Role of the N-terminal region in G protein-coupled receptor functions : negative modulation revealed by 5-HT2B receptor polymorphisms

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family

Re-evaluation of the effect of smoking on the methylation of N-terminal valine in haemoglobin

In view of the established extrapulmonary cancer sites targeted by smoking a multiplicity of compounds, and mechanisms might be involved. It has been debated that smoking caused increased incidence of N-methylvaline at the N-terminus of haemoglobin. Because this could indicate a relevance of methylating nitrosamines in tobacco smoke, data are presented from an industrial cohort of 35 smokers and 21 non-smokers repeatedly monitored between 1994 and 1999. In general, N-methylvaline adduct levels in haemoglobin of smokers were approximately 50% higher than those of non-smokers. The smoking-induced methylation of haemoglobin is likely to be caused by dimethylnitrosamine (N-nitroso-dimethylamine), a major nitrosamine in side-stream tobacco smoke. The biomonitoring data emphasise the potential value of N-methylvaline as a smoking-related biomarker and call for intensified research on tobacco smoke compounds that lead to macromolecular methylation process.

Palliative care phase : inter-rater reliability and acceptability in a national study

Background: The concept of palliative care consisting of five distinct, clinically meaningful, phases (stable, unstable, deteriorating, terminal and bereavement) was developed in Australia about 20 years ago and is used routinely for communicating clinical status, care planning, quality improvement and funding. Aim: To test the reliability and acceptability of revised definitions of Palliative Care Phase. Design: Multi-centre cross-sectional study involving pairs of clinicians independently rating patients according to revised definitions of Palliative Care Phase. Setting/participants: Clinicians from 10 Australian palliative care services, including 9 inpatient units and 1 mixed inpatient/community-based service. Results: A total of 102 nursing and medical clinicians participated, undertaking 595 paired assessments of 410 patients, of which 90.7% occurred within 2 h. Clinicians rated 54.8% of patients in the stable phase, 15.8% in the unstable phase, 20.8% in the deteriorating phase and 8.7% in the terminal phase. Overall agreement between clinicians’ rating of Palliative Care Phase was substantial (kappa = 0.67; 95% confidence interval = 0.61–0.70). A moderate level of inter-rater reliability was apparent across all participating sites. The results indicated that Palliative Care Phase was an acceptable measure, with no significant difficulties assigning patients to a Palliative Care Phase and a good fit between assessment of phase and the definition of that phase. The most difficult phase to distinguish from other phases was the deteriorating phase. Conclusion: Policy makers, funders and clinicians can be confident that Palliative Care Phase is a reliable and acceptable measure that can be used for care planning, quality improvement and funding purposes.

Discharge practices for the intensive care patient : a qualitative exploration in the general ward setting

OBJECTIVE: To explore how registered nurses (RNs) in the general ward perceive discharge processes and practices for patients recently discharged from the intensive care unit (ICU). BACKGROUND: Patients discharged from the ICU environment often require complicated and multifaceted care. The ward-based RN is at the forefront of the care of this fragile patient population, yet their views and perceptions have seldom been explored. DESIGN: A qualitative grounded theory design was used to guide focus group interviews with the RN participants. METHODS: Five semi-structured focus group interviews, including 27 RN participants, were conducted in an Australian metropolitan tertiary referral hospital in 2011. Data analyses of transcripts, field notes and memos used concurrent data generation, constant comparative analysis and theoretical sampling. RESULTS: Results yielded a core category of 'two worlds' stressing the disconnectedness between ICU and the ward setting. This category was divided into sub categories of 'communication disconnect' and 'remember the family'. Properties of 'what we say', 'what we write', 'transfer' and 'information needs' respectively were developed within those sub-categories. CONCLUSION: The discharge process for patients within the ICU setting is complicated and largely underappreciated. There are fundamental, misunderstood differences in prioritisation and care of patients between the areas, with a deep understanding of practice requirements of ward based RNs not being understood. The findings of this research may be used to facilitate inter departmental communications and progress practice development.

Withholding and withdrawing life-sustaining treatment in a patient's best interests : Australian judicial deliberations

•Intractable disputes about withholding and withdrawing life-sustaining treatment from adults who lack capacity are rare but challenging. Judicial resolution may be needed in some of these cases. •A central concept for judicial (and clinical) decision making in this area is a patient's “best interests”. Yet what this term means is contested. •There is an emerging Supreme Court jurisprudence that sheds light on when life-sustaining treatment will, or will not, be judged to be in a patient's best interests. •Treatment that is either futile or overly burdensome is not in a patient's best interests. Although courts will consider patient and family wishes, they have generally deferred to the views of medical practitioners about treatment decisions.

Informatics to support patient choice between diverse medical systems

Culturally, philosophically and religiously diverse medical systems including Western medicine, Traditional Chinese Medicine, Ayurvedic Medicine and Homeopathic Medicine, once situated in places and times relatively unconnected from each other, currently co-exist to a point where patients must choose which system to consult. These decisions require comparative analyses, yet the divergence in key underpinning assumptions is so great that comparisons cannot easily be made. However, diverse medical systems can be meaningfully juxtaposed for the purpose of making practical decisions if relevant information is presented appropriately. Information regarding privacy provisions inherent in the typical practice of each medical system is an important element in this juxtaposition. In this paper the information needs of patients making decisions regarding the selection of a medical system are examined.

A young immunocompetent patient with bilateral immune stromal keratitis due to varicella zoster and herpes simplex

This report describes the diagnostic features, clinical management and the issues associated with management of a young immunocompetent male who presented with a presumed left Herpes simplex immune stromal keratitis, and ten months later, a right immune stromal keratitis associated with Herpes zoster ophthalmicus.

A pilot trial of mobile, patient-performed teledermoscopy

BACKGROUND Early detection by skin self-examination (SSE) could improve outcomes from melanoma. Mobile teledermoscopy may aid this process. OBJECTIVES To establish clinical accuracy of SSE plus mobile teledermoscopy compared to clinical skin examination (CSE) and test whether providing people with detailed SSE instructions improves accuracy. METHODS Men and women 50-64 years (n=58) performed SSE plus mobile teledermoscopy in their homes between May and November 2013 and were given technical instructions plus detailed SSE instructions (intervention) or technical instructions only (control). Within three months, they underwent a CSE. Outcome measures included: a) body sites examined, lesions photographed, and missed; b) sensitivityof SSE plus mobile teledermoscopy compared to in-person CSE using either patients or lesions as denominator, and; c) concordance of telediagnosis with CSE. RESULTS: 49 of 58 randomised participants completed the study, and submitted 309 lesions to the teledermatologist (156 intervention; 153 control group). Intervention group participants were more likely to submit lesions from their legs compared to control (p=0.03), no other differences between groups in number or site of missed lesions.11 participants (22%) did not photograph 14 pigmented lesions the dermatologist considered worthwhile photographing or requiring clinical monitoring. Sensitivity of SSE plus mobile teledermoscopy was 81.8% (95% confidence interval 64.5-93.0) using the patient as the denominator and 41.9 (27.6-56.2) using the lesion as denominator.-There was substantial agreement between telediagnosis and CSE (Kappa =0.90) accounting for differential diagnoses. CONCLUSIONS SSE plus mobile teledermoscopy is promising for surveillance of particular lesions even without provision of detailed SSE instructions, but in the format tested in this study, consumers may overlook lesions and send many non-pigmented lesions. This investigation demonstrates that high quality dermoscopic images can be taken by patients at home and for those sent, telediagnosis is highly accurate.

Patient group directions : the application and integration of knowledge in advancing nursing practice

Background: The introduction of Patient Group Directions (PGD) has changed significantly the way in which nurses can now administer prescription only medicines as a one-off for patients requiring this level of service. PGD’s are a written authority to administer drugs to patients that are not identified at the time of treatment. Aim: The aim of this project was to develop a PGD for use within an Outreach team to administer colloid boluses to patients presenting with hypovolemia. Method: Using a case exemplar this paper will discuss the development of a PGD using aspects of transitional change theory to highlight the potential barriers that were encountered. Implications for Practice: The implications for this PGD are wide reaching. First it now enables members from the nursing Outreach team to administer colloid fluid boluses to a prescribed patient cohort without the need for prescription. Second, it ensures the deteriorating patient has interventions initiated in a timely and appropriate manner to reduce inadvertent admission to high care areas. Last, it will improve inter-professional team-working and communication so much so that collaborative patient care reduces health costs and identifies earlier those patients requiring substantially greater nursing and medical input. Conclusion: The experience of developing a working PGD for fluid administration has meant that the Outreach team is able to respond to patients in a more effective way. In addition, it is the experience of developing this PGD that has enabled the team to contemplate other PGD’s in the execution of Outreach work.

Alarm setting for the critically ill patient : A descriptive pilot survey of nurses’ perceptions of current practice in an Australian Regional Critical Care Unit

Aim: The aim of this survey was to assess registered nurse’s perceptions of alarm setting and management in an Australian Regional Critical Care Unit. Background: The setting and management of alarms within the critical care environment is one of the key responsibilities of the nurse in this area. However, with up to 99% of alarms potentially being false-positives it is easy for the nurse to become desensitised or fatigued by incessant alarms; in some cases up to 400 per patient per day. Inadvertently ignoring, silencing or disabling alarms can have deleterious implications for the patient and nurse. Method: A total population sample of 48 nursing staff from a 13 bedded ICU/HDU/CCU within regional Australia were asked to participate. A 10 item open-ended and multiple choice questionnaire was distributed to determine their perceptions and attitudes of alarm setting and management within this clinical area. Results: Two key themes were identified from the open-ended questions: attitudes towards inappropriate alarm settings and annoyance at delayed responses to alarms. A significant number of respondents (93%) agreed that alarm fatigue can result in alarm desensitisation and the disabling of alarms, whilst 81% suggested the key factors are those associated with false-positive alarms and inappropriately set alarms.