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1.  Novel Relationship of Serum Cholesterol with Asthma and Wheeze in the United States 
Background
Cholesterol exerts complex effects upon inflammation. There has been little investigation of whether serum cholesterol is associated with asthma, an inflammatory airways disease with great public health impact.
Objective
To determine relationships between levels of three serum cholesterol measures (total cholesterol [TC], high density lipoprotein-cholesterol [HDL-C], and non-HDL-C), and asthma/wheeze in a sample representative of the U.S. population.
Methods
Cross-sectional study of 7,005 participants aged ≥6 years from the 2005–2006 National Health and Nutrition Examination Survey.
Results
Serum TC and non-HDL-C were lower in current asthmatics than in subjects without current asthma in the overall population (TC: 188.5 vs. 192.2 mg/dL; non-HDL-C: 133.9 vs. 137.7 mg/dL; p<.05 for both), whereas HDL-C was not different. Adjusted odds ratios (ORs) from multivariate logistic regression per 1-standard deviation increase of TC and non-HDL-C for current asthma were 0.92 (95% confidence interval [CI], 0.86–0.98) and 0.91 (95% CI, 0.85–0.98), respectively. Upon racial/ethnic stratification, these relationships reflect marked reductions unique to Mexican Americans (MAs)(TC: 171.4 vs. 189.3 mg/dL [p<.001], OR 0.62 [95% CI, 0.48–0.80]; non-HDL-C: 119.8 vs. 137.9 mg/dL [p<.001], OR 0.62 [95% CI, 0.48–0.79]). Among MAs, the adjusted OR for wheeze requiring medical attention was 0.57 (95% CI, 0.43–0.75) for TC and 0.53 (95% CI, 0.33–0.85) for non-HDL-C. Relationships between cholesterol and asthma/wheeze were independent of body mass index and serum C-reactive protein, and similar between atopic and non-atopic participants.
Conclusion
Serum TC and non-HDL-C are inversely related to asthma in the U.S. population, chiefly reflecting a relationship among MAs.
doi:10.1016/j.jaci.2009.08.005
PMCID: PMC3936400  PMID: 19800678
Lung; Asthma; Wheeze; Cholesterol; Atopy; Hispanic
2.  Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military After September 11, 2001 
Pain medicine (Malden, Mass.)  2010;11(10):1469-1476.
Objective
Nearly half of Operation Enduring Freedom / Operation Iraqi Freedom (OEF/OIF) veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans.
Design
We determined serum neurosteroid levels by gas chromatography / mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates.
Setting
Durham VA Medical Center.
Results
Allopregnanolone levels were inversely associated with low back pain (p=0.044) and chest pain (p=0.013), and DHEA levels were inversely associated with muscle soreness (p=0.024). DHEAS levels were positively associated with chest pain (p=0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (p=0.002).
Conclusions
Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders.
doi:10.1111/j.1526-4637.2010.00927.x
PMCID: PMC2994993  PMID: 20735755
neuroactive steroid; allopregnanolone; pregnenolone; DHEA; nociception; pain; neurosteroid
3.  Allopregnanolone Levels are Reduced in Temporal Cortex in Patients with Alzheimer’s Disease Compared to Cognitively Intact Control Subjects 
Biochimica et biophysica acta  2010;1801(8):951-959.
Background
The neurosteroid allopregnanolone has pronounced neuroprotective actions, increases myelination, and enhances neurogenesis. Evidence suggests that allopregnanolone dysregulation may play a role in the pathophysiology of Alzheimer’s disease (AD) and other neurodegenerative disorders. Our prior data demonstrate that allopregnanolone is reduced in prefrontal cortex in male patients with AD compared to male cognitively intact control subjects, and inversely correlated with neuropathological disease stage (Braak and Braak). We therefore determined if allopregnanolone levels are also reduced in AD patients compared to control subjects in temporal cortex, utilizing a larger set of samples from both male and female patients. In addition, we investigated if neurosteroids are altered in subjects who are APOE4 allele carriers.
Methods
Allopregnanolone, dehydroepiandrosterone (DHEA), and pregnenolone levels were determined in temporal cortex postmortem samples by gas chromatography/mass spectrometry, preceded by high performance liquid chromatography (40 subjects with AD/41 cognitively intact control subjects).
Results
Allopregnanolone levels are reduced in temporal cortex in patients with AD (median 2.68 ng/g, n= 40) compared to control subjects (median 5.64 ng/g, n=41), Mann-Whitney p=0.0002, and inversely correlated with Braak and Braak neuropathological disease stage (Spearman r= −0.38, p=0.0004). DHEA and pregnenolone are increased in patients with AD compared to control subjects. Patients carrying an APOE4 allele demonstrate reduced allopregnanolone levels in temporal cortex (Mann-Whitney p=0.04).
Conclusions
Neurosteroids are altered in temporal cortex in patients with AD and related to neuropathological disease stage. The APOE4 allele is associated with reduced allopregnanolone levels. Neurosteroids may be relevant to the neurobiology and therapeutics of AD.
doi:10.1016/j.bbalip.2010.05.006
PMCID: PMC2907131  PMID: 20488256
4.  Premature ventricular complexes & risk of incident stroke: The Atherosclerosis Risk In Communities (ARIC) study 
Background
Ventricular premature complexes (PVCs) on a 2-minute electrocardiogram (ECG) are a common, largely asymptomatic finding, associated with increased risk of coronary heart disease (CHD) and death. They may reflect atherosclerosis or other pathogenic pathways that predispose to arrhythmias and stroke.
Methods/Results
We conducted a prospective evaluation of the Atherosclerosis Risk In Communities Study cohort (n=14,783) of middle aged men and women to assess whether the presence of PVCs at study baseline (1987-89) influenced the risk of incident stroke through 31st December 2004. PVCs were seen in 6.1% of the participants at baseline, and 729 (4.9%) had incident stroke. The unadjusted cumulative proportion of incident stroke in individuals with any PVC was 6.6% compared to 4.1% in those without PVC. The unadjusted hazard ratio (HR) of incident stroke in individuals with any PVC compared to those without any PVCs was 1.71 (95% Confidence Interval (CI) 1.33, 2.20).
Among individuals without hypertension and diabetes at baseline, PVCs were independently associated with incident stroke (HR: 1.72 (1.14, 2.59)). Among those with either diabetes or hypertension the presence of any PVCs did not increase the risk of stroke. The association was stronger for non-carotid embolic stroke than for thrombotic stroke and its magnitude increased with higher frequency of PVCs.
Conclusions
Frequent PVCs are associated with risk of incident stroke in participants free of hypertension and diabetes. This suggests that PVCs may contribute to atrio-ventricular remodeling or may be risk marker for incident stroke, particularly embolic stroke.
doi:10.1161/STROKEAHA.109.567800
PMCID: PMC2866170  PMID: 20167922
Stroke; Risk factors; Arrhythmia; Ventricular premature complexes; Atrial Fibrillation
5.  Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Intervention in Older Persons with Acute Coronary Syndrome—Part II 
Clinical geriatrics  2008;16(11):40-46.
This is Part II of a two-part article on treatment of acute coronary syndrome in the older population. Part I (published in the October issue of Clinical Geriatrics) analyzed the differential utilization of invasive therapies with respect to age and heart disease. Part II summarizes information from the literature on acute coronary syndrome outcomes from invasive treatments (percutaneous coronary interventions or coronary artery bypass grafting) among older persons.
PMCID: PMC2895738  PMID: 20607092
6.  Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Intervention in Older Persons with Acute Coronary Syndrome—Part I 
Clinical geriatrics  2008;16(10):39-44.
This is Part I of a two-part article on treatment of acute coronary syndrome in the older population. Part I analyzes the differential utilization of invasive therapies with respect to age and heart disease. Part II (to be published in the next issue of Clinical Geriatrics) will summarize information from the literature on acute coronary syndrome outcomes from invasive treatments (percutaneous coronary interventions or coronary artery bypass grafting) among older persons.
PMCID: PMC2856130  PMID: 20407617
7.  Disparities in lipid management for African Americans and Caucasians with coronary artery disease: A national cross-sectional study 
Background
Individuals with coronary artery disease are at high risk for adverse health outcomes. This risk can be diminished by aggressive lipid management, but adherence to lipid management guidelines is far from ideal and substantial racial disparities in care have been reported. Lipid treatment and goal attainment information is not readily available for large patient populations seen in the fee-for-service setting. As a result, national programs to improve lipid management in this setting may focus on lipid testing as an indicator of lipid management. We describe the detection, treatment, and control of dyslipdemia for African Americans and Caucasians with coronary artery disease to evaluate whether public health programs focusing on lipid testing can eliminate racial disparities in lipid management.
Methods
Physicians and medical practices with high numbers of prescriptions for coronary artery disease medications were invited to participate in the Quality Assurance Program. Medical records were reviewed from a random sample of patients with coronary artery disease seen from 1995 through 1998. Data related to the detection, treatment, and control of dyslipidemia were abstracted from the medical record and evaluated in cross-sectional stratified and logistic regression analyses using generalized estimation equations.
Results
Data from the medical records of 1,046 African Americans and 22,077 Caucasians seen in outpatient medical practices in 23 states were analyzed. African-American patients were younger, more likely to be women and to have diabetes, heart failure, and hypertension. The low density lipoprotein cholesterol (LDL-C) testing rate for Caucasian men was over 1.4 times higher than that for African-American women and about 1.3 times higher than that for African-American men. Almost 60% of tested Caucasian men and less than half of tested African Americans were prescribed lipid-lowering drugs. Tested and treated Caucasian men had the highest LDL-C goal attainment (35%) and African-American men the lowest (21%).
Conclusions
Although increased lipid testing is clearly needed for African Americans, improvements in treatment and control are also necessary to eliminate racial disparities in lipid management. Disparities in treatment and goal attainment must be better understood and reflected in policy to improve the health of underserved populations.
doi:10.1186/1471-2261-4-15
PMCID: PMC516441  PMID: 15317654

Results 1-7 (7)