Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.     

Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.

Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. INTRODUCTION: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men. MATERIALS AND METHODS: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3alpha,17beta-diol-3glucuronide (3G) and androstane-3alpha,17beta-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound. RESULTS: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume. CONCLUSIONS: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.     

Incremental versus maximum bite advancement during twin-block therapy: a randomized controlled clinical trial.

The aim of this study was to evaluate the effectiveness of incremental and maximum bite advancement during treatment of Class II Division 1 malocclusion with the Twin-block appliance in the permanent dentition. It was performed at 3 district general hospitals in the United Kingdom with 4 operators. Two hundred three patients, 10-14 years old, were randomized. Control patients had the initial bite taken edge-to-edge for appliance construction with a standard Twin-block. Experimental patients had 2 mm initial bite advancement and subsequent 2 mm advancements at 6 weekly intervals with a Twin-block appliance incorporating advancement screws. Data were collected at the start and the finish of Twin-block treatment. The use of incremental advancement of the Twin-block did not confer any advantages in terms of process and outcome of the treatment. However, patient compliance was influenced by operator and patient age. The duration of treatment was influenced by operator and initial overjet. Incremental bite advancement produced no advantages over maximum advancement.     

Mechanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent

Background BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. Methods and Results Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC₅₀ of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC₅₀ of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%) and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC₅₀ value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t_1/2) uptake was very rapid (approximately 35 seconds), and washout t_1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. Conclusions F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.     

Conceptual Framework and Issues for a Goals‐Oriented Treatment Perspective: A Commentary on “Where Do We Go From Here? The Goal Perspective in Psychotherapy”

This commentary provides an evolutionary framework for the argument that motivation—goal striving—is central to animal and human life and governs most psychological processes, with implications for clinical practice. Neglect of clients' goals may seriously misdirect treatment; Systematic Motivational Counseling systematizes treatment of clients' motivational structure. Treatment of the consequences and determinants of clients' goals appears useful, as demonstrated in the case of alcohol abuse. The commentary then reexamines some currently popular goal-related concepts, particularly intrinsic versus extrinsic valuation and internality versus externality of goals, and argues for their reconceptualization on grounds that current conceptualizations have probably led to fallacious conclusions and may impair therapeutic effectiveness.     

Molecular and signaling mechanisms of atherosclerosis in insulin resistance.

Although the prevalence of cardiovascular complications is increased in insulin-resistant individuals, the underlying causes of this link have been elusive. Recent work suggests that several intracellular signal transduction pathways are inappropriately activated by hyperinsulinemia, hyperglycemia, increased free fatty acids, dyslipidemia, various inflammatory cytokines and adipokines--factors that are increased in insulin resistance. Once activated, substantial cross talk occurs between these pathways, especially a self-reinforcing cascade of vascular inflammation and cell dysfunction, greatly increasing the risk and severity of atherosclerosis in the insulin-resistant individual. We review several key cell-signalling pathways, describe how they are activated in they insulin-resistant state and the damage they induce, and discusses possible therapeutic approaches to limit vascular damage.