Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter from Fresno, California initiate human monocyte inflammatory responses mediated by reactive oxygen species.

In urban areas, a correlation between exposure to particulate matter (PM) from air pollution and increased cardiovascular morbidity and mortality has been observed. Components of PM include bacterial contaminants, transition metals, salts, polycyclic aromatic hydrocarbons (PAH), and carbonaceous material, which could interact with various cell types to produce systemic responses when inhaled. We examined the effects of PM collected from Fresno, California on activation of human monocytes and their interaction with vascular endothelium, a key event in atherogenesis. PM exposure increased cytokine expression and secretion from monocytes and enhanced monocyte adhesion to human aortic endothelial cells, both of which were attenuated by neutralizing endotoxin. PM also increased monocyte CYP1a1 expression, and inhibition of the aryl hydrocarbon receptor reduced the CYP1a1 and inflammatory responses. PM-treated monocytes accumulated intracellular reactive oxygen species (ROS), and antioxidants attenuated inflammatory and xenobiotic responses. Finally, supernatants from PM-treated pulmonary microvascular endothelial cells induced monocyte inflammatory responses that were not a consequence of endotoxin transfer. These results suggest that certain components of urban PM, namely endotoxin and PAH, activate circulating monocytes directly or indirectly by first stimulating other cells such as pulmonary endothelial cells, providing several mechanisms by which PM inhalation could induce pulmonary and/or systemic inflammation.

Exposure of mice to concentrated ambient particulate matter results in platelet and systemic cytokine activation.

Increasingly, evidence suggests a role for a systemic procoagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter. The authors evaluated blood cell parameters and markers of platelet activation in mice exposed to concentrated ambient particulate matter (CAPs) from the San Joaquin Valley of California, a region with severe particulate matter (PM) pollution episodes. The authors exposed mice to an average of 88.5 microg/m(3) of CAPs in a size range less than 2.5 microm for 6 h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, aggregation, fibrinogen binding, P-selectin, and lysosomal-associated membrane protein-1 (LAMP-1) expression. Serum cytokines were analyzed by bead-based immunologic assays. CAPs-exposed mice had elevations in macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFalpha), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF)-bb, and RANTES (regulated upon activation, normally T-expressed, and presumably secreted). Platelets were the only peripheral blood cells that were significantly elevated in number in CAPs-exposed mice. Flow cytometric analysis of unstimulated platelets from CAPs-exposed mice indicated size and shape changes, and platelets from CAPs-exposed animals had a 54% increase in fibrinogen binding indicative of platelet priming. Stimulation of platelets by thrombin resulted in up-regulation of LAMP-1 expression in CAPs-exposed animals and an increased microparticle population relative to control animals. These findings demonstrate a systemic proinflammatory and procoagulant response to inhalation of environmentally derived fine and ultrafine PM and suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.

Graft outcomes of living donor renal transplantations in elderly recipients.

BACKGROUND: Despite the ever-lengthening renal transplant waiting lists, without more donors, living donors serve as a treatment option for patients on dialysis. In the past, patients of advanced age were not considered to be candidates for living donor renal transplantation. Therefore, this study sought to analyze whether older age affects the outcome of living donor renal transplantation. METHODS: A total of 527 primary living donor renal transplantations were performed between January 1, 1995 and January 1, 2006. The subjects were divided into 2 subgroups based on patient age at the time of transplantation. The elder group included all recipients at least 60 years vs the control group of younger patients. RESULTS: Significant differences were observed in readmission rate (elder group, 44%; young group, 31.33%; P = .031) and patient survival rate (P < .001). No significant difference was noted in graft survival rate (P = .201), acute rejection rate (elder group, 10.6%; young group, 13.3%; P = .7), serum creatinine level, or length of stay (elder group, 8.51 days; young group, 6.31 days; P = .083). CONCLUSIONS: Our results confirm that elder patients may benefit from living donor renal transplantation.

Prevalence and clinical course of BK virus nephropathy in pancreas after kidney transplant patients.

The influence of BK virus nephropathy (BKVN) in pancreas after kidney (PAK) transplantation is unclear. A retrospective analysis of PAK transplants performed at our center was conducted to determine the impact of BKVN. Among 40 PAK transplants performed using sequential immunosuppression, four patients developed BKVN, as defined by a >20% rise in serum creatinine and BK viremia (BK plasma load >4 log copies/mL), at a median of 19 months following PAK. In all four patients, treatment of BKVN consisted of reduction in tacrolimus, cessation of mycophenolate mofetil, and introduction of leflunomide. With this approach, two patients experienced improvement or stabilization of renal function. The remaining two patients progressed to dialysis dependence despite treatment. Plasma BK load < or =5 log copies/mL was associated with graft preservation. Gender, age, delay between transplants, cumulative Thymoglobulin dose, and type of kidney donor were not associated with BK virus infection. Pancreas graft rejection or dysfunction was not observed with the above immunosuppression modification. Mean amylase and lipase > or =6 months following BKVN treatment remained normal. BKVN is an important cause of kidney allograft loss in PAK patients. Screening and early treatment of BKVN may enable preservation of kidney and pancreas grafts.

Detection of alkaline ultrafine atmospheric particles at Bakersfield, California.

Two collected micro-orifice uniform deposit impactors (MOUDIs) and a filter-based sampler were used to measure the size distribution and chemical composition of atmospheric particulate matter at Bakersfield, CA, between January 14 and 23, 1999. The peak number concentration of airborne ultrafine particles measured was 1.45 x 10(11) m-3, which is a factor of approximately 3 higher than the peak airborne ultrafine-particle number concentration measured previously in Pasadena, CA. Chemical analysis revealed that airborne ultrafine particles (Dp < 0.1 micron) at Bakersfield contained significant amounts of water-soluble species, including calcium, sodium, ammonium ion, nitrate, and sulfate. Other chemical species detected in the ultrafine size range included potassium, iron, copper, zinc, and strontium. A balance of aqueous ions showed that ultrafine particles were alkaline in nature with calcium acting as the dominant cation. Bulk samples of airborne particles with diameter less than 2.0 microns (PM2.0) were essentially neutral, but particle acidity was found to be a strong function of particle size. The results of this experiment suggest that areas deep in the human lung that preferentially collect particles in the ultrafine size range could be exposed to locally acidic or alkaline conditions even if the integrated airborne particle complex is essentially neutral.

Measurement of emissions from air pollution sources. 3. C1-C29 organic compounds from fireplace combustion of wood.

Organic compound emission rates for volatile organic compounds (VOC), gas-phase semivolatile organic compounds, and particle-phase organic compounds are measured from residential fireplace combustion of wood. Firewood from a conifer tree (pine) and from two deciduous trees (oak and eucalyptus) is burned to determine organic compound emissions profiles for each wood type including the distribution of the alkanes, alkenes, aromatics, polycyclic aromatic hydrocarbons (PAH), phenol and substituted phenols, guaiacol and substituted guaiacol, syringol and substituted syringols, carbonyls, alkanoic acids, resin acids, and levoglucosan. Levoglucosan is the major constituent in the fine particulate emissions from all three wood types, contributing 18-30% of the fine particulate organic compound emissions. Guaiacol (2-methoxyphenol), and guaiacols with additional substituents at position 4 on the molecule, and resin acids are emitted in significant quantities from pine wood combustion. Syringol (2,6-dimethoxyphenol) and syringols with additional substituents at position 4 on the molecule are emitted in large amounts from oak and eucalyptus firewood combustion, but these compounds are not detected in the emissions from pine wood combustion. Syringol and most of the substituted syringols are found to be semivolatile compounds that are present in both the gas and particle phases, but two substituted syringols that have not been previously quantified in wood smoke emissions, propionylsyringol and butyrylsyringol, are found exclusively in the particle phase and can be used to help trace hardwood smoke particles in the atmosphere. Benzene, ethene, and acetylene are often used as tracers for motor vehicle exhaust in the urban atmosphere. The contribution of wood smoke to the ambient concentrations of benzene, ethene, and acetylene could lead to an overestimate of the contribution of motor vehicle tailpipe exhaust to atmospheric VOC concentrations.

Comparison of real-time instruments used to monitor airborne particulate matter.

Measurements collected using five real-time continuous airborne particle monitors were compared to measurements made using reference filter-based samplers at Bakersfield, CA, between December 2, 1998, and January 31, 1999. The purpose of this analysis was to evaluate the suitability of each instrument for use in a real-time continuous monitoring network designed to measure the mass of airborne particles with an aerodynamic diam less than 2.5 microns (PM2.5) under wintertime conditions in the southern San Joaquin Valley. Measurements of airborne particulate mass made with a beta attenuation monitor (BAM), an integrating nephelometer, and a continuous aerosol mass monitor (CAMM) were found to correlate well with reference measurements made with a filter-based sampler. A Dusttrak aerosol sampler overestimated airborne particle concentrations by a factor of approximately 3 throughout the study. Measurements of airborne particulate matter made with a tapered element oscillating microbalance (TEOM) were found to be lower than the reference filter-based measurements by an amount approximately equal to the concentration of NH4NO3 observed to be present in the airborne particles. The performance of the Dusttrak sampler and the integrating nephelometer was affected by the size distribution of airborne particulate matter. The performance of the BAM, the integrating nephelometer, the CAMM, the Dusttrak sampler, and the TEOM was not strongly affected by temperature, relative humidity, wind speed, or wind direction within the range of conditions encountered in the current study. Based on instrument performance, the BAM, the integrating nephelometer, and the CAMM appear to be suitable candidates for deployment in a real-time continuous PM2.5 monitoring network in central California for the range of winter conditions and aerosol composition encountered during the study.

A 3D Eulerian source-oriented model for an externally mixed aerosol.

A 3D Eulerian source-oriented model for an externally mixed aerosol is developed and then used to compute the contribution that different emission sources make to regional fine particle concentrations in the South Coast Air Basin surrounding Los Angeles, CA, on September 25, 1996. The model simultaneously tracks fine particle concentrations (PM2.5), inhalable particle concentrations (PM10), ozone, and other gaseous pollutant concentrations yielding a tool that can be used to study the control of all of the regulated contaminants in the atmosphere within a single unified framework. Model predictions identify geographical areas that are influenced by PM2.5 associated with crustal material other than paved road dust, paved road dust, diesel engines, food cooking, noncatalyst equipped gasoline engines, catalyst-equipped gasoline engines, combustion of high sulfur-content fuel, other primary particle sources, sea salt, and marine background sulfate particles. The contribution that each of these source types makes to regional fine particle concentrations is distinct, reflecting the unique chemical composition, spatial distribution, and diurnal trends of primary emissions. The single largest contribution to regional PM2.5 in the South Coast Air Basin surrounding Los Angeles is associated with the accumulation of secondary ammonium nitrate on background marine sulfate particles. This pattern indicates that control of PM2.5 concentrations in Los Angeles must be accomplished through a program that includes both reductions in the emissions of gaseous precursors of secondary PM2.5 as well as control of primary particle emissions.

Effect of emissions control programs on visibility in southern California.

A new method for the analysis and display of the effect of emissions controls on visibility is applied to conditions in southern California. An advanced mechanistic air quality model that represents airborne particles as a source-oriented external mixture first is used to track emissions source contributions to the size distribution and chemical composition of airborne particles at Claremont, CA, under heavy smog conditions. The resulting description of the aerosol is used in a Mie scattering calculation to determine the magnitude and particle size dependence of light scattering and absorption in the atmosphere. The resulting light scattering and absorption coefficient values are supplied to an image processing-based visibility model that creates full color representations of the appearance of the local terrain in the presence of the specified level of air pollution based on satellite-generated landscape images. By linking these models, a direct connection is established between source emissions and resulting visual air quality. The composite modeling system then is used to studythe effectthat different emissions control strategies would have on visibility in southern California. An aggressive program of 92 specific emissions control measures that include primary particle controls plus controls on reactive gases that act as secondary aerosol precursors would more than double visual range at Claremont under the 1987 historical conditions studied. Synthetic landscape images show that the mountains to the north of Claremont that are not visible at a range of 10 km under base-case conditions would be visible if the emissions controls described above were applied.

Comprehensive rehabilitation of patients having chronic low back pain.

Seventy-two patients having chronic back pain, representative of high-risk demographic and personality populations, received a broad range of therapeutic modalities designed around the theme of self-regulation. The self-regulation principle was used in: (1) biofeedback training for teaching self-regulated muscle relaxation; (2) psychological counseling emphasizing self-control techniques for the management of stress and anxiety, including assertion training; (3) patient-regulated medication program; (4) patient involved case conferences; (5) physical therapy program emphasizing reconditoning; (6) comprehensive vocational rehabilitation services; (7) a series of educational lectures; (8) a therapeutic milieu designed for relaxation, recreation and socialization. Utilizing a success criteria of functional physical activity at discharge (average length of stay, 45 days) and levels of vocational restoration (employable, in training, or employed at 30 days postdischarge), 57 of the patients demonstrated unimpaired physical functioning levels and 59 of the patients were at success levels of vocational restoration.