OBJECTIVE

To investigate the potential effects of lifetime cumulative ozone (O3) exposure on acute pulmonary responses to O3.

METHODS

Fifteen healthy subjects from a larger cohort of young adults were exposed to 200 ppb O3 for 4 hours followed by bronchoscopy and bronchoalveolar lavage 18 hours later. Lung function, symptom questionnaires, and blood samples were obtained before and after each exposure. Subjects' lifetime cumulative O3 exposures were estimated from residential histories and air-quality monitoring data.

RESULTS

Acute exposure to O3 caused decrements in forced expiratory volume in 1 second (FEV1), maximal mid-expiratory flow rate (FEF25-75), and forced expiratory flow rate at 75% of forced vital capacity (FEF75), and an increase in plasma clara cell protein (CC16) level. Changes in CC16 and lower respiratory symptoms, but not in lung function, were positively correlated with lifetime cumulative O3 exposure.

CONCLUSION

Higher lifetime cumulative O3 exposure was associated with airway injury and respiratory symptom responses, but not with airway inflammatory or lung function responses, to acute O3 exposure.

BACKGROUND

Use of more than one health care system to obtain care is common among adults receiving care within the Veterans Affairs (VA) medical system. It is not known what effect using care from multiple sources has on the quality of care patients receive.

OBJECTIVES

To examine whether use of recommended ambulatory care services differs between exclusive and dual VA users.

METHODS

Cross-sectional analysis of the 2004 Behavior Risk Factor Surveillance System, a nationally-representative survey of community-dwelling adults aged 18 years or older. Our outcome measures were self-reported use of 18 recommended services for cancer prevention, cardiovascular risk reduction, diabetes management, and infectious disease prevention. We used multivariable logistic regression to examine the association between exclusive and dual VA use and use of recommended ambulatory services.

RESULTS

There were 3470 exclusive VA users and 4523 dual VA users. Dual users were significantly more likely to be older and white, have higher incomes, have graduated from college, and be insured when compared with exclusive VA users. In unadjusted analyses, dual users received higher rates of recommended services. After adjustment for patient characteristics, use of recommended services was largely similar among exclusive and dual VA users. Exclusive VA users reported 14% greater use of breast cancer screening and 10% greater use of cholesterol monitoring among patients with hypercholesterolemia, and 6% lower use of prostate cancer screening and 7% lower use of influenza vaccination.

CONCLUSIONS

After adjustment for patient characteristics, exclusive and dual VA users reported similar rates of recommended ambulatory service use.

Consistent with previous reports, sphingosine at a high concentration (5 microM) was cardiotoxic as evidenced by increased infarct size in response to ischemia/reperfusion in an ex vivo rat heart. Sphingosine 1-phosphate (S1P) at 5 microM was cardioprotective. However, at a physiologic concentration (0.4 microM) sphingosine as well as S1P was effective in protecting the heart from ischemia/reperfusion injury both when perfused prior to 40 min of ischemia (preconditioning) or when added to reperfusion media following ischemia (postconditioning). Protection by sphingosine and S1P was evidenced with both pre- and post-conditioning by a >75% recovery of left ventricular developed pressure during reperfusion and a decrease in infarct size from 45% of the risk area to less than 8%. When VPC23019, an S1P(1and3)G-protein coupled receptor antagonist, was added to the preconditioning or postconditioning medium along with S1P, it completely blocked S1P-induced protection. However, VPC 23019 did not affect the ability of 0.4 microM sphingosine to either precondition or postcondition hearts. Studies of preconditioning revealed that inhibition of protein kinase C with GF109203X blocked preconditioning by S1P. However, GF109203X did not affect preconditioning by 0.4 microM sphingosine. Likewise, cotreatment with the PI3 kinase inhibitor wortmanin blocked preconditioning by S1P but not by sphingosine. By contrast, inhibition of protein kinase G with KT5823 had no effect on S1P preconditioning but completely eliminated preconditioning by sphingosine. Also, the protein kinase A inhibitory peptide 14-22 amide blocked preconditioning by sphingosine but not S1P. These data reveal for the first time that sphingosine is not toxic at physiologic concentrations but rather is a potent cardioprotectant that utilizes a completely different mechanism than S1P; one that is independent of G-protein coupled receptors and utilizes cyclic nucleotide-dependent pathways.

Venous thromboembolic disease is a common disease associated with significant morbidity and mortality. Accurate and timely diagnosis should be guided by the use of validated clinical prediction rules. The mainstay of therapy is anticoagulation, although alternative approaches, such as use of concurrent thrombolysis or placement of vena caval filters, may be appropriate in selected patients. Determination of duration of anticoagulation requires a detailed assessment of the risk factors associated with the event allowing estimation of recurrence risk, and careful assessment of bleeding risk. Although extremely effective, anticoagulants have a narrow therapeutic window; systems should be in place to reduce risk of adverse events associated with these agents.