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Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 487 records · Page 27Linked to original sources

Effect of denervation on the afferent arteriole in the SHR.

To study the role the renal nerves may play in the hypertension of the SHR, we conducted a morphometric study of the afferent arteriole of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) which were subjected to renal denervation (or sham-operation). Methacrylate casts were made of the renal vasculature after perfusion fixation with glutaraldehyde. These vascular casts were then examined and measurements made with the scanning electron microscope (SEM). Afferent arterioles of the denervated SHR were dilated in comparison to the sham-operated SHR, but there was no difference between the afferent arteriolar diameters of the 2 groups of WKYs. However, the afferent arteriolar diameters of the SHR (either group) were smaller than those of the WKY. Renal denervation caused a reduction in systolic blood pressure compared to sham-operated in both strains of rat. We concluded that the dilation changes of afferent arterioles of denervated SHRs may be related to renal autoregulation resulting from the decreased blood pressure. However, the effect of the loss of sympathetic innervation of the arterioles cannot be ruled out.

Animals↗

Influence of home monitoring on compliance with a reduced sodium intake diet.

To test the utility of a qualitative chloride titrator strip in facilitating compliance with a reduced sodium intake diet, we enrolled 32 patients into a randomized crossover trial comprising two study periods of four weeks each. The study periods were begun after the patients had undergone extensive instruction in the diet and the use of the strip. A high degree of correlation between the patient's and the laboratory's interpretation of the strip result was identified in 29 of the subjects. Ability to use the strip was not related to level of education. A total of 12 patients achieved compliance with the diet when using the strips. Of these, nine were able to achieve compliance without the strips. Ten patients (30%) had significantly lower sodium intake when using the strips than when they did not use them. We conclude that the use of the chloride titrator strip can be mastered by most patients and, in conjunction with dietary counseling, can facilitate compliance with a reduced sodium intake diet.

Adult↗

Estimation of dietary sodium intake in children.

To examine the utility of nocturnal urine collections in the estimation of dietary sodium intake in children, 29 families who agreed to lower their dietary sodium intake to less than 65 mEq/d were studied. A total of 58 adults and 95 children collected urine specimens weekly or biweekly before and after being instructed in a dietary sodium restriction regimen. Urine collections were fractionated into a diurnal and nocturnal portion. Sodium was measured directly, and estimated by measuring chloride excretion with a chloride titrator stick. Nocturnal chloride and 24-hour sodium excretion were highly correlated in adults (r = .75), and slightly less so (r = .56) in children. The slopes of the relationships were not different. Discriminant analysis showed that two or more chloride estimates permitted classification of both adults and children into the low sodium intake category with 100% accuracy, and into the normal sodium intake category with 75% accuracy. It was concluded that nocturnal chloride estimates are as useful in estimating compliance to a reduced sodium intake in children as in adults.

Adolescent↗

The utility of overnight urine collections in assessing compliance with a low sodium intake diet.

To develop methods of estimating sodium intake in free-living persons, we gave normal volunteers mean sodium intakes of 65, 110, and 200 mEq/day. The intake was randomly varied about each mean by an SD of 12.5% daily. Twenty-four-hour and night urinary sodium excretion were measured. Night urinary sodium excretion was also estimated by means of inexpensive quantitative and qualitative chloride titrator strips. The latter required no timed urine collection. A total of three 24-hour urine collections were necessary to differentiate the regimens with 95% accuracy. Three night urinary sodium excretory estimates by the quantitative chloride titrator provided 79% accuracy in identifying the level of dietary sodium intake. By applying the qualitative chloride titrator every other day, the dietary regimens could be differentiated with 95% accuracy. These techniques were not only useful in estimating sodium intake, but also provided a simple means of documenting compliance to sodium restriction. Patients should have no difficulty in applying these methods themselves in a home setting.

Adult↗

The effect of piperacillin dose on elimination kinetics in renal impairment.

The effect of drug dose on piperacillin elimination kinetics was examined in 27 adult subjects with varying renal function. Piperacillin, 15 mg/kg or 60 mg/kg, was given by bolus intravenous injection. The elimination half-life (t1/2) increased five-fold and plasma clearance (Clp) decreased by 80% in patients with renal failure. Both parameters were dose dependent in patients with normal renal function, but not in patients with renal insufficiency. Piperacillin dose dependent elimination is due primarily to capacity limited renal excretion.

Adult↗

Intervention in patients with renovascular hypertension and renal insufficiency.

We report on 21 severely hypertensive patients with renal artery stenosis and renal insufficiency in whom percutaneous transluminal angioplasty and/or renal artery surgery was done in an effort to lower blood pressure and to preserve renal function. Of 12 patients who underwent angioplasty renal function and blood pressure improved in 3. Of the 9 patients without improvement 4 suffered permanent oliguric renal failure. An operation was performed in 12 patients, 4 after having failed angioplasty (1 was treated at another institution before referral for surgery). Two patients died postoperatively but 10 improved, with followup in 6 exceeding 3 years. This retrospective experience suggests that percutaneous transluminal angioplasty is not likely to supplant an operation in the treatment of patients with atherosclerotic renovascular hypertension and renal insufficiency.

Aged↗

Pharmacokinetics of common antibiotics used in continuous ambulatory peritoneal dialysis.

To establish therapeutic guidelines for the use of antibiotics in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied the single-dose pharmacokinetics of cefazolin, tobramycin, and vancomycin given intravenously (IV) and intraperitoneally (IP) as well as cephalexin given orally. By the IV or oral route, the antibiotics exhibited half-lives similar to those described in nondialysed, functionally anephric patients. CAPD accounted for only a negligible fraction of the total body clearance when the drugs were given by the IV route. However, when given IP, the drugs were promptly absorbed and achieved therapeutic serum concentrations. The kinetic principle of superposition was applied to predict plasma concentrations after repetitive IP dosing. Therapeutic guidelines are provided.

Anti-Bacterial Agents↗

The effects of rapid saline infusion on sodium excretion, renal function, and blood pressure at different sodium intakes in man.

To examine the effects of increasing dietary sodium intake on natriuresis, filtration rate, and renal blood flow following rapid volume expansion, we infused 2-liter normal saline over 2 hr into normal men in balance at 10, 300, 600, and 800 mEq/day sodium intake. Natriuresis and kaliuresis were related to prior sodium intake. Fractional excretion of sodium (6%-7%) was maximal at the 600 mEq/day sodium intake and increased no further at the 800 mEq/day sodium intake. Although blood pressure increased with rapid saline infusion, natriuresis and blood pressure were not associated. Creatinine clearance decreased or remained constant, while PAH clearance decreased during saline infusion at each level. The data suggest that although natriuresis following rapid saline infusion is dependent upon prior sodium intake, under given circumstances it may be independent of glomerular filtration rate, renal blood flow, or blood pressure.

Adolescent↗

Mezlocillin kinetics in hepatic insufficiency.

To establish elimination kinetics of mezlocillin in patients with hepatic insufficiency, we gave eight normal subjects and four patients with hepatic insufficiency and normal renal function a single 3-gm dose of mezlocillin by intravenous infusion. Subjects with hepatic insufficiency all had serum bilirubins levels of above 3 mg/dl, prothrombin times more than 2 sec longer than control, and creatinine clearances above 60 ml/min. Mezlocillin concentrations were determined by microbiologic assay. Kinetic analysis was by model-independent methods. Elimination half-life was 0.96 hr for subjects with normal liver function and 2.62 hr for patients with hepatic insufficiency. Mean total body clearance for normal subjects was 247 ml/min, while in patients with hepatic insufficiency it was 125.4 ml/min. We conclude that hepatic insufficiency prolongs mezlocillin elimination and suggest that therapeutic guidelines be set up.

Adult↗

Tobramycin kinetics during continuous ambulatory peritoneal dialysis.

To establish therapeutic guidelines for tobramycin use in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied tobramycin single-dose kinetics in CAPD patients. Tobramycin was studied after a 1.5-mg/kg dose given either intravenously (TOB-IV) or intraperitoneally (TOB-IP). TOB-IV provided a plasma concentration above 3 mg/l at 12 hr with a t 1/2 of 39.5 hr. When tobramycin was given intraperitoneally, 52% of the dose was absorbed; peak plasma concentrations were only 1.8 mg/l, and the t 1/2 was 35 hr. CAPD accounted for only 15% to 20% of total body clearance in both groups. The kinetic principle of superposition was used to predict plasma concentrations after repeated TOB-IP. A model using once-a-day dosing predicted that a loading dose of 4 mg/kg followed by 1.5 mg/kg would achieve steady-state plasma concentrations of 2.8 to 4.2 mg/l. Another model using tobramycin in each exchange predicted that a loading dose of 3 mg/kg followed by 0.3 mg/kg would provide steady-state plasma concentrations of 2.8 to 3.1 mg/l. These data should be useful in treating CAPD patients with tobramycin who have nonperitoneal gram-negative aerobic bacterial infections, as well as those who require the drug for peritonitis.

Adult↗

Vancomycin kinetics during continuous ambulatory peritoneal dialysis.

To establish therapeutic guidelines for vancomycin usage in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied single-dose kinetics of vancomycin in CAPD patients. Vancomycin was studied after a 10-mg/kg dose was given intravenously (VAN-IV) or intraperitoneally (VAN-IP). VAN-IV provided a plasma concentration above 10 mg/l at 12 hr, with a t 1/2 of 81 hr. When VAN-IP was given, 65% was absorbed; peak plasma concentrations were only 6.3 mg/l, and t 1/2 was 66 hr. CAPD accounted for only 15% to 17% of total body clearance in both groups. The kinetic principle of superposition was used to predict plasma concentrations after repeated VAN-IP doses. A model with once-a-day dosing predicted that a loading dose of 30 mg/kg followed by 7 mg/kg would achieve steady-state plasma concentrations of 11 to 14.8 mg/l. Another model with vancomycin in each exchange predicted that a loading dose of 30 mg/kg followed by 1.5 mg/kg would provide plasma concentrations in excess of 10 mg/l at 180 hr. These data should be useful in vancomycin treatment of CAPD patients who have nonperitoneal gram-positive bacterial infections, as well as those who have peritonitis.

Adult↗

Cefazolin and cephalexin kinetics in continuous ambulatory peritoneal dialysis.

We studied single-dose cefazolin (CFZ) and cephalexin (CPX) kinetics in continuous ambulatory peritoneal dialysis (CAPD) patients to establish therapeutic guidelines for two cephalosporins commonly used to treat peritonitis in these patients. CFZ, 10 mg/kg, was given intravenously and intraperitoneally, while CPX, 500 mg, was given orally. CFZ led to serum concentrations of 25 microgram/ml at 24 hr, with a half-life (t 1/2) of 33 hr. CAPD accounted for only 20% of total body clearance. When CFZ was given intraperitoneally, 74% of the dose was absorbed and similar serum concentrations had much the same t 1/2. CPX, on the other hand, had a serum t 1/2 of 8.6 hr and resulted in much lower peritoneal concentrations than CFZ. The kinetic principal of superposition provided a model for the prediction of plasma concentrations after repeated intraperitoneal doses of CFZ. The model predicts that a 10-mg/kg intraperitoneal loading dose, followed by 5-mg/kg doses in each exchange the first day and 2.5-mg/kg doses thereafter, will lead to steady-state plasma concentrations of 50 to 65 microgram/ml. The data suggest that CFZ needs be given only intraperitoneally at doses lower than those in current use. CPX probably adds little to the treatment of peritonitis.

Administration, Oral↗

Glomerular endothelial injury related to renal perfusion. A scanning electron microscopic study.

To elucidate abnormalities in renal morphology related to perfusion preservation, we examined kidneys perfused for 60 hr with a scanning electron microscope. In addition to tubular necrosis and fused glomerular visceral epithelial foot processes, we identified changes in the glomerular endothelial and arterial endothelial surfaces. The glomerular endothelium revealed fenestrae that were smaller and more irregular than normal, as well as abnormal bulbous projections. The arterial endothelium displayed striking degenerative changes. These abnormalities may account for the altered glomerular function and intravascular coagulation that occur in some kidneys preserved by lengthy perfusion.

Adult↗

Aminoglycoside accumulation kinetics in rat renal parenchyma.

To test the hypotheses that the renal parenchymal accumulation kinetics of aminoglycosides can predict nephrotoxicity, we measured renal parenchymal concentrations in rats receiving gentamicin and tobramycin. In addition to comparing the drugs as single daily injections, we also examined the effect of multiple doses versus a single daily dose. Gentamicin accumulated to much greater concentrations in the kidney than did tobramycin. Gentamicin given twice daily accumulated more rapidly and to greater concentrations than did the same total dose given once daily. We conclude that aminoglycoside accumulation in the kidney depends on the drug and dose regimen. These differences may explain relative nephrotoxicities.

Aminoglycosides↗

Effect of gentamicin treatment on adenylate cyclase and Na+, K+-ATPase activities in renal tissues of rats.

Gentamicin (20 mg/kg) treatment of male rats reduced Na+,K+-ATPase activity by 32% in renal cortical plasma membranes. In contrast, adenylate cyclase stimulation by isoproterenol or a guanyl nucleotide or both was enhanced by as much as twofold in glomeruli and in plasma membranes of gentamicin-treated rats. These effects of gentamicin are suggested to be related to the changes in renal phospholipid metabolism produced by the drug.

Adenylyl Cyclases↗

Sodium sensitivity in normotensive human subjects.

Compelling evidence implicates a high sodium intake in the development and maintenance of arterial hypertension. However, dietary sodium restriction reduces blood pressure in only a fraction of hypertensive patients. Studies in normotensive persons suggest that blacks and older persons excrete a sodium load less efficiently than persons of the same sex and race who are also matched for body weight and body surface area. Blacks show a greater natriuresis and decrease in blood pressure in response to volume contraction with furosemide administration than whites. These observations are consistent with an intrinsic renal abnormality in blacks and older persons, resulting in modest volume expansion. Such changes may contribute to sodium sensitivity and promote the development and maintenance of hypertension in persons with a high sodium intake.

Adult↗