Platelet-activating factor mediates angiotensin II-induced proteinuria in isolated perfused rat kidney

Isolated kidney preparations (IPK) from male Sprague Dawley rats perfused at constant pressure were used to evaluate the effect of angiotensin II (AII) and platelet-activating factor (PAF) on renal function and urinary protein excretion. Compared with basal, intrarenal infusion of AII at 8 ng/min caused a progressive increase in protein excretion (11 +/- 6 versus 73 +/- 21 micrograms/min) in parallel with a decline in renal perfusate flow (RPF) (29 +/- 3 versus 18 +/- 3 ml/min). Addition to the perfusate of PAF at 50 nM final concentration also induced proteinuria (9 +/- 4 versus 55 +/- 14 micrograms/min) but did not change RPF (29 +/- 3 versus 30 +/- 3 ml/min). Preexposure of isolated kidneys to the PAF receptor antagonist WEB 2086 prevented the increase in urinary protein excretion induced by AII infusion (basal: 13 +/- 6; post-AII: 12 +/- 7 micrograms/min) but failed to prevent the vasoactive effect of AII (RPF, basal: 30 +/- 2; post-AII: 21 +/- 3 ml/min). In additional experiments, dexamethasone reduced the proteinuric effect of PAF remarkably. These results indicate that in isolated kidney preparation: (1) AII infusion induced proteinuria and decreased RPF; and (2) the effect of AII in enhancing urinary protein excretion was completely prevented by a specific PAF receptor antagonist, which, however, did not influence the AII-induced fall in RPF. It is suggested that PAF plays a major role in AII-induced changes in the permselective function of the glomerular capillary barrier.     

Isolation of 48 genetic markers appropriate for high throughput genotyping of inbred rat strains by B1 repetitive sequence-representational difference analysis

1. We examined whether zaprinast, a putative cGMP-specific phosphodiesterase inhibitor, affects neural control of renal function in pentobarbital-anaesthetized dogs. 2. Renal nerve stimulation (1 Hz, 1 ms duration) reduced urine flow rate, urinary Na+ excretion (UNaV) and fractional excretion of Na+ (FENa) with little change in either renal blood flow (RBF) or glomerular filtration rate (GFR). 3. Intrarenal arterial infusion of zaprinast (10 and 100 micrograms/kg per min) increased basal urine flow rate, UNaV and FENa but not RBF or GFR. Zaprinast infusion (100 micrograms/kg per min) also increased renal venous plasma cGMP concentration and urinary cGMP excretion. 4. Renal nerve stimulation-induced reductions in UNaV and FENa were attenuated during zaprinast infusion, whereas the reduction in urine flow rate was resistant to zaprinast. 5. Renal nerve stimulation increased the renal venous plasma noradrenaline concentration and renal noradrenaline efflux, which remained unaffected during infusion of zaprinast (100 micrograms/kg per min). 6. The results of the present study suggest that zaprinast induces natriuresis and counteracts adrenergically induced antinatriuresis by acting on renal tubular sites in the dog kidney in vivo.     

Improved kidney function with intravenous prostaglandin E1 in patients with terminal heart failure

In end stage congestive heart failure activation of a series of compensatory mechanisms increase renal vascular resistance and impair renal function. Prostaglandin E1 is increasingly used in the treatment of severe heart failure for its vasodilating actions. In various experimental settings prostaglandin E analogues are known to improve renal function by modulating renal filtration pressure and redistribution of renal blood flow. However, prostaglandin E1 decreases systemic blood pressure and thus, also renal perfusion pressure, a fact by which renal function might be further compromized in heart failure patients. The aim of the study was to evaluate the effects of prostaglandin E1 on excretory renal function in patients with end stage heart failure and to prove the hypothesis, that the well known local actions of prostaglandins on renal microcirculation might outweigh the negative impact of an expected decrease in perfusion pressure. 25 patients with terminal congestive heart failure were investigated. 13 patients received prostaglandin E1 at a dose of 13.5 +/- 1.9 ng/kg/min in combination with constant rates of dopamine and dobutamine (group A), 12 patients received prostaglandin E1 at a dose of 10.3 +/- 1.7 ng/kg/min without catecholamines (group B). There was no significant difference in prostaglandin dosages between groups. Kidney function was assessed by measuring plasma creatinine and urea nitrogen, urinary output, creatinine clearance, osmotic and free water clearance at baseline and after 72 h of infusion therapy. Hemodynamic parameters were measured by using a balloon tipped pulmonary arterial catheter. Hemodynamic measurements during infusion showed a significant improvement in all patients. At the same time as expected mean arterial pressure decreased in both groups (p < 0.001). Nevertheless, in both groups a significant increase of creatinine clearance during infusion was observed (in group A from 45 ml/min to 78 ml/min., p < 0.05, in group B from 59 ml/min to 105 ml/min., p < 0.001). Creatinine clearance in group B (without catecholamines) reached higher levels than group A (p < 0.05). Urinary volumes did not change during infusion therapy, whereas free water clearance significantly decreased, as an indication of an improvement of renal concentrations ability. We conclude, that in patients with end stage heart failure continuous infusion of prostaglandin E1 improves excretory kidney function. These findings suggest that the local effects of prostaglandin E1 on renal microcirculation can counterregulate the negative impact of prostaglandins on renal perfusion pressure.     

Poisoning with methanol and ethylene glycol:1H NMR spectroscopy as an effective clinical tool for diagnosis and quantification

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P=0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P=0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P=0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.     

Effect of sodium restriction and angiotensin II infusion in Bartter's syndrome

Five patients with Bartter's syndrome were investigated. Sodium restriction (less than 10 mEq/day for at least 5 days) showed a renal sodium wastage in only two patients (I and II) in spite of increased aldosterone secretion rate (from 151-427 to 680-842 mug/day). The effect of angiotensin II (A II) 80ng/kg/min for 30-180 min, on plasma renin activity (PRA), plasma aldosterone, and urinary sodium excretion was compared with the effect of a previous infusion of 5% dextrose given at the same rate, 0.5 ml/min for 1 hr. A II infusion resulted in increased plasma aldosterone levels: from 236-330 pg/ml to 800-881 pg/ml in 30 min. This increase was also observed in patient II (from 139 to 600 pg/ml). PRA was decreased by A II infusion (from 1,142-2,462 to 121-1,625 ng/liter/min). In patient IV, this decrease in PRA was also observed when he was on a salt-restricted diet (from 1,934 to 370 ng/liter/min); but the minimal PRA was still higher (370 ng/liter/min) than with a normal diet (121 ng/liter/min). In no case could normal PRA level be obtained. A II infusion induced an increase in urinary sodium excretion only in the two patients with renal sodium wastage (from 80-90 to 265-230 muEq/min in 30 min). Urinary sodium excretion decreased in the other patients from (37.5-213 to 4.30-46 muEq/min) and fractional sodium excretion was reduced in patient V (from 0.56% to 0.45% at 30 min and to 0.29% at 120 min). No significant change with A II infusion was observed in patient IV when he was on a sodium-restricted diet (from 1 to 2.5 muEq/min in 30 min). Urinary potassium excretion was similar to sodium excretion. No change was observed in plasma potassium and sodium.     

Abnormal distal tubular sodium reabsorption during dopamine infusion in patients with essential hypertension evaluated by the lithium clearance methods

The effects of low-dose dopamine infusion on renal hemodynamics, tubular function estimated by the lithium clearance technique and plasma levels of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were studied in 11 patients with essential hypertension (HT) and in 10 healthy control subjects (CS). Antihypertensive treatment was terminated at least 2 weeks prior to examination. Dopamine (2 micrograms/kg/min) was infused for two hours. Before dopamine infusion all measured parameters, but blood pressure, did not deviate significantly between the two groups, including 24 h urinary sodium excretion prior to investigation (HT: 166.9 mmol/24 h vs. CS: 183.4 mmol/24 h, medians). Dopamine infusion resulted in an exaggerated natriuresis in the HT group when compared with the CS group; sodium excretion: (HT: from 260 to 759 mumol/min vs. CS: from 255 to 432 mumol/min, p < 0.01) and fractional sodium excretion: (HT: from 1.6 to 4.2% vs. CS: from 1.6 to 2.4%, p < 0.01 median values). Distal fractional sodium reabsorption was significantly lower in the HT patients (HT: from 94.0 to 88.5% vs. CS: from 94.0 to 91.6%, p < 0.01). ANP decreased significantly only in the HT group (HT: from 4.8 to 3.5 pmol/l vs. CS: from 3.2 to 3.4 pmol/l, p < 0.01). Renal hemodynamics, blood pressure, urinary output, Ang II, Aldo, and AVP were changed to the same degree or unchanged in both groups. It is concluded that the exaggerated natriuretic response seen in patients with essential hypertension during low-dose dopamine infusion probably is due to a enhanced dopamine sensitivity mainly in the distal parts of the nephron.     

Antiarrhythmic effect related to the plasma concentration of pentisomide in vivo and the antiarrhythmic-concentration relationship in vitro

Pentisomide, 2-(2-diisopropylaminoethyl)-4-methyl-2-(pyridyl)- pentanamide, is a novel antiarrhythmic agent structurally related to disopyramide. Using a glass bead arrhythmic model, the authors studied the antiarrhythmic effect of pentisomide in dogs by monitoring the plasma concentrations. When pentisomide was infused at 1 mg/kg/min for 20 min, the ventricular tachycardia was significantly reduced at 5 min after starting the infusion; the arrhythmias were reduced to less than 5% at the end of the 20 min infusion. The plasma-free concentration of pentisomide was about 3 micrograms/ml at 5 min; it increased to about 10 micrograms/ml at the end of 20 min infusion. With 0.3 mg/kg/min infusion, the arrhythmias were reduced to about 60% but were not significant at 20 min of infusion. The plasma-free concentration of pentisomide did not reach 3 micrograms/ml until 20 min of infusion. The 3 micrograms/ml plasma-free concentration for pentisomide seems to be a critical concentration in inducing a significant antiarrhythmic effect. Pentisomide dose-dependently inhibited ischaemia-reperfusion arrhythmia at doses of 30 microM and higher concentrations in vitro. In conclusion, pentisomide inhibits arrhythmias dependent with the plasma concentration or with the concentration of the external solution. The critical plasma-free concentration for inhibition of arrhythmias was 3 micrograms/ml (not equal to 10 microM) and the in vitro effect also had a similar concentration. Therefore, the in vivo and in vitro antiarrhythmic concentrations were well correlated.     

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.     

The effects of a converting enzyme inhibitor (captopril) and angiotensin II on fetal renal function

1. Renal function was studied in chronically catheterized fetal sheep (119-128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2. An i.v. dose of 15 mg (about 319 micrograms kg-1) of captopril to salt-replete ewes followed by an infusion to the ewe of 6 mg h-1 (about 128 micrograms kg-1 h-1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 +/- 5.6 to 84.9 +/- 8.3 ml min-1 (mean +/- s.e. mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3. Ewes were treated for the next 2 days with 15 mg captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of captopril (6 mg h-1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 micrograms kg-1 h-1 of angiotensin II was infused directly into the fetus RBF fell from 69 +/- 10.1 ml min-1 to 31 +/- 13.9 ml min-1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses. 4. It is concluded that the small fall in fetal arterial pressure partly contributed to the fall in fetal GFR but in addition, efferent arteriolar tone fell so that the filtration pressure fell further. Thus maintenance of fetal renal function depends on the integrity of the fetal renin angiotensin system. These findings explain why use of ACE inhibitors in human pregnancy is associated with neonatal anuria.     

The influence of hyperinsulinaemia on calcium-phosphate metabolism in renal failure

BACKGROUND: Patients with renal failure are characterized by impaired insulin-mediated glucose uptake. Insulin plays a major role in the maintenance of phosphate homeostasis but it remains to be determined whether in uraemia insulin-dependent renal and extrarenal phosphate disposal is also affected. METHODS: The effect of hyperinsulinaemia on serum concentrations of phosphate, ionized calcium and intact PTH as well as renal excretion of calcium and phosphate was studied under euglycaemic conditions (glucose clamp technique) in patients with advanced renal failure and in healthy subjects. Fifteen patients with renal failure (mean serum creatinine 917 micromol/l) and 12 control subjects were included. All subjects underwent a 3-h euglycaemic clamp with constant infusion of insulin (50 mU/m2/min) following a priming bolus. The urine was collected for 3 h before and throughout the clamp. RESULTS: The tissue insulin sensitivity (M/I) was lower in patients with renal failure than in control subjects (5.3+/-2.4 vs 6.7+/-1.8mg/kg/min per mU/ml, P= 0.001) but the phosphate lowering action of insulin was larger in patients with renal failure than in control subjects. Urinary calcium excretion increased (P < 0.05) and phosphate excretion did not change during the clamp in both groups. Despite a decrease of serum ionized calcium in the group of patients with renal failure and no change in the control group, plasma PTH fell significantly in both groups but this effect was still significant after 180 min only in the renal failure group. A significant correlation was observed between changes in serum phosphate and PTH induced by hyperinsulinaemia (r = 0.48, P < 0.01 ) CONCLUSIONS: Phosphate-lowering effect of insulin is well preserved in severe renal failure despite the resistance to insulin-stimulated glucose uptake. The decrease of serum PTH observed during hyperinsulinaemia appears to be independent of serum ionized calcium.     

Diagnosis of thoracic outlet syndrome in the emergency department

Gadodiamide at a dose of 0.1 mmol/kg was administered intravenously to 10 renal transplanted patients with stable, impaired, or slowly deteriorating renal function (serum creatinine 194-362 mumol/l). The patients were referred for contrast medium enhanced magnetic resonance imaging to rule out possible graft circulation abnormalities. The excretion of gadodiamide in urine was prolonged as compared with healthy controls. After 120 h 92% of the injected dose was excreted in urine and only 0.4% in faeces. The plasma clearance of gadodiamide was 28.6 +/- (SD) 5.5 ml/min (n = 10), and the renal clearance (0-72 h) was 26.3 ml/min. The renal clearance of 125I-iothalamate for the same time period was 27.9 +/- 5.3 ml/min. Thus, gadodiamide is eliminated by glomerular filtration also in renal transplant patients with moderately to severe impaired renal function, and gadodiamide clearance may serve as an alternative marker for the determination of the glomerular filtration rate. Serum values of creatinine and beta(2)-microglobulin and creatinine clearance were unchanged by gadodiamide and neither was the urinary enzyme excretion significantly changed. These results suggest that the renal tolerance to gadodiamide is good also in renal transplant patients with impaired renal function.     

Significance of the karyopyknotic index in the course control of hormone-treated prostatic carcinoma

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).     

Release and clearance rates of epinephrine in man: importance of arterial measurements

Previous estimates of catecholamine kinetics in human subjects have been based on the measurement of the catecholamine levels in forearm venous plasma. However, the use of forearm venous measurements may introduce considerable error, since venous catecholamine levels may primarily reflect metabolism in the organ drained rather than in the total body. In this study, arterial levels of epinephrine were found to significantly exceed forearm venous levels, both basally (mean +/- SEM, 71 +/- 13 vs. 50 +/- 7 pg/ml; n = 6; P less than 0.05) and during infusions of epinephrine [0.1 microgram/min (112 +/- 9 vs. 77 +/- 11 pg/ml; P less than 0.005) or 2 micrograms/min (862 +/- 71 vs. 437 +/- 66 pg/ml; P less than 0.001)]. During the 2 micrograms/min epinephrine infusion, arterial plasma norepinephrine rose from 191 +/- 37 to 386 +/- 78 pg/ml (P less than 0.001), while venous norepinephrine levels did not change significantly. Fractional extraction (arterial - venous + arterial X 100) of epinephrine across the forearm was 26 +/- 8% in the basal state and increased to 33 +/- 6% and further to 51 +/- 4% during the epinephrine infusions. The addition of propranolol (5 mg, iv, plus an 80 micrograms/min infusion) reduced fractional extraction from 51 +/- 4% to 35 +/- 5%. Whole body clearance of epinephrine, calculated from arterial measurements, was 33 +/- 3 ml/kg . min during the 0.1 microgram/min infusion and 35 +/- 3 ml/kg . min during the 2 micrograms/min epinephrine infusion, values 50% lower than the clearance rates calculated from venous measurements. Propranolol infusion resulted in a fall in whole body clearance to 20 +/- 2 ml/kg . min (P less than 0.001), suggesting that epinephrine clearance is partly dependent on a beta-adrenergic mechanism. Basal endogenous release rate (clearance X basal epinephrine level) was estimated to be approximately 0.18 microgram/min, a value much less than that reported in studies using venous measurements. We conclude that arterial rather than venous measurements should be used to estimate catecholamine kinetics in vivo.     

Human growth hormone kinetics in critically ill patients

Several studies have shown that exogenous human growth hormone (HGH) exerts an anabolic effect on protein metabolism in surgical patients with mild or moderate catabolism. However, contradictory results have been demonstrated in polytrauma patients where HGH did not improve protein metabolism. Aim of this study was to evaluate whether the pharmacokinetics of recombinant biosynthetic human GH (r-HGH) are altered in critically ill patients. After an overnight fast, r-HGH was infused at a rate of 460 micrograms/h/kg/bw during 120 min to five intensive care unit (ICU) patients. The patients were catabolic (nitrogen balance -11 +/- 0.5), showed normal liver function, and only one patient had a slightly impaired kidney function (creatinine > 1.5 mg/dl). Endogenous GH secretion was suppressed by continuous infusion of 50 micrograms/m2/h somatostatin. From plasma GH curves, elimination half life (t1/2kle), whole body clearance (Cltot) and steady state distribution space (DS) were calculated in an open two compartment model. Additionally, the effects of r-HGH infusion on plasma insulin, glucagon and amino acid concentrations were evaluated. T1/2kle was 19.6 +/- 2.3 min, Cltot 2.9 +/- 0.4 ml/kg/bw/min and DS 76.4 +/- 3.8 ml/kg/bw for 90 min. The plasma levels of total amino acids including the branched chain amino acids valine, leucine and isoleucine and of glutamine were significantly higher during r-HGH infusion than during the basal and somatostatin periods. In conclusion, the elimination of r-HGH in catabolic ICU patients is not different from that of healthy volunteers.     

Terazosin in the treatment of hypertension and symptomatic benign prostatic hyperplasia: a primary care trial

In vitro experimental data show that magnesium increases beta-receptor affinity to agonists. We studied the effect of a mild increase in serum magnesium level on the bronchial dose-response curve to salbutamol in six patients with asthma (age 54 +/- 3.6 years, FEV1 49.2 +/- 4.9 per cent of predicted), with a normal serum magnesium level, in a double blind placebo-controlled design. The salbutamol dose-response curve was obtained on two separate days, starting 30 min after an intravenous infusion of saline or MgSO4 (20 mg/kg over 10 min, followed by 10 mg/kg/h). The baseline FEV1 values and the values after 30 min infusion on the two test days were not significantly different. During MgSO4 infusion, the serum magnesium level increased significantly from 0.86 +/- 0.01 to 1.31 +/- 0.19 mmol/litre after 30 min and 1.29 +/- 0.17 mmol/litre at the end of the study. FEV1 values after salbutamol were significantly higher during MgSO4 than during saline infusion at the low doses of salbutamol: 1480 +/- 253 vs. 1368 +/- 212 ml, P < 0.05, after 5 micrograms, and 1596 +/- 585 vs. 1378 +/- 532 ml, P < 0.01, after 10 micrograms of salbutamol. The maximum increase in FEV1 obtained after the maximum dose of salbutamol (400 micrograms) was not significantly different during saline and MgSO4 infusion. In conclusion, a mild sustained increase in serum magnesium level increases the bronchodilating effect of low doses of salbutamol, possibly through an increased beta-receptor affinity. There was no effect on the maximum bronchodilating effect of salbutamol.     

Oxygen administration increases plasma digoxin-like substance and renal sodium excretion in chronic hypoxic patients

Despite the absence of cardiac or renal pathologies, edema and mild hyponatremia may often occur in patients affected by chronic obstructive pulmonary disease (COPD). Therefore, it has been suggested that hypoxia may influence the release of different hormones regulating renal sodium handling. To evaluate the effect of hyperoxia and O2 removal on plasma digitalis-like substance (DLS) levels, 9 patients affected by COPD and 7 normal subjects were studied. After 1 h in supine position, O2 was administered for 3 h by a tight-fitting face-mask. Blood samples for plasma DLS were taken at time 0, 60, 180 min and then for 3 h after O2 removal. In normal subjects, plasma DLS did not vary after O2 administration (from basal values of 162.25 +/- 8.59 to 107.75 +/- 6.65 pg/ml at 180 min; NS), and O2 removal (143.7 +/- 16.87 pg/ml after 3 h from O2 removal; NS). On the contrary, in patients affected by COPD, plasma DLS levels increased during O2 administration (from basal values of 138.98 +/- 8.31 to 202.14 +/- 8.21 pg/ml at 180 min; p < 0.05), and returned to baseline levels (142.59 +/- 8.28 pg/ml) 3 h after O2 removal. In the same patients, DLS increase was accompanied by a rise in Na+ excretion (from 0.08 +/- 0.01 at time 0 to 0.16 +/- 0.02 mEq/min after 3 h of O2 administration; p < 0.05). In conclusion, our findings showed an oxygen-related increase in plasma DLS levels and in urinary Na+ excretion in patients affected by COPD. This phenomenon could promote Na+ urinary loss during prolonged O2 therapy in these patients and should be taken into account in their management.     

Effects of carperitide (alpha-human atrial natriuretic peptide) on acute congestive heart failure in dogs

Effects of carperitide (alpha-human atrial natriuretic peptide) on hemodynamics and renal function in dogs with congestive heart failure (CHF) produced by volume expansion and ligation of the left anterior descending coronary artery were compared with those of various anti-heart failure agents (cardiotonic, vasodilator and diuretic). Carperitide (0.1-1 microgram/kg/min) dose-dependently decreased the elevated left ventricular end-diastolic pressure (LVEDP). No significant changes in cardiac contractility (LV dP/dtmax) and heart rate (HR) were noted, although cardiac output (CO) tended to reduce during the infusion of carperitide. Nitroglycerin (NG; 3 micrograms/kg/min) and furosemide (1 mg/kg) also decreased LVEDP, but the potency was less than that of carperitide. Sodium nitroprusside (SNP; 10 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) caused a reduction in LVEDP and increased CO with an increase in HR. Hydralazine (H; 100 micrograms/kg/min) increased CO without reduction in LVEDP and induced a pronounced increase in HR. Double product (systolic blood pressure x HR), an index of myocardial oxygen consumption, was significantly reduced by carperitide, but significantly increased by DB and H. Carperitide, unlike NG, SNP, H and DB, increased urine volume and urinary electrolyte excretion. These results suggest that carperitide will be an useful therapeutic agent for the treatment of CHF.     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.     

Pharmacokinetics of cefapirin in patients with normal and impaired renal functions

The pharmacokinetics of 3-hydroxymethyl-7-[2-(4-pyridyl-thio)acetamido]-2-cephem-2-carboxylic acid acetate (cefapirin) was evaluated after 1.0 g i.m. to 14 patients with different glomerular and tubular functions. Peaks in normal renal function ranged between 9--17 micrograms/ml and was 3--4 times higher in patients with glomerular filtration rates below 30 ml/min. The serum half-life in normal renal function was 0.8 h and was somewhat increased in renal impairment. The distribution volume was little influenced by renal capacity. Recommendations for dosage are given.     

Trypanosoma cruzi meningoencephalitis in AIDS mimicking cerebral metastases: case report

BACKGROUND: It has been suggested that citrate salts might enhance aluminum (Al) absorption from a normal diet, posing a threat of Al toxicity even in subjects with normal renal function. We have recently reported that in normal subjects and patients with moderate renal failure, short-term treatment with tricalcium dicitrate (Ca3Cit2) does not significantly change urinary and serum Al levels. However, we have not assessed total body Al stores in patients on long-term citrate treatment. OBJECTIVE: The objective of this study was to ascertain body content of Al non-invasively using the increment in serum and urinary Al following the intravenous administration of deferoxamine (DFO) in patients with kidney stones and osteoporotic women undergoing long-term treatment with potassium citrate (K3Cit) or Ca3Cit2, respectively. METHODS: Ten patients with calcium nephrolithiasis and five with osteoporosis who were maintained on potassium citrate (40 mEq/day or more) or calcium citrate 800 mg calcium/day (40 mEq citrate) for 2 to 8 years, respectively, and 16 normal volunteers without a history of regular aluminum-containing antacid use participated in the study. All participants completed the 8 days of study, during which they were maintained on their regular home diet. Urinary Al excretion was measured during a two-day baseline before (Days 5, 6) and for 1 day (Day 7) immediately following a single intravenous dose of DFO (40 mg/kg). Blood for Al was obtained before DFO administration, and at 2, 5 and 24 hours following the start of the infusion. RESULTS: The median 24-hour urinary Al excretion (microgram/day) at baseline versus post-DFO value was 15.9 vs. 44.4 in the normal subjects and 13.3 vs. 35.7 in the patients. These values were all within normal limits and did not change significantly following DFO infusion (p = 0.003 and p = 0.0001, respectively). The median change of 17.1 micrograms/day in urinary Al in the normal subjects was not significantly different from the 18.7 micrograms/day change measured in the patient group (p = 0.30). Similarly, no change in the mean serum Al was detected at any time following the DFO infusion, either in the patient or control group (patients 4.1 to 4.3 ng/ml, controls 7.4 to 4.6 ng/ml). CONCLUSION: The results suggest that abnormal total body retention of Al does not occur during long-term citrate treatment in patients with functioning kidneys.