Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3) GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-diabetes.

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. Young adult ob/ob mice received once-daily intraperitoneal injections of saline vehicle or (Pro3)GIP over an 11-day period. Nonfasting plasma glucose levels and the overall glycemic excursion (area under the curve) to a glucose load were significantly reduced (1.6-fold; P <0.05) in (Pro3)GIP-treated mice compared with controls. GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P <0.05) and insulin (1.5-fold; P <0.05) responses to feeding. These changes were associated with significantly enhanced (1.6-fold; P <0.05) insulin sensitivity in the (Pro3)GIP-treated group. Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P <0.05) and partially corrected the obesity-related islet hypertrophy and ß-cell hyperplasia of ob/ob mice. These comprehensive beneficial effects of (Pro3)GIP were reversed 9 days after cessation of treatment and were independent of food intake and body weight, which were unchanged. These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes.

Decision making in childhood asthma exacerbation – a clinical judgement analysis

Background: Clinical decisions which impact directly on patient safety and quality of care are made during acute asthma attacks by individual doctors on the basis of their knowledge and experience. These include administration of systemic corticosteroids (CS), oral antibiotics, and admission to hospital. Clinical judgement analysis provides a methodology for comparing decisions between practitioners with different training and experience, and improving decision making. Methods: Stepwise linear regression was used to select clinical cues based on visual analogue scale assessments of the propensity of 62 clinicians to prescribe a short course of oral CS (decision 1), a course of antibiotics (decision 2), and/or admit to hospital (decision 3) for 60 â??paperâ?? patients. Results:When compared by specialty, paediatriciansâ?? models for decision 1 were more likely to include as a cue level of alertness (54% v. 16%); for decision 2 presence of crepitations (49% v. 16%), and less likely to include inhaled CS (8% v. 40%), respiratory rate (0% v. 24%), and air entry (70% v. 100%). When compared to other grades, the models derived for decision 3 by consultants/general practitioners were more likely to include wheeze severity as a cue (39% v. 6%). Conclusions: Clinicians differed in their use of individual cues and the number included in their models. Patient safety and quality of care will benefit from clarification of decision making strategies as general learning points during medical training, in the development of guidelines and care pathways, and by clinicians developing self-awareness of their own preferences.

Implementing a resuscitation policy for patients at the end of life in an acute hospital setting: qualitative study

Objective : To explore attitudes and experiences of doctors and nurses regarding cardiopulmonary resuscitation for patients with end stage illness in an acute hospital. Design : Qualitative study; thematic analysis of two audio-taped focus groups and four semi-structured interviews. Setting : Acute district hospital, Northern Ireland. Participants : Seven nurses and nine doctors; varying nationality, gender and years of professional experience; involved in cardiopulmonary resuscitation decision-making. Results : Participants reported different interpretations of resuscitation policy and of what do not attempt to resuscitate (DNAR) decisions meant in relation to practical care for patients. This confusion in translating policy into practice contributed to communication difficulties in initiating, documenting and implementing cardiopulmonary resuscitation decisions. Participants were aware of how clinical conditions could change and reported uncertainty in determining end stage illness; they expressed fears of potential consequences of DNAR decisions for patients' care. The more disease-centred approach of doctors to patients' management, compared to nurses' more patient-centred approach, contributed to inter-professional conflict within teams. Doctors identified training needs in applying resuscitation policy and ethical principles in `real life' and nurses identified a need for ongoing professional support, which was perceived as being less available to junior doctors. Personal relationships between staff and patients, cultural reluctance to address sensitive issues and local community expectations of relatives being involved in decisions added to policy implementation difficulties. Conclusions : The findings indicate a need for ongoing staff support and training in applying resuscitation policy to decisions for patients with end stage illness in an acute hospital. They support suggestions that reviews of local resuscitation policy and of national guidelines should be undertaken with openness and honesty regarding the goals, opportunities and difficulties involved in trying to deliver good end of life care in local settings. Palliative Medicine 2007; 21 : 305—312 Key Words: do not attempt resuscitation (DNAR) • end stage illness • inter-professional • policy • resuscitation decisions

Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation

Background. Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors. Methods. Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems. Results. Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb) <12 g/dl, females Hb <11g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 µmol/l vs 131.0 µmol/l, P <0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P <0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8, P = 0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R = -0.29, P <0.001), but not between EPO levels and eGFR (R = 0.02, P = 0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis. Conclusion. Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia. © The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.