Interleukin-5 is at 5q31 and is deleted in the 5q- syndrome

Human interleukin-5 (IL-5) is a selective eosinophilopoietic and eosinophil-activating growth hormone. By in situ hybridization this gene is mapped to chromosome 5q23.3 to 5q32. It is shown to be deleted in two patients with the 5q-syndrome and in one patient previously diagnosed with myelodysplasia whose condition had progressed to acute myeloblastic leukemia. The clustering of other genes involved in hematopoiesis (IL-3, granulocyte-macrophage colony-stimulating factor, feline sarcoma viral oncogene homolog, colony-stimulating factor 1) to the same region as IL-5 suggests a nonrandom localization and raises interesting questions concerning the evolution and regulation of these genes.     

An ‘early warning system’ for health needs: surveillance of the quality of clinical services by audit of extra-contractual referrals (ECRs)

Extra-contractual referrals (ECRs) can be a cause of considerable anxiety to purchasing authorities, mainly because of their potential to generate unexpected expenditure. But ECRs can also be used as a tool for monitoring the demand for, and quality of, clinical services. ECRs were studied in the Darlington Health Authority district using a variety of methods including inter-disciplinary meetings, a series of interviews with local GPs, and a questionnaire to general practitioners on 230 consecutive ECRs. The methods and results of the questionnaire study are presented. The commonest reasons for making ECRs included the mistaken belief that a contract existed with the ECR provider, patient dissatisfaction with the local provider, and referral to benefit from shorter waiting lists. ECRs for bone-mass densitometry, orthopaedics, and ear nose and throat services were over-represented. Questionnaire results were validated by comparison with an interview study of all GPs in the district. We conclude that trends in ECRs can be monitored as a convenient ‘early warning system’ to alert purchasing authorities to changes in demand or perceived problems with local provider units. ECR data must be interpreted in the context of further local background information from sources such as GPs and public health physicians. In the case of Darlington, scrutiny of ECRs has led to changes in services and contracts.     

Pharmacokinetics of MDL 63,246, a new semisynthetic glycopeptide antibiotic, in the rat.

Following intravenous administration in the rat, the concentration of MDL 63,246 in plasma was high and long-lasting. Concentrations fell with an apparent three-exponential decay. MDL 63,246 was distributed in a high volume and was cleared quite slowly. The pharmacokinetics of MDL 63,246 in the rat appear to be dose proportional in the dose range of 20 to 50 mg/kg of body weight. When administered subcutaneously, MDL 63,246 was slowly absorbed from the injection site, and the extent of availability was good, being 70.1%. MDL 63,246 was eliminated slowly by both renal and fecal excretion. MDL 63,246 is rapidly and extensively distributed into the tissues. At 0.5 h after drug administration, radioactivity was detected in all organs examined. At 24 h after administration, the total concentrations of radioactivity still increased in some organs which represent a slowly equilibrating compartment, but only the kidneys and liver showed a higher total concentration of radioactivity than plasma. Between 24 and 192 h after treatment, total concentrations of radioactivity decreased very slowly, and finally, apart from brain, all tissues showed higher concentrations than plasma, indicating a very high affinity of MDL 63,246 for tissues. The ratio of the concentration of radioactivity in blood to that in plasma ratio was 0.58, indicating that MDL 63,246 does not diffuse into erythrocytes and that binding to the erythrocyte membrane does not occur. All of these findings appear to correlate with the excellent in vitro and in vivo activities of the compound, suggesting that MDL 63,246 could be therapeutically efficacious at lower dosages and longer treatment intervals than those currently used for vancomycin and teicoplanin.