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Biomedical subjects

R A Adler

Publications and source records attributed to R A Adler.

At least 55 records · Page 3Linked to original sources
PubMed1983

Studies of anterior pituitary-grafted rats: I. Abnormal prolactin response to thyrotropin releasing hormone, clonidine, insulin, and fasting.

Although the rat implanted with extra anterior pituitary glands (AP) under the kidney capsule has been widely used as a model of chronic hyperprolactinemia, its hormonal status has not been fully characterized. Using conscious, unrestrained female pituitary-grafted rats and sham-operated littermates, we investigated prolactin (PRL) secretion in response to the following stimuli: thyrotropin releasing hormone (TRH), clonidine, insulin, and fasting. The AP-implanted rats had a greater and more sustained rise in serum PRL after TRH than control rats, reflecting a direct effect of TRH on the ectopic lactotropes. In contrast after clonidine, which acts via the hypothalamus, the serum PRL rose to much higher levels in sham-operated rats than in rats bearing ectopic pituitary tissue. Both insulin-induced hypoglycemia and fasting decreased serum PRL in control rats, but the AP-implanted animals manifested a rise in serum PRL in response to these stimuli. Thus, the AP-implanted rat is not only a valid model of excess and abnormal PRL secretion, but it may also be useful for distinguishing between stimuli requiring an intact hypothalamic-pituitary unit and agents which act directly on the pituitary gland.

Animals↗
PubMed1983

Studies of anterior pituitary-grafted rats: II. Normal growth hormone secretion.

Of the various animal models used to study chronic hyperprolactinemia, the otherwise intact rat implanted with extra anterior pituitary glands (AP) under the kidney capsule is assumed to be normal except for excess circulating prolactin (PRL). Since the ectopic glands contain numerous somatotropes in addition to abundant and active lactotropes, it was important to assess growth hormone (GH) secretion as well in this model of hyperprolactinemia. The structural and functional similarities of PRL and GH are such that it is necessary to demonstrate that metabolic abnormalities noted in AP-implanted rats are due to hyperprolactinemia and not to altered GH secretion. AP-implanted female rats have significantly higher resting serum PRL concentrations when compared to sham-operated control rats, but baseline serum GH levels are similar in normal and pituitary-grafted rats. Suppression of GH by insulin and clonidine is comparable in AP-implanted and control rats. The intrasellar pituitary GH concentration is also similar (ca. 20 micrograms/mg wet weight) in hyperprolactinemic and normal rats. We conclude that GH secretion is normal in the non-hypophysectomized AP-implanted rat, in contrast to the hypophysectomized AP-implanted rat model which has been reported to have diminished GH secretion. Despite the presence of recognizable somatotropes, the ectopic anterior pituitary does not appear to secrete significant amounts of GH, making the intact rat bearing multiple pituitary grafts an excellent model of chronic hyperprolactinemia.

Animals↗
PubMed1982

Glucose tolerance in rats with elevated circulating prolactin levels.

The consideration of prolactin as one of the anti-insulin hormones has been based on studies describing the ability of injected prolactin to raise the serum glucose. We studied the glucose tolerance of rats made hyperprolactinemic by the implantation of extra anterior pituitary glands under the kidney capsule. Surprisingly the hyperprolactinemic rats had lower serum glucose levels after a bolus injection of dextrose. Furthermore, their serum insulin levels were no higher than sham-operated control rats. AFter a fast of 18 or 24 hours, the serum glucose was lower in the hyperprolactinemic rats, and the serum insulin concentrations were similar in implanted and control rats. These data suggest that chronic hyperprolactinemia does not decrease glucose tolerance. Whether prolactin has a direct insulin-like effect or whether it may potentiate insulin's effects will require further study.

Animals↗
PubMed1982

Preparation of a biologically active rat prolactin devoid of antidiuretic activity.

Rat prolactin (NIH rPRL-B2) was purified using Sephadex chromatography and isoelectric focusing. SDS-gel electrophoresis of the original material showed a major band of 23K daltons, as well as several minor bands; the purified prolactin had a single 23K band. The original material contained 33 pg of immunoreactive vasopressin per 0.1 micrograms of material; vasopressin was not detectable in the purified material by either RIA or bioassay. The purified preparation had complete biological activity in a mammary gland bioassay and a receptor binding assay.

Animals↗
PubMed1981

Thyroid function after mantle irradiation in Hodgkin's disease.

We studied the thyroid function of 64 patients with Hodgkin's disease who received mantle irradiation during the period 1966 to 1976. More than two thirds (44 of 64) had some thyroid dysfunction. Twenty had mild dysfunction manifested by an abnormal thyroid-stimulating hormone response to thyrotropin-releasing hormone. Twenty had what could be termed compensated hypothyroidism while four were overtly hypothyroid. The severity of dysfunction was not related to age, sex, or chemotherapy. We found, however, that decreased thyroid function was inversely proportional to the length of time between a diagnostic lymphangiogram and the radiation therapy. These results are consistent with the hypothesis that the iodine load of the lymphangiogram renders the thyroid gland more radiosensitive. Thyroxine suppression of the thyroid gland during the period from the lymphangiogram through the termination of radiation therapy is suggested as a means of avoiding thyroid injury.

Ethiodized Oil↗
PubMed1981

Demonstration that rat prolactin has no intrinsic antidiuretic activity in the rat.

The proposition that rat prolactin has an intrinsic antidiuretic activity was examined using a conscious rat model (Brattleboro homozygotes, DI rats) which does not appear to produce arginine vasopressin (AVP). A preparation of rat prolactin obtained from NIAMDD, rat prolactin B1, produced a prompt antidiuresis when administered intravenously to these animals. Prolactin B1 was found to contain 150 ng of AVP/mg protein by RIA. All of the measurable AVP was removed from prolactin B1 by polyacrylamide gel electrophoresis and the electrophoresed prolactin was completely devoid of any antidiuretic activity. Addition of synthetic AVP to electrophoresed prolactin in an amount equivalent to the AVP contamination of prolactin B1 completely restored the originally observed antidiuretic activity. Synthetic AVP given alone produced a similar antidiuresis, but in the presence of electrophoresed prolactin these effects were produced by much smaller amounts of AVP. We believe that our data demonstrate that rat prolactin has no intrinsic antidiuretic activity, and that the antidiuretic activity associated with different prolactin preparations could be entirely due to their contamination with AVP. The data also show that the presence of prolactin enhanced by about five times the antidiuretic activity of AVP.

Animals↗
PubMed1980

Skeletal responsiveness in pseudohypoparathyroidism. A spectrum of clinical disease.

Three cases of pseudohypoparathyroidism with roentgenographic evidence of hyperparathyroid bone disease are described. Renal resistance to exogenous parathyroid hormone (PTH), the hallmark of pseudohypoparathyroidism, was documented by markedly blunted or absent urinary phosphate and cyclic AMP responses to parathyroid extract. At the time of diagnosis all patients were hypocalcemic and hyperphosphatemic with elevated serum alkaline phosphatase levels and subperiosteal resorption noted on skeletal films. Bone biopsy in one patient revealed a histologic appearance consistent with hyperparathyroidism. Serum PTH levels, measured in two patients while they were hypocalcemic, were elevated. None of the patients had short stature, brachydactyly, subcutaneous calcification or mental deficiency. These cases are compared to the 15 well-documented cases previously reported. The presently available information on pseudohypoparathyroidism indicates a variable skeletal response to PTH mediated by several factors extrinsic to bone and suggests that pseudohypoparathyroidism with hyperparathyroid bone disease is one extreme of a clinical spectrum of skeletal responsiveness to PTH. This disorder is part of an expanding clinical picture which makes pseudohypoparathyroidism a diagnostic consideration in any patient with unexplained hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase levels or metabolic bone disease.

Adolescent↗
PubMed1979

The effects of elevated circulating prolactin in rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain).

Administration of ovine or rat PRL to animals, including man, has resulted in decreased urine volume and increased urine osmolality. Contamination of PRL preparations with vasopressin is the most likely explanation for the apparent antidiuretic effect. In this study, diabetes insipidus rats lacking vasopressin(homozygous Brattleboro rats) had extra anterior pituitary glands implanted under the kidney capsule, resulting in hyperprolactinemia. The urine of such rats was not more concentrated than that of unoperated littermates or sham-operated littermates with diabetes insipidus. In fact, hyperprolactinemic male rats produced even less concentrated urine than control rats. Furthermore, the hyperprolactinemic rats responded to exogenous vasopressin in a manner similar to normoprolactinemic rats. These studies provide strong evidence against an antidiuretic action of PRL in mammals.

Animals↗
PubMed1976

Low dose radioiodide thyroid ablation in postsurgical patients with thyroid cancer.

Sixty-four patients with well-differentiated carcinoma of the thyroid were treated with initial high (80 to 100 mCi) or low (less than 30 mCi) doses of I131 after bilateral subtotal thyroidectomy. A total of 36 patients in the various histologic categories were initially treated with the low dose of I131 (group 1), and a total of 28 patients were treated with the higher dose (group 2). Disease-free criteria were no visible tissue in the neck or body, a protein-bound radioactive iodine (PBI131) of less than 0.005 per cent per liter at seven days and/or whole body retention of less than 3 per cent at seven days. Of the patients receiving less than 30 mCi (group 1), 56 per cent with papillary carcinoma, 67 per cent with follicular carcinoma and 56 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Of the patients receiving the higher dose of I131 (group 2), 67 per cent with papillary carcinoma, 50 per cent with follicular carcinoma and 67 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Disease-free mean follow-up time was 5.17 years (group 1) and 5.82 years (group 2). There was no statistical difference in these mean follow-up times, nor was there a statistical difference in the net (total minus initial) dose of I131 needed to render the patient disease-free. These data demonstrate that low dose I131 therapy is as effective as the larger more routine doses of I131 given in this disease.

Adenocarcinoma↗
PubMed1976

Hypothyroidism after x irradiation to the neck: three case reports and a brief review of the literature.

Three patients who developed hypothyroidism after x irradiation to the neck are presented. The first two cases demonstrate that patients can develop clinical and chemical hypothyroidism after a very short interval following radiotherapy. Hypothyroidism developed in the first patient in the absence of surgical manipulation of the neck, or a large iodine load 4 months after receiving 6800 rad of x-ray therapy to his neck for carcinoma of the larynx. The second patient developed hypothyroidism approximately 6 months after his radiotherapy for carcinoma of the esophagus. Both of these patients demonstrated high titers of serum antithyroid antibodies. A third patient with Hodgkin's disease did not manifest clinical symptoms and signs of hypothyroidism until 6 years after radiation therapy. These cases demonstrate the variability of onset of hypothyroidism after radiotherapy and emphasize the need for careful evaluation of thyroid function before and after neck irradiation.

Adult↗
PubMed1975

Hemiagenesis of the thyroid gland.

Three patients with hemiagenesis of the typhoid gland are described. One was clinically euthyroid, whereas the other two were more unusual in that one had coincident Graves' disease with thyrotoxicosis, and one had primary myxodema. In all three cases diagnosis of hemiagenesis was established by the administration of thyroid-stimulating hormone (TSH). The literature on hemiagenetic thyroid glands with and without associated thyroid disease is reviewed. Although the anomaly is uncommon, awareness and recogniton of its existence may clarify an otherwise puzzling clinical thyroid evaluation, and thus possible avert an unnecessary surgical procedure.

Adult↗
PubMed1975

Failure of oral water loading and intravenous hypotonic saline to suppress plasma prolactin in man.

To test the effect of acute changes in plasma osmolality on plasma prolactin concentrations, the hormone was measured before and during oral water loading, hypotonic saline infusion, and hypertonic saline infusion in normal subjects. In 10 normal men there was a small but statistically significant rise in mean prolactin, from 7.6 to 12.3 ng/ml, occurring within half an hour after the ingestion of a water load of 20 ml/kg. A small but statistically insignificant rise in mean plasma prolactin was observed in 11 normal women, although there was a significant negative correlation between plasma prolactin and plasma osmolality in these subjects. No effect of the intravenous infusion of either hypotonic saline (0.45%) or hypertonic saline (5%) on mean plasma prolactin was noted in 5 normal men. These studies do not confirm a previously reported suppression of prolactin concentrations by oral water loading of hypotonic saline infusions in normal subjects. While the data suggest a negative correlation between plasma osmolality and plasma prolactin, at least after water loading, they do not support a physiological role for prolactin in the short-term regulation of plasma osmolality in humans.

Administration, Oral↗
PubMed1975

Effect of an oral water load on serum TSH in normal subjects, and on TSH and prolactin response to thyrotropin-releasing hormone (TRH) in patients with primary hypothyroidism.

Reports of suppression of plasma prolactin (PRL) in humans by water loading led us to examine the effect of a 20 cc/kg water load on serum TSH in 21 normal volunteers. In addition, the effects of a water load on basal and TRH-stimulated TSH and PRL levels were evaluated in seven patients with primary hypothyroidism. The water load had no effect on pasal serum TSH levels in either normal or hypothyroid subjects, and did not alter the TSH response to TRH in hypothyroid subjects. Basal or TRH-stimulated plasma PRL was also unaffected by water loading in the hypothyrpid subjects. These data suggest that a water load of 20 cc/kg does not significantly affect TSH release by the anterior pituitary, and also provide further evidence that water loading does not consistently suppress PRL secretion.

Administration, Oral↗