Meal-induced 24-hour profile of circulating glycated insulin in type 2 diabetic subjects measured by a novel radioimmunoassay

Increasing evidence supports a role for glycated insulin in the insulin-resistant state of type 2 diabetes. We measured 24-hour profiles of plasma glycated insulin, using a novel radioimmunoassay (RIA), to evaluate the effects of meal stimulation and intermittent fasting on circulating concentrations of plasma glycated insulin in type 2 diabetes. Patients (n = 6; hemoglobin A(1c) [HbA(1c)], 7.2% +/- 0.6%; fasting plasma glucose, 7.4 +/- 0.7 mmol/L; body mass index [BMI], 35.7 +/- 3.5 kg/m(2); age, 56.3 +/- 4.4 years) were admitted for 24 hours and received a standardized meal regimen. Half-hourly venous samples were taken for plasma glycated insulin, glucose, insulin, and C-peptide concentrations between 8 Am and midnight and 2-hourly overnight. The mean plasma glycated insulin concentration over 24 hours was 27.8 +/- 1.2 pmol/L with a mean ratio of insulin:glycated insulin of 11:1. Circulating glucose, insulin, C-peptide, and glycated insulin followed a basal and meal-related pattern with most prominent increments following breakfast, lunch, and evening meal, respectively. The mean concentrations of glycated insulin during the morning, afternoon, evening, and night-time periods were 24.4 +/- 2.5, 28.7 +/- 2.3, 31.1 +/- 2.1, and 26.2 +/- 1.5 pmol/L, respectively, giving significantly higher molar ratios of insulin:glycated insulin of 18.0:1, 14.2:1, and 12.7:1 compared with 7.01 at night (P

Holding eternity in an hour: A practical exploration of the arts in the health care of older people with dementia

This project involved creative artists working with older people with dementia and staff from two Belfast Health and Social Care Trust supported housing centres in a mixed programme of dance, painting, music and drama which culminated in an open workshop with relatives and friends of the tenants. The study steered away from traditional medical models of art/music/dance therapy where the participant is perceived as a ‘patient’ in favour of identifying the participant as a ‘student’ who avails of a life-long learning experience. A key premise was that access to the arts is a human right, especially in the context of advancing age and cognitive impairment. . According to one the tenants of Mullan Mews, the project served to ‘awaken - or reawaken - folk with dementia to the endless vista of possibility already in their lives if they will only look for it’. A phenomenographic analysis of video data generated by the project emphasises the importance of the individual experiences of participants in the programme. The evidence from these storylines gained strength from the development of a documentary-style film text that has proved successful in capturing and translating the live experience of the project participants into a supportive text that goes beyond the written word.

Happy hour followed by hangover: financing the UK brewery industry, 1880-1913

In the last 15 years of the nineteenth century c.300 British brewers incorporated and floated securities on the stock market. Subsequently, in the 1900s, the industry suffered a long-lived hangover. In this paper, we establish the stylised facts of this transformation and estimate the gains enjoyed by brewery investors during the boom as well as the losses suffered by investors during the bust of the 1900s. However, not all brewery equity shares suffered alike. We find that post-1900 performance correlates positively with capital-market discipline and good corporate governance and negatively with family control, but does not correlate with indebtedness.

Beyond work-hour restrictions: a qualitative study of residents' subjective workload

INTRODUCTION: Following the introduction of work-hour restrictions, residents' workload has become an important theme in postgraduate training. The efficacy of restrictions on workload, however, remains controversial, as most research has only examined objective workload. The purpose of this study was to explore the less clearly understood component of subjective workload and, in particular, the factors that influenced residents' subjective workload.

METHOD: This study was conducted in Japan at three community teaching hospitals. We recruited a convenience sample of 31 junior residents in seven focus groups at the three sites. Audio-recorded and transcribed data were read iteratively and analyzed thematically, identifying, analyzing and reporting themes within the data and developing an interpretive synthesis of the topic.

RESULTS: Seven factors influenced residents' subjective workload: (1) interaction within the professional community, (2) feedback from patients, (3) being in control, (4) professional development, (5) private life, (6) interest and (7) protected free time.

DISCUSSION AND CONCLUSION: Our findings indicate that residents who have good interaction with colleagues and patients, are competent enough to control their work, experience personal development through working, have greater interest in their work, and have fulfilling private lives will have the least subjective workload.

Predictors of therapy resistant asthma: outcome of a systematic evaluation protocol

Background: It has been suggested that asthmatic subjects with persisting symptoms despite adequate maintenance therapy should be systematically evaluated to identify factors contributing to poor control. The aims of this study were to examine the prevalence of these factors in a cohort of sequentially referred poorly controlled asthmatics, and to determine if any factor or combination of factors predicted true therapy resistant asthma (TRA).

Methods: Patients were evaluated using a systematic evaluation protocol including induced sputum analysis, psychiatric assessment, ear, nose and throat examination, pulmonary function testing, high resolution CT scan of the thorax, and 24 hour dual probe ambulatory oesophageal pH monitoring; any identified provoking factor was treated. Asthma was managed according to BTS guidelines.

Results: Of 73 subjects who completed the assessment, 39 responded to intervention and 34 had TRA. Subjects with TRA had a greater period of instability, a higher dose of inhaled steroids at referral, more rescue steroid use, and a lower best percentage forced expiratory volume in 1 second (FEV1%). Oesophageal reflux, upper airway disease, and psychiatric morbidity were common (57%, 95%, 49%, respectively) but were not more prevalent in either group. Using multivariate logistic regression analysis, inhaled steroid dose >2000 µg BDP, previous assessment by a respiratory specialist, and initial FEV1% of <70% at referral predicted a final diagnosis of TRA.

Conclusions: In poorly controlled asthmatics there is a high prevalence of co-morbidity, identified by detailed systematic assessment, but no difference in prevalence between those who respond to intervention and those with TRA. Targeted treatment of identified co-morbidities has minimal impact on asthma related quality of life in those with therapy resistant disease.

What is a reasonable time from decision to delivery by Caesarean section? Evidence from 533 deliveries.

Objective To determine how long it takes from the decision to achieve delivery by non-elective caesarean section (DDI), the influence on this interval, and the impact on neonatal condition at birth. Design Twelve months prospective data collection on all non-elective caesarean sections. Methods Prospective collection of data relating to all caesarean sections in 1996 in a major teaching hospital obstetric unit was conducted, without the knowledge of the other clinicians providing clinical care. Details of the indication for section, the day and time of the decision and the interval till delivery were recorded as well as the seniority of the surgeon, and condition of the baby at birth. Results The mean time from decision-to-delivery for 100 emergency intrapartum caesarean sections was 42.9 minutes for fetal distress and 71.1 minutes for 230 without fetal distress (P<0.0001). For 22 'crash' sections the mean time from decision-to-delivery was 27.4 minutes; for 13 urgent antepartum deliveries for fetal reasons it was 124.7 minutes and for 21 with maternal reasons it was 97.4 minutes. The seniority of the surgeon managing the patient did not appear to influence the interval, nor did the time of day or day of the week when the delivery occurred. Intrapartum sections were quicker the more advanced the labour, and general anaesthesia was associated with shorter intervals than regional anaesthesia for emergency caesarean section for fetal distress (P<0.001). Babies born within one hour of the decision tended to be more acidaemic than those born later, irrespective of the indication for delivery. Babies tended to be in better condition when a time from decision-to-delivery was not recorded than those for whom the information had been recorded. Conclusion Fewer than 40% intrapartum deliveries by caesarean section for fetal distress were achieved within 30 minutes of the decision, despite that being the unit standard. There was, however, no evidence to indicate that overall an interval up to 120 minutes was detrimental to the neonate unless the delivery was a 'crash' caesarean section. These data thus do not provide evidence to sustain the recommendation of a standard of 30 minutes for intrapartum delivery by caesarean section.

Upregulation of adrenomedullin and its receptor components during cardiomyocyte hypertrophy induced by chronic inhibition of nitric oxide synthesis in rats

Adrenomedullin may provide a compensatory mechanism to attenuate left ventricular hypertrophy (LVH). Nitric oxide synthase inhibition, induced by chronic administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats, induces cardiac hypertrophy in some, but not all cases; there are few reports of direct assessment of cardiomyocyte parameters. The objective was to characterize hypertrophic parameters in left (LV) and right ventricular (RV) cardiomyocytes after administration of L-NAME to rats for 8 wk and to determine whether adrenomedullin and its receptor components were upregulated. After treatment with L-NAME (20 and 50 mg x kg(-1) x day(-1)), compared with nontreated animals, 1) systolic blood pressure increased (by 34.2 and 104.9 mmHg), 2) heart weight-to-body wt ratio increased 24.1% at the higher dose (P

Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

OBJECTIVE: To investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar-arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

Experiencing Kane: an affective analysis of Sarah Kane's 'experiential' theatre in performance

The article argues for a phenomenological approach to Kane's work in performance. It notes the rise in productions of Kane's work from 2004, and focuses on productions of Crave by 11th Hour Theatre in Melbourne and Acquiesce Speck in Sydney.