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Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 559 records · Page 31Linked to original sources

Minoxidil treatment of malignant hypertension. Recovery of renal function.

We treated eight severely hypertensive, long-term hemodialysis patients who failed to respond to ultrafiltration or conventional medication with minoxidil rather than with bilateral nephrectomy. Control of blood pressure and relief of symptoms was achieved in all eight. In addition, three of the patients, who were all severely oliguric, recovered sufficient renal function to allow the discontinuation of dialysis. Two are presently doing well, while one died of causes unrelated to uremia or minoxidil therapy. We presently reserve bilateral nephrectomy for those hypertensive dialysis patients who are awaiting transplantation.

Acute Kidney Injury↗

Intra-abdominal infection and acute renal failure.

The course of 76 consecutive patients with acute renal failure and severe intra-abdominal infection was reviewed to identify the microorganisms responsible, the factor precipitating reoperation, and prognostic indicators. Peritonitis occurred in 75 patients, 48 of whom had abscesses. Twenty-four patients (32%) survived. Anaerobes and fungi were commonly grown from blood. Gram-negative aerobic blood isolates were associated with the highest mortality. Leukocytosis, physical findings, and fever were factors that prompted reexploration whereas diagnostic procedures played an ancillary role. The finding of specifically correctable conditions at reoperation improved survival (P less than .05). Myocardial infarction and disseminated intravascular coagulation affected survival unfavorably whereas hyperalimentation had a favorable influence (P less than .05). Aggressive medical, nutritional, and surgical management results in improved survival rates in these patients.

Abdomen↗

Long term effect of cis-diamminedichloride platinum (CDDP) on renal function and structure in man.

To examine CDDP induced nephrotoxicity in patients with testicular carcinoma, we measured renal function prior to therapy and at six month intervals for twelve months in fifteen patients and twenty-four months in seven patients. CDDP was given iv at 20 mg/M2 per day for five days at three week intervals. Eight patients received three courses, four received four courses and three received more than four courses. The mean creatinine clearance +/- SD prior to treatment was 112 +/- 12 ml/min. By six months, it had decreased to 68.5 +/- ml/min (p less than 0.01) and it remained at that level. Plasma creatinine and blood urea nitrogen increased significantly. Subjects receiving other potential nephrotoxins in addition to CDDP developed a greater decrease in creatinine clearance (p less than 0.05). Proteinuria and functional tubular disturbances were not observed. Microscopic features were characterized by hydropic degeneration of the renal tubular epithelium, thickened tubular basement membranes and mild interstitial fibrosis. Electron microscopy revealed phagolysosomes filled with flocculent material. CDDP resulted in a permanant, nonspecific renal injury in our patients. Although the renal injury has remained subclinical, future courses of CDDP may lead to clinically important chronic renal failure.

Adolescent↗

Calcitriol in dialysis patients.

We conducted a 7-month randomized, single, double, single-blind comparison of calcitriol (1,25(OH)2D3) with vitamin D3 in 22 hemodialysis patients to study the effects on the biochemical abnormalities associated with osteodystrophy. Calcitriol was given for 3 mo. All patients had initial prestudy calcium values less than or equal to 9.5 mg/100 ml, and phosphate values less than or equal to 4.5 mg/100 ml. Data were analyzed using the Normalized Trend Index (NTI). Calcitriol induced a rise in calcium (8.7 to 10.25 mg/100 ml) (p less than 0.001) and a fall in alkaline phosphatase (p less than 0.005), while D3 had no appreciable effect. The mean dose of calcitriol during treatment was 0.579 microgram/day while that for D3 was 706 IU/day. The effect on serum phosphate concentration was variable. Hypercalcemia as high as 13.2 mg/100 ml occurred in 2 of 13 patients on 1,25(OH)2D3, but in every instance promptly returned to normal with dose reduction. No other adverse effects were noted with therapy. We conclude that calcitriol reverses the biochemical abnormalities of osteodystrophy. Since its effects are rapidly reversed with discontinuation, the drug is probably safe as well as effective.

Adult↗

Cisplatin pharmacokinetics in a patient with renal dysfunction.

Plasma and urine platinum concentrations were measured by atomic absorption spectrophotometry during a three-day course of cisdiamminedichloroplatinum (DDP, cis-platinum, cisplatin) therapy in a patient with acute renal failure who was being treated with hemodialysis. Twenty-four hour urine collections, obtained during the oliguric phase, accounted for only 0.36--0.56 percent of the daily DDP dose. The plasma t1/2beta of platinum was approximately 240 hours after the last DDP dose. Platinum could be measured in the dialysate only during the first two hours after DDP administration. Although the data show that the t1/2beta of DDP is prolonged three fold in a patient with profound renal failure, the clinical implications of these findings await further studies.

Acute Kidney Injury↗

A new approach to the difficult assessment of aldosterone secretion in anephric patients.

A new method for the assessment of endogenous formation of aldosterone in anephric patients is described. (1, 2-3H) aldosterone was administered i.v. to patients 1-2 days before hemodialysis, and then the specific activity (SA) of tetrahydroaldosterone glucosiduronate, the major aldosterone metabolite, was measured in the dialysate using a specific radioimmunoassay. The aldosterone secretion rate was determined from the extent of isotope dilution by endogenous metabolite. Aldosterone secretion rates measured in 10 patients were for the most part low. The secretion rate determined in blood from the aldosterone metabolic clearance rate and plasma aldosterone concentration closely approximate secretion rate values obtained by the isotope dilution method in 3 of 4 patients. In 2 patients in whom ACTH was administered chronically, radio-labeled aldosterone was administered at the start of the study and then the day to day aldosterone secretory response to ACTH was determined from the SA of tetrahydroaldosterone in blood. Aldosterone secretion continuously increased for as long as ACTH was administered.

Adolescent↗

Biochemical correlates of the increase in blood pressure with age.

1. Blood pressure, plasma renin activity, plasma aldosterone, urinary noradrenaline during sleep (UNA-S) and several estimates of sodium intake were determined in 379 normotensive subjects (age 13--70) to investigate the relationship of these variables to blood pressure. 2. Blood pressure was correlated with age, weight, plasma renin activity UNA-S, and estimates of sodium intake. There variables were frequently intercorrelated. 3. Multiple-correlation analysis revealed that after removal of the effects of age, blood pressure was related to weight, plasma renin activity, UNA-S and estimates of sodium intake. 4. However, multiple-regression analysis failed to demonstrate an effect of plasma renin activity, UNA-S, or estimates of sodium intake on blood pressure when the effects of age, weight, race and sex were removed. 5. Careful matching of subjects by age, weight, race and sex in studies of blood pressure and biochemical factors in normal subjects is crucial to proper interpretation of such data.

Aging↗

Iatrogenic factors in acute renal failure: can vigilance equal avoidance?

Physicians can aid substantially in reducing morbidity and mortality from acute renal failure by exercising particular care when using potentially nephrotoxic procedures or agents, by identifying patients at high risk before undertaking elective surgical procedures, and by acting promptly to correct predisposing conditions.

Acute Kidney Injury↗

Comparative nephrotoxicity of aminoglycoside antibiotics in rats.

Netilmicin, gentamicin, tobramycin, amikacin, kanamycin, streptomycin, and sisomicin were given daily for 15 days to groups of rats at three dosage levels corresponding to 10, 15, or 25 times the dose recommended for humans on a weight basis. Decreased urinary osmolality and increased urinary excretion of protein and beta-N-acetyl hexosaminidase were dose-related features of nephrotoxicity. Decreased tubular resorption of glucose and phosphate were observed with the most toxic regimens after extensive renal damage had occurred. All aminoglycosides accumulated in renal tissue; however, the concentration of drug in the renal cortex at the time the rats were killed was not useful for the prediction of renal impairment. Streptomycin and netilmicin exhibited a flat dose-reponse curve with respect to histological damage, as compared with the curves for the other drugs. Results of studies of creatinine clearance and examination of renal tissue suggested the following order of increasing toxicity of the treatment regimens: (1) 0.9% NaCl and uninjected controls; (2) streptomycin; (3) netilmicin; (4) tobramycin; (5) sisomicin, amikacin, and kanamycin; and (6) gentamicin.

Amikacin↗

Nephrotoxicity of netilmicin in combination with non-aminoglycoside antibiotics.

To assess the possibility that non-aminoglycoside antibiotics may adversely affect the nephrotoxicity of the new semisynthetic aminoglycoside netilmicin, we gave ampicillin, carbenicillin, methicillin, cefamandole, and clindamycin, either singly or in combination with netilmicin, at two dose concentrations in rats. Results were compared as to the effect of netilmicin given singly and to saline-injected and noninjected controls. Antibiotic combinations resulted in no greater nephrotoxicity than did netilmicin alone. Netilmicin concentrations in renal tissue were high, and these levels were not consistently affected by the other drugs. The data suggest that in rats the nephrotoxicity of netilmicin is not affected adversely by the presence of non-aminoglycoside antibiotics.

Aminoglycosides↗

Recovery from aminoglycoside nephrotoxicity with continued drug administration.

To examine the nephrotoxicity of prolonged gentamicin administration compared to the effect obtained when a less toxic aminoglycoside is substituted during the course of treatment, we gave gentamicin (67.5 mg/kg per day) to rats for 21 days, gentamicin for 14 days followed by either netilmicin or tobramycin for 7 days, or gentamicin for 14 days followed by saline diluent. After initial tubular, necrosis, the animals recovered from renal injury whether the drug was continued or discontinued or another drug was substituted. These data are consistent with the observation that regenerating renal epithelium is resistant to continued or additional nephrotoxic insults. These findings suggest that improvement in renal function during aminoglycoside therapy cannot necessarily be attributed to the substitution of another aminoglycoside or other therapeutic interventions.

Animals↗

Pharmacokinetics of netilmicin in patients with renal impairment and in patients on dialysis.

The pharmacokinetics of netilmicin were examined in 25 adult subjects, 7 normal subjects, and 18 patients with renal impairment. Five were dialysis patients who were studied on and off dialysis. Netilmicin, 2 mg/kg, was infused intravenously over 1 h. The peak serum concentration ranged from 9 to 11 mug/ml. The mean biological half-life of netilmicin for subjects with a creatinine clearance (Ccr) > 70 ml/min was 2.7 h, for those with Ccr > 25 < 70 ml/min it was 10 h, for those with Ccr > 4 < 25 ml/min it was 32 h, and for those who were anephric it was 42 h. Ccr was correlated positively with the elimination constant and the drug's serum clearance. It was negatively correlated with the drug's volume of distribution. The dialyzer clearance of netilmicin was positively correlated with plasma flow rate and was similar to values previously reported for gentamicin. Netilmicin behaves in a fashion similar to other aminoglycosides. Therapeutic guidelines are suggested.

Adult↗

Netilmicin: a review of toxicity in laboratory animals.

The data on the toxicity of netilmicin in laboratory animals as well as preliminary data in man are reviewed. Netilmicin is less toxic to the VIIIth nerve than is gentamicin in all species tested. The data suggest that it probably is less ototoxic than tobramycin, although confirmatory studies should be performed. Netilmicin is also nephrotoxic than gentamicin in all species tested. It is less nephrotoxic than tobramycin in the rat and dog. Comparisons in the rat suggest that netilmicin has a flat dose--response curve that resembles the curve produced by streptomycin. In animals, netilmicin produces more neuromuscular blockade than gentamicin; however, neuromuscular blockade with aminoglycosides in man is rare and thus far no episodes have been associated with netilmicin during clinical investigation. Initial clinical studies in man indicate that netilmicin is efficacious and well tolerated. Presently available data suggest that netilmicin offers distinct advantages over older aminoglycosides. Final conclusions must await prospective randomized double-blind trials in man.

Abnormalities, Drug-Induced↗

Prevailing patterns and predictor variables in patients with acute tubular necrosis.

The courses of 276 acute tubular necrosis patients referred for dialysis were reviewed in search for prognostic indicators. Sixty-three percent survived. Of 28 possible predictor variables, a posttoxic cause and nonoliguria were favorable, whereas myocardial infarction and peritonitis affected survival unfavorably. Total pareneral nutrition influenced survival favorably only in those with multiple complications or peritonitis. No single variable or combination predicted a lethal outcome. Since survivors were frequently restored to complete health, we advocate an aggressive therapeutic approach even in the face of multiple complications.

Acute Kidney Injury↗