Measurement of muscle disease by quantitative second-harmonic generation imaging.

Determining the health of muscle cells by in vivo imaging could impact the diagnosis and monitoring of a large number of congenital and acquired muscular or cardiac disorders. However, currently used technologies are hampered by insufficient resolution, lack of specificity, or invasiveness. We have combined intrinsic optical second-harmonic generation from sarcomeric myosin with a novel mathematical treatment of striation pattern analysis, to obtain measures of muscle contractile integrity that correlate strongly with the neuromuscular health of mice suffering from genetic, acquired, and age-related decline in skeletal muscle function. Analysis of biopsies from a pilot group of human volunteers suggests a similar power in quantifying sarcopenic changes in muscle integrity. These results provide the first strong evidence that quantitative image analysis of sarcomere pattern can be correlated with physiological function, and they invite the application of SHG imaging in clinical practice, either in biopsy samples or via microendoscopy.

Factors associated with skilled nursing facility transfers in dementia-specific assisted living.

BACKGROUND: Medical, functional, and behavioral problems are associated with transitions from assisted living (AL), but limited information is available on those at highest risk for transition. METHODS: We conducted a multidisciplinary geriatric team assessment of individuals newly admitted to 2 dementia-specific AL communities from January 2000 to March 2002. Transitions of individuals to permanent skilled nursing facilities (SNF) was assessed for 9 months. Multidisciplinary assessment on admission included medical and cognitive evaluations, physical function, nutritional status, and psychosocial adjustment. RESULTS: Twenty-four men and 24 women with a mean age of 83+/-6 years were assessed. Mental status score was 15+/-6. Residents had 2.1+/-1.7 comorbidities and were prescribed 1.7+/-1.2 medications. During follow-up, 23 (47.9%) transitioned to SNF and 9 (18.8%) individuals died (censored events). Significant predictors of transfer to nursing home from AL by one-predictor Cox proportional hazards model included depression score [hazard ratio (HR) 1.19; P=0.008], dependent activities of daily living (HR 1.18; P=0.014), gait speed (HR 1.15; P=0.004), modified Berg Balance Score (HR 0.88; P=0.004), and mental status score (HR 0.924, P=0.034). Our multivariate model selected by the forward procedure indicates that the modified Berg Balance Scale score predicted transfer to permanent nursing home with a interquartile HR of 0.91 (95% CI 0.8264, 0.989). CONCLUSIONS: A significant number of new residents of dementia-specific AL transitioned to SNF over 9 months. In univariate analysis, depression score, walking speed, balance, and mental status score were significantly associated with transition and in multivariate analysis, balance performance predicted transfer. These results suggest that fall risk should receive attention on admission to AL to potentially mitigate the high transfer rate.

The effect of short-term estradiol therapy on clotting and inflammatory markers in older men receiving hormonal suppression therapy for prostate cancer.

The cardio protective effect of estrogen in women has come under scrutiny as recent evidence from long-term trials has demonstrated negative findings. In contrast, the effect of endogenous sex hormones, specifically estrogen, on cardiovascular disease, inflammation and clotting parameters in men has not been well-studied. Men receiving androgen deprivation therapy for prostate cancer provide a unique model to study the effect of estrogen alone on inflammation and clotting factors. In a short-term randomized controlled trial of 17-beta estradiol (E(2)) versus placebo, we measured sex hormones, markers of inflammation including homocysteine (HC), C-reactive protein (CRP), interleukin-6 (IL-6) and coagulation factors including fibrinogen, plasminogen activator-inhibitor-1 (PAI-1) and anti-thrombin-III (AT-III) in 27 older men without bone metastases receiving androgen deprivation therapy or neoadjuvant treatment for prostate cancer. After 9 weeks of E(2) treatment, there was no difference in inflammation or clotting parameters between groups, but after 9 weeks of treatment AT-III increased in the E(2) treated group and decreased in the placebo group. CRP, homocysteine and IL-6 did not show any significant differences. We also evaluated the above parameters in 12 men 3 weeks after acute steroid withdrawal with androgen deprivation therapy and found no significant changes. We found an increase in AT-III in men receiving E(2) which may be related to gonadal steroid withdrawal, but no significant differences in other inflammatory or clotting factor parameters. While the current report is very preliminary in a small group of subjects, further studies are needed to determine the long-term effects of E(2) in this population of hypogonadal men.

The association between vitamin D and inflammation with the 6-minute walk and frailty in patients with heart failure.

OBJECTIVES: To identify relationships between anabolic hormones, inflammatory markers, and physical function. DESIGN: Cross-sectional. SETTING: Outpatient university heart failure program in Connecticut. PARTICIPANTS: Sixty patients with an ejection fraction of 40% or less. MEASUREMENTS: The 6-minute walk distance and frailty phenotype were measured. The relationship between physical measures of hormones and inflammatory mediators were examined. Linear and ordinal logistic regression analyses were performed for the physical measures. RESULTS: Forty-three men (mean age 77 +/- 9) and 17 women (mean age 78 +/- 12) participated. Longer 6-minute walk distance was correlated with higher 25-hydroxyvitamin D (25OHD) level, and a shorter walk was correlated with higher cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), and intact parathyroid hormone (PTH) (all P<.05). Percentage of free testosterone, DHEAS alone, and N-terminal pro-brain natriuretic peptide (NTpro-BNP) did not correlate with 6-minute walk distance. Higher frailty phenotype score (more frail) was correlated with higher high-sensitivity CRP, higher IL6, and lower 25OHD levels (all P<.05). Linear regression with the 6-minute walk distance as the dependent variable and independent variables of age, sex, percentage of free testosterone, DHEAS, 25OHD, intact PTH, hsCRP, IL6, cortisol/DHEAS ratio, and NTpro-BNP, revealed age, sex, 25OHD and hsCRP to be significant (coefficient of determination=53.5%). Ordinal logistic regression with the frailty phenotype and hormonal levels revealed that age, 25OHD, and hsCRP also predicted frailty status. CONCLUSION: Twenty-five-hydroxyvitamin D and hsCRP levels may contribute to lower aerobic capacity and frailty in patients with heart failure. A longitudinal study will further define the role of 25OHD and hsCRP on muscle strength and functional decline.

Marital status and variability in cortisol excretion in postmenopausal women.

Based on the premise that acute and chronic stresses stimulate and suppress cortisol secretion, respectively, and the hypothesis that marriage provides a buffer to stress, we tested whether extreme values of serum cortisol concentrations would be less likely in married women than in unmarried women. Three hundred women were recruited from two central Connecticut communities. Cortisol was measured in overnight urine samples using liquid chromatography-tandem mass spectrometry. Information on each subject's demographic characteristics, such as income and education level was collected. Mean log urinary cortisol was virtually identical in married and unmarried women, however, as predicted, the variance was significantly larger in the unmarried group (p=0.01). After adjustment for potential confounders, multivariate logistic regression still revealed that absolute deviation of log(10) cortisol from the mean was smaller for married versus unmarried women (p<0.01); deviation from the mean cortisol was also higher for non-working than working women. These results support the idea that marriage and employment reduce the extreme levels of cortisol secretion, and by extension, this may reflect differences in levels of stress in married and in working women compared to unmarried and non-working women.

Brief interventions for at-risk drinking: patient outcomes and cost-effectiveness in managed care organizations.

AIMS: Evaluate effectiveness and costs of brief interventions for patients screening positive for at-risk drinking in managed health care organizations (MCOs). METHODS: A pre-post, quasi-experimental, multi-site evaluation conducted at 15 clinic sites within five MCO settings. At-risk drinkers (N = 1329) received either: (i) brief intervention delivered by licensed practitioners; or (ii) brief intervention delivered by mid-level professional specialists (nurses); or (iii) usual care (comparison condition). Clinics were randomly assigned to three study conditions. Data were collected on the cost of screening and brief intervention. Follow-up interviews were conducted at 3 and 12 months. RESULTS: Participants in all three study conditions were drinking significantly less at 3-month follow-up, but the decline was significantly greater in the two intervention groups than in the control group. There were no significant differences between the two intervention conditions. Of the patients in the intervention conditions 60% reduced their alcohol consumption by > or =1 drink per week, compared with 53% of those in the control condition. No differences were found on a measure of the quality of life. Differential reductions in weekly alcohol consumption between intervention and control groups were significant at 12-month follow-up. Average incremental costs of the interventions were 4.16 US dollar per patient using licensed practitioners and 2.82 US dollar using mid-level specialists. CONCLUSION: Alcohol screening and brief intervention when implemented in managed care organizations produces modest, statistically significant reductions in at-risk drinking. Interventions delivered to a common protocol by mid-level specialists are as effective as those delivered by licensed practitioners at about two-thirds the cost.

The relationship of ultrasensitive measurements of prostate-specific antigen levels to prostate cancer recurrence after radical prostatectomy.

OBJECTIVE: To evaluate ultrasensitive (US) measurements of prostate-specific antigen (PSA) level in men with prostate cancer, and to correlate the findings with currently accepted values for PSA recurrence, as PSA is widely accepted as a surrogate marker for disease recurrence after treatment for prostate cancer, and although USPSA assays can detect minute quantities of PSA, the significance of this is unclear. PATIENTS AND METHODS: In all, 225 patients had a radical prostatectomy (RP) and were followed with USPSA measurements. PSA recurrence was defined as two or more consecutive increasing PSA values after RP of > or = 0.200 ng/mL. This was deemed clinically significant if it was associated with adjuvant treatment with a repeated nadir PSA level, or a PSA level that continued to increase on watchful waiting. USPSA values were compared between patients who recurred and those who did not, to determine any association with PSA recurrence and clinical outcomes. RESULTS: There was a PSA recurrence in 21 patients; all had clinical evidence of recurrence. Although the difference in mean USPSA levels was statistically significant for those patients who did and did not recur, the overlap in values invalidated any clinical utility. However, an undetectable level achieved during the follow-up appeared to confer a favourable prognosis. CONCLUSION: After RP patients might have PSA levels detectable by USPSA assays, i.e. <0.1 ng/mL. The amount of 'background noise' produced within this range precludes the ability to use this test as a clinical indicator of disease recurrence. However, undetectable levels appear to confer a favourable prognosis.

Cotinine levels and green tobacco sickness among shade-tobacco workers.

STUDY OBJECTIVE: Symptoms consistent with Green Tobacco Sickness (GTS) were found in 4% (13/331) to 15% (45/303) of the migrant, mostly Latino, shade-tobacco workers who sought medical care at a Connecticut clinic. The objective of this study was to determine whether or not shade-tobacco farm workers absorb nicotine from the tobacco leaves and have a corresponding increase in both salivary cotinine levels (a breakdown product of nicotine) and symptoms consistent with GTS. METHODS: The study utilized a prospective cohort design to evaluate salivary cotinine and symptoms consistent with GTS in a population of shade tobacco farm workers compared to a control group of nursery workers. The workers were assessed at two points in time, the early tobacco planting season and the harvest season. RESULTS: There was not a significant increase in salivary cotinine levels among shade-tobacco workers. Salivary cotinine levels over the work season did not significantly increase in shade-tobacco workers when compared with nursery workers. During the harvest season, none of the tobacco workers reported symptoms consistent with GTS. CONCLUSIONS: Migrant workers in Connecticut who harvest shade-tobacco appear to have a low-risk of occupational nicotine dermal absorption and a low incidence of GTS. The work practices associated with harvesting shade-tobacco, in addition to the fact that shade tobacco may actually have a lower level of nicotine than either burley or flue cured tobacco, may explain these results. Our study appears to reinforce the GTS prevention recommendations made by investigators in other tobacco growing regions, specifically the importance of minimizing close skin contact with tobacco leaves and avoiding dermal contact with the plants when they are wet.

Alcohol screening and brief intervention in primary care settings: implementation models and predictors.

OBJECTIVE: This study compared two different implementation strategies for Cutting Back, a primary care alcohol screening and brief intervention (SBI) program for hazardous and harmful drinkers. It also identified organizational factors contributing to the success or failure of SBI implementation. METHOD: Cutting Back was implemented in 10 primary care practices associated with managed care organizations (MCOs) in five states, through a system of planning, training, technical assistance and clinic feedback. Clinics were randomly assigned to one of two brief intervention systems: In the P Model, medical providers were responsible for delivering interventions, whereas in the S Model mid-level professionals (usually nurses) acted as the clinic specialists to provide that service. Data were collected to measure the performance of screening and delivery of interventions in each clinic. RESULTS: The S Model screened a higher percentage of patients than did the P Model during the best month of program operation (50% vs 44%) and over all months of operation (24% vs 19%). Of those patients who screened positive, more patients in the S condition received an intervention than in the P condition (73.1% vs 57.1%), but there was a considerable range of performance among the five sites within each condition. Results at the clinic level were mixed, with some MCOs performing alcohol SBI significantly better with the S model and others doing better with the P model. The ability of clinics to conduct SBI was significantly correlated with both provider characteristics and organizational factors (e.g., prior SBI experience, MCO stability, number of clinicians trained and the quality of the MCO coordinator's work). Lack of provider time, staff turnover and competing priorities correlated negatively with SBI performance. CONCLUSIONS: The extent to which a given delivery model is likely to work best within an MCO depends on complex provider and organizational characteristics.

Taurodontism and learning disabilities in patients with Klinefelter syndrome.

PURPOSE: The purpose of this descriptive clinical study was to determine the prevalence rates of taurodontism and learning disabilities in a sample of patients with Klinefelter syndrome. METHODS: Questionnaires and dental radiographs of Klinefelter syndrome patients were obtained and analyzed using previously published methods. Prevalence rates were determined for taurodontism and learning disabilities in the sample population and compared to the general population. Statistical analyses included a Fisher's exact 2-sided test to compare the prevalence rates to that found in the general population and subsequent determination of the positive predictive value. RESULTS: Taurodontism was found in 75% of the 24 participants. Eighty-three percent of the participants reported having a learning disability. These rates are significantly higher than the general population, as reported in the literature. CONCLUSIONS: The positive predictive value for Klinefelter syndrome, given a male patient with taurodontism and a learning disability, is 84%. In this case, the dentist should recommend karyotyping to the patient, parent, or physician. This demonstrates how important it is for dentists to understand and assist physicians in the diagnosis of genetic disorders.

Employment and quality of life outcomes among women with fibromyalgia compared to healthy controls.

The purpose of this study was to assess the effects of paid employment on health related quality of life among women with fibromyalgia compared to a group of women who were otherwise healthy. Participants were recruited from 118 rheumatology practices randomly sampled from the membership of the American College of Rheumatology. Three hundred and sixty-five patients were referred to the study and 287 completed a telephone interview. At the end of each interview, participants were asked to nominate 2 individuals to serve as control subjects. Because of lagging enrollment of control subjects, we initiated an additional method of asking control subjects to nominate controls. Of 381 control subjects nominated for the study, 286 or 75% completed the initial interview. As with patients, controls completed a computer assisted phone interview with a trained interviewer similar to that of the patient. The mean age of women with FMS was 47 years, most were married (59.6%), 87.8% were of white race and non-Hispanic ethnicity, 47.7% were employed, had an average of 14 years of education and household annual incomes generally exceeded $20,000, with 40.4% having incomes in excess of $50,000. There we no significant differences between women with FMS and those without FMS on these characteristics. Women with FMS had significantly worse physical and mental health related quality of life measured by SF-12 Physical (PCS) and Mental (MCS) Component Summary Scores; those who were not employed had significantly worse PCS scores but there were no differences by employment for MCS. Ordinal regression analysis adjusting for demographic characteristics showed that there were significant main effects for condition and employment on PCS in that those with FMS and those who were not employed had worse PCS scores. Initially, we also found an interaction effect between condition and employment in that the beneficial effects of employment was restricted to the FMS cases. However, when adjustments were made for the double nesting design, the interaction effect was no longer significant. For MCS, FMS cases had significantly worse health related quality of life, but there were no main effects for employment and no interactions were significant. Our results concur with findings in community studies that employed women report better quality of life than those not employed, but only for the physical dimension of quality of life. The findings regarding MCS are intriguing in that women with FMS are not very different from controls and that employment has little effect on the mental health component of quality of life.