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Biomedical subjects

P Boer

Publications and source records attributed to P Boer.

At least 73 records · Page 4Linked to original sources

Enhanced natriuretic effect of atrial natriuretic factor during mineralocorticoid escape in humans.

We examined the question of whether escape from the sodium-retaining effect of mineralocorticoid involves an increased natriuretic effect of atrial natriuretic factor (ANF). Seven healthy volunteers taking a 170 mmol Na/100 mmol K diet received an intravenous bolus (25 micrograms) followed by a 1-hour infusion (0.02 micrograms/kg/min) of ANF (human ANF-[99-126]) before and after 10 days of 9-fludrocortisone acetate, 0.5 mg b.i.d. Escape was accompanied by an increase in body weight (from 72.2 +/- 12.9 to 74.0 +/- 12.6 kg; p less than 0.05), mean arterial pressure (from 95 +/- 4 to 109 +/- 3 mm Hg; p less than 0.01), plasma ANF (from 9 +/- 2 to 24 +/- 4 pmol/L; p less than 0.01), and inulin clearance (from 124 +/- 9 to 137 +/- 7 ml/min; p less than 0.05). Indexes for renal sodium handling (lithium and free water clearance) were compatible with a decreased "proximal" and an increased "distal" tubular reabsorption fraction. ANF infusion raised inulin clearance comparably before and after escape to 138 +/- 10 and 152 +/- 7 ml/min, respectively, but the natriuretic effect was much larger (p less than 0.05) after escape (from 366 +/- 34 to 1294 +/- 278 mumol/min) than before (from 248 +/- 48 to 630 +/- 124 mumol/min). Indexes for tubular reabsorption were consistent with greater suppression of both "proximal" and "distal" tubular sodium reabsorption by ANF after versus before mineralocorticoid expansion. These results indicate that escape is accompanied not only by a rise in plasma ANF but also by potentiation of the natriuretic effect of ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An inexpensive method for sensitive enzymatic determination of oxalate in urine and plasma.

In this simple, sensitive, and rapid enzymatic method for the determination of oxalate in urine or plasma, oxalate oxidase (EC 1.2.3.4) prepared from barley seedlings is used to convert oxalate to carbon dioxide and hydrogen peroxide, which is determined photometrically at 600 nm, with use of horseradish peroxidase, by oxidative coupling of 3-methyl-2-benzothiazoline hydrazine with N,N-dimethylaniline. Plasma is pre-treated by ultrafiltration and co-precipitation of oxalate with calcium sulfate and ethanol, urine by dilution and reversed-phase chromatography on C18 columns. Analytical recovery for urine is 99 +/- 2%, for plasma 92 +/- 3%. The normal range for urinary excretion is 0.10 to 0.56 mmol/24 h, and for the concentration in plasma 0.4 to 3.7 mumol/L. There were no significant sex-related differences in urinary excretion or plasma concentration. Our within- and between-assay coefficients of variation were, respectively, less than 3.4% and less than 6.0% for urine, and less than 1.5% and less than 4.3% for plasma.

Ascorbate Oxidase↗

Lisinopril in hypertensive patients with and without renal failure.

Lisinopril (MK521), a lysine analogue of enalaprilic acid, the bioactive metabolite of enalapril, has a longer half-life than enalaprilic acid, and is excreted unchanged in the urine. Its kinetic profile and antihypertensive and hormonal effects have been investigated in an open study in 3 groups each of 6 hypertensive patients, with normal, moderate and severe impairment of renal function. Serum drug level, blood pressure, converting enzyme activity (CEA), plasma renin activity (PRA), aldosterone concentration (PAC), and serum potassium and creatinine were measured during 1 week following a single oral dose and subsequently following 8 daily doses of 5 mg lisinopril. Accumulation of lisinopril was found in the severe renal failure group. CEA was suppressed to less than 10% of its initial value from 4 to 24 h after the initial dose in all three groups, and the suppression was more marked and lasted longer in patients with severe renal failure. An inverse correlation was found in all patients between log serum lisinopril concentration and log CEA. Lisinopril lowered blood pressure in all three groups over 24 h. PRA rose and PAC fell similarly in the groups. Serum potassium increased in the renal failure groups and creatinine remained unchanged in all groups. Thus, when lisinopril 5 mg is given daily to patients with severe renal failure it may accumulate. The high serum lisinopril concentration does not cause an excessive antihypertensive effect. In patients with severe renal failure, adjustment of the dose or the dosing frequency to the degree of renal failure is recommended to avoid administration of doses in excess of those required to achieve adequate inhibition of converting enzyme.

Adult↗

Correction of hypokalemia in Bartter's syndrome by enalapril.

Seven patients with Bartter's syndrome were investigated before and after 3 months' treatment by enalapril. Serum potassium rose from 2.4 +/- 0.5 to 3.9 +/- 0.6 mmol/L. In all patients, serum magnesium rose and bicarbonate fell. Hormonal changes were as suspected: a further stimulation of renin and a decline in aldosterone. The BP sensitivity to angiotensin II normalized in the five patients in whom the test was performed. Clearance studies during maximal water diuresis, performed in four patients, were compatible with a high proximal fractional tubular sodium reabsorption and a relatively low distal fractional sodium reabsorption. Fractional free water excretion after furosemide was also low, confirming the concept of a primary sodium reabsorption defect in the furosemide-insensitive part of the nephron in Bartter's syndrome. The only consistent change after enalapril was a further decline in distal fractional sodium reabsorption. Initiation of therapy produced a BP fall in each subject. Clinical important hypotension associated with oliguria was seen twice, but these reactions were short-lasting. The BP rose to pretreatment values within 72 hours, despite continuation of converting-enzyme inhibition. Renal function recovered, though a moderate fall in function persisted. No other side effects were noticed. We conclude that converting-enzyme inhibition improves the potassium metabolism of patients with Bartter's syndrome, without ameliorating the abnormal renal sodium handling.

Adult↗

Effect of high-dose aldosterone infusions on renal electrolyte excretion in patients with renal insufficiency.

We investigated the effect of aldosterone infusion (0.5 mg/h for 6 h) on electrolyte excretion in 11 patients with severe renal insufficiency (creatinine clearance 6-20 ml/min), with normal or elevated serum potassium levels and a wide range of plasma aldosterone levels, and compared the data with those obtained in 7 healthy subjects. The studies were done under conditions of fixed sodium and potassium intake. In the normal subjects, aldosterone infusion caused a significant rise in potassium excretion and a significant fall in sodium and chloride excretion (p less than 0.01). In 1 patient with a high plasma aldosterone, virtually no response occurred to the aldosterone infusion. In the others, the increase in potassium excretion and reduction in chloride excretion were not different from the changes observed in the normals, but the fall in sodium excretion was less due to a higher urinary sodium before infusion in the normals (p less than 0.05). Fractional electrolyte excretions as well as the changes in fractional excretion by aldosterone were larger in the patients (p less than 0.05). Apparently, the renal tubules of patients with chronic renal failure are still responsive to maximal stimulation with aldosterone, in spite of their basically elevated fractional electrolyte output. These findings suggest that, with some exceptions, the hyperkalemia in patients with chronic renal failure is in part due to relative hypoaldosteronism.

Adult↗

Renin and blood volume in chronic renal failure: a comparison with essential hypertension.

Sixty-five patients with advanced chronic renal failure (CRF) but a normal extracellular fluid volume (ECFV), including 31 dialysis patients, were studied. Plasma volume, blood volume (BV), plasma renin activity (PRA), and mean arterial pressure were measured to examine whether hypertension (when present) is renin dependent, or whether it is related to an abnormal distribution of ECFV between the intra- and extravascular spaces. PRA was higher in dialysis than nondialysis patients, but the incidence of hypertension was the same. In both groups hypertensive patients with normal PRA and normotensive patients with elevated PRA were present. The patients were compared to 65 patients with essential hypertension (EH) and 56 normals. The BV and BV-to-interstitial fluid volume ratio were similar in these groups. We found no decreased BV in patients with EH as has previously been reported by others, possibly because we used an appropriate normalization index and matched control groups. In sum, hypertension in CRF patients with a normal ECFV cannot always be explained by elevated renin levels. In this respect, CRF patients resemble patients with EH. An abnormal extracellular fluid distribution does not seem to be involved in the maintenance of hypertension.

Blood Pressure↗

Changes in haemodynamics and body fluid volume due to enalapril in patients with essential hypertension on chronic diuretic therapy.

In 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment, the effect of 2 weeks of additional therapy with the converting enzyme inhibitor (CEI) enalapril on blood pressure and body fluid volumes has been evaluated. The objective was to examine the influence of a diuretic-stimulated renin-angiotensin-aldosterone system (RAAS) on haemodynamics and body fluid volume. Mean arterial pressure (MAP -21%), total peripheral resistance index (TPRI -22%) and plasma aldosterone concentration (PAC -39%) were decreased, and plasma renin activity (PRA 660%) was increased. The average heart rate (HR), cardiac index (CI), plasma volume (PV), blood volume (BV), extracellular fluid volume (ECFV) and body weight (BW) remained unchanged. A negative correlation was found between the per cent changes in ECFV and PAC. Thus, body fluid volumes during chronic diuretic treatment are well preserved even when the RAAS with its sodium retaining properties is suppressed by CEI. Possible mechanisms are a volume (not angiotensin II) - dependent stimulation of aldosterone and a fall in blood pressure.

Body Fluids↗

Comparison of enalapril and propranolol in essential hypertension.

In 40 patients with essential hypertension, enalapril was compared with propranolol as an antihypertensive agent in a double-blind study. The patients were randomly given either enalapril 5-10-20 mg bid or propranolol 40-80-120 mg bid in a treatment consisting of step-by-step increases in dosage. When the diastolic blood pressure remained greater than 90 mm Hg on the highest dosage, hydrochlorothiazide was added. Both enalapril and propranolol reduced blood pressure, although the patients tended to achieve lower blood pressures while on enalapril. More patients on propranolol required additional diuretic therapy than patients on enalapril. Propranolol reduced heart rate; with enalapril there were no changes in heart rate. Both drugs increased serum potassium and urea. Plasma renin substrate was reduced by enalapril, but raised by propranolol. Enalapril increased plasma renin activity and angiotensin I, while propranolol reduced both. Converting enzyme activity was lowered with enalapril but was unchanged with propranolol. Both drugs reduced angiotensin II. Plasma aldosterone concentration was more suppressed with propranolol than with enalapril.

Adult↗

Adaptation to chronic potassium loading in normal man.

To analyze factors involved in the maintenance of potassium balance during increased intake, 6 healthy males were studied on a normal (80 mEq) and high (300 mEq) potassium diet. After 18 days of potassium-rich diet, urinary potassium excretion had increased from 50 +/- 12 to 233 +/- 45 mEq/day. Plasma renin activity and body weight were unchanged, serum potassium and plasma aldosterone somewhat increased, and the ratio of plasma aldosterone to renin activity consistently elevated. Acetazolamide injection (1 g i.v.) increased sodium and potassium excretion rates equally on the two diets indicating that a sudden increase in distal solute delivery was not handled differently after potassium loading. The reaction to a high dose of aldosterone (1 mg i.v. followed by 0.5 mg/h infusion) in terms of sodium retention and potassium excretion was also comparable, indicating no altered sensitivity to aldosterone after adaptation to the potassium-rich diet. By contrast, the aldosterone antagonist canrenoate (100 mg i.v.) acutely raised NaCl excretion without changing the potassium excretion during the high potassium diet, but did not affect NaCl excretion during the normal diet. Subsequent oral administration of spironolactone for 5 days (200 mg daily) caused a more negative sodium balance associated with more weight loss and rise in renin activity during the potassium rich diet. Surprisingly we noticed no fall in renal potassium excretion in this period, but mean serum potassium was raised by 0.3-0.4 mEq/l at the end. These results suggest that adaptation of a healthy subject to a potassium-rich diet does not involve intrinsic changes of the distal tubule, but a shift of sodium reabsorption from a proximal to a distal (aldosterone-sensitive) nephron level.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

Transthoracic electrical impedance as an index of extracellular fluid volume in man.

Findings in 76 subjects without cardiac failure were analyzed to detect relationships between observed changes in transthoracic electrical impedance (TEI) and total body extracellular fluid volume (ECFV) during various manoeuvres and between absolute TEI and ECFV values. TEI was normalized to electrode distance (Z0/delta el) and ECFV to lean body mass (ECFV/LBM). A distinct relation was found between percent changes of TEI and ECFV (r = -0.76, p less than 0.0001) and between absolute Z0/delta el and ECFV/LBM values (r = -0.66, p less than 0.0001 for men; r = -0.61, p less than 0.0001 for women). It is concluded that in the same subject a change in TEI is possibly a sensitive index for a change in ECFV and that a single measurement of TEI, normalized to electrode distance, gives information about the state of hydration (ECFV) of patients without cardiac failure.

Adult↗

Sodium potassium ATPase activity in human rectal mucosa with and without renal insufficiency.

Studies in rats have shown that fecal potassium excretion and colonic mucosa Na-K-ATPase activity are elevated during dietary potassium loading and in chronic renal insufficiency. We studied Na-K-ATPase activity in human rectal mucosa in normal subjects as well as in patients with chronic renal insufficiency (creatinine clearance 2 to 72 mL/min). In normals, Na-K-ATPase activity was 4.34 +/- 0.83 mumol P/mg protein. After 2 weeks on a potassium intake of 300 mmol/d the mean activity did not differ significantly from the control value (2.49 +/- 1.30). In none of the patients with renal failure was Na-K-ATPase activity beyond the range found in the normal subjects, irrespective of serum potassium; the mean activity was 3.50 +/- 0.85. Like others, however, we found a two-fold increase in Na-K-ATPase activity in potassium loaded rats. Possible explanations for these differences are discussed.

Adenosine Triphosphatases↗

Apparently high plasma angiotensin II levels in patients with essential hypertension treated by converting enzyme inhibition.

Plasma angiotensin I and II (AI and AII) were measured in 13 patients with essential hypertension before and during chronic treatment with enalapril (MK 421) and in seven subjects during an acute study. Two techniques were used for simultaneous extraction of AI and AII. Despite appropriate correction for cross-reaction of AI with the AII antibody, one of the techniques gave consistently higher AII and lower AI levels in plasma of subjects treated with enalapril. The possibility of in vitro conversion of AI into AII-immunoreactive material during the purification or the radioimmunoassay steps should be considered. The use of the alternative technique is proposed for simultaneous processing of blood samples for AI and AII.

Angiotensin I↗

Plasma oxalate concentration and oxalate distribution volume in patients with normal and decreased renal function.

In twenty-one patients (sixteen male, five female) with various kidney diseases including primary hyperoxaluria type I (four patients), the plasma oxalate level was calculated from the isotopically determined oxalate clearance and the chemically determined urinary oxalate excretion. The apparent oxalate distribution volume was assessed as well. In patients with impaired kidney function (n = 12), the oxalate clearance was lower and the biological half-life and plasma concentration were higher than in patients with normal kidney function (n = 10). No differences were found in the oxalate-to-creatinine clearance ratio (mean value 1.93), urinary oxalate excretion and apparent oxalate distribution volume. A linear relation was found between the oxalate and creatinine clearance, while the clearance ratio was independent of the degree of renal failure. The apparent oxalate distribution volume was 1.45 times the estimated extracellular fluid volume. Because the isotopically determined plasma oxalate levels are lower than chemically measured ones, a quick and better estimation of plasma oxalate can be made from the urinary oxalate excretion and the creatinine clearance.

Adolescent↗

Blood to interstitial fluid volume ratio in chronic hypokalaemic states.

The distribution of extracellular fluid over the intra- and extravascular spaces was determined in hypokalaemic and normokalaemic patients. In six patients with Bartter's syndrome, four with pseudo-Bartter's syndrome, and twenty with essential hypertension (EH) chronically treated with chlorthalidone, serum potassium (serum K+) and extracellular fluid volume (ECFV) were decreased, while plasma volume (PV) and blood volume (BV) were normal (see Table 1 for means, standard deviations, and levels of significance). Consequently, the ratio of BV to interstitial fluid volume (IFV) was increased. In ten patients with EH on long-term combined enalapril chlorthalidone therapy, eight EH patients on long-term spironolactone treatment, and twenty-three EH patients treated by short-term sodium restriction, PV, BV, and ECFV were decreased, but serum K+ and BV/IFV were normal. In six patients with primary hyperaldosteronism (PHA) serum K+ was decreased, while PV, BV, and BV/IFV were elevated. Significant negative correlations between sK and BV/IFV were found in the Bartter patients (r = -0.88) and the pooled data of all patients (r = -0.50). These findings suggest an association between chronic hypokalaemia and a fluid shift from the extra- into the intravascular space. The hypothesis that this phenomenon is due to a decreased venous resistance as a consequence of chronic hypokalaemia is discussed.

Bartter Syndrome↗

Fractional oxalate clearance in subjects with normal and impaired renal function.

The 14C-oxalate clearance was determined in 13 healthy subjects and 22 patients with various diseases and varying degrees of renal function impairment, including 5 patients with primary hyperoxaluria (PH). The clearances of oxalate (Cox) and creatinine (Ccr) were correlated (r = 0.95). The regression line intersects the ordinate at the origin, while the regression coefficient is 2.0. This implies that the fractional Cox is constant, irrespective of the underlying disease and the degree of renal failure. Plasma oxalate (Pox), as calculated from the urinary oxalate excretion (Uox) and Cox, was elevated in patients with severely impaired kidney function and those with PH. Plasma creatinine (Pcr) and Pox were correlated as well (r = 0.83). Pox values of patients with PH were above the 95% confidence limits of the regression line. It is of practical importance that Pox can be estimated from Uox and Ccr when a 14C-oxalate clearance test cannot be performed. The reasons for the constancy of the Cox/Ccr ratio are discussed, and it is suggested that the effective renal plasma flow (ERPF) is the regulating factor for the tubular secretion of oxalate.

Adolescent↗