Defibrillation and external pacing in flight: incidence and implications.

INTRODUCTION: Emergency electrical intervention for patients in the form of defibrillation, cardioversion and external cardiac pacing can be life saving. Advances in medical technology have enabled electrical intervention to be delivered from small, portable devices. With the rising use of air transport for patients, electrical intervention during aeromedical transfer has an increasing incidence. Our aim was to describe the incidence of electrical intervention in a cohort of critically ill patients undergoing aeromedical transfer and review the risks associated with electrical intervention. METHODS: All secondary retrievals undertaken by a national aeromedical critical care retrieval service were reviewed over a 48-month period. RESULTS: In a mixed medical and trauma critical care population, 11 of 967 (1.1%) secondary retrievals required electrical intervention during aeromedical critical care retrieval. The median age of these patients was 77 years (range 32-86) and the median transport time was 70 min (range 40-100 min). All of these patients had an underlying primary cardiac condition and had been identified as high risk for developing an arrhythmia. CONCLUSIONS: Electrical intervention in a transport environment brings unique challenges, particularly during aeromedical transport. Our study in a European model shows that there is a small but significant incidence of electrical intervention required during aeromedical flight for critically ill patients. There are potential safety issues with electrical intervention in aeromedical flight; therefore, any service involved in the transport of critically ill patients needs to have a robust procedure in place to deliver this safely.

Trientine and renin-angiotensin system blockade ameliorate progression of glomerular morphology in hypertensive experimental diabetic nephropathy.

A comparison of the efficacy of the copper chelator, trientine, with combined renin angiotensin system (RAS) blockade on the progression of glomerular pathology in the diabetic (mREN-2)27 rat is reported. Animals were treated for 2 months with trientine, combined RAS blockers, combined trientine plus RAS blockers or none. Treatments began after inducing diabetes with streptozotocin. Physiological data were recorded monthly and light microscopic glomerular features were scored. Plasma allantoin and both plasma and renal protein carbonyls were measured as markers of oxidative stress. Trientine and RAS blockade decreased proteinuria and albuminuria and prevented an increase in creatinine clearance and kidney weight. Both reduced the diabetes-related glomerular features of mesangiolysis and glomerular segmental hypocellularity and trientine prevented severe tuft-to-capsule adhesion and reduced tubularization. Hypertension-related severe mesangial matrix expansion and global hypercellularity were increased by both treatments, which may reflect repair of mesangiolysis. Trientine reduced plasma but not renal protein carbonyls or plasma allantoin. In this model, trientine prevented the development of many diabetes-specific features similarly to RAS blockade. Amelioration of oxidative stress and features commonly observed in human diabetic nephropathy (DN), support a diabetes-related defect in copper (Cu) metabolism. The addition of Cu(II) chelation may improve current DN therapy.

Deliberate overdose with Epsom salts.

Epsom salts contains the active compound magnesium sulfate and is used most commonly as a laxative. There are potential serious toxic effects, including cardiac arrest, when the serum concentration rises above therapeutic values. We present a case of deliberate self poisoning with a large quantity of Epsom salts, resulting in a toxic serum magnesium concentration of 9.7 mmol/l (0.70-1.0 mmol/l). Clinical features included limb weakness, vomiting and confusion, with a subsequent rapid deterioration in level of consciousness and bradydysrhythmia. There was no significant response to calcium gluconate, so haemodialysis was urgently arranged. The patient made a full recovery. Hypermagnesaemia is unusual in patients with normal renal function. Although clinical severity does not always correlate with serum magnesium values, risk of cardiac arrest occurs with concentrations >6 mmol/l. Initial treatment is supportive. Dialysis should be considered when life threatening features or renal impairment are present.

Impact of a combined resistance and aerobic exercise program on motivational variables in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Short term exercise interventions have been shown to be beneficial for breast cancer survivors soon after treatments but longer term adherence is needed. PURPOSE: To examine the effects of a supervised exercise program on motivational variables in breast cancer survivors using Self-Determination Theory (SDT). METHOD: Sixty breast cancer survivors were randomized in a cross-over design to either an immediate exercise group (IEG; n = 30) that exercised from baseline to week 12 or a delayed exercise group (DEG; n = 30) that exercised from week 12 to 24. SDT variables were assessed at baseline, 6, 12, 18 and 24 weeks using the Behavioral Regulation for Exercise Questionniare-2 and the Basic Psychological Needs Satisfaction Scale. RESULTS: Fifty-eight participants completed the follow-up assessments and achieved a 61.3% adherence rate. Analyses of variance revealed significant time by group interactions for almost all psychological needs and motivations that favored the exercise intervention time periods. For example, autonomy increased in the IEG from baseline to 12 weeks by 2.0 points compared to the DEG where scores decreased by 0.1 points (mean group difference = 2.0, p < 0.001). The cross-over results further supported the main findings. CONCLUSION: Supervised exercise soon after breast cancer treatments may help to develop a positive exercise motivational profile among breast cancer survivors that could portend longer term adherence.

Self-determination theory and physical activity among breast cancer survivors.

The study aim was to examine constructs of autonomy support and competence as well as the motivation continuum from the self-determination theory (SDT) as a framework for understanding physical activity (PA) motivation and behavior in breast cancer survivors. Questionnaires assessing demographics, medical factors, PA, motivation continuum, perceived autonomy support, and competence were completed by 558 breast cancer survivors. Results showed that lymphedema (chi2 = 7.9, p < .01) (chi2 = 4.6, p < .05) were associated with meeting PA guidelines. Moreover, survivors meeting PA guidelines reported more identified regulations and intrinsic motivation (p < .01), autonomy support (p < .01), and competence (p < .01). Forced entry hierarchical regression analysis showed that SDT constructs explained 20.2% (p < .01) of the PA variance. Significant independent SDT predictors included identified regulation (Beta = .14, p < .05) and competence (Beta = .23, p < .01), with autonomy support approaching significance (Beta = .9, p = .057). SDT may be a useful model for understanding PA motivation and behavior in breast cancer survivors.

Effects of a combined aerobic and resistance exercise program in breast cancer survivors: a randomized controlled trial.

Few randomized controlled trials have examined the effects of combined aerobic and resistance training in breast cancer survivors soon after completing adjuvant therapy. Breast cancer survivors (N=58) within 2 years of completing adjuvant therapy were randomly assigned to an immediate exercise group (IEG; n=29) or a delayed exercise group (DEG; n=29). The IEG completed 12 weeks of supervised aerobic and resistance exercise, three times per week. The DEG completed the program during the next 12 weeks. Participants completed patient-rated outcomes at baseline, 6, 12, 18 and 24 weeks. The primary endpoint was overall quality of life (QoL) measured by the Functional Assessment of Cancer Therapy-Breast scale. Secondary endpoints were fatigue, social physique anxiety, and physical fitness. Follow-up data was obtained on 97% of participants and exercise adherence was 61.3%. Repeated measures analyses of variance revealed a significant group by time interaction for overall QoL (P<0.001). Specifically, QoL increased in the IEG from baseline to 12 weeks by 20.8 points compared to a decrease in the DEG of 5.3 points (mean group difference=26.1; 95% CI=18.3-32.7; P<0.001). From 12 to 24 weeks, QoL increased in the DEG by 29.5 points compared to an increase of 6.5 points in the IEG (mean group difference=23.0; 95% CI=16.3-29.1; P<0.001). Similar results were obtained for the secondary endpoints. Combined aerobic and resistance exercise soon after the completion of breast cancer therapy produces large and rapid improvements in health-related outcomes.

Personal accounts of exercise and quality of life from the perspective of breast cancer survivors.

OBJECTIVES: The purpose of the study was to examine breast cancer survivors' perceptions of exercise and their quality of life (QoL). METHODS: About 289 breast cancer survivors completed a survey addressing exercise attitudes, behaviour and perceived QoL. In addition, the breast cancer survivors completed two open-ended questions designed to explore perceptions of exercise and QoL throughout their cancer experience. Inductive and deductive content analyses were used to analyse responses. RESULTS: About 19 first-order themes were identified, which were clustered into five second-order themes that included; Exercise behaviour, Lifestyle, Limitations and barriers, Growth and priorities, and Personal beliefs and values. The findings identified a framework of multifaceted views held by breast cancer survivors in relation to their QoL and outlook on their disease. CONCLUSIONS: Given that cancer survivors are faced with a number of treatment related morbidities 2 years post-diagnosis, there is a need for health professionals to carefully address a cancer survivor's exercise needs in an attempt to help improve their future QoL.

Hypotension and ST depression as a result of disulfiram ethanol reaction.

A case report of a 27-year-old man who developed significant hypotension and ischaemic ECG changes as a result of a disulfiram ethanol reaction. He was treated with intravenous fluids and norepinephrine, which has been advocated as the pressor agent of choice. This case highlights the potential dangers of disulfiram, a drug that can be beneficial in the short term, but not proven to improve long-term outcome in the treatment of alcoholism.

Association between physical activity and quality of life among Western Australian breast cancer survivors.

Previous research has shown that physical activity (PA) may be beneficial to quality of life (QoL) in breast cancer survivors. Few studies however, have focused on the time period soon after the completion of adjuvant therapy or examined exercise issues separately for rural/urban or healthy weight/obese breast cancer survivors. Our study addressed these issues. Breast cancer survivors (N = 558) from the Western Australia Cancer Registry completed a survey that included the Godin Leisure Time Exercise Questionnaire (GLTEQ) and the Functional Assessment of Cancer Therapy-Breast (FACT-B) scale. Results showed that only 31% of breast cancer survivors were meeting the recommended PA guidelines post-treatment. Analysis of variance revealed that survivors meeting these guidelines reported higher scores on the FACT-B (mean difference 8.6; 95% CI = 5.0-12.1; p<0.001), the FACT-General (mean difference 6.3; 95% CI = 3.5-9.0; p<0.001), the trial outcome index (TOI; p<0.001), and several of the FACT-B subscales. Furthermore, healthy weight participants also reported higher scores than obese participants on the FACT-B (p = 0.058) and the breast cancer subscale (p = 0.033). There were no differences based on geographic location. We conclude that physically active and healthy weight breast cancer survivors report better QoL than their inactive and obese counterparts soon after completing adjuvant therapy.

An unusual cause of constipation presenting to the emergency department.

A case report of a 16-year-old girl who presented to the emergency department with constipation and recurrent urinary tract infections is examined. She gave a history of persistent coccygeal pain stemming from a fall on a trampoline 1 year ago. On examination, she was found to have an abdominal mass arising from the pelvis and paraesthesia of S1-S5 dermatomes in the right leg. An abdominal radiograph showed bony erosion of the sacrum. Magnetic resonance scanning revealed a mass arising from the sacrum and subsequent biopsy diagnosed the tumour as Ewing's sarcoma.

Generation of insulin-expressing cells from mouse embryonic stem cells.

The therapeutic potential of transplantation of insulin-secreting pancreatic beta-cells has stimulated interest in using pluripotent embryonic stem (ES) cells as a starting material from which to generate insulin secreting cells in vitro. Mature beta-cells are endodermal in origin so most reported differentiation protocols rely on the identification of endoderm-specific markers. However, endoderm development is an early event in embryogenesis that produces cells destined for the gut and associated organs in the embryo, and for the development of extra-embryonic structures such as the yolk sac. We have demonstrated that mouse ES cells readily differentiate into extra-embryonic endoderm in vitro, and that these cell populations express the insulin gene and other functional elements associated with beta-cells. We suggest that the insulin-expressing cells generated in this and other studies are not authentic pancreatic beta-cells, but may be of extra-embryonic endodermal origin.

The in vitro differentiation of rat neural stem cells into an insulin-expressing phenotype.

Mature beta-cells and nerve cells share many functional similarities despite originating from different embryonic germ layers. The aim of this study was to investigate the potential of neural stem cells (NSCs), isolated from foetal rat brain, as a starting material from which to generate functionally responsive, insulin-containing cells. Our results demonstrated that NSCs can be significantly expanded in vitro and can be induced to express increased preproinsulin mRNA levels. In addition, these NSC-derived cells expressed transcriptional and functional elements associated with a mature beta-cell phenotype. The differentiated cells showed functional responses typical of pancreatic beta-cells, including glucose-dependent increases in metabolism and rapid elevations in intracellular Ca(2+) in response to the sulphonylurea tolbutamide or to increased glucose concentration. These results suggest that NSCs may have potential as a starting material from which to generate beta-cell surrogates for the treatment of patients with Type 1 diabetes mellitus.

Uncoupling of nutrient metabolism from insulin secretion by overexpression of cytosolic phospholipase A(2).

We have generated MIN6 beta-cells that stably overexpress cytosolic phospholipase A(2) (cPLA(2)) and show a ninefold increase in cPLA(2) activity. Overexpression of cPLA(2) did not affect the capacity of MIN6 cells to show elevations in intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to tolbutamide and KCl, and these depolarizing stimuli produced insulin secretion profiles in cPLA(2)-overexpressing cells similar to those they produced in passage-matched nontransfected MIN6 cells. However, cPLA(2)-overexpressing MIN6 cells did not respond to elevations in extracellular glucose with increases in ATP, [Ca(2+)](i), or insulin secretion. Nontransfected MIN6 cells showed a rapid and sustained increase in NAD(P)H autofluorescence in response to 25 mmol/l glucose, and this was reduced by approximately 95% in MIN6 cells overexpressing cPLA(2). This effect was mimicked in nontransfected MIN6 cells by p-(trifluoromethoxy) phenylylhydrazone, a mitochondrial uncoupler. Quantitative RT-PCR indicated that mRNA for uncoupling protein-2 (UCP-2) was increased in the cPLA(2)-overexpressing MIN6 cells, and this could be prevented by exposure to 100 mumol/l methyl arachidonyl fluorophosphate, a cPLA(2) inhibitor. Glucose caused a decrease in rhodamine 123 fluorescence in control cells, but not in those overexpressing cPLA(2), consistent with the transfected cells being unable to maintain mitochondrial proton gradients as a consequence of UCP-2 upregulation. Our data indicate that overexpression of cPLA(2) results in severe impairment of the calcium and secretory responses of beta-cells to glucose through upregulation of UCP-2 and uncoupling of mitochondrial metabolism from ATP generation.

The reproducibility of closed-pouch sweat collection and thermoregulatory responses to exercise-heat stress.

Seven active male subjects cycled for 60 min at 29.5 (0.8)% peak work rate on three separate occasions in a hot environmental condition [36.0 (0.1) degrees C, 60 (1)% relative humidity] in order to determine the reproducibility of a closed-pouch sweat collection technique for sweat composition at the scapula, forearm and thigh. To confirm that sweat composition was not influenced by between-trial variations in sudomotor drive, local sweat rate, whole-body sweat rate, heart rate (HR), rectal temperature (T(re)) and mean skin temperature (T(sk)) responses were also measured, consequently reproducibility was also established for these variables. Sweat composition did not differ among trials, with the mean coefficients of variation (CVs) for sweat [Na(+)], [K(+)] and pH being 10.4 (7.4)%, 8.1 (6.5)% and 1.3 (1.1)%, respectively. Local sweat rates did not differ among the three trials (P>0.05) although whole-body sweat rate was reduced in the third trial (P<0.05). The mean CVs were 11.0 (7.8)% and 4.7 (1.6)% for local and whole-body sweat rates, respectively. Between-trial differences were not evident for T(re), T(sk) or HR with mean CVs of 0.3 (0.2)%, 0.7 (0.6)% and 3.9 (1.7)%, respectively, although HR tended to be greater in the first trial ( P=0.08). It is proposed that moderate variations in sweat composition were influenced by variations in the local sweat rate, which were induced by application of the pouch.

The role of cytosolic phospholipase A(2) in insulin secretion.

Cytosolic phospholipase A(2) (cPLA(2)) comprises a widely expressed family of enzymes, some members of which have the properties required of signal transduction elements in electrically excitable cells. Thus, alpha- and beta-isoforms of cPLA(2) are activated by the increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) achieved in depolarized cells. Activation is associated with a redistribution of the enzyme within the cell; activation of cPLA(2) generates arachidonic acid (AA), a biologically active unsaturated fatty acid that can be further metabolized to generate a plethora of biologically active molecules. Studies using relatively nonselective pharmacological inhibitors have implicated cPLA(2) in insulin secretory responses to stimuli that elevate beta-cell [Ca(2+)](i); therefore, we have investigated the role of cPLA(2) in beta-cell function by generating beta-cell lines that under- or overexpress the alpha-isoform of cPLA(2). The functional phenotype of the modified cells was assessed by observation of cellular ultrastructure, by measuring insulin gene expression and insulin protein content, and by measuring the effects of insulin secretagogues on cPLA(2) distribution, on changes in [Ca(2+)](i), and on the rate and pattern of insulin secretion. Our results suggest that cPLA(2) is not required for the initiation of insulin secretion from beta-cells, but that it plays an important role in the maintenance of beta-cell insulin stores. Our data also demonstrate that excessive production of, or exposure to, AA is deleterious to normal beta-cell secretory function through metabolic dysfunction.

Differential expression of insulin genes 1 and 2 in MIN6 cells and pseudoislets.

There is some evidence that the two rodent insulin genes are differentially regulated in mice, although there is no satisfactory consensus on the relative levels and patterns of expression for the two genes. Using the mouse insulinoma cell line MIN6, we have demonstrated by quantitative RT-PCR, differential patterns of expression for the two genes. In mouse islets and early passage MIN6 cells, expression of ins 1 and ins 2 were found to be approximately equal, but levels of ins 1 mRNA diminished rapidly with continued passage. Furthermore, the ins 1 gene was found to be up-regulated in response to glucose stimulation and as a result of increased cell-cell contact, but no effect on the ins 2 gene was observed. Since the MIN6 cell line is frequently used as a beta-cell model for gene expression studies, consideration should be given to both insulin genes.

A key role for beta-cell cytosolic phospholipase A(2) in the maintenance of insulin stores but not in the initiation of insulin secretion.

Cytosolic phospholipase A(2) (cPLA(2)) is a Ca(2+)-sensitive enzyme that has been implicated in insulin secretion in response to agents that elevate beta-cell intracellular Ca(2+) ([Ca(2+)](i)). We generated clones of the MIN6 beta-cell line that stably underexpress cPLA(2) by transfection with a vector in which cPLA(2) cDNA had been inserted in the antisense orientation. Reduced expression of cPLA(2) was confirmed by Western blotting. The insulin content of cPLA(2)-deficient MIN6 cells was reduced by approximately 90%, but they showed no decrease in preproinsulin mRNA expression. Measurements of stimulus-dependent changes in [Ca(2+)](i) indicated that reduced expression of cPLA(2) did not affect the capacity of MIN6 cells to show elevations in Ca(2+) in response to depolarizing stimuli. Perifusion experiments indicated that cPLA(2) underexpressing MIN6 pseudoislets responded to glucose, tolbutamide, and KCl with insulin secretory profiles similar to those of cPLA(2) expressing pseudoislets, but that secretion was not maintained with continued stimulus. Analysis of the ultrastructure of cPLA(2)-deficient MIN6 cells by electron microscopy revealed that they contained very few mature insulin secretory granules, but there was an abundance of non-electron-dense vesicles. These data are consistent with a role for cPLA(2) in the maintenance of insulin stores, but they suggest that it is not required for the initiation of insulin secretion from beta-cells.