Lysis of human fibroblast colony-forming cells and endothelial cells by monoclonal antibody (6-19) and complement

The murine IgG2a monoclonal antibody 6-19 binds to a wide variety of nonhematopoietic cells including human marrow-derived stromal cells but does not bind to marrow or peripheral blood cells. We studied the effects of this antibody and rabbit complement on marrow cells. Fibroblast colonies were eliminated from light density marrow cells by a single incubation with monoclonal antibody 6-19 and complement. The growth and composition of granulocytic and erythroid colonies were unaffected. Specific complement mediated cytotoxicity of the antibody was confirmed on passaged human fibroblasts derived from marrow (more than 99.6% of fibroblasts are killed by a single treatment). Similar results were obtained with human umbilical cord endothelial cells. In addition, such treatment abolished the initiation of Dexter culture stroma. Incubation of bone marrow cell suspensions with this antibody and complement will allow the study of stroma-free marrow cells in long- term liquid cultures.     

Molecular epidemiology of respiratory syncytial virus: rapid identification of subgroup A lineages

Methods for the rapid analysis of samples of respiratory syncytial (RS) virus are described using the polymerase chain reaction (PCR) followed by restriction mapping. Isolates (either clinical samples or tissue culture grown virus) can readily be divided into subgroups and then further classified into lineages. These methods enable examination of large numbers of isolates by molecular techniques, thereby facilitating research into the molecular epidemiology of the virus.     

Reduction of thrombus formation in vivo using a thrombolytic agent targeted at damaged endothelial cells.

Endothelial damage in saphenous vein harvested before coronary artery and peripheral vascular surgery has been well documented. Autogenous saphenous vein grafts are subject to early thrombotic occlusion, a process that is related to injury of this endothelial monolayer. A monoclonal antibody that binds to areas of endothelial damage (P14G11) and a non-specific immunoglobulin G (IgG) have been linked to urokinase. These conjugates were investigated in vivo using a rat vena cava model. The P14G11-urokinase conjugate significantly reduced thrombus formation compared with controls and non-conjugated urokinase (P < 0.02). No reduction in thrombus formation was seen with the IgG-urokinase conjugate. This shows that thrombus formation after endothelial damage in an in vivo model can be reduced with a targeted thrombolytic agent. Conjugates such as this may have a role in preventing early thrombotic occlusion in vein grafts.     

Standardizing the weaning process

The goal among critical care staff of discontinuing mechanical support in a prudent and expeditious manner emerges immediately after intubation. This goal, known as the weaning process, contains the three phases of optimizing the patient's condition, assessing and evaluating the patient's progress, and diagnostic testing. As a diagnostic test, the wean trial needs to be standardized for efficiency and safety. To maximize safe and efficient delivery of the trial, the primary nurse and respiratory therapist should be the responsible professional monitors. The standardized trial enhances staff confidence for safe extubation. A successful standardized weaning protocol eases the transition from mechanical ventilation to spontaneous breathing for the patient and improves the professional performance and confidence of critical care staff.     

Using unemployment rates to predict prescribing trends in England.

BACKGROUND. There are many factors underlying trends in prescribing levels in England. AIM. This study set out to examine prescribing trends and their relationship with three measures of morbidity. METHOD. A study was undertaken examining the interrelations between basic prescribing parameters for the 90 family health services authorities in England for the year 1 April 1989 to 31 March 1990. The trends were examined for their associations with three factors which have been linked to morbidity levels: standardized mortality ratios, the Jarman index (through its use as a deprivation index), and unemployment rates. RESULTS. Analysis revealed a strong inverse association between the number of items prescribed per patient and the net ingredient cost per item for the family health services authorities. These two factors together determined the net ingredient cost per patient. Cluster analysis was found to segregate approximately the family health services authorities geographically: the northern, urban areas of England were characterized by a high number of low cost items per patient while the southern semi-rural areas had a low number of high cost items per patient. The trend was such that the former area had a higher overall net ingredient cost per patient. Unemployment rates were the most robust determinant of the inverse trend of number of items and cost of items and were comparable with standardized mortality ratios in their individual correlations with the prescribing net ingredient cost per patient. The Jarman index was the weakest of the predictors. CONCLUSION. The results lend support to the argument that material deprivation, associated with unemployment, is an important determinant of prescribing trends, perhaps acting through its effect on morbidity, and that the Jarman index is a poor indicator of deprivation. The analysis alone cannot, however, determine cause and effect for the apparent relationship between unemployment and prescribing.     

The effect of systemic administration of baclofen on food intake in rats.

The effects of systemic administration of the GABAB agonist, baclofen was investigated on food intake in non-fasted rats. Baclofen (1.0, 2.0 and 4.0 mg/kg, s.c.) produced a dose-related increase in food intake in a free-feeding paradigm during the first 90 min after administration, with maximum increases occurring at a dose of 2 mg/kg (Experiment 1). Baclofen (0.5 and 1.0 mg/kg, s.c.) also increased food intake in the 40 min post-drug recording period in non-fasted rats, trained to make operant responses for food on a fixed-ratio schedule (Experiment 2). These results demonstrate that systemic administration of baclofen can stimulate ingestive behaviour in satiated rats and suggest a possible role for a GABAB receptor-mediated mechanism in the control of food intake.