PubMed Health⌕ Search

Biomedical subjects

M Blumenthal

Publications and source records attributed to M Blumenthal.

At least 19 recordsLinked to original sources
PubMed2006

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Aged↗
PubMed2001

Experimental studies of capsular equator rings of soft latex.

PURPOSE: To determine the efficacy of wide equatorial rings of various materials in reducing posterior capsule opacification (PCO) and maintaining the circular contour of the capsular equator in a rabbit model. SETTING: Laboratory for Intraocular Microsurgery and Implants, Goldschleger Eye Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel. METHODS: Closed rings made of poly(methyl methacrylate), Teflon(R), polyurethane, and latex were introduced into the capsular bags of rabbit eyes after removal of the lens material. The soft latex rings were deemed the only practical rings for atraumatic implantation through a small incision. Latex rings of 2 dimensions with rectangular edges were implanted in 8 rabbits. One eye served as a control after lens removal and no ring implantation. The eyes were followed for up to 5 months and then evaluated by light microscopy. RESULTS: Posterior capsule opacification was minimal or absent in all animals implanted with the latex rings. Mild to moderate inflammatory reaction was noted in most eyes. It was caused by the ring material or secondary to long-standing pressure on the ciliary tissue. The rings also maintained well the circular contour of the capsular bags. CONCLUSIONS: Equatorial rings of soft latex with sharp rectangular edges were effective in minimizing PCO and maintaining the shape of the capsule after lens removal in rabbits. Soft rings made of a biocompatible material may be effective in humans.

Animals↗
PubMed2001

Corneal endothelial cytotoxicity of diluted povidone--iodine.

PURPOSE: To assess corneal endothelial toxicity of diluted povidone-iodine (PI) in vivo and in vitro. SETTING: Cell Biology Laboratory and the Laboratory for Intraocular Microsurgery and Implants, Goldschleger Eye Research Institute, Sackler School of Medicine, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel. METHODS: In an in vitro study, cultured bovine corneal endothelial cells were exposed to diluted PI. The degree of cell damage was determined by staining with trypan blue and by comparing the results to those in a control group. In an in vivo study, a single dose of diluted PI was injected into the anterior chamber of rabbit eyes, completely replacing the aqueous humor. The eyes were evaluated by clinical examination, specular microscopy, pachymetry, pneumotonometry, and histopathology and compared to a control group injected with a balanced salt solution. RESULTS: In vitro, PI concentrations of 0.05% or less did not induce endothelial cell damage. Significant damage was observed with a PI concentration of 0.1%. Calf serum concentrations of 1% and higher in the culture media protected the endothelial cell monolayer from cytotoxic damage by PI. Aqueous humor did not have a similar effect. In vivo, PI concentrations of 0.1% or less did not induce changes in corneal endothelium morphology or function as assessed by specular microscopy and pachymetry. A PI concentration of 1% served as a positive control, causing corneal edema and endothelial cell loss as demonstrated by pachymetry, histopathology, and elevated intraocular pressure. CONCLUSIONS: The concentrations of PI tolerated by animal endothelium in vitro and in vivo were higher than the reported bactericidal levels. These findings justify further investigation of the safety and efficacy of PI for intracameral prophylaxis during surgery.

Animals↗
PubMed2000

Altered allergen binding capacities of Amb a 1-specific IgE and IgG4 from ragweed-sensitive patients receiving immunotherapy.

BACKGROUND: The mechanisms for the effectiveness of allergen immunotherapy (IT) are not well understood. The binding potential for immunoglobulins is a function of both antibody concentration and affinity (K(A)). PURPOSE: The purpose was to perform a cross-sectional preliminary study to investigate any differences in allergen-specific antibody affinity and concentration following ragweed immunotherapy by introducing a new concept of antibody binding capacity ([Ig] X K(A)). METHODS: The binding capacity of allergen-specific IgE and IgG4 was determined for ragweed-allergic individuals undergoing ragweed immunotherapy and compared with the capacity of ragweed-specific IgE and IgG4 for allergic individuals not receiving immunotherapy. RESULTS: The mean binding capacity for IgG4 after long-term immunotherapy was 1.6 log units higher (P < .0001) than for individuals not receiving IT. The binding capacity for allergen-specific IgE was 1.2 log units lower following long-term immunotherapy (P < .0001) compared with individuals not receiving ragweed IT. CONCLUSIONS: We hypothesize that a primary effect of immunotherapy is to increase IgG4 binding capacity and concomitantly decrease IgE binding capacity.

Adult↗
PubMed2000

Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations.

After a genomewide screen in the Hutterites was completed, the IL4RA gene was examined as the 16p-linked susceptibility locus for asthma and atopy. Seven known variants and one novel variant, representing all nonsynonymous substitutions in the mature protein, were examined in the Hutterites; on the basis of studies in the Hutterites, outbred white, black, and Hispanic families were genotyped for selected markers. All population samples showed evidence of association to atopy or to asthma (P values.039-.0044 for atopy and. 029-.0000061 for asthma), but the alleles or haplotypes showing the strongest evidence differed between the groups. Overall, these data suggest that the IL4RA gene is an atopy- and asthma-susceptibility locus but that variation outside the coding region of the gene influences susceptibility.

Alleles↗
PubMed1999

Digital assessment of the epicardial electrocardiogram: novel methodology for a core laboratory for clinical studies.

BACKGROUND: The epicardial electrocardiogram (ECG) is a sensitive marker for cardiac ischemia and has been used as a measure of ischemia in clinical trials. We sought to examine the utility of a central ECG laboratory for determining ischemic-type ST-segment shifts from epicardial ECG recordings obtained from multiple clinical sites. HYPOTHESIS: We speculated that an operator-assisted digital ECG core laboratory is feasible, reliable, and efficient, with the ability for rapid and accurate interpretation of the epicardial ECG. METHODS: The epicardial ECG was recorded via an angioplasty guidewire placed in a coronary artery of a patient undergoing angioplasty. Site investigators visually determined the time-to-onset of 0.1 and 0.3 mm ST-segment elevation, and the maximal ST-segment elevation during balloon inflation, and then compared the measurements with those made at an operator-assisted digital ECG core laboratory. RESULTS: Agreement between the two methods occurred in 78% of the time-to-onset measurements, but in only 39% of the maximal ST-segment measurements. Overall, the visual measurements of the clinical investigators of time-to-onset differed from the digital core laboratory by 11.8 +/- 11.6 s for 0.1 mV, and 15.8 +/- 20.6 s for 0.3 mV. Recorded maximal ST-segment shifts differed by a mean of 0.47 +/- 0.69 mV. CONCLUSION: The magnitude of inconsistency between the ECG core laboratory results using an operator-assisted digital method and the interpretations of clinical investigators using manual caliper-type analysis was surprisingly large. These results support the need for an ECG core laboratory in clinical trials where ECG ST-segment shifts are used as a response variable.

Adult↗
PubMed1999

Expression of IgH chain genes in antibody response to ragweed and purified Amb a 1: evidence for differential regulation of isotype production.

A survey of the work with Ig response to allergens carried out previously reveals an allergen-specific response both by IgE and all of IgG subclasses. Response of non-sensitive people is characterized by the appearance of a variety of the IgG subclasses. We have reexamined ragweed and Amb a 1 specific Ig response in 54 nonsensitive and 147 atopic or atopic-allergic people using a new inverse sandwich immunoassay allowing discrimination based on antibody affinity. We show that non-sensitive people present no, 0 out of 54, Ig response with affinities higher than Ka 10(7) M(-1). The subpopulation of 66 atopics who never have experienced desensitization responds vigorously and solely (56 out of 66) with genes of the sequence gamma2-alpha2. Only ten showed an additional weak response from gamma1-alpha1. This suggests a possible association between the atopic state and selective activation of part of the gene sequence.

Allergens↗
PubMed1999

Patterns of late corneal scarring after photorefractive keratectomy in high and severe myopia.

OBJECTIVE: To study the correlation between scarring 1 year after photorefractive keratectomy (PRK), final refraction, and degree of myopia. DESIGN: A retrospective, noncomparative case series. PARTICIPANTS: One hundred twenty eyes of 78 patients underwent PRK for high and severe myopia. Thirty-nine eyes had a pre-PRK spherical equivalent (SE) between -9.5 and -18.25 diopters (D) (severe myopia). Eighty-one eyes had a pre-PRK SE between -6.25 and -9.25 D (high myopia). Follow-up time ranged between 12 and 37 months with a mean of 18.2 months. INTERVENTION: Multizone PRK with the VISX 20/20 excimer laser. MAIN OUTCOME MEASURES: Corneal scarring, final best-corrected visual acuity (BCVA), and refraction. RESULTS: There were 71.7% of eyes with severe myopia and 60.5% of eyes with high myopia found to have any pattern of stromal scarring, which was classified as focal, semiannular, annular, and discoid. Discoid scars were rare (6.6%) and found in 12.8% of severe myopic eyes compared to 3.7% of high myopic eyes. Only 50% of the eyes with a discoid scar achieved final BCVA between 6/6 and 6/9 compared to 81.6% of the eyes with a clear cornea. The severe myopic eyes with a discoid scar had the highest level of final undercorrection (-5.0 D) compared to a maximum of -1.5 D in the high myopia group. The severe myopic eyes with a discoid scar had a higher number of retreatments (4 of 5) compared to the high myopia group (1 of 3). Other types of scars were less clinically significant. CONCLUSIONS: Photorefractive keratectomy was efficient in the correction of high myopia but less so in severe myopia, in which discoid scarring was more frequent and more clinically significant, being associated with significant regression. Other types of scarring were less clinically significant.

Adolescent↗
PubMed1999

Determination of Duffy genotypes in three populations of African descent using PCR and sequence-specific oligonucleotides.

The expression of the Duffy Antigen/Receptor for Chemokines (DARC) on red blood cells (RBC) has been commonly determined using hemagglutination tests. Because the vast majority of African individuals are Duffy-negative, screening for DARC expression on RBC is a valuable tool to assess Caucasian admixture in populations of African descent. Furthermore, blood group antigens have been frequently tested as potential risk factors for complex diseases. We established a dot-blotting protocol using sequence-specific oligonucleotides (SSOs) for the DARC-46T ("Duffy-positive") and -46C ("Duffy-negative") alleles. With this method, but not with serological methods, Duffy-positive individuals can be further characterized as homozygous or heterozygous for the dominant Duffy-positive allele, allowing more precise estimation of allele frequencies and admixture in heterogeneous populations. In unrelated African American (n = 235), Afro-Caribbean (n = 90) and Colombian (n = 93) subjects, the frequency of the -46T allele was 21.7%, 12.2% and 74.7%, respectively. The percentage of Duffy-positive individuals (homozygous or heterozygous for the -46T allele) in each population was in accordance with published frequencies. As expected, the -46C allele was not detected in 20 Caucasian subjects. This sensitive and specific method allows for the rapid and inexpensive screening of large samples for Duffy genotypes using small quantities of genomic DNA.

Alleles↗
PubMed1999

Effect of expandable full-size intraocular lenses on lens centration and capsule opacification in rabbits.

PURPOSE: To study the effects of expandable, hydrogel, full-size lenses (FSLs) on lens centration and posterior capsule opacification (PCO) in the rabbit model. SETTING: Center for intraocular Lens Research, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Small FSLs designed for human eyes were implanted unilaterally in 20 rabbit eyes. Lens centration and PCO in these eyes were compared with those in eyes with conventional poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) or aphakia in the fellow eyes. In a second experiment, medium-size or large FSLs designed for rabbit eyes were implanted in 20 rabbit eyes and the results compared with those in eyes with conventional PMMA IOLs. Slitlamp examination of all eyes was performed regularly, after enucleation, gross inspection and microscopic studies were performed. RESULTS: Decentration of FSLs occurred in the presence of an anterior capsule tear or very large capsulorhexis. Posterior capsule opacification developed only at sites where the implanted lens was not in contact with the capsule. Aphakic eyes and looped IOLs developed Soemmering's rings peripherally. In eyes with small FSLs, PCO developed between the lens and the center of the posterior capsule, whereas in eyes with large FSLs, only small amounts of central PCO developed. Retained high-viscosity viscoelastic material had no effect on PCO development. CONCLUSIONS: Complete refilling of the capsular bag by a full-size IOL was associated with excellent centration and only a small degree of PCO. Elastic lenses may thus serve as a starting point for the development of an artificial lens with accommodative function.

Animals↗
PubMed1999

The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group.

The objective of this study was to evaluate the hemodynamic and clinical effects of fosinopril in patients with heart failure. This was a prospective, multicenter, double-blind, randomized, parallel-group study. Patients 18 to 80 years of age who were receiving diuretics with a systolic blood pressure (SBP) > or = 90 mm Hg, New York Heart Association (NYHA) functional class II-IV, left ventricular ejection fraction < or = 40%, pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg, and a cardiac index (CI) < or = 2.6 L/min/m(2) were eligible. A total of 179 patients were randomized to a single, double-blind oral dose of placebo or fosinopril at 1, 20, or 40 mg, and hemodynamic monitoring was performed for 24 hours postdose; 155 patients with SBP > or = 90 mm Hg were re-randomized to 10 weeks of double-blind fosinopril at 1, 20, or 40 mg once daily. Hemodynamic monitoring was repeated at the last visit, beginning at 24 hours postdose (trough) and continuing for 12 hours thereafter. Significant decreases in preload (PCWP) and afterload (mean arterial blood pressure [MABP] and systemic vascular resistance [SVR]) were evident 3 to 4 hours after a single dose of fosinopril at 20 and 40 mg and continuing for up to 8 to 12 hours postdose for PCWP and SVR and for up to 24 hours postdose for MABP (P < or = .05 v placebo and baseline). Sustained decreases in PCWP, MABP, SVR, and heart rate and increases in CI and stroke volume index were observed after 10 weeks of treatment with fosinopril at 20 and 40 mg once daily (P < or = .05 v 1 mg group for PCWP and MABP at most time points and P < or = .05 v baseline for other parameters at most time points). Dose-related trends toward reduced supplemental diuretic use (P = .027) and reduced symptoms of dyspnea (P = .008) were observed with the 20-mg and 40-mg fosinopril dose groups. Once daily administration of fosinopril at 20 and 40 mg was safe and well tolerated, provided a sustained beneficial hemodynamic effect, improved left ventricular performance, and reduced symptoms of dyspnea, resulting in a reduced need for supplemental diuretic therapy.

Adult↗
PubMed1998

An automated method for determination of antibody affinity distribution functions with nanogram quantities.

We have developed a method to determine the binding affinity distribution functions (the probability density function for affinity constants will be referred to as affinity distribution throughout the text) for human serum antigen specific IgE for their respective allergens. This fully automated method, based on the Access technology of Sanofi Diagnostics Pasteur, is a highly sensitive two-step sandwich immunoassay requiring only nanogram quantities of antibodies. Allergen-antibody binding isotherms can be determined covering a range of 5 magnitudes of ligand (allergen) concentration. An affinity distribution function, describing the polyclonal nature of the antibody response, can be calculated from the binding isotherm. The validity of the method is assessed using mAbs against the purified allergen Der p 1. The resolving power and sensitivity of the method are demonstrated using selected sera from donors with high and low levels of specific IgE for these allergens. We are able to show that heterogeneous IgE populations can be determined using 100 microl of sera containing 150 pg of specific IgE per ml. Overall, the range of affinities that can be determined by this method is 1 x 10(6)-1 x 10(11) M(-1).

Allergens↗
PubMed1998

Experimental studies on viscofluids for intraocular surgery.

PURPOSE: To investigate the feasibility and efficacy of using diluted viscofluids during intraocular surgery. SETTING: Laboratory for Intraocular Microsurgery and Implants, Goldschleger Eye Research Institute, and the Sackler School of Medicine, Tel-Hashomer, Israel. METHODS: Diluted hyaluronic acid (0.06 to 0.12%) in balanced salt solutions were irrigated through the phacoemulsification machine or a separate irrigation line (i.e., anterior chamber maintainer). Irrigation was facilitated by increasing the atmospheric pressure in the bottle using compressed air. Experimental surgery was done in rabbit eyes. RESULTS: A viscous fluid could be irrigated at any practical rate by increasing the height of the bottle, increasing the atmospheric pressure within the bottle, or both. Experimental surgeries showed that viscofluids maintained intraocular pressure and anterior chamber volume, allowed safe intraocular manipulations, reduced turbulence in the anterior chamber, and probably provided tissue protection. CONCLUSION: Viscofluids irrigated using a high-pressure system combined the advantages of continuous irrigation of fluids and the protective qualities of viscoelastics in this rabbit eye study.

Animals↗