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D Newman

Publications and source records attributed to D Newman.

At least 55 records · Page 3Linked to original sources
PubMed1999

Azimilide decreases defibrillation voltage requirements and increases spatial organization during ventricular fibrillation.

INTRODUCTION: Drugs with class III antiarrhythmic properties generally decrease defibrillation threshold (DFT). However, the concentration effect relation for this effect and drug effects on ventricular fibrillation (VF) itself are not well understood. The objectives of this study were to determine the effect of azimilide (NE-10064), a new class III agent, on DFT, and on spatial organization during VF. METHODS: Defibrillation patch electrodes were sutured to the right and left ventricular epicardium in 12 open-chest anesthetized dogs. The delayed up-down algorithm was used to measure DFT and to estimate the shock strength (voltage) with a 50% probability of successful defibrillation (V50). The magnitude squared coherence (MSC), which measures the spatial relation in the frequency domain, was measured during VF between two unipolar epicardial electrodes 3 mm apart. The V50, MSC, electrophysiologic parameters, and plasma concentrations were determined before and after four cumulative i.v. doses of azimilide (2, 7, 17, and 30 mg/kg). RESULTS: Azimilide elicited a dose dependent reduction of V50 and increase in MSC. Compared with baseline, azimilide lowered mean V50 by 2 +/- 9%, 10 +/- 18%, 11 +/- 14% and 19 +/- 5%, and increased MSC by 17 +/- 20%, 32 +/- 31%, 20 +/- 44% and 27 +/- 20% (p < 0.05 for dose effect) at 2, 7, 17 and 30 mg/kg, respectively. Mean increases in monophasic action potential duration at 90% repolarization (3-11%), ventricular effective refractory period (6-13%) at 400 msec paced cycle length, and VF cycle length (5-37%) (p < 0.01 for dose effect) were observed with the 4 increasing doses of azimilide, respectively. CONCLUSION: Azimilide significantly decreases DFT and increases coherence in VF in a dose dependent manner.

Algorithms↗
PubMed1999

Different responses of human anti-HLA and anti-alphagal antibody to long-term intravenous immunoglobulin therapy.

Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose alpha1-3 galactose (alphaGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-alphaGal IgG. Levels of PRA, anti-alphaGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-alphaGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-alphaGal IgG, catabolism of anti-alphaGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-alphaGal IgG level it would be necessary to use IVIG depleted of this antibody.

Adult↗
PubMed1999

The class III effect of azimilide is not associated with reverse use-dependence in open-chest dogs.

Certain class III antiarrhythmic agents manifest loss of effect at short cycle lengths (CLs). This effect may limit their efficacy in the presence of tachycardia. We studied the frequency-dependent effect of azimilide (NE-10064), a new class III agent, on the right ventricular monophasic action potential (APD90) in 12 open-chest dogs. The monophasic action-potential duration at different pacing CLs (140-400 ms), during sinus rhythm, and ventricular fibrillation CL (VFCL) from left epicardial electrograms were recorded before and after increasing doses of intravenous azimilide. At pacing CL of 400 ms, APD90 was significantly prolonged after 7, 17, and 30 mg/kg of azimilide by 5.4, 7.7, and 10.7%, respectively. The extent of APD90 prolongation was independent of rate. Azimilide increased the APD90 by similar amounts at CL of 400 ms and at the fastest possible stimulation rate maintaining 1:1 capture (mean, 171 +/- 23 ms): by 2.6 +/- 8.6% and 5.6 +/- 5.9% at 2 mg/kg, 5.4 +/- 4.8% and 4.8 +/- 4.7% at 7 mg/kg, 7.7 +/- 5.6% and 9.9 +/-4.5% at 17 mg/kg, and 10.7 +/- 2.6% and 19.3 +/- 11.9% at 30 mg/kg, respectively. Azimilide caused no changes in arterial blood pressure or heart rate. Azimilide prolongs APD90 even at very short CLs. The absence of reverse use-dependence of effect on APD90 may have clinical importance.

Action Potentials↗
PubMed1999

Validation of a noninvasive measure of local myocardial repolarization in a conscious human model: adaptation of repolarization to changes in rate.

INTRODUCTION: A commercial pacemaker sensor measure of the unipolar endocardial stimulus to T wave interval may accurately reflect changes in the monophasic action potential duration at 90% repolarization (APD90). This sensor system was used to study the kinetics of adaptation of repolarization duration to changes in heart rate in humans. METHODS AND RESULTS: Patients were studied using an external pacemaker capable of displaying all stimulus to T wave intervals for each paced beat. Right ventricular stimulation was delivered via the pacemaker and compared simultaneously to APD90. Steady-state pacing was simulated by 60 seconds of pacing at cycle lengths (CLs) 350 to 700 msec. Adaptation to a new ventricular rate was analyzed with a sudden 200-msec decrease in CL. The relation between repolarization measure and steady-state CL (n = 16) was linear with a slope of 0.16 and 0.19 for APD90 and stimulus to T wave interval, respectively (P = NS). The adaptation of both repolarization measures to a sudden change in rate were best modeled by a biexponential function. Stimulus to T wave interval exhibited a parallel course to APD90, and an analysis of normalized differences between APD90 and stimulus to T wave interval followed an approximately normal distribution, with 93.5% of the paired differences within 2 SD of the mean. CONCLUSION: A pacemaker sensor measure of stimulus to T wave interval accurately parallels APD90 during both steady-state and sudden changes in rate. Repolarization in human endocardium follows a linear relation to steady-state CL and adapts to a new rate with a biexponential function. This model represents a novel method for studying human cardiac repolarization.

Action Potentials↗
PubMed1999

Measurement of thickness and density of thin structures by computed tomography: a simulation study.

The limited spatial resolution of clinical CT systems causes difficulties in the measurement of the density and thickness of thin structures such as the vertebral cortical shell. We simulated the imaging process by convolving experimentally determined point spread functions with rectangular and Gaussian profiles, for various fields of view or pixel sizes and reconstruction kernels. The simulations successfully explained the reported overestimation of thickness and underestimation of density when imaging thin structures. Both effects are larger for Gaussian profiles. For the rectangular profiles, experimental estimates of thickness and density will only be accurate when the true thickness is greater than about 1.5 times (for the bone reconstruction kernel) or 2.0 times (for the standard kernel) the full width at half maximum of the point spread function (PSF) of the imaging system. For Gaussian profiles imaged by a system with a Gaussian PSF, there are straightforward analytical expressions for the overestimation of thickness and underestimation of density: and these are useful approximations to the simulations of Gaussian profiles with experimental (pseudo-Gaussian) PSFs. We have demonstrated that thresholding of the vertebral image cannot provide accurate estimates of cortical thickness and density because the appropriate threshold level requires foreknowledge of the cortical thickness. To circumvent such difficulties we suggest that the average value of the peak CT numbers measured along the medial axis of the cortical shell be adopted as an index of cortical shell strength, since its value depends on both the density and the thickness of the shell.

Computer Simulation↗
PubMed1999

Shop floor safety initiatives: the example of atmospheric testing in telecommunications cable vaults.

Strategies for occupational safety and health campaigns often overlook the possibilities afforded by initiatives centered in the workplace itself, as opposed to those focused, for example, at the bargaining table or in the legislature. Workers themselves sometimes may be more cognizant and informed of immediate health and safety issues than are their union representatives, and may formulate innovative or unorthodox approaches to hazard remediation. Such approaches may in fact succeed despite ineffectual contract language or weak regulatory protection. This article examines a successful struggle by a small group of telecommunications technicians to get the employer to revise its obsolete procedures for atmospheric testing of unventilated, underground cable vaults. It demonstrates that increased consideration should be given to shopfloor actions and creative use of the grievance procedure as useful tools in the struggle for occupational safety and health.

Journal Article↗
PubMed1999

More on cystatin C.

Explore the source record for details and available documents.

Biomarkers, Tumor↗
PubMed1999

Genome-wide screen for atopy susceptibility alleles in the Hutterites.

A genome-wide screen for loci influencing positive skin prick tests (SPT) to airborne allergens was conducted in the Hutterites, a founder population of European ancestry. Positive SPT to 14 standardized allergens was measured in 370 subjects in our primary sample and 324 subjects in a replication sample. Evidence for linkage to positive SPT was assessed using the transmission disequilibrium test (TDT) with 337 autosomal markers (average spacing 9.13 cM, SD = 7.8 cM). Three loci showed the strongest overall evidence of linkage to atopy, with at least one allele-specific and a locus-specific p< 1 x 10(-4). This study provides evidence for at least three atopy-susceptibility loci in the Hutterites on chromosomes 1, 6 and 16.

Adult↗
PubMed1999

The effect of polymer coating biomaterials individually and incombination on the behavior of transformed RAW macrophage cells.

The use of homopolymers as coatings for biomaterials has received much attention in the last decade. However, the modifications and alterations induced by using such materials towards inflammatory cells have not been fully investigated. The specific objectives of this study were to investigate the role of hetero and homopolymers of amino acids on cell proliferation, and to determine the biochemical behavior associated with the incubation of RAW cells with various polymers. The RAW macrophage cell line was obtained from the American Type Culture Collection (Rockville, MD) and maintained in sterile media (RPMI) supplemented with 10% fetal bovine serum and 1% antibiotics and antimycotics. The cells were plated at a density of 1 x 10(6) cells/ml onto 24 well plates. The plates were divided into four groups of six wells per group per phase (24, 48, and 72 hours). Cells in the first group were treated with RGD, cells in group II were treated with poly-L-lysine, group III cells were treated with RGD + poly-L-lysine, and cells in group IV were treated with media alone, and served as controls. Cell number, as well as, protein, MDA, lactate dehydrogenase (LDH), and cytochrome C (cyto C) were determined at the end of 24, 48 and 72 hours. Data obtained from this investigation revealed that: (I) there were no significant difference in total cell counts between all experimental groups and control at the end of the 48 hour phase. However, at 24 hours there were fewer cells in the poly-L-lysine treated wells in comparison to control group (p < 0.05), (II) RGD and poly-L-lysine treatments did not cause changes in MDA or protein concentrations for the entire duration of the experiment, and (III) RGD treatment for 48 and 72 hours did not cause a reduction in the LDH activity compared to control and poly-L-lysine treated groups. Data obtained from this investigation could provide more insight regarding the design and development for safe and biocompatible orthopedic, dental and drug delivery devices.

Biocompatible Materials↗
PubMed1999

The effect on bioadhesive polymers either freely in solution or covalently attached to a support on human macrophages.

Cell surface adhesion receptors interact with a family of adhesion molecules known as integrins. It is assumed that the cells recognize and bind a specific amino acid sequence. It is likely that the host inflammatory response may be mediated via the recognition of the inflammatory cells with the specific integrin molecules. The mechanism of such behavior has not been fully elucidated. This investigation was designed to provide more insight regarding the cellular response associated with incubation of macrophages with polymers either freely in solution or adhered to surfaces. Peripheral macrophages were seeded at a density of 4 x 10(6) cells on supports coated with either amino-acid heteropolymers of RGE, RGD, or amino-acid homopolymer Poly-L-lysine. Cells were also seeded at the same density in 24 well plates and the wells were treated with RGD, RGE or Poly-L-lysine. The cells were examined morphologically and biochemically at 24, 48, and 72 hours. The results showed cells growing on supports coated with RGD had significantly (p < 0.05) higher numbers of cells adhering and remaining viable, in comparison to cells growing on Poly-L-lysine or RGE supports. Cells growing on supports coated with RGE appeared irregularly (elongated and spindle) shaped and unevenly spaced. The cells growing on Poly-L-Lysine coated supports showed cellular disruption and lysis, whereas cells growing on the RGD appeared intact, regularly spaced and began fusing into giant cells. Lactate dehydrogenase activity was used as a measure of membrane integrity, and cells grown on coated supports with Poly-L lysine showed a two-fold increase in activity over control and peptide treated groups. On the other hand, cells growing in media containing the free RGE, RGD and Poly-L-lysine showed no statistical differences in cell number, and did not show increased activity of LDH for the entire duration of the experiment. The data suggests that the RGD, RGE and Poly-L-lysine dissolved in solution are highly biocompatible to the macrophages. However, when they are attached to a support they can affect cellular adherence as well as cellular activation.

Amino Acid Sequence↗
PubMed1998

The Canadian Registry of Atrial Fibrillation: a noninterventional follow-up of patients after the first diagnosis of atrial fibrillation.

The Canadian Registry of Atrial Fibrillation (CARAF) is a nondirected, follow-up study of 1,086 patients who are enrolled at 6 centers across Canada at the time of initial electrocardiographically documented diagnosis of atrial fibrillation (AF). Enrollment commenced in 1991 with an intended 10-year follow-up. Comprehensive baseline data, including clinical history, laboratory, and echocardiographic variables were collected. The patients were treated by their own referring physicians and CARAF did not direct their care. Detailed follow-up was performed at 3 months, 1 year, then yearly, with echocardiograms repeated every 2 years. Several studies, which evaluated patient populations, predictors of events, and cardiac structure and functioning, have been performed and are ongoing. Thyroid function was evaluated at baseline, and, of 707 patients evaluated, only 6 patients were found to be hyperthyroid. Symptoms during AF were evaluated and a profile of the types of symptoms and the predictors of symptoms was compiled. Antiarrhythmic drug use is being followed. Sotalol and propafenone were the most commonly used medications, with the use of antiarrhythmic drugs increasing with recurrence of AF. The use of anticoagulants was assessed. The overall use of warfarin was relatively low, but its use increased dramatically with the presence of various risk factors including congestive heart failure, hypertension, and previous stroke. The one risk factor that did not result in increased use of warfarin was hypertension. Therefore, CARAF was able to identify that hypertension appears to be under-recognized and undertreated in its risk for thromboembolic events. CARAF is just now reaching maturity, with the majority of patients having > or=4 years of follow-up. Therefore, extensive investigations are currently under way that will evaluate the baseline characteristics and utilize these as predictors of recurrence of AF, progression to chronicity, and the occurrence of major events such as stroke and death. A very large cohort of patients with serial echocardiograms over 4 years will permit an understanding of the progression of structural and valvular disease. Therefore, CARAF offers a unique opportunity for comprehensive, nondirected follow-up of patients from their initial diagnosis of AF.

Atrial Fibrillation↗
PubMed1998

Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.

We report the cloning, sequence analysis, tissue distribution, functional expression, and chromosomal localization of the human pancreatic sodium bicarbonate cotransport protein (pancreatic NBC (pNBC)). The transporter was identified by searching the human expressed sequence tag data base. An I.M.A.G.E. clone W39298 was identified, and a polymerase chain reaction probe was generated to screen a human pancreas cDNA library. pNBC encodes a 1079-residue polypeptide that differs at the N terminus from the recently cloned human sodium bicarbonate cotransporter isolated from kidney (kNBC) (Burnham, C. E., Amlal, H., Wang, Z., Shull, G. E., and Soleimani, M. (1997) J. Biol. Chem. 272, 19111-19114). Northern blot analysis using a probe specific for the N terminus of pNBC revealed an approximately 7.7-kilobase transcript expressed predominantly in pancreas, with less expression in kidney, brain, liver, prostate, colon, stomach, thyroid, and spinal chord. In contrast, a probe to the unique 5' region of kNBC detected an approximately 7.6-kilobase transcript only in the kidney. In situ hybridization studies in pancreas revealed expression in the acini and ductal cells. The gene was mapped to chromosome 4q21 using fluorescent in situ hybridization. Expression of pNBC in Xenopus laevis oocytes induced sodium bicarbonate cotransport. These data demonstrate that pNBC encodes the sodium bicarbonate cotransporter in the mammalian pancreas. pNBC is also expressed at a lower level in several other organs, whereas kNBC is expressed uniquely in kidney.

Amino Acid Sequence↗
PubMed1998

A double-blind placebo-controlled evaluation of the human electrophysiologic effects of zatebradine, a sinus node inhibitor.

The purpose of this study was to evaluate the electrophysiologic effects of zatebradine, a sinus node inhibitor, in human subjects. Patients without structural heart disease were randomized to receive intravenous zatebradine (23 patients) or placebo (12 patients). Electrophysiologic measures were obtained at baseline and repeated at 40 and 70 min after drug administration. In the placebo group, there were no significant changes in any parameter over time. After zatebradine, sinus node function changed significantly at 40 min, with no further change at 70 min; sinus cycle length was prolonged by 16 and 17% (p < 0.001), and corrected sinus node recovery time was prolonged by 30 and 22% (p = 0.008). Similarly, atrioventricular node function changed significantly at 40 min, with no further change at 70 min; atrio-His interval was prolonged by 15 and 15% (p = 0.02), atrioventricular node effective refractory period was prolonged by 12 and 11% (p = 0.01), and Wenckebach cycle length was prolonged by 15 and 11% (p = 0.002). Atrial refractoriness, His-Purkinje conduction, ventricular refractoriness, and action-potential duration were not affected by zatebradine. Zatebradine, a sinus node inhibitor, alters the conduction and refractory properties of the human atrioventricular node, in addition to the expected effect on sinus node function.

Action Potentials↗
PubMed1998

When pacemakers fail: an analysis of clinical presentation and risk in 120 patients with failed devices.

Although pacemaker recalls are common, the optimal mechanism for risk assessment and triage of patients at risk for sudden loss of device system function is unknown. A retrospective chart review of 120 patients with factory proven failed devices was performed. Logistic regression analysis was used to determine clinical correlates of emergency room versus outpatient clinic presentation at time of device failure. Twenty-two patients (18%) presented to emergency and 98 (82%) to clinic. Sixty-three devices had no device output at the time of presentation. Multivariate logistic regression analysis revealed that antiarrhythmic drug use (odds ratio: 7.4, 95% CI: 2.0-28.0), atrioventricular nodal disease as an indication for pacing (odds ratio: 2.8, 95% CI: 1.2-3.0), and female gender (odds ratio: 2.2, 95% CI: 1.0-4.5) were the only significant correlates of emergency room presentations. Pacemaker dependency (escape heart rate < 40 beats/min) did not correlate with location of presentation even though no device output at the time of presentation was associated with emergency room presentation (odds ratio: 2.5, 95% CI: 1.1-5.8). Neither the presence of structural heart disease nor symptoms at the time of device implantation (syncope or presyncope) were correlated with location of presentation upon unexpected device failure. Although there were no deaths in the 120 failed devices studied, there were 26 deaths in the total group of 227 patients with recalled devices that could not be studied. Antiarrhythmic drug use, electrocardiographic pacing indication, and female gender may be more sensitive predictors of emergency room presentation and significant symptoms in the event of unanticipated pacemaker failure. The inability of any retrospective analysis to accurately assess mortality in the setting of pacemaker system failure underscores the need for prospective databases in recall situations.

Age Factors↗
PubMed1998

Axial heterogeneity of sodium-bicarbonate cotransporter expression in the rabbit proximal tubule.

It is generally accepted that Na(HCO3)n cotransport is the most important mechanism mediating basolateral bicarbonate efflux in the early proximal tubule. The presence of basolateral Na(HCO3)n cotransport in the late proximal tubule (S3 segment) and in the juxtamedullary S1 and S2 segments has been controversial. The renal sodium-bicarbonate cotransporter (NBC) has been recently cloned from rat (M. F. Romero, M. A. Hediger, E. L. Boulpaep, and W. F. Boron. J. Am. Soc. Nephrol. 7: 1259, 1996), salamander (M. F. Romero, M. A. Hediger, E. L. Boulpaep, and W. F. Boron. Nature 387: 409-413, 1997), and human (C. E. Burnham, H. Amlal, Z. Wang, G. E. Shull, and M. Soleimani. J. Biol. Chem. 272: 19111-19114, 1997). The localization of NBC in the kidney is unknown. The present study was designed to localize NBC mRNA expression in the rabbit proximal tubule. In situ hybridization studies were combined with functional studies of basolateral Na(HCO3)n cotransport in superficial and juxtamedullary S1, S2, and S3 segments of the rabbit proximal tubule. The results demonstrate that NBC mRNA is localized predominantly to the cortex, with less expression in the outer medulla. NBC expression was not detected in the inner medulla. The highest level of NBC mRNA is in the S1 proximal tubule. NBC is expressed at a low levels in the S3 segment, with intermediate expression in the S2 segment. In bicarbonate-buffered solutions, the rate of base efflux mediated by Na(HCO3)n cotransport followed a similar pattern in superficial and juxtamedullary proximal tubule segments, i.e., S1 > S2 > S3. The juxtamedullary S1 segment had the greatest rate of basolateral Na(HCO3)n cotransport and the highest level of NBC expression in the proximal tubule.

Animals↗
PubMed1998

Autonomic correlates of antidepressant treatment using heart-rate variability analysis.

OBJECTIVE: To assess the 24-hour temporal-domain heart-rate variability correlates of treatment with fluoxetine or doxepin for depression. METHOD: A randomized evaluation of fluoxetine and doxepin measured a 50% change in the Hamilton Depression Rating Scale (HDRS) score as a response to therapy and was correlated with measures of standard deviation of the mean of all 5-minute segments of normal electrocardiographic R-R intervals (SDANN), standard deviation of all normal R-R intervals (SDNN), root mean square of successive differences in R-R intervals (r-MSSD), and percentage difference between adjacent normal R-R intervals that are greater than 50 msec (pNN50) from 24-hour electrocardiogram (ECG) tapes. RESULTS: Ten out of 14 patients responded. Response was associated with an increase in SDANN of 17% (P < 0.05). Nonresponse was associated with a 17% decrease in SDANN and a 22% decrease in SDNN (both P < 0.05). No other measures correlated with therapeutic response. No heart-rate variability (HRV) differences between the 2 drug therapies were observed. CONCLUSION: Twenty-four-hour HRV measures may be useful in assessing response to antidepressant therapy.

Analysis of Variance↗
PubMed1998

Aftereffects and sense of presence in virtual environments: formulation of a research and development agenda.

This report represents a committee summary of the current state of knowledge regarding aftereffects and sense of presence in virtual environments (VEs). The work presented in this article, and the proposed research agenda, are the result of a special session that was set up in the framework of the Seventh International Conference on Human Computer Interaction. Recommendations were made by the committee regarding research needs in aftereffects and sense of presence, and, where possible, priorities were suggested. The research needs were structured in terms of the short, medium, and long term and, if followed, should lead toward the effective use of VE technology. The 2 most critical research issues identified were (a) standardization and use of measurement approaches for aftereffects and (b) identification and prioritization of sensorimotor discordances that drive aftereffects. Identification of aftereffects countermeasures (i.e., techniques to assist users in readily transitioning between the real and virtual worlds), reduction of system response latencies, and improvements in tracking technology were also thought to be of critical importance.

Adaptation, Physiological↗