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Biomedical subjects

D R Singer

Publications and source records attributed to D R Singer.

At least 55 records · Page 3Linked to original sources
PubMed1989

Immunoreactive N-terminal pro-atrial natriuretic peptide in human plasma: plasma levels and comparisons with alpha-human atrial natriuretic peptide in normal subjects, patients with essential hypertension, cardiac transplant and chronic renal failure.

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1-30). 2. Plasma levels of N-terminal ANP (means +/- SEM) were 235.3 +/- 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 +/- 36.3 pg/ml), in cardiac transplant recipients (1240.0 +/- 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 +/- 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10336.1 +/- 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of N-terminal ANP and alpha-human ANP (alpha-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P less than 0.05 in every case).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Potassium channel stimulation in normal subjects and in patients with essential hypertension: an acute study with cromakalim (BRL 34915).

We studied the acute effects of the potassium channel opener cromakalim on blood pressure, the renin-angiotensin-aldosterone system and renal function in eight patients with essential hypertension and five normal subjects. In the hypertensive patients, blood pressure decreased significantly from 2 to 6 h after treatment with cromakalim 1.5 mg compared with placebo, but was unchanged in the normotensives. In both groups, the heart rate and plasma renin activity increased after the administration of cromakalim compared with placebo; however, plasma aldosterone was unchanged. There was no significant change in urinary electrolyte excretion in either group; urine flow decreased after the administration of cromakalim compared with placebo in normal subjects, but not in patients with essential hypertension. Cromakalim lowers blood pressure acutely in patients with essential hypertension but not in normotensive subjects. This may be due to a greater reflex response in the normal subjects or to specific effects of cromakalim on mechanisms causing the high blood pressure.

Antihypertensive Agents↗
PubMed1989

Is renal lithium clearance altered in essential hypertension?

In order to assess whether enhanced fractional sodium reabsorption in the proximal tubule might contribute to the development of essential hypertension, we examined the relationship between arterial blood pressure and lithium clearance (CLi; used as an estimate of end-proximal fluid delivery) or fractional lithium excretion [FELi; measured using the clearances of creatinine and 51Cr ethylenediamine tetraacetic acid (EDTA) as estimates of glomerular filtration rate] in normal young males (n = 32) and in patients with essential hypertension (n = 44). In neither group was there evidence of a negative correlation between blood pressure and CLi or FELi. Mean values for CLi and FELi in a subgroup of hypertensive patients (n = 20) were almost identical to those in 20 normotensives matched for age, sex and race. These results provide no support for suggestions that a defect in proximal tubular sodium handling is an important factor in the development and/or maintenance of essential hypertension.

Adult↗
PubMed1989

Moderate sodium restriction, angiotensin converting enzyme inhibition, and thiazide diuretic in the management of essential hypertension.

Dietary sodium restriction alone is effective in lowering blood pressure in some, but not all, patients with essential hypertension. Homeostatic mechanisms, including activation of the renin-aldosterone system, may counteract the effects of sodium restriction. Angiotensin converting enzyme (ACE) inhibitors are also effective as sole therapy in many patients with essential hypertension, but may be less effective in those with low-renin hypertension. The combination of dietary sodium restriction with blockade of the renin system by an ACE inhibitor is a particularly effective way to improve blood pressure control. Addition of a thiazide diuretic will reduce pressure further.

Aldosterone↗
PubMed1989

Hormonal responses to gradual changes in dietary sodium intake in humans.

The effects of gradual (50 mmol/day) increases in dietary sodium intake from 10 to 350 mmol/day on plasma atrial natriuretic peptide (ANP), aldosterone, and plasma renin activity (PRA) were studied in six normal subjects. With the increases in sodium intake there was a progressive increase in urinary sodium from 12.2 +/- 4.4 to 314.8 +/- 31.4 mmol/24 h; plasma ANP increased gradually from 9.9 +/- 1.1 to 23.3 +/- 2.2 pg/ml, with the increases being closely associated with the changes in cumulative sodium balance. Plasma aldosterone decreased significantly from 2,519.7 +/- 147.4 pmol/l on the 10 mmol/day to 1,393.3 +/- 125.4 pmol/l when the sodium intake was increased to 50 mmol/day and decreased further to 251.6 +/- 78.7 pmol/l by the end of the study. The changes in PRA paralleled those in plasma aldosterone with the exception of no significant change in plasma PRA within 24 h of the initial increase in sodium intake. This marked sensitivity in the responses of both the ANP and the renin-aldosterone system to small increases in sodium intake clearly points to their importance in the renal adaptations to alterations in dietary sodium intake.

Adult↗
PubMed1988

Drug hypersensitivity causing granulomatous interstitial nephritis.

In association with treatment for pharyngitis, a 47-year-old white man developed a systemic illness with fever, myalgia, episcleritis, hemoptysis, pleurisy, eosinophilia, and renal impairment. Renal biopsy revealed granulomatous interstitial nephritis, which resolved due to no specific treatment other than withdrawing all medication. Both the severe systemic manifestations and spontaneous recovery are unusual in association with drug-induced granulomatous nephritis. The drugs that may have caused the reaction included dihydrocodeine, phenylpropanolamine, erythromycin, and amoxycillin. Although the latter three drugs have been previously implicated in the development of interstitial nephritis, there have been no previous reports of granulomatous interstitial nephritis with any of these drugs.

Amoxicillin↗
PubMed1988

Endocrine and renal response to water loading and water restriction in normal man.

1. Nine normal subjects (eight male, one female) on a fixed daily intake of 150 mmol of sodium and 80 mmol of potassium, were randomized to receive either 3 days of 1.0 litre total water intake/24 h (food + fluid) or 4 days of 6.8 litres total water intake/24 h, and were then crossed over after a 3 day control period (2.7 litres water/24 h). 2. During water restriction, urine volume fell from 1.94 litres/24 h to less than 1 litre/24 h by the first day and was 0.77 litre/24 h on the final day. Plasma atrial natriuretic peptide levels were unchanged from baseline despite a large increase in plasma vasopressin and plasma and urine osmolality. Urinary sodium was unaltered throughout, while urinary potassium was increased on the final 2 days of water restriction. 3. During water loading, urine volume increased from 1.85 litres/24 h to 5.44 litres/24 h on the first day and remained at approximately 6 litres/24 h for the final 3 days. Plasma atrial natriuretic peptide showed no change. Plasma vasopressin and plasma and urine osmolality were reduced. Urinary sodium and potassium output were unchanged from baseline. 4. These results suggest that changes in plasma atrial natriuretic peptide are unlikely to be involved in the normal homoeostatic response to changes in water balance in man.

Adolescent↗
PubMed1988

Plasma atrial natriuretic peptide in essential hypertension. Comparison with normotensive subjects and effects of changes in dietary sodium intake.

Plasma levels of atrial natriuretic peptide (ANP) in 106 patients with essential hypertension with a supine mean blood pressure (mean +/- SEM) of 128.9 +/- 1.6 mmHg and not on treatment were significantly higher than those in 47 normotensive subjects (supine mean blood pressure 93.9 +/- 1.2 mmHg) with mean values of 17.2 +/- 1.1 and 8.6 +/- 0.6 pg/ml, respectively (P less than 0.001). Similar results were found in a subgroup of 35 hypertensive patients identically matched in terms of age, sex, and race with 35 normotensive subjects. Plasma levels of ANP were correlated significantly with age in normotensive subjects and with age and blood pressure in the hypertensive patients. In 12 hypertensive patients studied on a low (10 mmol sodium/day), on their usual sodium intake (around 120 mmol sodium/24 hr) and on a high (350 mmol sodium/day) intake, plasma ANP increased approximately twofold by the fifth day of the high sodium intake, but there was no significant difference between the plasma levels on their usual sodium intake and those on the fifth day of the low sodium intake. Supine mean blood pressure on the patients' usual sodium intake was 119.3 +/- 2.7 mmHg and was reduced to 110.0 +/- 3 mmHg by the fifth day of the low sodium intake (P less than 0.005). However, there was no significant difference between the blood pressure levels on their usual and high sodium intake (118.3 +/- 3.0 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month's treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.

Captopril↗
PubMed1987

Infective complications of plasma exchange: a prospective study.

We examined the incidence and types of infective complications which occurred in 41 patients whose medical management included plasma exchange (PX) by intermittent cannulation; femoral, subclavian, or internal jugular catheter; or arteriovenous shunt. A high incidence of positive cultures from vascular access catheters was demonstrated. Of 23 patients for whom data were available, 13 had positive cultures, and results on 3 of these showed greater than 1 species. Gram-positive cocci were typically found. Of the 34 patients who received drug immunosuppression with PX, 1 patient developed severe shunt-site infection, and an additional 4 developed bacteremia. Seven patients were given PX alone, and none of these developed clinically significant infection; however, this difference in infection rate did not reach statistical significance. Clinically significant access-related infection remains an infrequent but potentially important hazard of therapeutic PX.

Adolescent↗
PubMed1987

Dissociation between plasma atrial natriuretic peptide levels and urinary sodium excretion after intravenous saline infusion in normal man.

1. Plasma immunoreactive atrial natriuretic peptide (ANP) and urinary sodium excretion were measured in six normal male subjects before, during and for 195 min after a 60 min infusion of 2 litres of saline (0.9% NaCl, 308 mmol of Na+). 2. During the saline infusion, there was a significant increase in plasma ANP and urinary sodium excretion and a significant decrease in plasma renin activity, aldosterone, albumin, creatinine and packed cell volume. 3. The maximal rise in mean plasma ANP occurred 15 min after stopping the infusion and the maximal rise in mean urinary sodium excretion in the collection period 30 min later. 4. Plasma ANP then decreased so that by the end of the study the level was the same as before the saline infusion. However, at this time, 195 min after the saline infusion was stopped, there was still a net positive sodium balance of 220 mmol and urinary sodium excretion remained significantly elevated. 5. Our results are compatible with the concept that increased ANP secretion may play a role in the immediate increase in sodium excretion after a saline load. However, they also suggest that other mechanisms may be more important for the longer term increase in sodium excretion.

Adult↗
PubMed1987

Does oral calcium supplementation lower high blood pressure? A double blind study.

Eighteen unselected patients with untreated mild to moderate essential hypertension, whose average supine blood pressure after 2 months' observation on no treatment was 154/103 mmHg, were entered into a double-blind randomized crossover study of 1 month's treatment with calcium lactate gluconate (40 mmol of elemental calcium/day) and treatment with placebo for a further month. Despite a significant increase in total plasma calcium (P less than 0.01) and in 24-h urinary excretion of calcium (P less than 0.025) while taking calcium lactate gluconate, there was no fall in blood pressure with calcium supplementation compared to treatment with placebo.

Adult↗
PubMed1987

Secretion of atrial natriuretic peptide from the heart in man.

Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava. These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.

Aged↗
PubMed1987

Captopril and nifedipine in combination for moderate to severe essential hypertension.

The effects of the addition of a calcium entry antagonist, nifedipine (20-mg tablet twice a day), to an angiotensin converting enzyme inhibitor, captopril (25 mg three times a day), and the addition of captopril to nifedipine were observed in two separate studies in patients with essential hypertension. After 4 weeks of captopril therapy alone, mean arterial pressure fell by 12 mm Hg, and with the addition of nifedipine to captopril for a further month, blood pressure fell by an additional 10 mm Hg. In a separate group of patients treated with the same doses, mean arterial pressure fell by 17 mm Hg with nifedipine treatment alone; when captopril was added to the nifedipine therapy for an additional month, mean arterial pressure fell by a further 11 mm Hg. These blood pressures were measured 2 hours after the last dose; however, there was less of a fall in blood pressure when it was measured 12 hours after the last dose. This study confirms that captopril and nifedipine have a marked additive effect on blood pressure in whichever order they are given, but it shows that the combination is relatively short-acting.

Adult↗