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Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 541 records · Page 30Linked to original sources
PubMed1980

The nephrotoxic potential of netilmicin as determined in a rat model.

The nephrotoxicity of netilmicin, an ethyl derivative of a dehydrogenated Cla gentamicin, was studied in Sprague-Dawley rats. Netilmicin toxicity was initially compared to gentamicin toxicity at equal doses across a broad range. These studies indicated that netilmicin was significantly less toxic than gentamicin. Netilmicin, gentamicin, tobramycin, amikacin, kanamycin, streptomycin, and sisomicin were then given to groups of rats at three dosage levels corresponding to 10, 15 or 25 times the recommended human dose on a weight basis daily for 15 days. Decreased urine osmolality, increased excretion of protein and Beta-n-acetyl hexosaminidase were dose related features of nephrotoxicity. All aminoglycosides accumulated in renal tissue. Streptomycin and netilmicin exhibited a flat dose response curve with respect to histologic damage, as compared to the other drugs. The examination of creatinine clearance and renal tissue suggested the following order of increasing toxicity: (1) controls, (2) streptomycin, (3) netilmicin, (4) tobramycin, (5) sisomicin, amikacin, and kanamycin, and (6) gentamicin. To assess the effect of non-aminoglycoside antibiotics on netilmicin nephrotoxicity, ampicillin, methicillin, carbenicillin, cefamandole, and clindamycin were given to groups of rats receiving netilmicin at either of two doses. These studies suggested that the nephrotoxicity was not affected by the administration of non-aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1980

Nocturnal urinary electrolyte excretion and its relationship to the renin system and sympathetic activity in normal and hypertensive man.

The categorization of patients with essential hypertension into low, normal, and high renin subgroups may be of some value as a research tool. We compared two different methods of renin-sodium indexing, relying on both 24 hr and 10 hr night urine specimens, to a renin suppression-stimulation method involving sodium loading with 2 L of intravenous saline and sodium depletion with 120 mg of oral furosemide plus a 10 mEq sodium diet. Age and race were considered in the analysis. The results from renin-sodium indices failed to consistently correspond with those obtained by the provocative maneuvers. Nocturnal UNaV exhibited a high degree of inverse correlation with renin in normals and all subgroups of hypertensives, whereas aldosterone was not correlated with nocturnal UNaV in patients with nonstimulable or nonsuppressible renin levels. UNeV and PNe were correlated inversely with UNaV and directly with UkV in normal subjects. Similar results were found in hypertensives. We conclude that renin-sodium indices and renin suppression-stimulation maneuvers do not necessarily identify the same hypertensive subgroups, particularly those with nonsuppressible renin. Aldosterone release is dependent on modulators other than sodium balance in patients at either end of the renin spectrum. Sodium intake influences sympathetic activity in normals and hypertensives. The relationship between potassium homeostasis and sympathetic activity warrants further study.

Adult↗
PubMed1979

Rapid blood pressure control with minoxidil: acute and chronic effects on blood pressure, sodium excretion, and the renin-aldosterone system.

Changes in blood pressure, heart rate, electrolyte excretion, and the renin-angiotensin-aldosterone system were monitored before and after minoxidil was added to a regimen of a diuretic and propranolol hydrochloride in 12 severely hypertensive patients. None required more than 40 mg of minoxidil daily for control. On a constant intake, urinary sodium excretion decreased, while urinary potassium excretion remained stable. Heart rate, body weight, and plasma volume increased, while creatinine clearance did not change. Although plasma renin activity increased fourfold, the plasma aldosterone concentration did not increase. Six subjects were restudied after two months of minoxidil treatment. Although blood pressure control continued to be excellent in these subjects, plasma renin values and plasma volume had returned to pretreatment levels. These studies suggest that minoxidil rapidly and effectively lowers blood pressure. Although sodium retention accompanies minoxidil administration acutely, the effect is independent of aldosterone and may be transient.

Adult↗
PubMed1979

Serologic diagnosis of access device-related staphylococcal bacteremia.

Staphylococcal bacteremia occurs frequently in patients undergoing long-term hemodialysis (dialysis patients). Although such bacteremia is frequently uncomplicated, it may be associated with endocarditis, metastatic infection or suppuration at the access site requiring excision of the access device for control of the infection (complicated bacteremia). To distinguish patients with uncomplicated bacteremia from those with complications, we measured staphylococcal teichoic acid antibodies by agar-gel diffusion and immunoglobulin G (IgG) antibodies by radioimmunoassay in 18 patients with staphylococcal bacteremia undergoing long-term hemodialysis. Although teichoic acid antibodies were not detected in five patients with uncomplicated bacteremia, they were observed in only three of 13 patients with complicated bacteremia. IgG staphylococcal antibodies were present in 10 of 13 patients with complicated bacteremia compared to none of five patients with uncomplicated bacteremia compared to none of five patients with uncomplicated bacteremia (p less than 0.05). Thus, radioimmunoassay was spuerior to agar-gel diffusion in identifying dialysis patients with complicated bacteremia. In patients with increased concentrations of IgG staphylococcal antibodies by radioimmunoassay, the diagnosis of endocarditis, metastatic infection and suppuration at the access site should be considered. Prolonged antibiotic therapy and/or operative removal of the access device may be necessary.

Antibodies, Bacterial↗
PubMed1979

Protection from gentamicin nephrotoxicity by cephalothin and carbenicillin.

In rats, cephalothin exerts a protective effect upon the nephrotoxicity of gentamicin. To examine the possibility that this effect is also observed with carbenicillin, we gave the following (milligrams per kilogram) to rats daily for 14 days: gentamicin alone, 60; gentamicin plus cephalothin, 100, 500, or 1,000; gentamicin plus carbenicillin, 50, 100, 250, 500, or 1,000. A 500-mg/kg dose of cephalothin afforded significant partial protection from gentamicin nephrotoxicity, as did a 100-mg/kg dose of carbenicillin. Increasing doses of either drug failed to increase protection. The data suggest that in rats not only does carbenicillin afford some protection from gentamicin nephrotoxicity, but also that it does so at a lower dose than cephalothin. These findings may in part explain the divergent observations regarding the nephrotoxicity of cephalothin-gentamicin combination therapy in rats and humans.

Animals↗
PubMed1979

Effect of cephalothin on measurement of creatinine concentration.

Cephalothin, an antibiotic implicated as nephrotoxic, falsely elevates the creatinine concentration as determined by the Jaffé reaction in vitro. We studied this effect in vivo and demonstrated variable degrees of interference in determinations of plasma and urinary creatinine concentrations by two automated methods. Clinicians should be aware of this phenomenon in patients receiving cephalothin, both when monitoring renal function and when assessing patient reliability in the collection of timed urine specimens.

Cephalothin↗
PubMed1979

Comparative nephrotoxicity of SCH 21420 and amikacin in rats.

The nephrotoxic potentials of the new aminoglycoside SCH 21420 and amikacin were compared in a rat model. Groups of rats received 100, 200, 300, or 600 mg of either drug per kg per day for 14 days. Enzymuria, urine osmolality, protein excretion, and blood urea nitrogen were monitored at periodic intervals, whereas creatinine clearance and pathological changes were determined at sacrifice. Amikacin caused more enzymuria at the two lower doses as well as greater proteinuria and blood urea nitrogen elevations at the highest dose than did SCH 21420 (P less than 0.05). Pathological changes were more severe with amikacin than with SCH 21420 at the three lower doses (P less than 0.05); however, at the 600 mg/kg per day dose, the pathological scores and creatinine clearances of animals receiving either drug were not significantly different (P greater than 0.05).

Amikacin↗
PubMed1979

Hydrolysis of cefamandole nafate in dialysis patients.

The hydrolysis of cefamandole nafate was examined in vivo in five dialysis patients and five subjects with normal renal function. The plasma half-life of cefamandole was prolonged in the patients with renal failure compared with normal subjects (18.3 +/- 4.5 [standard deviation] versus 10.35 +/- 1.4 min, P less than 0.01). The pharmacokinetics of cefamandole nafate best fit two-compartment, open-model kinetics. We conclude that patients with severe renal failure are capable of hydrolyzing cefamandole nafate to cefamandole and formate at a rate sufficiently rapid so as not to allow an accumulation of cefamandole nafate. The difference in half-life may be related to urinary excretion of cefamandole nafate in normal individuals.

Adult↗
PubMed1979

Ferritin- and apoferritin-induced immune complex glomerulonephritis in mice.

In order to study the effects of the protein moiety independent of the protein-iron complex in the development of ferritin-induced glomerulonephritis, we compared the effects of ferritin, equimolar amounts of apoferritin, and equimolar amounts of iron dextran in Swiss albino mice. The results were compared to both saline-injected and non-injected controls. Ferritin resulted in a glomerulonephritis associated with predominantly mesangial deposition of immune complexes. Tubulo-interstitial changes occurred as well. Iron dextran resulted in similar but less severe tubulo-interstitial changes and evoked no glomerular alterations. Apoferritin resulted in an immune complex glomerulonephritis usually associated with membranous deposits. No tubular or interstitial changes occurred. Proteinuria developed in animals receiving apoferritin. Since the protein-iron complex caused tubular and interstitial damage, apoferritin may provide a more suitable model of immune-complex-mediated glomerulonephritis.

Animals↗
PubMed1979

Effects of volume expansion and contraction in normotensive whites, blacks, and subjects of different ages.

We studied the blood pressure, natriuretic, kaliuretic and humoral responses of 347 normal subjects after volume expansion and volume contraction to examine possible differences among whites, blacks and subjects of different ages. According to outpatient 24-hour urine collections, blacks excreted less sodium and potassium than whites. After similar states of sodium intake were achieved among all subjects, 2 liters normal saline were given i.v. Blacks and subjects greater than or equal to 40 years excreted less sodium than whites or subjects less than 40 years, over a 24-hour period. In addition, blacks excreted less potassium. The delay in sodium excretion occurred during the first 12 hours after the salt load. Blacks had a greater suppression of plasma renin activity than whites 24 hours after saline. Blacks also had higher blood pressures than whites after saline administration; their pressure remained elevated until furosemide was given. Furosemide, 120 mg over 24 hours, evoked greater natriuresis, but less kaliuresis in blacks than in whites. The greater prevalence of hypertension in both blacks and older subjects may be related to relatively blunted natriuretic responses when these groups engage in the high sodium-low potassium intake characteristic of our society.

Adolescent↗
PubMed1979

Sensitivity and specificity of screening tests for renal vascular hypertension.

To facilitate the identification of patients with renal vascular hypertension, we evaluated four potential screening tests: rapid-sequence urography, systolic-diastolic abdominal bruit, upright plasma renin activity (PRA), and response to saralasin infusion. Our study included 379 normal subjects, 199 essential hypertensive patients with normal renal angiograms, and 64 patients with surgically responsive renal vascular hypertension. Thirty-nine percent of patients with renal vascular hypertension had systolic-diastolic bruits, 76% abnormal urograms, and 27% a PRA greater than 30 ng of angiotensin 1/mL.3 h. Only one half of the 23 patients with renal vascular hypertension tested had a depressor response to saralasin, as did two of 13 essential hypertensive patients. In essential hypertensive subjects, 1% had systolic-diastolic bruits, 2% abnormal urograms, and 5% upright renin values greater than 30 ng of angiotensin 1/mL.3 h. The screening combination of urogram, bruit, or upright renin value offered a test sensitivity of 93%, with a specificity of 92%. The results of saralasin infusion failed to increase the diagnostic yield.

Abdomen↗
PubMed1979

Percutaneous transluminal angioplasty for renal artery stenosis in a solitary functioning kidney.

In five patients with hypertension and marked impairment of renal function due to renal artery stenosis in a solitary functioning kidney, a nonsurgical technique, percutaneous transluminal angioplasty, was used to dilate the stenotic renal artery. Blood pressure improved in all five patients, and renal function improved in three. One patient subsequently died of multiple cardiovascular complications, and in one patient the procedure resulted in acute renal failure requiring hemodialysis. Although preliminary, this experience suggests that percutaneous transluminal angioplasty may provide an attractive alternative to surgery in severely ill patients at high surgical risk.

Aged↗
PubMed1979

The effect of extremely high sodium intake on plasma renin activity, plasma aldosterone concentration, and urinary excretion of aldosterone metabolites.

The effect of sodium intake on aldosterone production was examined in eight healthy men whose urinary sodium excretion approached their dietary sodium intake at levels of 10, 300, 800 and 1500 mEq sodium/day. Aldosterone secretion was estimated from the excretion rate of two aldosterone metabolites: Thaldo and aldosterone-18-glucuronide. Maximal suppression of aldosterone secretion appeared to have been reached when sodium intake was 800 mEq/day, since no further decrease in aldosteron metabolite excretion rates was observed at 1500 mEq/day dietary sodium. Both plasma renin activity and plasma aldosterone concentration were suppressed and approached or were below the detection limits of the respective radioimmunoassays when sodium intake reached 800 and 1500 mEq/day. Body weight and blood pressure significantly increased at each increment of sodium intake. Our findings show that when sodium intake is extremely high, aldosterone secretion does not decrease to zero but continues at a rate we estimate to be 10 to 30 microgram/day. We suggest that this nonsuppressible secretion of aldosterone may have contributed to the observed increases in weight and blood pressure.

Adult↗
PubMed1979

Effects of sodium loading and depletion in normotensive first-degree relatives of essential hypertensives.

To examine potential mechanisms responsible for the greater prevalence of hypertension among relatives of hypertensives than among relatives of normotensives, we subjected 43 normotensive first-degree relatives of known essential hypertensives and 43 age-, race-, and sex-matched normal subjects with no family history of hypertension to sodium loading and depletion. The data show that the relatives had higher blood pressures than did controls. They also had higher PRA values before and after a 2 L intravenous saline infusion over 4 hr. In addition, the relatives excreted less (p less than 0.05) sodium on the day of the infusion than did the controls. PA values and UNe excretion in the two groups did not differ. In the relatives, age correlated with systolic and diastolic blood pressure. Age correlated inversely with the 24 h urine sodium excretion on the sodium loading day. These correlations were not observed in controls. Normotensive first-degree relatives of hypertensives differ from relatives of nonhypertensives in that they have higher PRA values and a blunted natriuretic response to a saline load. These features may predispose them to the development of hypertension.

Adult↗