PET quantification of muscarinic cholinergic receptors with [N-11C-methyl]-benztropine and application to studies of propofol-induced unconsciousness in healthy human volunteers

This work evaluated kinetic analysis methods for estimation of the receptor availability of the muscarinic receptor using dynamic positron emission tomography (PET) studies with [N-(11)C-methyl]-benztropine. The study also investigated the effect of propofol on central muscarinic receptor availability during general anesthesia. Six volunteers were scanned three times, once for baseline while awake, once during unconsciousness, and once after recovery to conscious level. An irreversible two-tissue compartment model was used to estimate the [N-(11)C-methyl]-benztropine specific binding rate constant k(3), a measure of muscarinic receptor availability. Two different estimation methods were used: 1) optimization with positivity constraints on all the parameters; 2) optimization with additional constraints determined from a one-tissue compartment fit to the cerebellum. In regions with low to middle muscarinic receptor density, the k(3) values from method (2) had lower standard errors than that for method (1) and gave a higher correlation with the density of muscarinic receptors measured in human tissue by in vitro studies (r(2) of 0.98 for Method 2 and r(2) of 0.72 for Method 1). But the k(3) values determined by Method 2 had higher errors for regions with high muscarinic receptor density compared to Method 1. For both methods the mean k(3) values during unconsciousness were generally lower than those during awake for most regions evaluated. Therefore, the method with additional constraints derived from the cerebellum (Method 2) was deemed superior for regions with low to middle muscarinic receptor density, while the method with positivity constraint is the better choice in the regions with high muscarinic receptor density. Our results also suggest the existence of propofol-related reductions in muscarinic receptor availability.     

Guidelines for assessing postnatal problems: introducing evidence-based guidelines in Australian general practice

BACKGROUND: Postnatal morbidity is high, and many GPs lack the confidence and knowledge to deal with common postnatal problems. There is a high consultation rate, but few women disclose common health problems. OBJECTIVE: The aim of the present study was to increase the knowledge and skills of GPs to enable them to identify and manage common health problems experienced by women in the year following childbirth. METHODS: An educational programme [Guidelines for Assessing Postnatal Problems (GAPP)] embedded within a large randomized community intervention trial [Program of Resources, Information and Support for Mothers (PRISM)] with a before/after evaluation was undergone by Australian GPs working in four metropolitan and four rural communities. The programme comprised audit, interactive workshops, role-play and evidence-based guidelines, and was evaluated at baseline and 6 months through written questionnaires and a surgery consultation with a trained simulated patient evaluator. RESULTS: A total of 68 (86%) GPs took part in the full GAPP programme. The odds of a GP improving on the knowledge items ranged from 1.0 to 16, with the greatest change occurring in knowledge about the effectiveness of cognitive behavioural therapy for maternal depression. Of the GPs with an incorrect response at baseline, the percentage demonstrating improved knowledge at follow-up ranged from 22 to 100%. Around half of the GPs demonstrated excellent communication skills at baseline. Of the remaining GPs, more than half demonstrated greatly improved skills to detect common postnatal problems at follow-up. At baseline simulated patient visit, 70% of GPs inquired about sexual problems yet none inquired about the possibility of abuse, whereas at follow-up 94% inquired about sexual problems and 51.5% facilitated the disclosure of physical and emotional abuse. Anonymous feedback on the programme by participating GPs showed that 89% believed the programme positively influenced their actual practice. Interestingly, GPs demonstrated greater knowledge and skills in the simulated setting than on the written questionnaire. CONCLUSIONS: This relatively brief multifaceted educational programme assisted many participants in improving their knowledge and the skills required to improve both physical and emotional health after birth. Despite being experienced clinicians and participating actively in a programme on interviewing skills, half of the GPs did not facilitate disclosure of the underlying sensitive issue (abuse) during the follow-up consultation and could benefit from further in-depth training in effective communication skills.     

Balancing societal costs and users' quality of life--priority setting of interventions for the hard-of-hearing

In this paper, the need for priority setting in rehabilitation, especially in audiology, and various approaches to providing information for priority setting are discussed. A set of outcome measures is proposed, and their applicability to vertical and horizontal prioritization are considered. Two types of measures are proposed: individual problems assessment, and utility analysis. Results from a European multicentre study and a Swedish study illustrate the performance of the measures in the areas of mobility, hearing, and speech communication. For rehabilitation in the hard-of-hearing, the two types of measures provide different kinds of information, illustrated by the results of simultaneous use of the instruments.     

Poisoning in a paediatric hospital

Background Poisoning is a major cause of morbidity and mortality in children and adolescents. Pharmaceutical and household products are responsible for the majority of cases. Aim To analyse poisoning cases presenting to a paediatric hospital. Methods A retrospective study of all poisoning cases presenting to the Accident and Emergency (A&E) department of one hospital over a nine-month period. Children from birth to 15 years of age were included. The cases were categorised into accidental or intentional with or without suicidal intention. Demographic features included age, gender, toxin, location of poisoning, need for admission and mortality. Results A total of 148 cases were recorded, 47% were male, 31% were hospitalised and there was no mortality. Of ingestions, 74% were between 1 and 4 years of age and 86% were accidental. Of the intentional, 33% were suicidal, all 12 years or older. Conclusions Few unintentional ingestions in the paediatric group result in serious toxicity. Mortality is rare. There is increasing intentional poisoning and alcohol abuse in adolescents. Poison prevention should be part of all well child visits. Agencies catering for children should carry educational leaflets for parents on how to ‘poison proof’ a child’s environment, as the majority of incidents occur at home.     

An outbreak of Escherichia coli O157 gastroenteritis in a care home for the elderly

In the summer of 2001 an outbreak of Escherichia coli O157 gastroenteritis affected staff and residents of a care home for the elderly in the West Midlands, UK. E. coli O157 phage type 2 was isolated from faeces in eight patients and 12 staff members. Thirty-five staff and 40 residents met the case definition for clinical gastrointestinal infection. Serological testing identified a further 14 possible cases of infection amongst asymptomatic staff and residents. The outbreak was atypical, as the disease seemed to be milder than has been observed in past outbreaks in similar settings. The index case, a member of staff, developed bloody diarrhoea and haemolytic-uraemic syndrome (HUS), but only one resident developed bloody diarrhoea and required hospitalization. No deaths occurred, despite the high-risk nature of the affected population. The source of the outbreak could not be identified. The prolonged nature of the outbreak and observed lapses in infection control practices indicated that person-to-person spread was the likely route of transmission. This outbreak illustrates the importance of observing appropriate infection control measures in the institutions providing residential and nursing care to the elderly.     

Delayed hypotension and subendocardial injury after repeated umbilical cord occlusion in near-term fetal lambs

OBJECTIVE: This study was undertaken to determine whether myocardial injury occurs after repeated intrauterine asphyxia. STUDY DESIGN: Near-term fetal sheep with implanted instrumentation underwent either sham occlusions (n = 8) or repeated brief umbilical cord occlusions (n = 12) continued until the onset of severe (<20 mm Hg) or sustained hypotension. After 3 days of recovery, the fetal hearts were perfusion fixed. RESULTS: Repeated umbilical cord occlusions led to a severe metabolic acidosis (pH, 6.84 +/- 0.09; lactate concentration, 14.1 +/- 1.5 mmol/L) with increasing hypotension during occlusions, which were terminated after 128 +/- 38 minutes. After the occlusions, the mean arterial pressure showed a delayed fall, which resolved after 12 hours. Ultrastructural examination showed evidence of subendocardial injury, with dilatation of sarcoplasmic reticulum, margination and clumping of nuclear chromatin, and mitochondrial swelling. The most severe morphologic changes, including electron-dense mitochondrial inclusions, were found in the fetuses with delayed recovery of the fetal heart rate after the final occlusion. CONCLUSION: Subendocardial injury occurs after severe repeated intrauterine asphyxia in the late-gestation fetus, and this may contribute to cardiovascular compromise and the development of late decelerations.