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Biomedical subjects

J Roy

Publications and source records attributed to J Roy.

At least 19 recordsLinked to original sources
PubMed2006

Individual QTLs controlling quantitative variation in blood pressure inherited in a Mendelian mode.

We studied three possible genotypes at 10 well-defined blood pressure (BP) QTLs using congenic rat lines. The central question was whether the hypertensive or normotensive allele is dominant, or whether there is partial dominance. The congenic strains were employed to investigate the BP effects of alleles originating from normotensive rats in the background of hypertensive Dahl salt-sensitive (DSS) rats. The normotensive alleles at eight QTLs were fully dominant over DSS alleles, which we tentatively interpreted as indicating that DSS rats incurred a loss of function at these loci and that the QTLs produced BP-reducing agents. In contrast, the normotensive allele of only one QTL was recessive over its DSS counterpart, implying a gain of function at this QTL or a null allele involved in generating a BP-elevating agent. Only one locus, C17QTL, had alleles exhibiting partial dominance. These estimates of dominance differ considerably from those obtained by QTL analysis in a F2 cross. This disagreement demonstrates the importance of establishing a cause-effect relationship between a QTL and its phenotypic effect via congenic strains. The dominance relationships suggest pertinent strategies for gene identification and pharmaceutical intervention.

Alleles↗
PubMed2006

Monochromatic aberrations in eyes with different intraocular lens optic designs.

PURPOSE: To study the wavefront aberration profile of eyes with three different types of intraocular lenses (IOLs)--the Tecnis Z9000 (modified prolate surface design) (Pfizer, New York, NY), the Acrysof MA60BM (unequal biconvex optic) (Alcon, Ft Worth, Tex), and the Sensar Optiedge AR40e (equibiconvex optic) (AMO, Santa Ana, Calif)--in eyes following cataract surgery. METHODS: This study was conducted in two parts. The first part was a randomized open study of 32 eyes of 16 patients who underwent bilateral phacoemulsification with a foldable IOL in the capsular bag. A Tecnis Z9000 IOL was implanted in one eye and an Acrysof MA60BM IOL in the fellow eye. The ALLEGRETTO WAVE Analyzer (Wavelight Laser Technologies AG, Erlangen, Germany) was used to measure ocular aberrations 2 weeks after surgery. A paired t test was used to compare each Zernike term from Z3(-3) to Z6(6) between fellow eyes (pupil diameter = 6 mm). In the second part of the study, the wavefront aberrations of 16 eyes that underwent an identical surgical procedure as in the first part of the study but had a Sensar Optiedge AR40e IOL implanted were studied and compared with eyes with the Tecnis Z9000 and Acrysof MA60BM IOLs. RESULTS: The mean spherical aberration (Z4(0)) was statistically significantly lower in eyes with a Tecnis Z9000 IOL (Z4(0) = 0.07 +/- 0.12 microm) compared with eyes with an Acrysof MA60BM IOL (Z4(0) = 0.29 +/- 0.20 microm, P < .001) and with eyes with a Sensar Optiedge AR40e IOL (Z4(0) = 0.20 +/- 0.09 microm, P = .002). No statistically significant differences were noted in any of the Zernike terms between eyes with Acrysof MA60BM and Sensar Optiedge AR40e IOLs, or in the root-mean-square (RMS) of total higher order aberrations among the three IOL groups. CONCLUSIONS: The implantation of a Tecnis Z9000 IOL produces a significant reduction in spherical aberration of the eye. No significant differences were noted in the wavefront profile between eyes with Acrysof MA60BM and Sensar Optiedge AR40e IOLs. No significant differences were found in the RMS of total higher order aberrations among the three IOL groups.

Adult↗
PubMed2006

Wavefront aberrations in eyes with Acrysof monofocal intraocular lenses.

PURPOSE: To characterize and measure the ocular aberrations in eyes implanted with monofocal intraocular lenses (IOLs) and to study any correlation between postoperative aberrations and surgical factors. METHODS: A Tscherning aberroscope was used to measure the wavefront aberrations of 62 eyes that had undergone phacoemulsification with the implantation of foldable monofocal Acrysof MA60BM IOLs (Alcon Laboratories Inc, Ft Worth, Tex). The Zernike coefficients, measured with a pupil diameter of 6 mm, were compared with those of a normal dataset of 82 eyes of healthy young myopes. RESULTS: Spherical aberration (Z(0)4) was the most predominant higher order aberration, with a mean value of 0.37 +/- 0.16 microm. A statistically significant linear relationship was noted between the magnitude of postoperative spherical aberration and the dioptric power of the IOL. The mean spherical aberration was 33 times more in the pseudophakic group than in normal young myopic eyes. The other major higher order aberrations were trefoil (Z(-3)3) with a mean of -0.13 +/- 0.22 microm and vertical coma (Z(-1)3) with a mean value of -0.11 +/- 0.23 microm. On average, the root-mean-square of higher order aberrations in pseudophakic eyes was 2.1 times that in a normal population of young myopic eyes. CONCLUSIONS: Eyes that undergo cataract surgery with monofocal IOL implantation suffer from significant higher order aberrations. The optical design of the IOL is most likely responsible for the increase in spherical aberration, the magnitude of which is a function of the dioptric power of the IOL.

Acrylic Resins↗
PubMed2005

Inhaled but not intravenous milrinone prevents pulmonary endothelial dysfunction after cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass triggers a systemic inflammatory response that alters pulmonary endothelial function, which can contribute to pulmonary hypertension. Milrinone is a type III phosphodiesterase inhibitor. The objective of this study was to compare the effects of inhaled and intravenous milrinone on the pulmonary endothelium-dependent relaxations and hemodynamic and oxygenation parameters after cardiopulmonary bypass in a porcine model. METHODS: Five groups of Landrace swine were compared: (1) control group, no cardiopulmonary bypass; (2) bypass group, 90 minutes of normothermic bypass and 60 minutes of reperfusion; (3) inhaled milrinone group, bypass preceded by a 1.8-mg bolus of inhaled milrinone followed by a continuous milrinone nebulization; (4) intravenous milrinone group, bypass preceded by 2 mg of intravenous milrinone; and (5) inhaled NaCl group, bypass preceded by inhaled saline solution. After sacrifice, pulmonary arterial endothelium-dependent relaxations to acetylcholine and bradykinin were studied in organ chambers. RESULTS: Inhaled milrinone caused less hypotension ( P < .05), a lesser decrease in peripheral vascular resistances ( P < .01), and a lower heart rate ( P < .05) than intravenous milrinone. Inhaled milrinone prevented the alterations in relaxations of pulmonary arteries to acetylcholine caused by cardiopulmonary bypass, and relaxations to bradykinin were improved in the inhaled milrinone group ( P < .05) compared with the cardiopulmonary bypass and control groups. CONCLUSIONS: Inhaled milrinone prevents the occurrence of the pulmonary endothelial dysfunction seen after cardiopulmonary bypass. The hemodynamic and oxygenation profiles obtained with inhaled milrinone are safer than with intravenous milrinone. These strategies might be useful in preventing pulmonary hypertension after cardiac surgery.

Acetylcholine↗
PubMed2005

[Traumatic fibular tendon dislocation combined with medial malleolar fracture: a very uncommon association in ankle trauma].

We report two unusual cases of ankle injury involving dislocation of the fibular tendon and fracture of the medial malleolus. Only one case has been reported previously in the literature. We discuss the pathogenic mechanisms and the clinical and radiological aspects of this unusual ankle injury. The importance of early surgical treatment is emphasized.

Ankle Injuries↗
PubMed2005

What is the clinical significance of positive blood cultures with Aspergillus sp in hematopoietic stem cell transplant recipients? A 23 year experience.

Hematopoietic stem cell (HSC) transplantation is the most frequent underlying predisposing condition to invasive aspergillosis. However, the significance of positive blood culture with Aspergillus sp in this particular population remains uncertain. We retrospectively reviewed all blood cultures performed in 1453 patients who received HSC transplant at our institution between 1980 and 2002. We identified 19 patients with positive blood cultures with Aspergillus sp. Only one of these patients had clinical, histologic or microbiologic evidence of invasive aspergillosis. Thus, even in a population at highest risk for invasive aspergillosis, positive blood cultures with Aspergillus sp remain unusual, and cannot be readily associated with invasive aspergillosis. A case by case assessment by treating physicians of the clinical and radiologic parameters should be systematically made to establish the significance of aspergillemia. Single bottle positivity, obtained with the lysis-centrifugation blood culture system, is a common indicator of pseudoaspergillemia.

Adolescent↗
PubMed2005

Maintaining high autopsy rates in a Canadian blood and marrow transplant program: preserving a diagnostic and research tool.

Autopsy series have revealed patterns of injury in graft-versus-host disease and provided insight into infectious and toxic complications following hematopoietic stem cell transplantation (HSCT). Overall autopsy rates have declined significantly in recent decades including specialized services such as neonatal medicine and cardiac care. However, rates of post-mortem exams at HSCT centers have not been specifically documented. We reviewed hospital records between 1992 and 2002 to determine overall autopsy rates at our hospital and within the HSCT program. Although the overall autopsy rate declined steadily from 24% in 1992 to 9% in 2002, rates of post-mortem exams in the HSCT program remained relatively stable at 32% (24-46%). Autopsy rates were not significantly different for recipients of allogeneic vs autologous transplants and no clear difference was observed for the proportion of autopsies requested on weekdays compared with weekends. Autopsies confirmed major clinical diagnoses and/or suspected causes of death in 45 of 61 autopsies (74%) and yielded major or minor disagreements in clinical diagnosis in 10 cases (16%) and seven cases (11%), respectively. The preservation of high rates of autopsy within our HSCT program demonstrates that specialized programs are able to maintain elevated rates of post-mortem examinations despite overall declining rates.

Autopsy↗
PubMed2004

Antimicrobial and chemopreventive properties of herbs and spices.

Herbs and spices have been used for generations by humans as food and to treat ailments. Scientific evidence is accumulating that many of these herbs and spices do have medicinal properties that alleviate symptoms or prevent disease. A growing body of research has demonstrated that the commonly used herbs and spices such as garlic, black cumin, cloves, cinnamon, thyme, allspices, bay leaves, mustard, and rosemary, possess antimicrobial properties that, in some cases, can be used therapeutically. Other spices, such as saffron, a food colorant; turmeric, a yellow colored spice; tea, either green or black, and flaxseed do contain potent phytochemicals, including carotenoids, curcumins, catechins, lignan respectively, which provide significant protection against cancer. This review discusses recent data on the antimicrobial and chemopreventive activities of some herbs and spices and their ingredients.

Animals↗
PubMed2002

Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the effects of finasteride, a specific type II 5-alpha-reductase inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and urinary flow during a 7 to 8-year period. METHODS: A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued taking open-label finasteride, and more than 70 patients completed 7 to 8 years of treatment. The symptoms were scored using a patient self-administered modified Boyarsky symptom questionnaire. Prostate volume was measured by magnetic resonance imaging or ultrasonography, and the maximal urinary flow rate was assessed noninvasively. RESULTS: Treatment with finasteride for 7 to 8 years led to sustained improvement in symptoms, reduction in prostate volume (28% from baseline), and increased urinary flow (median 2.5 mL/s from baseline). Decreases in dihydrotestosterone (86%) and prostate-specific antigen (54%) levels were also maintained. Long-term finasteride treatment was safe and generally well tolerated. CONCLUSIONS: Long-term treatment with finasteride was well tolerated and resulted in durable symptom relief and improvement in prostate volume and urinary flow.

Adult↗
PubMed2001

Bounds on the CP asymmetry in b --> sgamma decays.

We have measured the CP asymmetry A(CP) identical with[gamma(b-->sgamma)-gammab-->sgamma)]/[gamma(b-->sgamma)+gamma(b-->sgamma)] to be A(CP) = (-0.079+/-0.108+/-0.022) (1.0+/-0.030), implying that, at 90% confidence level, A(CP) lies between -0.27 and +0.10. These limits rule out some extreme non-standard-model predictions, but are consistent with most, as well as with the standard model.

Journal Article↗
PubMed2001

Study of tau decays to six pions and a neutrino.

The tau decays to six-pion final states have been studied with the CLEO detector at the Cornell Electron Storage Ring. The measured branching fractions are B(tau(-)-->2pi(-)pi(+)3pi(0)nu(tau)) = (2.2+/-0.3+/-0.4)x10(-4) and B(tau(-)-->3pi(-)2pi(+)pi(0)nu(tau)) = (1.7+/-0.2+/-0.2)x10(-4). A search for substructure in these decays shows that they are saturated by intermediate states with eta or omega mesons. We present the first observation of the decay tau(-)-->2pi(-)pi(+)omega(nu)tau and the branching fraction is measured to be (1.2+/-0.2+/-0.1)x10(-4). The measured branching fractions are in good agreement with the isospin expectations but somewhat below the conserved-vector-current predictions.

Journal Article↗
PubMed2001

Measurement of the lambda(+)(c) lifetime.

The Lambda+c lifetime is measured using 9.0 fb(-1) of e+e- annihilation data collected on or just below the Upsilon(4S) resonance with the CLEO II.V detector at CESR. Using an unbinned maximum likelihood fit, the Lambda+c lifetime is measured to be 179.6+/-6.9(stat)+/-4.4(syst) fs. The precision of this colliding beam measurement is comparable to other measurements, which are based on fixed-target experiments, with different systematic uncertainties.

Journal Article↗
PubMed2001

Intercellular adhesion molecule-1 (ICAM-1) gene expression in human T cells is regulated by phosphotyrosyl phosphatase activity. Involvement of NF-kappaB, Ets, and palindromic interferon-gamma-responsive element-binding sites.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in adhesion phenomena involved in the immune response. The strength of adhesion has been shown to be modulated by changes in ICAM-1 gene expression. In T cells, signaling pathways are intimately regulated by an equilibrium between protein-tyrosine kinases and protein tyrosine phosphatases (PTP). The use of bis-peroxovanadium (bpV) compounds, a class of potent PTP inhibitors, enabled us to investigate the involvement of phosphotyrosyl phosphatases in the regulation of ICAM-1 gene expression in human T cells. Here, we demonstrate for the first time that inhibition of PTP results in an increase of ICAM-1 surface expression on both human T lymphoid and primary mononuclear cells. The crucial role played by the NF-kappaB-, Ets-, and pIgammaRE-binding sites in bpV[pic]-mediated activation of ICAM-1 was demonstrated using various 5' deletion and site-specific mutants of the ICAM-1 gene promoter driving the luciferase reporter gene. Co-transfection experiments with trans-dominant mutants and electrophoretic mobility shift assays confirmed the importance of constitutive and inducible transcription factors that bind to specific responsive elements in bpV-dependent up-regulation of ICAM-1 surface expression. Altogether, these observations suggest that expression of ICAM-1 in human T cells is regulated by phosphotyrosyl phosphatase activity through NF-kappaB-, Ets-, and STAT-1-dependent signaling pathways.

Base Sequence↗
PubMed2001

Outcome of patients treated with cobalt and 6 MV in head and neck cancers.

BACKGROUND: Since 1992, we have been using a 6-MV linear accelerator instead of a cobalt machine. The aim of the study is to evaluate the impact of this on neck control, particularly on postoperative patients in which subcutaneous tissues are at risk. METHOD: A retrospective study including all of 1,452 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All stages and subsites of the head/neck were included. Local and neck control were evaluated by the Kaplan Meier method, and comparisons were made between the cobalt and the 6-MV subgroups with a subsequent Cox analysis. For neck control analysis, the postoperative patients were divided in low and high risk (extracapsular extension [ECE], >two nodes, or T4). RESULTS: Radical radiotherapy: A better local control (LC) is observed with 6 MV than with cobalt, but neck control was similar. Postoperative radiotherapy: A better LC is observed with 6 MV. In high-risk patients, the neck control was higher for the cobalt group (79%) vs 60% for the 6-MV group (p = .09 and .03 in a Cox model). CONCLUSION: In postoperative patients at high risk for neck relapse, cobalt seems to give a better neck control. We are currently doing a prospective study in which a bolus is added for half the treatment when patients at high risk for neck relapse are treated with 6 MV.

Adult↗
PubMed2001

Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity.

A known impurity is formed in the production of a parenteral dosage form of diclofenac sodium if terminally sterilized by autoclave. This impurity has been detected as 1-(2,6-dichlorophenyl) indolin-2qone, which is also an intermediate from which diclofenac sodium is generally synthesized. It is only the condition of the autoclave method (i.e., 123 +/- 2 degrees C) that enforces the intramolecular cyclic reaction of diclofenac sodium forming the indolinone derivative and sodium hydroxide. The formation of this impurity has been found to depend on the initial pH of the formulation. The reaction follows first-order kinetics, and the energy of activation is 5.34 kcal/mol. The other excipients in the formulation do not have a role in this reaction. The concentration of the impurity in the resultant product in the ampule goes beyond the limit of the raw materials in the pharmacopoeias. It is thus preferable to use an alternative sterilization method; that is, an aseptic filtration method in which the formation of this impurity can be avoided.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Allogeneic transplantation for multiple myeloma: further evidence for a GVHD-associated graft-versus-myeloma effect.

We report a series of 37 consecutive patients with multiple myeloma (MM) who received an allograft between 1990 and 2000 at our institution. Median age was 47 years, and nearly 70% of patients were Durie-Salmon stage III. A median of five cycles of chemotherapy were given before transplant, with a median interval between diagnosis and transplant of 9.3 months. We report a nonrelapse mortality rate of 22% with a median follow-up period of 40 months, whereas complete remission (CR) rate at 12 months is estimated at 57%. Treatment failure rate and overall survival at 40 months are estimated at 52% and 32%, respectively. The number of chemotherapy cycles prior to allotransplantation achieved borderline statistical significance as a poor prognosis factor for overall survival (P = 0.05), while the presence of chronic graft-versus-host disease (cGVHD) was significantly correlated with CR achievement (P = 0.036). Our study confirms that early allografting in MM can yield toxicity rates significantly lower than those associated with historical cohorts, and supports the hypothesis that cumulative chemotoxicity has a negative influence on mortality and survival rates. More importantly, our study clearly demonstrates an association between cGVHD and CR and brings further evidence in favor of a graft-versus-myeloma effect.

Adult↗
PubMed2001

Phenotypic modulation of arterial smooth muscle cells is associated with prolonged activation of ERK1/2.

Arterial smooth muscle cells grown in primary culture on a substrate of fibronectin in serum-free medium are converted from a contractile to a synthetic phenotype. This process is dependent on integrin signaling and includes a major structural reorganization with loss of myofilaments and formation of a large secretory apparatus. Functionally, the cells lose their contractility and become competent to migrate, secrete extracellular matrix components, and proliferate in response to growth factor stimulation. Here, it is demonstrated that the mitogen-activated protein kinases ERK1/2 play a vital role in the fibronectin-mediated modification of rat aortic smooth muscle cells. Immunoblotting showed that phosphorylated ERK1/2 (p44/p42) were expressed throughout the period when the change in phenotypic properties of the cells took place. Moreover, phosphorylated ERK1/2 accumulated in the nucleus as revealed by immunocytochemical staining. Additional support for an active role of ERK1/2 in the shift in smooth muscle phenotype was obtained by the finding that PD98059, an inhibitor of the upstream kinase MEK1, potently suppressed both the expression of phosphorylated ERK1/2 and the fine structural rebuilding of the cells. In conclusion, the observations point to an important and multifaceted role of ERK1/2 in the regulation of differentiated properties and growth of vascular smooth muscle cells.

Animals↗