Symptom-related research from the agency for healthcare research and quality

Recent reports on research supported by the Agency for Healthcare Research and Quality are summarized. These reports relate to use of aspirin for cardioprotection by patients taking NSAIDs, end of life care for nursing home residents with advanced directives, Cancer Patients' Satisfaction With Primary Care Pain Management, the need for increased medical training about adverse drug events, and dorsal root entry zone lesioning for central neuropathic pain. The research summarized in this report was abstracted from the AHRQ Research Activities.     

Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model

Rationale: Previous pre-clinical studies with an anti-cocaine monoclonal antibody left open several issues critical to assessing the effectiveness of a vaccine for altering cocaine self-administration behavior. Objectives: The objectives of this study were to determine, first, whether changes in self-administration behavior would be systematically related to antibody level and, second, how the antibody affected the self-administration of different doses of cocaine. Methods: Two experiments were conducted using a second-order schedule of drug delivery in rats. The first was a passive-administration study using the anti-cocaine monoclonal antibody MO240 to examine the relationship between antibody level and cocaine self-administration behavior, and the second was an active-immunization study to examine the efficacy of the cocaine vaccine IPC-1010 for blocking various doses of self-administered cocaine. Results: The passive-administration experiment with control and 4-mg or 12-mg MO240 treatments showed that antagonism of the 1 mg/kg cocaine training dose was dependent on antibody level. In animals whose serum antibody levels were sustained above 0.05 mg/ml, there was a sufficient amount of antibody to reduce drug-seeking behavior and drug intake. In the active-immunization experiment, the cocaine vaccine IPC-1010 induced average serum antibody levels of 0.08 mg/ml and reduced the reacquisition of behavior by 1 mg/kg cocaine. Antagonism of cocaine self-administration after immunization was evident across a range of doses of cocaine and was only apparent in animals whose serum antibody levels exceeded 0.05 mg/ml. Furthermore, there was no evidence that the antagonism was surmountable within the dose range examined (up to 5.6 mg/kg). Conclusions: Antagonism of cocaine self-administration across a range of doses is feasible after immunization with a cocaine vaccine as long as antibody levels are of a sufficient concentration. Received: 2 April 1999 / Final version: 25 September 1999     

Calpain in cultured bovine lens epithelial cells

Calcium dependent proteolysis was examined in supernatant prepared from cultured bovine lens epithelial (BLE) cells. The presence of the calcium activated protease, calpain, was indicated by immunorecognition of 80 kDa and 30 kDa subunits of calpain in BLE cell supernatant. Degradation of 125I-alpha-crystallin and FITC labeled casein by BLE cell supernatant were shown to be calcium dependent. Inhibition of activity was achieved with EGTA, calpastatin or CbzValPheH. The data presented are the first measurement of calpain activity in cultured lens cells.     

Antenatal sonographic diagnosis of arthrogryposis multiplex congenita

Arthrogryposis Multiplex Congenita (AMC) was suspected on ultrasound examination of a fetus at 30.5 weeks of gestation. The criteria for establishing this prenatal diagnosis as well as the importance of establishing the diagnosis at any gestational age are discussed. The diagnosis of AMC was confirmed at birth in this case.