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1.  Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study 
Archives of Neurology  2008;65(2):193-198.
Objective
To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state.
Design
Randomized, double-blind, placebo-controlled, crossover clinical trial.
Setting
Academic movement disorders center.
Patients
Patients with Parkinson disease and motor fluctuations.
Intervention
Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (sub-threshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 μg/kg/h every 2 hours and 25 μg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 μg/kg/h every 2 hours and 100 μg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days.
Main Outcome Measures
Finger and foot tapping rates.
Results
There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P<.001) and trended toward increasing finger tapping compared with placebo infusions.
Conclusions
Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that pre-synaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease.
doi:10.1001/archneurol.2007.58
PMCID: PMC3390309  PMID: 18268187
2.  Reexamination of Testosterone, Dihydrotestosterone, Estradiol and Estrone Levels across the Menstrual Cycle and in Postmenopausal Women Measured by Liquid Chromatography Tandem Mass Spectrometry 
Steroids  2010;76(1-2):177-182.
Measuring serum androgen levels in women has been challenging due to limitations in method accuracy, precision sensitivity and specificity at low hormone levels. The clinical significance of changes in sex steroids across the menstrual cycle and lifespan has remained controversial, in part due to these limitations. We used validated liquid chromatography tandem mass spectrometry(LC-MS/MS) assays to determine testosterone (T) and dihydrotestosterone (DHT) along with estradiol (E2) and estrone (E1) levels across the menstrual cycle of 31 healthy premenopausal females and in 19 postmenopausal females. Samples were obtained in ovulatory women in the early follicular phase (EFP), midcycle and mid luteal phase (MLP).
Overall, the levels of T, DHT, E2 and E1 in premenopausal women measured by LCMS/MS were lower overall than previously reported with immunoassays. In premenopausal women, serum T, Free T, E2, E1 and SHBG levels peaked at midcycle and remained higher in the MLP, whereas DHT did not change. In postmenopausal women, T, free T, SHBG and DHT were significantly lower than in premenopausal women, concomitant with declines in E2 and E1. These data support the hypothesis that the changes in T and DHT that occur across the cycle may reflect changes in SHBG and estrogen, whereas in menopause, androgen levels decrease. LC-MS/MS may provide more accurate and precise measurement of sex steroid hormones than prior immunoassay methods and can be useful to assess the clinical significance of changes in T, DHT, E2 and E1 levels in females.
doi:10.1016/j.steroids.2010.10.010
PMCID: PMC3005029  PMID: 21070796
sex hormones; liquid chromatography mass spectrometry; menopause; menstrual cycle; testosterone; estradiol
3.  Physical Activity and the Risk of Dementia in Oldest Old 
Journal of aging and health  2007;19(2):242-259.
Objective
This study evaluated the protective role of physical activity (PA) against cognitive impairment (CI) in the oldest old (age ≥ 85).
Method
Prospective data on 66 optimally healthy, oldest old adults (mean age 88.5) were analyzed using survival analysis.
Results
In all, 12 men and 11 women reported exercising > 4 hours per week, and 38 participants developed CI (mean onset age 93; mean follow-up 4.7 years). The effect of exercise was modified by gender. In more active women (> 4 hours/week), the risk of CI was reduced by 88% (95% confidence interval 0.03, 0.41) compared to those less active. Less active women had 2 times the incidence rate of CI compared to less active men and almost 5 times the rate compared to active women.
Discussion
This study demonstrates the beneficial effects of exercise on healthy brain aging even in the oldest old and emphasizes the importance of increasing PA in older women.
doi:10.1177/0898264307299299
PMCID: PMC3110722  PMID: 17413134
oldest old; physical activity; exercise; dementia; cognitive impairment
4.  Using Built Environmental Observation Tools: Comparing Two Methods of Creating a Measure of the Built Environment 
Purpose
Identify an efficient method of creating a comprehensive and concise measure of the built environment integrating data from geographic information systems (GIS) and the Senior Walking Environmental Assessment Tool (SWEAT).
Design
Cross-sectional study using a population sample.
Setting
Eight municipally defined neighborhoods in Portland, Oregon.
Subjects
Adult residents (N = 120) of audited segments (N = 363).
Measures
We described built environmental features using SWEAT audits and GIS data. We obtained information on walking behaviors and potential confounders through in-person interviews.
Analysis
We created two sets of environviental measures, one based on the conceptual framework used to develop SWEAT and another using principal component analysis (PCA). Each measure’s association with walking for transportation and exercise was then assessed and compared using logistic regression.
Results
A priori measures (destinations, safety, aesthetics, and functionality) and PCA measures (accessibility, comfort/safety, maintenance, and pleasantness) were analogous in conceptual meaning and had similar associations with walking. Walking for transportation was associated with destination accessibility and functional elements, whereas walking for exercise was associated with maintenance of the walking area and protection from traffic. However, only PCA measures consistently reached statistical significance.
Conclusion
The measures created with PCA were more parsimonious than those created a priori. Performing PCA is an efficient method of combining and scoring SWEAT and GIS data.
doi:10.4278/ajhp.080603-QUAN-81
PMCID: PMC3105357  PMID: 20465151
Environment; Residence Characteristics; Walking; Principal Component Analysis; Research Design; Prevention Research
5.  Correlations Between Endoscopy Score and Quality-of-Life Changes After Sinus Surgery 
Objective
To assess whether change in endoscopy score correlates with change in health-related quality of life (HRQOL) following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS).
Setting
Tertiary rhinology clinic
Patients
One hundred two adult patients, with and without nasal polyposis, who elected to undergo ESS and were followed for 12 ± 2 months postoperatively.
Intervention
Patient characteristics and Lund-Mackay computed tomography scores were recorded preoperatively. Lund-Kennedy endoscopy scores and 2 HRQoL surveys, the Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey (CSS), were examined before and after surgery.
Main Outcome Measures
Postoperative changes in endoscopy score and HRQOL were examined using bivariate and multivariate analyses.
Results
Statistically significant improvements were found in endoscopy score (p<0.001) and for all total and subscale HRQoL measures (p<0.001). After controlling for baseline status and comorbid factors, improvement in endoscopy score significantly correlated with 12 month improvement on the total RSDI (p=0.01), the physical (p=0.01) and functional (p=0.02) subscales of the RSDI, and the symptom subscale of the CSS (p=0.003), but could explain only 25.5–36.6% of the linear variation for these HRQOL improvements.
Conclusions
For most patients, endoscopy scores and disease specific HRQOL significantly improved after endoscopic sinus surgery. Changes in endoscopy scores explain a portion of the improvement in HRQOL. For patients with CRS, improvements in disease specific HRQoL outcomes are complex, multidimensional constructs that cannot be entirely explained by surgical changes measured by endoscopic examination.
doi:10.1001/archoto.2010.34
PMCID: PMC2860109  PMID: 20403849
Endoscopic sinus surgery; endoscopy; outcomes; quality-of-life; chronic sinusitis
6.  Age differences in perception and awareness of emotion 
Neurobiology of aging  2007;30(8):1305-1313.
We investigated the effects of age and gender on emotional perception and physiology using electrodermal skin conductance response (SCR) and examined whether SCR related to subjective perceptions of emotional pictures. Older adults found pictures to be more positive and arousing than younger participants. Older women rated pictures more extremely at both ends of the valence continuum: they rated positive pictures more positively and negative pictures more negatively. Elders were less likely to show measurable SCRs. However, magnitude of SCRs when a response occurred did not differ between young and old. Subjective ratings of emotion correlated with physiological responses in younger participants, but they were unrelated in older participants. Thus, in older adults the perception of emotional events was disconnected from the physiological state induced by emotion.
doi:10.1016/j.neurobiolaging.2007.11.007
PMCID: PMC2733236  PMID: 18155323
7.  Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity 
Contraception  2009;80(2):119-127.
Objective
This study was conducted to determine whether increased body mass index (BMI) affects oral contraceptive (OC) pharmacokinetics and suppression of hypothalamic-pituitary-ovarian (HPO) axis activity.
Study design
Ovulatory reproductive-age women of normal (< 25 kg/m2; n = 10) and obese (> 30 kg/m2; n = 10) BMI received OCs for two cycles (prospective cohort). Subjects were admitted for two 48-h inpatient stays at the beginning and end of the hormone-free interval. Ethinyl estradiol (EE) and levonorgestrel (LNG) levels were evaluated during both inpatient stays. Gonadotropin pulsatility (FSH and LH) was measured during the second inpatient stay. Estradiol (E2) and progesterone (P) were measured daily during inpatient stays and twice per week in Cycle 2.
Results
BMI was greater in the obese, compared to the normal BMI group [37.3 kg/m2 (SD 6.0) versus 21.9 kg/m2 (SD 1.6); p < 0.05]. The LNG half-life was significantly longer in the obese group (52.1 ± 29.4 h versus 25.6 ± 9.3 h, p < 0.05) which correlated with a lower maximum LNG concentration on Cycle 2, Day 1 [1.9 ng/mL (SD 0.5) versus 2.5 ng/mL (SD 0.7)] and a longer time to reach steady-state (10 versus 5 days), in obese women. There were no significant differences in volume of distribution between groups. LH pulse parameters did not differ statistically between groups but trended towards greater HPO activity in the obese group. Additionally, more obese (6/10 versus 3/10 normal BMI, p > 0.05) women exhibited E2 levels consistent with development of a dominant follicle, and P levels consistent with ovulation (2/10 versus 1/10) during Cycle 2.
Conclusions
Compared to women of normal BMI, obese women exhibit differences in OC pharmacokinetics that are associated with greater HPO activity.
doi:10.1016/j.contraception.2009.04.011
PMCID: PMC2736633  PMID: 19631786
8.  A Bayesian approach to modeling associations between pulsatile hormones 
Biometrics  2009;65(2):650-659.
Many hormones are secreted in pulses. The pulsatile relationship between hormones regulates many biological processes. To understand endocrine system regulation, time series of hormone concentrations are collected. The goal is to characterize pulsatile patterns and associations between hormones. Currently each hormone on each subject is fitted univariately. This leads to estimates of the number of pulses and estimates of the amount of hormone secreted; however, when the signal-to-noise ratio is small, pulse detection and parameter estimation remains difficult with existing approaches. In this paper, we present a bivariate deconvolution model of pulsatile hormone data focusing on incorporating pulsatile associations. Through simulation, we exhibit that using the underlying pulsatile association between two hormones improves the estimation of the number of pulses and the other parameters defining each hormone. We develop the one-to-one, driver-response case and show how birth-death MCMC can be used for estimation. We exhibit these features through a simulation study and on the relationship between luteinizing and follicle stimulating hormones.
doi:10.1111/j.1541-0420.2008.01117.x
PMCID: PMC2845528  PMID: 18759850
9.  Influence of stressors on breast cancer incidence in the Women’s Health Initiative 
Objective
To examine associations among life events stress, social support, and breast cancer incidence in a cohort of postmenopausal women.
Design and main outcome measure
Women’s Health Initiative observational study participants, breast cancer free at entry, who provided assessment of stressful life events, social support, and breast cancer risk factors, were prospectively followed for breast cancer incidence (n=84,334).
Results
During an average of 7.6 years of follow-up, 2,481 invasive breast cancers were diagnosed. In age-adjusted proportional hazards models, one stressful life event was associated with increased risk, but risk decreased with each additional stressful life event. After adjustment for confounders the decreasing risk was not significant. Stressful life events and social support appeared to interact in relation to breast cancer risk such that women who had greater number of stressful life events and low social support had a decreased risk of breast cancer.
Conclusions
This study found no independent association between stressful life events and breast cancer risk. The results are compatible with a more complex model of psychosocial factors interacting in relation to breast cancer risk.
doi:10.1037/a0012982
PMCID: PMC2657917  PMID: 19290705
10.  Uninsurance among Children Whose Parents Are Losing Medicaid Coverage: Results from a Statewide Survey of Oregon Families 
Health Services Research  2008;43(1 Pt 2):401-418.
Context
Thousands of adults lost coverage after Oregon's Medicaid program implemented cost containment policies in March 2003. Despite the continuation of comprehensive public health coverage for children, the percentage of uninsured children in the state rose from 10.1 percent in 2002 to 12.3 percent in 2004 (over 110,000 uninsured children). Among the uninsured children, over half of them were likely eligible for public health insurance coverage.
Research Objective
To examine barriers low-income families face when attempting to access children's health insurance. To examine possible links between Medicaid cutbacks in adult coverage and children's loss of coverage.
Data Source/Study Setting
Statewide primary data from low-income households enrolled in Oregon's food stamp program.
Study Design
Cross-sectional analysis. The primary predictor variable was whether or not any adults in the household recently lost Medicaid coverage. The main outcome variables were children's current insurance status and children's insurance coverage gaps.
Data Collection
A mail-return survey instrument was designed to collect information from a stratified, random sample of households with children presumed eligible for publicly funded health insurance programs.
Principal Findings
Over 10 percent of children in the study population eligible for publicly funded health insurance programs were uninsured, and over 25 percent of these children had gaps in insurance coverage during a 12-month period. Low-income children who were most likely to be uninsured or have coverage gaps were Hispanic; were teenagers older than 14; were in families at the higher end of the income threshold; had an employed parent; or had a parent who was uninsured. Fifty percent of the uninsured children lived in a household with at least one adult who had recently lost Medicaid coverage, compared with only 40 percent of insured children (p=.040). Similarly, over 51 percent of children with a recent gap in insurance coverage had an adult in the household who lost Medicaid, compared with only 38 percent of children without coverage gaps (p<.0001). After adjusting for ethnicity, age, household income, and parental employment, children living in a household with an adult who lost Medicaid coverage after recent cutbacks had a higher likelihood of having no current health insurance (OR 1.44, 95 percent CI 1.02, 2.04), and/or having an insurance gap (OR 1.79, 95 percent CI 1.36, 2.36).
Conclusions
Uninsured children and those with recent coverage gaps were more likely to have adults in their household who lost Medicaid coverage after recent cutbacks. Although current fiscal constraints prevent many states from expanding public health insurance coverage to more parents, states need to be aware of the impact on children when adults lose coverage. It is critical to develop strategies to keep parents informed regarding continued eligibility and benefits for their children and to reduce administrative barriers to children's enrollment and retention in public health insurance programs.
doi:10.1111/j.1475-6773.2007.00764.x
PMCID: PMC2323132  PMID: 18199193
Insurance coverage; health care access; primary health care; Medicaid; children's health care
11.  The Relation between Neighborhood Built Environment and Walking Activity among Older Adults 
American Journal of Epidemiology  2008;168(4):461-468.
The association of neighborhood built environment with walking activity has received growing attention, although most studies have relied upon subjective measures of the built environment and few have examined the relation between built environment and walking among older adults. This 2001 study examined the relation between objectively measured characteristics of the local neighborhood and walking activity among a sample of 546 community-dwelling older adults in Portland, Oregon. A geographic information system was used to derive measures of the built environment within a quarter-mile (0.4 km) and half-mile (0.8 km) radius around each participant's residence. Multilevel regression analysis was used to examine the association of built environment with walking behavior. No association between built environment and the likelihood of walking or not walking was observed in this cohort of older adults. However, among those participants who reported some degree of walking activity, average time spent walking per week was significantly associated with amount of automobile traffic and number of commercial establishments in their local neighborhood. These findings suggest that built environment may not play a significant role in whether older adults walk, but, among those who do walk, it is associated with increased levels of activity.
doi:10.1093/aje/kwn158
PMCID: PMC2727277  PMID: 18567638
aged; environment design; geographic information systems; health behavior; regression analysis; residence characteristics; urban health; walking
12.  Analysis of Individual Social-ecological Mediators and Moderators and Their Ability to Explain Effect of a Randomized Neighborhood Walking Intervention 
Background
Using data from the SHAPE trial, a randomized 6-month neighborhood-based intervention designed to increase walking activity among older adults, this study identified and analyzed social-ecological factors mediating and moderating changes in walking activity.
Methods
Three potential mediators (social cohesion, walking efficacy, and perception of neighborhood problems) and minutes of brisk walking were assessed at baseline, 3-months, and 6-months. One moderator, neighborhood walkability, was assessed using an administrative GIS database. The mediating effect of change in process variables on change in brisk walking was tested using a product-of-coefficients test, and we evaluated the moderating effect of neighborhood walkability on change in brisk walking by testing the significance of the interaction between walkability and intervention status.
Results
Only one of the hypothesized mediators, walking efficacy, explained the intervention effect (product of the coefficients (95% CI) = 8.72 (2.53, 15.56). Contrary to hypotheses, perceived neighborhood problems appeared to suppress the intervention effects (product of the coefficients (95% CI = -2.48, -5.6, -0.22). Neighborhood walkability did not moderate the intervention effect.
Conclusion
Walking efficacy may be an important mediator of lay-lead walking interventions for sedentary older adults. Social-ecologic theory-based analyses can support clinical interventions to elucidate the mediators and moderators responsible for producing intervention effects.
doi:10.1186/1479-5868-6-49
PMCID: PMC2728705  PMID: 19643024
13.  Traditional smallpox vaccination with reduced risk of inadvertent contact spread by administration of povidone iodine ointment 
Vaccine  2007;26(3):430-439.
One concern with traditional smallpox vaccination is inadvertent spread of virus to atopic or immunocompromised contacts. To reduce this risk, we tested the ability of povidone iodine to inactivate infectious virus at the vaccination site beginning at 7 days after transcutaneous smallpox vaccination. This ointment rapidly inactivated virus on the skin without reducing neutralizing antibody titers or antiviral T cell responses. Moreover, there was no delay in healing/eschar separation following povidone iodine application. Together, this indicates that administration of an antiviral/antimicrobial cream can effectively block virus shedding after traditional smallpox vaccination and reduce the risks of autoinoculation or contact spread.
doi:10.1016/j.vaccine.2007.10.070
PMCID: PMC2323604  PMID: 18083278
Smallpox vaccination; Vaccinia; Povidone iodine ointment

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