoral neck (+5.5%; P less than .1), but the difference from the initial value was not statistically significant. The group given calcium alone lost bone at both sites, although the loss was not statistically significant at either site. The response to estrogen was greatest in those who were furthest from menopause (r = 0.38, P less than .05) and consequently among those who had the lowest bone mass (r = -0.34, P less than .05). Estrogen therapy appears to be an effective therapy for patients with established osteoporosis. Intervention is associated with a significant increase in bone mass compatible with reduced skeletal turnover and activation frequency.

Alkaline Phosphatase↗
PubMed1989

Estrogens in prevention and treatment of osteoporosis.

The osteoporosis is a common problem among postmenopausal women causing at least 1.5 million fractures each year in the USA. Osteoporotic fractures are also common in women with other hypo-estrogenic states. Bone mass among females is fairly constant until the 5th decade and then begins to decline at all skeletal sites. This fall coincides with the gradual onset of ovarian failure. We were able to demonstrate reduced bone mass within three years of oopharectomy, but not in hysterectomized women with intact ovarian function. Estrogen therapy has been shown in a variety of studies to prevent the loss of bone that follows menopause. Cessation of therapy results in restoration of bone loss. The use of estrogen preparations in women with intact uterus requires the addition of a progestogen to protect against the deleterious long-term effects of unopposed estrogen on the endometrium. This does not interfere with the effects of estrogens on the skeleton, but does result in the return of menses, which reduces compliance among the older female population. In our group estrogens are usually prescribed orally (0.625 mg Premarin or its equivalent, or by another route (percutaneous transdermal), provided estradiol levels can be maintained in the modfollicular range. Estrogens are given continuously and- for women with intact uterus--a progestogen is added (Provera 5 mg per day) for 12-14 days each month, starting on the first day of each calendar month. All women should be followed by a gynecologist and have mammography appropriate to their age range. Reduced bone mass at the time of menopause probably indicated an individual who is at increased risk of osteoporosis and should be treated. As alternatives to estrogens calcitonin and diphosphonates can be prescribed to women who do not wish to take estrogen treatment.

Aged↗
PubMed1989

Effects of tamoxifen on spinal bone density in women with breast cancer.

Bone densitometry (L2-L4) was performed on 10 postmenopausal women with breast cancer after 0, 6, and 12 months of tamoxifen treatment; the results were compared with data from 10 normal controls. The patients and controls differed significantly at 6 (P less than .05) and 12 (P less than .003) months. The tamoxifen group showed a nonsignificant mean gain in bone mineral density after 6 and 12 months of treatment (+0.024 +/- 0.014 and +0.022 +/- 0.018 g/cm2, respectively), whereas the controls showed a nonsignificant mean loss of bone mass at 6 months (-0.012 +/- 0.018 g/cm2) and a statistically significant loss of bone density after 12 months (-0.024 +/- 0.01 g/cm2). These preliminary data suggest that tamoxifen use is associated with preservation of bone mass during the first year of treatment.

Aged↗
PubMed1989

Bone mineral density in women with type II diabetes mellitus.

Bone mineral density (BMD) was assessed in 28 women with type II diabetes mellitus and compared to 207 age-matched nondiabetic women. Mean BMD, as measured by dual-photon absorptiometry, 1.12 +/- 0.3 g/cm2 (+/- SEM), was similar to the mean BMD of control subjects, 1.06 +/- 0.1 g/cm2. Only 1 of the 28 diabetic patients had a BMD less than 0.95 g/cm2 ("fracture threshold"), whereas 25% of the control subjects had a BMD below that level. When diabetic and control subjects were matched for weight as well as age, the data continued to show similar BMD among both groups. Moreover, the disparity between the proportion of weight-matched controls (25%) and diabetic subjects (1 of 28) with a BMD below the fracture threshold persisted. Among the group of 17 diabetic subjects receiving insulin, there was a positive relationship between BMD and insulin dose. There was no significant relationship between BMD, duration of diabetes, or hemoglobin Alc. Thus, women with type II diabetes are not at increased risk for diminished BMD and may be protected against bone loss.

Adult↗
PubMed1989

Bone resorption by isolated human osteoclasts in vitro: effects of calcitonin.

Human osteoclasts were isolated from 12- to 17-week-old fetal tissue and from transiliac crest bone biopsies for an in vitro study of their biology. A hypodermic needle was used to flush either the fetal long bones or the trabeculae of the iliac crest bone biopsy with tissue culture medium and the resulting cell suspension sedimented briefly either onto the surface of plastic tissue culture dishes, for time-lapse microcinematography, or onto slices of devitalized bovine cortical bone for quantitative assay of bone resorption. The osteoclasts were motile, tartrate-resistant acid phosphatase positive and capable of excavating pits in slices of devitalized bovine cortical bone. Human calcitonin, at doses of 1 ng/ml and 1 microgram/ml, caused a 70% inhibition of bone resorption by human fetal osteoclasts over a 24 h period but had no apparent effect on the morphology or motility of either fetal or adult osteoclasts.

Aging↗
PubMed1989

Blood coagulation profile in long-term hormone replacement therapy with mestranol.

The coagulation profile of oophorectomised women on long-term (15 yr) hormone replacement therapy with mestranol (30 micrograms/day) is compared to that of women on long-term placebo. Analysis of these data showed no significant difference in prothrombin time, partial thromboplastin time or in anti-thrombin III level in these groups.

Adult↗
PubMed1989

The use of an insulin bolus in low-dose insulin infusion for pediatric diabetic ketoacidosis.

The use of an initial bolus of insulin prior to the initiation of low-dose insulin infusion therapy was evaluated in 56 episodes of diabetic ketoacidosis (DKA) in 38 children. The cases were randomly assigned to a group that received a bolus of insulin (n = 24) and to a group that did not (n = 32). After the first hour of insulin therapy, the decline in serum glucose level and the changes in serum osmolality were statistically similar in the two groups, regardless of the degree of acidosis. The time required to reach a serum glucose level of less than 250 mg/dl and the total duration of insulin infusion likewise were similar in the two groups. The use of a bolus of insulin at the onset of treatment for DKA appears unnecessary.

Adolescent↗
PubMed1989

Effects of treatment with oestradiol/levonorgestrel on bone, lipoproteins and hormone status in postmenopausal women.

The aim of the study was to investigate the effects of an oestradiol/levonorgestrel regimen, administered parenterally, on bone metabolism, bone density, lipoprotein metabolism and hormone status. Twenty-five women who had undergone a surgical menopause had an oestradiol/levonorgestrel-containing vaginal ring pessary in situ for 6 months. Within the first month there were sustained changes in the biochemical indices of bone metabolism in keeping with a marked reduction in bone turnover and decrease in bone resorption. Bone mineral content in the distal forearm was measured in 14 patients and a small increase was noted in every patient. Levonorgestrel was well absorbed and the serum levels remained almost constant throughout treatment. There was a gradual increase in serum total oestradiol which became significant at 6 months. Dialysable oestradiol levels rose from 2.6% of total oestradiol at 0 time to 3.3% at 1 month with no further change thereafter. SHBG levels were 23% of pretreatment levels at 6 months. There were sustained decreases in triglyceride, VLDL and HDL cholesterol levels and a transient fall in LDL cholesterol. Total HDL, HDL2 and HDL3 cholesterol levels were reduced by 25, 40 and 21% respectively. The results suggest that levonorgestrel exerts a protective influence on bone either directly or by its effect on the proportion of oestradiol circulating in the free, physiologically active form. The effects on lipoproteins were predominately those of the progestogen component, the lipoprotein risk factors for coronary heart disease being adversely affected.

Administration, Intravaginal↗
PubMed1989

Osteoporosis: an updated approach to prevention and management.

Osteoporosis is a major public health problem whose impact will only continue to increase in the United States. Current evidence indicates that estrogen therapy will prevent bone loss and reduce the incidence of fractures. The major problem is identification of those most at risk of fracture. Currently, risk factor assessment and bone mass measurement used in combination offer the closest approximation to the ideal, although it is not yet completely clear how good identification is. Together these estimates of risk need only be used for those about whom there is a question concerning the use of estrogen, and need not be used for patients who have either already decided to initiate preventive treatment or have decided not to start such a program.

Age Factors↗
PubMed1989

Gait analysis of patients who have Paget disease.

Eighteen patients who had Paget disease were evaluated in our gait-analysis laboratory. The results were compared with those of ten healthy age-matched control subjects in order to quantitate the biomechanical changes and to describe the specific patterns of walking that occur secondary to bowing of a lower extremity. Kinetic and kinematic data were acquired using infrared video cameras and force platforms; electromyographic data were obtained using surface electrodes. Velocity and cadence were decreased and stride time and double-limb support time were increased in the patients who had Paget disease compared with the control subjects. Frequently, the knee of the limb that was affected by Paget disease was flexed during stance and flexed less during swing. When the involved knee was in varus angulation it also had an increased adduction moment, which may be related to the bowing deformity. Although the patterns of ground-reaction force were similar in the patients and the control subjects, the magnitudes of forces were reduced in the patients. Phasic muscle activity was similar in the two groups.

Aged↗
PubMed1988

Potentiation and suppression of mouse liver cytochrome P-450 isozymes during the acute-phase response induced by bacterial endotoxin.

Infection and inflammation are known to affect the metabolism and disposition of drugs and carcinogens. We report a detailed study of the effects of bacterial endotoxin on the constitutive and inducible expression and activities of cytochrome P-450 isozymes from families P-450I, P-450IIB, P-450IIC and P-450III. In general high doses of high endotoxin caused very marked suppression of P-450 isozymes and associated activities. However, this effect was differential, the expression of certain isozymes being only slightly reduced whereas others were suppressed to almost undetectable levels. Low doses of endotoxin also gave differential effects on cytochrome P-450 expression. Of particular interest was the very marked potentiation of the inductive effect of both 3-methylcholanthrene and phenobarbital. In the case of 3-methylcholanthrene the 10-fold induction of activity was increased to 24-fold by concomitant endotoxin administration. In this regard it was interesting that 3-methylcholanthrene was an effective inducer of a wide variety of acute-phase proteins including metallothionein, serum amyloid A, fibrinogen and hemopexin. These data show that endotoxin, and therefore bacterial infection and inflammation, can have profound and differential effects on components of the cytochrome-P-450 monooxygenase system which could result in significant changes in susceptibility to the effects of drugs, chemical toxins and carcinogens.

Acute-Phase Reaction↗
PubMed1988

Interaction of calcium nutrition and physical activity on bone mass in young women.

We have examined the relationships among calcium intake, mechanical stress (activity) and axial (lumbar) and peripheral (midradius) bone mass in a population of 60 young normal, healthy eumenorrheic women (age 25-34 years), selected on the basis of weight for height (within 20% of expected). In this population, vertebral bone mineral density was significantly related (r = 0.41, p less than 0.005) to activity pattern but not to calcium intake. Elimination of the effects of activity, however, disclosed a significant correlation between total calcium intake and vertebral bone mass (r = 0.36, p less than 0.02). Closer examination of this relationship suggested that vertebral bone mineral density did not appear to increase with calcium intakes above 800-1000 mg/day, implying a threshold effect and vertebral density was better expressed as a function of the logarithm of calcium intake (r = p less than 0.01). Radial mineral content was not related to activity (which was mostly walking and running), but it was significantly affected by calcium intake. These data suggest that skeletal status in the vertebrae in young women may be influenced by modulation of mechanical stress. However, bone mineral density is probably also dependent on nutritional status such that the optimum calcium intake for this effect is 800-1000 mg/day. If such effects, observed here cross-sectionally, can be substantiated in longitudinal studies and persist into the aging postmenopausal population, then the average age of onset of osteoporotic fractures would be expected to be delayed approximately 10 years, by relatively simple modifications of diet and activity.

Adult↗
PubMed1988

Management of osteoporosis.

Osteoporosis is clearly more easily prevented than treated. Prevention should start early for those thought to be most at risk. However, for the majority, menopause is the most convenient time point at which to evaluate the necessity for prevention. While oestrogens are the most effective therapeutic agent for prevention of postmenopausal bone loss, they must be used judiciously with attention to reduction in other nutritional and lifestyle risk factors. When given to women with an intact uterus, oestrogen prescription currently should be accompanied by progestogens, several of which may also reduce bone loss. All individuals should be encouraged to obtain an adequate calcium intake (100-1500 mg day-1) and to continue an active lifestyle. Therapy of the clinically overt disorder follows similar guidelines, with therapeutic options including calcitonin androgens and diphosphonates as well as oestrogens as antiresorptive agents. Methods of stimulating new bone formation are limited, the best documented effects being those of fluoride. However, care must be taken in its use and efficacy has yet to be finally established. Other modalities are as yet experimental. Much can be gained by careful attention to the general health of the patients and their environment, since reduction in risk of falls, and thus fracture, is at least as important as attempts to modify the skeleton.

Aging↗