Biomedical subjects

R Vincent

Publications and source records attributed to R Vincent.

At least 19 recordsLinked to original sources

PubMed2006

Structure analysis of embedded nano-sized particles by precession electron diffraction. eta'-precipitate in an Al-Zn-Mg alloy as example.

The Vincent-Midgley precession technique has been used to collect three-dimensional electron diffraction intensity data from a dispersion of coherent precipitates in a matrix. In order to suppress severe effects from multiple diffraction via matrix reflections, a fairly large precession (tilt) angle had to be used. This implied a high background from the surrounding matrix, and limited the number of reflections that could be measured from patterns on image plates. The heavily faulted hexagonal eta'-precipitates (a = 0.496 nm, c = 1.405 nm) with thickness 3-5 nm occur in four equivalent orientations relative to the aluminium matrix; with frequent overlap of reflections. A model of the average structure in the space group P6(3)/mmc with assumed composition Mg(2)Zn(5-x)Al(2+x), have been derived by Patterson analysis and intensity comparisons.

Journal Article↗

PubMed2006

What percentages of patients are suitable for prehospital thrombolysis?

OBJECTIVE: To apply the Joint Royal College Ambulance Liaison Committee (JRCALC) checklist to patients who were deemed eligible for thrombolytic therapy on arrival in an Accident & Emergency Department (A&E) to determine the proportion suitable for prehospital thrombolysis. DESIGN: Retrospective descriptive analysis. METHODS: The clinical notes of all patients thrombolysed in an A&E department in a year were reviewed against the JRCALC guidelines for prehospital thrombolysis. RESULTS: 14.2% of patients eligible for thrombolysis in a district general hospital were deemed suitable for prehospital thrombolysis according to the JRCALC criteria. The most common exclusion criteria were hyper/hypotension (50%), onset of symptoms (pain) >6 h previously (41.7%), or age >75 years (37%). Two or more contraindications to prehospital thrombolysis were present in 63.9% of patients. CONCLUSION: The JRCALC guidelines are an effective tool for identifying patients with potential contraindications to thrombolysis.

Adult↗

PubMed2006

Mutant p53 protein in serum could be used as a molecular marker in human breast cancer.

p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.

Adult↗

PubMed2005

An optimized protein in-gel digest method for reliable proteome characterization by MALDI-TOF-MS analysis.

Human lung epithelial cells (A549) were used as a model to develop a reliable proteome characterization method by peptide mass fingerprinting (PMF). Lung cell lysate proteins and protein standards were separated by 2D-gel electrophoresis, stained with Coomassie blue, gel plugs were subjected to commonly adapted as well as optimized in-gel digestion/sample preparation methods. Samples were analyzed by MALDI-TOF-MS. Optimization parameters included, use of NH(4)OAc in destaining and in-gel digestion buffers, detergent/salt removal prior to in-gel digestion, use of solvents of varying polarities (0%, 30%, 60% ACN containing 0.1% TFA) to improve peptide recoveries, matrix composition (alpha-cyano-4-hydroxycinamic acid-organic solvent combinations) and on-target salt removal. This led to enhanced mass spectral information and a sensitivity gain in the order of 6-10 fold compared to that of common procedures, yielding reliable, unambiguous protein identification with femtomol protein sensitivity by Autoflex MALDI-TOF-MS. Triplicate analyses by two analysts revealed consistent, wide range m/z values including in < 1200Da region by relieving matrix-exerted signal suppression, requiring one trial to obtain a unique protein identification with superior PMF results for the optimized method. Analyses of ten A549 proteins in replicates using the optimized method yielded fast, reliable characterization, suggesting the potential application of this method in high-throughput protein identification by PMF.

Cell Line↗

PubMed2004

Effects of ambient air particles on nitric oxide production in macrophage cell lines.

We assessed the in vitro toxicity of various particles on three murine macrophage cell lines, (J774A.1, WR19M.1, RAW264.7). The cells were exposed to aqueous suspensions (0-100 microg/30 mm2 well) of urban particulate matter (SRM-1648, SRM-1649, EHC-93), fine particulate matter (PM2.5), titanium dioxide (SRM-154b), and respirable cristobalite (SRM-1879) for 2 h and were then stimulated with lipopolysaccharide (LPS, 100 ng/ml) and recombinant interferon-gamma (IFN, 100 U/ml). After overnight incubation with the particles and LPS/IFN, nitric oxide production was estimated from culture supernatant nitrite. Cell viability was determined by monitoring the rate of AlamarBlue reduction. The dose-effect relationships for nitrite and viability were modeled as a power function (Fold change = [Dose+1]beta), where beta represents the slope of the dose-response curve. Potency was defined as the rate of change in nitrite production corrected for cell viability (beta(POTENCY) = beta(NITRITE) - beta(VIABILITY)). Overall, the urban particles decreased nitric oxide production (beta(POTENCY) < 0), while exposure of the cells to fine particulate matter or cristobalite increased the production of nitric oxide (beta(POTENCY) > 0). Titanium dioxide (TiO2) was essentially inactive (beta(POTENCY) approximately to 0). The decrease in nitric oxide production seen in cells exposed to the urban particles was directly correlated to a decrease in the expression of inducible nitric oxide (iNOS) as determined by Western blot analysis. The results indicate that particles are modulators of nitric oxide production in murine macrophages and may directly disrupt expression of iNOS during concomitant pathogen exposure. Pathways leading to enhanced NO production causing cell injury, and to decreased NO release resulting in lower bacterial clearance, may both be relevant to the health effects of ambient particles.

Air Pollution↗

PubMed2003

Differential production of metalloproteinases after instilling various urban air particle samples to rat lung.

Lung injury and inflammation are associated with exposure to various types of particulate air pollutants. The present study was used to determine whether metalloproteinases (MMPs) are secreted after instilling dust samples into the lung, and to relate levels of specific MMPs to different fractions of the ambient air particle sample EHC-93. Rats received an intratracheal injection of 5 mg dust samples in 0.5 ml water and were killed at intervals from 4 hours to 28 days later particle samples were EHC-93 whole dust, and the insoluble, leached, and soluble fractions of the same dust. Samples prepared from EHC-2K dust were also used, as were solutions of zinc and copper chloride. All samples induced inflammation as measured by increased inflammatory cells in bronchoalveolar lavage (BAL) fluid; the highest levels were found 1 to 3 days after instilling the whole dust. This dust also induced production of MMP-2 and MMP-9 as shown in zymograms. The leached dust induced predominantly MMP-9, which was maximal at 4 hours and 1 day. In contrast, the soluble fraction induced almost exclusive 4 MMP-2, also maximal at 4 hours and 1 day; this enzyme was also produced in response to soluble zinc, the most prevalent soluble metal in the EHC samples. The results demonstrate the rapid production and secretion of MMPs in the lung after particle deposition. A differential pattern of MMP production is seen with MMP-9, likely from inflammatory cells, being produced in response to the insoluble particles, and MMP-2, likey from epithelial cells, being produced in response to the water-soluble fraction of the atmospheric dust.

Air Pollutants↗

PubMed2002

Heart failure in patients admitted to hospital: mortality is still high.

BACKGROUND: Two separate cohorts of consecutive patients admitted to hospital with a primary diagnosis of heart failure were studied, the first in 1986 in Rochdale, and the second in 1995 in Brighton. METHODS: We observed the clinical profile, treatment and mortality during hospital admission and reviewed their status at 6 months. There were 132 patients in the Rochdale cohort and 223 in the Brighton cohort. RESULTS: The Rochdale cohort was characterised by a lower mean age and longer hospital stay. Significant differences were also observed in co-morbidity and the use of ACE inhibitors, but hospital mortality was almost identical (25% in Rochdale and 24% in Brighton). A low systolic blood pressure, hyponatraemia, hyperkalaemia and a raised blood urea at presentation were independent adverse prognostic factors. In contrast, prior treatment with ACE inhibitors in patients with congestive cardiac failure led to a more favourable hospital outcome. Age, gender and co-morbidity did not affect mortality apart from patients with acute myocardial infarction. Follow-up of these cohorts showed that mortality of the two groups remained high at 180 days after admission (40% in Rochdale and 39% in Brighton). There were marked differences in the use of ACE inhibitors in survivors, but target doses of ACE inhibitors (enalapril 20 mg/day or equivalent) were only achieved in 31%, despite direct communication between the hospital and primary care physicians. CONCLUSIONS: Although clinical and treatment profiles differed between the two periods studied, the hospital and 6-month mortality of patients with heart failure remained high. More emphasis needs to be given to optimising ACE inhibitor use in primary care.

Journal Article↗

PubMed2001

An automated high-performance liquid chromatography fluorescence method for the analyses of endothelins in plasma samples.

A high-performance liquid chromatographic method with fluorescence detection was developed to simultaneously analyze endothelins, a class of vasoactive peptides, in plasma samples. Sample preparation for HPLC analysis was carried out by initial stabilization of blood and plasma samples against transformation of big endothelins to mature endothelins and breakdown of mature endothelins by serine proteases, as well as oxidative modifications of endothelins. Deproteinization of plasma samples was achieved with acidified acetone, and the samples were further purified on molecular weight cutoff filters. Endothelins were separated on a reversed phase LC-318 column by gradient elution using a mobile phase containing acetonitrile and water (0.1% trifluoroacetic acid) and were analyzed by fluorescence detection (lambda(Ex), 280 nm; lambda(Em), 340). Limit of detection values were in the range of 0.2-0.5 pmol. Linear (R(2), 0.99) calibration curves were established for analyte amounts in the range of 1 to 100 pmols. Recoveries of endothelins from spiked plasma samples analyzed ranged from 60-95%. Under optimized conditions the HPLC-fluorescence method was determined to be sensitive and specific for the analysis of big endothelin-1, endothelin-1, endothelin-2, and endothelin-3 in plasma. Simultaneous measurement of these endothelins by the HPLC method should permit a better understanding of their specific roles and relationships under various pathological conditions.

2-Naphthylamine↗

PubMed2001

Associations between daily cause-specific mortality and concentrations of ground-level ozone in Montreal, Quebec.

The authors investigated the association between daily variations in ozone and cause-specific mortality. Fixed-site air pollution monitors in Montreal, Quebec, provided daily mean levels of ozone, particles, and other gaseous pollutants. Information on the date and underlying cause of death was obtained for residents of Montreal who died in the city between 1984 and 1993. The authors regressed the logarithm of daily counts of cause-specific mortality on mean levels of ozone, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, and weather variables. The effect of ozone on mortality was generally higher in the warm season and among persons aged 65 years or over. For an increase in the 3-day running mean concentration of ozone of 21.3 microg/m(3), the percentage of increase in daily deaths in the warm season was the following: nonaccidental deaths, 3.3% (95% confidence interval (CI): 1.7, 5.0); cancer, 3.9% (95% CI: 1.0, 6.91); cardiovascular diseases, 2.5% (95% CI: 0.2, 5.0); and respiratory diseases, 6.6% (95% CI: 1.8, 11.8). These results were independent of the effects of other pollutants and were consistent with a log-linear response function.

Accidents↗

PubMed2001

Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)).

Elevated levels of ambient particulate matter (PM(10)) have been associated with increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammatory response that includes stimulation of the bone marrow. This marrow response is related to mediators released by alveolar macrophages (AM) and in this study we measured cytokines produced by human AM exposed to ambient particles of different composition and size. Identified cytokines were also measured in the circulation of healthy young subjects exposed to air pollutants during the 1997 Southeast Asian forest fires. Human AM were incubated with particle suspensions of residual oil fly ash (ROFA), ambient urban particles (EHC 93), inert carbon particles, and latex particles of different sizes (0.1, 1, and 10 microm) and concentrations for 24 h. Tumor necrosis factor-alpha (TNF-alpha) increases in a dose-dependent manner when AM were exposed to EHC 93 particles (p < 0.02). The TNF response of AM exposed to different sizes of latex particles was similar. The latex (158 +/- 31%), inert carbon (179 +/- 32%), and ROFA (216 +/- 34%) particles all show a similar maximum TNF response (percent change from baseline) whereas EHC 93 (1,020 +/- 212%, p < 0.05) showed a greater maximum response that was similar to lipopolysaccharide (LPS) 1 microg/ml (812 +/- 320%). Macrophages incubated with an optimal dose of EHC 93 particles (0.1 mg/ml) also produce a broad spectrum of other proinflammatory cytokines, particularly interleukin (IL)-6 (p < 0.01), IL-1 beta (p < 0.05), macrophage inflammatory protein-1 alpha (MIP-1 alpha) (p < 0.05), and granulocyte macrophage colony-stimulating factor (GM-CSF) (p < 0.01) with no difference in concentrations of the anti-inflammatory cytokine IL-10 (p = NS). Circulating levels of IL-1 beta, IL-6, and GM-CSF were elevated in subjects exposed to high levels of PM(10) during an episode of acute air pollution. These results show that a range of different particles stimulate AM to produce proinflammatory cytokines and these cytokines are also present in the blood of subjects during an episode of acute atmospheric air pollution. We postulate that these cytokines induced a systemic response that has an important role in the pathogenesis of the cardiopulmonary adverse health effects associated with atmospheric pollution.

Aged↗

PubMed2001

The association between daily mortality and ambient air particle pollution in Montreal, Quebec. 2. Cause-specific mortality.

This study was undertaken to determine whether variations in concentrations of particulates in the ambient air of Montreal, Quebec, during the period 1984 to 1993, were associated with daily variations in cause-specific daily mortality. Fixed-site air pollution monitors in Montreal provided daily mean levels of various measures of particles and gaseous pollutants. Total sulfate was also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec). We used coefficient of haze (COH), extinction coefficient, and sulfate from the Sutton station to predict fine particles and sulfate from fine particles for days that were missing. We estimated associations between cause-specific mortality and PM(2.5), PM(10), predicted fine particles and fine sulfate particles, total suspended particles, coefficient of haze, extinction coefficient, and total sulfate measured at the Sutton station. We selected a set of underlying causes of death, as recorded on the death certificates, as the endpoint and then regressed the logarithm of daily counts of cause-specific mortality on the daily mean levels for the above measures of particulates, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, weather variables, and gaseous pollutants. We found positive and statistically significant associations between the daily measures of ambient particle mass and sulfate mass and the deaths from respiratory diseases and diabetes. The mean percentage change in daily mortality (MPC), evaluated at the interquartile range for pollutants averaged over the day of death and the preceding 2 days, for deaths from respiratory diseases was MPC(COH)=6.90% (95% CI: 3.69-10.21%), MPC(Predicted PM2.5)= 9.03% (95% CI: 5.83- 12.33%), and MPC(Sutton sulfate)=4.64% (95% CI: 2.46-6.86%). For diabetes, the corresponding estimates were MPC(COH)=7.50% (95% CI: 1.96-13.34%), MPC(Predicted PM2.5)=7.59% (95% CI: 2.36-13.09%), and MPC(Sutton sulfate)=4.48% (95% CI: 1.08-7.99%). Among individuals older than 65 years at time of death, we found consistent associations across our metrics of particles for neoplasms and coronary artery diseases. Associations with sulfate mass were also found among elderly persons who died of cardiovascular diseases and of lung cancer. These associations were consistent with linear relationships. The associations found for respiratory diseases and for cardiovascular diseases, especially in the elderly, are in line with some of the current hypotheses regarding mechanisms by which ambient particles may increase daily mortality. The positive associations found for cancer and for diabetes may be understood through a general hypothesis proposed by Frank and Tankersley, who suggested that persons in failing health may be at higher risk for external insults through the failure of regulating physiological set points. The association with diabetes may be interpreted in light of recent toxicological findings that inhalation of urban particles in animals increases blood pressure and plasmatic levels of endothelins that enhance vasoconstriction and alter electrophysiology. Further research to confirm these findings and to determine whether they are causal is warranted.

Aged↗

PubMed2001

Comparison of two oxytocin regimens to prevent uterine atony at cesarean delivery: a randomized controlled trial.

OBJECTIVE: To determine if high-dose oxytocin reduces the need for additional uterotonic agents at cesarean. METHODS: A randomized, double-masked trial of two oxytocin regimens was performed to prevent postpartum uterine atony in laboring women. The pharmacy prepared sequentially numbered oxytocin solutions containing either 10 U/500 mL or 80 U/500 mL of lactated Ringer's solution infused over 30 minutes after cord clamping. The need for additional uterotonic agents was determined by the surgical team. Hypotension was diagnosed and treated with crystalloid or a pressor agent. To detect a 50% decrease in the need for additional uterotonic agents and considering a beta error of 0.2, 220 patients would be required in each group (alpha = 0.05, two-tailed chi(2) test). RESULTS: The low-dose group (n = 163) received 333 mU/min, and the high-dose group (n = 158) received 2667 mU/min of oxytocin. The groups were similar with respect to risk factors for atony. Women in the low-dose group received additional uterotonic medication significantly more often than those in the high-dose group (39% compared with 19%, P <.001, relative risk 2.1, 95% confidence interval 1.4, 3.0). Moreover, more women in the low-dose group received methylergonovine, 15-methyl prostaglandin F(2alpha) or both (9% compared with 2%, relative risk 4.8, 95% confidence interval 1.4, 16) after additional oxytocin (median 20 U) had been added to the study solution. The incidence of hypotension was similar in both groups. CONCLUSION: Compared with an infusion rate of 333 mU/min, oxytocin infused at 2667 mU/min for the first 30 minutes postpartum reduces the need for additional uterotonic agents at cesarean delivery.

Adult↗

PubMed2001

Phase retrieval in TEM using Fresnel images.

As an alternative to sideband holography in an electron microscope, methods for phase recovery by in-line holography utilising Fresnel images of aperiodic objects were tested with computed simulations and experimental data. Phases were recovered by minimising an error functional defined as a measure of the differences between experimental and calculated image intensities. The probability of convergence to local minima of the error function was reduced by increasing the ratio of known to unknown parameters, partly by use of several Fresnel images at different defoci, and also by an incremental relaxation of the phase bandwidth. Iterative methods did not converge reliably to a global minimum, but a conjugate gradient algorithm usually recovered the phases exactly, even for object arrays which included large phase variations. In practice, it was essential to use analytic expressions for the error gradients with respect to the phases, defoci and beam direction. Phase shifts of several radians were measured near the edge of a contaminated aperture. The factors that limit the accuracy and reliability of phase recovery from Fresnel images are discussed.

Journal Article↗

PubMed2001

HLA-DRB1 gene transcripts in rheumatoid arthritis.

Susceptibility to rheumatoid arthritis (RA) is associated with defined HLA-DRB1 alleles. However the molecular basis of this association is not known. Peculiarities in the expression of disease-linked DRB1 alleles could be involved since in healthy controls HLA-DRB1 gene expression varies according to the alleles in B cells. Peripheral blood B cells of healthy controls and RA patients were examined for their level of allelic DRB1 transcripts using a competitive PCR approach. Levels of DRB1 transcripts were greatly modified in RA and influenced by HLA-DRB1 genotype: patients with double dose of RA-associated alleles displayed up-regulated amounts of DRB1 gene transcripts whereas patients carrying either a single or no at risk allele had low levels of DRB1 transcripts, compared to control individuals. These differential levels of DRB1 gene expression were not influenced in any way by clinical, biological or therapeutic features of the patients. Various amounts of DRB1 mRNA may be related to variations of the density of DR molecules on B cells and consequently could influence the response of CD4 T cells. This particular regulation of DRB1 gene expression in RA patients could therefore represent one of the molecular mechanisms involved in the association of HLA DRB1 genes to RA.

Alleles↗

PubMed2001

COLCHIC-occupational exposure to chemical agents database: current content and development perspectives.

Set up in 1987, COLCHIC is a database for occupational exposure to chemical agents. Eight French regional health insurance fund (Caisse Régionale d'Assurance Maladie-CRAM) interregional laboratories and the French national research and safety institute (Institut National de Recherche et de Securite-INRS) laboratories have stored results and information from chemical agent exposure measurements on this database. More than 10 years later, 400,000 measurement results of exposure to 600 substances are now stored on COLCHIC. Utilization of data from this base is limited by the quality and absence of certain information, so a working group has been formed to develop a new data retrieval system, which takes into account recommendations formulated by the AIHA-ACGIH and European working groups. Utilization of this new coding system should allow improved description of workplace exposure conditions in the near future. This data retrieval system is currently being validated and should be used by the laboratories concerned during the course of 2001.

Databases, Factual↗

PubMed2001

The effect of repeated exposure to particulate air pollution (PM10) on the bone marrow.

Studies have shown that exposure to ambient particulate matter is related to an increased cardiopulmonary morbidity and mortality. The present study was designed to measure the effect of repeated exposure to urban air particles (PM10) on the rate of production and release of polymorphonuclear leukocytes (PMN) from the bone marrow into the peripheral blood. Rabbits exposed to PM10 (5 mg) twice a week for 3 wk, were given a bolus of 5'-bromo-2'-deoxyuridine (BrdU) to label dividing cells in the marrow that allows us to calculate the transit time of PMN in the bone marrow mitotic and postmitotic pools. The PM10 exposure (n = 8) causes a persistent increase in circulating band cells (p < 0.05) and a shortening of the transit time of PMN through the postmitotic pool in the marrow (64.4 +/- 2.2 h to 56.3 +/- 2.2 h, p < 0.05) if compared with vehicle-exposed control subjects (n = 6). PM10 exposure increases the bone marrow pool of PMN particularly the mitotic pool of PMN (p < 0.05). The PM10 were distributed diffusely in the lung and caused a mild mononuclear inflammation. The percentage of alveolar macrophages containing PM10 correlated significantly with the bone marrow PMN pool size (total pool r2 = 0.56, p < 0.012, mitotic pool r2 = 0.61, p < 0.007) and the transit time of PMN through the postmitotic pool (r2 = -0.42, p < 0.043). We conclude that repeated exposure to PM10 stimulates the bone marrow to increase the production of PMN in the marrow and accelerate the release of more immature PMN into the circulation. The magnitude of these changes was related to the amount of particles phagocytosed by alveolar macrophages.

Air Pollution↗

PubMed2001

Particulate matter induces cytokine expression in human bronchial epithelial cells.

The present study was designed to determine cytokines produced by primary human bronchial epithelial cells (HBECs) exposed to ambient air pollution particles (EHC-93). Cytokine messenger RNA (mRNA) was measured using a ribonuclease protection assay and cytokine protein production by enzyme-linked immunosorbent assay. Primary HBECs were freshly isolated from operated lung, cultured to confluence, and exposed to 10 to 500 microg/ml of a suspension of ambient particulate matter with a diameter of less than 10 microm (PM(10)) for 2, 8, and 24 h. The mRNA levels of leukemia inhibitory factor (LIF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1alpha, and IL-8 were increased after exposure to PM(10), and this increase was dose-dependent between 100 (P < 0.05) and 500 (P < 0.05) microg/ml of PM(10) exposure. The concentrations of LIF, GM-CSF, IL-1beta, and IL-8 protein measured in the supernatant collected at 24 h increased in a dose- dependent manner and were significantly higher than those in the control nonexposed cells. The soluble fraction of the PM(10) (100 microg/ml) did not increase these cytokine mRNA levels compared with control values and were significantly lower compared with HBECs exposed to 100 microg/ml of PM(10) (LIF, IL-8, and IL-1beta; P < 0.05), except for GM-CSF mRNA (P = not significant). We conclude that primary HBECs exposed to ambient PM(10) produce proinflammatory mediators that contribute to the local and systemic inflammatory response, and we speculate that these mediators may have a role in the pathogenesis of cardiopulmonary disease associated with particulate air pollution.

Aged↗

PubMed2001

Identification of persons with cardiorespiratory conditions who are at risk of dying from the acute effects of ambient air particles.

This study was undertaken to identify subgroups of the population susceptible to the effects of ambient air particles. Fixed-site air pollution monitors in Montreal, Quebec, Canada, provided daily mean levels of various measures of particulates and gaseous pollutants. Total sulfates were also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec, Canada). We used coefficient of haze (COH), extinction coefficient, and Sutton sulfates to predict fine particles and sulfates from a fine particles model for days that were missing. We used the universal Quebec medicare system to obtain billings and prescriptions for each Montreal resident who died in the city from 1984 to 1993. These data were then used to define cardiovascular and respiratory conditions that subjects had before death. Using standard Poisson regression time-series analyses, we estimated the association between daily nonaccidental mortality and daily concentrations of particles in the ambient air among persons with cardiovascular and respiratory conditions diagnosed before death. We found no persuasive evidence that daily mortality increased when ambient air particles were elevated for subgroups of persons with chronic upper respiratory diseases, airways disease, cerebrovascular diseases, acute coronary artery disease, and hypertension. However, we found that daily mortality increased linearly as concentrations of particles increased for persons who had acute lower respiratory diseases, chronic coronary artery diseases (especially in the elderly), and congestive heart failure. For this latter set of conditions, the mean percent increase in daily mortality (MPC) for an increase in the COH across its interquartile range (18.5 COH units per 327.8 linear meters), averaged over the day of death and the 2 preceding days, was MPC = 5.09% [95% confidence interval (CI) 2.47-7.79%], MPC = 2.62 (95% CI 0.53-4.75%), and MPC = 4.99 (95% CI 2.44-7.60%), respectively. Adjustments for gaseous pollutants generally attenuated these associations, although the general pattern of increased daily mortality remained. In addition, there appeared to be a stronger association in the summer season. The positive associations found for persons who had acute lower respiratory diseases and congestive heart failure are consistent with some prevailing hypotheses and may also be consistent with recent toxicologic data implicating endothelins. Further epidemiologic studies are required to confirm these findings.

Aged↗