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Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 91 records · Page 5Linked to original sources
PubMed1997

Treatment of Kaposi's sarcoma after solid organ transplantation.

PURPOSE: This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS: The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS: Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION: KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

Adult↗
PubMed1997

[Therapeutic abortions: basis and ethical foundations].

For thirty years medical abortion is allowed by law. Since 1975 habits, medicine, society had tremendously changed. From a clinical study we research the different factors influencing medical abortion. We questioned foetus medical history, parents ability, medical staff, society and law about medical abortion. We were interested by ethical dilemma following severity assumption, quality of life and foetal evaluation. By the end we tried to separate medical abortion and eugenism and we suggested a practical course following ethical concerns.

Abortion, Legal↗
PubMed1997

[Analysis of delivery facilities and conditions in 1991 in mothers of infants with birth weights below 1500 grams and/or gestational age under 33 weeks].

AIMS: To identify maternities (in terms of level of activity and linkage with pediatric services) where, in 1991, mothers gave birth to infants of gestational age less than 33 weeks and/or with birth weight under 1500 g. To analyse factors linked to the probability of choosing a particular maternity as place of delivery for this population and measure the impact of maternal transferts on the rates of deliveries. To estimate the number of neonate transferts which could be avoided with simple recommendations. To propose policies that would allow France to come closer to the results of other reference countries in term of management of obstetrical and neonate care. MATERIAL AND METHOD: We extracted from a retrospective sample of 84,279 births (out of a total of 770,148), 717 infants meeting previously defined criteria and related to the population described above, using univariate and multivariate analysis and logistic regression. RESULTS: The Odds-ratio for a delivery to take place in a maternity with a volume of more than 2000 deliveries a year, compared with those doing less than 300 deliveries, is 4, 12. Only 15.8% of those deliveries took place in maternities linked to a level 3 pediatric unit (i.e where an intensive care neonates unit was located in the same building). 39.5% of births took place in level 1 maternities where no required pediatric service existed. Logistic regression techniques showed that the choice of a maternity for mother referral was more linked to the number of deliveries than to its level of pediatric services. In the studied population, 46% of the difference between the observed number of births in high volume maternities (compared to the expected number) could be explained by a maternal referral. The analysis of deliveries showed that for 34% of mothers who gave birth to a baby in a level 1 or 2 maternity, there was a possibility of being referred easily in a level 3 maternity. CONCLUSION: This study shows that the level of care of mothers at high risk of delivering a very premature and/or hypotrophic infant is far from international standards. Simple actions could double the number of births taking place in adapted maternities. We propose to both obstetricians and pediatrists, a common program to enhance the level of care.

Analysis of Variance↗
PubMed1997

[Cesarean sections in France: impact of organizational factors on different utilization rates].

In this study, we analysed the potential impact of organizational factors to explain the variation of cesarean sections' rates. We used a retrospective sample of 84,372 deliveries and two subsamples of low risk deliveries for cesarean sections. We determined different organisational factors that included: juridical and financial status of maternities, their architecture, the type of on-call for obstetricians, pediatrists and anesthetists, the annual number of deliveries and the level of pediatric staff and equipments of the maternities. We used multiple regression techniques to study the specific effect of each parameter, while controlling effects of age and parity of the mothers. We have found that even on the low risk samples, variation of rates were important. The type of on-call, the level of pediatric services and the architecture of maternities exerted a strong and significant effect on the rate of cesarean sections compared to the absence of impact of the number of deliveries. We discuss the reasons why, explaining the occurrence of those factors and then, stress the need to take into account the relevant factors for organizational audits. It appears that, in the context of the new regulation of the health system, these results should give obstetricians reasons to enhance their efforts to correct inefficient practices and to respect consensual guidelines and joint accreditation of obstetric and pediatric units.

Adult↗
PubMed1997

[Feasibility of bilateral sacrospinous ligament vaginal suspension with a stapler. Prospective studies with the 34 first cases].

OBJECTIVE: Evaluation of the feasibility of bilateral sacropinous ligament suspension with a stapler. Morbidity study and short term results. STUDY DESIGN: Prospective study from July 1994 to August 1996. RESULTS: Bilateral sacrospinous ligament suspension with a stapler was possible in 100% of cases and surgical technique is described. Our indications are stage III Bp and stage IV genital prolapses (according to the American Urogynecologic Society classification, 1996), with or without uterus, and when a Bologna's procedure is performed, in order to prevent enterocele. In 24 patients, the uterus was present. 20 vaginal hysterectomies and 4 conservative bilateral uterine suspensions were performed. The sacrospinous ligament suspension was associated to anterior colporrhaphy (in 74% of patients), repair of rectocele (82%), repair of enterocele (26%), posterior colpoperineorrhaphy (79%), bladder neck suspension (71%). No vascular injury nor post operative constipation was noted. In 2 patients, a small rectal laceration occurred, and in one patient one branch of the staple transfixed the rectal mucosa. Removal of the staple was easily performed without any post-operative complication. First results after an average 19 months follow-up (range 9 to 32) shows a perfect anatomic result in 77% of cases. We noted one recurrence of a vaginal vault prolapse; the patient underwent a second sacrospinous ligament fixation with good result. One patient had a stage II Aa cystocele post-operatively and three patients had a short vagina (< 6 cm). Patients who were continent before the sacrocolpopexy did not develop further urinary stress-incontinence. CONCLUSION: Bilateral transvaginal sacrospinous ligament suspension with a stapler facilitates the procedure. No post-operative constipation was noted with this method. Our first results are good. The cost of the stappler may limit its extensive use.

Adult↗
PubMed1996

Graft-infiltrating cells in rats receiving orthotopic semiallogeneic small intestine transplantation with portal or systemic venous drainage.

The effect of alterations in venous drainage, from either ivc to portal vein (pv), along with peritransplant systemic (ivc) or portal (pv) venous alloimmunization with irradiated semiallogenic cells, on cell subset recovery in lymphoid organs of Lewis rats receiving orthoptic small bowel allografts (from LewisXBrown Norway) F1, LBNF1) was examined. Combined portal, venous drainage and alloimmunization has been reported to increase graft/recipient survival in this model. FACS analysis using monoclonal antibodies specific for different lymphocyte subsets was performed on cell suspensions of peripheral (P) and mesenteric (M) lymph node (LN), small bowel intraepithelial lymphocytes (SBIEL), and Peyer's patch (PP) lymphocytes on days 2 and 8 posttransplantation. Donor cell contributions to these cellular analyses were estimated by comparison of FACS staining with polyclonal anti-Lewis or Lewis anti-LBNF1 antibodies. Control animals received syngeneic grafts. In both syngeneic and semi-allogenic transplants with pv or ivc drainage there was no consistent difference in cell subsets from in PLN compared with those of control nongrafted rats. Approximately 50% to 60% of these cells were alphabetaTcR+ with a CD4+/CD8+ ratio of 3-4:1 and a (CD4++CD8+)/alphabetaTcR+ ratio of 1:1. Some 5% to 12% ED3+ cells were also present. In IEL, MLN, and PP by contrast, there were significant differences in cells recovered from rats with ivc vs. pv drainage of grafts. The most striking changes reflected a decreased CD4+/CD8+ and alphabetaTcR+gammadeltaTcR+ cells in these tissues in rats predestined to show prolongation of allograft survival (ivc vs. pv injected IEL CD4/CD8+ ratios and alphabetaTcR+gammadeltaTcR+ ratios 1.0, 0.7 and 5.0, 1.0, respectively. These data are consistent with a proposed role for such gammadeltaTcR+ cells in the local regulation of graft rejection.

Animals↗
PubMed1996

A role for gamma(delta)TCR+ cells in regulation of rejection of small intestinal allografts in rats.

Lewis (LEW) rats received (Lewis x Brown Norway)F1 (LBNF1) small intestinal allografts (SIT) with graft venous drainage to either the portal vein (pv) or inferior vena cava (iv), along with immunization (pv or iv) with irradiated LBNF1 spleen cells. As reported earlier, in rats with pv drained grafts there was an increase in gammadeltaTCR+ cells infiltrating the Peyer's patches (PP) and mesenteric lymph node (MLN) compared with iv drained grafts. After restimulation in culture with irradiated LBNF1 spleen stimulator cells these PP and MLN cells from SIT rats with pv graft drainage were a prominent source of TGFbeta, IL-4, and IL-10. When subpopulations of cells from PP preparations were analyzed, an enriched (<2%betaTCR+) gammadeltaTCR+ population from SIT rats with pv graft drainage, but not iv drainage, was detected that suppressed in vitro type-1 cytokine production (IL-2, IFNgamma) from alphabetaTCR+ (<2%gammadeltaTCR+) cells derived from the MLN or peripheral lymph nodes (PLN) of these same animals. On adoptive transfer to naive LEW rats simultaneously receiving LBNF1 SIT, gammadeltaTCR+ enriched PP cells from these primary donors (pv immunized, SIT rats with pv graft drainage) produced prolonged graft/ animal survival compared with PP cells obtained from primary donors that had iv drained grafts. In addition, simultaneous infusion of anti-gammadeltaTCR monoclonal antibody into SIT rats with pv graft drainage blocked the graft enhancement normally seen in these animals. These data are consistent with an important role for type-2 cytokine producing gammadeltaTCR+ cells in the regulation of graft rejection in this model.

Animals↗
PubMed1996

Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia.

Alternative Splicing↗
PubMed1996

Evaluation of virological procedures to detect fetal human cytomegalovirus infection: avidity of IgG antibodies, virus detection in amniotic fluid and maternal serum.

Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection and fetal damage largely due to maternal primary infection. Virological procedures which are able to detect HCMV fetal infection were evaluated. HCMV IgG antibodies were detected in 62.5% of the pregnant women and 1.47% had a primary infection. From March, 1992 to August, 1995, 29 seroconversions were observed, and in 64 other cases. HCMV IgM antibodies were detected in the first serological test. The mean IgG antibody avidity test (AI) was 31% for the 11 seroconversions tested and 74% in 32 cases where IgG and IgM HCMV antibodies were detected in the first serum. In the 29 HCMV seroconversions, 19 amniocentesis were carried out and 12 fetuses (41.4%) were infected in utero. In four amniotic fluids positive in culture and PCR, the fetus or newborns were infected and in one out of the two cordocentesis undertaken, hepatitis, anemia, and thrombocytopenia were noted. In four other cases, investigations seeking HCMV in amniotic fluid were negative whereas infants were infected at birth. Among the 64 cases with positive HCMV IgM and IgG antibodies detected in the first serological test, three fetuses were infected in utero, but no amniotic fluid was available in these cases. Amniotic fluids were studied in 39 cases, and HCMV detection by culture and PCR-hybridization was negative. HCMV DNA was detected in the maternal sera of five out of 21 pairs of seroconversions and in two cases on the first negative serum. The assay was also carried out on 50 of the 64 HCMV IgM positive sera. Two had detectable HCMV DNA.

Amniotic Fluid↗
PubMed1996

Altered serum cytokines in hepatic and portal blood of rats at early times following portal venous infusion of semi-allogeneic cells.

The liver of anaesthetized adult ( > 350 g) Lewis rats was perfused in vitro after cannulation of both the hepatic and portal vein, with clamping of the hepatic artery. Heparinized blood (400 microliters) was withdrawn at 0, 6, 12, 18, 24, 30 and 36 h from each site, and serum and peripheral blood lymphocytes (PBL) isolated after ficoll/hypaque separation. Serum was tested in bioassays for cytokines known to modulate lymphocyte:endothelial interactions in vivo and in vitro (IFN gamma, TGF beta, TNF alpha, IL-6, IL-1). In some experiments rats received, via portal venous infusion, a sterile inoculum of 150 x 10(6) semi-allogeneic (LBN F1) spleen cells immediately or 12 h after the start of the study. In animals which were unchallenged with cells via the portal vein, subtle differences in detectable cytokines were observed between hepatic and portal blood samples, as reported in earlier studies. Within 12 h the minor perturbations observed in cytokine profiles following surgical insult resolved, and the changes between hepatic and portal venous samples remained constant throughout the study in control rats. However, in rats treated with LBNF1 cells, changes in the cytokine profiles were seen compared with control animals, and as a function of time post F1 cell infusion. Changes in mRNAs for different cytokines were observed in PBL taken from portal/hepatic blood in these same animals. These data point to one possible mechanism whereby the liver may influence immunological processes following portal venous antigen challenge.

Adoptive Transfer↗
PubMed1996

Pressure waves in root canals induced by Nd: YAG laser.

Recently, root canal preparation using Nd:YAG laser has been introduced. Laser interaction with matter may generate cavitation and subsequent pressure waves. This study characterized the pressure waves induced in root canals by either Nd: YAG laser, sonically vibrated files, or ultrasonically vibrated files. The root canals of 14 single-rooted teeth were prepared conventionally and filled with water. In 12 teeth, a pulsed Nd:YAG laser was activated in the canal using optical fibers of various diameters and various power settings. In the remaining two teeth, either a sonic or ultrasonic file was activated. The pressure waves induced in the canals were detected by a piezoelectric transducer. The results were analyzed using correlation coefficient and coefficient of variation. Laser irradiation resulted in pressure waves with amplitudes varying from 35.78 to 79.26 mV, being positively correlated with the laser power density (R2 = 0.870). Sonic and ultrasonic vibrations resulted in pressure waves with mean amplitudes of 60.51 mV and 7.02 mV, respectively. It was concluded that Nd:YAG laser irradiation induced pressure waves, with different characteristics from waves induced by freely vibrating sonic and ultrasonic endodontic instruments when applied to water-filled root canals.

Dental Pulp Cavity↗
PubMed1996

Quality of life following transplantation of the heart, liver, and lungs.

The purpose of this study was to describe the quality of life of patients who have received a transplant of the heart, liver, and lungs. We wished to document how the different patient groups fared in relation to each other with respect to physical, psychological, and social functioning, as well as in relation to published normative data. We also wished to identify factors that contribute to better functioning. We sent out a questionnaire by mail and received responses from 55 heart, 149 liver, and 59 lung transplant recipients (82% response rate). Measures included the SF-36, Mental Health Inventory, the State Anxiety Inventory, the UCLA Loneliness Scale-Revised, a quality of life measure that rated degree of improvement since transplantation, a measure of degree of difficulty in following medical and lifestyle regimens, sleep disturbance, and the Illness Intrusiveness Rating Scale. Results indicated that lung transplant patients reported better functioning than heart or liver transplant patients in all three domains of physical, psychological, and social functioning. Lung patients' level of functioning was equivalent to or better than published norms for the SF-36. Heart and liver recipients reported equivalent functioning to published norms in some domains, but reported impairment in the areas of physical and social functioning. Heart patients especially reported greater intrusiveness of their illness on their daily lives and indicated more difficulty complying with their lifestyle regimen. In all three groups, a large majority of patients reported feeling that life had improved since transplant with respect to health, energy level, activity level, and overall quality of life. Fewer patients reported improvements in the areas of sex life, marriage, family relationships, and social relationships. Where there were differences among the three patient groups, again it was the lung patients who reported more improvement in life since transplantation. Patients with better physical functioning tended to have more energy and pep, to be younger, to see themselves as being in better health, to feel less intrusion on their lives of their illness, and to be employed. Those with better psychological functioning tended to report less sleep disturbance, less loneliness, better social functioning, more vitality, and to be older. Better social functioning was associated with better mental health, less illness intrusiveness, and less role impairment as a result of physical or emotional factors. Relatively few patients-roughly a quarter of the total sample-reported that they were working either full or part time. We conclude that transplantation results in improved quality of life overall, but that problems persist for some patients in their physical and social functioning. Interventions aimed at improving rehabilitation in specific targeted areas may enable patients to resume a more fulfilling lifestyle posttransplant.

Activities of Daily Living↗
PubMed1996

Pharmacodynamic analysis of sparse data from concentration- and effect-controlled clinical trials guided by a pilot study. An investigation by simulations.

The purpose of this investigation was to explore, by computer simulation, the utility of two different clinical trial designs with sparse sampling (three concentration--effect measurements per subject) for population pharmacodynamic studies when the targeted drug concentration or effect measurements are determined by application of optimal sampling theory based on the results of a preceding, data-intensive pilot study. The two design paradigms were concentration-controlled and pharmacologic effect-controlled randomized clinical trials, respectively. The drug concentration--pharmacologic effect relationship was assumed to be describable by the Hill (sigmoid Emax) equation without hysteresis. Intersubject variability was represented by coefficients of variation of 30, 40, and 30% for Emax, EC50, and gamma, respectively. Random controller imprecision and measurement errors were included. Concentration and effect data for 100 subjects were generated by Monte Carlo simulation (ADAPT II), and pharmacodynamic parameter values were obtained by iterative two-stage analysis. These were then used to predict effect intensities over a range of drug concentrations, and the results were compared with those obtained by use of the true parameter values. Concentration- and effect-controlled trial designs were simulated in two forms: unconstrained and constrained with respect to the highest allowed targeted drug concentration or effect intensity. It was found that both types of unconstrained trials yielded good and comparable parameter estimates whereas the constrained trials (which are clinically more realistic) yielded more biased and imprecise estimates of individual pharmacodynamic parameters. Nevertheless, use of the latter to determine the effect intensities produced by different drug concentrations yielded good estimates but only in the range covered by the targeted concentration or effect measurements. For concentration-controlled trials it appears essential that the individuals in the pilot group and the clinical study group be drawn from the same population. Effect-controlled trials gave good results even when the pilot group was not representative of the population (e.g., for an aberrant subpopulation).

Clinical Trials as Topic↗
PubMed1996

Feasibility of effect-controlled clinical trials of drugs with pharmacodynamic hysteresis using sparse data.

PURPOSE: To explore, by simulation procedures, the feasibility of characterizing, from sparse data, the concentration-effect relationship of drugs with pharmacodynamic hysteresis. METHODS: For computer simulations, the concentration-effect relationship was assumed to be describable by the Sigmoid-Emax equation, the site of drug action was located in a distinct effect compartment (keo = 10 x kelim), and the pharmacokinetics were those of either a linear one- or two-compartment system. In view of the poor estimability of the parameters of the Sigmoid-Emax model under the usual clinical conditions, central compartment post-distributive drug concentrations required to elicit various intensities of effect within the therapeutic range were used as data descriptors. Effect intensities of 5 and 25, or 25 and 50 units (with the "unknown" Emax = 100 units) were targeted in multiple-dose (steady state) trial designs. From these data, drug concentrations required to produce effect intensities of 15 and 50 units were estimated by both log-linear and linear interpolation and the actual effect intensities produced by these concentrations were calculated. These simulations were performed over a wide range of Hill coefficient values (0.5 to 4.0) and dosing intervals (0.1 to 1.5 x elimination t1/2. RESULTS: Acceptable results could be obtained by measuring drug concentrations and effect intensities at or near the end of a dosing interval. The largest deviations of effective concentration estimates (in terms of effect intensity) occurred at a Hill coefficient value of 0.5 and the results were very little affected by changing the dosing interval. CONCLUSIONS: Our results demonstrate that effect-controlled clinical trials, with sparse data, of drugs with pharmacodynamic hysteresis for determining concentration-effect relationship in the therapeutic range are feasible in principle.

Clinical Trials as Topic↗
PubMed1996

Population pharmacodynamics: strategies for concentration-and effect-controlled clinical trials.

OBJECTIVE: To explore and evaluate various strategies for drug concentration-and effect-controlled clinical trials, respectively, in the context of studies of population pharmacodynamics (concentration-effect relationships). METHODS: The relative utility of drug concentration- and pharmacologic effect-controlled, randomized clinical trials with two or three concentration-effect measurements for each subject has been explored by computer simulation. The basis for these simulations was a sigmoid-Emax (maximum effect) pharmacodynamic model with Emax = 100%, EC50 (drug concentrations required to produce an effective intensity of 50%) = 10 concentration units, gamma = 2, and no hysteresis. Emax and gamma were held constant whereas EC50 was assumed to be log-normally distributed with a 26% coefficient of variation of the natural lognormalized data. A smaller random variability and variability due to measurement error also were incorporated in the simulations. To explore the implications of variable and unknown Emax and gamma values, the suitability of linear and log-linear interpolation procedures for two-point concentration-effect data in different regions of the sigmoid-Emax curve was compared. RESULTS: Pharmacologic effect-controlled clinical trials with 300 hypothetical subjects and targeted effect intensities of 25% and 75% yielded very good estimates of drug concentrations required to produce effect intensities of 35%, 50%, and 65%, whereas concentration-controlled trials yielded much poorer estimates. Moreover, the concentration-controlled trials, despite optimum choice of targeted concentrations, yielded a large number of data points with poor information content (effect intensities of < 15% or > 85%). Determinations based on targeted effect intensities of 25% and 75% yielded better estimates of individual EC50 values than those targeted for 25% and 50% or 50% and 75% effect intensity. Results were not significantly improved by adding a third measurement (targeted to 50% effect) to the 25% and 75% effect design. Estimations of drug concentrations required to produce an effect intensity of 50%, based on log-linear interpolation of exact concentration-effect data at 25% and 75%, yielded exact results independent of gamma value (0.5-8.0) whereas linear interpolation produced large overestimates at gamma = 0.5 or 1.0 but satisfactory estimates at gamma > or = 2.0. Similar calculations for an effect intensity of 15% based on exact concentration-effect data at 5% and 25% yielded reasonably good estimates by both methods of interpolation over a wide range of gamma values. A review of the clinical literature showed that gamma values are usually 2 or higher. CONCLUSIONS: Population pharmacodynamic studies of reversibly acting drugs without pharmacodynamic hysteresis or time dependency (e.g., tolerance) can be successfully conducted using a pharmacologic effect-controlled randomized clinical trial design with only two properly selected target effect intensities per subject.

Computer Simulation↗