Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.

A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing.     

Changes to osteoporosis prevalence according to method of risk assessment.

The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk. INTRODUCTION: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. MATERIALS AND METHODS: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. RESULTS: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. CONCLUSIONS: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.     

Positive, negative, unknown: assumptions of HIV status among HIV-positive men who have sex with men.

Serosorting (i.e., engaging in unprotected sex with partners known to be of the same serostatus) can be a difficult process for men who have sex with men (MSM) who frequently make assumptions about their partners' serostatus. This process can be further complicated by a partner's dishonesty as well as other individual and contextual factors. The present study specifically examined how assumptions of serostatus made about unknown serostatus partners impact on the sexual behavior of 110 alcohol-abusing HIV-positive MSM. Although previous research has shown that HIV-positive MSM are more likely to serosort with other known HIV-positive men than with known HIV-negative men, our data suggest that unprotected sex behavior may not be specifically driven by whether or not they made assumptions of seroconcordance or serodiscordance. The types of assumptions these HIV-positive MSM made about their unknown status sexual partners and the basis for such assumptions were also examined. Owing to the ambiguities involved in assumptions of a partner's serostatus in sexual encounters, the 'unknown status' partner category is analytically distinct from 'known status' categories, and needs to be more fully explored because of its impact on perceived serosorting, rather than actual serosorting, among HIV-positive men.     

Correlates of nonparticipation in an HIV prevention program for MSM.

Providing HIV prevention services to high-risk individuals remains challenging. We assessed factors associated with nonparticipation among high-risk, sexually active MSM found eligible to participate in a brief, telephone-delivered HIV prevention trial designed to evaluate the efficacy of motivational enhancement therapy (the Sex Check). Two levels of nonparticipation are evaluated: eligible participants who did versus those who did not complete their baseline/enrollment interview, and enrolled participants who did versus those who did not attend any of their counseling sessions. Nonenrollers were younger, less educated, more closeted, and were more likely to report sex with an injection drug using partner. Enrolled participants who did not engage in their counseling session(s) were less educated, reported greater use of alcohol and drugs during sex and use of injection drugs. Innovative methods to reduce barriers to engaging high-risk, sexually active MSM in risk reduction counseling are needed.     

The effects of illicit drug use and HIV infection on sex hormone levels in women.

Drug use and HIV infection may affect sex hormone levels in women. One hundred and ninety-six women with and without a history of illicit drug use (50 HIV-negative and 148 HIV-infected), with regular menses, who never used antiretrovirals, were evaluated. Luteinizing hormone levels were significantly higher in women with a CD4 cell count <200/microl (p < 0.002). Current methadone use was associated with lower levels of total testosterone (p = 0.03) and higher levels of prolactin (p = 0.002); mean estradiol levels were 43% lower in women who used intravenous drugs (p < 0.001). Alcohol and crack cocaine use was not associated with sex hormone levels. Age, race, body mass index and degree of HIV immunosuppression were also associated with differences in sex hormone levels.     

Hemiballismus from a parietal stroke in a Parkinson patient.

Stroke-induced hemiballismus (HB) has been reported to improve motor function in people with Parkinson's disease (PD). We report on a patient who developed HB from a parietal infarct. The HB was improved by very low-dose clozapine but the HB did not improve the parkinsonism. This suggests that HB itself, whether from a lesion in the subthalamic nucleus or elsewhere, is not what improves motor function in PD; instead, the physiological function of the damaged structure is the determining factor.     

肱骨干骨折--髓内钉与钢板固定的比较

总体而言，这些报道提示：采用髓内钉治疗肱骨干骨折较采用钢板带来更多的并发症，尤其是采用顺行人路。同时，这些报道没有提供确切的证据证明何种方法在骨折愈合、减少感染或上肢总体功能上优于另一种。     

Effect of bite tray impression technique on relocation accuracy in frameless stereotactic radiotherapy.

A previously developed method for achieving patient relocation in fractionated stereotactic radiotherapy (attachment of an infrared fiducial system to a bite tray) relies on the integrity of a bite tray system that incorporates moulding to the patient's upper dentition. Reproducible and accurate patient positioning requires stability of the bite tray and mould during the full treatment process, both during the time the bite tray is inserted in the patient's mouth, and between separate bite tray insertions. The optimum construction method for a stable reproducible tray has not been sufficiently investigated. We undertook a study to identify factors which might influence the integrity of the hard palate bite tray system. Reprosil Fast Set Putty was used to construct 3 impression conditions; teeth only; teeth and alveolar sulcus; and teeth, alveolar sulcus, and the hard palate. Reproducibility was assessed by volunteers inserting the impressions multiple times and recording the locations of 8 standard reference points. Our results showed the optimal impression technique (i.e., the one that led to the smallest ranges in positional and rotational errors) was that which incorporated the teeth, alveolar sulcus, and hard palate.     

A comprehensive strategy for the evaluation and triage of the chest pain patient: A cost comparison study

BACKGROUND: Our objective was to determine the cost-effectiveness of a comprehensive, risk-based triage system, composed of multiple critical pathways, with the use of early myocardial perfusion imaging (MPI) in low-risk patients. We found previously that a chest pain evaluation system that uses MPI in low-risk patients was safe and effective, but the cost-effectiveness of this approach was not studied. METHODS AND RESULTS: We compared two groups. The Acute Cardiac Team (ACT) group (n = 874) was assigned prospectively to 1 of 4 risk levels by emergency department (ED) physicians. Level 1, 2, and 3 patients were admitted; level 4 patients were evaluated in the ED. Level 3 and 4 patients underwent ED MPI. The control group (n = 713) represented consecutive patients evaluated in the prior year according to standard care and assigned retrospectively to an ACT level based on the presenting electrocardiographic and clinical data. Record and hospital administrative data were assessed for clinical variables, outcomes, lengths of stay, and all expenses incurred within 30 days of the index visit. The baseline characteristics of the two groups were similar, including age, sex, myocardial infarction prevalence, and 30-day revascularization rates within each level or between the two groups. Mean costs per encounter were reduced for the ACT patients for each level, which was significant when all patients were compared ($5,030 +/- $7,081 vs $6,044 +/- $10,432, P =.02). Use of MPI in the low-risk patients was associated with reduced costs (level 3, $4,958 +/- $4,948 vs $5,051 +/- $7,036; level 4, $1,529 +/- $2,664 vs $1,794 +/- $6,854) and was associated with a significantly lower angiography rate and shorter length of stay. CONCLUSIONS: Implementation of a comprehensive strategy for chest pain evaluation and triage reduced overall costs for patients with chest pain on presentation. Acute MPI in the ED setting did not increase net cost.