PubMed Health⌕ Search

Biomedical subjects

A M Lawrence

Publications and source records attributed to A M Lawrence.

At least 19 recordsLinked to original sources
PubMed1992

In vivo studies of ethanol on prolactin and luteinizing hormone in rats and mice.

The interaction of ethanol (EtOH), prolactin (Prl) and luteinizing hormone (LH) was examined in two studies. In the first study, adult male C57B1/6J mice were given a single intraperitoneal injection of either vehicle or Prl at 5, 10 and 20 mg/kg and a significant dose-related suppression of ethanol consumption was found. This injection did not cause any differences in food intake or body weight. Additionally, a 5 mg/kg dose of Prl was also given to adult male Long Evans Hooded rats and, similarly, there was a significant suppression of ethanol consumption. In a second study, when rats were given a free choice between water and 5% EtOH, three subgroups were found regarding the amount of EtOH consumption: low, medium and high. After 2 weeks of free choice, hypothalamic, but not serum Prl and LH levels, were significantly increased in EtOH-imbibing groups compared to controls. These findings suggest important interactions between EtOH consumption and ambient levels of Prl and LH.

Alcohol Drinking↗
PubMed1992

The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA.

Previous work by our laboratory has described the presence and widespread distribution of a PRL-like immunoreactive protein in brain. The persistence of this PRL in brain after hypophysectomy provided substantial evidence that brain PRL represented the product of a synthetic pool separate from that of the anterior pituitary PRL. To pursue this concept of independent synthesis further, we sought to determine whether brain tissue expressed PRL mRNA. Although we were easily able to detect a single species of PRL mRNA in pituitary by Northern hybridization, we could not visualize message in hypothalamus or extrahypothalamic brain by this technique. Therefore, we performed the polymerase chain reaction on cDNAs from anterior pituitary, hypothalamus, discrete extrahypothalamic brain regions, and other tissues. Hypothalamus and extrahypothalamic brain parts, including the cerebellum, caudate, brain stem, amygdala, thalamus, cortex, and hippocampus, were all positive to varying degrees. Lung and liver were negative, and anterior pituitary was consistently positive. All positive tissues, including anterior pituitary, expressed two hybridization signals: the expected amplified product and another smaller one. The smaller amplified product is presumably the result of an alternatively spliced transcript that is missing part of the PRL gene. Hypophysectomized animals did not express PRL message in brain, but expression was restored in hypophysectomized animals treated with testosterone. Transcripts for Pit-1 (GHF-1), a transcription factor important in regulation of pituitary PRL, were not detected in hypothalamus or any of the extrahypothalamic brain parts. The finding of testosterone stimulation of brain PRL message and undetectable levels of Pit-1 (GHF-1) in hypothalamic and extrahypothalamic brain regions indicates that the transcriptional regulation of PRL in the brain is different from that in the anterior pituitary.

Animals↗
PubMed1992

Necessity and safety of completion thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: The diagnosis of thyroid carcinoma during the course of lobectomy for a dominant nodule occasionally cannot be rendered on the basis of frozen section. Once the diagnosis of carcinoma is made, the question of completion thyroidectomy arises. The decision to perform completion thyroidectomy and the timing, safety, and efficacy of this procedure are reviewed. METHODS: During the past 25 years (1965 to 1990), we operated on 351 consecutive patients with thyroid carcinoma. One hundred of these patients (84 women and 16 men) were initially treated by unilateral thyroid lobectomy for the previously stated reasons. Histopathologic examination of the permanent sections of the initial thyroid lobectomy specimen demonstrated papillary carcinoma in 70 patients and follicular carcinoma in 30 patients. Within a few months, a completion thyroidectomy was performed. RESULTS: The completion thyroidectomy specimen contained papillary carcinoma in 33 (47%) of the 70 patients with papillary carcinoma and 10 (33%) of the 30 patients with follicular carcinoma. Overall, 43 of these 100 patients harbored thyroid carcinoma in the contralateral lobe. Complications of completion thyroidectomy were transient recurrent nerve paresis in two patients and temporary hypoparathyroidism in three patients, requiring calcium and vitamin D therapy for a few months. CONCLUSIONS: Although the significance and treatment of papillary carcinoma are debated on the basis of size and grade of the primary lesion and age and sex of the patients, once the diagnosis is made in one lobe we believe that a completion thyroidectomy should be considered, not only for papillary carcinomas but also for follicular carcinomas because 47% (papillary) to 33% (follicular) of these patients will harbor the neoplasm in the contralateral lobe.

Carcinoma↗
PubMed1991

High phosphate diet-induced primary hyperparathyroidism: an animal model.

Primary hyperparathyroidism (PHPT) is increasing in incidence and detection, primarily because of the aging of our population and the widespread use of automated serum calcium determination. As a result, a substantial number of "early" cases or "biochemical" PHPT are being detected. The indications for parathyroidectomy in such early cases of PHPT are currently under debate, primarily because of economic issues. These factors underscore the importance of research into the basic mechanisms and natural history of PHPT. We investigated an animal model of diet-induced PHPT that retains two crucial aspects of PHPT: elevation of endogenously produced parathyroid hormone (PTH), accompanied by gross and microscopic changes in the native parathyroid glands. Female Long-Evans rats were divided into six groups of 15 each and fed a control diet (Ca/P of 1:2) or a high-phosphate diet (Ca/P of 1:7) for 1-, 2-, or 3-month intervals. Compared with the control animals, serum PTH levels were elevated at all three time intervals in the experimental group, whereas serum calcium levels were decreased at all time intervals. Serum creatine levels were also elevated at all time intervals, whereas serum phosphorus levels did not change. Parathyroid histopathologic studies demonstrated no change at 1 month, whereas nine of 15 experimental animals showed mild hyperplasia at 2 months and 13 of 14 showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2 and 3 months in the experimental groups. In conclusion, the high-phosphate diet successfully induced the earliest changes of PHPT: elevated PTH levels and parathyroid hyperplasia. However, because renal function was mildly compromised early on, some element of early secondary (renal) hyperparathyroidism may have supervened quickly. Because this model is simple, it may be useful to investigate this complex syndrome further, as well as its natural history and the complications it produces in other organs such as the kidneys.

Animals↗
PubMed1991

Anaplastic thyroid carcinoma: risk factors and outcome.

Anaplastic thyroid carcinoma, in contrast to well-differentiated thyroid carcinoma, has a dismal prognosis, and little progress has been made in improving survival for this disease. We reviewed our experience during a 23-year period to identify risk factors and possible methods to improve outcome. Between 1966 and 1989, 340 patients with thyroid carcinoma underwent operation. Of these, 17 (5%) were undergoing operative treatment of anaplastic or undifferentiated thyroid carcinoma. The female/male ratio was 3.5:1, and mean age at presentation was 63 years. The most common presenting symptoms included neck mass, voice change, or dysphagia. Unusual presentations included symptomatic bradycardia from compression of the vagus nerve and superior vena cava syndrome. Four patients had a history of well-differentiated thyroid carcinoma. Nine patients had been diagnosed or treated in the past for "goiter" or a neck mass, and four patients had concurrent differentiated thyroid carcinoma associated with the anaplastic tumor. Thus 13 (76%) of 17 patients had a previous thyroid disorder, benign or differentiated malignant, and eight (47%) of 17 patients had previous or concurrent differentiated thyroid carcinoma. At the time of presentation, six patients had unilateral true vocal cord paralysis. At operation, 14 patients had local extension of the tumor and four required tracheostomy. Only five of 12 patients showed response to postoperative radiation therapy. Overall median survival was 12 months, and 13 (76%) of 17 patients died. The two patients alive longer than 12 months had only small foci of anaplastic carcinoma in association with well-differentiated carcinoma. Anaplastic thyroid carcinoma is a locally and systemically aggressive disease, with long-term survival seen only in those with well-localized anaplastic tumor. The major risk factor in this series is a history of previous benign or malignant thyroid disease. Because of this, a more aggressive approach to thyroid masses may be warranted. Long-standing goiters or benign nodules should be followed carefully and considered for resection if they grow or do not respond to medical therapy, and total thyroidectomy for malignant disease may obviate the subsequent development of anaplastic carcinoma. This method of early diagnosis and resection of abnormal thyroid tissue seems to be the only method currently available to improve the nearly uniform fatality of this disease.

Adult↗
PubMed1991

Thyroid carcinoma and hyperparathyroidism after radiation therapy for adolescent acne vulgaris.

Thyroid and parathyroid disease after head and neck irradiation in infancy and childhood is well known. Patients irradiated for facial acne were older and received a comparatively lower dose of radiation. These mitigating factors suggest a decreased incidence of thyroid and parathyroid disease in these patients. Over the past 28 years (1961 through 1989), 347 consecutive patients were operated on for radiation-associated thyroid and/or parathyroid disease. One hundred and ten patients in this group were irradiated for treatment for adolescent facial acne vulgaris. The interval between radiation exposure and thyroidectomy ranged from 7 to 57 years (mean, 30 years). The overall incidence of thyroid carcinoma was 31% (34 of 110 patients). Regional metastases in 10 patients (29%) were treated with modified radical neck dissection. Hyperparathyroidism, detected in 31% (34 of 110 patients) of this population, was treated with sub-total parathyroidectomy in all cases. The association of thyroid carcinoma and hyperparathyroidism after adolescent radiation exposure for acne vulgaris appears to be more than coincidental. The incidence of thyroid and parathyroid disease may be independent of the timing and dosage of radiation treatment. These thyroid and parathyroid tumors may develop decades after the initial radiation exposure.

Acne Vulgaris↗
PubMed1990

The effect of in vitro ethanol exposure on LHRH release from perifused rat hypothalami.

A variety of indirect data suggest that the luteinizing hormone (LH) lowering effects of ethanol (ETOH) are mediated at a hypothalamic level decreasing the synthesis and/or release of LH-releasing hormone (LHRH). Little direct data support this concept, however. The current study was, therefore, designed utilizing a perifusion system with frequent sampling for LHRH with and without ethanol added to determine if ethanol had a direct effect on basal or stimulated LHRH release. A variety of secretagogues, including dopamine, norepinephrine, naloxone, prostaglandin E2, and a high dose of potassium were utilized. Ethanol at a dose of 300 mg% did not alter either basal or secretagogue-stimulated LHRH release from the hypothalami of ethanol-naive male rats. Thus, ethanol did not appear to have a direct effect on LHRH in this system. Alterations in LHRH release by ethanol may occur at a suprahypothalamic level, involving neurotransmitter-LHRH interactions. Alternatively, the well-described lowering effect of ethanol on LH may be secondary to a direct pituitary locus of action, or involve a metabolic breakdown product of ethanol rather than ethanol itself.

Animals↗
PubMed1990

Rat spleen lymphocytes contain an immunoactive and bioactive luteinizing hormone-releasing hormone.

An interaction between the immune and endocrine systems has been long known. This association is further strengthened by the finding that splenic lymphocytes have the capacity to produce molecules similar to if not the same as classical hormones, including several members of the opiate family, PRL, GH, and neuropeptide Y. Because of such findings and because of information from other laboratories suggesting that LHRH might have direct effects upon the immune system, we hypothesized that immune cells themselves might contain LHRH. Lymphocytes were purified from spleens of intact adult male Sprague-Dawley rats and the cells were lysed with sodium hydroxide. The concentration of immunoreactive LHRH was 403 +/- 184 pg/20 X 10(6) lymphocytes. Increasing amounts of lymphocyte lysate displaced [125-I]LHRH from LHRH antibody in a manner parallel to that produced by synthetic hypothalamic LHRH, suggesting immunologic similarity between lymphocyte and hypothalamic LHRH. Lymphocyte LHRH-like immunoactivity coeluted from Nova-Pak C18 columns with synthetic hypothalamic LHRH. When lymphocyte lysates were applied to rat anterior pituitary cells in monolayer culture, significant stimulation of LHRH secretion was seen, from 2,144 +/- 54 pg LH/ml.4 h to 15,364 +/- 587 pg LH/ml.4 h (P less than 0.001), a finding verified in five additional experiments. In other studies, this LH response evoked by lymphocyte lysates was found to be dose dependent and could be significantly inhibited by an LHRH-antagonist. Furthermore, when lymphocyte lysate and identically treated synthetic LHRH were HPLC fractionated, there was coelution of lysate and hypothalamic LHRH bioactivity. The lysate itself contained no substantial LH immunoreactivity. Thus, lymphocytes from spleens of adult male rats contain an immunoactive and bioactive LHRH, a finding further strengthening an association between the endocrine and immune systems.

Animals↗
PubMed1990

Hypothalamic prolactin stimulates the release of luteinizing hormone-releasing hormone from male rat hypothalamus.

Previous works from our laboratory and others have shown that there is a PRL-like immunoreactive protein with immunological, chromatographic, and biological characteristics identical to those of pituitary PRL, and this is widely distributed in the rat central nervous system. Since pituitary PRL is important in controlling hypothalamic LHRH release, we have hypothesized that hypothalamic PRL-like immunoreactive protein might serve a similar role, that of an endogenous neuromodulator influencing hypothalamic LHRH release. To this end, we have examined the effect of PRL antiserum and normal rabbit serum on the release of immunoreactive LHRH from rat hypothalamic fragments cultured in vitro. In the first experiment, LHRH release from hypothalami of intact rats, bathed in PRL antiserum (1:200 in Krebs-Ringer bicarbonate buffer), was significantly lower than that from hypothalami bathed in normal rabbit serum (1:200 in Krebs-Ringer bicarbonate buffer) for 90 min of incubation. It was, however, possible that the PRL, immunoneutralized in the first experiment, was material that represented contamination from pituitary PRL. Therefore, we repeated the experiment using hypothalami from animals that had been hypophysectomized 2 weeks before death. Again, PRL antibody significantly inhibited the release of LHRH compared with that by hypothalami incubated in normal rabbit serum. Since testosterone is important to LHRH synthesis, a third experiment was carried out using hypothalami from hypophysectomized male rats that had been implanted sc with testosterone-containing capsules 72 h before death. By 72 h serum testosterone levels had normalized. PRL antibody added to medium containing hypothalamic explants from these animals substantially inhibited in vitro LHRH release, a pattern essentially similar to that seen in intact and hypophysectomized animals without testosterone replacement. From these studies we have concluded that hypothalamic PRL is an important neuromodulator that promotes the release of LHRH from the hypothalamus. Testosterone, at least under the experimental conditions employed, appears not to be essential in this hypothalamic PRL-LHRH interaction.

Animals↗
PubMed1990

Follicular cell predominance in the cytologic examination of dominant thyroid nodules indicates a sixty percent incidence of neoplasia.

The interpretation of aspiration cytologic smears that contain a predominance of follicular components often presents a dilemma to the clinician who is treating a patient who has a dominant thyroid nodule, especially when thyroid-stimulating hormone suppression does not produce any significant involution of the dominant nodule. We reviewed a consecutive series of 555 fine-needle aspiration cytologic examinations of dominant thyroid nodules. All specimens that contained colloid or follicular cells mixed with lymphocytes or Hürthle cells were excluded from this review. Additionally, nine aspirates contained degenerated follicular cells with insufficient material for cytologic diagnosis. The remaining 76 specimens contained a predominance of follicular cells: 27 specimens were interpreted as containing "normal" follicular cells, and the remaining 49 specimens were read as "atypical" follicular cells. Histopathologic examination of the resected specimens indicated a 60% incidence of neoplasia (30% carcinoma, 30% adenoma) in which the aspiration cytologic study was interpreted as "normal" follicular cells. On the other hand, a 63% incidence of neoplasia (27% carcinoma, 36% adenoma) occurred in which the cytologic study was read as "atypical." In conclusion, aspirates showing a predominance of follicular cells, whether "normal" or "atypical" indicate a 60% incidence of neoplasia in dominant thyroid nodules that do not decrease significantly in size with thyroid-stimulating hormone suppression.

Adenocarcinoma↗
PubMed1990

Long-term results of adrenal autotransplantation in Cushing's disease.

Many advances have been made in the diagnosis and treatment of patients with Cushing's disease. Currently, partial or total transsphenoidal resection of the pituitary gland is the surgical approach favored by many authorities, with cure rates of 80% to 90% reported for selected patients. However, long-term follow-up is still needed for this treatment modality, and recurrence rates of up to 50% have been reported. In addition, less favorable results are seen with this approach when there is recurrence after initial transsphenoidal surgery or when there is not a single microadenoma responsible for the disease of the pituitary gland. We report a series of 14 patients who were treated with bilateral adrenalectomy and autotransplantation. Follow-up is 4 to 14 years. Four patients show iodocholesterol uptake at the site of autotransplantation. Of these, three patients have been weaned from cortisone for 12, 10, and 2 years. The fourth patient, after being weaned from all medications, underwent partial resection of a hyperfunctioning autotransplant and currently, 7 years after the original operation, is being weaned from cortisone. A fifth patient was weaned to a reduced dose of cortisone for 8.5 years, but the dose was recently increased. There is no evidence of Nelson's syndrome in any of these patients with clinical evidence of functioning autotransplants. We believe that bilateral adrenalectomy with autotransplantation still plays an important role in the long-term management of selected cases of Cushing's disease and that autotransplantation, when successful, results in few complications and allows long-term freedom from exogenous steroid medication.

Adolescent↗
PubMed1990

Parathyroid autotransplantation in total thyroidectomy.

Although parathyroid autotransplantation during the course of thyroidectomy was first described by Halsted in 1907, it is only during the past 20 years that this simple and effective method of preserving parathyroid function is being used by an increasing number of surgeons. Our group has autotransplanted normal parathyroids since 1965, whenever these glands could not be preserved in situ with adequate blood supply. With increasing experience, we find it much simpler to autotransplant parathyroid glands attached to the thyroid, than to dissect their precarious blood supply, hoping they will survive postoperative edema and fibrosis. Furthermore, it is our impression that in operations for thyroid carcinoma, attempts to preserve the blood supply to the parathyroids may compromise the completeness of the thyroidectomy or of the dissection of cervical nodes in the tracheoesophageal groove. In a review of our experience during the past four years (January 1, 1984 to December 31, 1988), 87 patients underwent total thyroidectomy. Parathyroid glands that could not be saved in situ were biopsied to confirm their identity by frozen section and autotransplanted in the ipsilateral sternocleidomastoid muscle. Among the 87 patients undergoing total thyroidectomy, 34 required no autotransplantation, whereas 52 had one to three glands autotransplanted, and one had four glands autotransplanted. Postoperatively, 23 patients (26 percent) developed hypocalcemia, whereas 18 required CaCO3 and five required vitamin D in addition. All patients (98%) except two had normal parathyroid function at four-month follow-up and thereafter, as judged by serum calcium, phosphorus and parathormone, when indicated.

Adult↗
PubMed1989

Selective postoperative radioactive iodine treatment of thyroid carcinoma.

In a consecutive series of 234 patients with differentiated thyroid carcinoma of follicular cell origin (Hürthle cell tumors excluded), a radioactive iodine (131I) scan was obtained 3 to 6 months after thyroidectomy and 4 weeks after cessation of thyroid hormone treatments, only if extrathyroidal tumor extension or nodal or distant metastases were present. Twenty-one patients (9%) with 131I uptake of 3% or more (group 1) were treated with 150 to 200 mCi of 131I. Forty-four patients (19%) with less than 3% uptake (group 2) and 169 patients (72%) without evidence of metastases or extrathyroidal spread (group 3) were treated only with thyroid hormone. All patients initially underwent total thyroidectomy and modified neck dissection if cervical lymph node metastases were present. Three patients in group 1 and one patient in group 2 had recurrent tumor with a mean follow-up of 8.9 and 8.4 years. There were no recurrences in group 3 with a mean follow-up of 7.2 years. Death rate from thyroid carcinoma was 5% in group 1 (one patient) and 0% in groups 2 and 3. In conclusion, 131I scanning and therapy may be omitted in patients with differentiated thyroid carcinoma in the absence of local tumor extension or regional or distant metastases. Therapy with 131I is not demonstrated to be of benefit in this population of patients.

Adenocarcinoma↗
PubMed1989

Presence of prolactin-like immunoreactivity and bioactivity in rat spinal cord.

Pursuant to our identification of prolactin-like immunoreactivity (PLI), widely distributed in rat brain, the spinal cord was examined for the presence of this pituitary-hormone-like protein. PLI was present in all spinal cord extracts examined and averaged 500 +/- 53 pg/mg protein. Hypophysectomy, causing a fall in serum prolactin to undetectable levels, was not associated with any change in levels of PLI in spinal cord. Recovery of rat prolactin standards added to spinal cord homogenates was 97.6 +/- 3.9%. When increasing concentrations of spinal cord extract were assayed in a prolactin radioimmunoassay, displacement of rat 125I-Prolactin from antiserum was parallel to that displacement produced by increasing concentrations of rat anterior pituitary standards. Upon subjection to gel permeation chromatography, the elution profiles of immunoreactive prolactin from spinal cord were different from the profiles of anterior pituitary prolactin. In addition to an immunoreactive prolactin peak eluting with pituitary prolactin, spinal cord extracts showed a large void volume peak and late eluting low-molecular-weight materials not seen with anterior pituitary. In the Nb2 lymphoma cell assay, all spinal cord extracts demonstrated prolactin-like bioactivity with a bioactivity/immunoreactivity ratio of 1.05 +/- 0.13. We conclude: (1) PLI, widely distributed in rat brain, is also present in spinal cord; (2) spinal cord prolactin levels are independent of levels in pituitary and peripheral circulation; (3) this immunoreactive prolactin is bioactive, and (4) differing gel permeation chromatographic elution profiles indicate that there may be some molecular differences between pituitary and spinal cord prolactin.

Animals↗
PubMed1989

In-vivo effect of ethanol on release of LH-releasing hormone and LH in rats.

The effect of exposure to ethanol on hypothalamic LH-releasing hormone (LHRH) release in vivo was investigated in rats both acutely (i.p. injection) and after 3 days of administration, utilizing a permanent gastric cannula. In both designs, the animals were castrated before being given ethanol and, in both experiments, ethanol successfully lowered the post-castration LH rise compared with control castrated animals. In both the acutely and chronically treated groups, basal LHRH release was not impaired, despite the documented decrease in LH levels. Finally, stimulated LHRH release was investigated with depolarizing concentrations of potassium and, again, no change was noted between the hypothalamic release of this decapeptide in the ethanol-exposed compared with the ethanol-naive animals. Thus, ethanol failed to inhibit basal or stimulated LHRH secretion in the acutely and chronically treated animal. This lack of effect on LHRH occurred despite a concomitant lowering of serum concentrations of LH.

Animals↗
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↗