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Biomedical subjects

B M Sherman

Publications and source records attributed to B M Sherman.

At least 73 records · Page 4Linked to original sources

The effects of an antihistamine and/or a glucocorticoid on the prolactin response to surgical procedures.

Prolactin (PRL) release in response to surgical stress has been demonstrated in a variety of species. Previous studies in rats indicate this response is blunted or blocked by pretreatment with either glucocorticoids or antihistamines. The present study was designed to investigate this phenomenon in man. Serum PRL levels before, during, and after major gynecologic surgery were measured in 20 women randomly assigned to one of four pretreatment regimens: (1) dexamethasone, (2) promethazine, (3) both agents, and (4) neither agent. Type of operation, preanesthetic medication, anesthetic agents, and estrogen status of patients were similar in all groups. Untreated controls exhibited the expected five- to tenfold increase in serum PRL concentration with surgery. Pretreatment with either dexamethasone or promethazine alone failed to suppress this response (in contrast to reported findings in the rat) and in fact promethazine appeared to cause an augmented response. However, patients given dexamethasone and promethazine together exhibited only a two- to threefold PRL increase, a significantly lesser response than that in any of the other groups. Thus, PRL release in response to general anesthesia and surgery is inhibited by the combination of an antihistamine (H-l) receptor antagonist and a glucocorticoid, whereas either agent alone has no suppressive effect.

Adult↗

Spontaneous pregnancy in women with a prolactin-producing pituitary adenoma.

The occurrence of spontaneous pregnancy in patients with amenorrhea-galactorrhea, hyperprolactinemia, and radiographic evidence of a pituitary tumor is unusual. We present here two patients who conceived spontaneously. One had an uneventful pregnancy. Following delivery, transsphenoidal pituitary surgery was performed, confirming the presence of a prolactin-producing adenoma. The second patient had an early pregnancy termination (at 12 weeks of gestation). These patients provide evidence that ovulation and pregnancy can occur in spite of elevated prolactin levels.

Adenoma↗

The treatment of hyperprolactinemia with a new ergot derivative, lergotrile mesylate.

Lergotrile mesylate is an ergot alkaloid derivative modified to eliminate the vasoconstrictive properties of the parent compound while preserving the properties that inhibit pituitary secretion. Administration of the drug to women with amenorrhea-galactorrhea resulted in the lowering of serum prolactin concentrations. The duration of action was short, so that prolactin levels were near base line 6 to 8 hours after a 2.0-mg dose and morning prolactin concentrations were not persistently suppressed. Initial therapy was accompanied by the development of postural hypotension. Tolerance to this side effect of the drug developed after several days of treatment with gradually increasing doses. In one patient, long-term treatment resulted in reduction of breast secretions, resumption of menses, and conception.

Acetonitriles↗

Evaluation of the pituitary. Patients with suspected prolactin-producing tumors.

We have reviewed our experience in the radiographic and ophthalmologic evaluation of 1001 patients with symptoms suggesting the presence of a pituitary, prolactin-secreting adenoma. Twenty-seven patients had abnormal or suspicious radiographic examination of the sella turcica. Twenty-two of those had hyperprolactinemia. In only one instance was an abnormality noted on polytomography that was not seen on a conventional four-view study of the skull. Based on these findings, a four-view plain conventional radiographic assessment of the skull suffices as a screening procedure in patients with amenorrhea, galactorrhea, or both. Thin section tomography should be reserved to more thoroughly evaluate those patients with elevated serum prolactin concentrations and/or abnormal conventional radiographs. We found visual field testing to be of little value as an initial screening procedure in these patients.

Adenoma↗

Menstrual cycle patterns and breast cancer risk factors.

Using a data set of women who longitudinally recorded menstrual and reproductive events, we examined menstrual cycle characteristics in relationship to early and late menarche, early and late menopause, and deferred parity, three variables epidemiologically related to breast cancer incidence. Women with late onset of menarche had longer and more variable cycles in the 10 years after menarche than did those with early onset. Women with late onset of menopause had longer and more variable cycles in the premenopausal interval than did those with early onset. Cumulative fertility in women after marriage did not differ according to cycle length and variance. Late menopause may be a breast cancer risk factor due to relative estrogen excess and progesterone lack as reflected in longer, more varied cycle patterns. Observed cycle differences between women with early and late menarche await further study of the endocrine physiology of the menstrual cycle in those groups.

Adolescent↗

Results and merit of estrogen receptor data derived from metastatic tumors of the breast.

It is clear that a variety of metastatic deposits can successfully be assayed and found to contain estrogen receptor protein even up to 13 years following the initial tumor surgical procedure. Whether or not the patient has received previous treatment, estrogen receptor status does not appear to be influenced, and biopsies of the 23 metastatic lesions were found to contain estrogen receptors. Fourteen of nineteen patients with metastatic tumors containing estrogen receptors who were treated and evaluated demonstrated remission after hormonal manipulation. Only one patient with a tumor with no estrogen receptors demonstrated tumor regression after hypophysectomy and suggests that a previous response to hormone manipulation may warrant a further trial even when estrogen receptors are not found. The results of estrogen receptor values on metastatic disease of the breasts are extremely valuable in the therapeutic decision making process and should be routinely obtained.

Aged↗

Cardiac size and function in acromegaly.

Sixteen acromegalic patients underwent echocardiography, phonocardiography, stress electrocardiography with Thallium perfusion scanning and gated radioisotope left ventricular angiocardiograms. Abnormalities consisting of increased echo left ventricular mass index, low velocity of circumferential fiber shortening or elevated pre-ejection period to left ventricular ejection time ratio were found in six patients with coexistent hypertension or coronary disease. Concentric left ventricular hypertrophy was also found in three patients with no known etiology other than acromegaly of greater than thirteen years' duration or with fasting growth hormone concentrations greater than 100 ng/ml. One of these three also had left ventricular dysfunction. Neither hypertrophy nor ventricular dysfunction was found in other acromegalics with shorter duration of disease or lower growth hormone concentrations or with normal growth hormone concentrations after therapy. A high prevalence of coronary artery and hypertensive heart disease is associated with acromegaly. A few patients with acromegaly have a specific, potentially reversible cardiomyopathy probably related to prolonged acromegaly or very high growth hormone concentrations.

Acromegaly↗

Regulation of lactogenic hormone binding in rat liver by steroid hormones.

We have measured the effects of testosterone propionate, medroxy-progesterone acetate and cortisol on the binding of ovine [125I]iodoprolactin to 100,000 X g particulate fractions from liver of normal and estrogen-treated female rats. In untreated animals 6.7 +/- 1.1% (SD) of the radioactivity added to 0.5 mg of membrane protein was specifically bound to the hormone receptor. Specific binding was significantly (P less than .05) decreased after 7 daily doses of testosterone (1.0 mg) to 2.8 +/- 1.4%, medroxyprogesterone (0.25 mg) to 2.7 +/- 0.2% and cortisol (5.0 mg) to 3.1 +/- 1.3%. The serum prolactin concentration, 4.2 +/- 3.4 ng/ml in normal animals, was not affected by the hormone treatment. Ethinyl estradiol, 10 mug/day for 7 days, increasing the binding of [125I]iodo-prolactin to 16.6 +/- 6.0% and increased serum prolactin to 50.6 +/- 11.5 ng/ml. Simultaneous administration of testosterone, medroxyprogesterone or cortisol with estradiol did not diminish the estradiol-induced increase in serum prolactin, but completely prevented the increase in prolactin binding. Testosterone or cortisol given to animals pretreated with estradiol suppressed prolactin binding from 16.4 +/- 4.2% to less than 2.5% after 48-72 h. Parellel results were obtained with 125I labeled human growth hormone whereas 125I labeled-insulin binding was not affected by these treatments. Scatchard analysis showed that the decrease in lactogenic hormone binding was due to a reduced concentration of receptors with no significant change in affinity. Since serum levels of prolactin were not changed, we conclude that treatment with testosterone, medroxyprogesterone, and cortisol decreased lactogenic hormone binding by a direct action on the liver.

Animals↗

Transcervical thymectomy: an integral part of neck exploration for hyperparathyroidism.

Thirty-two neck explorations for hyperparathyroidism were done in 18 months. The indication for transcervical thymectomy was a failure to locate either inferior gland. Six of eight patients had adenomatous or hyperplastic glands located within or adjacent to the thymus. One infrathymic lesion was a parathyroid carcinoma and the other was a functioning parathyroid cyst. The abnormal parathyroid gland was not visible in any of these six patients until the thymus had been removed. Had this step been omitted, a sternotomy would probably have been required. Two patients had bilateral normal parathyroid glands within or deep to the thymus. Unless some normal parathyroid tissue has been identified and preserved, the indiscriminate use of transcervical thymectomy could result in the inadvertent excision of both inferior glands and possible iatrogenic hypoparathyroidism.

Humans↗

Serum estradiol response to gonadotropin-releasing hormone: studies in normal women and in women with secondary amenorrhea.

Serum estradiol (E2), luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were measured in blood samples obtained prior to and at frequent intervals for 360 or 480 minutes following the subcutaneous administration of gonadotropin releasing hormone (Gn-RH) to eight normal women and nine patients with hypothalamic secondary amenorrhea. In the normal subjects given 100 mug of Gn-RH on day 7 of the menstrual cycle, there was no significant increase in the mean E2 concentration above basal levels. Six women with secondary amenorrhea received Gn-RH, 100 mug, for 4 successive days; frequent blood samples were obtained on days 1 and 4. On day 1, the mean E2 concentration at 360 minutes was significantly greater than the mean basal level. On day 4 no significant increase in E2 was detected, although the mean LH and FSH responses and basal E2 level were not different from those of day 1. Four women with secondary amenorrhea received daily doses of 500 mug of Gn-RH for 7 days. Significant increases in mean serum E2 concentration (100 to 150 pg/ml) were noted at 6 and 8 hours after administration on day 1 and at 8 hours on day 4. No significant rise in E2 was detected on day 7. The mean LH and FSH responses did not differ from those observed in women who received the 100-mug dose, and there were no significant differences in responses on successive days of Gn-RH administration.

Adult↗

The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women.

Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.

Adolescent↗

FSH-secreting pituitary adenomas: stimulation and suppression studies in two patients.

Two patients with pituitary adenomas, partial hypopituitarism and abnormally high serum concentrations of FSH are described. In neither patient was FSH increased after the administration of LH releasing hormone and in one patient tested, there was no FSH response to clomiphene citrate. The decrease in serum FSH in response to high concentrations of testosterone (greater than 1100 ng/dl) was less than in normal men. These results indicate partial autonomy of FSH producing adenomas. Since the elevated serum FSH produced no obvious clinical symptoms, it may be undetected unless serum FSH concentrations are measured routinely in patients with pituitary tumors.

Adenoma↗

Gonadotropin response to LH-RH in anorexia nervosa.

The gonadotropin-ovary axis of patients with anorexia nervosa was assessed with the aim of distinguishing between an intrinsically hypophysial deficiency and pituitary malfunction secondary to hypothalamic impairment. The most consistent endocrine abnormality was low serum luteinizing and follicle stimulating hormone (LH and FSH) levels associated with depressed serum estradiol levels. Gonadotropin levels responded to luteinizing hormone-releasing hormone (LH-RH), thus indicating a primarily hypothalamic dysfunction. The increase in serum FSH was at least as great as that of LH. The LH levels were additionally depressed and their increase after LH-RH injection somewhat blunted by three-day treatment with ethinyl estradiol.

Adolescent↗

Radioligand assay in reproductive biology.

Radioligand assays have been developed for the principal reproductive steroids and peptide hormones. Specific binding reagents have included antibodies, plasma binders, and intracellular receptors. In each assay, problems of specificity, sensitivity, and nonspecific inhibitors were encountered. Many features of the endocrine physiology in childhood, during puberty, and in adulthood have been characterized. Hormonal evaluations of endocrine disorders of reproduction are characterized on the basis of their characteristic pathophysiologic alterations.

Adult↗

Evaluation of amino acid infusions as protein-sparing agents in normal adult subjects.

Blackburn et al. (1, 2) reported nitrogen equilibrium and/or positive balance in surgical patients maintained on a 3% amino acid solution at a level of 1 g/kg body weight per day. We have measured nitrogen balance and fat mobilization in six normal adult volunteers durig the infusion of two compositionally different amino acid solutions at 1 g/kg body weight per day, and compared these to values noted during isocaloric infusion of glucose solutions. Nitrogen balance was negative during all infusion periods, but was significantly less negative (P smaller than 0.01) during amino acid infusion periods (--5.8 plus or minus 1.1 g/day) than during glucose infusion (--9.8 plus or minus 1.8 g/day). No significant differences in nitrogen balance were noted between amino acid infusion periods, despite compositional differences in solutions. Elevated plasma levels of free fatty acids (0.71 plus or minus 0.37 mM) and ketone bodies (1.3 plus or minus 0.3 mM) observed during amino acid infusion periods reflected the availability of body lipids as energy substrate. The disparity between our results and those reported by Blackburn et al. (1, 2) may in part reflect the previous nutritional debilitation of the surgical subjects studied by these investigators.

Adult↗

Hormonal characteristics of the human menstrual cycle throughout reproductive life.

The changes in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FHS), estradiol, and progesterone that occur both early and late in reproductive life were characterized and compared with findings in young, normal women and in patients with certain menstrual disorders. A total of 50 complete menstrual cycles in 37 were examined. Five distinct patterns of hormonal regulation were found, three of which are reported here: (a) A long follicular phase and delayed follicular maturation in young women with long, unpredictable intermenstrual intervals from menarche; (b) a short follicular phase with increasing age and in short cycles in perimenopausal women; and (c) true anovulatory vaginal bleeding in long cycles in perimenopausal women. The short cycles before and during the menopausal transition were found to have lower E2 levels and high FSH concentrations throughout, while LH remained in the normal range. During long cycles in perimenopausal women, concentrations of LH and FSH were in the menopausal range. However, follicular maturation was observed months after high levels of gonadotropins were attained. These studies permit the characterization of the menstrual history of the normal woman in terms of the hormonal changes that occur and provide a basis for the definition of several disorders of follicular maturation.

Adolescent↗