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Biomedical subjects

W B Malarkey

Publications and source records attributed to W B Malarkey.

At least 55 records · Page 3Linked to original sources
PubMed1991

Preserved atrial natriuretic peptide secretory function after cardiac transplantation.

The purpose of this investigation was to determine whether atrial natriuretic peptide (ANP) secretory function is preserved after cardiac transplantation. Thirteen hemodynamically stable outpatients performed supine exercise on a bicycle an average of 7 months after orthotopic cardiac transplantation. Right atrial pressure increased 2.2-fold (6 +/- 1 to 13 +/- 2 mm Hg) and pulmonary artery wedge pressure 2.1-fold (11 +/- 1 to 23 +/- 7 mm Hg) with exercise in the transplant recipients. Resting venous ANP level (114 +/- 19 pg/ml) and peak exercise venous level (373 +/- 61 pg/ml) was elevated in transplant recipients (p less than 0.001) compared with control subjects (21 +/- 1 and 92 +/- 14 pg/ml, respectively. This represents a 3.3-fold (114 +/- 19 to 373 +/- 61 pg/ml) increase in the ANP level from resting to exercise in transplant recipients and a 4.4-fold (21 +/- 1 to 92 +/- 14 pg/ml) increase in control subjects. A correlation between venous ANP levels and hemodynamics (right atrial pressure) was observed r = 0.49 p = 0.01. It is concluded that ANP levels at rest are elevated after cardiac transplant, the levels correlate with the intracardiac hemodynamics, and exercise-induced augmentation of plasma levels occurs.

Adult↗
PubMed1991

Endocrine effects in female weight lifters who self-administer testosterone and anabolic steroids.

It appears that the self-administration of testosterone and anabolic steroids is increasingly practiced by women in sports where strength and endurance are important. We recently evaluated endocrine parameters in nine female weight lifters using steroids and seven not using these agents. Of the nine anabolic steroid users, seven took multiple anabolic steroids simultaneously. Thirty-fold elevations of serum testosterone were noted in the women injecting testosterone. In three of these women serum testosterone levels exceeded the upper limits for normal male testosterone concentrations. A significant compensatory decrease in sex hormone-binding globulin and a decrease in thyroid-binding proteins were noted in the women steroid users. Also, a 39% decrease in high-density lipoprotein cholesterol was noted in the steroid-using weight lifters. Most of the subjects in this study used anabolic steroids continuously, which raises concern about premature atherosclerosis and other disease processes developing in these women.

Adult↗
PubMed1991

Facilitation of dimethylbenz[a]anthracene-induced rat mammary tumorigenesis by restraint stress: role of beta-endorphin, prolactin and naltrexone.

In order to investigate the involvement of opioid peptides and prolactin in stress-facilitated mammary cancer, we studied the effect of chronic restraint stress on dimethylbenz[a]-anthracene (DMBA)-induced mammary tumorigenesis and the effect of an opiate antagonist, naltrexone, on this process. Female Fischer-344 rats (n = 160) were administered 15 mg DMBA/ml of sesame oil/rat by intragastric intubation. Eighty rats were subjected to daily 30 min restraint stress in a plastic cylinder, and 80 rats served as control not subjected to the stressor. Half of the rats from each group received naltrexone (1 mg/kg, i.p. daily). Five rats from each group (restraint stress +/- naltrexone and control +/- naltrexone) were killed every 2-3 weeks. Rats subjected to restraint stress developed a greater number of tumors earlier. Naltrexone decreased the tumor incidence in the stressed animals from 32 to 12% (P less than 0.001) and in unstressed rats from 27 to 15% (P less than 0.001) at the end of 18 weeks. Stressed rats showed a decrease of 48% (P less than 0.001) in the level of hypothalamic beta-endorphin. Plasma prolactin increased from 4-13 ng/ml in the control rats to 109-396 ng/ml (P less than 0.001) in the stressed rats throughout the 18 week period. The beneficial effect of naltrexone was associated with 42% (P less than 0.01) increase in T cell proliferation, but greater than 90% (P less than 0.001) decrease in plasma prolactin level was observed in naltrexone-treated rats compared to the untreated animals. Rats subjected to restraint stress showed a 15% (P less than 0.001) decrease in weight gain at the end of the experiment (18 weeks). Neither restraint stress nor naltrexone administration affected the caloric intake of rats during this period. Thus, we believe that restraint stress facilitates DMBA-induced mammary tumors by releasing beta-endorphin and prolactin, and naltrexone shows a beneficial effect by opposing the effect of beta-endorphin on prolactin release in the stressed animals.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

The influence of academic stress and season on 24-hour concentrations of growth hormone and prolactin.

Stress has been considered a physiological regulator of GH and PRL secretion in humans. The stressors used in studies have often been extreme. The influence of commonplace stressors on the endocrine system has not been clarified. Therefore, to better define the role of commonplace stressors on GH and PRL secretion, we evaluated the effect of examination stress on GH and PRL secretion in 37 male medical students. We performed hourly sampling for 24 h for GH and PRL 4 weeks before, during exam week, and 2 weeks after major examinations in the fall and spring of their first year. Stress, as evaluated by the Perceived Stress Scale (PSS), increased as expected during examination weeks, but there was no correlation between the PSS scores and mean day or night GH and PRL secretion. Twenty-four-hour GH and PRL secretion was not significantly altered during examinations in either fall or spring. A significant seasonal influence, however, was noted on GH secretion, with both daytime and nocturnal GH secretion being consistently higher in the Fall than in the Spring. We conclude that examination stress does not significantly influence mean daytime or nocturnal GH and PRL concentrations. We suggest that serum GH and PRL levels may not be significantly altered in man by commonplace stressors. Also, seasonal effects may be operative in the control of human GH secretion.

Adult↗
PubMed1991

Continuous subcutaneous octreotide infusion: dose-response relationships between metabolic effects and octreotide clearance in patients with insulin-dependent (type 1) diabetes.

Octreotide (Sandostatin), a potent and long-acting octapeptide analogue of somatostatin, exhibits variable metabolic effects in type 1 diabetes. We have postulated that interindividual variability in octreotide metabolism could be responsible in part for the differences in metabolic responses reported in previous clinical studies. To this end, we determined plasma levels and MCR of octreotide during 24-hour continuous SC infusion (low dose, 200 micrograms; high dose, 400 micrograms) in nine female, C peptide-negative patients with type 1 diabetes. The metabolic effects of the analogue were assessed by measuring serum glucose, free insulin, glucagon, GH, and PP levels before and at 1- to 2-hour intervals during each dose of the analogue or control (0.9% saline solution) infusion in a single-blind randomized manner. Mean daytime (0800-0000 hours) and bedtime (0000-0800 hours) serum glucose levels decreased significantly (p less than 0.05 to 0.02) during analogue therapy compared with control. Mean serum free insulin levels were significantly (p less than 0.02) greater during octreotide infusion compared with control, despite the similar daily insulin requirements. Both doses of the analogue effectively suppressed 24-hour GH by 50%, glucagon by 50%, and PP by 80%. Steady-state octreotide levels varied considerably among patients (low, mean +/- SEM), 1000 +/- 101, range 638 to 1375 pg/ml; high, mean 1940 +/- 147, range 1032 to 2462 pg/ml). Although mean MCR values were similar with both doses, we observed greater interindividual variability (low, mean 2.45 +/- 0.30, range 1.31 to 3.78 ml/kg/min; high, mean 2.36 +/- 0.19, range 1.68 to 3.48 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1990

The response of serum growth hormone and prolactin to training in weight-maintaining healthy males.

Resting levels of serum growth hormone (GH) and prolactin (PRL) were measured pretraining, 3 weeks and 10 weeks posttraining in seven college age males. The exercise consisted of thrice weekly sessions at 70% VO2max for 20 minutes plus warmup and cool down. Body weight remained constant during the ten week training period. However, body fat decreased significantly. Resting daytime levels of GH decreased significantly with training while resting PRL levels were unchanged. The hormone responses suggest attenuation of resting GH levels with training and may relate to changes in body fat.

Adipose Tissue↗
PubMed1989

Response of a GH- and TSH-secreting pituitary adenoma to a somatostatin analogue (SMS 201-995): evidence that GH and TSH coexist in the same cell and secretory granules.

A 29-year-old male presented with acromegaly and hyperthyroidism and was found to be hypersecreting both GH and TSH. A somatostatin analogue, SMS 201-995, at doses of 50 and 100 micrograms s.c. 3 times a day produced an acute decrease in serum GH and TSH levels to less than 20% of basal concentrations. An increase in serum SMS 201-995 levels preceded the decline in serum GH and TSH levels. Partial resolution of signs and symptoms related to GH excess occurred and the patient developed normal serum thyroxine levels. These latter effects were maintained during the 3.5 months of SMS 201-995 therapy; however, pituitary adenoma size as judged by MRI was unchanged. Side effects of therapy were minimal and included transient abdominal pain, diarrhea and weight gain. Adenomatous pituitary tissue was surgically removed and placed in monolayer culture. It was observed that SMS 201-995 produced significant inhibition of GH and TSH release. Histology revealed a partly chromophobic, partly acidophilic adenoma containing GH and TSH. Electron microscopy showed a pituitary adenoma which appeared to consist of smaller cells resembling somatotrophs and larger cells exhibiting ultrastructural features of thyrotrophs. Immunoelectron microscopy localized the two biochemically distinct peptides in the same cell type, often in the same secretory granules. No morphologic abnormality, attributable to SMS 201-995 medication, was evident. Thus it can be concluded that pituitary adenomas can simultaneously secrete GH and TSH which produce acromegaly and hyperthyroidism. These bi-hormonal tumors may synthesize GH and TSH in the same cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1989

Persistence of large molecular weight prolactin secretion during pregnancy in women with macroprolactinemia and its presence in fetal cord blood.

Two hyperprolactinemic women with marked increases in circulating 150K PRL were studied from conception throughout pregnancy and delivery. The serum PRL increase during pregnancy in these women was considerably less than that in normal pregnant women (2- and 3.5-fold vs. 10- to 20-fold increases, respectively). The 150K PRL species persisted as the predominant circulating form of PRL throughout each trimester of pregnancy in these women. In contrast, the predominant form of PRL in serum from normal pregnant women was the 22K PRL form. Gel filtration analysis of the umbilical venous cord serum of infants of the macroprolactinemic women demonstrated excessive concentrations of 150K and 50K PRL compared to the molecular species of PRL in the cord serum of normal infants. Repeat analysis of the PRL species in one infant at age 3 yr continued to reveal excessive secretion of 150K PRL (11% vs. less than 6% in normals). These data suggest that genetic influences may be operative in determining PRL heterogeneity.

Adult↗
PubMed1989

Interleukin-1 beta and other cytokines stimulate adrenocorticotropin release from cultured pituitary cells of patients with Cushing's disease.

Interleukin-1 (IL-1) is a cytokine that is secreted by macrophages and monocytes which stimulates rodent hypothalamic CRH release and possibly pituitary ACTH secretion. We studied the effect of IL-1 beta and other cytokines (gamma-interferon, thymosin fraction-5, and granulocyte colony-stimulating factor) on ACTH release from corticotroph adenoma tissue obtained from two patients with Cushing's disease. IL-1 beta (0.001-10 mumol/L) increased ACTH release 3-fold. Thymosin fraction-5 (10 mumol/L), gamma-interferon (1 mumol/L), and granulocyte colony-stimulating factor (1 mumol/L) also stimulated ACTH release. These cultured cells secreted little or no GH, PRL, TSH, LH, and FSH, and their release was not stimulated by any cytokine. These results suggest that ACTH release in patients with Cushing's disease may be responsive to stimulation by various cytokines.

Adenoma↗
PubMed1989

The effect of angiotensin-converting enzyme inhibition on prolactin responses in normal and hyperprolactinemic subjects.

Recent observations implicate angiotensin-II (AII) as a possible PRL-releasing factor. These observations prompted us to investigate the role of the renin-angiotensin system in PRL release in man. Nine normal volunteers ingesting a 20-40 mmol/day sodium, 70 mmol/day potassium diet and eight normal volunteers ingesting a 120 mmol/day sodium, 70 mmol/day potassium diet were infused with metoclopramide (2.5 mg over 1 min) and later with TRH (500 micrograms), two agents known to cause PRL release. The infusions were repeated after 36 h of oral administration of converting enzyme inhibitor [CEI; captopril (50 mg, orally, four times daily) or enalapril (5 mg, orally, twice daily)]. On a separate occasion, AII was infused at 10 ng/kg.h for 1 h into normal volunteers on normal salt diet. CEI administration lowered mean arterial pressure by 6-7 mm Hg and stimulated the release of active renin. The PRL responses on low and normal salt diet as well as before and after CEI were not statistically different. There was also no difference in the PRL responses of patients placed on captopril vs. those on enalapril. AII increased blood pressure by 11-25 mm Hg, but did not increase PRL significantly above basal concentrations during the control dextrose infusion. Five hyperprolactinemic volunteers were also given CEI for up to 4 weeks. They demonstrated no significant change in serum PRL levels. We conclude that AII in the pituitary does not significantly alter either basal PRL levels or metoclopramide- and TRH-induced PRL responses in normal subjects on low and high salt diets. In addition, CEI is not a useful therapy in patients with pathological hyperprolactinemia. These findings, however, do not exclude a role for AII in physiological regulation, since CEI does not cross the blood-brain barrier and would not be expected to alter hypothalamic AII.

Adult↗
PubMed1989

Metabolic effects of long-acting somatostatin analogue (sandostatin) in type I diabetic patients on conventional therapy.

We evaluated the effectiveness of a more potent and longer-acting somatostatin analogue (SMS 201-995) as an adjunct to insulin therapy, in a double-blind placebo-controlled randomized study of 26 C-peptide-negative type I (insulin-dependent) diabetic patients (20 women, 6 men, aged 22-40 yr) on their conventional drug regimens for 12 wk. Eight patients received a low dose (10 micrograms) of the analogue, 9 received a high dose (50 micrograms) of the analogue, and 9 received placebo subcutaneously before breakfast and dinner. Twenty-four-hour serum glucose, free insulin, plasma growth hormone (GH), and glucagon profiles were obtained before and during treatment at 4-wk intervals. The mean age, duration of diabetes, daily insulin dose, and body weight were not significantly different among the groups. The mean weekly capillary blood glucose values and exogenous insulin requirements were not changed by the SMS 201-995 therapy. Mean glycosylated hemoglobin A1 levels were unchanged in both the analogue- and placebo-treated groups at wk 12. Basal and postprandial glucose, free insulin, GH, and glucagon profiles were not influenced by the SMS 201-995 therapy throughout the study. Nocturnal glucose turnover rates (D-[3-3H]glucose technique) remained unaltered by the analogue therapy. Dose-dependent gastrointestinal (GI) adverse effects (e.g., diarrhea) were documented in the analogue-treated patients. Visual acuity and fundic photomicrographs of our patients were not changed by the analogue therapy. In conclusion, the prominent adverse GI effects our patients experienced preclude the use of larger doses of the analogue that may be necessary to suppress GH and glucagon and improve glucose control in type I diabetic patients.

Adult↗
PubMed1988

Pituitary response to TRH in bulimia.

The response to thyrotropin-releasing hormone (TRH) of thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin (PRL) was examined in nine normal weight female bulimics without endogenous depression and eight female controls. Four bulimics had delayed peak TSH response, but none demonstrated a blunted TSH response, unlike that which has been reported in endogenous depression. Bulimics had elevated mean +/- SD serum GH levels (controls 1.6 +/- 1.4 ng/ml, bulimics 5.6 +/- 3.9) and an inappropriate GH release following TRH. Their mean +/- SD serum PRL (3.1 +/- 1.7 ng/ml) was lower than that of controls (4.7 +/- 1.3); however, the PRL response to TRH was significantly greater in bulimics than in controls. These data show that neuroendocrine abnormalities exist in normal weight bulimic women without endogenous depression and provide further evidence for a neuroendocrine component to this illness.

Adolescent↗
PubMed1988

Growth hormone and somatomedin-C in bulimia.

Somatomedin-C (SOM-C) concentrations are regulated by circulating growth hormone (GH) concentrations; however, other factors, such as nutrition, also influence SOM-C concentrations. We evaluated the GH-SOM-C axis in seven normal-weight female bulimics one day after hospital admission, and in seven age-, sex-, and weight-matched normal controls. Subjects were medication-free for at least one month. Fasting morning serum GH concentrations were higher in all bulimics (range 2.5-13.3 ng/ml) than in all controls (range less than 1.0-1.8 ng/ml). The mean (+/- SD) maximum GH response to TRH (500 micrograms) was greater in the bulimics (12.9 +/- 4.9 ng/ml) than in the controls (3.7 +/- 2.7 ng/ml) (p less than .001). Despite this GH elevation, the mean (+/- SD) SOM-C concentration was comparable in the bulimics (2.0 +/- 0.6 U/ml) and the controls (1.6 +/- 0.8 U/ml). This suggests that SOM-C generation is resistant to the elevated circulating GH in bulimia and that SOM-C is not inhibiting GH secretion in the pituitary-hypothalamic axis.

Adult↗
PubMed1988

Long-term assessment of patients with macroprolactinemia.

Three patients presenting with hyperprolactinemia associated with normal menses, retained fertility, and minimal lactation were followed for a period of 5 to 7 years. All had associated thyroid autoimmune disorders (one with chronic thyroiditis and two with Graves' disease). Their major form of circulating prolactin (PRL) was in the large-molecular weight (150K) form (macroprolactinemia). Whereas normal serum content of 150K PRL is less than 10% of the total, these three patients had 150K PRL fractions of 97%, 96%, and 67%. The retention of normal menses and fertility of these subjects suggested that the 150K PRL had diminished biologic activity as patients with elevations of 22K PRL will have amenorrhea and infertility. Over time, the serum PRL levels of these three patients decreased with a coincident fall in the percentage of 150K PRL. Although serum thyroid concentrations usually influence serum PRL levels, no such effects were seen in these patients whether they were hypothyroid or hyperthyroid, neither was a causal relationship between the macroprolactinemia and autoimmune thyroid disease established. Macroprolactinemia cannot be considered to be a completely benign condition as occasionally it may be associated with infertility and osteopenia.

Adult↗
PubMed1988

Effect of adrenal function on gastrointestinal peptide release in experimental cardiac arrest.

Pancreatic polypeptide (PP), neurotensin, substance P, and vasoactive intestinal polypeptide (VIP) are peptides that modify various autonomic and neural functions. These substances are secreted into the blood in response to physiologic stimuli affecting the gastrointestinal tract. To determine the effect of adrenal hormones on gastrointestinal peptide release we measured blood levels of PP, VIP, substance P, and neurotensin in adrenalectomized and intact dogs undergoing cardiac arrest and cardiopulmonary resuscitation (CPR), a condition associated with maximal adrenal stimulation. One hour after completion of abdominal surgery consisting of bilateral adrenalectomy or exposure of the adrenal glands (sham operation), ventricular fibrillation was induced in 19 dogs by direct ventricular discharge. Despite marked elevations of plasma epinephrine and norepinephrine, CPR was associated with minimal endocrine gastrointestinal involvement, restricted to increased VIP levels in sham-operated dogs. No specific gastrointestinal peptide response to cardiac arrest was seen in adrenalectomized animals, but their plasma PP and VIP levels were higher than those of sham-operated dogs. Therefore, acute maximal adrenal stimulation is associated with selective VIP release. In addition, the higher level of the vagally controlled plasma PP in adrenalectomized animals suggests a tonic inhibitory effect of adrenal secretions on the release of this peptide.

Adrenal Glands↗