Search PubMed⌕ Search

Biomedical subjects

R Levine

Publications and source records attributed to R Levine.

At least 109 records · Page 6Linked to original sources
PubMed1985

Effect of gentamicin on lipid peroxidation in rat renal cortex.

We examined the hypothesis that lipid peroxidation participates in the pathogenesis of aminoglycoside-induced nephrotoxicity. Male Sprague-Dawley rats were injected subcutaneously with gentamicin, 100 mg/kg per day, for 1-4 days. Twenty-four or forty-eight hours after the last injection the rats were killed and the renal cortex was processed for total phospholipids, malondialdehyde (MDA), phospholipid fatty acid composition, superoxide dismutase, catalase and glutathione. Gentamicin induced a significant increase in total renal cortical phospholipids which was evident after a single injection and by the third injection reached a plateau 17% above the baseline level. MDA, an end product of lipid peroxidation, increased from 0.674 +/- 0.021 nmole/mg protein in the control group to 0.931 +/- 0.053 nmole/mg protein (P less than 0.001) 48 hr after the fourth injection. As another index of lipid peroxidation, we determined the shift from polyunsaturated to saturated fatty acids of renal cortical phospholipids. By the second injection of gentamicin we detected a significant decline of arachidonic acid (20:4) present in phospholipid. By the fourth injection, arachidonic acid had fallen 48% below control and was accompanied by reciprocal increases of more saturated fatty acids including linoleic (18:2), oleic (18:1) and palmitic (16:0) acids. The number of double bonds per mole of fatty acid declined from a baseline value of 1.62 +/- 0.01 to 1.20 +/- 0.02 (P less than 0.001) by the fourth injection of drug. Superoxide dismutase showed no consistent alteration, whereas catalase activity (k) fell from the control value of 0.221 +/- 0.007 min to 0.155 +/- 0.009 min (P less than 0.01) by the third injection, where k is the first-order rate constant. Total and reduced glutathione declined after the fourth injection of gentamicin accompanied by a shift to oxidized glutathione with an increase in the ratio of oxidized to total glutathione. These data support the conclusion that accelerated lipid peroxidation occurs early in the course of gentamicin administration and raise the possibility that lipid peroxidation is a proximal event in the injury cascade of gentamicin nephrotoxicity.

Animals↗
PubMed1985

Characterization and automatic identification of ECG conduction abnormalities using segmental multiharmonic Fourier analysis of gated blood-pool scintigrams.

This study of biventricular segmental timing sequences compared patterns of the first-harmonic phase with those of multiharmonic Fourier-analysis-derived parameters to determine their suitability for the classification of patients using an automatic pattern recognition scheme. The study involved nine patients with normal ECGs, six with left bundle branch block, 4 with right bundle branch block, and 6 with right-ventricular pacemakers; all patients had normal left-ventricular function. The segmental sequence described by the time of end systole was similar to that described by the first-harmonic phase, with a lower correlation using the time of maximum filling rate, and a rather poor correlation of the time of maximum ejection rate with the other parameters. Thus, despite theoretical difficulties, timing patterns described by phase best agreed with those of the time of end systole. Intersegmental timing differences were used as criteria for discriminating between groups by means of a sequential logic tree. Using either phase, time of end systole or time of maximum ejection rate, all patients were correctly classified into the four ECG categories. More intersegmental timing differences were useful as criteria for phase (57) than for the time of end systole (45) or the time of maximum ejection rate (30). The first-harmonic phase was more efficient than the time of end systole for separating patient groups. Sequential biventricular timing disorders can be objectively classified using either first-harmonic or multiharmonic Fourier analysis, and their patterns can be automatically recognized and used for classification.

Bundle-Branch Block↗
PubMed1985

Twin pregnancy: routine use of ultrasound examinations in the prenatal diagnosis of intrauterine growth retardation and discordant growth.

A prospective study was undertaken in 42 normal twin pregnancies to determine the value of routine ultrasound evaluation in the prenatal diagnosis of intrauterine growth retardation (IUGR) and intra-pair growth discordancy in twin gestations. Use of multiple sonographic parameters significantly improved diagnostic accuracy when compared with the use of single parameters, such as biparietal diameter (BPD) alone in the prepartum diagnosis of these two entities.

Adolescent↗
PubMed1985

Public health investigations of hazardous organic chemical waste disposal in the United States.

Despite marked national concern, the number of published public health investigations of organic chemical hazardous wastes is small. Moreover, the extant literature provides little or no convincing evidence, either positive or negative, as to the question whether waste sites are harmful to human health. In this review, available literature is characterized as to time, place, and person. The majority of studies began 2 years or more after the end of exposure and 10 years after the start of exposure. Vast geographic areas of exposure have never been investigated. The number of study subjects evaluated has generally been too small to detect rare but important effects. The most common determinant of sites chosen for investigation has been the concern of local citizen groups. Several hypotheses are advanced to explain this pattern: methodologic and logistic difficulties; extensive litigation surrounding many waste sites; governmental reorganization which transferred environmental health from public health authority in the 1970s; and the presence of forces which have worked to block active community diagnosis.

Child↗
PubMed1985

CT of splenic and perisplenic abnormalities in septic patients.

Splenic and perisplenic pathology, demonstrated by CT examination in 14 septic patients, was correlated with the clinical course and with surgical and pathologic findings available. Twelve patients were intravenous drug addicts and two patients developed bacteremia associated with bacterial endocarditis. The CT findings were divided into three groups: (1) Single wedge-shaped peripherally located defects were seen in five patients; there was good response to medical therapy without other complications. (2) Larger and/or multiple, rounded or oval lesions were present in five patients; two of these patients had splenic abscesses proven on subsequent splenectomy. (3) Multiple splenic lesions and fissures associated with perisplenic and subphrenic fluid collections were seen in four patients; infected splenic infarcts, splenic fractures, and infected perisplenic hemorrhagic fluid collections were found in this group of patients. The CT examination in septic patients can reliably demonstrate splenic and perisplenic pathology, and its appearance contributes greatly to the overall clinical assessment and surgical approach.

Abscess↗
PubMed1985

Contrasting effects of gentamicin and mercuric chloride on urinary excretion of enzymes and phospholipids in the rat.

Gentamicin induces a phospholipiduria in the rat. We sought to determine whether the phospholipiduria reflected shedding of brush border membrane by measuring the urinary excretion of membrane marker enzymes, by defining the composition of the urinary phospholipids, and by examining the renal cortex and urinary sediment using transmission electron microscopy of rats injected with gentamicin sulfate (100 mg/kg of body weight for 1 to 6 days). The results were compared and contrasted with those of rats injected with mercuric chloride, a nephrotoxin known to cause selective injury to the brush border membrane. Gentamicin-injected rats exhibited a phospholipiduria that by the third day was 10-fold above the baseline level. In contrast the brush border membrane enzymes alanine aminopeptidase and gamma-glutamyl transferase and the lysosomal enzyme N-acetyl-beta-glucosaminidase increased less than 1-fold above baseline. Electron microscopy of the renal cortex revealed the presence of myeloid bodies within lysosomes of proximal tubule cells and lying free within the lumen. The brush border membrane was largely intact. The urine sediment was dominated by the presence of myeloid bodies; there was little evidence of brush border membrane fragments. The urinary phospholpids were enriched in phosphatidylinositiol, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. This pattern is similar to that of a lysosomal fraction enriched in myeloid bodies. Rats injected with mercuric chloride exhibited a phospholipiduria associated with sharp increases (7- to 15-fold) in the urinary excretion of brush border membrane enzymes, whereas N-acetyl-beta-glucosaminidase increased less than 3-fold. Electron microscopy revealed blebbing of the apical membrane with loss of microvilli of proximal tubular cells particularly evident along the pars recta. The urinary sediment contained microvilli and fragments of plasma membrane but no myeloid bodies. The urine contained large quantities of sphingomyelin. In the rat renal cortex the brush border membrane is the major source of this phospholipid. We conclude that the phospholipiduria induced by mercuric chloride is derived primarily from the shedding of brush border membrane fragments into the urine. In contrast, the urinary excretion of phospholipid induced by gentamicin reflects primarily the extrusion of the lysosomal myeloid body from proximal tubular cells. We speculate that the origin of the phospholipids making up the lysosomal myeloid body may be the endocytic vesicle that mediates the transport of aminoglycosides into the lysosomal system.

Aminopeptidases↗
PubMed1985

Effect of netilmicin on the phospholipid composition of subcellular fractions of rat renal cortex.

The purpose of this study was to determine the subcellular site(s) of the renal cortical phospholipidosis induced by aminoglycosides. For this purpose we injected male Sprague-Dawley rats s.c. with netilmicin, containing tracer quantities of [3H]netilmicin, at 100 mg/kg/day for 2 days; control rats were injected with saline. Twenty-four hours after the second injection of drug the rats were sacrificed and the renal cortex was fractionated by differential ultracentrifugation and Percoll gradient density techniques to obtain purified lysosomes, mitochondria, microsomes, brush border membranes and basolateral membranes. The total phospholipid content of the renal cortex was 300 +/- 5 nmol/mg of protein in control rats and 340 +/- 5 nmol/mg of protein in netilmicin-injected rats. The total phospholipid content of the lysosomal fraction of netilmicin rats, which was enriched in myeloid bodies and [3H]netilmicin, was 91% greater than that of control rats and reflected significant increases of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. This pattern is identical to that reported previously for the rat renal cortical phospholipidosis induced by aminoglycosides. The total phospholipid contents of the mitochondrial, microsomal, brush border membrane and basolateral membrane fractions of netilmicin-injected rats were higher by approximately 10% than the respective fractions of control rats and each fraction exhibited a significant increase of one or more of the four phospholipids elevated in the renal cortical homogenate and in the lysosomal fraction. The data indicate that the myeloid body is the primary source of the lysosomal phospholipidosis induced by netilmicin which provides support for the hypothesis that the lysosomal phospholipidosis is secondary to aminoglycoside-induced inhibition of phospholipid degradation. In addition the findings of increased phospholipid content and altered phospholipid composition of the other subcellular fractions raise the possibility that aminoglycoside antibiotics cause a more generalized disturbance of phospholipid metabolism characterized by altered synthesis as well as degradation in renal proximal tubular cells.

Acetylglucosaminidase↗
PubMed1985

[3H]netilmicin binding constants and phospholipid composition of renal plasma membranes of normal and diabetic rats.

We examined the hypothesis that the decreased renal accumulation of aminoglycosides in rats with streptozotocin-induced diabetes mellitus is due to decreased membrane binding of drug consequent to reduced membrane content of the putative aminoglycoside receptor, phosphatidylinositol. Renal brush border membrane (BBM) and basolateral membrane (BLM) vesicles were prepared from normal and diabetic Sprague-Dawley rats by differential centrifugation and Percoll gradient techniques which yielded relatively pure membrane fractions as assessed by measurements of marker enzymes and by electron microscopy. Binding of [3H]netilmicin to plasma membranes was performed using a fast filtration technique. Scatchard analysis of the binding data indicated that netilmicin bound to a single class of receptors on BBM and BLM from normal rats with an affinity constant of 33 +/- 2 X 10(3)M-1 and 23 +/- 2 X 10(3)M-1, respectively. The maximal binding capacity of BLM (70 +/- 4 nmol/mg of protein) was significantly greater (P less than .01) than that of BBM (38 +/- 1 nmol/mg of protein). The affinity constants and maximal binding capacities of BBM and BLM from diabetic rats were not significantly different from those of normal rats. Moreover, 2 days of gentamicin injections at 100 mg/kg/day for 2 days had no appreciable effect on these binding parameters in either group. In control rats the total phospholipid content of BLM (785 +/- 19 nmol/mg of protein) was significantly greater (P less than .01) than that of BBM (592 +/- 19 nmol/mg of protein) and reflected significantly greater quantities of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Sensitivity of renal brush-border Na+-cotransport systems to anions.

The effect of anions on Na+-cotransport of succinate, lactate, glucose, and phenylalanine was studied under voltage clamped conditions in brush-border membrane vesicles prepared from rabbit renal cortex. The initial rate of succinate uptake varied by an order of magnitude depending on the anion: the highest rates were obtained with fluoride and gluconate, and the lowest with iodide. The anion sequence corresponded with the inverse of the anion hydration energies. The kinetics of succinate uptake were measured in the presence of fluoride and chloride. There was no difference in the maximal rates of uptake, but the Kt in fluoride (0.30 mM) was less than half that in chloride (0.70 mM), i.e. Cl- behaved as a competitive inhibitor of succinate transport with a Ki of 150 mM. The uptake of L-lactate, D-glucose and L-phenylalanine was less sensitive to anions, and there was no correlation with hydration energies. We conclude that the anion effects on sugar and amino acid uptakes measured under open-circuit conditions are largely due to variations in membrane potential, but in the case of the dicarboxylate transporter anions behave as weak competitive inhibitors. The specificity of the anion inhibition suggests that the dicarboxylate binding sites have a weak field strength relative to water.

Animals↗
PubMed1984

Comparison of digital subtraction arteriography and conventional film screen subtraction arteriography for neuroradiology.

Sixty-nine patients with 91 separate abnormal findings were studied by both intra-arterial digital subtraction arteriography (ADSA) and conventional film screen subtraction arteriography (CFSA) in the same projection, with the same magnification. Digital subtraction arteriography has distinct advantages over CFSA in the form of reduced contrast utilization, better patient tolerance of arteriography because of reduced contrast concentration, superior contrast resolution, and rapid, on-line visualization of the abnormalities. Digital subtraction arteriography is limited by its availability in only a single plane, by decreased spatial resolution which affected the image quality for intracranial blood vessels at an image intensifier (I.I.) field of 12 inches, and by relatively limited field of view both intracranially and extracranially for I.I. fields of 6 and 9 inches.

Adolescent↗
PubMed1984

Social implications of immobility.

The patient who loses his or her independence in the community inevitably forfeits the will to live. One factor that repeatedly surfaces is the inability of our society to realistically deal with immobility of the elderly. Of the estimated 95 per cent of the elderly who do not live in institutional settings (nursing homes), 43 per cent require assistance in some aspect of their daily lives.

Activities of Daily Living↗
PubMed1982

Direct effect of cortisol and cortisone on insulin and glucagon secretion.

The direct effects of cortisol and cortisone on insulin and glucagon secretion by the isolated perfused rat pancreas were examined. Cortisone, but not cortisol, in a final concentration of 10(-4) M acutely and strongly inhibited both phases of glucose- and arginine-induced insulin secretion. In repeated pulse administrations, the second infusion of cortisone elicited an inhibition of insulin release equal to the first response. Glucagon output was slightly suppressed by cortisol and more significantly by cortisone in a glucose-free medium. The blockade of alpha-adrenergic receptors by phentolamine attenuated, but did not prevent, the strong inhibitory action of cortisone on insulin secretion.

Animals↗