Apparent improvement in diabetic autonomic neuropathy induced by captopril

Eight diabetic subjects with moderately elevated blood pressure (BP) (systolic (SBP) greater than 140 and/or diastolic (DBP) greater than 90 mmHg) were studied. Each had evidence of mild asymptomatic autonomic neuropathy (impairment of forced sinus arrhythmia). The effect of a single oral 25 mg dose of captopril on BP and some aspects of autonomic function was compared with matched placebo in a double-blind, cross-over study. Resting supine SBP and DBP fell significantly (P less than 0.01) over 90 minutes following captopril, indicating that the hypotensive effect of the drug was not dependent on intact autonomic function. There was no significant change in resting heart rate. The bradycardic response to apnoeic face immersion was significantly (P less than 0.01) enhanced following captopril. Sinus arrhythmia did not change. The BP responses to standing and to the cold pressor test were unaffected. There was no exacerbation of postural hypotension. The ingestion of a single dose of captopril appears to increase vagal function, without affecting sympathetic nervous function, in diabetics with evidence of mild vagal impairment.     

Distribution of dehydration rates generated by maximal Gardos-channel activation in normal and sickle red blood cells

The Ca(2+)-activated K+ channels of human red blood cells (RBCs) (Gardos channels, hIK1, hSK4) can mediate rapid cell dehydration, of particular relevance to the pathophysiology of sickle cell disease. Previous investigations gave widely discrepant estimates of the number of Gardos channels per RBC, from as few as 1 to 3 to as many as 300, with large cell-to-cell differences, suggesting that RBCs could differ extensively in their susceptibility to dehydration by elevated Ca2+. Here we investigated the distribution of dehydration rates induced by maximal and uniform Ca2+ loads in normal (AA) and sickle (SS) RBCs by measuring the time-dependent changes in osmotic fragility and RBC volume distributions. We found a remarkable conservation of osmotic lysis and volume distribution profiles during Ca(2+)-induced dehydration, indicating overall uniformity of dehydration rates among AA and SS RBCs. In light of these results, alternative interpretations were suggested for the previously proposed low estimates and heterogeneity of channel numbers per cell. The results support the view that stochastic Ca2+ permeabilization rather than Gardos-channel variation is the main determinant selecting which SS cells dehydrate through Gardos channels in each sickling episode.     

Relational ethics of delirium care: Findings from a hospice ethnography

Delirium, a common syndrome in terminally ill people, presents specific challenges to a good death in end‐of‐life care. This paper examines the relational engagement between hospice nurses and their patients in a context of end‐of‐life delirium. Ethnographic fieldwork spanning 15 months was conducted at a freestanding residential hospice in eastern Canada. A shared value system was apparent within the nursing community of hospice; patients’ comfort and dignity were deemed most at stake and therefore commanded nurses’ primary attention. This overarching commitment to comfort and dignity shaped all of nursing practice in this hospice, including practices related to end‐of‐life delirium. The findings of this study elaborate the ways in which hospice nurses interpreted and responded to the discomfort of their patients in delirium, as well as the efforts they made to understand their patients’ subjective experiences and to connect with them in supportive ways. In addition to what is already known about clinical assessment and treatment of delirium in palliative care settings, the findings of this study offer points of reflection for nurses anywhere who are contending with the relational challenges that delirium presents in end‐of‐life care.     

Challenges for opioid receptor nomenclature: IUPHAR Review 9

Recent developments in the study of the structure and function of opioid receptors raise significant challenges for the definition of individual receptor types and the development of a nomenclature that precisely describes isoforms that may subserve different functions in vivo. Presentations at the 2013 meeting of the International Narcotics Research Conference in Cairns, Australia, considered some of the new discoveries that are now unravelling the complexities of opioid receptor signalling. Variable processing of opioid receptor messenger RNAs may lead to the presence of several isoforms of the μ receptor. Each opioid receptor type can function either as a monomer or as part of a homo- or heterodimer or higher multimer. Additionally, recent evidence points to the existence of agonist bias in the signal transduction pathways activated through μ receptors, and to the presence of regulatory allosteric sites on the receptors. This brief review summarizes the recent discoveries that raise challenges for receptor definition and the characterization of signal transduction pathways activated by specific receptor forms.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

The Participation of Disabled Children and Young People: A Social Justice Perspective

There is an increasing expectation that children, young people and their parents should participate in decisions that affect them. This includes decisions about their health and social care and collective or public decisions about the way in which such services are designed, delivered and evaluated. Indeed this has become a policy priority across the United Kingdom. The participation of disabled children and young people, however, has been slow to develop in the United Kingdom and concerns have been expressed about progress in this area. Drawing on the results of an Economic and Social Research Council-funded, mixed-methods study, the aim of this article is to explore the participation of disabled children and young people through a social justice lens. Participants, recruited by purposeful sampling, included 18 disabled children and young people, 77 parents and 90 professionals from one health and social care trust in Northern Ireland. There were four phases of data collection: surveys to parents and professionals, parent interviews, interviews with children and young people using creative and participatory techniques, and a focus group with professionals. Results showed that for most disabled children and young people, decision-making was firmly grounded in a family-centred model. However, when children and young people were drawn into participatory processes by adults and recognised as partners in interactions with professionals, they wanted more say and were more confident about expressing their views. Choices, information and resources were at times limited and this had a key impact on participation and the lives of these children, young people and their parents. The article concludes by exploring implications for further research and practice. The need for a two-pronged, social justice approach is recommended as a mechanism to advance the participation agenda.     

Usefulness of early exercise testing after non-Q-wave myocardial infarction in predicting prognosis

The value of an early symptom-limited maximal exercise test in predicting coronary anatomy, left ventricular ejection fraction and hemodynamics was assessed prospectively in 64 patients after an acute non-Q-wave myocardial infarction (MI). Exercise tests and cardiac catheterization were performed at a median of 6 and 7 days, respectively, after non-Q MI. Forty-one percent of the patients had a negative exercise test response (no angina, less than 1 mm of ST depression and normal blood pressure responses). Twenty-five percent had a positive response (1 to 1.9 mm of ST depression or angina); 34% had a "strongly positive" exercise test response (at least 2 mm of ST depression or abnormal blood pressure responses). A negative response predicted the absence of 3-vessel disease (at least 70% stenosis) or critical stenoses (at least 90% stenosis) involving major coronary arteries (negative predictive accuracy 92%), whereas a strongly positive response predicted their presence (positive predictive value 77%, specificity 88%). Cardiac index and mean pulmonary artery wedge pressure did not vary significantly among the 3 exercise groups, whereas left ventricular ejection fraction was slightly higher in the exercise test group with a positive response (p less than 0.025). Thus, in patients who have had a non-Q MI, early exercise testing can be used to predict the extent and severity of coronary artery disease, and the decision to perform coronary angiography should be guided by the exercise test results.