Penicillamine Neurotoxicity: An Hypothesis

Penicillamine, dimethyl cysteine, thiovaline, remains the drug of choice for the treatment of patience with Wilson disease. It is also of value in the treatment of cysteinuria and rheumatoid arthritis, it has also been suggested that it has value in the management of other rare diseases. It also has multiple toxicities. The majority of these can be explained as chemical toxicity, for instance its weak antipyridoxine action and its ability to interfere with lysyloxidea resulting in skin lesions. More important are its ability to induce immune reactions such as SLE, immune complex nephritis, the Ehlers Danlos syndrome and Goodpasture's syndrome. However the sudden increase in neurological signs which may occur in a small number of patients remains unexplained. The theory is proposed that this is due to lethal synthesis. In susceptible patients the–SH radical is liberated from penicillamine and will inhibit–SH dependent enzymes in the Krebs cycle leading to death in neurones. Other toxic metabolites may also be produced such as methyl mercaptan and ethyl mercaptan either of which could produce a similar metabolic block

Protocol for a longitudinal qualitative interview study: maintaining psychological well-being in advanced cancer - what can we learn from patients' and carers' own coping strategies?

IntroductionPeople with advanced cancer and their carers experience stress and uncertainty which affects the quality of life and physical and mental health. This study aims to understand how patients and carers recover or maintain psychological well-being by exploring the strategies employed to self-manage stress and uncertainty.Methods and analysisA longitudinal qualitative interview approach with 30 patients with advanced cancer and 30 associated family or informal carers allows the exploration of contexts, mechanisms and outcomes at an individual level. Two interviews, 4–12?weeks apart, will not only enable the exploration of individuals’ evolving coping strategies in response to changing contexts but also how patients’ and carers’ strategies inter-relate. Patient and Carer focus groups will then consider how the findings may be used in developing an intervention. Recruiting through two major tertiary cancer centres in the North West and using deliberately broad and inclusive criteria will enable the sample to capture demographic and experiential breadth.Ethics and disseminationThe research team will draw on their considerable experience to ensure that the study is sensitive to a patient and carer group, which may be considered vulnerable but still values being able to contribute its views. Public and patient involvement (PPI) is integral to the design and is evidenced by: a research advisory group incorporating patient and carers, prestudy consultations with the PPI group at one of the study sites and a user as the named applicant. The study team will use multiple methods to disseminate the findings to clinical, policy and academic audiences. A key element will be engaging health professionals in patient and carer ideas for promoting self-management of psychological well-being. The study has ethical approval from the North West Research Ethics Committee and the appropriate NHS governance clearance.RegistrationNational Institute for Health Research (NIHR) Clinical Studies Portfolio, UK Clinical Research Network (UKCRN) Study number 11725

Correlates of Physical Activity in a Cypriot Sample of Sixth-Grade Children

This study examined the association between self-reported physical activity and a number of potential correlates in a sample of 256 Grade 6 children. Physical activity was assessed in both summer and winter, and children and parents completed questionnaires assessing potential correlates of physical activity. Analyses revealed that gender, time spent playing outside, self-efficacy in overcoming barriers, and number of items of exercise equipment at home were variables associated with physical activity in both seasons. School location was a variable associated with physical activity only in the summer, whereas private-lesson attendance, sports-club attendance, and best friend's physical activity were variables associated with physical activity only in winter. Variance explained in physical activity were 42% and 51% in winter and summer, respectively

How do I sound to me? Perceived changes in communication in Parkinson's disease

Objective: To examine self and carer perceived changes in communication associated with Parkinson's disease and relate these to speech intelligibility, gender, age and other disease measures. Design: Cross-sectional survey of a hospital- and community-based sample of 176 people with Parkinson's disease and their carers using a questionnaire based on semantic differential techniques. Participants: One hundred and four people with Parkinson's disease with no history of communication difficulties prior to onset of their Parkinson's disease and 45 primary carers who returned completed questionnaires. Main outcome measures: Differences in ratings for `before' the onset of Parkinson's disease versus present status. Results: There was a strong perception of negative impact on communication between `before' and `now', irrespective of age and gender and largely independent of disease severity and duration, intelligibility and cognitive status. Activities of daily living (assessed by Unified Parkinson's Disease Rating Scale (UPDRS) II) and depression rating scale scores had the strongest association with change (adjusted R 2 0.27). There was a significant correlation between the rank order of perceived change in features examined in people with Parkinson's disease versus their carers, though in general carers rated change as having less impact. Conclusions: Parkinson's disease exercises a strong influence on communication even before apparent alterations to intelligibility or motor status

Stochastic dominance to account for uncertainty and risk in conservation decisions

Practical conservation normally requires making decisions in the face of uncertainty. Our attitude toward that uncertainty, and the risks it entails, shape the way conservation decisions are made. Stochastic dominance (SD), a method more commonly used in economics, can be used to rank alternative conservation actions by comparing the probability distributions of their outcomes, making progressive simplified assumptions about the preferences of decision makers. Here, we illustrate the application of SD to conservation decisions using the recovery plan for an endangered frog species in Australia as a case study. Stochastic dominance is simple and intuitively appealing for conservation decisions; its broader application may encourage conservation decision makers to consider probabilistic uncertainty in light of their preferences, which may otherwise be difficult to recognize and assess transparently. A better treatment of attitudes towards uncertainty and risk may help ensure rational decision making in conservation and remove potential causes of stakeholder conflict

Bile acid metabolism with special reference to the intravenous cholic acid tolerance test of liver function

1. Historical. The chemistry of the bile acids and their relationship to some other steroids is briefly reviewed. The nature of conjugation, the biological splitting of conjugated bile acids, and the action of bacteria on bile acids is discussed. The physiological importance of bile salts is briefly indicated, and it is suggested that the distribution of the different bile acids in the various animal species has an evolutionary significance. Animal experiments on bile acid metabolism and the effects of oral and intravenous administration of bile salts in animals and man are described. An account of the analytical methods which have been used in the determination of bile salts in body fluids is given.2. Experimental. The colour reaction used here in the estimation of bile salts is described in detail, with recovery of added cholates from blood and the accuracy to be expected. Blood cholate levels in subjects without liver disease, show little diurnal variation, but some alteration over a period of months. Significant differences are found both between the blood cholate levels in subjects with and without liver disease, and in different types of jaundice. There is, however, considerable scatter, so that the estimation is of little diagnostic value. The intravenous cholic acid tolerance test of liver function is compared with other liver function tests, the general biochemical findings, and the histological appearance of the liver. The results of the test in normal subjects, and in obstructive jaundice, active and latent cirrhosis, acute hepatitis, secondary malignant liver disease, and haemolytic jaundice are discussed. The intravenous cholic acid tolerance test has proved insensitive as a liver function test and unsuitable for routine clinical use, but interesting information about the metabolism of bile salts in liver disease has been obtained.<p

Werewolves and warning signs: Cultural responses to tropical cyclones in Mauritius

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