[The selective toxic effect of dialdehyde derivatives of the pyrimidine nucleosides on human tumor cells].

The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1-ß-D-eritrofuranozyl uracil and 3'-O-ß-D-ribofuranosyl-2'-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1-ß-D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.

Harmonisation of ethics committees' practice in 10 European countries.

BACKGROUND: The Directive 2001/20/EC was an important first step towards consistency in the requirements and processes for clinical trials across Europe. However, by applying the same rules to all types of drug trials and transposing the Directive's principles into pre-existing national legislations, the Directive somewhat failed to meet its facilitation and harmonization targets. In the field of ethics, the Directive 2001/20/EC conditioned the way of understanding and transposing the "single opinion" process in each country. This led to a situation in which two models of research ethics committees organisation systems exist, being the model in which the "single opinion" is considered to be the decision made by a single ethics committee more effective and simpler in terms of administrative and logistic workload. METHOD: A survey was conducted in 10 European countries. Members of the European Clinical Research Infrastructures Network working party number 1, with expertise in the field of ethics, responded. RESULTS: There is a major heterogeneity in the composition of ethics committees among the surveyed countries based on the number of members, proportion of experts versus lay members and expertise of the scientific members. A harmonized education of the ethics committees' membership based in common curricula is recommended by the majority of countries. CONCLUSIONS: Despite the efforts for harmonization of the European Clinical Trial Directive, from an ethical point of view, there remains a plurality of ethics committees' systems in Europe. It is important to comprehend the individual national systems to understand the problems they are facing.

Stepped treatment of older adults on laxatives. The STOOL trial.

OBJECTIVES: To investigate the clinical effectiveness and cost-effectiveness of bulk-forming, stimulant and osmotic laxatives, and also of adding a second type of laxative agent in the treatment of patients whose constipation is not resolved by a single agent. Additionally, to define the meaning of constipation in older people from the perspective of GPs and older patients, and to investigate the use of prescribed and non-prescribed treatments for constipation in older people together with their adherence to prescribed treatments. DESIGN: A multicentre pragmatic, factorial randomised controlled trial with economic evaluation and qualitative study using in-depth interviews and focus groups with older people, GPs and community nurses. SETTING: General practices in north-east England. PARTICIPANTS: People aged 55 years or over with chronic constipation living in private households. INTERVENTIONS: Six stepped-treatment strategies using three classes of laxatives: bulk, stimulant and osmotic preparations, singly and in combination. MAIN OUTCOME MEASURES: The primary outcome was the constipation-specific Patient Assessment of Constipation--Symptoms/Patient Assessment of Constipation--Quality of Life. Secondary outcomes included EuroQoL 5 Dimensions, reported number of bowel movements per week, the presence/absence of the other Rome II criteria for constipation, adverse effects of treatment and relapse rates. RESULTS: Recruitment to the trial was difficult and the trial was closed after recruiting 19 participants. GP participants provided patient-centred definitions that focused on the idea of a change from the norm as defined by the individual patient and 'textbook definitions' that focused on reduced frequency of defecation associated with a range of unpleasant sensations and other clinical symptoms. Nurses' definitions of constipation included both a patient-centred perspective and the description of particular symptoms associated with constipation. Older participants defined constipation in terms of frequency of bowel movements and changes in normal bowel routine. Older participants perceived constipation as follows: linked to specific diseases, medical conditions or health problems; caused by the consumption of specific medications or surgical procedures; caused by diet or eating habits; part of the ageing process; due to not going to the toilet when having the urge to defecate; hereditary; caused by stress or worry; and caused by environmental exposure. GP participants suggested that constipation is due to changes in diet and lifestyle; the physiology and degenerative processes of ageing; and the iatrogenic impact of opiate medications. Nurse participants identified that constipation is linked to decreased mobility, decreased food intake, decreased fluid intake and consumption of certain medications. For many older people their constipation emerged as a problem over a period of time; for some the 'condition' had existed for many years. Self-management of constipation had typically been their first response to the symptoms and continued once professional help had been sought. Older participants had a wide experience of different management strategies and treatments for constipation, and at the time of the study had firm preferences about the laxatives they would use. GP participants recognised the experience and use of laxatives of their patients. They exhibited strong personal preferences for different laxatives, often prescribing them in combination. Nurses were more likely than GPs to treat and prevent constipation using non-laxative measures; these included providing advice on appropriate dietary changes, increasing fluid intake and, if possible, encouraging exercise and mobility. CONCLUSIONS: There is little shared understanding between patients and professionals about 'normal' bowel function with little consensus in general practice of the optimum management strategies for chronic constipation and the most effective strategies to use. Chronic constipation is seen as less important than other conditions prevalent in general practice (e.g. diabetes) because it is not an agreed management target within national frameworks. Consequently, practitioners had little interest in constipation as a research topic. Patient preferences and the absence of patient equipoise formed an enormous barrier to the recruitment of patients in the implementation of this trial. Studies are needed to investigate different methods of recruitment within the constraints of current ethical guidelines on 'opting in' and to identify barriers and facilitators to recruitment to complex trials in general. Patient preference trials and natural cohort observational studies are also needed to investigate the effectiveness or cost-effectiveness of different laxatives and treatment strategies in the management of chronic constipation.

A qualitative study of the physical, social and attitudinal environments influencing the participation of children with cerebral palsy in northeast England.

PURPOSE: The social model of disability considers participation to be determined by the social, attitudinal and physical environments experienced by an individual. This study aims to ascertain from families of children with cerebral palsy the features of such environments which facilitate or restrict participation. METHOD: Thirteen in-depth interviews using a topic guide were conducted with the parents of children with cerebral palsy. Interviews were tape-recorded, transcribed and analysed with NVivo software. RESULTS: The main themes emerging from the interviews were the importance of mobility, transport, support by and to parents and attitudes of individuals and institutions towards children. Most parents did not raise the policies and legislation determining participation barriers, although these are also likely to be influential. CONCLUSIONS: This study confirms the importance of the environment for the participation of children with cerebral palsy. Statutory agencies need to attend the attitudes and policies in their organization in order to plan the inclusive environments which parents report will facilitate their child's participation. This study also contributes to the development of a tool to quantify the environment to allow the development of models to determine the environments which maximize children's participation.

Determining "need" for a Removable Partial Denture: a qualitative study of factors that influence dentist provision and patient use.

OBJECTIVE: To identify factors that influence Removable Partial Denture (RPD) provision, and patient use of RPDs in the UK. DESIGN: Exploratory qualitative interview study. SUBJECTS: There were two sample groups. A purposive sample of 16 male and female dentists was categorised in terms of level of RPD provision, experience, and practice characteristics. A purposive sample of 17 male and female partially dentate patients was categorised in terms of RPD use and demographic characteristics. DATA COLLECTION: Semi-structured in-depth interviews. RESULTS: For dentists, RPD provision was indicated by patient demand and physical function of the remaining teeth, but was mediated by NHS fee structures and professional satisfaction. For patients, RPD use was influenced by the trade-off between improved appearance and the unpalatable presence of an RPD in their mouth. The location of the gap(s) was important, but other issues were relevant such as ability to "manage" without the RPD. CONCLUSION: When defining "need" for an RPD, dentists focused on physical function of the teeth whereas patients focused on social meanings of the mouth. These differing priorities may improve understandings of patient non-compliance in RPD use. Further research on the relationship between denture use and social identity could be beneficial.

The effect of low level radiofrequency electromagnetic radiation on the excretion rates of stress hormones in operators during 24-hour shifts.

The aim of the study was to investigate the effect of long term exposure to low level radiofrequency (RF) electromagnetic (EM) radiation on the excretion rates of stress hormones in satellite station operators during 24-hour shifts. Twelve male operators at a satellite station for TV communications and space research were studied during 24-hour shifts. Dosimetric evaluation of the exposure was carried out and showed low level exposure with specific absorption of 0.1127 J.kg-1. A control group of 12 unexposed male operators with similar job task and the same shift system were studied, too. The 11-oxycorticosteroids (11-OCS), adrenaline and noradrenaline were followed by spectrofluorimetric methods on 3-hour intervals during the 24-hour shifts. The data were analyzed by tests for interindividual analysis, Cosinor analysis and analysis of variance (ANOVA). Significant increase in the 24-hour excretion of 11-OCS and disorders in its circadian rhythm, manifested by increase in the mesor, decrease in the amplitude and shift in the acrophase were found in the exposed operators. The changes in the excretion rates of the catecholamines were significant and showed greater variability of both variables. The long term effect of the exposure to low-level RF EM radiation evoked pronounced stress reaction with changes in the circadian rhythm of 11-OCS and increased variability of catecholamines secretion. The possible health hazards associated with observed alteration in the stress system need to be clarified by identification of their significance and prognostic relevance.