Steven C. Grambow

Seasonal Variations in Air Pollution Particle-Induced Inflammatory Mediator Release and Oxidative Stress

Health effects associated with particulate matter (PM) show seasonal variations. We hypothesized that these heterogeneous effects may be attributed partly to the differences in the elemental composition of PM. Normal human bronchial epithelial (NHBE) cells and alveolar macrophages (AMs) were exposed to equal mass of coarse [PM with aerodynamic diameter of 2.5–10 μm (PM2.5–10)], fine (PM2.5), and ultrafine (PM < 0.1) ambient PM from Chapel Hill, North Carolina, during October 2001 (fall) and January (winter), April (spring), and July (summer) 2002. Production of interleukin (IL)-8, IL-6, and reactive oxygen species (ROS) was measured. Coarse PM was more potent in inducing cytokines, but not ROSs, than was fine or ultrafine PM. In AMs, the October coarse PM was the most potent stimulator for IL-6 release, whereas the July PM consistently stimulated the highest ROS production measured by dichlorofluorescein acetate and dihydrorhodamine 123 (DHR). In NHBE cells, the January and the October PM were consistently the strongest stimulators for IL-8 and ROS, respectively. The July PM increased only ROS measured by DHR. PM had minimal effects on chemiluminescence. Principal-component analysis on elemental constituents of PM of all size fractions identified two factors, Cr/Al/Si/Ti/Fe/Cu and Zn/As/V/Ni/Pb/Se, with only the first factor correlating with IL-6/IL-8 release. Among the elements in the first factor, Fe and Si correlated with IL-6 release, whereas Cr correlated with IL-8 release. These positive correlations were confirmed in additional experiments with PM from all 12 months. These results indicate that elemental constituents of PM may in part account for the seasonal variations in PM-induced adverse health effects related to lung inflammation.

Potential role of increased iron stores in diabetes.

Diabetes mellitus (DM) is an important risk factor for the development of cardiovascular disease. Extensive clinical, epidemiologic, and basic studies suggest that excessive tissue iron stores may contribute to the occurrence and complications of DM. Secondary diabetes occurs in inherited pathologic iron overload syndromes of European- and African-derived populations and is an established complication of transfusional iron overload. Epidemiologic studies have repeatedly shown positive correlation between levels of serum ferritin and those of fasting glucose, insulin, and glycosylated hemoglobin. Iron reduction therapy in hereditary hemochromatosis and transfusional iron overload is associated with improved glucose tolerance and reduced incidence of secondary diabetes. Trials of iron reduction therapy in diabetes mellitus, although limited and inconclusive, have shown clinical improvement in some patients. The current article reviews evidence suggesting that tissue iron contributes to DM and its complications and presents preliminary data that emphasize the potential importance of iron overload in DM of African Americans.

Congestive heart failure patients’ perceptions of quality of life: the integration of physical and psychosocial factors

Congestive heart failure (CHF) lowers survival and worsens the quality of life (QOL) of over four million older Americans. Both clinicians and standardized instruments used to assess the QOL of patients with CHF focus primarily on physical symptoms rather than capturing the full range of psychosocial concerns. The purpose of this study was to gather descriptions of the components of QOL as understood by patients living with CHF. Focus groups were conducted with patients with known CHF, New York Heart Association (NYHA) class I–IV, and left ventricular fraction of <40%. Focus groups were audiotaped, transcribed, and reviewed for common and recurrent themes using the methods of constant comparisons. We conducted three focus groups (n = 15) stratified by NYHA stage with male patients ranging in age from 47–82 years of age. Five patients were classified with NYHA stage III/IV and ten with NYHA stage I/II. Thirty attributes of QOL were identified which fell into five broad domains: symptoms, role loss, affective response, coping, and social support. Expectedly, patients reported the importance of physical symptoms; however, participants also identified concern for family, the uncertainty of prognosis, and cognitive function as dimensions of QOL. Changes in patients’ lives attributed to CHF were not always considered deficiencies; rather, methods of coping with CHF were identified as important attributes representing possible opportunities for personal growth. Clinicians must understand the full range of concerns affecting the QOL of their older patients with CHF. The findings suggest that psychosocial aspects and patient uncertainty about their prognosis are important components of QOL among CHF patients.

Prostate Cancer: A Significant Risk Factor for Late-Life Suicide

OBJECTIVE The authors sought to determine the incidence of suicide and its relevant correlates among men with prostate cancer. METHODS This was a population-based, retrospective cohort review of men age 65 and older, residing in South Florida between 1983 and 1993. Average annual suicide rate was calculated for prostate cancer-related suicides and contrasted with age and gender-specific rates in the same geographic area. RESULTS Of 667 completed suicides, 20 were prostate cancer-related (3% of the total male suicide sample). The average annual incidence of suicide for men was 55.32 per 100,000 persons, but for men with prostate cancer, the rate was 274.7 per 100,000. The risk of suicide in men with prostate cancer was 4.24 times that of an age- and gender-specific cohort. The clinical correlates included depression (70%), cancer diagnosis within 6 months of suicide (80%), physician visit within 1 month of suicide (60%), and being foreign-born (70%). CONCLUSION The incidence of suicide among older men with prostate cancer is higher than previously recognized. Depression, recent diagnosis, pain, and being foreign-born are important clinical correlates. Screens for depression and suicide in older men with prostate cancer should be done after diagnosis and redone during the first 6 months regularly, particularly in the primary-care setting. Public education is needed to decrease the stigma associated with having a cancer diagnosis.

Do Unmet Expectations for Specific Tests, Referrals, and New Medications Reduce patients' Satisfaction?

AbstractBACKGROUND: Patient-centered care requires clinicians to recognize and act on patients’ expectations. However, relatively little is known about the specific expectations patients bring to the primary care visit. OBJECTIVE: To describe the nature and prevalence of patients’ specific expectations for tests, referrals, and new medications, and to examine the relationship between fulfillment of these expectations and patient satisfaction. DESIGN: Prospective cohort study. SETTING: VA general medicine clinic. PATIENTS/PARTICIPANTS: Two hundred fifty-three adult male outpatients seeing their primary care provider for a scheduled visit. MEASUREMENTS AND MAIN RESULTS: Fifty-six percent of patients reported at least 1 expectation for a test, referral, or new medication. Thirty-one percent had 1 expectation, while 25% had 2 or more expectations. Expectations were evenly distributed among tests, referrals, and new medications (37%, 30%, and 33%, respectively). Half of the patients who expressed an expectation did not receive one or more of the desired tests, referrals, or new medications. Nevertheless, satisfaction was very high (median of 1.5 for visit-specific satisfaction on a 1 to 5 scale, with 1 representing “excellent”). Satisfaction was not related to whether expectations were met or unmet, except that patients who did not receive desired medications reported lower satisfaction. CONCLUSIONS: Patients’ expectations are varied and often vague. Clinicians trying to implement the values of patient-centered care must be prepared to elicit, identify, and address many expectations.

The role of soluble components in ambient fine particles-induced changes in human lungs and blood.

Normal individuals developed pulmonary neutrophilic inflammation and increased blood fibrinogen following inhalation of concentrated ambient particles (CAPS). In this study, we sought to determine how soluble components in CAPS contributed to these changes. We expanded and reanalyzed data from 37 young healthy volunteers from a previous study (Ghio et al., 2000) who were exposed to either filtered air or CAPS. Postexposure bronchoalveolar lavage (BAL) as well as pre- and postexposure venous blood samples was analyzed for cellular and acute inflammatory endpoints. Nine most abundant components in the water-soluble fraction of CAPS were correlated with these endpoints using principal component analysis. We found that a sulfate/Fe/Se factor was associated with increased BAL percentage of neutrophils and a Cu/Zn/V factor with increased blood fibrinogen. The concentrations of sulfate, Fe, and Se correlated highly with PM mass (R > 0.75) while the correlations between PM and Cu/Zn/V were modest (R = 0.2-0.6). These results from controlled human exposure linked specific PM components to pulmonary neutrolphil influx and blood fibrinogen increase, and indicated the soluble components of pollutant particles may differentially affect pulmonary and hematological systems in humans exposed to PM.

A Randomized Trial of a Low-Carbohydrate Diet vs Orlistat Plus a Low-Fat Diet for Weight Loss

BACKGROUND Two potent weight loss therapies, a low-carbohydrate, ketogenic diet (LCKD) and orlistat therapy combined with a low-fat diet (O + LFD), are available to the public but, to our knowledge, have never been compared. METHODS Overweight or obese outpatients (n = 146) from the Department of Veterans Affairs primary care clinics in Durham, North Carolina, were randomized to either LCKD instruction (initially, <20 g of carbohydrate daily) or orlistat therapy, 120 mg orally 3 times daily, plus low-fat diet instruction (<30% energy from fat, 500-1000 kcal/d deficit) delivered at group meetings over 48 weeks. Main outcome measures were body weight, blood pressure, fasting serum lipid, and glycemic parameters. RESULTS The mean age was 52 years and mean body mass index was 39.3 (calculated as weight in kilograms divided by height in meters squared); 72% were men, 55% were black, and 32% had type 2 diabetes mellitus. Of the study participants, 57 of the LCKD group (79%) and 65 of the O + LFD group (88%) completed measurements at 48 weeks. Weight loss was similar for the LCKD (expected mean change, -9.5%) and the O + LFD (-8.5%) (P = .60 for comparison) groups. The LCKD had a more beneficial impact than O + LFD on systolic (-5.9 vs 1.5 mm Hg) and diastolic (-4.5 vs 0.4 mm Hg) blood pressures (P < .001 for both comparisons). High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups. Low-density lipoprotein cholesterol levels improved within the O + LFD group only, whereas glucose, insulin, and hemoglobin A(1c) levels improved within the LCKD group only; comparisons between groups, however, were not statistically significant. CONCLUSION In a sample of medical outpatients, an LCKD led to similar improvements as O + LFD for weight, serum lipid, and glycemic parameters and was more effective for lowering blood pressure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00108524.

Teledermatology's Impact on Time to Intervention among Referrals to a Dermatology Consult Service

The aim of this study was to determine if a teledermatology consult system, using store-and-forward digital imaging technology, results in patients achieving a shorter time from referral date to date of initial definitive intervention when compared to a traditional referral process. Patients being referred to the dermatology consult service from the primary care clinics at the Durham VA Medical Center were randomized to either a teledermatology consultation or usual care. A usual care consultation consisted of a text-based electronic consult request. A teledermatology consultation included digital images and a standardized history, in addition to the text-based electronic consult. Time to initial definitive intervention was defined as the time between referral date and the date the patient was scheduled for a clinic visit for those patients that the consultant requested a clinic-based evaluation, or the time between referral date and the date the consult was answered by the consultant if a clinic visit was not required. Patients in the teledermatology arm of the study reached a time to initial definitive intervention significantly sooner than did those patients randomized to usual care (median 41 days versus 127 days, p = 0.0001, log-rank test). Additionally, 18.5% of patients in the teledermatology arm avoided the need for a dermatology clinic-based visit compared to zero patients avoiding a dermatology clinic visit in the usual care arm of the study (p < 0.001, z-test). Teledermatology consult systems can result in significantly shorter times to initial definitive intervention for patients compared to traditional consult modalities, and, in some cases, the need for a clinic-based visit can be avoided.

An economic analysis of a store and forward teledermatology consult system.

Our objective was to assess the economic impact of store-and-forward teledermatology in a United States Department of Veterans Affairs (VA) health care setting. Patients being referred to the Dermatology Consult Service from the Primary Care Clinics at the Durham, North Carolina VA Medical Center were randomized either to usual care or to a teledermatology consultation. Fixed and variable costs for both consult modalities were identified using a microcosting approach. The observed clinical outcomes from the randomized trial generated probability and effectiveness measures that were inserted into a decision model. A cost analysis and a cost-effectiveness analysis that compared the two consult modalities was performed. Teledermatology was not cost saving when compared to usual care using observed costs and outcomes. Sensitivity analyses indicated that teledermatology has the potential to be cost saving if clinic visit costs, travel costs, or averted clinic visits were higher than observed in the study. Teledermatology was cost-effective for decreasing the time required for patients to reach a point of initial definitive care. Cost-effectiveness ratios ranged from

Amyotrophic Lateral Sclerosis among 1991 Gulf War Veterans: Evidence for a Time-Limited Outbreak

0.12-0.17 (U.S.) per patient per day of time to initial intervention.