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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 109 records · Page 6Linked to original sources

The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation.

Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for pituitary desensitization may impair the outcome of IVF as compared to classical short-acting formulations. Whether the negative effects are directed against the corpus luteum, the endometrium, or both is unknown. However, the presence of high affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human endometrium suggests a possible role of these analogues on this target organ, affecting embryo implantation. In the present study, we tested direct effects of two different forms of GnRHa on implantation using the ovum donation model. Patients were prospectively allocated to one of the three study groups: the short-acting form of the analogue leuprolide acetate (group I; n=64), the long-acting form of the same analogue (group II; n=58), and the long-acting preparation of the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo transfer was carried out in group I, whereas 67 were performed in group II and 65 in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because of bleeding while being on the waiting list for anonymous oocyte donation. The number of oocytes donated, fertilization rates and embryos replaced in each group were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6% respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1 and 17.0%. These data suggest that the use of a long-acting form of GnRHa provides success rates similar to the short-acting preparations, resulting in more convenient medication for patients with ovarian function included in ovum donation programmes.

Adult↗

Acute renal effects of endothelin-A blockade: interspecies differences.

The acute renal effects of LU135252 (LU), a selective endothelin-A (ETA) receptor antagonist, were studied in conscious rats after i.p. administration of 1-10 mg/kg LU, and in clearance studies in anesthetized dogs during left intrarenal infusion of 0.01-0.1 mg/kg/min. In the rat (n = 12), LU (10 mg/kg i.p.) decreased diuresis (-36%), excretion of Na (-55%) and Cl (-38%) but not of K and creatinine, as measured in 8-h collections in metabolic cages. Excretion of oral NaCl load (5% of body weight) during 4 h decreased from 68 +/- 2% (vehicle) to 50.5 +/- 5% (LU; n = 12, p < 0.01). Blood pressure was not affected. In contrast, left intrarenal LU infusion at 0.01, 0.03 and 0.1 mg/kg/min in the dog (n = 4) had no effect on renal hemodynamics or excretory function, whereas it mildly decreased blood pressure. In addition, intrarenal LU (0.03 mg/kg/ min; n = 6) had no effect on the renal response to volume expansion (7% bw) by 0.9% NaCl i.v. These markedly different effects of acute ETA blockade were observed at similar systemic plasma levels of LU in the two species. It is concluded that in the rat, but not in the dog, acute blockade of ETA receptors can impair renal excretory function, most likely at the tubule level. This interspecies difference in the role of endogenous ET in the regulation of renal function is probably due to a different ET receptor profile and distribution in rat and dog kidneys.

Animals↗

Alternative locations for internal defibrillator electrodes.

Successful defibrillation is described in two patients in whom the defibrillating electrode was positioned in the coronary sinus and right ventricular outflow tract as alternative sites. Internal cardiac defibrillation has been successful with single or multiple endocardial electrodes, epicardial patch electrodes, and subcutaneous surface electrodes (patch, array) in varying combinations and recently with an active can electrode. While the traditional location of the endocardial electrode has been the right ventricular apex, we describe two patients in whom defibrillation was successful in alternate locations, the coronary sinus and the right ventricular outflow tract.

Aged↗

Influence of sensor size on the accuracy of in-vivo ligament and tendon force measurements.

In-vivo tendon forces are commonly measured using transducers, which detect tension in the tendon fibers. A poorly understood source of measurement errors is the difference in stress distribution within the tendon between experimental and transducer calibration conditions. The objective of this study was to investigate this source of error, and to determine whether these errors could be minimized by proper selection of transducer size. The study was conducted using the infrapatellar ligament (patellar tendon) of New Zealand White rabbits. Tendon force was measured with two different size implantable force transducers (IFTs), one Wide and one Narrow, and by a strain gaged load cell in series with the tendon. Tests were conducted at five different loading conditions selected to produce five different stress distributions within the tendon. One loading condition corresponded to a typical post-experiment calibration, and the data from that condition were used to develop a calibration equation for the transducer. The errors that resulted from using this calibration were determined by comparing the tendon force measured by the in-series load cell with the force predicted from the IFT output using the calibration equation. Changes in stress distribution produced measurement errors up to 64 N with the Narrow IFT but only 24 N with the Wide IFT. We found the measurement error was dependent on sensor width. Our results support the hypothesis that measurement errors can be caused by differences in tendon stress distribution between calibration and experimental conditions. We further showed that these errors can be minimized by using an IFT, which samples the tension in a large percentage of the tendon fibers. Information from this study can be used for selection of an appropriately sized implantable force transducer for measuring tendon and ligament force.

Animals↗

Helicobacter pylori containing only cytoplasmic urease is susceptible to acid.

Helicobacter pylori, an important etiologic agent in a variety of gastroduodenal diseases, produces large amounts of urease as an essential colonization factor. We have demonstrated previously that urease is located within the cytoplasm and on the surface of H. pylori both in vivo and in stationary-phase culture. The purpose of the present study was to assess the relative contributions of cytoplasmic and surface-localized urease to the ability of H. pylori to survive exposure to acid in the presence of urea. Toward this end, we compared the acid resistance in vitro of H. pylori cells which possessed only cytoplasmic urease to that of bacteria which possessed both cytoplasmic and surface-localized or extracellular urease. Bacteria with only cytoplasmic urease activity were generated by using freshly subcultured bacteria or by treating repeatedly subcultured H. pylori with flurofamide (1 microM), a potent, but poorly diffusible urease inhibitor. H. pylori with cytoplasmic and surface-located urease activity survived in an acid environment when 5 mM urea was present. In contrast, H. pylori with only cytoplasmic urease shows significantly reduced survival when exposed to acid in the presence of 5 mM urea. Similarly, Escherichia coli SE5000 expressing H. pylori urease and the Ni2+ transport protein NixA, which expresses cytoplasmic urease activity at levels similar to those in wild-type H. pylori, survived minimally when exposed to acid in the presence of 5 to 50 mM urea. We conclude that cytoplasmic urease activity alone is not sufficient (although cytoplasmic urease activity is likely to be necessary) to allow survival of H. pylori in acid; the activity of surface-localized urease is essential for resistance of H. pylori to acid under the assay conditions used. Therefore, the mechanism whereby urease becomes associated with the surface of H. pylori, which involves release of the enzyme from bacteria due to autolysis followed by adsorption of the enzyme to the surface of intact bacteria ("altruistic autolysis"), is essential for survival of H. pylori in an acid environment. The ability of H. pylori to survive exposure to low pH is likely to depend on a combination of both cytoplasmic and surface-associated urease activities.

Benzamides↗

Drug acetylation in liver disease.

N-Acetylation is a phase II conjugation reaction mediated in humans by the polymorphic N-acetyltransferase 2 (NAT2) and N-acetyltransferase 1 (NAT1). Acetylation of some drugs may be modestly decreased in patients with chronic liver disease, whereas acute liver injury has no effect on drug acetylation. For NAT2 substrates, the impairment in acetylation capacity seems to be phenotype-specific, with a more prominent effect being exerted in rapid than slow acetylators. Thus, in the presence of significant hepatic dysfunction, the activity of NAT2 may not exhibit its usual bimodal distribution, and hence phenotypic assignment may not be reliable. Furthermore, it remains to be evaluated whether the precautions advised for slow acetylators when treated with drugs metabolised by NAT2 apply to all patients (regardless of phenotype) with liver cirrhosis.

Acetylation↗

Tuberculosis control in refugee populations: a challenge to both relief agencies and national programs.

Today's worldwide tuberculosis epidemic and the movement of a growing number of refugees overlap geographically and have made tuberculosis control in refugee populations an issue of increasing importance. However, in developing countries, where both of these problems are concentrated, tuberculosis control in refugee populations remains a largely unmet need. Experience shows that despite difficult field conditions, tuberculosis control programs can be managed successfully in this setting. The range of outcome results reported for treatment completion and defaulting is, however, wide. Analyzing possible determinants for observed variation in treatment outcome results, this paper outlines prerequisites for establishing a tuberculosis control program in a refugee setting. An attempt is made to formulate a general strategy for the main policies which, if applied consistently, will reduce morbidity, mortality and transmission of tuberculosis among refugee populations living in camps. Criteria for the evaluation and monitoring of such a program are discussed.

Communicable Disease Control↗

Radioreceptor assay of an endothelin A receptor antagonist in plasma and urine.

Orally active nonpeptide antagonists of endothelin (ET) receptors may prove beneficial in the treatment of cardiovascular and renal disease. The pharmacodynamics and pharmacokinetics of these drugs are not sufficiently known, and practical methods for their analysis have not been developed. We describe a simple, sensitive, and reproducible radioreceptor assay (RRA) for LU135252, a selective antagonist of the ETA receptor, using porcine aortic smooth muscle membranes as the acceptor and 125I-endothelin-1 as the ligand. With methanol extraction of plasma and urine samples, recovery of LU135252 ranged from 79% to 91% at 60-1000 nmol/L. The logit-log transformed calibration curves constructed with LU135252 added to plasma or to urine were linear (r = 0.993 +/- 0.005, n = 11) in the range from 18.7 to 2400 nmol/L. The detection limit with plasma- and urine-based calibration curves was 19 nmol/L. The interassay coefficient of variation was 12.6% at 70 nmol/L (n = 9) and 6.5% at 590 nmol/L (n = 9). Endothelin-1 did not interfere in the RRA at pathophysiologically and clinically relevant concentrations [up to 15 pmol/L (40 pg/ mL)]. When LU135252 was added to plasma, the signal was completely stable after storage for 1 week at 4 degrees C, although there was a modest loss of the signal after 24 h at room temperature. The practical performance of this RRA was then tested in plasma samples obtained from (a) rats after a single oral administration of LU135252, (b) from coronary-ligated rats chronically treated with LU135252, and (c) in plasma and urine samples obtained from dogs during intrarenal infusion of LU135252.

Administration, Oral↗

Going home: community reentry of light care nursing facility residents age 65 and over.

Issues of consumer choice, and rising public expenditures of nursing facility care for the rapidly increasing elderly population have fueled interest in community reentry of nursing facility residents. The Minimum Data Set Plus (MDS+) contains a wealth of information which can be used to provide a better understanding of nursing facility residents including those who discharge. This study employs the Andersen model of health services utilization and logistical regression on MDS+ data to examine characteristics of higher functioning nursing facility residents age 65 and over related to community reentry in one midwestern state. Findings include having Medicaid as a payer source significantly decreased the likelihood of discharge. In contrast, being younger than 85, retaining decision making responsibilities, and having no cognitive impairments were found to increase the likelihood of discharge. Policy and program implications related to identifying and assisting nursing facility residents in resuming community living are discussed.

Activities of Daily Living↗

Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: a report of the U.S. Multicenter Liver Study Group.

BACKGROUND: A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. METHODS: Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. RESULTS: Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. CONCLUSIONS: Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

Adolescent↗

The rhinophores sense pheromones regulating multiple behaviors in Aplysia fasciata.

Pheromones released during mating and egg laying in Aplysia facilitate various aspects of behavior. We now show that the chemosensory rhinophores sense these pheromones. Ablating the rhinophores causes a significant decrease in the time spent mating. In addition, the lesion blocks the increases of feeding in response to pheromones released by egg cordons and by mating conspecifics. Respiratory pumping is significantly increased in response to egg cordons, mating conspecifics and egg laying hormone (ELH). The increase in response to egg cordons is blocked by ablating the rhinophores, but not by lesioning the osphradium, a second chemosensory organ.

Animals↗