New health promotion indicators: the general health policy model

This article provides an overview of a general health policymodel and associated measures of health status. It describessome pervasive issues in health measurement, the applicationsof the model in screening, prevention and in tertiary care anddiscusses the studies of cost-benefit and cost-utility in policyanalysis. The author gives examples from primary, secondaryand tertiary prevention studies that suggest the general applicabilityof the model and argues that a general health policy model canbe used to quantify the health effects of health promotion.     

Addiction versus stages of change models in predicting smoking cessation

Prospective data from the California Tobacco Surveys (n=2066) were used to perform a critical test of the Prochaska et al. (1991) stages of change model. When the stages of change model was used as a stand alone predictor, smokers in preparation at baseline were more likely to be in cessation at follow-up than smokers in pre-contemplation at baseline (OR adj="1.9)" When stage membership was combined with baseline measures of addiction including smoking behaviors and quitting history, it was not a significant predictor of future cessation. A prediction equation that combined daily vs. occasional smoking, cigarettes per day smoked, life-time quits of at least a year, and quits of more than 5 days in the previous year discriminated smokers in cessation at follow-up of 1 to 2 years better than did the stages of change model. The area under the ROC curve for the equation based on addiction measures was 69.3% vs. 55.1% for the stages of change. Cessation rates ranged from 7.7% to 35.7% for the four-category addiction equation compared with 15.1% to 24.9% for stages of change model.     

HAEMODYNAMIC EFFECTS OF DILTIAZEM DURING FENTANYL-NITROUS OXIDE ANAESTHESIA: An In Vivo Study in the Dog

The haemodynamic effects of diltiazem were studied in six dogsduring fentanyl-nitrous oxide (in oxygen) anaesthesia. A bolusof diltiazem 300 µg kg^–1 was given, followed byinfusions at 30, 60 and 90 µg kg^–1 min^–1 whichproduced plasma diltiazem concentrations of 392±30, 908±54and 1483±134 ng ml^–1, respectively. Diltiazem significantlyreduced systemic vascular resistance index, mean arterial pressure,heart rate and PR interval. The decrease in afterload increasedcardiac index, since there was little change in myocardial contractility(LV dP/dt). Five dogs developed second degree atrioventricular(AV) block in association with the highest dose. Administrationof calcium chloride 20 mg kg^–1 did not reverse the haemodynamicor electrophysiological effects of diltiazem. Isoprenaline increasedheart rate and restored sinus rhythm in four dogs with AV block. Presented in part at the 59th International Anesthesia ResearchSociety Congress, Houston, Texas, 1985.     

A monoclonal antibody directed against a granule membrane glycoprotein (GMP-140/PADGEM, P-selectin, CD62P) inhibits ristocetin-induced platelet aggregation

P-selectin (also called CD62, GMP-140, PADGEM, CD62P) is a recently described member of a family of vascular adhesion receptors expressed by activated platelets and endothelial cells that are involved in leucocyte cell adhesion. The aim of this study was to characterize a new monoclonal antibody (LYP7) directed against activated human blood platelets that inhibits ristocetin-induced platelet aggregation. Immunoadsorbent affinity chromatography and immunoprecipitation studies showed that LYP7 (IgG₁) bound a surface-labelled glycoprotein (GP) which changed its apparent molecular mass (M_r) on reduction from 138 kD (situated below GPIIb) to 148 kD (above GPIIbα). LYP7 and S12, a monoclonal antibody directed against P-selectin immunoprecipitated the same band. Using ELISA assay, purified P-selectin was shown to bind LYP7 and S12 monoclonal antibodies. Binding sites of ¹²⁵I-labelled LYP7, which was greatly increased on thrombin-stimulated (2 U/ml) washed platelets (10825±2886, mean ±SD) (K_d=1.5±0.5 nm ) compared to resting platelets (2801±1278, mean ±SD) (K_d=1.5±0.6 nm ), was found to be normal on thrombin-stimulated platelets taken from a patient with grey platelet syndrome or a patient with Glanzmann thrombasthenia. LYP7 (IgG₁, F(ab′)₂ or Fab fragments) inhibited ristocetin-induced platelet aggregation of platelets in a dose-dependent fashion without affecting the binding of von Willebrand (vWf ) factor. However, agglutination of formaldehyde-fixed platelets induced by ristocetin was not affected by monoclonal antibody LYP7. In addition, the binding of thrombin-activated platelets to neutrophils was inhibited by monoclonal antibody LYP7. These results strongly suggest that P-selectin, by promoting cell–cell contact, may play an active role in platelet–platelet interactions.     

REDIRECTING T LYMPHOCYTE SPECIFICITY USING T CELL RECEPTOR GENES

Redirecting T cells by transferring T cell receptor (TCR) genes from tumor-associated antigen (TAA)-reactive T cell clones into human peripheral blood lymphocytes (PBL) has therapeutic potential for the treatment of diseases, including cancer. T cell specificity can be altered using retroviruses encoding TCR &#102 and TCR &#103 chain genes, or chimeric immunoglobulin (cIg) genes containing signaling domains of CD3 &#145 or Fc &#108 RI- &#110. This review evaluates recent studies using TCRs and cIgs to redirect T cell specificity and discusses some of the technical and biological hurdles that need to be addressed before these approaches can be successfully used to treat patients.