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Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 595 records · Page 33Linked to original sources

Enzymuria in gentamicin-induced kidney damage.

To assess their potential value as early indicators of gentamicin-induced kidney damage, lysosomal hydrolases were measured in the 24-h urines of rats receiving 30 or 60 mg of gentamicin per kg per day for 15 days. Proteinuria, urine osmolality, blood urea nitrogen, and creatinine clearance were also measured. Kidney tissue was examined by both light and electron microscopy. Beta-galactosidase, beta-n-acetyl-hexosaminidase, and alpha-fucosidase were sensitive indicators and were significantly elevated above control values by day 3 at both doses (P < 0.01). Proteinuria, urine osmolality, and tests reflecting glomerular filtration rate were later indicators of nephron damage. Changes by light microscopy were detected on day 5. Necrosis was most prominent in the proximal convoluted tubules on day 10. Electron microscopy revealed numerous cytosomes with myeloid bodies within the proximal tubular epithelium on day 5. Lysosomal enzymuria appears to be an early manifestation of gentamicin nephrotoxicity and may possibly be related to the lysosomal abnormalities seen on electron microscopy.

Animals↗

Acute renal failure following operation for aortic aneurysm.

Thirty-eight patients with acute renal failure following operation for aortic aneurysm were analyzed retrospectively in search of predictors of survival. Of 14 potential predictor variablesonsidered, none taken singly were significant; however, the combination of age, operative interruption of renal blood flow and prior renal dysfunction served as a significant predictor, p less than 0.05. Low survival rates occurred if the patient was over 70 years of age, if renal blood flow required interruption or if preoperative renal impairment was present. High survival rates occured in patients less than 70 years of age who had no interruption of renal blood flow and who had normal preoperative renal function. Although the total mortality rate of these patients with acute renal failure was 61 per cent, only one of 12 patients with favorable prognostic indicators died. Acute renal failure following aortic aneurysm repair has no worse prognosis that that stated in the literature for acute renal failure following other surgical procedures. A virorous therapeutic approach should be maintained despite the advent of complications.

Acute Kidney Injury↗

Experimental aminoglycoside nephrotoxicity.

The nephrotoxicities of gentamicin and three other experimental aminoglycosides were compared at a single 60 mg. per kilogram per day dose in rats. Renal function, lysosomal enzymuria, and antibiotic concentrations in plasma, urine, and renal tissue were measured at regular intervals throughout the course of treatment. Kidney tissue was examined by light and electron microscopy in animals killed at intervals throughout the period of antibiotic administration. Proteinuria and enzymuria were early indicators of nephron dysfunction, whereas endogenous creatinine clearance declined later in the course of treatment. All animals were killed 24 hours after a previous antibiotic injection and displayed sustained renal tissue antibiotic concentrations which were 5 to 10 times higher than those in serum or urine. When assayed separately, renal cortical tissue had a fivefold greater antibiotic concentration than renal medulla. Light microscopy displayed necrosis of the pars convoluta of the proximal tubule. Electron microscopy revealed appearance of cytosegrosomes with myeloid bodies. It is possible that impaired cytoplasmic degradation of sequestered organelle membranes, resulting from aminoglycoside accumulation, is responsible for the myeloid body formation and subsequent tubular necrosis.

Aminoglycosides↗

Comparison of the distribution of tobramycin and gentamicin in body fluids of dogs.

Tobramycin serum, thoracic lymph, renal lymph, and urine concentrations were measured in mongrel dogs after intravenously administered 5, 10, and 20 mg/kg doses. These were compared with intravenous gentamicin delivered at 5 and 20 mg/kg. Both drugs achieved similar concentrations in serum and thoracic lymph. At 20 mg/kg, tobramycin showed consistently higher renal lymph and urine concentrations than gentamicin. At 5 mg of tobramycin per kg, renal lymph and urine concentrations were higher than with gentamicin only within the 1st h after administration. Thereafter the difference was no longer significant. These data suggest that on the basis of distribution in the body fluids of dogs, tobramycin is a reasonable alternative to gentamicin.

Animals↗

Effect of noise stress and ethanol intake on hearts of spontaneously hypertensive rats.

The pathogenesis and progression of hypertensive heart disease are unclear; however, both involve a genetic predisposition and environmental influences. To test the role of exogenous factors, we examined the hearts of spontaneously hypertensive rats (SHR) exposed to noise stress and ethanol intake. Twenty-two SHR and nine normotensive Wistar rats (NWR) were continuously exposed to a 65 db, 4 and 250 Hz tone for 52 weeks. Twelve of these SHR aged 20-22 weeks were concomitantly given 20% ethanol in their drinking water up to week 52. Eight SHR and 12 NWR served as controls. We examined hemodynamic parameters, the cardiac configuration, the cardiac microvasculature, interstitial tissue, and ischemic myocardial lesions. We found that noise stress significantly increased the microvessel wall area, the number of microvessels with an outer diameter > 19 microns, the degree of cardiac fibrosis, and the extent of ischemic myocardial lesions in SHR, but not in NWR. These effects were all ameliorated and the diastolic blood pressure was lowered by the ingestion of ethanol. Cardiac weights and dimensions, heart rate and dp/dtmax were not influenced by either noise or ethanol intake. These results suggest that hypertensive heart disease in SHR can be aggravated by noise stress. Ethanol ameliorates these changes by mechanisms which remain to be explored.

Animals↗

Piperidine renin inhibitors: from leads to drug candidates.

Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalizes albuminuria and kidney tissue damage in these rats when given over a period of 4 weeks. These data suggest that treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status.

Animals↗

Atrial natriuretic factor--a circulating hormone stimulated by volume loading.

The cardiocytes of mammalian cardiac atria contain granules very similar to those in endocrine cells. The number of these atrial granules is related directly to salt loading and blood volume. Furthermore, crude extracts of rat atria and granule preparations have powerful natriuretic and diuretic effects. These effects are mediated by peptides identified previously as atrial natriuretic factor (ANF). The peptides are derived from a common precursor, whose structure has been elucidated recently. Although there is indirect evidence from morphological studies that at least some of these peptides may be released into the blood and function as hormones, their presence in the blood has not yet been demonstrated. Here we describe a sensitive and specific radioimmunoassay for ANF and its stimulation on volume loading.

Animals↗

Gender-specific response to interstitial angiotensin II in human white adipose tissue.

Angiotensin II is synthesized locally in various tissues. However, the role of interstitial angiotensin II in the regulation of regional metabolism and tissue perfusion has not as yet been clearly defined. We characterized the effect of interstially applied angiotensin II in abdominal subcutaneous adipose tissue of young, normal-weight, healthy men (n = 8) and women (n = 6) using the microdialysis technique. Adipose tissue was perfused with 0.01, 0.1, and 1 micro M angiotensin II. Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured to assess changes in blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. Baseline ethanol ratio and dialysate lactate were both significantly higher, whereas dialysate glucose was significantly lower in men vs. women. In men, ethanol ratio and dialysate glucose, lactate and glycerol did not change significantly during perfusion with angiotensin II. In women, however, angiotensin II induced a significant increase in ethanol ratio and dialysate lactate and a decrease in dialysate glucose close to values found for men and this response was almost maximal at the lowest angiotensin II concentration used. Dialysate glycerol did not change significantly. We conclude that baseline blood flow and glucose supply and metabolism is significantly higher in women than in men. In men, interstitial Ang II has only a minimal effect on adipose tissue blood flow and metabolism. In women, however, a high physiological concentration of interstitial angiotensin II can reduce blood flow down to values found in men. This is associated with an impaired glucose supply and metabolism. Additionally, Ang II inhibits lipolysis.

Abdomen↗

Long-term studies of the effect of rifampin on nasal carriage of coagulase-positive staphylococci.

Eighty healthy men with nasal carriage of coagulase-positive staphylococci were given cloxacillin, rifampin, cloxacillin plus rifampin, or no drug. Treatment with rifampin alone or with rifampin plus cloxacillin eradicated the original strain from 80% of the men for 12 weeks after treatment; 15%-20% of the 80 subjects acquired a strain of a different phage type. Treatment with cloxacillin alone did not significantly alter the rate of carriage. Only one of 40 men receiving rifampin (either alone or with cloxacillin) acquired rifampin-resistant, coagulase-positive staphylococci; seven of the 40 acquired rifampin-resistant, coagulase-negative staphylococci. Rifampin-resistant organisms did not persist in repeat nasal cultures five months after treatment. Of the 40 subjects given rifampin alone or rifampin plus cloxacillin, 60% had repeat nasal cultures done one year later. Only 50% were found to be carriers of coagulase-positive staphylococci. In another study, coagulase-positive staphylococci were eradicated from 70% of 20 carriers undergoing renal dialysis who received rifampin plus cloxacillin.

Carrier State↗

Infections or neoplasm as causes of prolonged fever in cancer patients.

Thirty-six consecutive patients with cancer who met the classical criteria for fever of unexplained origin (FUO) were identified. A total of 18 patients had infections including all 12 with leukemia, four of 12 with Hodgkin's disease, and two with solid tumors. Fungal infections were found in nine: histoplasmosis, three; candidiasis, three; and aspergillosis, systemic sporotrichosis, or cryptococcal meningitis, one each. Six patients had unresolved pyogenic infections and one had tuberculous pericarditis. Two others had viral etiologies. Granulocytopenia was significantly more common in the FUO patients with documented infections. Clinical or laboratory abnormalities suggesting involvement of a specific organ or organ system provided important clues indicating infections. Morphological examination of biopsy specimens, with cultures, was the best method for diagnosis. In 18 patients, 12 with lymphomas and 6 with solid tumors, only the neoplasm appeared responsible for the fever. In these patients there was a paucity of abnormalities indicating organ system involvement with infection. Regardless, physicians' diagnostic efforts should not be deterred in such patients. Repeated thorough evaluations for infection are warranted.

Adolescent↗

Natriuretic responses in labile hypertension.

To characterize humoral and renal excretory responses following provocative maneuvers in subjects with labile hypertension, we measured plasma renin activity (PRA), plasma aldosterone (PA), plasma norepinephrine (PNe), urinary norepinephrine (UNe), urinary sodium excretion (UNaV), urinary potassium excretion (UKV), and fractional excretion of sodium (FENa) following both volume expansion with a 150 mEq Na diet and intravenous administration of 2L normal saline over four hours, and volume contraction with a 10 mEq Na diet and 120 mg oral furosemide. Results from 37 labile hypertensives were compared to those from the same number of age-, race-, and sex-matched normal subjects or patients with fixed essential hypertension. PRA, PA, PNe, UNe, and UKV responses were no different in the three groups. UNaV and FENa during the saline load was greater in labile hypertensives than in the other groups. While FENa was inversely related to PRA in both normals and fixed hypertensives, no such relationship was found in subjects with labile hypertension. In labile hypertensives, FENa was correlated with PNe concentrations. Furthermore, in these subjects sodium excretion and norepinephrine excretion were associated as well. We suggest that labile hypertensives exhibit exaggerated natriuresis which may be mediated by neurogenic mechanisms.

Adult↗

Genetic and environmental influences on coping styles: a twin study.

OBJECTIVE: Coping styles are generally considered to be environmentally driven, primarily by family influences. However, because personality traits are commonly influenced by genetic effects, we hypothesized that heredity is also important for coping. METHODS: We tested this hypothesis by assessing 19 coping styles, as well as four secondary coping factors, by questionnaire in 212 pairs of monozygotic and dizygotic twins. We then examined heredity by structural equation modeling. RESULTS: All coping styles showed evidence of genetic influences. The coping styles shared one common genetic factor. In addition, each coping style was also influenced by other separate genetic factors. Shared environment had no significant influence on coping styles. Three of 19 more specific coping styles showed shared environmental effects as well as genetic influences, 14 were solely under genetic influences, and two showed only shared environment effects. CONCLUSIONS: We suggest that hereditary effects on certain coping style preferences cannot be explained solely by genetic influences on major personality traits and temperament. An analysis of the relationships between coping and personality in twin subjects may elucidate the distinction between genetic and environmental effects.

Adaptation, Psychological↗