Pharmacological evaluation of a selective bradykinin B1 antagonist in a canine model of arthritis.

The effects of a selective bradykinin 1 receptor antagonist, compound A, were evaluated in a canine model of acute inflammatory model of arthritis. Despite detection of the B1 receptor in canine type B synoviocytes using a fluorescent ligand, oral administration of compound A (9 and 27 mg/kg) did not improve weight bearing of dogs injected intra-articularly with IL-1ß in a force plate analysis. Analysis of the synovial fluid of IL-1ß-treated dogs indicated high levels of bradykinin postchallenge. Excellent exposure, coupled with evidence of the presence of the B1 receptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.

The medical status of methadone maintenance patients in treatment for 11-18 years.

To assess the safety and potential health consequences of long-term methadone maintenance treatment, we identified 111 male patients admitted to methadone maintenance treatment between 1965 and 1968, still enrolled in 1980 and in continuous treatment for at least 10 years. We were able, between 1980 and 1985, to examine patients or review records of 110 patients (99%). Most medical diagnoses, symptomatic complaints, physical examination findings and laboratory test results occurred with similar frequency in the long-term methadone maintenance patients and in a group of 56 long-term heroin addicts. These data suggest that prolonged methadone maintenance treatment is safe and is not associated with unexpected adverse effects.

The Yorkshire antenatal anti-D immunoglobulin trial in primigravidae.

2069 Rh(D)-negative women in their first pregnancy received 100 micrograms doses of anti-D immunoglobulin at 28 and 34 weeks' gestation and a further dose at delivery if the infant was Rh(D)-positive. The antibody status was determined at 28 weeks, 34 weeks, at delivery, and 6 months after delivery. The findings were compared with those in a control group of 2000 Rh(D)-negative primigravidae who gave birth to Rh(D)-positive infants and received the standard post-delivery injection of anti-D immunoglobulin. 2 women in the trial group and 18 in the control group became actively immunised during the first pregnancy. 325 women in the trial group have had a further Rh(D)-positive pregnancy and in 2 anti-D antibodies were detected for the first time. 528 control women have had a further Rh(D)-positive pregnancy and anti-D was demonstrable in 29-18 in whom antibodies developed during the first pregnancy and 11 in whom antibodies first appeared during the second. The reduction in the incidence of sensitisation was significant. It is estimated that the extra cost in anti-D immunoglobulin was approximately pounds 1600 for each woman sensitised.

The contribution of transfusion to HCV infection in England.

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.