The diagnosis, treatment and prevention of CAPD peritonitis

Introduced in 1976, continuous ambulatory peritoneal dialysis (CAPD) is an effective and increasingly popular form of long-term dialysis. Infective peritonitis is its main drawback. This can be caused by a wide variety of micro-organisms, but usually by bacteria from the skin or gut. The commonest and most troublesome causative organism is the coagulase-negative staphylococcus. Although improvements in methods of diagnosis, treatment and prevention were made during the first five years of its use, CAPD continued to be plagued by peritonitis in most centres.This study was carried out between 1982 and 1984 in the Queen Elizabeth Hospital, Birmingham. A CAPD service began there in 1981 and peritonitis quickly became the main threat to its success. It was soon evident that the methods then in use for the microbiological diagnosis of CAPD peritonitis were inadequate. A simple method of culture was developed which greatly increased the chances of a positive microbiological diagnosis. This method became the cornerstone of a more effective and economical laboratory service to the CAPD progranme.The antibiotic sensitivities of organisms causing CAPD peritonitis were studied with the aim of establishing a more effective initial treatment policy. Vancomycin was found to be the most consistently active of the antibiotics tested against Gram positive isolates in general and the coagulase-negative staphylococcus in particular. Aminoglycosides were the most consistently active against Gram negative isolates. A trial of intra-peritoneal vancomycin and tobramycin showed that this combination was much more effective in the initial treatment of CAPD peritonitis than cefuroxime, previously the antibiotic of first choice. However, potentially ototoxic levels of tobramycin were encountered.With the aim of making initial treatment both simpler and safer, a modified protocol involving once-daily intra-peritoneal vancomycin and gentamicin was developed. One hundred episodes of CAPD peritonitis were treated, of which 88 were cured without recourse to other antibiotics. This study showed for the first time that most episodes of CAPD peritonitis could be safely treated at home using intra-peritoneal antibiotics self-administered oncedaily. The problem of aminoglycoside toxicity was not solved, however.Many episodes of CAPD peritonitis follow contamination of the administration set with organisms on the patient's hands. Contamination usually occurs during the dialysate exchange procedure. We studied how effectively bacteria were removed from the patients' hands by washing with povidone iodine detergent or 70% ethyl alcohol. Surprisingly, povidone iodine was often found to be counter-productive. Ethyl alcohol was much more effective and convenient.Despite improvements in the diagnosis and treatment of CAPD peritonitis, its incidence at the Queen Elizabeth Hospital has recently increased. This may in part be due to a steady decline in the amount of time staff can devote to training and supervising individual patients: staffing of the programme has failed to keep pace with the rapid rise in patient numbers. The thesis ends with a review of a variety of recently developed techniques and strategies which aim to prevent CAPD peritonitis

Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity

The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy) to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the ‘obesity epidemic' - the large increase in body weight and adiposity of a large proportion of individuals in many countries since the 1980s. An alternative model, called the settling point model, is based on the idea that there is passive feedback between the size of the body stores and aspects of expenditure. This model accommodates many of the social and environmental characteristics of energy balance, but struggles to explain some of the biological and genetic aspects. The shortcomings of these two models reflect their failure to address the gene-by-environment interactions that dominate the regulation of body weight. We discuss two additional models - the general intake model and the dual intervention point model - that address this issue and might offer better ways to understand how body fatness is controlled

Young people's access to tobacco, alcohol, and other drugs

Young people in the UK can easily obtain cigarettes and alcoholic drinks from a range of social and illicit commercial sources before they reach the legal minimum purchase age; many also report having access to illicit drugs. Prices of alcoholic drinks and most illicit drugs, but not cigarettes, have been falling in real terms. Increasing the price of tobacco and alcohol is likely to reduce young people’s demand for them. Enforcing or raising minimum purchase ages can reduce under-age sales of tobacco and alcohol, and has also been shown to reduce young peope’s hazardous use of alcohol. Unenforced voluntary agreements with retailers, and intervening in illicit distribution systems, have not been shown to influence young people’s use of tobacco, alcohol or other drugs