Iatrogenic hyperthyroidism of long duration in an individual with thyroxine-binding globulin deficiency.
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Adult↗
Biomedical subjects
E Gold
Publications and source records attributed to E Gold.
Flutamide-mediated androgen blockade evokes osteopenia in the female rat.
Androgens are believed to play a role in building and maintaining bone in the female, as well as in the male. The antiandrogen drug flutamide inhibits responses to androgens from both the gonads and the adrenals. Antiandrogens prevent androgens stimulating bone cell proliferation and differentiation in vitro, but effects of androgen blockade on bone metabolism in vivo have not been tested. The present study was undertaken to determine whether androgen blockade with flutamide (15 mg/kg body weight orally daily) would influence bone turnover or bone composition (1) in female rats with intact ovaries and (2) in rats made estrogen-deficient with the luteinizing hormone releasing hormone (LHRH) agonist, buserelin (25 micrograms/kg body weight per day SC). Four groups of rats with 45Ca-labeled skeletons were studied for 4 weeks: group A, placebo; group B, buserelin; group C, flutamide; group D, flutamide+buserelin. Total-body calcium values (mean +/- SD) were (mg) 2007 +/- 109, 1779 +/- 138 (P < 0.01 versus group A), 1818 +/- 140 (P < 0.01 versus group A), and 1690 +/- 75 (P < 0.01 versus group A) in groups A-D, respectively. Thus both buserelin and flutamide induced osteopenia. Skeletal 45Ca changes suggested buserelin-mediated estrogen deficiency bone loss was due to increased bone resorption, but flutamide-mediated androgen deficiency bone thinning was caused principally by reduced bone formation. These findings support the view that androgens play an important role in preserving bone mass in the female rat. Importantly, adequate estrogen status did not compensate for flutamide-mediated osteopenia.(ABSTRACT TRUNCATED AT 250 WORDS)
Androgens↗
Norethindrone acetate only partially protects the skeleton of rats treated with the LHRH agonist buserelin from oestrogen-deficiency osteopaenia.
In women with endometriosis there is concern that therapeutic use of LH-releasing hormone (LHRH) analogues, to lower ovarian oestrogen production and control endometrial hyperplasia, leads to unwanted oestrogen-deficiency bone loss. We have developed an animal model of this LHRH-mediated oestrogen-deficiency bone loss in the rat, using buserelin. The aim was to use this model to determine whether the progestogen, norethindrone acetate, could counter oestrogen-deficiency bone loss associated with prolonged treatment with the LHRH agonist buserelin. Four groups of animals which had their bones labelled with 45Ca were studied for 4 weeks: group A, control; group B, buserelin treated; group C, norethindrone acetate treated; group D, norethindrone acetate+buserelin treated. Buserelin was given daily (19.2 pmol/kg body wt); norethindrone was given orally three times/week (1.47 mumol/kg body wt). Bone resorption was monitored by measuring the urinary excretion of hydroxyproline and 45Ca and bone 45Ca content. Buserelin-treated rats developed similarly depressed plasma oestradiol-17 beta values in the presence and absence of progestogen, and both groups given buserelin had significantly smaller uteri than controls or rats given norethindrone without buserelin. However, norethindrone did not prevent buserelin-mediated increases in bone resorption. At the end of the study total body calcium values (mean +/- S.D.) in the four groups were (mg) respectively; 2594 +/- 123; 2260 +/- 92 (P < 0.001 compared with controls); 2616 +/- 221; 2415 +/- 130 (P < 0.02 compared with controls). Rats given norethindrone and buserelin in combination had higher values (P < 0.02) than animals given buserelin alone, but significantly less total body calcium than controls (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Tamoxifen in the rat prevents estrogen-deficiency bone loss elicited with the LHRH agonist buserelin.
In young women chronic use of luteinizing hormone releasing hormone (LHRH) agonists such as buserelin to treat endometriosis leads to estrogen-deficiency bone loss. Tamoxifen citrate is an estrogen agonist/antagonist which protects the skeleton from osteopenia when ovarian hormones are depleted. The present study was undertaken to determine whether tamoxifen citrate (20 mg/kg body wt/week s.c.) could prevent the osteopenic effect of buserelin (25 micrograms/kg body wt/day s.c.). Four groups of rats with 45Ca-labelled bones were studied for 4 weeks: group A--placebo controls; group B--buserelin; Group C--tamoxifen; group D--buserelin+tamoxifen. Bone resorption was monitored by measuring the urinary excretion of 45Ca and hydroxyproline. Interestingly buserelin lowered both blood 17 beta-estradiol values and uterine weights in the presence and absence of tamoxifen. However, tamoxifen slowed bone breakdown and inhibited the bone-thinning effects of buserelin. Total body calcium values (mg; means +/- S.D.) were: 2227 +/- 137; 1926 +/- 124; 2233 +/- 94 and 2268 +/- 163, in groups A to D respectively. Osteopenia was thus present only in group B (P less than 0.001). Because tamoxifen inhibits estrogen-deficiency bone loss in buserelin-treated rats without depressing the hypoestrogenic actions of this LHRH-agonist, we suggest that use of tamoxifen to protect the skeleton during LHRH-agonist therapy in young women should be explored. Tamoxifen citrate might also help to prevent postmenopausal osteoporosis.
Animals↗
DNA diagnosis with mutation-specific artificial methylation sites: application to rapid screening of delta F508.
Many polymerase chain reaction (PCR)-based methods for diagnosis of minute mutations are suboptimal for automated screening because of their reliance on gel electrophoresis or probe hybridization. In the method reported here, PCR products containing artificial methylation sites are analyzed by measuring incorporation of radiolabeled methyl groups. Primers are designed to amplify the possible mutation-containing region such that the 3' end of one primer lies adjacent to the possible mutation. Sequence modification near that end creates either a mutation- or wild type (WT)-specific artificial methylation site in the PCR product. The product is briefly incubated with an appropriate DNA methylase and tritiated S-adenosylmethionine ([3H]SAM), separated from free SAM by column chromatography, and analyzed for incorporation of tritium. Applying this technique to the cystic fibrosis delta F508 deletion, we accurately diagnosed five homozygotes, five heterozygotes, and five normal individuals within 40 min of PCR completion. The method can be generalized to rapid, automated detection of a variety of point mutations and small deletions.
Base Sequence↗
Reactions to ethanol and diazepam in healthy young men.
The reactions to oral ethanol (0.75 ml/kg), IV low-dose diazepam (0.12 mg/kg) and IV high-dose diazepam (0.2 mg/kg) were evaluated over four test sessions in the same 48 healthy young men. The data demonstrated similar subjective feelings after the low-dose diazepam and ethanol, but significantly greater effect after high-dose diazepam. Despite the similarities on subjective feelings, the low-dose diazepam challenge resulted in significantly more impairment than did ethanol on measures of memory, body sway and the evaluation of the passage of time. The similarities in subjective aspects of intoxication for ethanol and low-dose diazepam have potential implications for increasing our understanding of possible enhanced vulnerabilities for abuse of benzodiazepines among alcohol-abusing patients. The trend for similarities in subjective intoxication but greater impairment in motor and cognitive performance after low-dose diazepam compared to ethanol might indicate that subjects might be less aware of their actual levels of performance difficulties after the benzodiazepine. It is hoped that these data will help clinicians understand more about the quality of intoxication with benzodiazepines and the types of impairments likely to be observed.
Adult↗
Buserelin-mediated osteoporosis: effects of restoring estrogen on bone resorption and whole body calcium content in the rat.
In the rat, prolonged administration of the luteinizing, hormone-releasing hormone agonist buserelin (25 micrograms/kg body wt/day s.c.) lowers blood estradiol, raises bone resorption, and induces osteopenia. The present study was undertaken to determine whether withdrawal of buserelin normalizes blood estradiol, slows bone resorption, and corrects buserelin-mediated osteopenia. Four groups of female rats with 45Ca-labeled bones were studied: group 1A received 0.2 ml saline s.c. daily for 4 weeks; group 2A received 0.2 ml buserelin s.c. daily for 4 weeks; group 1B received 0.2 ml saline s.c. daily for 8 weeks; group 2B received 0.2 ml buserelin s.c. daily for 4 weeks followed by 0.2 ml saline s.c. daily for 4 weeks. Bone resorption was monitored by measuring urinary 45Ca and hydroxyproline. The rats in groups 1A and 2A were killed after 4 weeks and those in groups 1B and 2B after 8 weeks. The mineral contents of the femoral bones and the whole skeletons were measured. Buserelin lowered blood estradiol, elevated urinary 45Ca and urinary hydroxyproline, and lowered femur and total body calcium and 45Ca in group 2A vs. 1A (P less than 0.05). By contrast all these measurements became similar in groups 2B and 1B. Thus, osteopenia generated by a 4-week period of buserelin-mediated hypo-estrogenism is reversible by withdrawing buserelin for 4 weeks. Consequently, buserelin administration and withdrawal may be used to study effects of inducing and reversing estrogen-deficiency bone loss in the rat.
Animals↗
Effects of clomiphene and tamoxifen in vivo on the bone-resorbing effects of parathyroid hormone and of high oral doses of calcitriol (1,25(OH)2D3) in rats with intact ovarian function consuming low calcium diet.
Two experiments were undertaken to study the abilities of clomiphene citrate (20 mg/kg body wt/wk s.c.) and tamoxifen citrate (20 mg/kg body wt/wk s.c.) to slow bone resorption mediated by (a) endogenous parathyroid hormone (PTH) and (b) exogenous calcitriol (1,25(OH)2D3) in vivo in rats with intact ovarian function. Groups of rats with 45Ca-labelled bones were fed a low-calcium (0.01% Ca) diet to stimulate secretion of PTH. Neither clomiphene nor tamoxifen showed the mobilization of 45Ca from femoral bone or prevented the reduction in bone calcium induced by feeding this diet. Moreover these drugs did not depress the urinary excretion of 45Ca or hydroxyproline. These observations indicated that clomiphene and tamoxifen did not inhibit PTH-mediated bone resorption. Administering calcitriol (50 ng/day) orally for 14 days raised plasma calcium, increased urinary 45Ca and its specific activity and decreased femur 45Ca: all these responses were similar in animals receiving calcitriol alone and calcitriol with clomiphene or tamoxifen. The femur 45Ca values (dpm X 10(-3) were: (mean +/- SD, n = 8) placebo, 1901 +/- 127; 1,25(OH)2D3, 1727 +/- 96**; clomiphene + 1,25(OH)2D3, 1694 +/- 93**; tamoxifen + 1,25(OH)2D3, 1664 +/- 61**. (** = P less than 0.01). Thus neither clomiphene nor tamoxifen prevented calcitriol-mediated bone resorption in vivo in the rat.
Animals↗
Neurological improvement following respiratory support in syringomyelia: case report.
Respiratory failure in syringomyelia has rarely been reported. We report a patient with syringomyelia who showed some neurological improvement after intermittent respiratory support with negative and positive pressure ventilation.
Adult↗
Estrogens and progestogens conserve bone in rats deficient in calcitonin and parathyroid hormone.
To examine the abilities of estrogens and progestogens to slow bone resorption and conserve bone in ovariectomized rats deficient in calcitonin (CT) or parathyroid hormone (PTH), nine groups of animals with 45Ca-labeled bones were studied for 12 wk. Rats were thyroidectomized (TX), parathyroidectomized (PTX), or given sham neck operations (Sham) and treated orally with either estrogen, 300 micrograms 17 beta-estradiol.kg body wt-1.wk-1; progestogen, 500 micrograms norethisterone acetate.kg body wt-1.wk-1; or placebo (Plac). The TX rats had parathyroid autografts and thyroxine replacement. In all surgical groups, estradiol (E2) and norethindrone (Nor) slowed urinary 45Ca excretion and conserved bone (P less than 0.001). However E2 lowered urinary hydroxyproline more than Nor. Total body Ca values (mg +/- SD) were Sham + Plac, 3,079 +/- 201; Sham + E2, 3,886 +/- 335; Sham + Nor, 3,567 +/- 459; TX + Plac, 3,123 +/- 159; TX + E2, 3,869 +/- 235; TX + Nor, 3,540 +/- 422; PTX + Sham, 3,067 +/- 249; PTX + E2, 3,775 +/- 414; PTX + Nor, 3,635 +/- 467. Importantly, E2 and Nor conserved bone as effectively in TX and PTX groups as in Sham rats, although the PTX rats had slower bone resorption and lower plasma 1,25-dihydroxyvitamin D values (P less than 0.001) than groups with intact parathyroids. We conclude that the effects of estrogens and progestogens to slow bone resorption and conserve bone are independent of CT and PTH. These findings appear relevant to the pathogenesis and treatment of postmenopausal osteoporosis.
Animals↗
A new way to induce oestrogen-deficiency osteopaenia in the rat: comparison of the effects of surgical ovariectomy and administration of the LHRH agonist buserelin on bone resorption and composition.
Prolonged administration of LHRH agonist suppresses pituitary gonadotrophin secretion, thereby lowering blood oestrogen. This study was undertaken to compare the osteopaenic effects of bilateral ovariectomy and chronic administration of the LHRH agonist, buserelin, in the rat. Four groups of animals which had their skeletons labelled with 45Ca were studied for 4 weeks. Group 1 underwent a sham-ovariectomy, group 2 were surgically ovariectomized, group 3 were given buserelin by daily s.c. injection and group 4 were given a continuous infusion of buserelin by osmotic minipump. Plasma concentrations of oestradiol were measured weekly. Bone resorption was assessed by measuring the urinary excretion of 45Ca and hydroxyproline and determining bone 45Ca content. Ovariectomy and buserelin treatments lowered blood oestradiol, increased biochemical indices of bone resorption and decreased femur and total body calcium and 45Ca values. The degree of oesteopaenia elicited by ovariectomy and buserelin treatment was similar. Bone responses to s.c. buserelin and to continuous buserelin infusion were alike. We attribute evidence of increases in bone resorption and induction of osteopaenia with buserelin treatment to hypo-oestrogenism. We have shown for the first time by bone analysis that buserelin induces osteopaenia as effectively as bilateral ovariectomy. This appears to be the first demonstration in the rat that long-term administration of LHRH agonist influences bone. Administration of buserelin provides a new way of inducing oestrogen-deficiency osteopaenia in the rat without removing the ovaries.
Animals↗
Enumerative, Bayesian, and analytic statistical analysis of nosocomial infection for quality improvement: first of two parts.
Readmission rates are used by the Health Care Financing Administration (HCFA) as an indicator of a hospital's quality of care. Specifically, HCFA seeks to relate readmission to complications of the primary admission. A recent study at the Cleveland Clinic Foundation examined patients readmitted within 30 days of dismissal during two non-consecutive months to the cardiovascular surgery, cardiology, and gastroenterology services at this 1,008 bed hospital, accounting for 31% (1640-5342) of all hospital discharges. Only 17% (25/149) of readmissions were due to a complication of the previous hospital admission. Examining those who were readmitted for complications of their primary admission, we found that 36% (9/25) of such readmitted patients had infections that occurred during their primary admission. Otherwise stated, 5.4% (9/149) of readmissions were for nosocomial infections. These patients were compared with 20 retrospectively matched, non-readmitted patients chosen randomly from a group of 100 patients retrospectively matched for gender, age, type, and date of surgery. Using these controls, a computer-based expert system was used to help identify patient variables that are associated with readmission due to nosocomial infection. We found if a patient had (1) a weight less than 66 Kilograms or (2) had a first postoperative total serum protein greater than 6.1 or (3) was reoperated, we could predict with 100% specificity and 60% sensitivity that the patient would have an unplanned readmission. Total readmission rates do not accurately reflect complications of the primary admission.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Outbreak of Campbell de Morgan spots in a nursing home--Alberta.
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Adult↗
Effects of dietary NaCl supplementation on bone synthesis of hydroxyproline, urinary hydroxyproline excretion and bone 45Ca uptake in the rat.
High sodium chloride intakes are regarded as a risk factor for osteoporosis because they increase the obligatory urinary calcium loss and stimulate parathyroid activity. Sodium chloride loads induce osteopenia in the rat. The effect could be due to a decrease in bone formation or a rise in bone resorption. Two experiments were undertaken to study the effects of dietary NaCl supplementation on 3H-hydroxyproline synthesis and 45Ca uptake in femoral bone. Salt-treated rats excreted 1.7 times more total urinary hydroxyproline (P less than 0.001) and 2.1 times more recently labelled 3H-hydroxyproline than controls (P less than 0.02) but they did not accumulate less 3H-hydroxyproline or less 45Ca in their bones than controls. These results indicate that salt-mediated osteopenia is due to an increase in bone resorption, rather than to a decrease in bone formation.
Animals↗
Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving beta-estradiol.
To examine the interactions between estrogen deficiency and glucocorticoid excess on bone metabolism the osteopenic effects of a standard dose of prednisolone (2 mg/kg BW.day) were studied in sham-ovariectomized (Sham-OVX), ovariectomized (OVX), and OVX rats given replacement beta-estradiol (OVX + E2). For 12 weeks six groups of female albino rats aged 4 months which had their skeletons labeled with 45Ca were fed matched amounts of low-calcium (0.1% Ca) hydroxyproline-free diet. The six treatment groups were: group 1, Sham-OVX; group 2, Sham-OVX + prednisolone; group 3, OVX; group 4, OVX + prednisolone; group 5, OVX + E2; group 6, OVX + E2 + prednisolone. Bone resorption was estimated by studying the urinary excretion of hydroxyproline and 45Ca. Parathyroid function was assessed indirectly from urinary cAMP excretion. Treatments did not influence parathyroid activity or serum levels of calcium or 1,25-dihydroxyvitamin D. However, ovariectomy increased bone resorption and induced osteopenia whereas prednisolone decreased bone resorption and formation and caused osteopenia. Ovariectomy increased the rate of bone resorption in prednisolone-treated rats; prednisolone lowered the rates of bone resorption and formation in OVX rats. The osteopenic effects of prednisolone and ovariectomy were additive and independent. E2 protected bone from the osteopenic effects of ovariectomy but did not affect bone loss induced by prednisolone. These results suggest prophylactic estrogen should help to avoid bone loss from estrogen deficiency in patients requiring chronic high dose glucocorticoid treatment.
Animals↗
Plasma cortisol levels following ethanol in sons of alcoholics and controls.
We used the pattern of change in plasma cortisol level following ethanol challenges to help characterize differences in response to alcohol in sons of alcoholics and controls. Thirty healthy, drinking young adult sons of alcoholics were matched with 30 sons of nonalcoholics on demography, drug use, and alcohol use histories. Each was tested on three occasions, when he received, in random order, placebo, 0.75 mL/kg of ethanol, and 1.1 mL/kg of ethanol. Subsequent blood samples for cortisol determinations were obtained every 30 minutes over the next four hours. The sons of alcoholics, at higher risk for the future development of alcoholism, demonstrated lower cortisol levels after drinking. The data are consistent with our prior measures of self-reported feelings of intoxication and family group differences in ethanol-induced decrements in performance.
Adult↗
Parental occupations and cancer.
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Child↗
Serum prolactin levels in sons of alcoholics and control subjects.
The authors evaluated changes in serum prolactin levels as a measure of differences in response to ethanol between 30 healthy, drinking, young adult sons of alcoholics and 30 matched control subjects with no family history of psychiatric or substance abuse problems. The control subjects were matched for demographic variables, drug use histories, and alcohol use histories. Each individual was tested on three occasions, receiving, in random order, placebo, 0.75 ml/kg of ethanol, and 1.1 ml/kg of ethanol. Controlling for baseline prolactin measures and hormonal changes after placebo, the authors found that the sons of alcoholics had significantly lower prolactin levels in response to the high-dose ethanol challenge.
Adult↗