Search

Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown previously that insulin receptor substrate 2 (IRS2), a molecule highly critical to insulin resistance and metabolism, has an anti-inflammatory role in Th2-skewed lung inflammation and pulmonary vascular remodeling. Here, we investigated the hypothesis that IRS2 has an immunomodulatory role in human and experimental PH. Expression analysis showed that IRS2 was significantly decreased in the pulmonary vasculature of patients with pulmonary arterial hypertension and in rat models of PH. In mice, genetic ablation of IRS2 enhanced the hypoxia-induced signaling pathway of Akt and Forkhead box O1 (FOXO1) in the lung tissue and increased pulmonary vascular muscularization, proliferation, and perivascular macrophage recruitment. Furthermore, mice with homozygous IRS2 gene deletion showed a significant gene dosage-dependent increase in pulmonary vascular remodeling and right ventricular hypertrophy in response to hypoxia. Functional studies with bone marrow-derived macrophages isolated from homozygous IRS2 gene-deleted mice showed that hypoxia exposure led to enhancement of the Akt and ERK signaling pathway followed by increases in the pro-PH macrophage activation markers, vascular endothelial growth factor-A and arginase 1. Our data suggest that IRS2 contributes to anti-inflammatory effects by regulating macrophage activation and recruitment, which may limit the vascular inflammation, remodeling, and right ventricular hypertrophy that are seen in PH pathology. Restoring the IRS2 pathway may be an effective therapeutic approach for the treatment of PH and right heart failure.

Summary Omega-3 fatty acids play an important role in various aspects of human health, but many people do not consume them in sufficient quantities, resulting in deficiencies in some populations. The enrichment of commonly consumed foods with omega-3 fatty acids has been proposed to address this deficit. Feeding omega-3–rich ingredients to animals can enrich their products, increasing the consumption by the population without requiring any major dietary changes. Eggs can be enriched to a high degree, and currently, omega-3–enriched eggs are widely available. Oftentimes, a missed opportunity for the poultry industry is in valorizing the spent hen. In this short-term study, a docosahexaenoic acid (DHA)–rich protist was fed to layer hens at three different inclusion levels to determine the degree of enrichment observed in the eggs and concomitantly in the breast, thigh, liver, and kidney. The addition of the protist ingredient had no negative impact on the bird health or performance. Significant increases in egg DHA concentration were observed, with 60, 164, 259, and 410 mg DHA/100g of egg collected from birds supplemented with the DHA-rich protist at a rate of 0, 0.5, 1, and 2.5% of the diet, respectively. This enrichment could increase the value of spent hen meat when used in the production of human and companion animal food as DHA-enriched products can be sold for a premium. Moreover, this enriched spent hen meat could potentially be used as a partial substitute for less-sustainable sources of dietary omega-3 including fish meal and fish oil.

All UK H&I laboratories and transplant units operate under a single national kidney offering policy, but there have been variations in approach regarding when to undertake the pre-transplant crossmatch test. In order to minimize cold ischaemia times for deceased donor kidney transplantation we sought to find ways to be able to report a crossmatch result as early as possible in the donation process. A panel of experts in transplant surgery, nephrology, specialist nursing in organ donation and H&I (all relevant UK laboratories represented) assessed evidence and opinion concerning five factors that relate to the effectiveness of the crossmatch process, as follows: when the result should be ready for reporting; what level of donor HLA typing is needed; crossmatch sample type and availability; fairness and equity; risks and patient safety. Guidelines aimed at improving practice based on these issues are presented, and we expect that following these will allow H&I laboratories to contribute to reducing CIT in deceased donor kidney transplantation.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Service Executive Health and Wellbeing, Saolta University Healthcare Group OnBehalf Croí the West of Ireland Cardiac Foundation, Galway, Ireland and the National Institute for Prevention and Cardiovascular Health Introduction People living with obesity are at an increased risk of cardiovascular disease (CVD). While development of obesity is multifactorial, lifestyle modification is fundamental to obesity treatment and risk factor reduction. We sought to measure the effects of a structured lifestyle modification programme on the physical and mental health of people living with obesity. Purpose This study investigated the impact of a 10-week, community based, lifestyle modification programme on CVD risk factors in people living with obesity (BMI ≥35kg/m2 with a co-morbidity or BMI ≥40kg/m2) who were referred from a specialist bariatric service. Methods Delivered by an interdisciplinary team (Nurse, Dietitian & Physiotherapist) the programme included weekly group-based exercise sessions and health promotion workshops. A wide range of topics were addressed in workshops, including nutrition, food labels, emotional eating, physical activity, sedentary behaviour, stress management and CVD risk factor reduction. Outcomes were measured at initial and end of programme assessments. Results 1122 people participated in the intervention between 2013 and 2019 with 78% (n = 877) completing the programme. At initial assessment 26.7% of participants had a diagnosis of type 2 diabetes; 37.3% were at high or very high risk of CVD; 44.7% were hypertensive and 31.4% had a history of depression. Mean BMI was 47.0kg/m2 with 56.4% of participants having a BMI >45kg/m2. The intervention had significant positive impacts on key outcomes such as psychosocial health, lipid profiles, blood pressure, adiposity and cardiovascular fitness. One of the most significant outcomes observed was the improvement in psycho-social health. Scores of anxiety and depression, assessed using the HADS, decreased by 1.5 and 2.2 points respectively (p 3% of initial bodyweight. The percentage of participants achieving the recommended physical activity guidelines increased by 31% (p Conclusions A lifestyle modification programme delivered by an interdisciplinary team, aimed at individuals living with obesity, is not only acceptable to participants but also significantly reduces CVD risk factors. These findings should influence the design of future programmes and healthcare policies in Ireland and abroad.

Background With the prevalence of coronary heart disease increasing globally it is imperative that we explore alternative methods of delivering cardiac rehabilitation (CR) to improve patient outcomes in accordance with national and international CR guidelines. This study examines the feasibility and effectiveness of delivering a community based CR programme on medical and lifestyle risk factor management in the west of Ireland. Methods Patients with coronary heart disease; meeting the inclusion criteria for referral to CR were invited to attend a 12- week CR programme consisting of a professional multi-disciplinary (nurse, dietitian, physiotherapist) lifestyle intervention, with appropriate risk factor and therapeutic management delivered within a community setting. Risk factors such as blood pressure, lipids, smoking, BMI (body mass index), waist circumference and estimated MET max were assessed at baseline and end of programme (EOP). Results 255 patients enrolled in the CR programme. Mean age of the participants was 66.6 yrs, 72.9% were male and 35.4% had previous cardiac history. The programme adopted an integrated approach to care and in addition to cardiac patients it included a cohort of Stroke (17%) and Peripheral Vascular Disease (PVD) (4%) patients. Outcome data on 196 patients who completed the 12 week programme were analysed (table 1). Conclusions Data from this multi-component comprehensive community based CR programme suggest that the management of CR patients can be successfully integrated and delivered within a community setting by a specialist multi-disciplinary team (MDT). This study has demonstrated improvements in patient outcomes across biomedical, anthropometric and lifestyle risk factors. Benefits were also noted in the psychosocial health and wellbeing of the participants including improvements in quality of life (QoL) measures.

Minimally invasive thoracic surgery has improved outcomes, including reduced length of postoperative admission, reduced postoperative pain, shorter postoperative stay, reduced wound complications, reduced blood loss, improved cosmesis, and improved equivalent oncological outcomes compared to traditional thoracotomy. Robotic thoracic surgery (RTS) is an improvement on video-assisted thoracoscopic surgery in that it allows the surgeon a greater degree of freedom with instrument movement and better surgical field visualization. Thoracic insufflation and one-lung ventilation both significantly alter and compromise the patient’s baseline cardiopulmonary physiology. Due to this, adequate preoperative workup, deftness at double-lumen endotracheal tube management, and advanced understanding of how RTS affects cardiopulmonary physiology are essential.

Five female and four male guinea pigs, 2.0 ± 0.5 months of age and weighing 702 ± 72 g, were used in a crossover design to compare sedative and anesthetic effects of IM injection (INJ) of tiletamine-zolazepam (10 mg kg−1) – ketamine (4 mg kg−1) – xylazine (5 mg kg−1) – butorphanol (0.1 mg kg−1) (TKXB-H), tiletamine-zolazepam (5 mg kg−1) – ketamine (2 mg kg−1) – xylazine (2.5 mg kg−1) – butorphanol (0.05 mg kg−1) (TKXB-L), and medetomidine (0.5 mg kg−1) – ketamine (20 mg kg−1) – butorphanol (0.2 mg kg−1) (MBK) combinations. Yohimbine (YOH), 2 mg kg−1 IM, YOH, 1 mg kg−1 IM, and atipamezole (ATI), 2.5 mg kg−1 IM, were used to reverse (REV) xylazine and medetomidine in three groups, respectively, at 100 minutes after INJ. Heart rate (HR), Doppler systolic blood pressures (BP) (neonatal size cuff), respiratory rate (RR), and SpO2 were measured at baseline and every 10 minutes after INJ and at 5 and 10 minutes following REV. Jaw tone, palpebral reflex, corneal reflex, toe pinch, skin pinch, ECG and body temperature were monitored every 10 minutes after INJ for 100 minutes. In addition, four female and three male guinea pigs from the original group were anesthetized with TKXB-H for castration and ovariohysterectomy. Cardiorespiratory functions were monitored during the surgery. Following surgery, YOH (2 mg kg−1 IM) was used to shorten recovery. anova for repeated measures and Tukey's honestly significant test were used for analysis (p

The purpose of this study was to determine the cardiovascular, analgesic, and sedative effects of IV medetomidine (M, 20 µg kg−1), medetomidine–hydromorphone (MH, 20 µg kg−1 − 0.1 mg kg−1), and medetomidine–butorphanol (MB, 20 µg kg−1 − 0.2 mg kg−1) in dogs. Using a randomized cross-over design and allowing 1 week between treatments, six healthy, mixed-breed dogs (five males and one female) weighing 20 ± 3 kg, were induced to anesthesia by face-mask administration of 2.9% ET sevoflurane to facilitate instrumentation prior to administration of the treatment combinations. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (PAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output via thermodilution using 5 mL of 5% dextrose, and recording the average of the three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. After instrumentation was completed, administration of sevoflurane was discontinued, and the dogs were allowed to recover for 30 minutes prior to administration of the treatment drugs. After collection of the baseline samples for blood gas analysis and recording the baseline cardiovascular variables, the test agents were administered IV over 10 seconds and the CV variables recorded at 5, 10, 15, 30, 45, and 60 minutes post-injection. In addition, arterial blood was sampled for blood gas analysis at 15 and 45 minutes following injection. Intensity and duration of analgesia (assessed by toe-pinch response using a hemostat) and level of sedation were evaluated at the above time points and at 75 and 90 minutes post-injection. Data were analyzed using anova for repeated measures with posthoc differences between means identified using Bonferroni's method (p

Objective—To compare effects of isoflurane and sevoflurane on intracranial pressure and cardiovascular variables at 1.0, 1.5, and 2.0 times the minimum alveolar concentration (MAC) in mechanically ventilated normocapnic dogs. Animals—6 healthy male Beagles. Procedures—The individual MAC was determined for each agent with an electrical stimulus. After a minimum of 1 week, anesthetic induction by use of a mask with one of the inhalation anesthetics selected randomly was followed by mechanical ventilation and instrumentation for measurement of intracranial pressure and cardiovascular variables. Heart rate; systolic, mean, and diastolic arterial blood pressures; central venous pressure; mean pulmonary arterial pressure; pulmonary artery occlusion pressure; cardiac output; intracranial pressure (ICP); core body temperature; end-tidal inhalation anesthetic and carbon dioxide concentration; and arterial blood gas values were measured after attaining equilibrium at 1.0, 1.5, and 2.0 MAC of each inhalation anesthetic. Cardiac index, systemic vascular resistance, pulmonary vascular resistance, and cerebral perfusion pressure (CPP) were calculated. Results—Mean ICP did not differ within and between anesthetics at any MAC. Compared with equipotent concentrations of isoflurane, the CPP and mean values for systolic, mean, and diastolic arterial blood pressures were increased at 2.0 MAC for sevoflurane, whereas mean values for mean and diastolic arterial blood pressures and systemic vascular resistance were increased at 1.5 MAC for sevoflurane. Conclusions and Clinical Relevance—Although ICP was similar in healthy normocapnic dogs, CPP was better maintained during 2.0 MAC for sevoflurane, compared with isoflurane.

Early childhood infection with respiratory viruses, including human rhinovirus, respiratory syncytial virus (RSV) and influenza, is associated with an increased risk of allergic asthma and severe exacerbation of ongoing disease. Despite the long recognition of this relationship, the mechanism linking viral infection and later susceptibility to allergic lung inflammation is still poorly understood. We discuss the literature and provide new evidence demonstrating that these viruses induce the alternative activation of macrophages. Alternatively activated macrophages (AAM) induced by RSV or influenza infection persisted in the lungs of mice up to 90 days after initial viral infection. Several studies suggest that AAM contribute to allergic inflammatory responses, although their mechanism of action is unclear. In this commentary, we propose that virus-induced AAM provide a link between viral infection and enhanced responses to inhaled allergens.

To define the role of semaphorin 4A (Sema4A) in allergic response, we employed Sema4A⁻/⁻ and wild-type (WT) mice in the experimental model of ovalbumin (OVA)-induced allergic airway inflammation. We observed a selective increase in eosinophilic airway infiltration accompanied by bronchial epithelial cell hyperplasia in allergen-treated Sema4A⁻/⁻ mice relative to WT mice. This enhanced inflammatory response was associated with a selective increase in bronchoalveolar lavage (BAL) interleukin 13 (IL-13) content, augmented airway hyperreactivity, and lower regulatory T cell (Treg) numbers. In vivo allergen-primed Sema4A⁻/⁻ CD4+ T cells were more effective in transferring T helper type 2 (Th2) response to naive mice as compared with WT CD4+ T cells. T-cell proliferation and IL-13 productions in OVA₃₂₃₋₃₃₉-restimulated Sema4A⁻/⁻ cell cultures were upregulated. Generated bone marrow chimeras showed an equal importance of both lung-resident cell and inflammatory cell Sema4A expression in optimal disease regulation. These data provide a new insight into Sema4A biology and define Sema4A as an important regulator of Th2-driven lung pathophysiology.

Summary Post anaesthetic myelopathy is a rare but devastating complication of equine anaesthesia and there is a need for better understanding of the condition and to raise veterinary awareness. The aim of this study was to collect data on unreported cases and combine those with reported cases to better identify possible risk factors and early clinical signs and outcomes of horses developing post anaesthetic myelopathy (PAM). A survey was conducted to identify cases of equine PAM. Records were also requested via the American College of Veterinary Anaesthesiologists listserve. Additional cases of PAM were located through review of the literature. Eighteen new cases and 12 published cases were identified. Large-framed breeds between 6–24 months of age were more commonly affected (23/30). The majority of horses were positioned in dorsal recumbency during anaesthesia. Lack of movement and deep pain of the rear limbs, loss of anal tone and lack of panniculus response from the mid to caudal thorax distally were the most common clinical findings. Reported treatments resulted in no improvement of clinical signs and all horses died or were subjected to euthanasia from a few hours to 8 days post operatively. Poliomyelomalacia of the caudal spinal cord is the most common histopathological finding. Although a rare complication it is a catastrophic risk that can be eliminated by performing a standing operation. Hopefully in the future better understanding of this condition will lead to prevention and treatment strategies.

Objective To evaluate and compare hemostatic variables and clinical bleeding following the administration of 6% hetastarch (600/0.75) or lactated Ringer’s solution (LRS) to dogs anesthetized for orthopedic surgery. Study design Randomized blinded prospective study. Animals Fourteen, healthy adult mixed-breed hound dogs of either sex, aged 11–13 months, and weighing 20.8 ± 1.2 kg. Methods The dogs were randomly assigned to receive a 10 mL kg−1 intravenous (IV) bolus of either 6% hetastarch (600/0.75) or LRS over 20 minutes followed by a maintenance infusion of LRS (10 mL kg−1hour−1) during anesthesia. Before (Baseline) and at 1 and 24 hours after bolus administration, packed cell volume (PCV), total protein concentration (TP), prothrombin time (PT), activated partial thromboplastin time (APTT), von Willebrand’s factor antigen concentration (vWF:Ag), factor VIII coagulant activity (F VIII:C), platelet count, platelet aggregation, colloid osmotic pressure (COP) and buccal mucosal bleeding time (BMBT) were measured. In addition a surgeon who was blinded to the treatments assessed bleeding from the incision site during the procedure and at 1 and 24 hours after the bolus administration. Results Following hetastarch or LRS administration, the PCV and TP decreased significantly 1-hour post-infusion. APTT did not change significantly compared to baseline in either treatment group, but the PT was significantly longer at 1-hour post-infusion than at 24 hours in both groups. No significant change was detected for vWF:Ag, FVIII:C, platelet aggregation or clinical bleeding in either group. The BMBT increased while platelet count decreased significantly at 1-hour post-infusion in both groups. The COP decreased significantly in both treatment groups 1-hour post-infusion but was significantly higher 1-hour post-infusion in the hetastarch group compared to the LRS group. Conclusions and clinical relevance At the doses administered, both hetastarch and LRS can alter hemostatic variables in healthy dogs. However, in these dogs undergoing orthopedic surgery, neither fluid was associated with increased clinical bleeding.

Sir,Clinical signs of facial ageing result from multiple histological and anatomical changes. Skin care and traditional surgery have much to offer patients desiring cosmetic improvement. However, t...

The Fick and thermodilution (TD) methods are two currently popular techniques for determination of cardiac output (CO) in adult horses. To our knowledge, a comparison of these two techniques has not been reported. Six healthy, resting, fit, adult horses of either sex and weighing 516.5+/-33.2 kg (mean+/-SD) were instrumented to enable measurement of cardiac output. Resting CO was determined by the Fick method and by thermodilution while the horses stood quietly in the stocks. Fick and thermodilution CO measurements were repeated under conditions of increased cardiac output achieved with the use of a dobutamine infusion (5 microg kg(-1) min(-1), IV), and again under conditions of decreased CO induced by administration of xylazine (0.5 mg/kg, IV). Fick and thermodilution cardiac outputs were compared using Bland-Altman analysis for repeated measures. The mean of the differences+/-1.96SD (bias and precision) between the two techniques was 1.88+/-24.17 L/min. Variability between measurements with the two techniques was decreased to 3.41+/-46.78 mL kg(-1) min(-1) when CO was normalized for body size by calculation of cardiac index.

Objective To determine the effects of intravenous (IV) butorphanol on the cardiopulmonary system and on the bispectral index (BIS) in isoflurane-anesthetized alpacas. Study design Randomized, blinded cross-over experimental trial. Animals Eight healthy, young (3 ± 1 SD years) adult female alpacas weighing 64 ± 9 SD kg. Methods Alpacas were anesthetized with isoflurane by mask followed by tracheal intubation and maintenance of anesthesia with isoflurane in oxygen and intermittent positive pressure ventilation. Animals were assigned to two treatments, butorphanol (0.1 mg kg −1 , IV) and saline (0.01 mL kg −1 , IV) in a randomized manner allowing a 2-week interval between treatments. Cardiovascular variables included systolic, diastolic, and mean arterial blood pressure, heart rate, pulmonary arterial pressure, pulmonary arterial occlusion pressure (PAOP), central venous pressure, cardiac output, and pulmonary temperature (TEMP). Cardiac index, systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Bispectral index was also measured. Arterial and mixed venous blood samples were collected for blood gas analysis. All variables were recorded at baseline (time 0) and at 5, 10, 15, 30, 45 and 60 minutes following injection and were analyzed by using repeated-measures anova ( p t -tests. Results Butorphanol decreased SVR at all times when compared with the baseline, but no difference was detected between treatments. TEMP decreased with time in both treatments, but they were not different from each other. Other cardiovascular, BIS, and blood gas variables were not different between groups. Conclusion and clinical relevance We conclude that butorphanol had minimal effects on the cardiovascular system of the alpacas, causing a mild decrease in SVR.

South American camelids, alpacas and llamas, are increasing in popularity. As a result, veterinarians in North American and European countries are treating increasing numbers of these species in their practices. This article reviews some of the common anesthetic and analgesic practices used in camelids.

This investigation was carried out to compare the postoperative analgesia and plasma morphine concentrations in dogs given epidural morphine or epidural morphine combined with medetomidine prior to surgery. Twelve dogs (seven males and five females) with ruptured cranial cruciate ligaments presented to the Washington State University Veterinary Teaching Hospital. Six dogs received an epidural injection of morphine (0.1 mg/kg) and six dogs received epidural morphine (0.1 mg/kg) combined with medetomidine (0.005 mg/kg). Numeric rating scale (NRS) pain scores and cumulative pain scores (CPS) were assigned to 10-min segments of video. Video segments, heart rates and respiratory rates were recorded prior to premedication and at 4, 8, 12, 18 and 24 h after epidural injection. Blood was sampled from the cephalic vein at each of these times and during anesthesia at 0.5, 1, 2 and 3 h after epidural injection. Data were analyzed using either Friedman's test or one-way anova for repeated measures. In the morphine group, significant increases compared with premedication values were detected at 4, 8 and 12 h after epidural injection for NRS and at 4 and 12 h after epidural injection for CPS. In the morphine plus medetomidine group, NRS was significantly higher at 4 and 8 h whereas there were no differences from baseline values for CPS. Plasma morphine concentrations were not significantly different between treatment groups, but were significantly increased compared with preinjection values at 0.5, 1, 12, 18, and 24 h in the morphine plus medetomidine group. Epidurally administered morphine combined with medetomidine was associated with only minor benefits based on subjective pain scoring when compared with morphine alone in these dogs undergoing repair of a ruptured cranial cruciate ligament.

Allergic diseases, including asthma, represent a major threat to human health. Over the three last decades, their incidence has risen in western countries. Aspirin treatment has been shown to improve allergic diseases, especially asthma, and the decreased use of aspirin has been hypothesized to contribute to the increase in childhood asthma. Because salicylate compounds suppress a number of enzymatic activities, and signaling through IL-4R participates in the development of allergic responses, we tested the effect of salicylates on IL-4 signal transduction. We found that treatment of cell lines and primary cells with aspirin and salicylates, but not acetaminophen, inhibited the activation of STAT6 by IL-4 and IL-13. This effect correlated with the inhibition of IL-4-induced CD23 expression. Although salicylates inhibited the in vivo activation of Janus kinases, their kinase activity was not affected in vitro by salicylates, suggesting that other kinases were involved in IL-4-induced STAT6 activation. Furthermore, we found that an Src kinase was involved in STAT6 activation because 1) Src kinase activity was induced by IL-4, 2) Src kinase activity, but not Janus kinase, was inhibited by salicylates in vitro, 3) cells expressing viral Src had constitutive STAT6 phosphorylation, and 4) cells lacking Src showed low STAT6 phosphorylation in response to IL-4. Because STAT6 activation by IL-4 and IL-13 participates in the development of allergic diseases, our results provide a mechanism to explain the beneficial effects of aspirin and salicylate treatment of these diseases.

Aims. To estimate the prevalence of blindness in the Republic of Ireland and the associated financial and total economic cost between 2010 and 2020.Methods. Estimates for the prevalence of blindness in the Republic of Ireland were based on blindness registration data from the National Council for the Blind of Ireland. Estimates for the financial and total economic cost of blindness were based on the sum of direct and indirect healthcare and nonhealthcare costs.Results. We estimate that there were 12,995 blind individuals in Ireland in 2010 and in 2020 there will be 17,997. We estimate that the financial and total economic costs of blindness in the Republic of Ireland in 2010 were€276.6 million and€809 million, respectively, and will increase in 2020 to€367 million and€1.1 billion, respectively.Conclusions. Here, ninety-eight percent of the cost of blindness is borne by the Departments of Social Protection and Finance and not by the Department of Health as might initially be expected. Cost of illness studies should play a role in public policy making as they help to quantify the indirect or “hidden” costs of disability and so help to reveal the true cost of illness.

Objective—To determine the cardiovascular and respiratory effects of water immersion in horses recovering from general anesthesia. Animals—6 healthy adult horses. Procedure—Horses were anesthetized 3 times with halothane and recovered from anesthesia while positioned in lateral or sternal recumbency in a padded recovery stall or while immersed in a hydropool. Cardiovascular and pulmonary functions were monitored before and during anesthesia and during recovery until horses were standing. Measurements and calculated variables included carotid and pulmonary arterial blood pressures (ABP and PAP, respectively), cardiac output, heart and respiratory rates, arterial and mixed venous blood gases, minute ventilation, end expiratory transpulmonary pressure (PendXes), maximal change in transpulmonary pressure (ΔPtpmax), total pulmonary resistance (RL), dynamic compliance (Cdyn), and work of breathing (). Results—Immersion in water during recovery from general anesthesia resulted in values of ABP, PAP, PendXes, ΔPtpmax, RL, and that were significantly greater and values of Cdyn that were significantly less, compared with values obtained during recovery in a padded stall. Mode of recovery had no significant effect on any other measured or calculated variable. Conclusions and Clinical Relevance—Differences in pulmonary and cardiovascular function between horses during recovery from anesthesia while immersed in water and in a padded recovery stall were attributed to the increased effort needed to overcome the extrathoracic hydrostatic effects of immersion. The combined effect of increased extrathoracic pressure and PAP may contribute to an increased incidence of pulmonary edema in horses during anesthetic recovery in a hydropool. (Am J Vet Res 2001;62:1903–1910)

Background: In 2013 a Technology Adoption Program for sheep farmers was established to encourage the implementation of best management practices on sheep farms in Ireland. There were 4,500 participants in this programme in 2013. As part of this programme, farmers had the option to carry out a drench test to establish the efficacy of their anthelmintic treatment. Results: Flock faecal samples were collected before and after treatment administration and gastrointestinal nematode eggs enumerated. In total there were 1,893 participants in the task, however only 1,585 included both a pre- and post-treatment faecal sample. Of those, 1,308 provided information on the anthelmintic product that they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and macrocyclic lactone (ML) product respectively. The remaining farmers used a product inapplicable for inclusion in the task such as a flukicide or BZ/LEV combination product. Samples were included for analysis of drench efficacy if the pre-treatment flock egg count was >= 200 eggs per gram and the interval post-sampling was 10-14 days for BZ products, 4-7 days for LEV products and 14-18 days for ML products. These criteria reduced the number of valid tests to 369, 19.5% of all tests conducted. If the reduction post-treatment was >= 95% the treatment was considered effective. Only 51% of treatments were considered effective using this criterion. There was a significant difference in efficacy between the anthelmintic drug classes with BZ effective in only 30% of treatments, LEV effective in 52% of cases and ML effective in 76% of cases. Conclusions: Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms, have a high failure rate. There was a significant difference between the efficacies of the anthelmintic classes with BZ the least effective and ML the most effective.

N-ECCO (Nurses-European Crohn's & Colitis Organisation) has been an active member of ECCO since 2007, with the purpose of providing nurse education and the opportunity for nurses to network internationally. N-ECCO aims through its activity to improve nurses' knowledge of Inflammatory Bowel Disease (IBD), share best practice and thus improve the quality of care accessed across Europe by patients with IBD. It has long been acknowledged in N-ECCO that nurses across Europe perform and provide varying roles in caring for patients with IBD, given the country-specific variances in role, title, salary and level of training. ### 1.1 Aims The intentions of the N-ECCO Consensus statements are to identify the positioning of nurses (adult and paediatric) in the care of patients with IBD and to provide a consensus on the ideal standard of minimum care that patients with IBD might expect, irrespective of the level of nurse training, title or country. The ‘ideal’ standard of nursing care was deemed an accurate measure and appropriate by the group in order to provide a standard for all nurses working with people with IBD. ### 1.2 Methods The N-ECCO Committee agreed the need for the consensus statements on the nurses' role in June 2011. Following the Standard Operating Procedure (SOP) of ECCO (www.ecco-ibd.eu/) a proposal for guidelines, along with draft contents for the statements, was submitted to the Governing Board. This was approved in November 2011, with a recommendation to conduct a survey to gain a clear understanding of the current situation of nurses within Europe in caring for patients with IBD. The survey was developed and refined within the N-ECCO committee in time for N-ECCO February 2012, when all attending nurse delegates were asked to complete it. Results of this survey will be published separately. There was an official call from the ECCO Office for nursing participants to be …

Cytokines are small, secreted proteins that control immune responses. Within the lung, they can control host responses to injuries or infection, resulting in clearance of the insult, repair of lung tissue, and return to homeostasis. Problems can arise when this response is over exuberant and/or cytokine production becomes dysregulated. In such cases, chronic and repeated inflammatory reactions and cytokine production can be established, leading to airway remodeling and fibrosis with unintended, maladaptive consequences. In this report, we describe the cytokines and molecular mechanisms behind the pathology observed in three major chronic diseases of the lung: asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. Overlapping mechanisms are presented as potential sites for therapeutic intervention.

Lateral rostrotentorial and caudal suboccipital approaches to the brain were performed on six beagles. Intracranial pressure (ICP) was measured as the two craniectomies were connected by removing the bone of the nuchal crest and occluding the transverse venous sinus. Intracranial pressure remained constant after acute occlusion of the sinus with bone wax and there was no gross evidence of brain edema. All six dogs survived the surgery and five dogs survived for a minimum of 3 months. One dog died acutely during the postoperative period. The exact cause of the cerebellar hemorrhage and infarction found at necropsy in the latter dog was not evident. Anemia occurred in three of the six dogs as a result of intraoperative hemorrhage. All dogs surviving the perioperative period had mild, transient hypermetria and conscious proprioceptive deficits, but were neurologically normal 72 hours after surgery. Results of this study indicate that acute, unilateral transverse sinus occlusion is possible without an increase in ICP. The ability to do this allows access to the rostral aspect of the ipsilateral cerebellum and brain stem.

Longitudinal division of the corpus callosum was performed in six normal beagles to determine surgical morbidity. The corpus callosum was divided sagittally on the midline and the effect on neurological function was determined. Five of six dogs were clinically normal within 14 days or less after surgery. One dog had persistent but improving clinical signs consistent with a forebrain disturbance at 30 days after surgery. Overall, minimal morbidity and no mortality was associated with this surgical procedure. Further study is indicated to determine the efficacy of this surgical treatment for seizure control in dogs with idiopathic epilepsy.

Research suggests that simulation technology has potential to enhance student achievement, particularly for students having a preference for hands-on learning. The aim of this study was to compare ventilation learning outcomes in students attending traditional lecture versus students using an active learning ventilation simulation. A computer simulation was developed to advance students' learning of mechanical ventilation. Forty-one students were divided into upper and lower strata based on performance rankings and were then randomly assigned to first complete a simulation scenario or view a lecture. Two distinct ventilation topics, controls and clinical, were developed for each instructional method. Students completed examinations three weeks following each respective instructional intervention (lecture or simulation scenarios) as well as one long-term examination and survey six weeks following the second examination. Upper-ranking students who learned the clinical topic through the simulation scenarios outperformed students who learned by traditional lecture. In addition, upper-ranking students scored higher than lower-ranking students in both the clinical and long-term composite examinations. No differences in student scores attributed to instructional method or class rank were identified for the controls topic. Survey results indicated that students were more engaged as learners when using the simulation and wished to have the simulation available during their clinical intensive care unit (ICU) rotations. Use of the simulation was associated with improved performance of upper-ranking students on the clinical-topic exam and was equivalent to lecture as an instructional intervention on the controls-topic exam. The simulation was perceived as an engaging, desirable tool providing immediate feedback.

Background The IL-4 receptor α (IL-4Rα) chain has a broad expression pattern and participates in IL-4 and IL-13 signaling, allowing it to influence several pathological components of allergic lung inflammation. We previously reported that IL-4Rα expression on both bone marrow-derived and non-bone marrow-derived cells contributed to the severity of allergic lung inflammation. There was a correlation between the number of macrophages expressing the IL-4Rα, CD11b, and IAd, and the degree of eosinophilia in ovalbumin challenged mice. The engagement of the IL-4Rα by IL-4 or IL-13 is able to stimulate the alternative activation of macrophages (AAM). The presence of AAM has been correlated with inflammatory responses to parasites and allergens. Therefore, we hypothesized that IL-4Rα+ AAM play an active role in allergic lung inflammation. To directly determine the role of AAM in allergic lung inflammation, M-CSF-dependent macrophages (BMM) were prepared from the bone-marrow of IL-4Rα positive and negative mice and transferred to IL-4RαxRAG2-/- mice. Wild type TH2 cells were provided exogenously. Results Mice receiving IL-4Rα+/+ BMM showed a marked increase in the recruitment of eosinophils to the lung after challenge with ovalbumin as compared to mice receiving IL-4Rα-/- BMM. As expected, the eosinophilic inflammation was dependent on the presence of TH2 cells. Furthermore, we observed an increase in cells expressing F4/80 and Mac3, and the AAM marker YM1/2 in the lungs of mice receiving IL-4Rα+/+ BMM. The BAL fluid from these mice contained elevated levels of eotaxin-1, RANTES, and CCL2. Conclusions These results demonstrate that transfer of IL-4Rα + macrophages is sufficient to enhance TH2-driven, allergic inflammation. They further show that stimulation of macrophages through IL-4Rα leads to their alternative activation and positive contribution to the TH2-driven allergic inflammatory response in the lung. Since an increase in AAM and their products has been observed in patients with asthma exacerbations, these results suggest that AAM may be targeted to alleviate exacerbations.

Timely access to safe hospital care remains a major concern. Target bed-occupancy rates have been proposed as a measure of the ability of a hospital to function safely and effectively. High bed-occupancy rates have been shown to be associated with greater risks of hospital-associated infection and access block and to have a negative impact on staff health. Clinical observational data have suggested that bed occupancies above 85% could adversely affect safe, effective hospital function. Using this figure, at least initially, would be of value in the planning and operational management of public hospital beds in Australia. There is an urgent need to develop meaningful outcome measures of patient care that could replace the process measures currently in use.

Quantitative EEG was assessed in six dogs anaesthetized with 1.8% end-tidal isoflurane concentration and following diazepam (0.2 mg/kg i.v.) administration. Ventilation was controlled to maintain normocapnia. Five dogs were subsequently given the benzodiazepine antagonist, flumazenil (0.04 mg/kg i.v.), and quantitative EEG was recorded. One dog received a saline injection following diazepam (as a control) and quantitative EEG was recorded for an additional 2.5 h. Heart rate, arterial blood pressure, esophageal temperature, arterial pH and blood gas tensions, end-tidal CO2 tension and end-tidal isoflurane concentration were monitored throughout the study. A 21 lead linked-ear montage was used for recording EEG. Quantitative EEG data were stored on an optical disc for analysis at a later date. Values for absolute power of EEG were determined for theta, delta, alpha, and beta frequencies. Cardiovascular parameters remained stable throughout the study. Diazepam administration was associated with decreased absolute power in all frequencies of EEG at all electrode sites. The duration of diazepam-induced decreased absolute power of EEG was at least 3 h in one dog. Administration of flumazenil antagonized diazepam-induced decreased absolute power of EEG in all frequencies at all electrode sites. We conclude that quantitative EEG provides a relatively non-invasive, objective measure of diazepam- and flumazenil-induced changes in cortical activity during isoflurane anaesthesia.

Objective— To determine the hemodynamic response to radiofrequency ablation (RFA) of normal adrenal tissue in dogs. Study Design— Experimental study. Animals— Healthy adult mixed-breed dogs (n=6). Methods— During general anesthesia a Swan–Ganz thermodilution catheter was flow directed into the pulmonary artery and used to quantify cardiac output. An arterial catheter was used for direct blood pressure measurements. An RFA device was introduced into the left adrenal gland under observation through laparoscopic instrumentation. Blood samples were collected and hemodynamic variables studied after a stable surgical anesthetic depth was achieved (time 1), during CO2 insufflation of the abdomen (time 2), during adrenal RFA (time 3), and after completed RFA (time 4). Catecholamine determinations were performed with a human enzyme immunoassay. Histopathology was performed to verify medullary necrosis. Results— Arterial, pulmonary arterial and central venous pressure, and plasma norepinephrine increased more during RFA than during abdominal insufflation. Heart rate and cardiac index did not differ between time points. High baseline epinephrine was present and significant differences between time points were not detected. Systemic vascular resistance had very high individual variation and differences were not detected. Conclusions— RFA of normal adrenal tissues is associated with severe hemodynamic alterations. Further studies of the optimal blockage of catecholamine-induced hypertension in dogs are warranted. Clinical Relevance— Clinicians should prepare for potential hypertensive crisis during RFA of adrenal masses, especially if treating a margin of normal tissue.

Summary Quantitative EEG monitoring is useful for objectively measuring CNS responses to agonist-antagonist adjuncts or responses to noxious stimuli in anaesthetized dogs.

We have previously demonstrated that the vasospastic attacks of Raynaud's disease can be induced despite blockade of efferent digital nerves and that feedback-induced vasodilation is mediated through a non-neural, beta-adrenergic mechanism. Here, we sought to determine the role of sympathetic activity, as measured by plasma epinephrine and norepinephrine, during finger temperature feedback and autogenic training. Thirty-one female patients with idiopathic Raynaud's disease were randomly assigned to receive finger temperature feedback or autogenic training over 28 days. Half of each group began and finished training during the follicular phase of the menstrual cycle, the other half during the luteal phase. During training, significant temperature elevations were shown by feedback patients but not by autogenic patients. There were no significant effects for norepinephrine and epinephrine for either group. Cycle phase did not interact with training effects or with catecholamines. These findings do not support the role of decreased sympathetic activation in behavioral treatments for Raynaud's disease.

This study contrasted six subscales of the Brief Psychiatric Rating Scale (BPRS) to determine their sensitivity to psychosocial treatment outcome. An expanded version of the BPRS was administered to 216 clients on admission to a day program. The subscale measuring hostility and suspiciousness discriminated at intake clients who were therapeutically discharged from clients who did not complete the program and predicted discharge status after the investigators controlled for the effects of demographic variables. Significant reductions in scores were obtained on five subscales for a subset of clients to whom the BPRS was readministered before discharge. The results support the use of the expanded BPRS as an evaluative tool in psychosocial rehabilitation programs.

Improper homeostasis of Th1 and Th2 cell differentiation can promote pathological immune responses such as autoimmunity and asthma. A number of factors govern the development of these cells including TCR ligation, costimulation, death effector expression, and activation-induced cell death (AICD). Although chronic morphine administration has been shown to selectively promote Th2 development in unpurified T cell populations, the direct effects of chronic morphine on Th cell skewing and cytokine production by CD4+ T cells have not been elucidated. We previously showed that morphine enhances Fas death receptor expression in a T cell hybridoma and human PBL. In addition, we have demonstrated a role for Fas, Fas ligand (FasL), and TRAIL in promoting Th2 development via killing of Th1 cells. Therefore, we analyzed whether the ability of morphine to affect Th2 cytokine production was mediated by regulation of Fas, FasL, and TRAIL expression and AICD directly in purified Th cells. We found that morphine significantly promoted IL-4 and IL-13 production but did not alter IL-5 or IFN-γ. Furthermore, morphine enhanced the mRNA expression of Fas, FasL and TRAIL and promoted Fas-mediated AICD of CD4+ T cells. Additionally, blockade of Fas/FasL interaction by anti-FasL inhibited the morphine-induced production of IL-4 and IL-13 and AICD of CD4+ T cells. These results suggest that morphine preferentially enhances Th2 cell differentiation via killing of Th1 cells in a Fas/FasL-dependent manner.

Aims: This was a pilot study to determine if protein profiles generated using SELDI-MS could differentiate plasma from patients with colorectal cancer, dysplastic polyps or normal colons. Methods: 5ml of plasma was collected from patients with colorectal cancer (n=19) or dysplastic polyps (n=7). Patients who had undergone a full colonoscopy which was normal were used as control patients (n=22). The serum was fractionated using an anion exchange column. Two fractions were then applied to a CM-10 and IMAC-30 ProteinChip. Protein profiles were collected using two settings, one for low and one for high molecular weight proteins. The samples were normalised using TIC and externally calibrated. Peaks were detected using Biomarker Wizard. An algorithm was generated by a J48 decision analysis tree to differentiate normal from polyps and cancer samples. Results: We were able to differentiate normal from polyps/tumour samples with 88.2%sensitivity and 99.2% specificity. Conclusions: This pilot study provides encouraging results suggesting that protein profiling may have a role to play in screening for colorectal cancer. The numbers involved in this study were small and a larger, prospective study will be required to confirm these preliminary results.

To present a model for the assessment, investigation, and management of an atypical outbreak of infectious endophthalmitis of indeterminate aetiology. A published statistical model was used to determine when the case-load constituted an outbreak. Intraocular surgery was discontinued and a multidisciplinary infection control team was formed aimed at identifying potential causative factors among the following categories: environment around theatre, preoperative preparation, intraoperative theatre practices, intraoperative surgical practices, postoperative practices, equipment maintenance guidelines, cleaning/sterilization practices, and microbiological screening. Five cases of postoperative endophthalmitis developed following uncomplicated phacoemulsification cataract surgery by different surgeons over a 7-month period. Despite full investigation no single focus of infection could be determined. Four out of five cases were culture positive. Three grew Streptococcus viridansof different strains. The fourth culture grew Staphylococcus aureus. In the absence of a single causative factor, it was postulated the combined effect of multiple potential factors may have led to an increased bacterial load and subsequent infection rate. Improved practices were initiated including new cleaning protocols to combat the build-up of debris on phacoemulsification instruments. Cataract surgery was resumed with 3-monthly microbiological monitoring. There have been no further cases in the 12 months following the changes. Outbreaks of endophthalmitis typically present over a short time period and could often be attributed to a single infective cause. We present our experience of detecting and managing this cluster and recommend a ‘ground-up’ multidisciplinary model to manage future outbreaks of this devastating condition.