Biomedical subjects

A M Lawrence

Publications and source records attributed to A M Lawrence.

At least 73 records · Page 4Linked to original sources

PubMed1986

Hypothalamic prolactin: characterization by radioimmunoassay and bioassay and response to hypophysectomy and restraint stress.

Prompted by immunohistochemical reports of prolactin-like immunoreactivity in cell bodies within the rat hypothalamus, a study was undertaken to quantitate the immunologic and biologic activity of this material. Hypothalamic concentrations of prolactin-like immunoreactivity averaged 402 +/- 23 pg/mg of protein (n = 30). 97% recovery of rat prolactin standards added to homogenates of hypothalamus insured that neuronal tissue, as prepared for these studies, did not interfere with the radioimmunoassay of rat prolactin. Examination of the elution profile from Sephadex G-75 columns of the prolactin-like immunoreactivity in hypothalamic extracts showed that the majority of hypothalamic prolactin-like substance was of a larger molecular size than pituitary prolactin. While increasing amounts of brain extract progressively displaced more I125 prolactin from antibody-binding sites, the displacement curve produced by adding hypothalamic extract was not parallel to that produced by the addition of increasing amounts of anterior pituitary prolactin standards of rat origin. Hypothalamic extracts from hypophysectomized animals, analyzed for biologic activity in the Nb2 lymphoma cell assay, revealed prolactin-like bioactivity, but the bioactivity/immunoactivity (B/I) ratios for hypothalamic extracts were significantly lower than the B/I ratios for pituitary prolactin (0.71 +/- 0.04 for pituitary, vs. 0.19 +/- 0.06 in the hypothalamus; p less than 0.001). Hypophysectomy, which led to the expected fall in serum prolactin to undetectable levels, and restraint stress, which resulted in a statistically significant 4-fold rise in serum prolactin, caused no change in prolactin concentrations in the hypothalamus, indicating that brain prolactin-like substance is regulated independently of pituitary prolactin and circulating serum prolactin levels.

Animals↗

PubMed1986

Impact of endocrine manipulations on brain-based rat growth hormone.

Our laboratory has previously described the widespread distribution of an immunoreactive and bioactive rat growth hormone (rGH)-like protein in rat brain. It has also been demonstrated that regulation of pituitary rGH secretion is at least partly mediated by a short-loop negative feedback system. In such a system, increased levels of rGH, acting at a suprapituitary locus, would decrease pituitary GH secretion. Thus, the present study has dealt with attempts to further investigate the hypothesis that one function of brain-based rGH might be as a mediator of the short-loop negative feedback system controlling pituitary rGH release. If brain-based rGH were to function as a mediator of such a system, then in situations where serum rGH levels are decreased, brain rGH concentrations should increase, indicating activation of a negative feedback loop. In the present communication we report that significantly decreased serum GH levels in oophorectomized and in thyroidectomized rats were coupled with a significant increase in rGH concentrations in the hypothalamus and in the amygdala. By contrast, adrenalectomy, which was not associated with any changes in levels of GH in serum caused no perturbations in levels of rGH in the brain. These discordant changes in serum and brain-based rGH are findings compatible with the hypothesis that one function of brain-based rGH is as a mediator of the short-loop negative feedback system regulating the release of pituitary GH.

Adrenal Cortex Hormones↗

PubMed1986

Parathyroid autotransplantation in forty-four patients with primary hyperparathyroidism: the role of thallium scanning.

Forty-four patients with primary hyperparathyroidism were followed for 18 to 126 months after subtotal or total parathyroidectomy and parathyroid autotransplantation. Indications for autotransplantation included the devascularization of parathyroid glands during concomitant thyroid lobectomy or total thyroidectomy and the excision of the only remaining parathyroid tissue in patients with persistent hyperparathyroidism after previous unsuccessful parathyroidectomies. Before implantation, all parathyroid tissue was histologically evaluated by frozen-section light microscopy with hematoxylin and eosin stain. Fifteen patients had histologically normal implants; to date none of these patients have developed recurrent hyperparathyroidism. Twenty-nine patients had either adenomatous or hyperplastic parathyroid tissue used for implants; two of these patients developed graft-dependent recurrent hyperparathyroidism 4 and 7 years later. In both patients the grafts were preoperatively localized by thallium scanning and their resection restored eucalcemia. One hundred thirty-one patients from 11 series in the current literature had a cumulative incidence of 17.5% for presumed graft-dependent recurrence and a 9.2% incidence of graft excision followed by eucalcemia. In comparison, in the present series the incidence of graft-dependent recurrent hyperparathyroidism in patients with either adenomatous or hyperplastic implants stands at 6.9%. In contrast, in 15 patients with normal parathyroid tissue implants, the incidence was zero.

Adenoma↗

PubMed1986

The incidence of thyroid carcinoma in solitary cold nodules and in multinodular goiters.

The incidence of carcinoma in patients with multinodular goiters has been reported to be considerably lower than in patients with a single cold nodule. However, the definition of a "single cold nodule" is highly subjective and has therefore been modified by qualifiers such as "clinically solitary" or "clinically dominant." In this retrospective study, we find no significant difference in the incidence of carcinoma in patients with multinodular goiters compared with patients with a solitary cold nodule confirmed by operation and histopathologic examination. In a consecutive series of thyroidectomies over a 22-year period, all patients with factors predisposing them to neoplasia, such as a history of radiation exposure and thyroiditis, were eliminated. Furthermore, all patients thought to have additional nodules documented by gross examination at operation or subsequently by histopathologic examination were also eliminated. The remaining 69 patients with clinically evident multinodular goiters were compared with the remaining 96 patients with a solitary cold nodule. The incidence of carcinoma in the 96 patients with a solitary cold nodule was 17%. In the 69 patients with clinically evident multinodular goiters, the incidence of carcinoma was 13%. The difference is not significant. It is of interest that male patients with multinodular goiters had the highest incidence of carcinoma at 29%, whereas, males with a solitary cold nodule had an incidence of only 13%. In conclusion, once known factors that predispose patients to neoplasia are eliminated, there does not seem to be a significant difference in the incidence of thyroid carcinoma between patients with operatively and histopathologically proved solitary cold nodules and those with multinodular goiters.

Carcinoma↗

PubMed1985

Brain thyroid-stimulating hormone: effects of endocrine manipulations.

We have previously described the presence of and the immunologic, chromatographic and biologic characteristics of a thyroid-stimulating hormone (TSH)-like peptide, widely distributed in the rat and monkey central nervous system (CNS). In order to test the hypothesis that brain TSH, specifically hypothalamic TSH, participates in the turnover of pituitary TSH, we have assessed the effect on hypothalamic TSH of two endocrine manipulations, castration and adrenalectomy, known to significantly decrease pituitary and/or serum TSH in the rat. Orchidectomy led to a significant decline of pituitary and serum TSH while a significant increase in hypothalamic TSH concentrations was seen. Adrenalectomy also led to decreased pituitary concentration of TSH linked with a significant increase in hypothalamic TSH levels. Neither manipulation led to changes in TSH in the extrahypothalamic brain. The inverse relationship wherein serum and/or pituitary TSH decrease is accompanied by an increase in hypothalamic TSH is compatible with a role for hypothalamic TSH in pituitary TSH regulation. The possible significance of these findings in terms of TSH triiodothyronine interactions in the CNS is discussed.

Adrenal Cortex Hormones↗

PubMed1985

The impact of aging on luteinizing hormone (LH) and thyroid-stimulating hormone (TSH) in the rat brain.

Immunoreactive and bioactive luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and growth hormone (GH) have been described by this and other laboratories to be present in discrete areas of the rodent and primate brain. In the present studies, LH and TSH concentrations in serum, pituitary, hypothalamus, brainstem, cerebellum, cerebral cortex and hippocampus were measured in male Sprague-Dawley rats at 2.5 months of age, when 11-12 months old and at 24 months of age. There was a significant decrease in hypothalamic TSH concentrations in the 11-12-month-old rats compared to younger animals (672 +/- 127 ng/mg vs 86 +/- 17 ng/mg, P less than 0.001). This was unaccompanied by any changes in TSH levels in serum, anterior pituitary, or in any of the extrahypothalamic brain areas that were examined. In contrast, there was a significant 50% drop in LH concentrations in the anterior pituitary gland of 11-12-month-old animals when compared with young controls (72 +/- 58 micrograms/mg vs 137.2 +/- 27 micrograms/mg, P less than 0.05) without any noted change in serum or brain LH concentrations. Similar decreases in LH concentration were also seen in the anterior pituitary glands of two-year-old animals. These discordant profiles between pituitary and brain LH and TSH provide additional circumstantial evidence that these brain peptides do not represent contaminants from the anterior pituitary. Further, these significant changes in TSH and LH concentrations that develop with aging may implicate these particular peptides in the development of certain features of senescence.

Aging↗

PubMed1985

Management of type II diabetes mellitus. Achieving optimum metabolic control.

Exciting information is rapidly accruing about diabetes and suggests that maintenance of good metabolic control may prevent onset or delay progression of diabetic complications. Patients, as well as their families and health care providers, should be encouraged by the knowledge that tools are available for successful management of type II diabetes. Treatment consists of a diet-exercise-sulfonylurea regimen and, in a substantial number of patients, administration of insulin. Proper assessment of these modalities is essential if optimum metabolic control is to be achieved.

Adult↗

PubMed1985

Total thyroidectomy in irradiated patients. A twenty-year experience in 206 patients.

During a period of 20 years (1965-1985), 206 consecutive patients were operated on for radiation-associated nodular thyroids. The ages ranged between 8 and 76 years (mean 38.7). there were 136 women and 70 men. The average duration between radiation exposure and operation was 27 years. The operations performed were total thyroidectomy (192) or, in patients who had undergone a previous lobectomy in another institution, another lobectomy (14). In addition, 25 patients required a neck dissection for nodal metastases and 27 underwent simultaneous subtotal parathyroidectomy for coexistent hyperparathyroidism. The pathologic findings were: 87 (42.2%) carcinoma (73 papillary, 13 follicular, 1 undifferentiated); 92 (44.7%) follicular adenomas; and 27 (13.1%) thyroiditis. To date, with an average follow-up of 6 years (0.5-31 years), only two patients have expired from recurrent disease. A third died of unrelated cause. A comparison of the first 100 patients (12 years) with the last 106 patients (8 years) demonstrated that the incidence of carcinoma has dropped from 48 to 37%, the incidence of lymph node metastases has decreased from 35 to 26%, and the incidence of bilaterality has fallen from 75 to 54%. On the basis of this series, it was concluded that total thyroidectomy is still indicated for radiation-associated nodular thyroids. However, if the trend of decreasing incidence, bilaterality, and metastatic disease persists, this approach may have to be reevaluated in the near future.

Acne Vulgaris↗

PubMed1985

Subcellular localization of hypothalamic luteinizing hormone.

Ultracentrifugation and sucrose gradient separation techniques have been applied to study of the subcellular distribution of hypothalamic luteinizing hormone (LH). Subcellular particle-bound LH accounted for 42% of the total LH while cytoplasm contained 58% of the total immunoassayable LH in these extracts. 70% of particle-bound LH was present in the P2 fraction and most of the particle-associated LH was found in subfractions of P2 rich in synaptosomes but poor in myelin and mitochondria. While actual amounts of LH in the P3 and P4, the microsomal fractions, were relatively small, the concentration of LH, expressed as nanograms per milligram of protein was quite high. Both content and concentration of LH in the nuclear pellet, P1, were substantially lower. These findings provide further framework for speculation on the role of brain-based LH.

Animals↗

PubMed1985

Hypothalamic luteinizing hormone increases dramatically following intracerebroventricular injection of colchicine.

We have previously described the presence and wide distribution of a luteinizing hormone (LH)-like peptide, widely distributed in the rat central nervous system, with highest levels in the hypothalamus. We have found that intracerebroventricular injection of 100 micrograms colchicine causes a significant rise in hypothalamic LH, from 549 +/- 170 pg/mg protein (n = 12) in controls to 1,679 +/- 279 pg/mg protein (n = 13) in treated animals, p less than 0.01. There was no associated change in levels of LH in the pituitary. Since colchicine stops axoplasmic flow, these findings of colchicine-induced increase in hypothalamic LH indicate that at least a portion of hypothalamic LH is present in long-axoned neuronal elements with cell bodies within the hypothalamus and axons extending to the extrahypothalamic brain. Thus, hypothalamic LH does not solely represent measurement of LH in cells of the contignous pars tuberalis.

Animals↗

PubMed1985

Thyroid carcinoma in Graves' disease.

The prevailing hypothesis of thyroid carcinogenesis is that thyroid-stimulating hormone (TSH) is a prime factor in the growth and possibly the genesis of thyroid carcinoma. On the other hand, Graves' disease is a hyperthyroid state caused presumably by human thyroid-stimulating immunoglobulin (HTSI), not TSH. However, the literature does contain scattered reports of an association between Graves' disease and thyroid carcinoma. With this background, we retrospectively reviewed our series of 117 consecutive patients operated on for Graves' disease from 1961 through 1984. The series contains 23 male and 94 female patients, with a mean age of 26.3 years at operation (median 26 years; range 8 to 58 years). Of these patients, six (two males and four females) were found to have carcinoma, four papillary and two follicular, for an incidence of 5.1%. Four of the 117 patients had a history of head and neck irradiation; two (50%) subsequently developed carcinoma. For the six patients with carcinoma, mean follow-up has been 8.1 years (median 8 years; range 1 to 14 years). To date there have been no recurrences of carcinoma, and all six are alive and well. Thus our series shows a carcinoma rate of 5.1% in patients with Graves' disease, which is markedly higher than the 0.1% to 0.2% incidence in random autopsy series of all patients. This raises the question of a possible carcinogenic role for HTSI, similar to that hypothesized for TSH, in patients with presumably suppressed TSH.

Adenocarcinoma↗

PubMed1985

Localization of ectopic parathyroid adenomas by the technetium-thallium subtraction scan.

Among numerous methods utilized for preoperative localization of hyperfunctioning ectopic parathyroid tissue, the technetium-thallium scan appears to be a major advance. Eight patients are presented where this method located ectopic parathyroid tissue in the neck, in the mediastinum, within the pericardium, and within the thyroid gland. To date, these findings have been confirmed operatively in five of the eight patients. On the basis of our limited experience, the authors believe that this is a valuable method in the preoperative localization of ectopic parathyroid tissue, especially in patients with persistent or recurrent hyperparathyroidism following a thorough neck exploration.

Adenoma↗

PubMed1985

The incidence of thyroid carcinoma in patients with Hashimoto's thyroiditis and solitary cold nodules.

The reported incidence of thyroid carcinoma in Hashimoto's thyroiditis varies widely. For this reason the specific subpopulation of patients with Hashimoto's thyroiditis and a solitary cold nodule was analyzed. Between 1972 and 1984 we operated on 146 consecutive patients with solitary cold nodules and Hashimoto's thyroiditis. There were 47 carcinomas, for an incidence of 32%. The mean age of the 146 patients was 43 1/2 years (median 44 years), with 126 females and 20 males. There was a history of prior head and neck radiation exposure in 54 patients, with a 33% incidence of thyroid carcinoma. The 92 patients without a history of radiation exposure had a 31.5% incidence of carcinoma. The frequency of multicentricity (bilateralism) was 33% in the group that underwent radiation and 24% in the group that did not. To date, with a mean follow-up of 4.7 years, there have been no deaths and no evidence of recurrence. In conclusion, we report a 32% incidence of thyroid carcinoma in patients with Hashimoto's thyroiditis and a solitary cold nodule, with no apparent difference between the patients with or without a history of radiation exposure, although there was a higher incidence of bilateralism (33% versus 24%) in the carcinomas of the patients with a history of head and neck irradiation. We suggest that the operative management of these patients is total thyroidectomy for those with a history of head and neck radiation and thyroid lobectomy for patients with no history of radiation, followed by contralateral lobectomy if a carcinoma is demonstrated.

Adenocarcinoma↗

PubMed1985

Parathyroid carcinoma. A report of five cases.

Parathyroid carcinoma, although rare, represents 0.5-4.0 per cent of the cases of hyperparathyroidism. The authors have encountered five cases of parathyroid carcinoma in their experience treating 445 patients with primary hyperparathyroidism (1.1%) since 1965. All five patients were women, ranging in age fro 29 to 60 years, and had marked hypercalcemia at the time of presentation, with values up to 26 mg/dl in one case. All the tumors were locally adherent to surrounding structures at the time of parathyroidectomy. Pathologically they were characteristic with a dense sclerotic reaction and fibrous bands criss-crossing islands of parathyroid cells. Three patients with local as well as distant metastases have died as a result of recurrent parathyroid carcinoma (follow-up: 2, 3, and 6 years). The remaining two patients became normocalcemic following resection, and have been asymptomatic for 1 and 7 years, respectively. The overall survival and clinical course, in our limited experience with five parathyroid carcinoma cases demonstrates that the morbidity and mortality in these patients is mainly due to local recurrence with the resultant metabolic disturbances, as has been previously noted in the literature.

Adult↗

PubMed1985

Hürthle cell tumors of the thyroid gland.

The recent controversy concerning the prognosis of Hürthle cell tumors instigated the review of our experience with 34 patients treated between 1972 and 1984. On the basis of strict histopathologic criteria, 14 patients with Hürthle cell hyperplasia, 10 with Hürthle cell adenoma, and 10 with Hürthle cell carcinoma were identified. There was a 40% incidence of bilateralism in Hürthle cell carcinoma, whereas we documented bilateral disease in only one of 10 patients with Hürthle cell adenoma. Lobectomies were performed in patients with tumors considered histopathologically benign and total thyroidectomy in patients with histologically malignant lesions as well as in most patients with a history of radiation exposure. Follow-up ranges from 4 months to 12 years (mean 3.1 years). To the present time there has been no evidence of recurrence and no deaths from Hürthle cell tumors. Consequently, in our experience, Hürthle cell tumors seem to behave in a rather benign manner. Therefore it seems that the appropriate treatment for Hürthle cell adenoma and nodular hyperplasia is a lobectomy. Total thyroidectomy is reserved for patients with Hürthle cell carcinoma primarily because of the high incidence of bilateralism.

Adenoma↗

PubMed1984

Release of immunoreactive luteinizing hormone (LH) from rat hypothalamus-pars tuberalis explants.

A luteinizing hormone (LH)-like molecule has been described in the rodent central nervous system and has been shown to have immunologic, chromatographic, and biologic activity similar to that of pituitary LH. In this communication we report that a depolarizing stimulus, high potassium concentration in the presence of calcium, causes in vitro release of LH from hypothalamic explants containing the pars tuberalis. Release from other brain areas containing LH was not seen nor was release of LH, in vitro, significantly provoked from dorsal segments of the hypothalamus, thus suggesting that most, if not all, of the releasable LH from intact hypothalamic explants may come from cells of the pars tuberalis.

Animals↗

PubMed1984

Disappearance of glucagonoma rash after surgical resection, but not during dietary normalization of serum amino acids.

Hypoaminoacidemia and skin rash are features of the glucagonoma syndrome. A glucagonoma patient with earlier insulin treated, noninsulin-dependent diabetes, and functional liver metastases, 3 yr postresection of pancreatic tumor, was treated with a high protein diet for 2 wk, then switched to a high carbohydrate diet for 3 wk followed by 3 wk on high protein diet, which continued for 3 months with additional carbohydrate. While on the high protein diet urine nitrogen indicated frank retention and total plasma amino acid levels normalized each time. Plasma amino acid decreased again after 1 wk on the high carbohydrate diet. Skin rash varied irrespective of amino acid levels, but cleared 4 days after resection of metastases. However, total amino acid did not reach normal levels on a conventional diet 3 wk postsurgery, but were normal 6 wk later. A high protein diet can normalize plasma amino acids and allow nitrogen retention in glucagonoma, apparently overriding the gluconeogenic drive of the high circulating glucagon levels. The skin rash may not be only attributed to hypoaminoacidemia.

Adenoma, Islet Cell↗

PubMed1984

Chronic propranolol administration impairs glucagon release during insulin-induced hypoglycemia in normal man.

Failure of a plasma glucagon rise in response to insulin-induced hypoglycemia was demonstrated in normal subjects taking therapeutic doses of the nonselective beta-adrenergic blocker, propranolol, for 7 days before testing. This is the first study to examine glucose homeostasis in normal subjects exposed to chronic propranolol therapy and helps to explain the development of spontaneous hypoglycemia in patients, either diabetic or nondiabetic, during beta-adrenergic receptor blockade. Previous studies of the acute parenteral effects of propranolol administration failed to show any significant effect on glucagon secretory dynamics in response to insulin-induced hypoglycemia. In the present study, however, chronic oral administration of propranolol resulted in severe impairment of the expected glucagon rise in response to hypoglycemia and was associated with severe hypoglycemia in one normal subject.

Adult↗