PubMed Health⌕ Search

Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 19 recordsLinked to original sources
PubMed1992

Formation and excretion of dipyrone metabolites in man.

The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml.min-1.kg-1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml.min-1.kg-1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.

Administration, Oral↗
PubMed1992

Captopril test in children with reflux nephropathy.

We studied the plasma renin activity (PRA) and blood pressure (BP) responses to a single oral dose of captopril in children with renal scarring due to vesicoureteral reflux. The test was performed on 19 children, of whom 13 were normotensive and 6 hypertensive. Basal PRA was within the normal range for age for all except 1 patient. Mean basal PRA values for normotensive and hypertensive patients were not significantly different. At 90 min post captopril, the mean PRA increase was 3.61 ng/l per second (SD = 7.07) in the normotensive group but only 0.77 ng/l per second (SD = 0.83) in the hypertensive group. In 11 patients the average systolic BP 60-90 min post captopril was 0.9%-12.4% lower than the basal value. Diastolic BP decreased after captopril administration in 10 patients and increased in 9. The changes in mean arterial pressure and PRA between 0 and 90 min post captopril were inversely correlated (r = 0.605, P less than 0.01). Because of the PRA responsiveness in the normotensive patients with renal scarring, we suggest that there was activation of the renin-angiotensin axis in this group. However, it is not apparent whether such patients are more at risk of developing hypertension at a later time.

Adolescent↗
PubMed1992

Prolonged QT interval in neonates: benign, transient, or prolonged risk of sudden death.

To determine the factors relating to prognosis, the records of 15 neonates with persistent prolongation of the QT interval on the electrocardiogram after the fourth day of life were reviewed. Patients were admitted for symptoms (syncope, cardiac failure, or seizures), abnormal auscultation with an irregular heart rate or bradycardia, or because of a family history of a long QT syndrome. All infants had a long QTc, ranging from 0.46 to more than 0.70 second. Eight patients who had a QTc over 0.60 second developed severe ventricular arrhythmias (torsades de pointes, ventricular tachycardia) or second-degree AV block. Twelve of 15 were treated with beta-blocking agents, combined with ventricular pacing in five cases. Four infants died in the first month of life; they all had a very long QT interval and had experienced ventricular arrhythmias and AV block. Six children are still being treated with beta-blocking agents for the long QT syndrome and are doing well. In five infants, electrocardiographic abnormalities were transient and the QT interval returned to normal within 1 year. Therefore (1) prolongation of the QT interval in neonates may be transient or may represent an early form of the long QT syndrome and (2) the length of the QT interval may provide data on prognosis: those with a QTc less than 0.50 second returned to normal; those with a QTc greater than 0.60 second were associated with severe arrhythmias and four of eight infants died.

Adrenergic beta-Antagonists↗
PubMed1992

Morbidity associated with total colon Hirschsprung's disease.

Increased awareness of total colon Hirschsprung's disease (TCH) has led to improvement in patient care and a decrease in the associated mortality. Morbidity has remained high and necessitates close follow-up to prevent the development of life-threatening complications. We retrospectively reviewed the records of 20 children with TCH treated at this institution since 1961. Follow-up averaged 40.4 months (range, 1 to 150). All patients were diverted with an ileostomy or jejunostomy. Eight children had a Swenson pull-through, three had a Martin procedure, and eight had a Kimura procedure. One child with multiple anomalies died after his ileostomy. There were no postoperative deaths. Complications following ileostomy and pull-through procedures included excessive fluid losses, wound infections, stoma problems, and bouts of enterocolitis. Three children had no reported complications. Seventeen complications were reported in eight children with the Kimura procedure, 10 in the three children with the Martin procedure, and 22 in the eight children with the Swenson procedure. These complications resulted in an average of 4.4 admissions per patient (range, 1 to 11) with an average length of stay of 96 days per patient (range, 10 to 598). Twelve patients required an average of 63 days of total parenteral nutrition and eight needed 328 days (range, 23 to 867) of supplemental nasogastric feedings. Ten patients required at-home rectal irrigations and seven patients required rectal dilations. Nearly half of all patients were kept on antimotility agents long term. Since 1985 we have performed the Kimura procedure for all children with TCH and have seen a decrease in morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1992

Significant weight reduction in obese subjects enhances carbamazepine elimination.

Single-dose (200 mg) carbamazepine pharmacokinetics was evaluated in six obese, otherwise healthy subjects, before and after a mean +/- SEM weight reduction of 30.0 +/- 5.0 kg over 11.3 +/- 1.2 months. After weight loss the mean +/- SEM plasma elimination half-life (t1/2) of carbamazepine was significantly shortened (60.3 +/- 3.1 versus 30.8 +/- 3.3 hours, p less than 0.01) and the total plasma clearance (CL) increased (20.4 +/- 1.8 versus 31.6 +/- 5.0 ml/min, p less than 0.05). The apparent volume of distribution (Varea) decreased (106.2 +/- 9.9 versus 77.7 +/- 4.5 L, p less than 0.01); however, no difference was evident when carbamazepine Varea was corrected for body weight. In addition, weight loss coincided in all participants with a complete sonographic disappearance of the initial fatty liver infiltration noted on enrollment. In conclusion, obesity associated with fatty liver presents an enlarged carbamazepine Varea, prolonged carbamazepine t1/2, and reduced carbamazepine CL. Whenever carbamazepine is initiated in obese subjects, steady-state concentrations should be expected only after twice the time required to achieve steady state in lean subjects. Thus carbamazepine maintenance dose should be reduced, dose interval prolonged, and monitoring of carbamazepine plasma levels provided.

Administration, Oral↗
PubMed1992

Hostility: relationship to lifestyle behaviors and physical risk factors.

The relationship between hostility and coronary artery disease may be partially mediated by unhealthy lifestyle behaviors. This study examined the relationship between hostility, lifestyle behaviors, and physical risk factors in 138 adult men and women. Subjects completed the Cook and Medley Hostility Scale (Ho scale) and self-reports of their dietary habits, consumption of alcohol and cigarettes, and physical activity. Recent findings indicated that a composite hostility score from three rationally derived subscales of the Ho scale tapping the dimensions of cynicism, hostile affect, and aggressiveness was a better predictor of mortality than the total Ho score. Thus, this composite measure of hostility and the total Ho score were used in data analyses. Measures of resting blood pressure, height, weight, and adiposity were also obtained. In men and women, both measures of hostility were positively associated with cholesterol intake and vigorous physical activity. Among women, both hostility measures were positively related to animal fat intake and negatively related to fiber intake. The composite measure was positively related to their resting systolic pressures. Among men, both hostility measures were positively related to cigarette smoking and sugar intake and negatively associated with systolic blood pressure and calcium intake. Findings are discussed in terms of previous research linking hostility to lifestyle behaviors and CAD.

Adult↗
PubMed1992

Theiler's virus replication in brain macrophages cultured in vitro.

Infection of the mouse with Theiler's virus is one of the best animal models for the study of multiple sclerosis, a chronic demyelinating disease of the human central nervous system. The identification of the virus target cell(s) is fundamental to an understanding of the viral persistence as well as the inflammation and demyelination observed in the chronic phase of the disease. This paper reports that a small fraction of brain macrophages grown in vitro can be efficiently infected with Theiler's virus without significant cytolytic effect. Viral replication as well as continuous production of infectivity were observed in these cultures.

Animals↗
PubMed1992

Attempts to alter the heterogeneous response to ANP in sodium-retaining caval dogs.

Chronic caval dogs with ascites were identified as being natriuretic "responders" or "nonresponders" (delta UNaV less than 20 microequiv./min) following an infusion of atrial natriuretic peptide (ANP) (100 ng.kg-1.min-1). To learn more about the factors modulating tubular resistance to ANP, we attempted to convert responders into nonresponders and vice versa by manipulating the physiological environment. To responding dogs, we readministered ANP in the presence of noradrenaline (n = 5), angiotensin (n = 5), indomethacin (n = 4), and adenosine receptor blockage with theophylline (n = 4), and with purposeful reduction of blood pressure (n = 5). To nonresponding dogs, we readministered the ANP in the face of alpha-adrenergic blockade (n = 4), saralasin (n = 4), dipyridamole to block adenosine cellular uptake (n = 5), and elevation of blood pressure (n = 4). In no case were we able to alter the initial natriuretic response to ANP. Binding parameters of ANP receptors in suspensions of renal papillary cells were equivalent in responding caval dogs (n = 6), nonresponding dogs (n = 7), and normal controls (n = 7), as was cGMP generation. We conclude that the tubular resistance to ANP in caval dogs unresponsive to this natriuretic peptide is not due to antagonism from catecholamines or angiotensin but may be due to a post-cGMP problem in signal transduction, or a reduction in the delivery of ANP to the distal nephron.

Animals↗
PubMed1992

Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling.

The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1992

Portal venous infusions of L-glutamine in anaesthetized dogs do not influence renal function.

It has been reported that the intraportal infusion of glutamine in Munich-Wistar rats will cause depression of renal perfusion and the urinary excretion of salt and water. We have attempted to reproduce these findings in anaesthetized dogs. L-Glutamine was infused at doses between 120 and 150 mumol/min into the portal vein and femoral vein of anaesthetized dogs. No effect was observed on portal venous pressure, blood pressure, or kidney function. Similar data were obtained with D-glutamine. Liver biopsy revealed no abnormalities. When 1.5-3 micrograms histamine (free base) was infused into the portal system, portal venous pressure rose from 15.2 +/- 0.33 to 24.8 +/- 0.40 cmH2O (p < 0.05) (1 cmH2O = 98.1 Pa). Glutamine infusions do not appear to initiate hepatorenal reflexes in dogs as they have been reported to do in rats.

Anesthesia↗
PubMed1992

Modification of the renal response to endopeptidase inhibition and atrial natriuretic peptide infusion in normal dogs.

Inhibition of intrarenal neutral endopeptidase 24:11 (NEP) increases the natriuretic response to infused atrial natriuretic peptide (ANP). In various models of canine heart failure, angiotensin and kinins have been shown to modulate ANP and (or) NEP activity. In the present study, we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery (or by denervating the left kidney) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 (a potent NEP inhibitor) and ANP (75 ng.kg-1.min-1). Four dogs received angiotensin (1.5 ng.kg-1.min-1) into the left renal artery, 8 dogs received saralasin (5 micrograms/min), 5 dogs received noradrenaline (2 micrograms/min), and 6 dogs received bradykinin (3 micrograms/min). Five dogs underwent left renal denervation. Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP. Saralasin augmented the natriuretic response. None of the other protocols influenced sodium excretion. We conclude that angiotensin may modulate either the enzymatic degradation of ANP or influence its renal tubular effects.

Angiotensin II↗
PubMed1992

Renal tubular responsiveness to atrial natriuretic peptide in sodium-retaining chronic caval dogs. A possible role for kinins and luminal actions of the peptide.

60% of chronic caval dogs with ascites did not respond to atrial natriuretic peptide (ANP) (75 ng.kg-1.min-1) with a natriuresis (TIVC-NR; delta UNaV = 2 +/- 0.8 mu eq/min) whereas the remaining 40% responded normally (TIVC-R; delta UNaV = 216 +/- 50 mu eq/min). Since proximal tubule neutral endopeptidase 24:11 (NEP) destroys most of intrarenal luminal ANP and kinins, we attempted to convert TIVC-NR into TIVC-R by providing NEP inhibition with SQ 28603 at 30 mg/kg. This potent and specific NEP inhibitor produced a natriuresis when administered alone to nine TIVC-NR dogs (delta UNaV = 67 +/- 2 mu eq/min) and permitted a natriuresis in the presence of ANP (delta UNaV = 97 +/- 18 mu eq/min). A natriuretic response to ANP could also be induced in TIVC-NR dogs by providing renal arterial bradykinin or intravenous captopril, a kininase inhibitor. Urodilatin, a natriuretic peptide not destroyed by intrarenal NEP was without effect in TIVC-NR dogs but increased UNaV when given to TIVC-R and normal dogs. Providing bradykinin to TIVC-NR now permitted an increment in delta UNaV (62 mu eq/min) when urodilatin was reinfused. TIVC-R dogs could be converted into TIVC-NR by pretreating with a specific bradykinin antagonist before infusing ANP. We conclude that TIVC-NR dogs are deficient in intrarenal kinins but are converted to responding dogs after NEP inhibition because of increased kinin delivery to the inner medullary collecting duct.

Alanine↗