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Biomedical subjects

R G Dluhy

Publications and source records attributed to R G Dluhy.

At least 55 records · Page 3Linked to original sources
PubMed1986

Lymphocyte dysfunction in autoimmune oophoritis. Resumption of menses with corticosteroids.

In a 32-year-old woman with secondary amenorrhea and biopsy-proven oophoritis, the circulating T lymphocytes were examined utilizing monoclonal antibody L243 to the nonpolymorphic region of the Ia antigen. The percentage of peripheral T cells expressing the Ia "immune-associated' antigen was 5.6 percent (normal 3 percent or less). With corticosteroid therapy, the percentage decreased to 2 percent and menses resumed after secondary amenorrhea of two years' duration. Following cessation of steroid administration, the percentage of Ia-positive T cells rose to 7.0 percent and secondary amenorrhea redeveloped in the patient. After corticosteroid therapy was reinstituted, menses resumed and the percentage of Ia-positive T cells fell to normal. This report represents additional new evidence of immune dysfunction in patients with "autoimmune" oophoritis.

Adult↗
PubMed1985

Recurrent prolactinoma and meningioma following irradiation and bromocriptine treatment.

This case report describes a 45-year-old man with a massive extrasellar prolactinoma, treated initially with surgery and radiotherapy, who experienced a dramatic reduction of the bulk of his tumor but persistence and subsequent progression of an extrasellar portion while receiving long-term bromocriptine therapy, despite stable, suppressed prolactin levels. Although the residual tumor was thought to be adenomatous tissue unresponsive to bromocriptine, a meningioma was ultimately diagnosed. Because the meningioma may have been radiation-induced, clinicians are reminded to consider a second neoplasm in cases of apparent bromocriptine treatment failures, especially when prolactin levels are stable.

Adult↗
PubMed1985

beta-Endorphin stimulates plasma renin and aldosterone release in normal human subjects.

To determine the effect of beta-endorphin on the renin-angiotensin-aldosterone system, human synthetic beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min) was infused iv in normal subjects. Each dose was administered for 30 min, and a control infusion of 5% dextrose and water was given on another day. Ten subjects were studied recumbent and in balance while ingesting a 10-meq Na+ diet. Plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (F) were measured basally and every 30 min for 210 min. The increments in PRA and PA above basal significantly (P less than 0.05) increased (3.1 +/- 1.2 ng/ml X h and 12.2 +/- 5.3 ng/dl, respectively; P less than 0.05) at the end of the beta-endorphin infusion. beta-Endorphin also significantly (P less than 0.01) suppressed F levels. Since in the low salt study, beta-endorphin suppressed F release while stimulating renin secretion, an additional five subjects were pretreated with dexamethasone (0.5 mg every 6 h) and were studied in balance while ingesting a 200-meq Na+ diet to suppress the renin-angiotensin system. Significant (P less than 0.025) increments in PRA (2.1 +/- 0.7 ng/ml X h) and PA (4.1 +/- 1.7 ng/dl) levels above basal were again found during the sequential dose infusion of beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min). However, PA elevations were sustained for at least 120 min after the beta-endorphin infusion was stopped despite a drop in PRA 90 min earlier. In additional studies, an attempt was made to define the minimal effective dose of beta-endorphin by 60-min infusions (0.03, 0.1, and 0.3 micrograms/kg X min) in subjects on a 200-meq Na+ diet who were dexamethasone pretreated. The PRA and PA levels rose significantly (P less than 0.05) above basal at the 0.3 micrograms/kg X min dose, but not at the 0.03 or 0.1 micrograms/kg X min dosage levels. There were no changes in blood pressure or potassium during either the 10 or 200-meq Na+ studies. Thus, beta-endorphin stimulates aldosterone release in vivo. However, the underlying mechanisms are complex, since renin levels also increased. The data suggest that the early aldosterone rise may be secondary to an increase in renin release, but renin cannot account for the sustained postinfusion elevations of aldosterone.

Adult↗
PubMed1984

Ia-positive T lymphocytes in recently diagnosed idiopathic Addison's disease.

The Ia (DR, immune-associated) antigen is absent on normal circulating T lymphocytes, but present on activated T lymphocytes. Utilizing monoclonal antibody L243, the expression of this glycoprotein on circulating T lymphocytes was studied in five patients with recent-onset idiopathic Addison's disease, one patient with recent-onset adrenal hemorrhage, and nine patients with long-standing adrenal insufficiency (five with idiopathic Addison's disease and four after bilateral adrenalectomy for Cushing's disease). The patient with adrenal hemorrhage and the nine patients with long-standing adrenal insufficiency had percentages of circulating Ia-positive T cells within the normal range. All five patients with recent-onset idiopathic Addison's disease had an elevated percentage of circulating Ia-positive T cells (7 to 29 percent). The expression of Ia antigen on T cells in recent-onset idiopathic Addison's disease probably reflects immunologic activation, which may be of pathophysiologic importance.

Addison Disease↗
PubMed1984

Captopril enhances vascular and adrenal responsiveness to angiotensin II in essential hypertension.

The converting-enzyme inhibitor captopril (25-50 mg orally every 6 h for 66 h) was used to dissociate the circulating levels of angiotensin II (ANG II) from changes in sodium balance in 11 patients with normal renin essential hypertension on 10 mmol of sodium/day intake. Pressor, renal vascular and adrenal responses to graded infusions of ANG II (0.3, 1 and 3 pmol kg-1 min-1) were measured before and after captopril administration. Systemic vascular responses were assessed by measuring diastolic blood pressure (DBP), renovascular responses by measuring p-aminohippurate (PAH) clearance and adrenal responses by measuring plasma aldosterone. After receiving captopril for 66 h the hypertensive subjects showed a significantly (P less than 0.004) enhanced blood pressure response to the infused ANG II but not to noradrenaline when compared with the response before captopril. ANG II (3 pmol kg-1 min-1) also produced a significantly (P less than 0.03) greater reduction in PAH clearance after (-194 +/- 40 ml/min) compared with before (-104 +/- 15 ml/min) captopril. These results suggest that the responsiveness to ANG II in these two target tissues is determined by the circulating ANG II level. In the adrenal gland the aldosterone responses to ANG II also were significantly greater after (P less than 0.01) than before captopril (increment at 3 pmol kg-1 min-1: 660 +/- 88 vs 381 +/- 94 pmol/l). These results are in distinct contrast with the responses previously reported for normotensive subjects and support the hypothesis that the regulation of aldosterone secretion is altered in subjects with essential hypertension.

Adrenal Glands↗
PubMed1983

Dopaminergic blockade of the renin-angiotensin-aldosterone system: effect of high and low sodium intakes.

Recent investigations suggest that dopamine inhibits aldosterone secretion. To test the hypothesis that dopamine contributes to the reduced aldosterone secretion on a high sodium intake, eight normal subjects were studied in metabolic balance on both 200 and 10 mmol sodium diets. On each diet, the subjects received a constant 4 h intravenous infusion of the dopamine antagonist, metoclopramide (MCP). Although MCP significantly increased plasma aldosterone (PA) throughout the infusion on both diets, the maximum increment in PA was greater on the low (37 +/- 5 ng/dl) than on the high (14 +/- 4 ng/dl) sodium intake (P less than 0.02). The greater response on the low sodium intake could not be ascribed to changes in potassium, cortisol or ACTH. However, plasma renin activity (PRA) and angiotensin II (AII) levels were significantly (P less than 0.01) increased by MCP while on the low but not the high sodium intake. We conclude that the rise in PA while on a high sodium intake reflects dopaminergic antagonism by MCP directly at the level of the adrenal gland. On the low sodium intake, the enhanced PA response to MCP probably reflects both a direct adrenal effect and an indirect effect mediated via activation of the renin-angiotensin system.

Adult↗
PubMed1983

Defect in the sodium-modulated tissue responsiveness to angiotensin II in essential hypertension.

In normal subjects, dietary sodium intake modulates renovascular, adrenal, and pressor responses to infused angiotensin II (AII). To examine the hypothesis that this modulation is abnormal in some patients with essential hypertension, we studied 18 hypertensives and 9 normal subjects twice--during dietary sodium restriction and during loading. Paraaminohippurate (PAH) clearance was used to assess renal plasma flow. AII was infused in graded doses (0.3-3.0 ng/kg per min). Plasma aldosterone, cortisol, renin activity, AII, sodium, potassium, and PAH clearance were measured at the onset and end of each AII dose. During dietary sodium repletion, eight of the subjects with essential hypertension showed a normal renovascular response (greater than 125 ml/min per 1.73 m2) to AII infusion (3 ng/kg per min). The decrement in renal blood flow in these normal responders (NR) was 168 +/- 10, which was comparable to the range in normotensive subjects (206 +/- 25 ml/min per 1.73 m2). All of the remaining hypertensive patients, designated abnormal responders (AbR), had lower (less than 125) renal blood flow responses to the same dose of infused AII (mean decrement: 84 +/- 11 ml/min per 1.73 m2) compared with the NR and normotensive subjects. Renal blood flow responses to all AII doses were statistically greater on a high-vs.-low salt diet in the NR (P less than 0.001, chi-square) and normotensives (P = 0.004, chi-square) but sodium intake had no effect on this response in the AbR. Basal renal blood flow in NR increased significantly (P less than 0.001, paired t test) with dietary sodium repletion, from 491 +/- 36 (low salt) to 602 +/- 40 ml/min per 1.73 m2 (high salt), but was almost identical in the AbR on differing dietary sodium intakes (429 +/- 24 vs. 425 +/- 26 ml/min per 1.73 m2). The adrenal responses to sodium intake and infused AII also differed in the two subgroups. In the NR, the adrenal response to AII was significantly greater (P = 0.011, Wilcoxon signed rank test) after sodium restriction. In contrast, there was no significant difference in the aldosterone response to AII infusion between the low and high sodium diets in the AbR. Thus, a substantial subgroup of essential hypertensives has an abnormality in responsiveness to AII in two systems central to volume homeostasis: the kidney and adrenal. They fail to modulate their renal blood flow and aldosterone responses to AII with changes in dietary sodium intake. Moreover, basal renal blood flow does not increase appropriately with increased sodium intake. These abnormalities, which may be due to an increased local production of AII or a defect in the AII receptors in these three target tissues, could contribute to the elevated blood pressure.

Adolescent↗
PubMed1983

Dopaminergic modulation of aldosterone responsiveness to angiotensin II with changes in sodium intake.

The aldosterone response to infused angiotensin II (AII) is blunted by sodium (Na) loading. Since dopamine levels increase on a high Na diet and dopamine can inhibit aldosterone secretion, it is possible that dopamine mediates the blunted aldosterone secretion in this setting. To test this hypothesis, we assessed whether the dopamine antagonist, metoclopramide (MCP) would enhance the aldosterone response to infused AII. Six normal subjects received graded infusions of AII when they were in metabolic balance on diets containing both 10 and 200 meq Na/day (control infusions). The infusions were then repeated (on the same diets) during the administration of MCP (0.1 mg/kg iv bolus, then 0.05 mg/kg . h). During the control AII infusions, the aldosterone response to the highest dose of AII was significantly less on the 200 meq Na intake than on 10 meq (plasma aldosterone levels increased 17 +/- 5 vs. 30 +/- 8 ng/dl respectively; P less than 0.01). However, MCP administration eliminated this difference in aldosterone responsiveness by significantly enhancing (P less than 0.02) the response to infused AII during the 200 meq Na intake (plasma aldosterone increment of 25 +/- 9 ng/dl). This effect of MCP was limited to the adrenal response to AII: on a given Na intake, the mean blood pressure response to AII was similar both with and without concomitant MCP. These results suggest that dopamine may be an important regulator of the alterations in aldosterone responsiveness to AII that occur during changes in dietary sodium intake.

Adult↗
PubMed1983

beta-endorphin suppresses adrenocorticotropin and cortisol levels in normal human subjects.

To determine the effect of beta-endorphin on the pituitary-adrenal axis, human synthetic beta-endorphin was infused iv in 10 normal human subjects. Either beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg . min, each dose for 30 min) or a control (sham) infusion of 5% dextrose water was administered in a blind fashion in the same subjects on 2 successive days. Plasma ACTH and cortisol and serum human GH and PRL levels were measured 30 min before and then every 30 min for 210 min during and after both the beta-endorphin and control infusions. In all subjects, cortisol levels decreased below the basal level in response to the infusion of beta-endorphin. The threshold dose was 1.0 micrograms/kg . min, with the mean control cortisol level (12 +/- 2 micrograms/dl) declining significantly to 7 +/- 1 micrograms/dl (1.0 micrograms/kg . min) and 6 +/- 1 micrograms/dl (3.0 micrograms/kg . min; P less than 0.01). ACTH levels also were significantly lower than the control value (48 +/- 6 pg/ml) at the 1.0 microgram/kg . min dose (32 +/- 4 pg/ml; P less than 0.05). The decline in ACTH and cortisol levels was also significantly different from levels obtained during the control infusions (P = 0.001 and P = 0.01, respectively). The results are consistent with short feedback loop inhibition of pituitary ACTH release or suppression of hypothalamic corticotropin-releasing factor release by beta-endorphin.

Adrenocorticotropic Hormone↗
PubMed1983

Endogenous angiotensin II as a determinant of sodium-modulated changes in tissue responsiveness to angiotensin II in normal man.

Dietary sodium restriction reduces vascular smooth muscle, particularly renovascular, responsiveness to infused angiotensin II (AII), while the responsiveness of the adrenal and the AII-renin short feedback loop to AII is enhanced. To determine whether circulating AII mediates these changes in responsiveness, we studied 11 sodium-restricted and 9 sodium-replete normal subjects before and after 75 h of converting enzyme inhibitor pretreatment with MK421. All subjects received infusions of paraaminohippurate (PAH) to assess renal plasma flow during graded AII infusion (0.3-10 ng/kg X min) before and after MK421 administration. Plasma aldosterone, cortisol, PRA, AII, sodium, potassium, and PAH clearance were measured at the onset and end of each AII dose. In sodium-restricted subjects, preinfusion AII and aldosterone levels were significantly reduced, (P less than 0.001) to the range found in sodium-replete subjects, after 75 h of MK421 administration, whereas blood pressure and PAH responses to infused AII were significantly enhanced (P less than 0.01). Blood pressure and PAH responses to infused AII in sodium-replete subjects were not significantly modified by MK421 treatment, confirming that the drug effect was specific. In contrast, the plasma aldosterone increment and PRA decrement after AII infusion were similar before and after MK421 on both diets. Thus, sodium-modulated changes in PAH and blood pressure responsiveness to infused AII depend on circulating AII levels. However, circulating AII does not mediate sodium modulation of adrenal or PRA short-feedback loop responsiveness to infused AII. Two different mechanisms determine sodium modulation of tissue responsiveness to AII; in one, circulating AII via a receptor mechanism is the mediator, and in the other, some other factor(s) also linked to sodium intake must be responsible.

Adolescent↗
PubMed1982

Parallel adrenal and renal abnormalities in young patients with essential hypertension.

To determine whether the previously described abnormalities in adrenal secretion and renal blood flow in essential hypertension are associated, we examined the responses to the relevant systems in 18 patients with essential hypertension. Young patients, under 30 years of age, were studied to minimize the likelihood that the phenomena were secondary to long-standing hypertension. To achieve a wide span of sodium balance, studies were performed during a high (200 mEq) sodium intake, a restricted (10 mEg) sodium intake and a restricted sodium intake supplemented by a further short-term diuretic-induced volume deficit (furosemide, 180 to 300 mg, to reduce body weight by 1 to 1.5 kg). The indexes measured included cardiac output (indocyanine green indicator dilution), plasma volume (125 I albumin space), renal blood flow (radioxenon transit), plasma renin activity and aldosterone levels and aldosterone secretory rate. All of these variables, with the exception of blood pressure and total peripheral resistance, were within the normal range during the two diets. However, the aldosterone secretory response to diuretic-induced volume depletion on a low-sodium diet was clearly blunted in nine subjects. These nine subjects (abnormal responders) had a virtually absent aldosterone increment (23 +/- 34 micrograms per 24 hours) compared with the normal responders (502 %/- 70 micrograms per 24 hours). In addition, renal blood flow was significantly higher in these same nine subjects during both a high sodium intake (434 +/- 19 versus 342 +/- 26 ml/100 g per minute) and a restricted sodium intake /446 +/- 11 versus 285 +/- 39 ml/100 g per minute). Yet, there were no significant differences between these two groups in sodium or potassium balance, blood pressure, plasma volume, cardiac index or plasma renin activity during a high or low sodium intake. Normally, control of both aldosterone release by the adrenal and renal perfusion is dominated by angiotensin; an apparently blunted response of both systems suggests that there may be a generalized abnormality in the way angiotensin interacts with its target tissues in many young patients with essential hypertension.

Adrenal Glands↗
PubMed1982

Abnormal renin short feedback loop in essential hypertension is reversible with converting enzyme inhibition.

The suppression of renin release by angiotensin II (AII) (the so-called short feedback loop) is blunted in essential hypertension. To determine whether this abnormality is reversible, renin release was assessed in sodium-restricted essential hypertensives and normal controls: (a) during the administration of captopril for varying intervals and (b) following the infusion of graded doses of AII (0.3-3 ng/kg per min) before and after plasma levels of AII had been chronically reduced with captopril (25-50 mg every 6 h) for 70 h. In control subjects, the maximal increment above control in plasma renin activity (PRA) after a single dose of captopril (11.9+/-3 ng/ml per h) was significantly (P < 0.02) greater than in hypertensives (8.1+/-1.7 ng/ml per h) despite similar reductions in AII levels and significantly greater decrements in diastolic blood pressure in the hypertensives. When captopril was continued for 70 h, the PRA increments above base line in hypertensive subjects (11.4+/-2.9 ng/ml per h) rose to levels seen in the controls (11+/-2.6 ng/ml per h); there were no significant differences in the AII or diastolic blood pressure decrements between the two groups. Compared with normotensive subjects, AII failed to suppress renin release in hypertensive subjects despite significantly greater diastolic blood increments and comparable AII levels achieved at each AII dose. After captopril treatment, AII now produced significant declines in PRA in the hypertensives; moreover, comparing declines pre- and postcaptopril, greater PRA decrements were seen either at comparable rises in levels of AII or diastolic blood pressure. Finally, the suppression of PRA by AII postcaptopril in hypertensives was now indistinguishable from that seen in normal controls. Thus, the impaired regulation of renin by AII is reversible with prolonged captopril treatment, suggesting that this abnormality is not due to a fixed structural defect but to a reversible lesion.

Angiotensin II↗
PubMed1982

Cortisol suppression test in patients with elevated adrenocorticotropic hormone levels.

Increased adrenocorticotropic hormone (ACTH) levels after bilateral adrenalectomy could be secondary to a pituitary tumor, under replacement with cortisol, or an abnormality in the hypothalamic-pituitary-adrenal feedback loop. To distinguish between these possibilities, ACTH levels were measured before and after cortisol infusion (20 mg/h for 4 hours) in five groups: normal volunteers; patients with idiopathic adrenal insufficiency; and with bilateral adrenalectomy for Cushing's syndrome with no roentgenographic evidence of pituitary tumor, with pituitary tumors, and with equivocal roentgenographic studies (suspect pituitary tumors). Control ACTH levels in all groups of patients were higher than in normal volunteers but there was overlapping. Cortisol infusion suppressed ACTH in all subjects but the reductions in the last two groups were less than in the first three. The cortisol suppression test appears to be useful in determining whether increased ACTH level after adrenalectomy is due to a pituitary tumor.

Adrenalectomy↗
PubMed1981

Plasma angiotensin II concentration regulates vascular but not adrenal responsiveness to restriction of sodium intake in normal man.

1. Sodium restriction increases adrenal and decreases vascular sensitivity to angiotensin II (ANG II). These responses may be mediated either by the circulating level of ANG II or other mechanisms also modified by a change in sodium balance. To assess the importance of the ANG II level, captopril, an oral converting enzyme inhibitor, was used to lower the plasma ANG II level to the sodium-loaded range while maintaining subjects in low sodium balance. 2. Normal volunteer subjects received an infusion of ANG II in increasing doses in three states: high sodium intake, low sodium intake and low sodium intake after pretreatment with captopril. 3. Basal levels of ANG II on high-sodium diet and low-sodium diet plus captopril were similar. In the ANG II infusion studies the slope of the aldosterone--ANG II regression line on low sodium intake was significantly steeper than that on high sodium intake. After the addition of captopril the slope was not decreased, indicating that the endogenous ANG II concentration is not necessary to maintain adrenal sensitivity during sodium restriction. 4. In the ANG II infusion studies the slope of the mean blood pressure--ANG II regression line on high sodium intake was significantly steeper than that on low sodium intake. The addition of captopril to sodium-restricted subjects caused the slope of the regression relationship to increase significantly, consistent with an enhanced vascular responsiveness when endogenous ANG II levels were lowered. However, the slope on low sodium plus captopril did not increase to the level of subjects on a high-sodium diet, suggesting that factors in addition to the circulating ANG II level are also important in regulating the vascular responsiveness to ANG II.

Adrenal Glands↗
PubMed1981

Dietary chloride modifies renin release in normal humans.

The effect of high and low chloride diets on the responses of plasma renin activity (PRA), angiotensin II (ANG II), and aldosterone (Aldo) to upright posture was studied in the same normal subjects in balance on constant sodium intake. Diet 1 consisted of 10 meq Na/day (low Na) and either 50 or 150 meq Cl/day. Diet 2 consisted of 200 meq Na/day (high Na) and either 20 or 200 meq Cl/day. The mean recumbent PRA level on the high Na-high Cl diet tended to be lower than on the high Na-low Cl diet but was not significantly different. However, the absolute peak upright PRA levels, 8.8 +/- 1.0 vs. 4.4 +/- 0.8 ng . ml-1 . h-1, and the incremental difference (delta PRA) between recumbent and peak upright PRA levels, 5.5 +/- 0.8 vs. 2.2 +/- 0.5 ng . ml-1 . h-1, were significantly less on the high Na-high Cl diet compared with the high Na-low Cl diet. Similar significant changes were seen in ANG II and Aldo levels. However, there were no significant changes in PRA, ANG II, and Aldo responses to upright posture on the low Na diet when the dietary Cl was varied. It is concluded that dietary Cl is another factor modifying renin release. However, Cl is probably less important than Na because Cl-induced changes in PRA were not seen in the low salt state.

Adult↗
PubMed1981

Alterations in aldosterone biosynthesis in essential hypertensives.

We studied hypertensives with decreased adrenal responsiveness to infused angiotensin II (AII) to assess their responsiveness to other aldosterone secretagogues, ACTH and potassium, which are thought to stimulate aldosterone synthesis in sites different from one another and from AII. All subjects, following sodium restriction, received an infusion of AII in increasing doses (0.1-3 ng/kg per min). The increment in aldosterone between control and the highest infusion dose divided by the increment in plasma AII was used as the index of adrenal responsiveness. All normotensive controls (NC) had a ratio greater than 0.5. Hypertensives with a normal ratio were designated normal responders (NR) and those with a lower ratio were abnormal responders (AbR). The slope of the regression line between aldosterone and AII was significantly less for the AbR (0.02 +/- 0.04) than for the NR (1.20 +/- 0.02, P less than 0.001) and the NC (1.00 +/- 0.03, P less than 0.001) groups. During infusion of cosyntropin in increasing doses (0.05-1.5 mIU/kg per 30 min), the aldosterone response of the AbR was significantly less than that of the NR (P less than 0.016) or the NC (P less than 0.05) groups. Similarly, after infusion of potassium (0.33 mEq/min), the increment in aldosterone in the AbR group (7.6 +/- 2.2 ng/dl) was significantly less than that in the NR (14.2 +/- 2.5 ng/dl, P less than 0.05) and the NC (18 +/- 5 ng/dl, P less than 0.05) groups. Thus hypertensives with decreased aldosterone responsiveness to infused AII also had decreased responsiveness to infused ACTH and potassium, suggesting that their defect lies in the intracellular aldosterone biosynthetic pathway.

Adrenocorticotropic Hormone↗