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Biomedical subjects

F C Reubi

Publications and source records attributed to F C Reubi.

At least 19 recordsLinked to original sources

Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin.

1. Serum concentrations of amoxycillin and clavulanic acid were measured in patients with end-stage renal disease (ESRD) following intravenous administration of 1.2 g Augmentin. Augmentin was administered on a non-dialysis day and 2 h prior to a 4 h dialysis session. 2. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for amoxycillin on the non-dialysis day were 14.4 ml min-1, 19.2 h, 14.9 l and 13.6 h, respectively. 3. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for amoxycillin were 77.1 ml min-1, 91.5 ml min-1, 0.64 and 2.30 h, respectively. 4. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for clavulanic acid on the non-dialysis day were 43.6 ml min-1, 4.4 h, 11.0 l and 3.05 h, respectively. 5. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for clavulanic acid were 92.8 ml min-1, 136 ml min-1, 0.65 and 1.19 h, respectively. 6. The total serum clearance on the non-dialysis day, which represents non-renal clearance, was lower than that in normal subjects for both amoxycillin and clavulanic acid. These data would suggest some degree of hepatic impairment in patients with ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Armand Trousseau (1801-1867) and the placebo effect].

In 1834 Armand Trousseau (1801-1867) used a placebo, consisting of pills containing only starch, to show that these pills were as effective as homeopathic dilutions. On another occasion he claimed to have produced marked diuresis in patients with edema by cutaneous application of digitalis and scilla solutions; in fact the diuresis resulted from prior high-dose oral digitalis therapy. Complete ignorance of pharmacokinetics at that time was largely responsible for his error.

France

Acute changes in renal function induced by bisoprolol, a new cardioselective beta-blocking agent.

The acute effects of bisoprolol 10 mg i.v., a new beta1-selective adrenoceptor antagonist, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), para-aminohippuric acid clearance (CPAH), sodium clearance, urine volume and plasma renin activity (PRA), were studied in 6 patients with essential hypertension. Heart rate decreased by 23%, mBP remained unchanged, and GFR decreased by 14% and CPAH by 23%. PRA was depressed on average by 25%. Urine volume and sodium clearance also declined by 9 and 13%, respectively, but the changes were not statistically significant. The fall in heart rate was significantly correlated with that in GFR and CPAH. Changes in GFR were correlated significantly with those in CPAH. The acute changes in renal function induced by bisoprolol are considered to be due to a reduction in cardiac output and increased systemic vascular resistance.

Adrenergic beta-Antagonists

Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin.

Amoxicillin and clavulanic acid are prescribed as a fixed drug combination. The purpose of the present study was to assess the influence of various degrees of renal insufficiency (glomerular filtration rate [GFR], less than 5 to greater than 75 ml/min per 1.73 m2) on the pharmacokinetics of amoxicillin and clavulanic acid following oral (500 and 125 mg of amoxicillin and clavulanic acid, respectively) and intravenous (1,000 and 200 mg, respectively) dosing. The volume of distribution and the systemic availability were independent of the renal function, while the total body clearance and the renal and the nonrenal clearance of amoxicillin and clavulanic acid decreased with decreasing renal function. The decrease in the total body clearance was more pronounced for amoxicillin than for clavulanic acid. This explains the increase in the ratio of the area under the plasma concentration versus time curve of amoxicillin to that of clavulanic acid with decreasing glomerular filtration rate after oral dosing; for example for a GFR of 75 ml/min, the ratio of amoxicillin to clavulanic acid was 4.9 +/- 1.2; for a GFR of 35 to 75 ml/min, 5.3 +/- 2.4; for a GFR of 10 to 35 ml/min, 11.9 +/- 5.8; for a GFR of 5 to 10 ml/min, 13.4 +/- 9.1; and for patients on hemodialysis, 14.7 +/- 5.3. Dosage recommendations are suggested which prevent undue accumulations of amoxicillin while maintaining adequate concentrations of clavulanic acid.

Amoxicillin

Blood levels and renal effects of atrial natriuretic peptide in normal man.

Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important but not sole mechanism of natriuresis and diuresis induced by alpha hANP in man.

Atrial Natriuretic Factor

Cardiovascular, endocrine and renal effects of atrial natriuretic peptide in essential hypertension.

Plasma concentrations of human atrial natriuretic peptide (hANP) and effects of synthetic alpha-hANP on blood pressure (BP), on endocrine and metabolic variables, and on renal function were investigated in 10 patients with essential hypertension. Alpha-human atrial natriuretic peptide was given intravenously as a 50-micrograms bolus followed by a 45-min infusion at 0.1 microgram/kg per min. The following effects were observed: (1) a marked rise in plasma alpha-hANP, (2) a progressive fall in BP (from 181/127 to 165/109 mmHg) and plasma volume, (3) a probably baroreflex-mediated sympathetic activation, evidenced by raised heart rate and plasma norepinephrine levels, (4) an increase in serum free fatty acids and circulating insulin (+45%), (5) an enhanced diuresis (+770%) and excretion of sodium (+665%), chloride (+524%), phosphate (+518%), other electrolytes, amino acids and free water clearance, (6) biphasic responses in the glomerular filtration rate (GFR) and p-aminohippurate (PAH) clearance, with initial increases (+40 and 30%, respectively) followed by a rapid return to (GFR), or even a fall below (PAH clearance) control values, and (7) a marked rise in the filtration fraction. Plasma antidiuretic hormone and urinary prostaglandin E2, F2 alpha and dopamine levels were not modified during alpha-hANP infusion, while plasma renin increased. Discontinuation of alpha-hANP was followed by rises in plasma aldosterone, the aldosterone:renin ratio and cortisol. Compared with previously studied normal subjects, in the hypertensive patients alpha-hANP caused a distinctly greater diuresis and electrolyte excretion but lowered BP only slightly more. In essential hypertension, as in normal man, alpha-hANP circulates in the blood and may exert a wide spectrum of cardiovascular, metabolic, endocrine and renal actions.

Adult

Rapidly progressive glomerulonephritis accompanying Legionnaires' disease.

A rapidly progressive, crescentic glomerulonephritis with acute oliguric renal failure occurred simultaneously with legionnaires' disease (LD) in a 52-year-old man. The diagnosis of LD was based on a sixfold rise in indirect fluorescent antibody titer against Legionella pneumophila serogroup 4. Treatment with erythromycin lactobionate resulted in a clinical resolution of pulmonary manifestations. The impairment of kidney function, however, was progressive and within two weeks led to end-stage renal failure requiring regular hemodialysis. This observation suggests that LD may trigger severe acute glomerulonephritis.

Antibodies, Bacterial

Interrelationships between sodium clearance, plasma aldosterone, plasma renin activity, renal hemodynamics and blood pressure in renal disease.

This study was designed to evaluate the role of aldosterone, glomerular filtration and blood pressure on sodium excretion in renal disease. Sodium clearance (CNa), plasma aldosterone (PA), plasma renin activity (PRA), glomerular filtration rate (GF), paraaminohippurate clearance (CPAH) and blood pressure were measured simultaneously in 19 normal subjects, 38 patients with benign essential hypertension, 3 with renal artery stenosis, 48 with chronic glomerulonephritis, 20 with the nephrotic syndrome, 24 with tubulo-interstitial disease and 21 with a renal homograft. CNa was significantly depressed in patients with the nephrotic syndrome. Mean PA and PRA were increased in renal artery stenosis but within the normal range in other groups. CNa correlated inversely with PA in all groups but one (tubulo-interstitial disease). CNa correlated directly with GF in the nephrotic syndrome and with the mean blood pressure (mBP) in chronic glomerulonephritis and tubulo-interstitial disease. PA correlated directly with PRA and inversely with GF or CPAH in most groups. It is concluded that PA is an important determinant of the basal natriuresis in renal disease with the exception of tubulo-interstitial nephropathies. In the nephrotic syndrome sodium retention is largely determined by the interaction of PA and GF. In chronic nephropathies, but not in benign essential hypertension, the fractional sodium excretion is partly blood pressure-dependent. Impairment of renal function is often accompanied by a rise in PA.

Adolescent

Increased ratio between changes in blood pressure and plasma norepinephrine in essential hypertension.

The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of plasma catecholamine levels and the pressor sensitivity to endogenous norepinephrine. The latter was estimated indirectly by the ratio between changes in blood pressure and those in plasma norepinephrine after adrenergic neuronal blockage with debrisoquine (given orally for 6 weeks). Normal subjects and patients with borderline or established essential hypertension had comparable pretreatment levels of plasma norepinephrine and epinephrine. Debrisoquine lowered plasma norepinephrine by a similar degree (almost 50%) in these three groups; in contrast, blood pressure decreased only slightly in normal or borderline hypertensive subjects [-3.4 +/- 3.2% and -5.4 +/- 1.6% (SE), respectively] but fell significantly more (P less than 0.005) in patients with established essential hypertension (-20.7 +/- 3.9%). The ratio between percentile changes in blood pressure and those in endogenous norepinephrine levels was comparable in normal and borderline hypertensive subjects (0.03 +/- 0.08 and 0.17 +/- 0.04, respectively), but increased (P less than 0.001) in established essential hypertension (0.62 +/- 0.11). This suggests that essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma norepinephrine levels with increased norepinephrine pressor sensitivity.

Blood Pressure

[Significance of noradrenaline in the pathogenesis of essential hypertension. Preliminary report].

The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of urinary and plasma catecholamine levels and pressor sensitivity to endogenous noradrenaline. The latter was estimated indirectly by the ratio between percentile changes in blood pressure and plasma noradrenaline following adrenergic neuronal blockade with the agent debrisoquine. In normal and mildly hypertensive (141/91 to 160/105 mm Hg) subjects, supine or upright plasma levels and excretion rates of noradrenaline correlated (p less than 0.01) with age and were comparable; no correlation was present in patients with moderate to severe hypertension (greater than 160/105 mm Hg) who tended to have supernormal noradrenaline levels under the age of 40 years. Adrenaline values were normal in essential hypertension. Pressor sensitivity to noradrenaline was comparable in normal and mildly hypertensive subjects (0.03 +/- 0.08 [SE] and 0.17 +/- 0.04, respectively) but increased (p less than 0.001) in moderate to severe hypertension (0.62 +/- 0.11). These findings suggest that moderate to severe essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma noradrenaline levels with increased noradrenaline pressor sensitivity. This may also provide a rational basis for the use of pharmacologic adrenergic inhibition in the treatment of moderate to severe essential hypertension.

Adolescent

Pathogenesis and renal function in acute toxic nephropathies.

Acute toxic nephropathy may be produced by a variety of poisons and drugs. Cellular poisons, such as mercuric bichloride, produce tubular necrosis. Many drugs induce an immunologically mediated response presenting as interstitial nephritis, glomerulonephritis or angiitis. Substances, which are not primarily nephrotoxic but induce dehydration, shock, hemolysis, rhabdomyolysis and/or electrolyte disturbances may also lead to secondary acute renal failure. Reduced renal blood flow, suppressed glomerular filtration, increased tubular pressure due to obstruction, and tubular leakage are responsible for the functional breakdown. In addition, specific tubular functions may be impaired. Complete or incomplete recovery is the rule.

Acute Kidney Injury