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Biomedical subjects

R A Adler

Publications and source records attributed to R A Adler.

At least 19 recordsLinked to original sources
PubMed1992

Mild vitamin D deficiency and secondary hyperparathyroidism in nursing home patients receiving adequate dietary vitamin D.

OBJECTIVE: To compare the vitamin D metabolite and nutritional status of institutionalized elderly males with a noninstitutionalized control group. DESIGN: Case-control study. SETTING: Veterans Administration Medical Center Nursing Home (NH) in Richmond, Virginia. PATIENTS: Fifty-seven consecutive nursing home subjects were screened. After excluding blacks, those receiving anticonvulsants, glucocorticoids, or vitamin supplements, and those with liver or renal failure (creatinine greater than 1.5 mg/dL), 35 subjects were enrolled, and 22 completed the study. The noninstitutionalized control group (n = 18) consisted of consecutive volunteers, meeting the above criteria, from either a senior citizen group or a geriatric clinic. MEASUREMENTS AND MAIN RESULTS: The serum 25-hydroxy-vitamin D level in the NH residents was significantly lower than in community dwellers (17.4 +/- 5.2 ng/mL vs 31.2 pg/mL +/- 8.0 ng/mL, P less than 0.0001). No significant difference was demonstrated in 1,25-dihydroxyvitamin D levels (36.5 pg/mL +/- 10.5 in NH residents vs 42.0 pg/mL +/- 11.1 in controls). In the NH group PTH levels were inversely correlated with 25 OHD levels (P less than 0.008) and positively correlated with length of stay in the NH (P less than 0.016). There was no significant seasonal variation in vitamin D metabolite levels in the NH group. In the NH patients, the mean dietary intake of vitamin D was 232 +/- 378 mg/day and of calories was 1811 +/- 447 kcal/day. CONCLUSION: Despite apparently adequate calories, calcium, and vitamin D intake, hypovitaminosis D with compensatory PTH elevations occurs, regardless of season, in the nursing home population.

25-Hydroxyvitamin D 2↗
PubMed1992

Longitudinal changes in lumbar bone density among thyrotoxic patients after attainment of euthyroidism.

Hyperthyroidism increases bone turnover, which, in turn, may lead to bone loss from the spine and hip. Treatment of thyrotoxicosis may restore bone mass, but there are few long term prospective studies. We examined lumbar bone mineral density (BMD) in 21 subjects [11 with hyperthyroidism (HT) and 10 controls of similar age] by dual photon absorptiometry in 1986 and by dual energy x-ray densitometry in 1991. All 11 HT patients were successfully treated and remained euthyroid (mean TSH, 2.25 +/- 0.80 mU/L) for more than 3 yr. Lumbar BMD increased 11.03 +/- 2.38% (P < 0.001) in HT patients, but only 2.6 +/- 2.15% (P = 0.10) in control subjects. Among HT patients, the higher the T3 concentration during hyperthyroidism, the greater the subsequent increase in lumbar BMD (r = 0.72; P < 0.03). Age at treatment, in contrast, was not a significant predictor of eventual spinal bone mass. In conclusion, successful treatment of hyperthyroidism produced a significant increase in lumbar BMD. Hence, bone loss associated with thyrotoxicosis may not be permanent. Future work designed to examine the effect of thyroid hormone on skeletal homeostasis should include large scale longitudinal studies of both men and women.

Absorptiometry, Photon↗
PubMed1991

Characterization of a new animal model of chronic hyperprolactinemia.

Animal models of chronic prolactin (PRL) excess have included rats bearing transplantable pituitary tumors that have produced other hypophyseal hormones in addition to PRL. We report characterization of a new model, the Buffalo rat implanted with the MMQ tumor, a line developed from the 7315a line. Rats implanted with the MMQ tumor have serum PRL levels that increase with time and correlate with the estimated volume of the subcutaneous tumor. When rats are killed 4 weeks after implantation, serum PRL levels are strikingly higher in tumor-bearing rats compared with controls (females, 2,723 +/- 266 v 192 +/- 46 ng/mL, P less than .0001; males, 1,637 +/- 213 v 99 +/- 11 ng/mL, P less than .0001). Serum PRL levels measured by the Nb2 lymphoma assay were higher than immunoassay measurements in both tumor-bearing and control Buffalo rats. Sephadex chromatography of serum from tumor-bearing rats showed that most of the PRL immunoreactivity co-eluted with 125I-rPRL. Neither serum growth hormone (GH) nor luteinizing hormone (LH) levels were different from controls in tumor-bearing rats. Female MMQ-bearing rats had lower estradiol levels. At death, the wet weights of adrenal glands, kidneys, and gonads were not affected by the presence of tumor. In contrast, tumor-bearing rats had increased spleen weight and histological evidence of white pulp hyperplasia. The Buffalo rat implanted with the PRL-only MMQ tumor is a promising new tool for the study of chronic hyperprolactinemia.

Animals↗
PubMed1991

Hypercalciuria in a new rat model of hyperprolactinemia.

Hypercalciuria has been reported in rats with mild hyperprolactinemia due to implantation of anterior pituitary glands under the kidney capsule and in rats bearing transplantable tumors that secrete large amounts of prolactin (PRL) and growth hormone (GH). We studied Buffalo rats implanted subcutaneously with the new MMQ pituitary tumor line that secretes only PRL. Urinary calcium excretion increased as the tumors grew. Three weeks after tumor implantation in female rats, the urinary calcium excretion was 1.102 +/- 0.092 mg/100 g body weight (BW).24 hours compared with controls, 0.296 +/- 0.079, P less than .0005. Male tumor-bearing rats also had increased urinary calcium excretion compared with male controls. In tumor-bearing rats the urinary calcium excretion factored for urinary sodium excretion, dietary calcium intake, or urinary creatinine excretion was elevated. Urinary calcium excretion was correlated with serum PRL levels and with estimated tumor volume. Serum calcium, immunoassayable parathyroid hormone, and urinary cyclic adenosine monophosphate (cAMP) excretion were normal in the tumor-bearing rats. There was some evidence of loss of bone calcium in rats bearing the MMQ tumor, and serum levels of calcitonin were decreased. These results are similar to those found in anterior pituitary-grafted hypercalciuric rats. It is unlikely that parathyroid hormone (PTH) abnormalities are responsible for the hypercalciuria in the MMQ-bearing rats. The pituitary gland may have an effect on the distal renal tubule to decrease calcium reabsorption.

Animals↗
PubMed1991

Normal food intake and growth in hyperprolactinemic rats.

Normal lactation, a state of chronic hyperprolactinemia, is often accompanied by increased food intake. Two recent reports suggested that, in rats, prolactin (PRL) administration or chronic endogenous PRL excess led to increased food intake and growth. Similar methods of achieving augmented circulating levels of PRL in rats have been employed in our laboratory. Rats with extra anterior pituitary (AP) grafts under the kidney capsule have chronically elevated circulating PRL levels. However, in several experiments, weight gain, food intake, and fecal weight were the same in AP-grafted rats and in control muscle-grafted rats. In addition, the AP-grafted rat model was modified to demonstrate that PRL-induced increases in adrenal glucocorticoids and decreases in estrogens did not provoke alterations in eating behavior. Injection of homologous PRL for 8 days did not increase weight gain in normal or hypophysectomized rats. These data suggest that neither the chronic PRL excess caused by AP grafts nor the acute PRL excess caused by rat PRL injections increases food intake or weight gain.

Animals↗
PubMed1990

Exercise patterns and trabecular bone density in college women.

To assess the effects of physical activity patterns on trabecular bone density in college women, we studied three groups of nonsmoking eumenorrheic women with different (but chronic) exercise regimens. There were nine sedentary (SED) women exercising less than 1 h/week, nine women who performed aerobic (AER) exercise greater than 2.5 h/week, and nine women who supplemented aerobics with muscle-building activities (MB) for more than 1 h/week. Resting energy expenditure, calorie, protein, and calcium intake, total body weight, and body mass index were not statistically different among the three groups. AER and SED women had similar lumbar bone mineral density (BMD). MB women had significantly greater spinal bone density (p less than 0.007 versus SED, AER). IGF-1 (insulin-like growth factor) concentrations were greatest in MB (p less than 0.01), and hours muscle building per week correlated with IGF-1 (r = 0.86, p less than 0.03). For all 27 women (mean age 24.5 years), body mass index was the single best predictor of lumbar BMD (r = 0.42, p less than 0.03); hours in muscle-building exercise per week conferred an additive effect on lumbar BMD. This cross-sectional study of young women suggests chronic muscle-building exercises may augment lumbar bone mass. The additive effect of anaerobic exercise on bone density may be mediated by both local weight-bearing changes and possible systemic factors.

Adult↗
PubMed1990

T lymphocyte surface antigen markers in osteoporosis.

Two distinct syndromes of osteoporosis have been postulated: type I, which is characterized by accelerated bone loss occurring in women during the early postmenopausal period; and type II, an age-related process of bone loss affecting both men and women in and after the seventh decade. Recently there has been indirect evidence linking local products of the immune system with bone remodeling. We therefore studied peripheral blood profiles of specific lymphocyte phenotypes in women with type I osteoporosis and in older women and men with type II osteoporosis. The ratio of CD4-bearing (T helper) cells to CD8-bearing (T cytotoxic-suppressor) cells (CD4/CD8 ratio) was elevated in women with symptomatic type I disease. In addition there was a significant negative correlation (r = -0.62, P less than 0.001) between the CD4/CD8 ratio and the spinal bone mineral density measured by dual-photon absorptiometry. In contrast, older men with a history of fracture (hip or spine) had CD4/CD8 ratios similar to control men. The number of T cells bearing IL-2R or VLA-1 was not different between osteoporotic subjects and controls in either men or women. This study supports the concept that local products of the immune system may be directly or indirectly involved in the pathogenesis of type I osteoporosis.

Adult↗
PubMed1989

Hypogonadism does not mediate urinary calcium loss in pituitary-grafted rats.

Rats rendered chronically hyperprolactinemic by implantation of extra anterior pituitary glands (AP) under the kidney capsule have excess urinary calcium excretion. Although serum testosterone levels are normal in male AP-grafted rats, more subtle androgen deficiency might contribute to the increased calcium loss. Female AP-grafted rats lose the normal estrous cycle, which might also alter calcium homeostasis. The urinary calcium and calcium/sodium excretion ratio in gonadectomized AP-grafted rats of both sexes were compared with that of otherwise intact AP-grafted rats and muscle-grafted control rats. AP-grafted rats had increased urinary calcium excretion and calcium/sodium excretion ratio, regardless of gonadal status. Treatment of castrated male AP-grafted animals with testosterone or dihydrotestosterone did not have a significant effect on urinary calcium loss, nor did estrogen replacement of ovariectomized female AP-grafted rats. These studies indicate that the hypercalciuria of the AP-grafted rat is not mediated via an anti-gonadal effect of the prolactin-secreting pituitary graft.

Calcium↗
PubMed1989

Growth hormone (GH) secretion in the pituitary-grafted male rat: in vivo effects of GH-releasing hormone and isoproterenol and in vitro release by individual somatotropes.

Although the pituitary-grafted rat is a classic model of chronic PRL excess, the presence of somatotropes in grafted pituitary tissue indicates a potential for GH secretion. The current study was designed to investigate GH-releasing hormone (GRH)-induced GH secretion and beta-adrenergic inhibition of GH release in animals bearing ectopic pituitary tissue free from hypothalamic control. Positive findings with regard to these in vivo experiments led us to an initial determination of GH secretion by individual somatotropes from transplanted pituitary tissue. In litters of 10 30-day-old Fisher rats, 2 male animals received subcapsular renal grafts of 3 littermate pituitary glands each. Thirty-five days after grafting, 1 group received saline (SAL) followed by GRH, and the other received the beta-adrenergic agonist isoproterenol (ISO) followed by GRH. Blood samples were taken before and after SAL or ISO treatment, GRH was then infused, and sampling was continued. Plasma was assayed for GH and PRL, and the reverse hemolytic plaque assay was used to determine GH release by individual somatotropes from transplanted pituitary tissue. Plasma PRL was clearly elevated in pituitary-grafted compared to muscle-grafted animals, but there was no difference in either body weight gain or basal GH levels between the groups. As shown previously, ISO itself induced a brief release of GH due to its direct effect on the pituitary gland. The GH response to GRH was greater in pituitary-grafted animals than in muscle-grafted controls after both SAL and ISO. GRH-induced GH release was suppressed by ISO pretreatment in muscle-grafted animals, but not in pituitary-grafted animals. The reverse hemolytic plaque assay unequivocally showed that transplanted pituitary tissue was capable of tonic as well as GRH-stimulated GH release. These results demonstrate that despite similar basal GH levels, animals bearing pituitary grafts release significantly greater amounts of GH in response to GRH. The evidence for GH secretion by individual somatotropes from transplanted pituitary tissue directly shows the grafted tissue to be a source of GRH-stimulated GH. The lack of beta-adrenergic inhibition of GRH-induced GH release in pituitary-grafted animals is consistent with the hypothesis that beta-adrenergic inhibition of GRH-induced GH secretion is mediated by an effect on the hypothalamus.

Animals↗
PubMed1989

Insulin pump treatment of type I diabetes mellitus in a patient with C6 quadriplegia.

A 40-year-old patient with insulin-dependent (Type I) diabetes mellitus since childhood suffered a C6 spinal transection. Recurrent episodes of hypoglycemia resolved after the patient was placed on an insulin pump. The patient is able to set the insulin delivery rate and maintain the pump without assistance. Spinal cord injured patients may lack both the clinical symptoms of, and the ability to respond to, hypoglycemia. The mixing of NPH insulin and regular insulin requires fine motor skills; even with prefilled syringes, the quadriplegic person may have difficulty with subcutaneous injection. The use of an "open loop" insulin pump averts these problems and may provide better glucose control for selected spinal cord injury patients with Type I diabetes.

Adult↗
PubMed1987

Examination of hypercalciuria in anterior pituitary-implanted rats.

The anterior pituitary (AP) grafted, adrenalectomized, steroid hormone-replaced male rat is characterized by hyperprolactinemia and hypercalciuria. To determine the origin of the hypercalciuria, clearance experiments were performed under Inactin anesthesia in adrenalectomized Fischer rats 8-10 wk after implantation of extra AP glands under the kidney capsule. Glomerular filtration rate, ultrafilterable calcium, and fractional sodium excretion were comparable in the AP and control groups. However, fractional calcium excretion was significantly higher in the AP-implanted rats, P less than 0.05, resulting in a marked dissociation of the calcium/sodium clearance ratio. Because filtered calcium load did not change, these results clearly demonstrate that AP-implanted animals have a defect in tubular calcium reabsorption. The dissociation of calcium transport from sodium transport suggests the distal tubule as a likely site of action. Parathyroidectomy did not alter the calciuric response to AP implantation. To test whether hyperprolactinemia was responsible for decreased calcium reabsorption in AP-implanted rats, purified rat prolactin was infused into normal rats to achieve high blood prolactin levels, or was injected into normal rats daily for 8 days. Changes in fractional calcium excretion and the ratio of calcium to sodium clearance were identical in animals receiving prolactin or control infusions. Thus, hypercalciuria in the AP-implanted rat may be attributed to an unidentified factor, perhaps secreted from the implanted anterior pituitaries, rather than to prolactin excess.

Adrenalectomy↗
PubMed1986

Hypercalciuria in hyperprolactinemic rats: effects of benzthiazide.

There is evidence that prolactin (PRL) excess plays a role in the etiology of osteoporosis associated with human prolactinoma. Calcium balance in human hyperprolactinemia has not been thoroughly investigated. In the present study, rats with excess circulating PRL levels (male anterior pituitary-grafted Fischer 344 rats) had urinary calcium excretion twice that of control rats (4.16 +/- 0.43 v 2.25 +/- 0.30 mg/24h X 100 g BW). Calcium excretion expressed per mg of calcium intake was also high in pituitary-grafted rats. The excess calcium excretion in hyperprolactinemic rats was not accompanied by a concomitant rise in sodium excretion. This dissociation suggests that PRL has an effect on the renal handling of calcium. Since thiazide diuretics have a well-described hypocalciuric action, their effect was tested in these rats. In normal rats, benzthiazide, a long-acting agent, significantly reduced urinary calcium excretion in a dose-dependent fashion. Hyperprolactinemic rats responded to benzthiazide in a manner similar to control rats. In pituitary-grafted rats, benzthiazide also decreased the calcium excretion to intake ratio and normalized the calcium to sodium excretion ratio. Since the hypercalciuria of experimental hyperprolactinemia can be corrected by thiazide diuretics, these agents may have therapeutic potential in human PRL excess.

Animals↗
PubMed1986

Increased water excretion in hyperprolactinemic rats.

The role of PRL in mammalian salt and water balance remains controversial. To avoid the methodological problems of exogenous PRL administration, endogenous hyperprolactinemia was established in normal rats by implantation of extra anterior pituitary glands under the kidney capsule. To eliminate excess glucocorticoid secretion in these rats, they were adrenalectomized, implanted with corticosterone replacement pellets, and given 0.9% saline drinking fluid. A highly significant increase in urine flow was found in pituitary-grafted male Fischer rats compared to control rats (38.9 +/- 3.8 vs. 20.7 +/- 1.6 ml/24 h X 100 g BW; P less than 0.0005). Urine osmolality was lower in pituitary-grafted rats, but sodium and potassium excretion were not abnormal. Although fluid intake was also greater in hyperprolactinemic rats, the urine flow remained elevated when adjusted for fluid intake. Renal binding sites for radioactive PRL were not decreased in pituitary-grafted rats. Thus, the hyperprolactinemic rat has increased water excretion that may be attributed to a direct renal effect rather than to glucocorticoid excess or a primary change in thirst. Since it is possible that water absorption in the gut is also increased by PRL, multiple effects of PRL may be responsible for the diuresis observed in hyperprolactinemic rats.

Animals↗
PubMed1985

Thyroxine 5'-deiodinase activity in anterior pituitary glands transplanted under the renal capsule in the rat.

The conversion of T4 to T3 by the anterior pituitary gland appears to be of considerable physiological importance in the control of pituitary function. To determine a possible role of hypothalamic factors in controlling this enzymatic process, iodothyronine 5'-deiodinase (I5'D) activity was studied in rats 6 weeks after homologous transplantation of pituitary (implanted animals) or muscle tissue (sham animals) under the renal capsule. Intrasellar pituitaries remained intact, and serum T3, T4, and TSH levels were similar in both groups. I5'D activity was determined by quantifying T3 production rates in tissue homogenates at T4 concentrations of 0.002-4 microM, and with 20 mM dithiothreitol. Sellar pituitaries from sham and implanted animals displayed similar nonlinear reaction kinetics, suggesting the presence of two enzymatic processes having approximate Michaelis-Menten constant (Km) values of 2 nM and 0.3 microM. Maximum velocity (Vmax) was 51.3 +/- (SE) 4.0 fmol T3/min X mg protein (units) and 40 +/- 6 U for the low and high Km components, respectively. In transplanted pituitary tissue, I5'D activity was markedly altered; the low Km activity was significantly decreased (Km, 6 nM; Vmax, 13.0 +/- 1.1 U; P less than 0.001 compared to sellar pituitaries), whereas the high Km activity was increased 15-fold (Km, 5 microM; Vmax, 620 U). The in vitro addition of 6-n-propyl-2-thiouracil (0.1 mM) inhibited high Km I5'D activity in homogenates of both transplanted pituitary and renal tissue by approximately 50% (P less than 0.001), but had no effect on low Km I5'D activity in either sellar or transplanted pituitaries. In sham and implanted animals rendered hypothyroid by the inclusion of 1 g/dl NaClO4 in their drinking water for 6 weeks, low Km I5'D activity was increased approximately 3-fold in sellar and transplanted pituitary tissue. The levels of activity reached in transplanted tissue, however, were only 20-30% of those noted in sellar pituitary homogenates (P less than 0.001). High Km I5'D activity was estimated to be decreased 55% in transplanted tissue from hypothyroid animals. These studies demonstrate that transplantation of the anterior pituitary gland under the renal capsule in the rat results in marked alterations in two distinct components of pituitary I5'D activity. This suggests that neuroendocrine factors are important in the control of pituitary T4 to T3 conversion. Furthermore, it provides evidence for a unique mechanism whereby the hypothalamus, by modulating local thyroid hormone metabolism, may influence pituitary function.

Animals↗