Biomedical subjects

P R Conlin

Publications and source records attributed to P R Conlin.

43 records · Page 3Linked to original sources

PubMed1990

Rate and concentration dependence of parathyroid hormone dynamics during stepwise changes in serum ionized calcium in normal humans.

The relationship between circulating levels of PTH and the concentration and rate of change of ionized calcium (CaI) was studied in normal humans by measuring intact PTH during stepwise changes in CaI. Six normal subjects received two different citrate infusion protocols that produced stepwise decreases in CaI; one infusion produced a rapid decrement in calcium, and a second infusion produced a slower approach to the same (approximately 0.05 mmol/L) decline in calcium for each of four steps. The rapid decline in CaI resulted in a more marked increase in levels of PTH, which subsequently fell to levels similar to those with the slower infusion. For similar absolute changes in calcium, the mean maximal increment in PTH levels was significantly greater with the rapid infusion (36.4 +/- 3.1 ng/L) than with the slower infusion (19.4 +/- 2.1 ng/L; P = 0.001). Six additional subjects received infusions of citrate and calcium in a stepwise manner to induce either decreases or increases in CaI, followed by a return to baseline. During induced hypocalcemia, when calcium was changing slowly or not at all (i.e. at the plateau of each calcium change) PTH levels were not affected by the direction of change in calcium and appeared to be dependent upon the calcium concentration per se. At elevated levels of CaI, the PTH response to a stepwise decrease in calcium was blunted over that seen when CaI declined to or below baseline. Thus, the relationship between CaI and levels of PTH is dependent not only on the concentration but also on the rate of change in calcium, particularly during induced hypocalcemia; different rates of change in calcium result in different inverse sigmoidal relationships between PTH and CaI. When calcium is changing slowly or not at all, however, PTH levels appear to be dependent on the calcium concentration per se and are not affected by the previous direction or rate of change. Therefore, the role of the extracellular calcium concentration in the control of PTH secretion is part of more complex and dynamic regulatory mechanisms.

Adult↗

PubMed1989

The role of dopamine in nonmodulating hypertension.

Dopamine may exert a tonic inhibitory effect on aldosterone secretion and enhance renal sodium excretion. Nonmodulating hypertension in part is characterized by decreased aldosterone secretion in response to angiotensin II (AII) as well as a decreased natriuretic response to a saline load. This study assesses whether an abnormally increased dopaminergic inhibition of aldosterone secretion underlies the adrenal defect in nonmodulating hypertension and whether abnormalities of renal dopamine formation contribute to sodium retention. We measured the plasma dopamine concentration in 39 patients with nonmodulating hypertension and in 32 patients with normal modulation on a 10-meq sodium intake. Dopamine levels were significantly higher (P less than 0.05) in nonmodulators. The aldosterone response to AII (3 ng/kg.min) was assessed before and during administration of the dopamine antagonist metoclopramide in 13 patients. Metoclopramide did not change the adrenal response to AII in either hypertensive subgroup. In 12 normal subjects mean urinary dopamine levels were higher in a sodium-replete state (200-mmol intake) than in a low sodium state (10-mmol intake; 1.68 +/- 0.28 vs. 0.92 +/- 0.22 mumol/day; P less than 0.01) as expected. Modulators demonstrated this same effect, while nonmodulators did not [modulators, 3.66 +/- 0.82 and 1.37 +/- 0.14 mumol/day; nonmodulators, 1.33 +/- 0.28 and 1.68 +/- 0.90 mumol/day; P less than 0.02]. The sodium-retaining tendency of nonmodulators may reflect, at least in part, reduced intrarenal dopamine production in the sodium-replete state, but the adrenal defect in aldosterone release in nonmodulators is not mediated by excess dopaminergic inhibition of aldosterone secretion.

Adrenal Glands↗

PubMed1989

Hysteresis in the relationship between serum ionized calcium and intact parathyroid hormone during recovery from induced hyper- and hypocalcemia in normal humans.

We have used an immunoradiometric assay for intact PTH in conjunction with calcium and citrate infusions to study whether levels of intact PTH are responsive to reversal of the direction of change in ionized calcium in normal humans. Eleven normal subjects received graded infusions of citrate or calcium on separate days to produce linear rates of decrease or increase in calcium. After discontinuation of the infusions, the return of calcium toward baseline was followed. Six subjects were given an infusion of citrate after the calcium infusion to speed the recovery of calcium toward baseline. Citrate-induced hypocalcemia produced a rise in serum PTH levels from 28.1 +/- 3.6 to 69.4 +/- 4.8 ng/L as calcium fell from 1.26 +/- 0.01 to 1.06 +/- 0.02 mmol/L. As calcium returned toward baseline, PTH levels fell dramatically, reaching levels indistinguishable from baseline despite persistent hypocalcemia. Slopes of regression lines defining the PTH-calcium relationships during decreasing and increasing calcium levels were significantly different. Those subjects receiving a calcium infusion alone showed a prompt suppression of PTH levels. As calcium returned toward baseline after the infusion, a modest decline in calcium produced no significant change in the PTH-calcium relationship. When citrate was used to return calcium to baseline, PTH levels rose from 7.8 +/- 2.0 to 55.0 +/- 6.8 ng/L as calcium fell from 1.42 +/- 0.02 to 1.26 +/- 0.02 mmol/L and defined a regression relationship significantly different from the period of increasing calcium. Thus, a hysteretic relationship between ionized calcium and levels of intact PTH can be induced in normal humans by reversing the direction of change in calcium. Therefore, the role played by calcium concentration per se in controlling PTH secretion may be part of more complex and dynamic regulatory mechanisms.

Adult↗

PubMed1989

Adrenocorticotropin stimulation of aldosterone: prolonged continuous versus pulsatile infusion.

Continuous iv administration of ACTH leads to a sustained stimulation of cortisol but a transient stimulation of aldosterone followed by a decline to prestimulation levels by 72 h. Since CRH and ACTH are released in a pulsatile pattern in man, this study sought to investigate whether pulsatile administration of alpha-cosyntropin-(1-24) would lead to the maintenance of aldosterone stimulation over time. Eight normal male subjects on a 10-meq sodium, 100-meq potassium diet received both a continuous and a pulsatile (0.33 U ACTH/pulse over 15 min, pulsed every 2 h) infusion of cosyntropin (4 U/24 h) for 48 h (n = 4) or 72 h (n = 4). Aldosterone and cortisol were sampled every 6 h, and PRA and angiotensin-II every 24 h. Continuous infusion led to a stimulation of aldosterone followed by a progressive decline to preinfusion levels by 72 h [preinfusion 29 +/- 5 ng/dL (810 +/- 139 pmol/L); 72 h, 38 +/- 10 ng/dL (1054 +/- 277 pmol/L); P = 0.40]. Pulsatile infusion led to a stimulation of aldosterone which was maintained up to 72 h [preinfusion 33 +/- 7 ng/dL (915 +/- 194 pmol/L); 72 h, 85 +/- 13 ng/dL (2358 +/- 361 pmol/L); P less than 0.05]. Regression analysis of aldosterone (y) over time (x) from the peak level at 18 h for the continuous infusion showed a significant negative relation (r = 0.63; P = 0.001), indicating a progressive decline in aldosterone. However, for the pulsatile infusion, there was no relation (r = 0.02; P = 0.85), indicating maintenance of aldosterone levels. There were no significant differences in sodium, potassium, PRA, angiotensin-II, or cortisol between infusions to explain these differences in aldosterone levels. Therefore, pulsatile infusion of cosyntropin maintains aldosterone secretion over time.

Adrenocorticotropic Hormone↗

PubMed1988

Relationship between the concentration and rate of change of calcium and serum intact parathyroid hormone levels in normal humans.

We employed variable rates of infusion of EDTA or calcium gluconate to examine the relationships between the concentration and rate of change of serum total and plasma ionized calcium and serum immunoreactive intact PTH concentrations in normal subjects. Use of a sensitive immunoradiometric assay specific for PTH-(1-84) made it possible to determine the full range of PTH responses to perturbations in the extracellular calcium concentration. By progressively increasing the rate of administration of calcium gluconate or EDTA during rapid or slow infusions, linear rates of change in the serum calcium concentration were achieved in eight men. The slopes were 2-fold greater during the rapid infusions. Both the calcium infusions decreased serum PTH-(1-84) levels from a mean of 23.2 +/- 2.0 (+/- SE) to 6.4 +/- 1.0 and 5.6 +/- 1.0 ng/L for the rapid and slow infusions, respectively, with no obvious rate dependence. The rapid or slow EDTA infusions increased serum PTH levels to the same maximal extent (95.0 +/- 20.2 and 99.9 +/- 14.5 ng/L, respectively), also with no significant rate dependence. Thus, there was no effect of the rate of change of calcium on the PTH response, which was reflected in similar inverse sigmoidal relationships between PTH and serum total and plasma ionized calcium when the data for the slow and rapid infusions were pooled separately. Similar sigmoidal curves were found in normal women. These data suggest the feasibility of using calcium and EDTA infusions combined with an intact PTH assay to define the relationships between circulating levels of PTH-(1-84) and calcium in states of normal and deranged parathyroid physiology.

Adult↗

PubMedDate not supplied

The dietary approaches to stop hypertension (DASH) clinical trial: implications for lifestyle modifications in the treatment of hypertensive patients.

Lifestyle modifications, such as weight loss, sodium restriction, and limiting alcohol consumption, are important components of the initial treatment of hypertensive patients. The Dietary Approaches to Stop Hypertension (DASH) study investigated the effects of dietary patterns on blood pressure in individuals with diastolic blood pressure between 80-95 mmHg. Two different dietary patterns were tested in this feeding study. A diet enriched in fruits and vegetables and a diet enriched in fruits, vegetables, and low-fat dairy products and low in total and saturated fat (combination diet) were compared with a control diet. Dietary intake was adjusted so that participants did not lose weight, and all study diets had comparable sodium intake (approximately 3 grams/day). All meals were provided for 459 participants for an 11-week period. Those randomized to the combination diet (n = 151) had a significant change in systolic (-5.5 mmHg; p < 0.001) and diastolic blood pressure (-3.0 mmHg; p < 0.001) after subtracting the response to the control diet (n = 154). The fruits-and-vegetables diet (n = 154) produced a significant but lesser decrease in blood pressure (systolic, -2.8 mmHg; p < 0.001 and diastolic, -1.1 mmHg; p = 0.07). Hypertensive individuals and African Americans had particularly favorable responses with blood pressure reductions, which were significantly greater than other subgroups. The combination diet was well-accepted and adherence to the diet was high (>90%) for all participants. The DASH combination diet is an effective lifestyle modification for lowering blood pressure in patients with high-normal or Stage 1 hypertension.

Adult↗

PubMedDate not supplied

Benefits of angiotensin converting enzyme inhibition and angiotensin II receptor antagonists in hypertension.

It is through blood pressure lowering that reductions in cardiovascular morbidity and mortality are achieved. The treatment of hypertension patients should also focus on prevention and management of cardiovascular complications, not merely on achieving a target level of blood pressure. In making treatment decisions it is appropriate to assess patients for the presence or absence of risk factors and/or clinical cardiovascular disease. Clinicians should strive to use the least intrusive means possible to achieve goal blood pressure and the treatment regiment should be individualized for each patient. The review has illustrated specific clinical conditions where the use of an hypertensive agent that inhibits the renin-angiotensin system may offer added benefit to the patient while producing the needed anti-hypertensive effects.

Angiotensin Receptor Antagonists↗