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Biomedical subjects

D Mark

Publications and source records attributed to D Mark.

At least 19 recordsLinked to original sources
PubMed2002

Personal exposure monitoring of particulate matter, nitrogen dioxide, and carbon monoxide, including susceptible groups.

AIMS: To investigate the relation between personal exposures to nitrogen dioxide, carbon monoxide, and PM(10), and exposures estimated from static concentrations of these pollutants measured within the same microenvironments, for healthy individuals and members of susceptible groups. METHODS: Eleven healthy adult subjects and 18 members of groups more susceptible to adverse health changes in response to a given level of exposure to nitrogen dioxide, carbon monoxide, and/or PM(10) than the general population (six schoolchildren, six elderly subjects, and six with pre-existing disease-two with chronic obstructive pulmonary disease (COPD), two with left ventricular failure (LVF), and two with severe asthma) were recruited. Daytime personal exposures were determined either directly or through shadowing. Relations between personal exposures and simultaneously measured microenvironment concentrations were examined. RESULTS: Correlations between personal exposures and microenvironment concentration were frequently weak for individual subjects because of the small range in measured concentrations. However, when all subjects were pooled, excellent relations between measured personal exposure and microenvironment concentration were found for both carbon monoxide and nitrogen dioxide, with slopes of close to one and near zero intercepts. For PM(10), a good correlation was also found with an intercept of personal exposure (personal cloud) of 16.7 (SD 10.4) micro g/m(3). Modelled and measured personal exposures were generally in reasonably good agreement, but modelling with generic mean microenvironment data was unable to represent the full range of measured concentrations. CONCLUSIONS: Microenvironment measurements of carbon monoxide and nitrogen dioxide can well represent the personal exposures of individuals within that microenvironment. The same is true for PM(10) with the addition of a personal cloud increment. Elderly subjects and those with pre-existing disease received generally lower PM(10) exposures than the healthy adult subjects and schoolchildren by virtue of their less active lifestyles.

Adult↗
PubMed2001

HIV-related diarrhea is multifactorial and fat malabsorption is commonly present, independent of HAART.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has significantly decreased the incidence of infectious diarrhea affecting HIV-infected patients. Still, diarrhea remains a common symptom in HIV. We sought to determine the incidence of fat malabsorption as a cause of diarrhea in HIV patients receiving non-HAART (nucleoside analog only) and HAART (protease inhibitor-containing) antiretroviral regimens. METHODS: From June, 1995, to April, 1999, 88 HlV-infected patients underwent evaluation for diarrhea, which included endoscopy. We examined the incidence of fat malabsorption with a 24-h stool collection for fecal fat in a cohort of these patients (N = 33). Patients were divided into two groups, those receiving protease inhibitor-containing HAART and those receiving less intensive, nucleoside analog-only, non-HAART regimens. RESULTS: Thirty of 33 patients (90.9%) had fat malabsorption. Twenty of 21 patients not receiving HAART (95.2%) had fat malabsorption with a mean of 34 +/- 38 g of stool fat and a mean stool weight of 797 +/- 454 g. Ten of 12 patients receiving HAART (83.3%) had fat malabsorption with a mean of 46 +/- 86 g of stool fat and a mean stool weight of 800 +/- 647 g. Stool weight correlated with the degree of fat malabsorption (R = 0.77). CONCLUSION: Fat malabsorption represents a commonly undiagnosed entity in HIV-infected patients with diarrhea, whether or not they are receiving HAART therapy. Fecal fat determination should be considered a routine part of the diagnostic workup of HIV-infected patients experiencing diarrhea.

AIDS-Related Opportunistic Infections↗
PubMed2001

The effect of exposure to sulphuric acid on the early asthmatic response to inhaled grass pollen allergen.

Particulate sulphates, including sulphuric acid (H2SO4), are important components of the ambient aerosol in some areas and are regarded as air pollutants with potentially important human health effects. Challenge studies suggest little or no effect of H2SO4 exposure on lung function in asthmatic adults, although some epidemiological studies demonstrate an effect of acid species on symptoms in subjects with asthma. To date, the effect of H2SO4 on allergen responsiveness has not been studied. The effect of exposure to particulate H2SO4 on the early asthmatic response to grass pollen allergen has been investigated in 13 adults with mild asthma. After establishment of the provocative dose of allergen producing a 15% fall in forced expiratory volume in one second (FEVI) (PD15) for each subject, they were exposed to air, 100 microg m(-3) or 1,000 g x m(-3) H2SO4 for 1 h, double-blind in random order > or =2 weeks apart, through a head dome delivery system 14 h after each exposure subject underwent a fixed-dose allergen challenge (PD15). Ten subjects completed the study. The mean early asthmatic responses (maximum percentage change in FEV1 during the first 2 h after challenge) following air, 100 microg x m(-3) H2SO4, and 1,000 microg m(-3) H2SO4, were -14.1%, -16.7%, and -18.4%, respectively. The difference between 1,000 microg x m(-3) H2SO4 and air was significant (mean difference: -4.3%, 95% confidence interval (CI: -1.2-7.4%, p=0.013). The difference between air and 100 microg m(-3) H2SO4 approached significance (mean difference: -2.6%, 95% CI: 0.0-5.3%, p = 0.051). These results suggest that, at least at high mass concentration, sulphuric acid can potentiate the early asthmatic response of mild asthmatic subjects to grass pollen allergen, although the effect is limited.

Administration, Inhalation↗
PubMed2000

Canadian-American differences in the management of acute coronary syndromes in the GUSTO IIb trial: one-year follow-up of patients without ST-segment elevation. Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) II Investigators.

BACKGROUND: Little information exists concerning practice patterns between Canada and the United States in the management of myocardial infarction (MI) patients without ST-segment elevation and unstable angina. METHODS AND RESULTS: We examined the practice patterns and 1-year outcomes of 2250 US and 922 Canadian patients without ST-elevation acute coronary syndromes in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial. The US hospitals more commonly had on-site facilities for angiography and revascularization. These procedures were performed more often and sooner in the United States than Canada, whereas Canadian patients were more likely to undergo noninvasive stress testing. The length of initial hospital stay was 1 day longer for Canadian than US patients. Recurrent and refractory ischemia was more common in Canada. One-year mortality was comparable between the 2 countries. However, at 6 months, even after baseline differences were accounted for, the (re)MI rate was significantly higher in Canadian than US patients with unstable angina (8.8% versus 5.8%, P:=0.039), as was the composite rate of death or (re)MI (13.1% versus 9.1%, P:=0.016). CONCLUSIONS: One-year mortality was comparable between Canada and the United States in both MI and unstable angina cohorts despite higher intervention rates in the United States. However, outcomes at 6 months among patients with unstable angina differed. Whereas more frequent coronary interventions were not associated with reduced recurrent MI or death among MI patients without ST elevation, they may favorably affect outcomes in patients with unstable angina.

Analysis of Variance↗
PubMed1999

Development of a personal monitoring method for nitrogen dioxide and sulfur dioxide with Sep-Pak C18 cartridge sampling and ion chromatographic determination.

Personal monitoring methods for the determination of hourly integrated concentrations of NO2 and SO2 in ambient air have been developed. Triethanolamine (TEA)-impregnated C18 Sep-Pak cartridges were used to collect NO2 and SO2 simultaneously. After sampling, NO2 and SO2 as their nitrite, nitrate, sulfite and sulfate analogues were stripped from the cartridges with a solution of 5% methanol in distilled, deionized water (DDW) and then determined by ion chromatography. Laboratory tests were conducted to evaluate the sampling rate, collection and recovery efficiencies, breakthrough volumes, absorption capacity, interference and sample stability on the cartridge during storage. NO2 and SO2 detection limits of 0.3 and 0.4 ppb respectively for 1 h samples were obtained. Recoveries for both NO2 and SO2 exceeded 85%.

Air Pollutants↗
PubMed1999

Decreased CD8 cell-mediated viral suppression and other immunologic characteristics of women who transmit human immunodeficiency virus to their infants.

CD8 T cell function, lymphocyte surface phenotype, serum markers of immunologic activation, and viral burden were assessed in 75 human immunodeficiency virus (HIV)-infected pregnant women, including 9 who transmitted infection to their infants. Serial studies during and after pregnancy showed no significant differences in levels of cell-surface or serum activation molecules in transmitting compared to nontransmitting mothers, with the exception of a postpartum increase in tumor necrosis factor alpha in transmitting women. The transmitting women had a median plasma viral load of 65,516 RNA copies/mL at delivery versus 5139 in nontransmitting women. During the third trimester, the CD8 cells of 81% of the nontransmitting and 44% of the transmitting mothers suppressed HIV production in vitro by >50%. Women with <50% suppression had a 3.4 times greater risk of transmitting HIV to their infants. CD8 suppression and viral load were interrelated, but when either CD4 percent or AZT use was controlled for, suppression was still significant.

CD3 Complex↗
PubMed1998

Training in cognitive, supportive-expressive, and drug counseling therapies for cocaine dependence.

This study assessed the effects of training on the performance of 65 therapists in delivering manual-guided therapies to 202 cocaine-dependent patients. Changes in ratings of therapists' adherence and competence was assessed in 3 treatment modalities: supportive-expressive dynamic therapy (SE), cognitive therapy (CT), and individual drug counseling. Effects of manual-guided training on the therapeutic alliance were also assessed. Training effects were examined through a hierarchical linear modeling approach that examined changes both within cases and across training cases. A large effect across cases was detected for training in CT. Supportive-expressive therapists and individual drug counselors demonstrated statistically significant learning trends over sessions but not over training cases. Training in SE and CT did not have a negative impact on the therapeutic alliance, although alliance scores for trainees in drug counseling initially decreased but then rebounded to initial levels.

Adult↗
PubMed1998

When innovative therapies make economic sense: economic analysis of enoxaparin versus unfractionated heparin in the ESSENCE trial--an overview. Efficacy and Safety of Subcutaneous in non-Q Wave Coronary Events.

An economic substudy using intention-to-treat analysis was conducted prospectively to compare the costs of enoxaparin and unfractionated heparin (UFH) therapy in 936 patients enrolled in the United States arm of the multicentre, international Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial. Hospital billing data were used for 655 of the American patients. Hospital costs for the remainder of the patients were imputed using a multivariate linear regression model (r2 = 0.86). Physician fees were estimated from the Medicare Fee Schedule. Results indicated that, compared with UFH patients, enoxaparin patients made use of fewer resources during initial hospitalization, with the largest difference in resource use seen for coronary angioplasty patients (15% for enoxaparin versus 20% for UFH patients; P = 0.04). This trend persisted at 30 days, with the largest reductions in resource use occurring in diagnostic catheterization (57% versus 63%, respectively; P = 0.04) and coronary angioplasty (18% versus 22%, respectively; P = 0.08). Although the mean cost for a course of enoxaparin was US $155, compared with US $80 for UFH, total medical costs for hospitalization, physician care and drugs during the initial treatment phase were US $11,857 for enoxaparin therapy versus US $12,620 for UFH therapy, producing a cost advantage of US $763 for enoxaparin therapy (P = 0.18). Cumulative cost savings associated with enoxaparin treatment at 30 days were US $1,172 (P = 0.04). Results suggested that enoxaparin therapy compared with standard UFH therapy improves key clinical outcomes and saves money in patients with acute coronary syndrome.

Coronary Disease↗
PubMed1997

A collaborative European study of personal inhalable aerosol sampler performance.

Following the adoption of new international sampling conventions for inhalable, thoracic and respirable aerosol fractions, a working group of Comité Européen de Normalisation (CEN) drafted a standard for the performance of workplace aerosol sampling instruments. The present study was set up to verify the experimental, statistical and mathematical procedures recommended in the draft performance standard and to check that they could be applied to inhalable aerosol samplers. This was achieved by applying the tests to eight types of personal inhalable aerosol sampler commonly used for workplace monitoring throughout Europe. The study led to recommendations for revising the CEN draft standard, in order to simplify the tests and reduce their cost. However, some further work will be needed to develop simpler test facilities and methods. Several of the samplers tested were found to perform adequately with respect to the inhalable sampling convention, at least over a limited range of typical workplace conditions. In general the samplers were found to perform best in low external wind speeds, which are the test conditions thought to be closest to those normally found in indoor workplaces. The practical implementation of the CEN aerosol sampling conventions requires decisions on which sampling instruments to use, estimation of the likely impact that changing sampling methods could have on apparent exposures, and adjustment where necessary of exposure limit values. The sampler performance data obtained in this project were affected by large experimental errors, but are nevertheless a useful input to decisions on how to incorporate the CEN inhalable sampling convention into regulation, guidance and occupational hygiene practice.

Europe↗
PubMed1996

Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.

Activation of naive T cells requires at least two signals. In addition to the well characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma.

Airway Resistance↗
PubMed1996

Regulation of CTLA-4 expression during T cell activation.

T cell activation requires at least two distinct signals, including signaling via the Ag-specific TCR and a costimulatory pathway. The best characterized costimulatory pathway involves the CD28 molecule, which is expressed constitutively on T cells and binds the family of B7 counter-receptors on APCs. Inhibition of this costimulatory pathway prevents T cell activation and can lead to long-term T cell unresponsiveness or anergy. In contrast, CTLA4, which is homologous to CD28, has been shown to be a negative regulator of T cell activation. The CTLA4 molecule is not expressed on resting T cells, but is induced after the initial steps of T cell activation. To address the regulation of CTLA4 expression, we have analyzed CTLA4 at the level of cell surface expression, mRNA, rate of transcription, and rate of decay of message. Nuclear runoff results show an increase in the rate of transcription following T cell activation. Our analyses of non-T cells, including B cells, mastocytoma, and fibroblasts, by Northern blot analysis detect only T cell expression of CTLA4. Reporter gene analysis indicates that 335 bp of upstream CTLA4 sequence are sufficient to control inducibility. We have identified important regulatory regions that control inducible and cell-specific CTLA4 expression. These results also suggest that both positive and negative response elements modulate the transcriptional regulation of CTLA4 gene expression. Understanding the regulation of CTLA4 should provide insight into the regulation of T cell activation at the molecular level.

Abatacept↗
PubMed1996

Semi-empirical model for the aspiration efficiencies of personal aerosol samplers of the type widely used in occupational hygiene.

This paper extends what it known about the aspiration efficiencies of blunt aerosol samplers at large angles and under 'orientation-averaged' conditions to the important case of personal samplers worn by workers. Attention is focused on three sampling devices which have particular relevance to industrial hygiene sampling in Britain, the United States and elsewhere. A semi-empirical model for aspiration efficiency is described, based on physical considerations of the nature of air and particle motion near an asymmetric sampling system, like that relevant to personal sampling. The resultant model contains a number of coefficients which are fitted by non-linear regression to experimental data sets which were available from previously published experiments for the three samplers in question. Agreement for all three data sets is good, with an overall Rcorr2 of 68%. Such semi-empirical models can be useful for predicting and interpreting sampler performance until practical versions of more rigorous mathematical and numerical models become available.

Air Pollutants, Occupational↗
PubMed1996

Colonoscopy evaluations: justification by cost?

The type of colonic imaging (radiological vs colonoscopic) for evaluating symptomatic patients without evidence of bleeding in both an efficacious and cost-conserving manner has become a very debated issue. In a randomized, controlled clinical trial, the authors hoped to examine the prevalence of neoplasm and the effectiveness and cost-effectiveness of initial diagnostic strategies of colonoscopy versus flexible sigmoidoscopy and air contrast barium enema in patients without evidence of intestinal bleeding. One hundred forty-nine patients over the age of 40 with symptoms suggestive a colonic disease without evidence of bleeding (no hematechezia, negative test for fecal occult blood, and normal serum hemoglobin) were randomized to undergo either initial colonoscopy or flexible sigmoidoscopy plus barium enema. Patients with incomplete lower GI tests were referred for the corresponding alternative imaging modality. Cost analyses using sensitivity analysis were performed. Baseline information with respect to age, race, sex, inpatient status, reason for referral, mean weight loss, hemoglobin, blood urea nitrogen, and albumin were similar in both groups. Eighteen patients (24%) who initially received air contrast barium enema and flexible sigmoidoscopy then required colonoscopy, whereas only five patients (6%) who initially underwent colonoscopy first required air contrast barium enema plus flexible sigmoidoscopy. The study found that: a) The prevalence of cancer in the study was low (one of 149 patients); b) initial colonoscopy detected more persons with adenomas than that of air contrast barium enema plus flexible sigmoidoscopy (23 of 75 patients vs 13 of 74 patients, odds radio, 2.07, CI,0.90-4.92; this approached significance); and c) air contrast barium enema plus flexible sigmoidoscopy detected more diverticulosis (46 of 74 patients vs 31 of 75 patients, odds ratio, 0.41, 95% CI, 0.21-0.87). The significant conclusions were that patients undergoing flexible sigmoidoscopy plus air contrast barium enema were more likely to undergo alternative procedures and that sensitivity analysis suggested that, for most areas in the United States, initial colonoscopy would be more cost-effective for the outcome of detection of adenomas (1).

Barium Sulfate↗