bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient supersensitivity to α‐adrenoceptor agonists, and distinct hyper‐reactivity to vasopressin and angiotensin II after denervation of rat tail artery
Authors: Tripovic Diana , Pianova Svetlana , McLachlan Elspeth M , Brock James A 
Published: December 2009

Background and purpose: Vascular ‘denervation’ hyper‐reactivity has generally been investigated 1–2 weeks after administration of chemicals that temporarily prevent transmitter release, but do not necessarily inactivate the neuronal noradrenaline transporters (NETs). We have investigated the reactivity of rat tail arteries over longer periods after removing the terminals by surgical denervation.Experimental approach: Two and 7 weeks after denervation, myography was used to assess contractions of isolated arterial segments to phenylephrine, methoxamine, clonidine, vasopressin and angiotensin II (AII). Denervation was confirmed by lack of tyrosine hydroxylase immunoreactive nerve terminals.Key results: The NET inhibitor, desmethylimipramine, increased the pEC50for phenylephrine in control, but not denervated arteries after both 2 and 7 weeks. Relative to controls, pEC50s for phenylephrine (with desmethylimipramine), methoxamine, clonidine and vasopressin were increased at 2 but not 7 weeks after denervation. The pEC50for phenylephrine in the absence of desmethylimipramine was greater than control after both 2 and 7 weeks' denervation. The maximum contraction to vasopressin was larger than in controls at 2 but not 7 weeks after denervation, whereas contractions to AII were markedly enhanced at both time points.Conclusions and implications: Increased vascular reactivity to α1‐ and α2‐adrenoceptor agonists, and vasopressin is transient following denervation. After 7 weeks, increased reactivity to phenylephrine can be entirely accounted for by the loss of NETs. Maintained supersensitivity to AII indicates that denervation differentially and selectively affects vascular reactivity to circulating vasoconstrictor agents. This might explain persistent vasoconstriction in denervated skin of humans after nerve injuries.
TREK‐1 channels do not mediate nitrergic neurotransmission in circular smooth muscle from the lower oesophageal sphincter
Authors: Zhang Y , Miller DV , Paterson WG 
Published: December 2009

Background and purpose:  The ionic mechanisms underlying nitrergic inhibitory junction potentials (IJPs) in gut smooth muscle remain a matter of debate. Recently, it has been reported that opening of TWIK‐related K+ channel 1 (TREK‐1) K+ channels contributes to the nitrergic IJP in colonic smooth muscle. We investigated the effects of TREK‐1 channel blockers on nitrergic neurotransmission in mouse and opossum lower oesophageal sphincter (LOS) circular smooth muscle (CSM).Experimental approach:  The effects of TREK‐1 channel blockers were characterized pharmacologically in murine and opossum gut smooth muscle using conventional intracellular and tension recordings.Key results:  In LOS, L‐methionine depolarized the resting membrane potential (RMP) but did not inhibit the nitrergic IJP. Cumulative application of theophylline hyperpolarized the RMP and inhibited the nitrergic IJP concentration dependently. The induced membrane hyperpolarization was prevented by pre‐application of caffeine, but not by 1H‐[1,2,4]oxadiazolo‐[4,3‐a]quinoxalin‐1‐one. 8‐Br‐cAMP significantly hyperpolarized membrane potential and increased the amplitude of the nitrergic IJP. In opossum LOS muscle strips, L‐methionine increased resting tone but had no effect on nerve‐mediated LOS relaxation. On the other hand, theophylline markedly inhibited tone. In CSM from mouse proximal colon, L‐methionine caused modest inhibition of nitrergic IJPs.Conclusions and implications:  TREK‐1 channels were not involved in the nitrergic IJP in LOS CSM. Not only does L‐methionine have no effect on the nitrergic IJP or LOS relaxation, but the effect of theophylline appears to be due to interruption of Ca2+‐releasing pathways (i.e. caffeine‐like effect) rather than via blockade of TREK‐1 channels.
Colitis affects the smooth muscle and neural response to motilin in the rabbit antrum
Authors: Depoortere Inge , Thijs Theo , Janssen Sara , De Smet Betty , Tack Jan 
Published: December 2009

Background and purpose: The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum.Experimental approach: Myeloperoxidase (MPO) activity, NF‐κB activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6‐trinitrobenzenesulphonic acid colitis. Smooth muscle and neural responses to motilin were studied in antral smooth muscle stripsin vitro.Key results: Colitis did not affect MPO activity, but increased NF‐κB activity in the antrum. Motilin receptor density in the antrum was not affected. Under control conditions, motilin induced a slowly developing tonic smooth muscle contraction. Five days post‐inflammation, tonic contractions to motilin were reduced and preceded by a rapid initial contraction. Other kinases were recruited for the phosphorylation of myosin light chain (MLC) (a multi‐functional MLC kinase), and for the inhibition of MLC phosphatase (Rho kinase in addition to protein kinase C) to mediate the motilin‐induced contractions during inflammation. Colitis potentiated the cholinergic neural on‐contractions in the antrum. This was associated with a hyper‐reactivity to motilin and an increased muscle response to ACh.Conclusions and implications: Colitis altered the course of the motilin‐induced smooth muscle contraction in the antrum. This involved changes in the kinases phosphorylating MLC. Increased cholinergic excitability to motilin in the antrum may play a role in the pathogenesis of inflammation‐associated gastric motility disorders.
Gender, Politics and Policy Change: The Case of Welfare Reform Under New Labour
Authors: Annesley Claire 
Published: December 2009

AbstractPolitics and gender scholarship is increasingly seeking to understand the relationship between the presence of women in politics and gendered policy outcomes – the substantive representation of women (SRW). Yet its focus remains squarely on the activities of ‘critical actors’ in parliaments and women's policy agencies and on ‘feminist’ rather than ‘mainstream’ policy areas. In contrast, this article investigates the impact of feminist actors in a range of institutional settings on recent processes of welfare reform in the UK. It finds that the gendered welfare reform introduced by New Labour was initiated and pushed through by a coalition of committed feminist actors across a range of institutions. Crucially, the reforms relied on the existence of ‘strategic actors’ and ‘gate openers’, defined as feminist actors in positions of significant institutional power. It makes a contribution to the actor-centred SRW scholarship, develops an institutionalist approach to this research and identifies the need for a political economy perspective to understanding how women can shape policy outcomes.
A Novel Technique for Tethered Dialysis Catheter Removal Using the Laser Sheath
Authors: Carrillo Roger G. , Garisto Juan D. , Salman Loay , Merrill Donna , Asif Arif 
Published: December 2009

AbstractTraction and cutdown techniques can successfully remove a tunneled dialysis catheter (TDC) in a great majority of patients. However, these methods may not be successful in patients with catheters that are tethered or attached to the central veins or the atrium. A forceful application of traction can lead to catheter breakage with subsequent retention of the broken piece and carries a potential risk of vascular and atrial wall avulsion. Open thoracotomy has been employed to remove an attached TDC. However, this procedure is invasive and bears a significant morbidity. This report presents three cases of tethered TDCs that underwent laser sheath extraction. The TDCs had been in place for an average of 26 months. The patients underwent initial unsuccessful removal attempt using the traction method with surgical exploration all the way to the venotomy site. The laser technique that is used to remove pacemaker/implantable cardioverter defibrillator leads was then applied to these stuck catheters. All three catheters were successfully removed without any damage to the catheter, central veins, or the right atrium. There were no retained catheter fragments left in the central veins or the atrium. One patient demonstrated a significant thrombus that extended from the tip of the catheter all the way to the right ventricle. The external sheath of the laser device successfully aspirated the thrombus. There were no procedure‐related complications. In this small series, a laser sheath successfully extracted tethered dialysis catheters. The study found the procedure to be effective, easy to perform, and minimally invasive. We suggest that this approach be considered for the removal of tethered catheters that cannot be removed using traditional approaches.
Retrograde Angiography and the Risk of Arteriovenous Fistula Perforation
Authors: Salman Loay , Asif Arif , Beathard Gerald A. 
Published: December 2009

AbstractAssessment of the inflow segment of an arteriovenous fistula is mandatory for optimum access evaluation. Retrograde angiography (RA) is routinely used to image this region of the access system. Traditionally, RA is performed by manually occluding the outflow track of an arteriovenous fistula (AVF) and forcing the radiocontrast into the inflow segment against arterial pressure. While this technique is largely successful in visualizing the juxta‐anastomotic region, anastomosis and a portion of the feeding artery, the approach carries a potential risk of vascular rupture between the occluded portion of the fistula and the anastomosis. This article presents six cases of fistulas that suffered vascular rupture during RA. In three cases, vascular damage occurred prior to the application of angioplasty. The remaining cases suffered perforation after angioplasty. Balloon tamponade was successful in salvaging two fistulas. Another AVF with a perforation did not require any intervention to maintain flow. The complication was successfully managed in one AVF by the insertion of an endovascular stent graft. Two fistulas were lost due to vascular damage. This report demonstrates that RA performed by occluding the outflow track of an AVF to assess the results of angioplasty of an inflow stenosis can result in vascular rupture. There is a risk of such adversity even before the application of angioplasty in this region. It is suggested that the first of these be avoided and the latter be done with care.
Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: Blood–Membrane Interactions During Dialysis
Authors: Huang Zhongping , Gao Dayong , Letteri Jeffrey J. , Clark William R. 
Published: December 2009

AbstractIn extracorporeal renal replacement therapies, the dialyzer is not only the site at which solute removal occurs but also the extracorporeal circuit component having the largest surface area exposed to blood. Therefore, it is not surprising that interactions between blood components and the dialyzer membrane influence the dialysis procedure in several ways. Based on engineering principles, fluid flow along a surface such as membrane results in the development of a boundary layer which can influence solute removal. Furthermore, the exposure of blood to any extracorporeal artificial surface results in the activation of several pathways within the body, including those involving coagulation and complement activation. One of the byproducts of this generalized activation process is protein adsorption to the membrane surface, another phenomenon which can have a significant impact on solute removal. In this article, a detailed review of the ways in which blood–membrane interactions influence solute removal during hemodialysis and related therapies is provided. The influences of secondary membrane formation and boundary layer/concentration polarization effects on solute removal are specifically discussed. Furthermore, the importance of adsorption as a specific removal mechanism for low‐molecular weight proteins by highly permeable synthetic membranes is highlighted.
Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: The Implantable Artificial Kidney
Authors: Fissell William H. , Roy Shuvo 
Published: December 2009

AbstractThe confluence of an increasing prevalence of end‐stage renal disease (ESRD), clinical trial data suggestive of benefit from quotidian dialysis, and ongoing cost/benefit reanalysis of healthcare spending have stimulated interest in technological improvements in provision of ESRD care. For the last decade, our group has focused on enabling technologies that would permit a paradigm shift in dialysis care similar to that brought by implantable defibrillators to arrhythmia management. Two significant barriers to wearable or implantable dialysis persist: package size of the dialyzer and water requirements for preparation of dialysate. Decades of independent research into highly efficient membranes and cell‐based bioreactors culminated in a team effort to develop an implantable version of the University of Michigan Renal Assist Device. In this review, the rationale for the design of the implantable artificial kidney is described.
Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: Renal Cell Therapy and Beyond
Authors: Song Joon Ho , Humes H. David 
Published: December 2009

AbstractAlthough current dialysis techniques have transformed acute and chronic renal failure from uniformly fatal clinical disorders into treatable diseases, these therapies replace only the water and solute clearance function of the kidney and have reached a point where little further therapeutic improvement can be anticipated. In addition to their metabolic and endocrine functions, renal tubule cells presumably play an important role in the systemic inflammatory balance by participating in the complex and dynamic network of leukocyte action and pro‐ and anti‐inflammatory cytokines. Loss of this function may result in a propensity to develop systemic inflammatory response syndrome (SIRS), multiorgan dysfunction, and a high risk of death in acute kidney injury (AKI), and may relate to chronic inflammatory state in end‐stage renal disease (ESRD). A renal tubule cell assist device (RAD) containing animal or human renal tubule cells has been recently developed with the purpose of integrating the functions of tubule cells with the filtration function of current dialysis to offer a more complete renal replacement therapy. The viability and functionality of this device were confirmed in in vitro experiments and large animal studies, and recently the RAD’s clinical therapeutic benefit was demonstrated with a series of FDA‐approved human trials. Another novel synthetic membrane extracorporeal device that binds and inhibits circulating leukocytes has been developed with the purpose of reducing microvascular damage promoted primarily via activated circulating leukocytes in AKI and SIRS. This device, called a selective cytopheretic inhibitory device, mimics immunomodulation and duplicates RAD efficiency in preliminary studies. Both devices may become comprehensive treatments, replacing full renal function and correcting inflammatory imbalance in patients with acute and chronic renal disorders.
Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: Inflammation and Insulin Resistance as Novel Mechanisms of Wasting in Chronic Dialysis Patients
Authors: Da Costa José Abrão Cardeal , Alp Ikizler T. 
Published: December 2009

AbstractOver the last decade, there have been no proven therapies to lower the mortality and morbidity risk for chronic dialysis patients. One of the most important determinants of this poor clinical outcome is protein energy wasting (PEW), a unique and highly prevalent nutritional and metabolic abnormality primarily characterized by increased protein breakdown in the skeletal muscle compartment. Although the etiology and mechanisms leading to increased protein breakdown in chronic dialysis patients are complex and mostly ill‐defined, two well‐recognized and presumably interrelated metabolic abnormalities, insulin resistance and chronic inflammation, are likely to play a critical role in the pathogenesis of this condition. Multiple studies demonstrate the anabolic effects of insulin that extend beyond simple carbohydrate metabolism. Insulin is a mediator of accelerated protein breakdown in the catabolic condition such as advanced kidney disease. Chronic inflammation, a condition known to cause muscle catabolism in experimental conditions, has a strong association with advanced kidney disease in epidemiologic studies. Chronic inflammation is also known to induce insulin resistance, primarily by the induction of proinflammatory cytokines. The protein catabolic effects of inflammation and insulin resistance involve common cellular pathways. Thus, it is reasonable to speculate that chronic inflammation of advanced kidney disease mediates its protein catabolic effects by inducing insulin resistance of protein metabolism at both the physiologic and cellular levels. Modulating inflammatory response or insulin signaling by pharmacologic interventions could allow us to clarify the mechanisms contributing to the development of PEW in the setting of these particular metabolic derangements.
Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: More of the Same: Improving Outcomes Through Intensive Hemodialysis
Authors: McFarlane Philip A. 
Published: December 2009

AbstractThe typical dialysis patient faces both a poor quality of life and a significantly shortened survival. This is often blamed on “uremia.” However, defining the clinical entity of uremia is surprisingly difficult. It represents the clinical sequelae of the effects of retention products, other effects of renal disease, and the effects of other comorbid conditions. The list of retention products that could act as uremic toxins is lengthy, but it would appear that urea itself does not contribute significantly to the uremic state. Larger molecular weight substances are likely the major contributors to the uremic milieu. Regardless of the causes, the uremic state persists in many patients who are reaching their dialysis adequacy targets as defined by urea clearance. This raises the possibility that more intensive hemodialysis could improve patient outcomes. Hemodialysis can be intensified by increasing dialysis efficiency without changing duration or frequency. Alternatively, hemodialysis duration, frequency, or both can be increased. All intensification methods increase small solute removal, but the removal of larger molecular weight retention products depends more upon treatment time. Modalities such as short daily hemodialysis, long intermittent hemodialysis, and quotidian nocturnal hemodialysis have been associated with a variety of clinical improvements, as well as improvements in quality of life and a lower standardized mortality ratio. However, the HEMO study approach of intensifying small solute clearance without significant modifications of the dialysis schedule does not appear to be effective. Future research will help to define the optimal treatment duration and frequency in hemodialysis patients.
Service Versus Education: Finding the Right Balance: A Consensus Statement from the Council of Emergency Medicine Residency Directors 2009 Academic Assembly “Question 19” Working Group
Authors: Quinn Antonia , Brunett Patrick 
Published: December 2009

AbstractMany emergency medicine (EM) residency programs have recently received citations for their residents’ responses to Question 19 of the Accreditation Council on Graduate Medical Education annual survey, which asks residents to rate their program’s emphasis on clinical education over service obligations. To the best of our knowledge, no prior investigations or consensus statements exist that specifically address the appropriate balance between educational activity and clinical service in EM residency training. The objective of this project was to create a consensus statement based on the shared insights of academic faculty and educators in EM, with specific recommendations to improve the integration of education with clinical service in EM residency training programs. More than 80 EM program directors (PDs), associate and assistant PDs, and other academic EM faculty attending an annual conference of EM educators met to address this issue in a discussion session and working group. Participants examined the current literature on resident service and education and shared with the conference at large their collective insight and experience and possible solutions to this challenge. A consensus statement of specific recommendations and effective educational techniques aimed at balancing service and education requirements was created, based on the contributions of a diverse group of academic emergency physicians. Recommendations included identifying the teachable moment in all clinical service; promoting resident understanding of program goals and expectations from the beginning; educating residents about the ACGME resident survey; and engaging hospitals, institutional graduate medical education departments, and residents in finding solutions.