Biomedical subjects

A M Lawrence

Publications and source records attributed to A M Lawrence.

At least 55 records · Page 3Linked to original sources

PubMed1989

In vitro effect of ethanol exposure on basal and GnRH-stimulated LH secretion from pituitary cells.

The question of whether ethanol's (ETOH's) known suppressive effect on serum luteinizing hormone (LH) could be mediated directly at the anterior pituitary level was addressed by examining the effects of ETOH in vitro on release of LH from cultured male rat pituitary cells. The impact of added ethanol concentrations ranging from 50 to 400 mg% on LH release was examined in the basal state and after stimulation by gonadotropin-releasing hormone (GnRH) at a dose of 5 x 10(-10) M. While ETOH did not significantly suppress basal LH release, secretion stimulated with GnRH was noted to be attenuated with higher doses of ETOH (greater than or equal to 100 mg%) compared to stimulated control cells. It is concluded that ETOH exposure in vitro alters stimulated LH secretion by acting directly on pituitary gonadotropes.

Animals↗

PubMed1989

Anatomical and functional effects of estrogen-induced prolactinomas on the rat hypothalamus.

Although estrogen-induced prolactinomas have been widely studied, little attention has been accorded to local pressure effects of the tumor on the hypothalamus and portal vasculature. To portray the magnitude of this phenomenon, four groups of 12-13-week-old female Fisher 344 rats were studied. Group 1 was an intact control receiving a subcutaneously (SC) placed placebo pellet; group 2 was an ovariectomized control with a SC placed placebo pellet; group 3 was ovariectomized with a 10 mg SC placed diethylstilbestrol (DES) pellet; and group 4 was ovariectomized receiving both 10 mg DES and 10 mg SC placed bromocriptine pellets. Blood samples were obtained at 4 weeks, and the animals were sacrificed at 8 weeks after pellet implantation at which time blood, pituitary and hypothalami were obtained. At 4 weeks serum prolactin levels were similarly and significantly elevated above the control groups in both the DES and DES/bromocriptine groups. By 8 weeks, however, serum prolactin level(s) in the DES-treated animals had tripled from the 4-week value, while levels in the DES/bromocriptine-treated animals were unchanged from the 4-week values. This finding matched the observation that the DES-treated animals had pituitaries 2.5-fold heavier than the DES/bromocriptine animals. The gross and histologic structure of the hypothalami and portal vessels were markedly disrupted in DES-treated rats and much less so in the DES/bromocriptine-treated group. These findings lead us to speculate that the pathogenesis of DES-induced prolactinomas proceeds in two phases: First, there is an early chemical induction phase in which estrogen directly and indirectly stimulates lactotrope proliferation and, second, a mechanical disinhibition phase, where tumor-induced destruction of the hypothalamus and portal vessels unleashes the pituitary from the dopaminergic restraining effects of the hypothalamus.

Animals↗

PubMed1989

Adult nesidioblastosis. An unusual cause of fasting hypoglycemia.

Laidlaw coined the term nesidioblastosis in 1938 to characterize the neodifferentiation of the islet cells of Langerhans from pancreatic duct epithelium. It is well recognized in the pediatric population as a frequent cause of persistent neonatal hypoglycemia. However, its occurrence in adults is presumed to be rare and, therefore, it is not appreciated as a cause of hyperinsulinism. Three women, aged 29, 42, and 63, with adult onset hyperinsulinism secondary to nesidioblastosis are reported. All three patients required near-total pancreatectomy. The preoperative findings were consistent with hyperinsulinemic hypoglycemia as with insulinomas. Results of pancreatic imaging studies were normal in two patients and one patient had a pancreatic examination by computerized tomography and magnetic resonance imaging, with false-positive results. Two of the three patients had previously undergone a 50 per cent distal pancreatectomy in which the resected specimens were interpreted as normal in one patient and consistent with nesidioblastosis in the second. Both patients subsequently developed recurrent symptomatic hyperinsulinemic hypoglycemia that persisted despite dosage adjustments in diazoxide therapy. The oldest patient underwent a 95 per cent pancreatectomy at the initial surgical exploration because an insulinoma could not be identified. The other patients underwent a completion 95 per cent pancreatectomy. In both, histochemical examination of each specimen disclosed nesidioblastosis, characterized by clusters of islet cells interspersed throughout the exocrine tissue.

Adult↗

PubMed1989

Improving postoperative recurrence rates for carcinoma of the thyroid gland.

Differentiated carcinoma of the thyroid gland is regarded as an indolent disease. However, this notion is dispelled when the population is stratified according to age, gross and microscopic tumoral characteristics and according to the occurrence of local and distant metastases in the early postoperative period. The adverse effect of local and distant recurrences on survival time has been emphasized in multiple series from the United States and Europe. However, the critical question that has yet to be answered is whether or not inadequately treated differentiated carcinomas of the thyroid gland seemingly cured in younger patients will recur as aggressive, malignant tumors when the same patients reach the graying golden years. A provisional answer to this question may indeed be found in the incidence of early postoperative nodal and distant recurrence rates. Some authors have concluded that the extent of operative treatment does not have a major influence on the course of differentiated carcinoma of the thyroid gland. This conclusion prompted the present follow-up study of 250 patients with differentiated carcinoma of the thyroid gland to examine the clinical course and results of therapy. We report a cumulative mortality rate of 2.4 per cent and a recurrence rate of 1.6 per cent, consisting of a 1.2 per cent incidence of cervical nodal recurrence and a distant recurrence rate of 0.4 per cent (one patient), after a median follow-up period of seven years and a mean of six years. Since there were no differences in treatment and outcome in 191 patients we studied who had papillary and 59 who had follicular carcinoma, they were analyzed as a single group for this report. Total thyroidectomy was the minimal treatment of all operable patients. In addition, 21.0 per cent required a modified dissection of the neck and 8.4 per cent of the patients had postoperative radioactive iodine administered to ablate either remnants of normal tissue or previously undetected metastases to cervical nodes or lungs. Potential factors contributing to improved local and distant recurrence rates included early detection of disease, especially in children who had irradiation and who were recalled and screened (34 per cent in this series); the use of needle aspiration cytologic study, leading to earlier diagnosis and treatment; total thyroidectomy, and the effective use of radioactive iodine administered as a single large dose within the first six months after thyroidectomy.

Adenocarcinoma↗

PubMed1988

New modalities in diabetes treatment.

It is certainly acknowledged, albeit rather recently, that adequate control of hyperglycemia in type II diabetic patients is generally poor at best. A heightened realization of this fact and hopes that control of hyperglycemia may prevent complications or limit their severity have spawned newer approaches toward achieving improved glycemic control through changes in standard programmatic care with diet, exercise, oral agents or insulin therapy, and management of hypertension and obesity. Insulin taken at bedtime to control nocturnal hepatic glucose output, multiple doses of regular insulin coupled with frequent blood sugar measurements, and combined insulin and oral agents are approaches currently under trial in several centers. Interest in combination therapy stems in part from residual concern that hyperinsulinemia may contribute to the development of atherosclerosis, and to evidence that the sulfonylureas, especially the second-generation drugs, improve sensitivity to the glycolytic effects of insulin, thereby reducing insulin resistance. More than a dozen serious studies of combined therapy have been reported since the early 1980s. This study is unique, however, in several respects since non-obese, type II, insulin-requiring diabetic persons were chosen for study and were hospitalized prior to initiating the actual investigation in order to secure optimal diabetic control and thereby ensure greater sensitivity of the beta cell. Twenty type II diabetic patients were studied in a double-blinded, placebo-controlled trial with insulin and glyburide. All were treated with intermediate-acting insulin and adjustments were made as necessary to achieve optimal control, after which the patients were randomly assigned to either an insulin-and-glyburide program or to insulin-plus-placebo treatment. Thereafter, patients were followed in an outpatient setting for four months, after which time they were rehospitalized for final assessment. Standard chemistries, urinary glucose, glycosylated hemoglobins, and urinary C-peptide levels were measured. The fasting serum glucose level remained normal in the glyburide/insulin-treated group, whereas these were significantly higher in the placebo-plus-insulin group at four and at eight weeks. Glycosylated hemoglobin levels rose progressively in the placebo- and insulin-treated group and by 16 weeks were significantly higher than measurements from the insulin- and glyburide-treated group of patients (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗

PubMed1988

Resection of parathyroid tumor in the aorticopulmonary window without prior neck exploration.

Of 522 patients with hyperparathyroidism operated on from 1973 to 1987 at our institution, there were seven (1.3%), each with an ectopic, hyperfunctioning mediastinal parathyroid adenoma, who required median sternotomy. In three of these seven patients, the tumor was located in the aorticopulmonary window. A 61-year-old woman with primary hyperparathyroidism had a preoperative thallium-technetium subtraction scan that showed thallium uptake at the base of the heart without any uptake in the neck. After further workup and without prior neck exploration, a parathyroid adenoma was found in the aorticopulmonary window through a median sternotomy. Six months later, serum calcium, phosphorus, and parathyroid hormone values remain normal. Two other cases of parathyroid adenoma in the aorticopulmonary window are presented. Of these two patients, the thallium scan was a key element in the immediate mediastinal exploration of one, who was transferred from another hospital comatose and intubated, in acute hypercalcemic crisis. Since mediastinal parathyroid tumors that necessitate median sternotomy occur in less than 2% of patients with primary hyperparathyroidism, we do not advocate routine preoperative localization studies before an initial cervical operation; localization, however, may be justified in selected cases, such as in critically ill patients or in instances of acute hyperparathyroidism, when the first operation needs to be curative.

Adenoma↗

PubMed1988

Nodular thyroid disease in children and adolescents: a high incidence of carcinoma.

Over a period of 32 years from 1954 to 1986, 65 patients under the age of 21 years, 52 girls and 13 boys, were operated for nodular thyroids: the overall incidence of carcinoma was 37 per cent. It was 46 per cent in those patients presenting with a solitary nodule. Among the 24 patients with a malignancy, the carcinoma was of the papillary variety in 63 per cent, follicular in 25 per cent and medullary in 12 per cent. Two thirds of the patients had metastatic disease at the time of presentation. All patients with thyroid carcinoma were treated with total thyroidectomy. Other measures included neck dissection and radioactive iodine. When the eight patients with a history of head and neck irradiation and the three patients with medullary carcinoma were excluded, the incidence of carcinoma was 28 per cent. In summary, in spite of the decline in radiation associated cases, the incidence of carcinoma in nodular thyroid disease in the population under 21 years, remains at the relatively high figure of 28 per cent.

Adenocarcinoma↗

PubMed1988

Carcinoma of the thyroid in patients with autonomous nodules.

Over a period of 25 years (1961-1986), 30 consecutive patients were operated upon for solitary "HOT" nodules. The autonomy of these nodules was substantiated by cytomel nonsuppressibility on 131I or 123I scanning, or TSH stimulated enhancement of the remaining suppressed thyroid tissue (n = 24); or as a solitary toxic hot nodule with suppression of the remaining thyroid tissue (n = 6). Seventeen of these patients were euthyroid and 13 were thyrotoxic and required preoperative preparation with antithyroid medication. Five patients had a history of head and neck irradiation. The population consisted of 24 women and six men. Their ages ranged from 14 to 68 years. The tumors ranged in size from 1.5 to 7 cm. The pathologic findings consisted of "colloid" adenoma in nine patients, follicular adenoma in 19 patients, and a follicular carcinoma in two patients, for an incidence of 6 per cent. It is of interest that neither of the patients with thyroid carcinoma were toxic or had a history of radiation exposure. These findings support the concept that the incidence of carcinoma in truly autonomous "HOT" thyroid nodules is not negligible.

Adenocarcinoma↗

PubMed1987

Extrahypothalamic brain prolactin: characterization and evidence for independence from pituitary prolactin.

Prompted by reports of immunohistochemical localization of a prolactin-like immunoreactivity (PLI) within the rat brain, a study was undertaken to define the immunologic and biologic characteristics of this material in extrahypothalamic regions of the rat brain. Ninety-seven percent recovery of rat prolactin standard, added to homogenates of brain parts, insured that neuronal tissue did not interfere with the radioimmunoassay for rat prolactin. PLI was consistently found in the cerebellum, thalamus, brainstem (pons-medulla), hippocampus, cerebral cortex and caudate. Examination of the elution profile of each of the extrahypothalamic brain parts from Sephadex G-75 columns showed that, although a small amount of brain PLI elutes in the vicinity of the anterior pituitary prolactin marker, the bulk of brain-based PLI migrates with the void volume and as late eluting, low molecular weight material. While increasing amounts of brain extracts progressively displaced more 125I-prolactin from antibody binding, the displacement curve was not parallel to that produced by the addition of increasing amounts of anterior pituitary prolactin standards of rat origin. Extracts of various brain parts from hypophysectomized animals, analyzed for biologic activity in the Nb2 lymphoma cell assay, revealed prolactin-like bioactivity, but the bioactivity/immunoreactivity ratio for some of the brain parts was significantly lower than that for pituitary prolactin. 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 extrahypothalamic brain parts, indicating that brain PLI is regulated independently of pituitary prolactin and of circulating serum prolactin levels.

Animals↗

PubMed1987

Subcellular distribution of hypothalamic prolactin-like immunoreactivity.

Prompted by interest in immunohistochemical reports of prolactin-like immunoreactivity (PLI) in the rat hypothalamus, we investigated and have reported that an immunoreactive and bioactive prolactin-like material can be extracted from the rat hypothalamus. In the present communication the subcellular distribution of this protein is reported. Using a sensitive and specific radioimmunoassay for rat prolactin and a standardized procedure for subcellular fractionation of neuronal tissue, we have found that 90% of hypothalamic PLI is particulate-bound with only 10% remaining in the S4 or cytosolic fraction. Almost 80% of the particulate-bound PLI is found in the P2 fraction containing myelin, synaptosomes and mitochondria. When P2 is further fractioned on a discontinuous sucrose density gradient, approximately 66% of the P2-associated PLI was found in subfractions rich in synaptosomes and poor in myelin and mitochondria. Such findings support the probability that hypothalamic PLI functions trans-synaptically as a neuromodulator in the brain.

Acetylcholinesterase↗

PubMed1987

Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma.

The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently.

Adenoma↗

PubMed1987

In vitro LH release from the hypothalamus-pars tuberalis; effects of gonadotropin-releasing hormone (GnRH), beta-endorphin and biogenic amines.

Immunoreactive and bioactive luteinizing hormone (LH) has been shown to be widely distributed in the rodent central nervous system (CNS), particularly in the hypothalamus. Subcellular localization of this LH in fractions rich in synaptosomes and in vitro release by potassium-induced depolarization suggests that this peptide may act in trans-synaptic neuromodulatory roles. Furthermore, a variety of experiments have proved that this brain-based LH is not of pituitary origin. In the in vitro studies reported here characterization of brain-based LH release, in response to gonadotropin-releasing hormone (GnRH), beta-endorphin, and biogenic amines, was examined. Adult male rats were sacrificed by decapitation, hypothalami removed, quartered, and incubated in Krebs Ringer's Bicarbonate (KRB). High potassium concentration and GnRH induced release of LH from these hypothalamic explants in short-term culture and serotonin significantly inhibited release of LH from these explants. In contrast, however, beta-endorphin, norepinephrine, dopamine, and acetylcholine, agents known to modulate pituitary LH release, had no effect on the release of LH from hypothalamic tissues in vitro. Furthermore, beta-endorphin did not alter potassium-induced release of LH from the hypothalamus. Whereas there are some similarities between LH release from the pituitary and from the CNS, the differences reported here suggest that hypothalamic LH does not simply serve as a supplemental source for LH in the general circulation but more likely subserves an entirely different role(s) than its pituitary counterpart, presumably acting in a neuromodulatory fashion within the brain.

Animals↗

PubMed1987

Anaesthesia with alphaxalone plus alphadolone acetate decreases serum concentrations of LH in castrated rats.

Alphaxalone is considered the anaesthetic of choice in neuroendocrine reproductive studies in female rats, since it appears to have little, if any, effect on release of gonadotrophin-releasing hormone. There has been less study of the effects of this anaesthetic on the male reproductive neuroendocrine axis, however. Accordingly, the time-dependent effects of alphaxalone, as well as of urethane and ketamine, on the increased levels of LH in castrated rats were determined. Each anaesthetic was administered i.p. and each depressed LH levels significantly compared with those in castrated unanaesthetized rats killed by decapitation (controls). The effect of the anaesthetics was noted 15 min after administration and persisted at 30 and 60 min in animals anaesthetized with alphaxalone and urethane. Only in ketamine-anaesthetized animals did serum concentrations of LH finally rise to concentrations not significantly different from those in control rats. Thus alphaxalone, though useful in female neuroendocrine studies, is as profoundly disruptive as other anaesthetics on the male rat hypothalamic-pituitary reproductive unit.

Anesthetics↗

PubMed1987

Routine use of the thallium-technetium scan prior to parathyroidectomy.

The merit of the preoperative localization of parathyroid tumors with thallium-technetium subtraction imaging is a subject of current debate in the treatment of primary hyperparathyroidism. Eighty patients with hyperparathyroidism underwent preoperative subtraction scintigraphy with 201Tl Cl and 99mTcO4; scan results were correlated with the operative identification and histopathology of the resected parathyroid tissue. The true-positive, false-positive and false-negative rates of these scans were compared between patients with tumors in normal and ectopic anatomic locations and between patients undergoing an initial and reoperative neck exploration. The scan was clearly valuable in patients with one or more prior neck explorations. True-positive scans were obtained in seven (77%) of nine such patients. The scan was also valuable in patients who had ectopic tumors (six mediastinal, seven intrathyroid, and two in the carotid sheath). Twelve (80%) of these 15 ectopic tumors were correctly localized either prior to their first operation or before subsequent explorations. In contrast, only 33 (50%) of 65 patients had a true-positive scan prior to their first operation and when the tumor was not in an ectopic location. In summary, in this series, the thallium-technetium scan was correct in only 50 per cent of patients undergoing an initial operation. However, it was positive in 77 per cent of patients who had at least one prior neck exploration and in 80 per cent of patients with an ectopic parathyroid tumor. These results support the selective use of this valuable imaging and localization tool.

Adenoma↗

PubMed1987

Combined glyburide and insulin therapy in type II diabetes.

Present treatment of type II diabetes mellitus often fails to normalize post-prandial glucoses. A placebo-controlled, double-blinded design tested the effects of combined glyburide-insulin therapy over 4 months in 20 patients after achieving good control of fasting glucose with diet and intermediate insulin alone. Insulin requirements significantly decreased in both groups during the initial hospitalization when drug or placebo was added, presumably because of enforced dietary compliance. Thereafter, post-prandial glucoses worsened in the placebo group, as did hemoglobin A1c; neither of these parameters changed on the glyburide group by week 16, except for modest reduction of the 2h post-lunch glucose. Thus, while combined therapy provides little advantage beyond what can be accomplished with effective doses of intermediate insulin alone, it did reduce the need for this exogenous insulin.

Adult↗

PubMed1987

Improvement of vocal cord paresis after thyroidectomy.

Iatrogenic vocal cord paralysis is a well-publicized complication of thyroid and parathyroid operations. Less appreciated is the improvement of vocal cord function after resection of a thyroid or parathyroid tumor. Over the last 22 years, 14 patients presented with vocal cord paresis in the presence of thyroid or parathyroid tumors. Of these 14 patients, nine had complete resolution of paresis following resection of the thyroid or parathyroid tumors: three had a thyroid carcinoma impinging upon the nerve, three had large colloid goiters, two had a follicular adenoma and one had a parathyroid adenoma displacing the nerve. In five of the 14 patients the vocal cord paralysis persisted after operation. In three, the pathology accounted for the vocal cord paralysis and was not amenable to operative improvement: one patient had an unresectable anaplastic thyroid carcinoma, one patient had long-standing idiopathic unilateral vocal cord paralysis, and one patient had laryngeal adenoid cystic carcinoma with thyroid invasion. The fourth patient had an extensive thyroid hemangioma. The paralysis persisted after resection. The fifth patient had long-standing idiopathic vocal cord palsy. A preoperative vocal cord paresis in a patient with thyroid or parathyroid disease does not indicate permanent loss of recurrent nerve function, even in the presence of carcinoma. In this series, vocal cord function was restored in 9 of 10 patients with resectable thyroid or parathyroid tumors.

Adult↗

PubMed1987

The incidence of thyroid carcinoma in Hashimoto's thyroiditis.

The incidence of thyroid carcinoma in Hashimoto's thyroiditis has been a widely debated issue. Previous authors have reported on this topic by analyzing series of patients with Hashimoto's thyroiditis or patients with thyroid carcinoma, but not both of those populations in the same series. The population consists of a consecutive series of 800 patients operated on for thyroid nodules not associated with a radiation history. Among 161 patients with the diagnosis of thyroid carcinoma, 61 (38%) had coexistent Hashimoto's thyroiditis. In comparison, among 161 sex- and age-matched patients with colloid nodules in the same population, 18 (11%) had Hashimoto's thyroiditis. Furthermore, in the series as a whole, the incidence of Hashimoto's thyroiditis in 423 patients with colloid nodules was 10 per cent. From the perspective of the Hashimoto's thyroiditis population in the same series of 800 thyroidectomies, among 267 patients with Hashimoto's thyroiditis 61 (23%) had coexistent carcinoma. In comparison, among 267 age- and sex-matched patients with colloid nodules there were only ten coexistent carcinomas for an incidence of 4 per cent. The high incidence of carcinoma of the thyroid in Hashimoto's thyroiditis lends credence to the hypothesis that Hashimoto's thyroiditis is a predisposing factor in the development of thyroid carcinoma.

Adolescent↗

PubMed1986

The effect of alcohol on quantitative and qualitative changes in luteinizing hormone (LH) in the female rat.

In order to study the impact of short-term ethanol feeding on pituitary luteinizing hormone (LH) levels, LH release and hormone microheterogeneity, 28 female oophorectomized rats were fed either a diet containing 36% ethanol or an isocaloric diet without ethanol for 16 days. On the 14th day of the experiment, all rats were given 50 micrograms of estradiol subcutaneously to provide a uniform steroid milieu and to induce an LH surge, and sacrificed 48 hours later. Total levels of pituitary and serum immunoreactive LH were identical between the ethanol and control groups. However, when pituitary LH was analyzed by isoelectric focusing on agarose gel a distinct difference was found. Four distinct immunoreactive peaks at pI's 3.50-4.55, 5.20-6.50, 7.00-7.50, 8.15-9.30 were noted. Ethanol-treated animals exhibited an 8-fold increase in the acidic LH subspecies in the pI range 3.50-4.55 and similarly more LH was determined at pI 7.00-7.50 compared to controls (P less than 0.01). More LH was found at the basic pI's from control pituitaries, compared to LH from the ethanol-exposed animals (P less than 0.01). In summary, short-term ethanol feeding in the female rats does not cause quantitative changes in pituitary LH levels or in the estrogen-induced LH surge. However, qualitative changes are present in isoelectric focusing patterns. A significant shift to the more acidic species of the pituitary LH isohormone was noted for ethanol-fed animals as compared to controls. These qualitative changes in the LH molecule, seen before quantitative changes could be appreciated, may help to explain why excessive exposure to alcohol results in reproductive impairments both in rats and in humans.

Animals↗