Search PubMed⌕ Search

Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 415 records · Page 23Linked to original sources

Immunopathological findings in idiopathic nephrosis: clinical significance of glomerular "immune deposits".

Idiopathic nephrosis (IN), which includes minimal change (MCD), diffuse mesangial proliferation (DMP) and focal segmental glomerular sclerosis (FSGS), is classically characterized by the absence of significant deposits by immunofluorescence microscopy (IF), except for the focal lesions of segmental sclerosis and/or hyalinosis of FSGS, which fix IgM and C3 antiserums. Since IF is available in most centres, an increasing number of unexpected findings has been reported. In order to evaluate the clinical significance of the glomerular deposits revealed by IF in some instances, we reviewed the renal biopsy findings of 222 consecutive children presenting with IN and in whom IF microscopy was available. By light microscopy, 122 patients showed MCD, 10 DMP, and 90 FSGS with DMP (11 cases) or without (79 cases). By IF, 125 specimens were negative and served as controls; 54 showed mesangial IgM deposits, 24 mesangial IgG deposits (associated with Clq deposits in 16), 15 scattered granules of C3 and 4 predominant deposits of mesangial IgA. We correlated these findings with initial response to steroid therapy and outcome and could find no significant difference between the various categories defined by IF and the control group. Repeat biopsies, performed in 21 cases, showed the persistence of deposits in 11 and their transformation in 10. The particular problem raised by the patients who present with IN and mesangial IgA deposits is discussed. Our results demonstrate that patients presenting with IN and "positive IF", whether showing IgM, IgG and Clq, C3 or IgA, do not represent distinct clinicopathological entities.

Child↗

Influence of food on the pharmacokinetics of dipyrone.

Twelve healthy volunteers were given a single oral dose of dipyrone 1 g, once while fasting and once after a standard breakfast. Plasma levels of the active dipyrone metabolite-Methylaminoantipyrine (MAA) were measured and the calculated pharmacokinetic parameters were compared. Taking dipyrone with food resulted in a small delay in the mean time to peak from 1.5 h to 1.9 h (p less than 0.01). However, there was no significant difference in AUC, Cmax or K(elim) between fasting and nonfasting conditions. The rate of absorption, expressed as the mean K(abs), was somewhat slower in the nonfasting state, but not significantly so. It is suggested that dipyrone may be taken regardless of the times of eating.

Administration, Oral↗

A phenotypic and functional analysis of long-lived B and T lymphocytes.

The lymphocyte composition of spleen, lymph nodes, bone marrow, and thymus of mice submitted to hydroxyurea treatments for four consecutive days was studied. The treatment selects for small lymphocyte populations that represent between 4 and 20% of control numbers in the various organs. Spleen and bone marrow contain the same B cell population with a low IgM, high IgD, low I-E phenotype, which respond to LPS at control clonal frequencies. The T cell compartment is equally depleted, and the lymphocytes remaining contain frequencies of clonable cells in response to mitogens and IL-2 that are comparable to those detected in normal spleen cells. Overall, the results suggest that only a minor fraction of all lymphocytes in a normal young adult mouse have life spans longer than 4 days.

Animals↗

Molecular forms of atrial natriuretic peptides in dog atrium and plasma.

The level of immunoreactive ANP (iANP) as determined by radioimmunoassay, exhibits a fairly even distribution throughout the canine atria. However, the maximal concentration was found in the appendages of both the left and right atrium, and the level was significantly higher on the left side in all analyzed localizations. Reverse-phase HPLC of atrial extracts, coupled with RIA, revealed the presence of three iANP fractions. The dominant fraction (65% of iANP) has an estimated molecular weight 16,300, showing that it corresponds to the hormone precursor. By contrast, in the plasma extract, 92% of iANP coelutes with synthetic human ANP99-126, thus confirming the structural identity of dog and human ANP.

Animals↗

Atrial natriuretic peptide: blood levels in human disease and their measurement.

The atrial hormonal system consists of 126 amino acid-containing prohormone (proANP) stored in the secretory granules of atrial myocytes and 28 amino acid-containing hormone (ANP) that is secreted into the bloodstream in response to raised atrial pressure. ANP participates in the homeostasis of body fluid volume through its main receptor-mediated effects; natriuresis, inhibition of renin and aldosterone secretion, and vasodilation. It counteracts the renin-angiotensin system with the putative primary role of regulating the circulating blood volume. Although in man, the physiologic volume stimuli lead to relatively modest increases of ANP secretion, its plasma level undergoes striking changes in pathology. Marked elevations in conditions accompanied by fluid retention, most conspicuously in heart failure and renal failure, have been explained as a compensatory reaction to volume overload. The recent data suggest a decreased target organ responsiveness as one of the causes of a relative inefficiency of the high circulating levels of ANP in inducing an appropriate natriuresis in these volume overload conditions. The well established radioimmunoassay and the more recent methods of plasma ANP measurement are reviewed, and the authors' results with a commercial RIA are presented.

Animals↗

Worldwide perspective of IgA nephropathy.

It is becoming evident that IgA nephropathy (IgAN) is the most common glomerular disease, and a frequent cause of end-stage renal failure in both white and Asian populations. Its significance as a public health problem is not known since little epidemiologic research is available in most countries. The apparent geographic variations in the percentage of IgAN in kidney biopsy specimens may reflect different clinical policies for diagnostic tests. As a consequence, the frequency of IgAN cannot be accurately extrapolated from these data for any given population. The highest percentages, reported in Singapore and Japan, may be influenced by the systematic screening of urines in both countries. By contrast, IgAN has been detected rarely in blacks either from the United States or from Africa. However, biopsies are performed infrequently in African patients with only microscopic hematuria. Such ethnic differences may suggest a possible role of genetic factors in the etiology of IgAN. As shown recently in France and Italy, antibiotic therapy of streptococcal infections apparently has not influenced the percentage of IgAN in kidney biopsy specimens. These facts and the rarity of the glomerulonephritis in blacks suggest that infections may not be responsible for the etiology of IgAN. The traditional search for causal agents should be approached more vigorously. It will require innovative epidemiologic efforts to understand the mechanisms by which multiple factors (environmental and genetic) acting together influence the risk of disease.

Biopsy↗

An epidural intracranial pressure monitor for experimental use in the rat.

We described the construction and use of a simple and reliable catheter system that can be used to monitor intracranial pressure (ICP) from the epidural space in rats in an experimental setting. The catheter system is easily fabricated in the laboratory from readily available materials. The monitor is fitted flush with the inner table through a burr hole in the temporal squama. A side port is used to fill the system with saline and to irrigate the system should be catheter become obstructed. The distal end of the catheter is fitted to a pressure transducer that is connected to a graphic display and recording system. This system was used to record ICP in 30 anaesthetized adult rats. Seven were subjected to baseline ICP recording only and 23 were subjected to baseline recordings followed by epidural balloon compression of the contralateral hemisphere. Baseline ICP varied between 0 and 8 mmHg and respiratory variation could be detected on the tracings for 24 rats (75%). ICP responded directly and sensitively to epidural balloon inflation in all 23 rats tested. In 5 rats that died during balloon inflation, the decrease in ICP after death followed closely the loss of arterial blood pressure. There was a close correlation of numerical values obtained in two rats in which ICP was recorded simultaneously from the epidural catheter and from a catheter in the subarachnoid space at the cisterna magna. In one rat in which ICP increased to more than 70 mmHg, the epidural catheter continued to record ICP accurately while the cisternal catheter became obstructed with herniated brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An ambulatory program for surgical residents and medical students.

Teaching in the ambulatory setting is important for medical educators because of the economic, social, and medical trends that are pushing patients into this health care setting. While medical education in the hospital setting maintains its important role, education in ambulatory care demands innovations and new strategies. A pilot program based in a freestanding ambulatory surgery center has been developed as part of a surgical residency training program. In the present article, the author describes the program, outlines its curriculum, and details the daily activities of the residents and medical students. A brief history of ambulatory surgery is given.

Ambulatory Surgical Procedures↗

Pharmacokinetic interaction between nifedipine and propranolol.

In 8 healthy volunteers, single-dose nifedipine pharmacokinetics were compared with and without the coadministration of propranolol. An elevation of the mean Cmax was found, from 73.9 +/- 14.1 when nifedipine was taken alone, to 115.7 +/- 12.1 (SE) ng/ml (P less than 0.02) when the agent was combined with propranolol. The AUC0----infinity increased as well, from 287.1 +/- 33.5 to 363.0 +/- 54.3 (SE) (micrograms.hr)/l (P less than 0.01), indicating an increase in bioavailability. Propranolol treatment did not significantly affect the nifedipine half-life (alpha or beta phase) or the estimated volume of distribution, whereas systemic clearance tended to decrease in 6 of the subjects. The most likely explanation for increased bioavailability of nifedipine when coadministered with propranolol is by a reduction of the hepatic "first-pass" clearance, as a result of changes in hepatic blood flow.

Administration, Oral↗

Activities of compound G2 isolated from alfalfa roots against dermatophytes.

An antimycotic agent, compound G2, isolated from alfalfa roots exhibited considerable activity against the six most common dermatophytes. MICs in agar and broth dilutions ranged from 10 to 30 micrograms/ml and from 2 to 10 micrograms/ml, respectively. G2 was fungicidal at 5 to 22 micrograms/ml. Structure and toxicity relations are discussed.

Antifungal Agents↗

Euvolemic cirrhotic dogs in sodium balance maintain normal systemic hemodynamics.

Dogs with chronic biliary cirrhosis and portal hypertension commonly develop plasma volume expansion, urinary sodium retention, ascites, and perturbed systemic hemodynamics, i.e., a rise in cardiac output and a fall in peripheral vascular resistance. Our laboratory has previously demonstrated that creating a side-side portacaval anastomosis in such animals, and so venting hepatoportal pressure, will prevent sodium retention and ascites formation and will maintain the animals euvolemic. In the present study, in four cirrhotic dogs with such an anastomosis, observations made at 12 weeks postbiliary duct ligation, and in the presence of grossly disturbed liver function and morphology, failed to demonstrate any change from control conditions in arterial blood pressure, cardiac output, or peripheral vascular resistance. We conclude that venting hepatoportal pressure in cirrhotic dogs with markedly disturbed liver function prevents the advent of a hyperdynamic circulation, possibly by preventing volume expansion.

Animals↗

Renal dose response and pharmacokinetics of atrial natriuretic factor in dogs.

The present studies investigated the dose-plasma level-response relationships with the use of increasing doses of atrial natriuretic factor [ANF-(99-126)] administered by constant infusion in conscious dogs. The preinfusion plasma immunoreactive ANF increased 12, 19, 23, and 35 times during 45-min consecutive infusions of 50, 75, 125, and 175 ng.kg-1.min-1, respectively. Over this pharmacological range, natriuresis increased linearly with the infused dose (r = 0.99, n = 5) to a maximum response of +1,550%, despite the significant gradual fall of blood pressure, which attained a minimum of 83 mmHg (-26%) at 125 ng.kg-1.min-1. There was no change of glomerular filtration rate (GFR) or renal plasma flow at any dose. A very similar renal response was found in 13 other dogs infused with the highest dose only in which the pharmacokinetic parameters of ANF-(99-126) were estimated. Metabolic clearance rate during the infusion was 1.09 +/- 0.19 l/min. The postinfusion decay curve of plasma immunoreactive ANF was best described by a biexponential function. Plasma disappearance half time was 1.44 min during the rapid phase and 10.3 min during the slow phase of elimination. The results show that 1) natriuretic response to ANF in the pharmacological range is dose dependent and occurs despite a pronounced hypotension, 2) increase in GFR is not a prerequisite of ANF-induced natriuresis, and 3) ANF is rapidly eliminated from the circulation, suggesting an intensive uptake and/or degradation in the target tissues.

Animals↗

C3b receptor (CR1) on phagocytic cells from SLE patients: analysis of the defect and familial study.

In vitro CR1-dependent phagocytosis of C3b-coated erythrocytes, by monocytes and PMN, was found to be significantly decreased in SLE patients. This was in many cases related to a specific defect of CR1 receptors, since the FcR-ingestion of EIgG was normal. On the other hand, CR1 levels of PMN stimulated by FMLP were also found to be decreased in SLE patients, while both the expression of circulating PMN (cells isolated at 4 degrees C) and the total cellular CR1 content were normal. On the basis of the available data, we propose that the impaired phagocytosis is due to a functional defect of CR1 or a defective anchorage of the receptor to the plasma membrane, possibly related to the decreased capacity of CR1 to be up-regulated by FMLP. To study the importance of the genetic background in the CR1 abnormalities, the families of 22 young SLE patients, in which the onset of the disease had occurred before the age of 15, were studied. The expression of CR1 on erythrocytes, and the total CR1 content of PMN, in parents and siblings of these patients did not differ significantly from normal controls. By contrast, the ingestion of EIgGC3b by PMN from healthy relatives of these patients was decreased (65% of the normal mean of PI), while EIgG phagocytosis was normal. A relation between this CR1 functional defect and the familial occurrence of autoimmune disorders is therefore possible.

Erythrocytes↗

Experimental sclera-implanted keratoprosthesis.

An experimental design of keratoprosthesis anchored into the limbal sclera is presented. The surgical procedure enables a watertight junction between the keratoprosthesis and the globe. Dehiscence of the keratoprosthesis-limbal sclera junction occurs when an area of locus resistentia minoris is created in the lower limbus. An artificial drainage system is necessary for the durability of such a keratoprosthesis.

Animals↗

Adverse reactions to over-the-counter analgesics: an epidemiological evaluation.

Over-the-counter (OTC) analgesics, i.e. aspirin, paracetamol, and dipyrone, continue to be the most widely used drug group. Recently, some non-steroidal anti-inflammatory drugs became available as OTC drugs. Our concern has persisted during the past decade in view of the following adverse effects: hepatotoxicity (including the drug aetiology of Reye's Syndrome), analgesic nephropathy, blood dyscrasias, gastrointestinal complications, and certain hypersensitivity reactions. Of particular interest are the identification of high risk groups and questions relating to geographical risk variations. Although the above adverse reactions are thought to be rare, the massive use of OTC analgesics requires quantitative estimates of the risk involved. What is needed is not only the relative risk, but an estimate of the excess risk of reactions in users. This is the parameter to be used in comparative evaluation of the public health hazard and the resulting regulatory action. Such data are generally lacking. A recent international population-based case-control study on the drug aetiology of agranulocytosis and aplastic anaemia is a rare example of such research. Unfortunately, on occasion the experience with that study has been that the provision of reassuring quantitative data is not a guarantee for scientifically based decisions in the face of heated pharmaco-political debates. Still, because government bodies do not foster the needed research, it remains for the pharmaceutical industry to assume the responsibility for continued pharmacoepidemiological assessment of the safety of OTC analgesics.

Analgesics↗

[Short-axis thallium 201 tomography. Changes in the isotope fixation on the circumference of the left ventricle].

Several authors have studied variations in myocardial thickness on short-axis sections cut through healthy postmortem hearts. The circumferential profiles showed a series of minima and maxima, with a minimum at the septum, a maximum at the anterior interventricular junction and another at the anterolateral papillary muscle, a minimum at the inferior wall followed by a maximum at the posterior papillary muscle, then at the posterior interventricular junction, after which came a septal minimum again. When examined by short-axis thallium 201 tomography, the left ventricle does not look like a ring of even density. The purpose of this study was to try and explain the changes in density observed by variations in thickness and to devise a quantification method that would take anatomical features into account. 23 patients with normal coronary angiography underwent thallium 201 scanning after exercise. Circumferential profiles were drawn from short-axis sections with the angle on the abscissa and the number of sections on the ordinate. 29 other patients with a more than 75 p. 100 stenosis of coronary vessels (anterior interventricular artery 15, right coronary artery 10, circumflex artery 8, diagonal artery 4) had the same examination. The circumferential profiles of normal subjects closely resembled those of anatomical sections, with a minimum at the upper and anterior septal wall (the limit between the two areas being undefinable), a maximum at the anterolateral papillary muscle and adjacent myocardium, a minimum at the inferior wall and a maximum at the posterior papillary muscle and adjacent septum. These curves enabled us to determine the relative perfusion values of one area compared with another, which will serve as reference.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Effects of octopamine on renal function in anaesthetized dogs.

Increased levels of octopamine in adrenergic nerve terminals and plasma have been implicated in the circulatory and renal disturbances of chronic hepatic failure. Little is known about its renal actions in normal animals. In the present study, DL-octopamine was administered both i.v. and into one renal artery of anaesthetized dogs in doses ranging between 25-200 micrograms/min (1.6-20 micrograms/kg/min). Octopamine was hypertensive in doses of 100 micrograms/min and more and this change was associated with a significant decrement in GFR and renal perfusion. This amine also exerted a direct tubular effect since decreased excretion of sodium and water occurred in the absence of blood pressure or renal perfusional changes when given i.v. When given into one renal artery octopamine produced only an ipsilateral antidiuresis and antinatriuresis, in the absence of any change to GFR or renal perfusion. Lithium clearances suggest that octopamine acts beyond the proximal tubule in altering the tubular reabsorption of salt and water. Because octopamine was found to increase blood pressure in the presence of a hypertensive infusion of noradrenaline, it is likely that this amine exerts a primary pharmacological effect rather than liberating noradrenaline from nerve terminals. Saline expansion (7% body weight), acute biliary obstruction, chronic cirrhosis with ascites, and chronic thoracic caval constriction with the production of ascites all abolish the effect of octopamine when administered at 100 micrograms/min. Though octopamine may directly influence renal perfusion, its possible role in liver disease remains uncertain.

Animals↗

Pathophysiology of the hepatorenal syndrome and potential for therapy.

Acute renal failure is frequently observed in patients with ascites and alcoholic cirrhosis of the liver. In the absence of any discernible anatomic or clinical cause for the renal failure, the decrease in renal perfusion is usually associated with significant arterial hypovolemia. If there is no contraction of the effective blood volume, then the functional renal failure is entitled to be labeled "hepatorenal syndrome." This implies that there is some unique cause for intrarenal vasoconstriction independent of a contracted effective arterial blood volume. A possible cause for such vasoconstriction may be abnormal intrarenal production of prostaglandins. Therapy is ineffective, but calcium antagonists may have some therapeutic potential.

Animals↗