Biomedical subjects

Y Shenker

Publications and source records attributed to Y Shenker.

At least 37 records · Page 2Linked to original sources

PubMed1988

Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995.

A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long-acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion.

Acromegaly↗

PubMed1988

Atrial natriuretic hormone effect on renal function and aldosterone secretion in sodium depletion.

The effects of atrial natriuretic hormone (ANH) on aldosterone secretion and renal function have been well documented, but the physiological role of ANH is still unknown. To address this issue, eight normal men were infused for 4 h with low-dose (1.1 pmol.kg-1.min-1) human [Ser-Tyr28]ANH after 3 days of low-salt (LS) diet. The same subjects were also studied with placebo infusion on LS and high-salt (HS) diet. ANH infusion caused doubling of urine flow, a fourfold increase in urinary sodium excretion, and a slight increase in potassium excretion. Immunoreactive ANH levels increased from 3.1 +/- 0.5 to 21.0 +/- 1.9 pmol/l during ANH infusion. ANH infusion suppressed plasma renin activity (PRA) to one-third of the basal value, and plasma aldosterone was suppressed from 46.5 +/- 6.5 to 20.9 +/- 2.6 ng/dl. Low-dose ANH infusion caused a marked increase in urine flow and urinary sodium excretion and prominent suppression of PRA and plasma aldosterone in sodium-depleted subjects. These results suggest a physiological significance of ANH in regulation of kidney function and aldosterone secretion.

Adult↗

PubMed1988

Effect of vasopressors on atrial natriuretic factor and hemodynamic function in humans.

To assess the effects of vasopressors on plasma levels of immunoreactive atrial natriuretic factor (ANF), 13 normal men were studied on two occasions. On the experimental day, subjects received sequential 15-minute intravenous infusions of angiotensin II in doses of 4, 8, and 16 pmol/kg/min. Following a 30-minute recovery period, subjects received sequential 15-minute infusions of phenylephrine in doses of 0.4 and 0.8 micrograms/kg/min. Right atrial pressure, mean pulmonary capillary wedge pressure, pulmonary artery pressure, mean systemic arterial pressure, and plasma levels of renin activity, aldosterone, angiotensin II, and immunoreactive ANF were obtained sequentially throughout the protocol. During the control day, vehicle was infused and plasma samples were obtained for hormone measurements. Infusion of angiotensin II and phenylephrine increased mean systemic arterial pressure in a stepwise fashion. Both right atrial pressure and pulmonary capillary wedge pressure increased significantly during both doses of phenylephrine, but only the highest dose of angiotensin II significantly increased atrial pressures. Plasma levels of immunoreactive ANF increased parallel with the changes in right atrial pressure and pulmonary capillary wedge pressure, with significant increases occurring only at the highest dose of both pressors. Angiotensin II and aldosterone levels increased and renin activity decreased during infusion of angiotensin II. There were no significant changes in plasma levels of immunoreactive ANF during the control day. These studies demonstrate that infusion of vasopressors increases plasma levels of ANF, but only when the vasopressor effect is associated with significant increases in right atrial and pulmonary capillary wedge pressures. Atrial stretch is the most likely mediator of the increase in plasma levels of immunoreactive ANF during vasoconstriction.

Adult↗

PubMed1987

Atrial natriuretic hormone secretion in patients with renal failure.

To study the effects of volume overload and renal failure on plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH), we measured levels of this hormone in normal subjects, in patients with advanced chronic renal failure (CRF) with and without clinically evident volume overload, and in patients with end-stage renal disease (ESRD) treated with chronic hemodialysis. The levels were 13 +/- 2 pmol/l in normal volunteers, 77 +/- 24 pmol/l in patients with CRF without volume overload, and 219 +/- 50 pmol/l in patients with CRF and clinically evident volume overload (analysis of variance, p less than 0.001, alpha = 0.05 compared to normals). In patients with ESRD, the levels of IR-ANH were 145 +/- 46 pmol/l before dialysis and decreased to 87 +/- 31 after dialysis (p less than 0.025). No correlation was found between the decrease in IR-ANH levels and the decrease in weight during dialysis. A significant positive correlation was found between the IR-ANH levels and blood urea nitrogen in patients with CRF (r = 0.658, p less than 0.01). Volume overload appears to be the most important stimulatory factor for ANH secretion in renal failure patients but other mechanisms, especially a decrease in metabolic clearance, may also contribute to elevated plasma levels. The increased secretion of ANH in patients with renal failure may be an important adaptive response to volume overload and hypertension.

Adult↗

PubMed1987

Atrial natriuretic hormone is not elevated during dopamine induced natriuresis.

To evaluate the possibility that atrial natriuretic hormone (ANH) is involved in dopamine induced natriuresis and diuresis, we studied five normal male volunteers. Each was studied on two occasions. During the first two hours of each study, normal saline, 25 ml/hr, was infused. During the second two hours either normal saline, 25 ml/hr, or dopamine, 4 micrograms/kg/min, in normal saline, was infused. Dopamine infusion caused prominent and significant natriuresis and diuresis but plasma levels of immunoreactive ANH levels did not change. We conclude that the ANH is not involved in dopamine induced natriuresis and that dopaminergic stimulation is not responsible for ANH secretion.

Adult↗

PubMed1987

Epinephrine increases plasma immunoreactive atrial natriuretic hormone levels in humans.

Six normal human subjects each underwent sequential 80-min infusions of saline and epinephrine (EPI) at 0.55 and 2.75 micrograms X min-1 X m-2 to determine the role of EPI in the control of atrial natriuretic hormone (ANH) in humans. Plasma immunoreactive-ANH (IR-ANH) levels nearly doubled in response to the infusion of EPI at 0.55 microgram X min-1 X m-2 (P less than 0.05) and then plateaued; heart rate accelerated significantly (P less than 0.01) with increasing plasma EPI levels, whereas systolic blood pressure increased only with higher plasma EPI levels (P less than 0.05). To determine whether beta-adrenergic mechanisms mediate the EPI-induced increase in IR-ANH, six additional subjects each received infusions on two separate days of saline for 240 min and the beta-adrenergic antagonist propranolol followed by propranolol plus EPI at 2.75 micrograms X min-1 X min-2 each for 80 min. Neither saline nor propranolol plus EPI caused a significant increase in plasma IR-ANH. We conclude that EPI increases plasma IR-ANH through beta-adrenergic mechanisms in humans. beta-Adrenergic-mediated increases in plasma IR-ANH levels appear to be unrelated to changes in the heart rate.

Atrial Natriuretic Factor↗

PubMed1986

The scintigraphic localization of mineralocorticoid-producing adrenocortical carcinoma.

I-131-6 beta-iodomethylnorcholesterol (NP-59) was used to localize mineralocorticoid-secreting adrenocortical carcinomas in two patients and functioning metastases in a third patient studied after the removal of the primary tumor. The presence of sufficient NP-59 activity within these lesions for discernable imaging is unusual and would not have been expected based on previous experience with other functioning and nonfunctioning carcinomas of the adrenal cortex. These cases serve to illustrate the variable spectrum of iodocholesterol uptake into adrenocortical malignancies and suggest that scintigraphic studies, preoperatively for localization and postoperatively to confirm the presence of recurrence or metastases, might be useful to identify and characterize these rare neoplasms.

19-Iodocholesterol↗

PubMed1986

Plasma levels of immunoreactive atrial natriuretic factor increase during supraventricular tachycardia.

A significant diuretic and natriuretic response occurs during paroxysmal supraventricular tachycardia (SVT). Although the diuresis may be secondary to suppression of vasopressin secretion, the etiology of the natriuresis remains unexplained. To determine if atrial natriuretic factor (ANF) could contribute to the polyuric response during SVT, 10 patients were studied: five during spontaneous SVT and five during simulated SVT produced by rapid simultaneous atrial and ventricular pacing. Plasma immunoreactive ANF (IR-ANF) levels measured by radioimmunoassay were obtained at baseline (before and/or 24 to 48 hours after SVT) and after at least 15 minutes of SVT in all patients. During spontaneous and simulated SVT, IR-ANF was significantly elevated (mean +/- SE; 275 +/- 68 pmol/L) compared to baseline (28 +/- 7 pmol/L; p = 0.0036). Similar increases in IR-ANF were noted during both simulated and spontaneous SVT. To determine if this IR-ANF release was related to the increase in heart rate or the rise in right atrial pressure during SVT, IR-ANF levels were also measured in five patients with sinus tachycardia and in six patients with congestive heart failure. IR-ANF was significantly related to right atrial pressure (r = 0.93; p = 0.0009) but not to heart rate (r = 0.46). Thus, IR-ANF is elevated during SVT and may contribute to the natriuretic response. The stimulus to IR-ANF secretion during SVT appears to be related to the rise in right atrial pressure rather than to the increase in heart rate.

Adult↗

PubMed1986

Plasma levels of immunoreactive atrial natriuretic hormone in patients with diabetes mellitus.

In order to determine whether atrial natriuretic hormone (ANH) secretion is altered in diabetic patients with autonomic neuropathy, plasma immunoreactive ANH (IR-ANH) levels were measured in 23 patients with insulin-dependent diabetes mellitus, 12 of whom had definite cardiac autonomic neuropathy determined by noninvasive maneuvers. Levels were also measured in 31 healthy control subjects. Whereas only one of the 11 diabetics without cardiac autonomic neuropathy had elevated IR-ANH levels, four of the 12 diabetics with cardiac autonomic neuropathy had elevated IR-ANH levels (P = 0.03 compared to control subjects). 24-h urinary sodium excetion was not different among the groups. There was no significant correlation between IR-ANH levels and diabetes control and any of the parameters of autonomic nervous system activity nor between IR-ANH levels and plasma norepinephrine or epinephrine levels. Furthermore, no relationship was observed in the diabetic subjects between IR-ANH levels and left ventricular ejection fraction determined by radionuclide ventriculography. Thus, elevated IR-ANH levels occur with greater frequency in diabetic patients with autonomic neuropathy. These elevations do not appear to be due to alterations in dietary sodium intake or left ventricular dysfunction.

Adult↗

PubMed1986

The relationship between plasma levels of immunoreactive atrial natriuretic hormone and hemodynamic function in man.

To evaluate the relationship between plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH) and different hemodynamic parameters in man, we studied 34 patients undergoing right heart catheterization. Plasma levels of IR-ANH in blood samples withdrawn from the femoral vein (n = 28), right ventricle (n = 27), and left ventricle (n = 17) were determined by radioimmunoassay. Right atrial pressure, pulmonary arterial wedge pressure, heart rate, and mean arterial pressure were found to be independent and significant predictors of IR-ANH plasma levels. The closest correlations were between right atrial pressure and either right ventricular IR-ANH levels (r = .78, p greater than .001) or femoral vein IR-ANH levels (r = .52, p less than .006). Five patients with isolated left ventricular failure had elevated IR-ANH levels out of proportion to their right atrial pressure levels. Pulmonary arterial wedge pressure also correlated with right ventricular IR-ANH levels (r = .46, p less than .002) and with femoral vein IR-ANH levels (r = .58, p less than .002). A single patient with isolated right heart failure had markedly elevated IR-ANH levels despite normal pulmonary arterial wedge pressure. Right ventricular levels were twice femoral vein levels and were closely correlated (181 +/- 40 vs 90 +/- 20 pmol/liter; r = .90, p less than .001). Right ventricular and left ventricular levels were almost identical (155 +/- 46 vs 146 +/- 43 pmol/liter; r = .99, p less than .001). Patients with volume overload states had elevated IR-ANH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Immunoreactive atrial natriuretic hormone levels increase in deoxycorticosterone acetate-treated pigs.

Extensive evidence reported here and elsewhere indicates a hormonal role for atrial natriuretic factor. In the light of this evidence, it appears that atrial natriuretic hormone is a more appropriate term for these peptides than atrial natriuretic factor. Plasma levels of immunoreactive atrial natriuretic hormone were measured daily in seven pigs before and 1 week after subcutaneous implantation of deoxycorticosterone acetate (DOCA). Nine other animals underwent daily measurements of mean arterial pressure and central venous pressure during similar treatments. Plasma immunoreactive atrial natriuretic hormone levels rose progressively during the first 3 days after implantation, from a basal level of 60 +/- 9 pmol/L to a peak level of 159 +/- 21 pmol/L (p less than 0.05), and they remained significantly elevated throughout the rest of the 7-day observation period. In two animals that were restudied 6 weeks after DOCA implantation, plasma immunoreactive atrial natriuretic hormone had returned to preimplantation levels. The rise in plasma hormone levels after DOCA implantation closely paralleled the previously reported time course of mineralocorticoid escape. Whether atrial natriuretic hormone plays an important part in the escape phenomenon remains to be determined.

Animals↗

PubMed1986

Ectopic prolactinoma in a patient with hyperparathyroidism and abnormal sellar radiography.

In a patient with hyperparathyroidism and chronic renal failure due to polycystic kidney disease, a finding of destroyed sellar and parasellar structures and hyperprolactinemia suggested the diagnosis of invasive pituitary prolactinoma. At surgery no tumor was found, and pathological examination of the sphenoid bone revealed a parathyroid bone lesion (brown tumor) as well as ectopic prolactinoma in the clivus. This patient demonstrates that a tumor may develop in ectopic pituitary tissue. The combination of radiographically abnormal sellar structures with pituitary hormone hypersecretion should not be regarded as absolute proof of a pituitary adenoma.

Choristoma↗

PubMed1986

Acromegaly due to ectopic growth hormone (GH)-releasing hormone (GHRH) production: dynamic studies of GH and ectopic GHRH secretion.

Dynamic studies of GH and GH-releasing hormone (GHRH) secretion were performed in a man with a GHRH-producing carcinoid tumor and acromegaly. Insulin hypoglycemia stimulated and metoclopramide inhibited both GH and GHRH acutely. Bromocriptine suppressed GH both acutely and chronically without altering circulating GHRH levels and also blunted the GH response to exogenous GHRH. TRH acutely stimulated GH, but not GHRH, secretion, and iv bolus doses of synthetic GHRH-(1-40) stimulated GH release acutely. Somatostatin infusion decreased both GH and GHRH concentrations and blunted the GH responses to TRH and GHRH-(1-40). We conclude that prolonged exposure of the pituitary gland to high concentrations of GHRH is associated with chronic GH hypersecretion and may be accompanied by a preserved acute GH response to exogenous GHRH; a paradoxical response of GH to TRH may be mediated at the pituitary level, consequent to prolonged pituitary exposure to GHRH; bromocriptine suppression of GH in acromegaly is due to a direct pituitary effect of the drug; and somatostatin inhibits both ectopic GHRH secretion as well as GH responsiveness to GHRH in vivo. Since GH secretory responses in patients with somatotroph adenomas are similar to those in this patient, augmented GHRH secretion may play a role in development of the "classic" form of acromegaly.

Acromegaly↗

PubMed1985

Central serotonergic stimulation of aldosterone secretion.

Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.

5-Hydroxytryptophan↗

PubMed1985

Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake.

Adult↗

PubMed1985

Alpha-melanocyte-stimulating hormone stimulation of aldosterone secretion in hypophysectomized rats.

Intact and hypophysectomized male rats on low and high sodium diets were treated with sc infused ACTH and alpha MSH, and the levels of aldosterone and corticosterone were determined in truncal blood. Plasma aldosterone levels were lower in hypophysectomized animals on the low sodium diet than in intact animals on the low sodium diet. Alpha MSH (8 micrograms/day) restored plasma levels of aldosterone to normal in hypophysectomized rats on the low sodium diet. ACTH (6 micrograms/day) did not cause significant changes in plasma levels of aldosterone in hypophysectomized animals. ACTH restored plasma corticosterone to normal in hypophysectomized rats, whereas alpha MSH had no effect on corticosterone. Alpha MSH did not increase plasma aldosterone levels in intact rats. These data suggest that alpha MSH may be important in the regulation of aldosterone secretion in the rat and that zona glomerulosa responsiveness to alpha MSH in vivo is increased by hypophysectomy. The mechanisms of alpha MSH action on glomerulosa cells are different from those of ACTH.

Adrenocorticotropic Hormone↗

PubMed1985

Peripheral serotonin2 receptor blockade does not inhibit 5-hydroxytryptophan-induced aldosterone stimulation.

To assess the effects of serotonin receptor blockade on 5-hydroxytryptophan (5HTP)-induced aldosterone secretion, we studied six normal men using the serotonin antagonists ketanserin and methysergide. The subjects were studied on three separate occasions, and pretreatment with dexamethasone was given before each study. On two occasions, the pretreatment period also included administration of a serotonin antagonist, either ketanserin (120 mg/day) or methysergide (6 mg/day). On the day of study, the subjects were given a single oral 200-mg dose of 5HTP. Plasma levels of aldosterone increased significantly after 5HTP treatment compared to basal levels during each stage of the study. No significant difference in response in the three studies was found. We conclude that peripheral blockade of serotonin2 receptors does not abolish 5HTP-induced aldosterone stimulation, and that this stimulation is most likely mediated by central pathways.

5-Hydroxytryptophan↗

PubMed1984

Candidemia and sternal Candida albicans osteomyelitis in a patient with chronic lymphatic leukemia.

Sternal osteomyelitis caused by Candida albicans without previous surgery or trauma occurred in a patient with chronic lymphatic leukemia and recurrent skin cancer. The osteomyelitic process healed without antifungal treatment. Three weeks later, following a radical neck dissection, candidemia, without recurrence of the osteomyelitis, was diagnosed and treated successfully with intravenous amphotericin B and 5-fluorocytosin. The presentation of Candida osteomyelitis as a manifestation of disseminated candidiasis in immunocompromised hosts is discussed and the relevant literature is briefly reviewed.

Bone Marrow↗