Simulation model of renal replacement therapy: predicting future demand in England.

BACKGROUND: The demand for renal replacement therapy (RRT) in England has risen steadily, although from a lower base than many other developed countries. Predicting the future demand for RRT and the impact of factors such as the acceptance rate, transplant supply and patient survival, is required in order to inform the planning of such services. METHODS: A discrete event simulation model estimates the future demand for RRT in England in 2010 for a range of scenarios. The model uses current prevalence and current and projected future acceptance rates, survival rates and the transitions between modalities to predict future patient numbers. National population and mortality data, published literature and data from the UK Renal Registry and UK Transplant, are used to estimate unmet need for RRT, the impact of changing demography and incidence of Type 2 diabetes, patient haemodialysis (HD) survival and transplant supply. RESULTS: By 2010 the predicted prevalence will have increased from about 30,000 in 2000 to between 42 and 51,000 (900-1000 p.m.p.), an average annual growth of 4.5-6%. Changing transplant supply has a small effect on overall numbers but changes the proportion of patients with functioning graft by up to 8%. Even with an optimistic increase in transplant supply (11% p.a. for 5 years), numbers on HD will continue to rise substantially, especially in the elderly. The factors most influencing future patient numbers are the acceptance rate and dialysis survival. CONCLUSION: This model predicts a substantial growth in the RRT population to 2010 to a rate approaching 1000 p.m.p., particularly in the elderly and those on HD, with a steady state not being reached for at least 25 years.     

Evidence for motility and pinocytosis in ramified microglia in tissue culture

Ramified microglial cells were investigated in primary cultures of dissociated cerebral cortical tissue from rats. The identification of these cells was confirmed through immunohistochemical staining with 7 monoclonal antibodies selective for microglia. While there was significant variation in staining intensity with different antibodies, all stained the identified ramified cells; the antibodies OX-42 and ED1 yielded the most intense immunoreactivity. Based on distinctive morphological features, the microglia could be identified in living cultures where they were monitored using time-lapse video recording. This technique revealed extremely dynamic features of cellular plasticity and motility. Ramified microglia exhibited constant and rapid alterations in the size and shape of their cell body with an associated extension and retraction of processes; concomitantly, the cells moved about in a circumscribed area. These features of plasticity and motility were unique to this cell type, and correlated with OX-42 immunostaining. The microglia also possessed a differentially high level of pinocytotic activity; this too was correlated with OX-42 staining. From the nature of their morphological plasticity and motility, high pinocytosis, and cellular distribution, it is hypothesized that the ramified microglia specifically function as a system of fluid cleansing in normal brain tissue.     

Interactions of angiotensin IV and oxytocin on behaviour in mice.

INTRODUCTION: Angiotensin (Ang) IV enhances learning and memory in rats but there are strain differences in its effects in mice. Oxytocin (OT) also influences learning and memory in rats and mice and, in the light of the proposed effects of Ang IV on oxytocinase, the hypothesis that the effects of Ang IV on cognition in mice involve OT was tested. MATERIALS AND METHODS: The effects of Ang IV and OT, alone and combined, were determined in rat isolated uterine smooth muscle and in object recognition and forced swim tests in BKW mice. RESULTS: Ang potentiated the contractile effects of OT in the uterus. Neither peptide had any effect on object recognition nor locomotor activity. Ang IV had no effect in the forced swim test but abolished the effects of OT. CONCLUSIONS: Ang IV influences the actions of OT in vitro and in vivo, possibly by inhibition of oxytocinase, but the lack of effect of Ang IV on object recognition in BKW mice is unlikely to be a consequence of a deficiency endogenous OT. Unlike OT, Ang IV alone has no effect on learned helplessness in the forced swim test, an effect often used to predict potential antidepressant efficacy in humans.     

Treatment of pediatric acute lymphoblastic leukemia: Progress achieved and challenges remaining

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Careful building upon past clinical trials and thoughtful application of our limited knowledge of pharmacology have provided steady improvement in outcome for newly diagnosed patients. Precise identification of the many patients who are unlikely to relapse with current effective regimens is required to avoid the morbidity of further intensification of therapy. Progress is sorely lacking for relapsed patients. Most patients who relapse die. Gene expression arrays and comparative genomic hybridization have further extended our appreciation of the known immunophenotypic and genetic diversity of childhood ALL. Insight into the molecular mechanisms of treatment failure may provide guidance for future efforts.     

Obstetrician-gynecologists as primary care physicians: The Oregon experience—Early perceptions regarding the effects of legislative action

OBJECTIVE: Our purpose was to assess whether legislative action influenced the role of obstetrician-gynecologists as primary care physicians. STUDY DESIGN: An observational study was performed on the basis of a questionnaire sent to 410 obstetrician-gynecologists and 27 medical directors of managed-care organizations. RESULTS: Of 67% of obstetrician-gynecologists and 96% of medical directors who responded, there was agreement as to the content of primary care, but a minority (38%) of obstetrician-gynecologists identified themselves as primary care providers. A minority of medical directors (35%) felt that obstetrician-gynecologists should serve in that role. Both obstetrician-gynecologists and medical directors felt that legislation had little impact. CONCLUSION: The reticence of obstetrician-gynecologists to assume a major role in primary care appears to be the result of an uneasiness with accepting a more comprehensive role in patient management and gatekeeping. They appear comfortable with the more traditional roles but feel that training and experience has not prepared them well for the management of more complex medical problems. (Am J Obstet Gynecol 1998;178:1222-8.)