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Biomedical subjects

J Levy

Publications and source records attributed to J Levy.

At least 55 records · Page 3Linked to original sources
PubMed2001

Development of verteporfin therapy: a collaboration between pharmaceutical companies, device manufacturers and clinical investigators.

The potential for photodynamic therapy to provide new treatment options for patients with choroidal neovascularization has been of interest to ophthalmologists for many years. Verteporfin (Visudyne, Novartis AG) is the first photodynamic drug to receive regulatory approval for use in ophthalmology. The development of verteporfin therapy was more complex than that of many other drugs because of the need to develop both the light-activated drug and the laser system used to activate it. This article provides an overview of the development of verteporfin therapy, focussing on the contributions of the pharmaceutical companies, device manufacturers, and investigators who were involved in the program.

Choroidal Neovascularization↗
PubMed2001

Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid.

Carnosic acid, the polyphenolic diterpene derived from rosemary, is a strong dietary antioxidant that exhibits antimutagenic properties in bacteria and anticarcinogenic activity in various cell and animal models. In the present study, we show that carnosic acid (2.5-10 microM) inhibits proliferation of HL-60 and U937 human myeloid leukemia cells (half-maximal inhibitory concentration = 6-7 microM) without induction of apoptotic or necrotic cell death. Growth arrest occurred concomitantly with a transient cell cycle block in the G1 phase, which was accompanied by an increase in the immunodetectable levels of the universal cyclin-dependent kinase inhibitors p21WAFI and p27Kipl. Carnosic acid caused only a marginal induction of differentiation, as monitored by the capacity to generate superoxide radicals and the expression of cell surface antigens (CD11b and CD14) and receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine. However, at low concentrations, this polyphenol substantially augmented (100- to 1,000-fold) the differentiating effects of 1,25-dihydroxyvitamin D3 and all-trans retinoic acid. Furthermore, such combinations of carnosic acid and any of these differentiation inducers synergistically inhibited proliferation and cell cycle progression. These results indicate that carnosic acid is capable of antiproliferative action in leukemic cells and can cooperate with other natural anticancer compounds in growth-inhibitory and differentiating effects.

Abietanes↗
PubMed2001

Fetal serum levels of insulin, growth hormone and insulin-like growth factor-I in concordant and discordant twin gestations.

OBJECTIVE: To examine the role of insulin, growth hormone and insulin-like growth factor (IGF)-I in concordant and discordant twin pairs. METHODS: Umbilical cord serum samples were obtained from 20 twin pairs with weight discordancy (intertwin birth weight difference > 20%) and from 20 concordant twins (intertwin birth weight difference < 20%), both groups of similar gestational age, gravidity, and parity. The serum samples were analyzed for the levels of IGF-I, growth hormone and insulin in both maternal and fetal compartments. RESULTS: Among the group of discordant twins, the normally grown twin, in all cases, had significantly higher cord serum IGF-I levels than their growth-restricted co-twin (108 +/- 73 ng/ml vs. 39 +/- 24 ng/ml; p < 0.01). There were no significant intertwin differences in the cord blood IGF-I levels in the concordant twin pairs (87 +/- 44 vs. 88 +/- 48 ng/ml; p = 0.986). Insulin and growth hormone levels did not correlate with intertwin birth weight differences. CONCLUSION: These data demonstrate that IGF-I is important in the regulation of both normal and restricted fetal growth in utero, and its action appears to be, at least in part, through an endocrine action. The precise role of growth hormone and insulin in fetal growth restriction remains uncertain.

Female↗
PubMed2001

Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study.

BACKGROUND: Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use. METHODS: Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment. RESULTS: Mean QTc among patients taking the drug was 408+/-18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2+/-20 ms. CONCLUSIONS: In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.

Arrhythmias, Cardiac↗
PubMed2001

Electrogastrographic norms in children: toward the development of standard methods, reproducible results, and reliable normative data.

BACKGROUND: Surface electrogastrography (EGG) is a noninvasive technique that detects gastric myoelectrical electric activity, principally the underlying pacemaker activity generated by the specialized interstitial cells of Cajal. Interest in the use of this methodology has grown because of its potential applications in describing functional gastrointestinal disorders, particularly as a tool in the evaluation of nausea, anorexia, and other dyspeptic symptoms. METHODS: Fifty-five healthy volunteers (27 female), ranging in age from 6 to 18 years (mean, 11.7 years), were studied for a 1-hour baseline preprandial period and a 1-hour postprandial period after consumption of a standard 448-kcal meal. Recordings were obtained with an EGG Digitrapper or modified Polygraph (Medtronic-Synectics, Shoreview, MN). Spectral analysis by an autoregressive moving average method was used to extract numerical data on the power and frequency of gastric electrical activity from the EGG signal. RESULTS: The authors present normative data for healthy children and adolescents studied under a standardized protocol. Mean dominant frequency was found to be 2.9 +/- 0.40 cycles per minute preprandially and 3.1 +/- 0.35 postprandially, with 80% +/- 13% of test time spent in the normogastric range (2-4 cycles per minute) before and 85% +/- 11% after the test meal. The response of several key parameters to meal consumption was considered, and the effects of age, gender, and body mass index (BMI) on the EGG were sought. CONCLUSIONS: There is a postprandial increase in the rhythmicity and amplitude of gastric slow waves, as other investigators have shown in adults. Key normative values are not dependent on age, gender, or BMI. The authors discuss limitations in the data set and its interpretability. The authors establish a normative data set after developing a standardized recording protocol and test meal and show that EGG recordings can be obtained reliably in the pediatric population. Development of similar norms by investigators using the EGG is crucial for future exploration of the validity and clinical application of the EGG. Differences in test conditions of signal detection and analytic methods influence EGG results substantially, and caution should be used when comparing results across centers.

Adolescent↗
PubMed2001

Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life.

OBJECTIVE: To describe patterns of clinical and immunologic progression in children who are vertically infected with the human immunodeficiency virus. METHODS: Children who were born to mothers who were infected with the human immunodeficiency virus in 11 European centers were enrolled at birth in a prospective study and followed according to a standard protocol. At each visit, a clinical and immunologic class was allocated according to guidelines of the Centers for Disease Control and Prevention (CDC). Progression to serious disease and death was assessed, allowing for available and actual antiretroviral therapy (ART). CDC class at each visit was assessed cross-sectionally. RESULTS: More than 15% of infected children will have progressed to category C or death by age 1 year and nearly 50% by 10 years. Just under 20% of children will have evidence of severe immunodeficiency by age 1 and 75% by 10 years. In general, immune status poorly reflected clinical condition. Children who were born after 1994, when the recommendation of earlier initiation of more active therapy was introduced, were significantly less likely to progress than those who were born when treatment was not widely available or was largely confined to zidovudine monotherapy. Estimated progression to CDC class C or death initially was faster in untreated than in treated children, but by 10 years estimated cumulative progression was similar in both groups. Treatment started before class C disease was associated with significantly slower progression. Cross-sectional analysis showed that children largely are symptom-free throughout their lives. After 4 years of age, fewer than 25% of infected children had symptoms at any one time, irrespective of ART received. CONCLUSION: Vertically infected children are without serious symptoms or signs for most of the time. The prognosis has improved with more widespread availability and use of combination ART. These findings have implications for health, education, and other support-service provision.

Age Distribution↗
PubMed2001

Video vs. CD-ROM for teaching pelvic anatomy to third-year medical students. A comparison.

OBJECTIVE: To compare the effectiveness and student acceptance of video and CD-ROM review of pelvic anatomy in third-year obstetrics and gynecology students. STUDY DESIGN: A 34-item pretest was administered on the first day of the clerkship. Students were then randomized to watch a 45-minute video or use an interactive CD-ROM at home. All students took a posttest identical to the pretest. Examination scores were compared by paired and unpaired t test. Students completed a questionnaire on each method's ease, appropriateness, organization, appeal and time spent and whether they would recommend the method to others. RESULTS: One hundred seventy-six students were randomized, 88 to CD and 88 to video. There was 100% compliance, although not all questionnaire items were completed. The mean pretest score for both groups was 50%. The posttest CD mean score was significantly different from the posttest video mean (64% vs. 70%). Both groups significantly improved after the intervention. The video group noted ease of use, but only 49% recommended it for the future. The CD-ROM was recommended by 80%. Student comments favored the CD-ROM. CONCLUSION: Use of video review resulted in short-term significantly higher test scores, but students preferred an interactive CD-ROM. This method should be made available to all students during the rotation.

CD-I↗
PubMed2001

Is dual-task slowing instruction dependent?

When 2 tasks must be performed concurrently, each requiring a choice of response, dual-task slowing is typically found. However, E. H. Schumacher et al. (1997) reported that dual-task slowing can be eliminated when equal priority is assigned to each task. Experiment 1 largely confirmed this with the same tasks as Schumacher et al. (tasks using stimulus-response combinations of visual-manual and auditory-vocal pairings). Experiment 2 retained the equal-priority instructions but switched the task pairings (to visual-vocal and auditory-manual); substantial dual-task slowing occurred. Experiment 3 used the same two response sets but only a single stimulus; slowing was again obtained despite equal priority instructions. Equalizing task priority was not sufficient to eliminate interference; relatively unusual cases in which dual-task interference is eliminated seem to depend on task-specific features.

Choice Behavior↗
PubMed2001

Hemispheric asymmetries for global and local visual perception: effects of stimulus and task factors.

Although neurotogical and physiological studies indicate a right hemisphere superiority in global processing and a left hemisphere superiority in local processing of Navon-type hierarchical letters (D. Navon, 1977), most investigations of lateralized perception in healthy participants report neither asymmetry. In 6 experiments the authors examined the influence of attentional demands, stimulus properties, and mode of response on perceptual asymmetries for global and local perception. Consistent with their theoretical predictions, asymmetries were more robust on divided- than focused-attention tasks and in response to stimuli in which local and global levels were equally salient compared with those with greater global than local saliency. Contrary to their prediction, perceptual asymmetries were not influenced by the complexity of the motor response.

Adolescent↗
PubMed2000

Regulated expression of an MHC class II gene from a promoter-inducible retrovirus.

Specific immune tolerance to fully allogeneic kidney grafts can be achieved in a miniature swine transplantation model by retrovirus-mediated transfer of allogeneic MHC class II genes into bone marrow cells (BMCs) of recipient animals. Graft survival correlated with transient expression of the somatic transgene (Tg) in the induction phase of tolerance. With the aim of investigating the effects of timing and threshold levels of Tg expression on induction of hyporesponsiveness to the grafted tissues, two recombinant retrovirus constructs containing the tetracycline binary regulatory system were used to achieve conditional expression of either the green fluorescent protein (tetGFP) as a control, or the porcine MHC class II DRbeta chain (tetDRB). Effective downregulation of GFP gene transcription was demonstrated in transduced murine fibroblasts after doxycycline treatment, leading to a > 90% reduction of GFP fluorescence. Similar diminution of the DRB gene transcription was achieved in transduced pig endothelial cells (ECs). Drug-dependent downregulation of DRBc gene expression in SLAd pig ECs coincided with complete inhibition of allogeneic activation of anti-class IIc-primed SLAd T cells. These in vitro results suggest that the binary tetracycline retrovirus system may also be adequate to regulate MHC class II Tg expression in vivo.

Animals↗
PubMed2000

Mesoscopic microwave dispersion in ferroelectric thin films

The microwave dielectric response of a ferroelectric thin film is measured locally using time-resolved confocal scanning optical microscopy. Measurements performed on an ensemble of nanometer-scale regions show a well-defined phase shift between the paraelectric and ferroelectric response at 2-4 GHz. Application of a static electric field produces large local variations in the phase of the ferroelectric response. These variations are attributed to the growth of in-plane ferroelectric nanodomains whose size-dependent relaxation frequencies lead to strong dielectric dispersion at mesoscopic scales.

Journal Article↗
PubMed2000

Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies.

Congenital insensitivity to pain with anhidrosis (CIPA), a rare and severe disorder, comprises absence of sensation to noxious stimuli, inability to sweat, and recurrent episodes of hyperthermia. It has a relatively high prevalence in the consanguineous Israeli-Bedouins. Clinical studies of 28 patients are reported here. Using the linkage analysis approach, we linked the disease in 9 of 10 unrelated Israeli-Bedouin families with CIPA to the TrkA gene, which encodes the receptor for nerve growth factor. In one family, linkage was excluded, implying that another gene, yet unidentified, is involved. Two new mutations in the tyrosine kinase domain of the TrkA gene were identified in our CIPA patients: a 1926-ins-T in most of the southern Israeli-Negev CIPA patients, and a Pro- 689-Leu mutation in a different isolate of Bedouins in northern Israel. Eight prenatal diagnoses were made in the southern Israeli-Negev Bedouins, two by linkage analysis and six by checking directly for the 1926-ins-T mutation. Three polymorphisms in the TrkA protein kinase encoding domain were also observed.

Arabs↗
PubMed2000

Effectiveness of antiretroviral therapy initiated before the age of 2 months in infants vertically infected with human immunodeficiency virus type 1.

UNLABELLED: The effectiveness and tolerance of antiretroviral therapy with a combination of three reverse transcriptase inhibitors starting at the time of diagnosis (before 2 months of age) was evaluated in four infants with vertically acquired HIV-1 infection. Plasma HIV-1 RNA levels ranged from 230,000 to 1,000,000 copies/ml before onset of triple therapy and fell below 50 copies/ml at 12 to 33 weeks of life in three of the infants. These three children, currently aged 158, 105 and 72 weeks, are asymptomatic, have normal lymphocyte subsets and no hypergammaglobulinaemia. Two children experienced a profound reduction in the amount of proviral DNA detected in blood and have become HIV-1 seronegative, although one of them has had HIV-1 RNA detectable on a single occasion at 114 weeks of life (303 copies/ml). Transient interruption of therapy resulted in a rapid but reversible increase in HIV-1 RNA levels in the third child and was associated with the production of HIV-specific antibodies. The fourth child whose parents were not compliant to treatment and follow-up had a poor virological response. CONCLUSION: Early treatment of vertically acquired human immunodeficiency virus type 1 infection with three reverse transcriptase inhibitors is well tolerated and can result in such suppression of viral replication that specific antibodies are not produced, that proviral DNA falls to the lower limit of quantitation in blood and that all clinical and immunological manifestations of infection are avoided. Parental adhesion is crucial to the effectiveness of therapy.

Anti-HIV Agents↗
PubMed2000

The effects of antibiotic use on gastrointestinal function.

The bacterial flora of the gastrointestinal (GI) tract plays an important role in maintaining the integrity of the enterocyte, modulating metabolic and immunologic processes, and protecting against colonization by invasive pathogens. Disruption of this finely tuned and stable gut flora by antibiotics, infection, chemotherapy, or radiation has profound effects on the protective barrier and results in overgrowth by pathogens, invasion and translocation of toxins, and life-threatening infections. Use of antibiotics promotes the emergence of resistant organisms, and multiple-antibiotic resistance has become a major public health issue. Preservation of protective species or recolonization with nonpathogenic yeasts or lactobacilli during periods of stress (infections, drugs) has begun to show promise in the management of patients receiving multiple antibiotics, particularly in hospital-acquired infections.

Animals↗
PubMed2000

Phagocytic killing and antibody response during the first year after tetravalent meningococcal vaccine in complement-deficient and in normal individuals.

Seven individuals with late complement component (LCC) deficiency and seven control subjects were vaccinated with tetravalent meningococcal vaccine. The response to vaccination was evaluated by measuring the antibody titer and the phagocyte killing of the bacteria, before, 5-7 weeks, and 12-14 months after vaccination. Prior to vaccination, no phagocytic killing and a low titer of antibody was found in the LCC-deficient group and a low killing (mean of 40-58%, according to the serogroup) in normal controls. The phagocytic killing increased significantly 5-7 weeks after vaccination. However, while in normal controls the phagocytic killing was close to 100% after 5-7 weeks and decreased only slightly during the first year, the mean killing of the various meningococcal subgroups in LCC-deficient individuals was 70-89% and dropped to only 53-71% one year after vaccination. Six weeks after vaccination the mean antimeningococcal antibody titer increased similarly in the sera of LCC-deficient patients and controls. One year after vaccination the controls maintained the high concentration, while the LCC-deficient patients had tendency toward a decrease. In addition, the interpersonal variability of the antibody concentration, both in LCC-deficient individuals and in normal controls, was much higher than the phagocytic killing, with only a very mild increase in some individuals. Thus, it is possible that in spite of adequate increase of antimeningococcal antibody titer after vaccination of LCC-deficient individuals their immunity against the bacteria may not be optimal. Our data show also that phagocytic killing of meningococci is probably a more consistent assay than antibody titer levels for antimeningococcal immunity, especially in LCC-deficient patients.

Antibodies, Bacterial↗