Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
2011
2011
2011
BACKGROUND
A variety of studies carried out using either human subjects or laboratory animals suggest that vitamin D and its analogues possess important beneficial activity in the cardiovascular system. Using Cre-Lox technology we have selectively deleted the vitamin D receptor (VDR) gene in the cardiac myocyte in an effort to better understand the role of vitamin D in regulating myocyte structure and function.
METHODS AND RESULTS
Targeted deletion of the exon 4 coding sequence in the VDR gene resulted in an increase in myocyte size and left ventricular weight/body weight versus controls both at baseline and following a 7-day infusion of isoproterenol. There was no increase in interstitial fibrosis. These knockout mice demonstrated a reduction in end-diastolic and end-systolic volume by echocardiography, activation of the fetal gene program (ie, increased atrial natriuretic peptide and alpha skeletal actin gene expression), and increased expression of modulatory calcineurin inhibitory protein 1 (MCIP1), a direct downstream target of calcineurin/nuclear factor of activated T cell signaling. Treatment of neonatal cardiomyocytes with 1,25-dihydroxyvitamin D partially reduced isoproterenol-induced MCIP1 mRNA and protein levels and MCIP1 gene promoter activity.
CONCLUSIONS
Collectively, these studies demonstrate that the vitamin D-VDR signaling system possesses direct, antihypertrophic activity in the heart. This appears to involve, at least in part, suppression of the prohypertrophic calcineurin/NFAT/MCIP1 pathway. These studies identify a potential mechanism to account for the reported beneficial effects of vitamin D in the cardiovascular system.
View on PubMed2011
BACKGROUND
Sudden cardiac death is the leading cause of on-duty death in United States firefighters. Accurately assessing cardiopulmonary capacity is critical to preventing, or reducing, cardiovascular events in this population.
METHODS
A total of 83 male firefighters performed Wellness-Fitness Initiative (WFI) maximal exercise treadmill tests and direct peak VO2 assessments to volitional fatigue. Of the 83, 63 completed WFI sub-maximal exercise treadmill tests for comparison to directly measured peak VO2 and historical estimations.
RESULTS
Maximal heart rates were overestimated by the traditional 220-age equation by about 5 beats per minute (p < .001). Peak VO2 was overestimated by the WFI maximal exercise treadmill and the historical WFI sub-maximal estimation by ~ 1MET and ~ 2 METs, respectively (p < 0.001). The revised 2008 WFI sub-maximal treadmill estimation was found to accurately estimate peak VO2 when compared to directly measured peak VO2.
CONCLUSION
Accurate assessment of cardiopulmonary capacity is critical in determining appropriate duty assignments, and identification of potential cardiovascular problems, for firefighters. Estimation of cardiopulmonary fitness improves using the revised 2008 WFI sub-maximal equation.
View on PubMed2011
2011
ABSTRACT: BACKGROUND: Secondhand tobacco smoke (SHS) is associated with increased risk of respiratory illness, cancer, and cardiovascular disease. Prior to smoking bans on airlines in the late 1980s, flight attendants were exposed to a significant amount of SHS. In the present study, we examine associations between flight attendant SHS exposure and development of respiratory illnesses and cardiovascular disease. METHODS: Between December 2006 and October 2010, three hundred sixty-two flight attendants completed an online questionnaire with information regarding experience as a flight attendant, medical history, smoking history, and SHS exposure. Rates of illnesses in flight attendants were compared with an age and smoking history matched population sample from NHANES 2005-2006. Logistic regression analysis was used to examine the association of reported medical conditions and pre-ban years of exposure. RESULTS: Compared with the sample from NHANES 2005-2006, flight attendants had increased prevalence of chronic bronchitis (11.7% vs. 7.2%, p < 0.05), emphysema/COPD (3.2% vs. 0.9%, p < 0.03), and sinus problems (31.5% vs. 20.9%, p < 0.002), despite a lower prevalence of medical illnesses including high blood pressure, diabetes, high cholesterol, heart failure, cancer, and thyroid disease. Amongst flight attendants who reported never smoking over their lifetimes, there was not a significant association between years of service as a flight attendant in the pre-smoking ban era and illnesses. However, in this same group, there was a significantly increased risk of daily symptoms (vs. no symptoms) of nasal congestion, throat, or eye irritation per 10-year increase of years of service as a flight attendant prior to the smoking ban (OR 2.14, 95% CI 1.41 - 3.24). CONCLUSIONS: Flight attendants experience increased rates of respiratory illnesses compared to a population sample. The frequency of symptoms of nasal congestion, throat or eye irritation is associated with occupational SHS exposure in the pre-smoking ban era.
View on PubMed2011
We investigated whether early life chronic exposure to woodsmoke, using personal passive 48-h carbon monoxide (CO) as an indicator, is associated with children's neurodevelopmental and behavioral performance. CO measures were collected every 3 months from 2002 to 2005 among mother-child dyads during the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial in San Marcos, Guatemala. From March to June, 2010, study children of age 6-7 years, performed a follow-up non-verbal, culturally adapted neurodevelopmental assessment. We found inverse associations between CO exposure of pregnant mothers during their 3rd trimesters (m=3.8ppm ± 3.0ppm; range: 0.6-12.5 ppm) and child neuropsychological performance. Scores on 4 out of 11 neuropsychological tests were significantly associated with mothers' 3rd trimester CO exposures, including visuo-spatial integration (p<0.05), short-term memory recall (p<0.05), long-term memory recall (p<0.05), and fine motor performance (p<0.01) measured using the Bender Gestalt-II's Copy, Immediate Recall, and an adapted version of a Delayed Recall Figures drawing, and the Reitan-Indiana's Finger Tapping Tests, respectively. These 4 significant finding persisted with adjustment for child sex, age, visual acuity, and household assets (socio-economic status). Summary performance scores were also significantly associated with maternal 3rd trimester CO when adjusted for these covariates. Other variables accounting for variance but were excluded in our final multiple regression models included the following: HOME environment stimulation score, child examiner, WHO height-for-age percentile, and age that the infant stopped breastfeeding. This seems to be the first study on woodsmoke exposure and neurodevelopment, and the first longitudinal birth cohort study on chronic early life CO exposures, determined by high quality measures of mothers' and infants' personal CO exposures, and using well-established, reliable child neuropsychological tests. Further research is needed to replicate our results and inform future interventions and air quality standards for woodsmoke and CO.
View on PubMed2011
OBJECTIVE AND DESIGN
Increasing evidence supports a parallel between HIV-1 infection and immune aging, which is particularly apparent with common changes in naive versus memory T-cell proportions. Here, we aimed at refining the value of common T-cell-associated markers of immunosenescence during HIV disease progression or aging, and at exploring further the impact in this context of old age as well as cytomegalovirus (CMV) co-infection, which is predominant in HIV-1-infected individuals.
METHODS
Frequencies of naive or CD57(+) memory T cells as well as the magnitude of CMV-pp65 T cells were measured in HIV-1-infected patients grouped according to disease progression status, treatment and age.
RESULTS
Our results indicate that the decline in naive T-cell levels rather than the accumulation of CD57(+) senescent T cells identifies best the premature development of an immunosenescence phenotype with HIV disease progression. Moreover, advanced age or mounting of strong CMV-specific responses impact independently on CD4(+) T-cell counts and recovery with antiretroviral therapy.
CONCLUSIONS
The present findings indicate that HIV-1 infection amplifies the effect of age on naive T-cell levels, and highlight the constraint on the capacity of treated patients to reconstitute their CD4(+) T-cell compartment due to age and CMV co-infection.
View on PubMed2011
2011