Evidence of impaired pain modulation in adolescents with idiopathic scoliosis and chronic back pain

BACKGROUND CONTEXT

Although 40% of adolescent idiopathic scoliosis (AIS) patients present with chronic back pain, the pathophysiology and underlying pain mechanisms remain poorly understood. We hypothesized that development of chronic pain syndrome in AIS is associated with alterations in pain modulatory mechanisms.

Sexual abuse in patients with eating disorders

The incidence of sexual abuse in eating disorder patients appears significant. Fifty percent of both our anorectic and bulimic patients reported a history of sexual abuse while only 28% of a non-anorexic, non-bulimic control population reported similar problems (p less than 0.01). Several patterns of behavior seemed related to previous sexual assault. In one, the eating disorder was used to change the body image of the patient and therefore to provide a defense to future abuse. Other behaviors which occurred more specifically in bulimic women dealt with a projection of repressed anger toward male authority figures. Forty six percent of the bulimic women seen in our study exhibited some promiscuous behavior, using sex either as a gauge of their own self worth or as a means of punishing men. It is essential that sexual issues be addressed early in the treatment of patients with eating disorders. Disclosure is often difficult particularly in outpatient situations where the patient lives at home with her family. It usually does not occur in such cases until the later stages of therapy, or until the patient is hospitalized. Rape is the exception since our data suggests that it is usually revealed early in the course of treatment (p less than 0.001). Once disclosure occurs, a dramatic change is usually seen in the patient and treatment becomes more effective. As the patient deals with the issues of sexual abuse, they no longer need to deny their sexuality or punish themselves or others. Issues of guilt, depression, repressed anger, low self-esteem, social isolation and inadequacy are important and need to be addressed during the course of therapy with sexually abused patients.     

Chloropentafluorobenzene: short-term inhalation toxicity, genotoxicity and physiologically-based pharmacokinetic model development.

Ten Fischer 344 rats and six B6C3F1 mice of each sex were exposed to air, 0.25, 0.80, or 2.50 mg chloropentafluorobenzene (CPFB)/liter of air for three weeks, excluding weekends. Exposure to 2.50 mg/liter caused a reduction in the growth rate of rats but did not affect the growth rate of mice. Following the exposure there was reduced SGOT activity in the blood serum of exposed rats and a dose related increase in liver weights. Increased liver weights were observed in mice as well; the response in the female groups was clearly dose dependent. Histologically the livers of both rats and mice presented single cell necrosis. In exposed mice hepatocytes exhibited mild hepatocytomegaly with increased granular eosinophilic cytoplasm. In evaluations for its potential to induce chromosomal damage following this exposure regimen, CPFB did not alter the rate of bone marrow cellular proliferation. Assessment of the micronucleated polychromatic erythrocytes and normochromatic erythrocyte populations during the inhalation exposures indicated a general absence of genotoxic activity.     

ICCVAM Evaluation of the Murine Local Lymph Node Assay: III. Data Analyses Completed by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods

To evaluate the reliability of the murine local lymph node assay (LLNA), a test for allergic contact dermatitis activity, the inter- and intralaboratory consistency statistics (h and k, respectively) were calculated for validation studies testing multiple chemicals. The analysis indicated the absence of excessive variability in the dose calculated to induce a threefold or greater increase in the stimulation index (SI). To assess the appropriateness of using an SI of 3 as the decision criteria for identifying a sensitizing compound, LLNA results based on SI values of 2.0, 2.5, 3.0, 3.5, and 4.0 were compared with guinea pig or human results. The results supported the use of an SI of 3 as the decision criteria. Assay performance was determined by comparing LLNA results to results obtained for guinea pigs or humans. The accuracy of the LLNA was 89% when compared with results from the guinea pig maximization test (GPMT)/Buehler assay (BA). The performance of the LLNA and the GPMT/BA was similar when each was compared to human maximization test results plus substances included as human patch test allergens. The LLNA offered advantages over the GPMT in respect to both the time required to conduct the test and the assay cost.     

Antiretroviral Drug Discovery Targeting the HIV-1 Nef Virulence Factor

While antiretroviral drugs have transformed the lives of HIV-infected individuals, chronic treatment is required to prevent rebound from viral reservoir cells. People living with HIV also are at higher risk for cardiovascular and neurocognitive complications, as well as cancer. Finding a cure for HIV-1 infection is therefore an essential goal of current AIDS research. This review is focused on the discovery of pharmacological inhibitors of the HIV-1 Nef accessory protein. Nef is well known to enhance HIV-1 infectivity and replication, and to promote immune escape of HIV-infected cells by preventing cell surface MHC-I display of HIV-1 antigens. Recent progress shows that Nef inhibitors not only suppress HIV-1 replication, but also restore sufficient MHC-I to the surface of infected cells to trigger a cytotoxic T lymphocyte response. Combining Nef inhibitors with latency reversal agents and therapeutic vaccines may provide a path to clearance of viral reservoirs.     

ICCVAM evaluation of the murine local lymph node assay. Conclusions and recommendations of an independent scientific peer review panel.

The validation status of the murine local lymph node assay (LLNA), a method for assessing the allergic contact dermatitis potential of chemicals, was evaluated by an independent peer review panel (Panel) convened by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). The LLNA measures lymphocyte proliferation using incorporation of radioactive thymidine or iododeoxyuridine into cells of the draining lymph nodes of mice topically exposed to a test article. The Panel concluded that the assay performed as well as currently accepted guinea pig methods [guinea pig maximization test (GPMT)/Buehler assay (BA)] for the hazard identification of strong to moderate chemical sensitizing agents, but that it might not correctly identify all weak sensitizers or metals (potential false negative response) or all strong irritants (potential false positive response). The Panel concluded also that the LLNA involves less pain and distress than conventional guinea pig methods. The Panel unanimously recommended the LLNA as a stand-alone alternative for contact sensitization hazard assessment, provided that certain protocol modifications were made. These included collection of individual, rather than pooled, animal response data; the inclusion of a concurrent positive control; and consideration of dose-response information and statistical analyses. A standardized LLNA protocol is provided.     

In vitro characteristics of tobramycin aerosol from ultrasonic and jet nebulizers

STUDY OBJECTIVE: To compare the in vitro performance of an ultrasonic nebulizer and a jet nebulizer in producing a respirable aerosol of tobramycin solution for injection. DESIGN: In vitro observational study DEVICES: Ultrasonic and jet nebulizers. INTERVENTION: Output was determined by measuring the difference in nebulizer weight before and after nebulizing 3 ml of tobramycin injection solution. Mass median aerodynamic diameter (MMAD) and respirable mass were determined by sampling tobramycin aerosol into a cascade impactor. MEASUREMENTS AND MAIN RESULTS: Mean (SD) output was 1.14 (0.09) ml/minute for the ultrasonic nebulizer and 0.64 (0.08) ml/minute (p<0.001) for the jet nebulizer. Mean MMAD for the jet nebulizer (2.31 [0.10] microm) was less than that of the ultrasonic nebulizer (2.81 [0.17] microm, p<0.001). The majority of tobramycin aerosol produced was in the respirable range for both the ultrasonic (65.1% [4.10%]) and jet (60.6% [0.73%], p=0.008) nebulizers. CONCLUSION: Despite small, clinically unimportant differences in aerosol size and respirable fraction, either device would be acceptable to administer tobramycin injection solution.