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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 181 records · Page 10Linked to original sources
PubMed1995

Endothelial modulation of vasoconstrictor responses to endothelin-1 in human placental stem villi small arteries.

1. The aim of this study was to assess the role of endothelial cells in the modulation of vasocontractile responses to endothelin-1 (ET-1) of human placental vasculature. 2. Isolated stem villi small arteries (diameter = 170-250 microns) were obtained from healthy parturients who underwent caesarean surgery during the 39th week of pregnancy for cephalo-pelvic disproportion. Isometric tension was measured in vascular rings mounted in a myograph system and challenged with ET-1 (10(-12) to 10(-6) M). 3. The vasocontractile response to ET-1 was significantly (P < 0.001) increased in endothelial-denuded (active tension = 1156 +/- 214 mN mm-1) as compared with endothelial-preserved vascular rings (active tension = 458 +/- 48 mN mm-1). This difference was significantly (P < 0.05) but only partly abolished by the NO synthase inhibitor N omega-nitro-L-arginine (L-NOARG, 10(-4) M). 4. In endothelial-preserved rings submaximally precontracted with 5-hydroxytryptamine (10(-6) M), ET-1 (10(-12) to 10(-9) M) induced dose-dependent relaxation (maximum relaxation = 70 +/- 7%) at 10(-9) M, which was followed, at higher doses (10(-8) to 10(-6) M), by a contraction. In contrast, no relaxation was seen in endothelial-denuded rings. The relaxation in rings with endothelium was significantly (P < 0.001) reduced by L-NOARG (10(-4) M. Moreover, it was totally abolished by combined pretreatment with L-NOARG (10(-4) M) and the sulphonylurea glibenclamide (10(-5) M). 5. In conclusion, endothelial cells modulate the vascular responses to ET-1 through the release of NO and a substance acting on the ATP-sensitive K+ channel of smooth muscle of stem villi small arteries from healthy parturients.

Arginine↗
PubMed1995

Amphotericin-induced heart-rate decrease in children.

We describe six children with acute decreases in heart rate temporally related to amphotericin B administration. All patients had achieved their maximal dose within 3 to 4 days. Heart-rate drops occurred as early as day 3 but could be delayed up to day 7 after start of therapy. The mean heart rate dropped from 104 +/- 8/min (range 96 to 114) to 62 +/- 8/min (range 48 to 72) (P = 0.0001). A slower heart rate than baseline was noted during the entire duration of drug administration, from 60 minutes of starting the infusion to 220 minutes (mean 120 +/- 40) after discontinuation of the infusion. This reaction was noted in six of 90 (6.7%) patients who had amphotericin. These six children were compared with six age-matched children who received the drug but in whom such changes in heart rate did not develop. The method of administration of amphotericin B was similar in both patients and controls, starting with 0.25 mg/kg/day and increasing by 0.25 mg/kg/day up to 1 mg/kg/day. Children with heart-rate drop received amphotericin for 4.6 +/- 1.8 days, significantly shorter than their controls (12.6 +/- 6.9 days) (P = 0.02), suggesting that this adverse effect has led to early discontinuation of amphotericin therapy. Physicians and nurses caring for children receiving amphotericin B should be aware of this potential adverse effect, which can be serious in a patient with an underlying heart condition or in a patient who is already on heart-rate-lowering drugs.

Adolescent↗
PubMed1995

Carbamazepine pharmacokinetics in obese and lean subjects.

OBJECTIVE: To compare carbamazepine pharmacokinetic parameters between obese and lean subjects following the administration of a single 200-mg tablet. DESIGN: Single-dose intervention, open study. SETTING: Teaching university hospital. SUBJECTS: Eighteen obese (group A) otherwise healthy subjects, referred to the metabolic outpatient clinic, and 13 healthy lean (group B) volunteers. Inclusion criterion for the obese subjects was a body mass index (BMI = weight/height2) of more than 30 kg/m2. In the obese group, mean +/- SD total body weight (TBW), BMI, and percent of ideal body weight (IBW) were 111.4 +/- 19.9 kg, 38.8 +/- 6.0 kg/m2, and 182.7% +/- 30.7%, respectively. These values were significantly greater than the respective values of 63.2 +/- 8.3 kg, 22.4 +/- 1.6 kg/m2, and 105.8% +/- 5.8% obtained in the lean group (p < 0.001). INTERVENTION: Single-dose oral administration of carbamazepine 200-mg tablet (Teril, Taro, Israel). OUTCOMES: Carbamazepine elimination half-life (t1/2), apparent volume of distribution (Varea/F), and its oral clearance (Clpo/F) were derived from the drug concentration-time curves. RESULTS: Carbamazepine Varea/F and t1/2 were significantly greater in group A than in group B (98.4 +/- 26.9 vs. 60.7 +/- 8.5 L, respectively, p < 0.001; and 59.4 +/- 14.7 vs. 31.0 +/- 5.0 h, respectively, p < 0.001), but its Clpo/F was reduced only slightly in obese as compared with lean subjects (19.8 +/- 5.2 vs. 23.0 +/- 4.6 mL/min, respectively, p = 0.07). Correction for IBW yielded similar results for Varea/F and t1/2, but Clpo/F per kg of IBW was significantly smaller in the obese than in the lean subjects (0.32 +/- 0.07 vs. 0.39 +/- 0.06 mL/min/kg of IBW, respectively, p < 0.02). Linear correlations were observed between Varea/F and TBW for both group A (r = 0.92, p < 0.001) and group B (r = 0.77, p < 0.002). CONCLUSIONS: In comparison with lean subjects, carbamazepine Varea/F is significantly greater in obese subjects and its t1/2 is markedly prolonged. The minor nonsignificant effect of obesity on carbamazepine Clpo/F suggests that in obese subjects the carbamazepine daily dose should be based on IBW, not on TBW.

Adolescent↗
PubMed1995

Maturation of the contractile response and its endothelial modulation in newborn porcine intrapulmonary arteries.

Pulmonary vascular reactivity is thought to be greater in the newborn than adult lung. To determine the influence of the endothelium on smooth muscle cell contractility, responses of rings of isolated intrapulmonary arteries were studied from pigs at birth aged < 2 h, 2 d, 3 d, and 10 d (n = 4 per age group) and from eight adult animals. At birth, the response to KCl (25 mM) and prostaglandin F2 alpha (PGF2 alpha) (3 microM) but not histamine (0.1 mM) was greater in rings with endothelium (E+) than without (E-). The response to PGF2 alpha decreased between birth and 3 d by which time the contraction was less in E+ rings than E-, but L-nitro monomethyl arginine augmented contraction at all ages. In the immature piglets, the response to phenylephrine was less in E+ rings than E-, an effect which was reversed by L-N omega-nitro-L-arginine methyl ester. The response to all contractile agonists increased between 10 d and adulthood. The concentration of plasma endothelin-1 was determined in all animals by RIA and was higher at birth than at 3 d or later. In summary, 1) at birth, endothelium enhanced contractility, when plasma endothelin was greatest, but released NO in the presence of phenylephrine and PGF2 alpha; 2) contractile response to all agonists was small at birth; and 3) a complex interaction existed between the contractile agonist and the effect of endothelial maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Clinical pharmacokinetics of dipyrone and its metabolites.

The pharmacokinetics of dipyrone are characterised by rapid hydrolysis to the active moiety 4-methyl-amino-antipyrine (MAA), which has 85% bioavailability after oral administration in tablet form, and takes a short time to achieve maximal systemic concentrations (tmax of 1.2 to 2.0 hours). Absolute bioavailability after intramuscular and rectal administration is 87 and 54%, respectively. MAA is further metabolised with a mean elimination half-life (t1/2) of 2.6 to 3.5 hours to 4-formyl-amino-antipyrine (FAA), which is an end-metabolite, and to 4-amino-antipyrine (AA), which is then acetylated to 4-acetyl-amino-antipyrine (AAA) by the polymorphic N-acetyl-transferase (t1/2 of AA is 3.8 hours in rapid acetylators and 5.5 hours in slow acetylators). Urinary excretion of these 4 metabolites accounts for about 60% of the administered dose of dipyrone. Protein binding of the 4 main metabolites is less than 60%. The volume of distribution of MAA is about 1.15 L/kg of lean body mass. All 4 metabolites are excreted into breast milk. A single-dose study (0.75, 1.5 and 3g) and a multiple-dose study (1g 3 times a day for 7 days) revealed nonlinear pharmacokinetics consistent with a shift of MAA metabolism from FAA to AA. Apparent MAA clearance decreased by 22% during multiple administration. MAA clearance was reduced by 33% in the elderly. In patients with cirrhosis of the liver, the apparent clearance of all metabolites is generally reduced. In patients with renal disease, apparent clearance of MAA remains unchanged, whereas elimination of the renally excreted metabolites AAA and FAA is markedly impaired. No clinically important drug interactions have thus far been recognised. Dipyrone does not affect the pharmacodynamic response to alcohol (ethanol), glibenclamide (glyburide), oral anti-coagulants or furosemide (frusemide). The low toxicity of dipyrone and its efficacy support its use in clinical practice, despite some complex aspects of its disposition.

Acetylation↗
PubMed1995

The prevalence and severity of microvascular complications in pancreatic diabetes and IDDM.

OBJECTIVE: To investigate and compare the prevalence, associations, and severity of retinopathy and nephropathy in patients with pancreatic diabetes (PD) and insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Thirty patients with PD due to alcohol-induced chronic pancreatitis were matched for age, sex, and duration of diabetes with 30 patients with IDDM. Retinopathy was assessed by fluorescein angiography using the Wisconsin classification. Renal function was assessed by albumin excretion rates (AERs) in at least two timed overnight urine collections and glomerular filtration rates (GFRs) by single injection of 51Cr-EDTA. Microalbuminuria was defined as AER 20-200 micrograms/min and nephropathy as AER > 200 micrograms/min. RESULTS: Retinopathy was found in 33% of patients with PD and in 40% with IDDM. The spectrum of disease was similar in the two groups. The geometric mean of AER was 15 micrograms/min (range 1-1,541) in the PD group and 24 micrograms/min (2-2,288) in the IDDM group. Nephropathy was found in 7 PD and in 5 IDDM patients, and a reduced GFR was present in 8 (26%) and 4 (13%) of the two groups, respectively. Microalbuminuria occurred in 9 (33%) and hyperfiltration in 3 (10%) in each group. These differences were insignificant. Retinopathy correlated with AER in both groups. Retinopathy and AER correlated with duration of diabetes in the IDDM but not in the PD group. CONCLUSIONS: Microvascular complications are equally common and severe in PD and IDDM, and improved glycemic control should be the goal in both.

Albuminuria↗
PubMed1995

Dental amalgam: toxicological evaluation and health risk assessment.

Dental amalgam releases small amounts of mercury, which is absorbed by the body. Available data are not sufficient to indicate whether this poses a health hazard to the general population. There is an urgent need for research into the potential health effects of mercury absorption from this source. However, considering the multiple benefits of dental amalgam, unless new scientific research dictates otherwise there is currently no justification for discontinuing the use of this material. Placing a priority on the preservation of healthy tooth structure through preventive strategies and the judicious use of all restorative materials could lessen current concerns over toxicity and unnecessary treatments.

Absorption↗
PubMed1995

Caffeine pharmacokinetics in obesity and following significant weight reduction.

OBJECTIVES: To compare caffeine pharmacokinetics (200 mg single oral dose) between obese and lean subjects and in obese subjects prior to and following weight reduction. In the obese group antipyrine (1000 mg single oral dose) pharmacokinetics were also evaluated one week before caffeine administration. SETTING: Teaching university hospital. DESIGN: Single dose, open study. SUBJECTS: Twenty obese subjects (Group A) (BMI exceeding 30 kg/m2), referred from the outpatient metabolic clinic and 14 lean (Group B) subjects participated in the study. Weight (mean +/- s.d.) and BMI were significantly greater in the obese than the lean subjects (110.4 +/- 19.2 vs 66.9 +/- 13.3 kg respectively, and 38.5 +/- 5.8 vs 22.6 +/- 1.7 kg/m2 respectively, P < 0.001). INTERVENTIONS: Single dose oral administration of caffeine (200 mg) and antipyrine (1000 mg) in Group A and only caffeine in Group B. Twice single dose oral administrations of caffeine (200 mg) in six subjects (Group C), prior to and following weight loss. MAIN OUTCOME MEASURES: Caffeine and antipyrine pharmacokinetics were derived from the plasma concentrations-time curves. RESULTS: Caffeine elimination half-life (T1/2) and clearance (CLo) were similar in obese and lean subjects (6.54 +/- 2.85 vs 6.08 +/- 2.23 h respectively and 100.7 +/- 49.5 vs 82.6 +/- 34.0 ml/min respectively, P > 0.05). Caffeine Varea was greater in group A than in Group B (48.3 +/- 11.4 vs 40.1 +/- 13.0 L respectively, P = 0.06) but when corrected for body weight significantly reduced values were obtained in the obese group (0.44 +/- 0.06 vs 0.59 +/- 0.10 L/kg respectively, P < 0.001). In group A subjects caffeine and antipyrine Varea were similar (48.3 +/- 11.4 vs 49.9 +/- 9.3 L respectively, P > 0.3). Caffeine T1/2 and CLo were not significantly altered by the 30.2 +/- 12.3 kg weight loss obtained in Group C subjects, but caffeine Varea was significantly reduced (55.6 +/- 9.3 L before, 47.8 +/- 9.5 L after, P < 0.04) and Varea corrected for body weight was significantly increased (0.46 +/- 0.03 L/kg before, 0.52 +/- 0.05 L/kg after, P < 0.05). CONCLUSIONS: Caffeine pharmacokinetics are only minimally altered by obesity. The use of caffeine containing drugs in obese subjects does not necessitate significant dosage modification.

Administration, Oral↗
PubMed1995

Familial Mediterranean fever in the "Chuetas" of Mallorca--origin in inquisition?

The aim of our study was to compare the features of familial Mediterranean fever (FMF) in Mallorcan "Chuetas" with those in non-Ashkenazi Jews in Israel. The clinical and laboratory data of FMF were evaluated in a recently identified cluster of 50 FMF patients from Mallorca (the Chuetas) and 45 patients from Israel. We found that the prevalence and clinical manifestations of FMF were similar among the Chuetas and the Israeli group. Furthermore, in contrast to other ethnic groups with FMF, joint involvement was quite common in both the Chuetas (70%) and the Israeli group (75%). The Chuetas are descendants of Mallorcan Jews who emigrated from Spain to the island in the 12th century. The non-Ashkenazi Jews originated mainly in North Africa and are descendants of refugees who escaped from Spain as a result of the Inquisition in the 15th century. We suggest that the non-Ashkenazi Jews and the Chuetas may have a common gene defect for FMF.

Adolescent↗