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.     

Useful predictors of bile duct stones in patients undergoing laparoscopic cholecystectomy. McGill Gallstone Treatment Group.

OBJECTIVE: The authors determined the most useful predictors of common bile duct (CBD) stones as diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent laparoscopic cholecystectomy (LC). METHODS: Prospective and retrospective collection of historical, biochemical and ultrasonographic data was used. Receiver operating characteristics curve analysis was used to determine optimal biochemical cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones also was employed. Prospective validation of the model was performed on an independent group of patients. RESULTS: Endoscopic retrograde cholangiopancreatographies were performed before LC in 106 patients, and after LC in 33. Only four of ten clinical variables evaluated independently predicted the presence of CBD stones. The optimal model predicted a 94% probability of CBD stones in a patient older than 55 years of age who presented with an elevated bilirubin (over 30 mumol/L) and positive ultrasound findings (a dilated CBD, and a CBD stone seen on ultrasound). This model was validated prospectively in a subsequent series of 49 patients in which the probability of CBD stone was only 8% when all four predictors were absent. CONCLUSIONS: The identified independent clinical predictors of a CBD stone helps select a population of symptomatic gallstone bearers who benefit most from cholangiographic assessment.     

Interleukin-6, a marker of preservation injury in clinical lung transplantation.

Interleukin-6 (IL-6) is one of the cytokines produced by human alveolar macrophages, lung parenchyma, and other cells in response to injury and infection. We hypothesized that IL-6 is released from poorly preserved lung grafts and may serve as a marker of preservation injury. Sixteen patients who received lung allografts were enrolled in this study. The average ischemic time was 284 +/- 78 minutes. Serum IL-6 level was measured before and at 4 and 24 hours after reperfusion of the grafts by an enzyme-linked immunosorbent assay. Preservation injury was assessed by (1) the need for prolonged intubation (> 7 days), (2) the arterial/alveolar oxygen tension ratio (PaO2/PAO2 ratio) at 4 hours after graft reperfusion (only in heart-lung or double lung recipients), (3) the presence of diffuse alveolar damage on first lung biopsy, and (4) the 30-day graft survival rate. IL-6 level peaked at 4 hours after reperfusion and returned to baseline at 24 hours. The patients were divided into group I (n = 6) and group II (n = 10), depending on whether the 4-hour IL-6 level was more than 1000 pg/ml or less than 500 pg/ml, respectively. Group I patients required longer intubation (p < 0.01) and had a lower PaO2/PAO2 ratio (p < 0.001), more diffuse alveolar damage (p < 0.01), and a lower graft survival rate (p < 0.01) than those of group II. No bacterial, fungal, or viral infection was found during postoperative week 1 in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Helping families of homicide victims: A multidimensional approach

Homicide inflicts massive injury upon the intrapsychic and interpersonal realities of the surviving kin of murder victims. A New York City pilot program of outreach and counselling to 1182 families of Brooklyn homicide victims suggests that surviving kin undergo the symptoms of traumatic stress disorder. Recovery is prolonged by knowledge that the perpetrator is usually alive and in some cases unpunished, by repetitive confrontations with the criminal justice system and by the multiple losses endured: loss of a family member, loss of illusions of safety and invulnerability, loss of a sense of trust in the surrounding community, and loss of a belief system. Effective help to survivors requires interventions that respond to all aspects of the survivors' losses.     

Rubber band as external assist device to provide simple grip for quadriplegic patients

The rubber band as an external assist device provides an effective grip for the hand of high spinal cord injury quadriplegic patients. This technique can also be useful for preoperative patients who are undergoing physical and occupational therapy or to assess patients' needs for surgery. The rubber band as an adaptive device is preferred because of its availability, low visibility, and ease of application. We attempt to provide a more standardized method of the rubber band technique and to popularize it.     

Efficacy of a patient-training videotape on motor fluctuations for on-off diaries in parkinson's disease

Patient on-off diaries are used in clinical trials, but a method to assure agreement between patient and examiner has never been developed. We tested whether a patient-teaching tape increased the rate of agreement between patient diary ratings and simultaneous neurologic assessment by a trained professional. A total of 32 consecutive patients who had Parkinson's disease with motor fluctuations independently completed a 4-h on-off diary (nine ratings) at the same time as an examiner. Those with <80% agreement with the examiner (n = 20) were randomized to view either a training tape that showed motor fluctuations (experimental group) or another videotape of general patient educational material (control group). All patients then underwent the same 4-h assessment of motor fluctuations. To test for long-term retention, they returned 1 month later and, without reviewing the videotape, underwent a final 4-h correlation assessment. After the training tape, the experimental group showed significant improvement, whereas the control group showed no improvement. Furthermore, another month later, the improvement in the experimental group was retained. Based on these findings, we suggest that future clinical trials assessing motor fluctuations incorporate this tape into their basic methodology.