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Cardiac surgery has two distinct treatment pathways; approximately half of the 32,000 adult cardiac surgery episodes in the UK per year are planned (mean waiting time of 104 days) and half are urgent inpatients (mean waiting time of 11 days), plus a small number of emergency cases [[3]]. Prehabilitation is the practice of enhancing a patient's functional capacity before surgery, with the aim of improving postoperative outcomes [[1]]. 1 Table Pre-operative assessment (POA) service and prehabilitation components in urgent and elective cardiac surgery pathways from 34 cardiac surgery centres. [Extracted from the article]

Viscoelastic point-of-care tests are commonly used to provide prompt diagnosis of coagulopathy and allow targeted treatments in bleeding patients. We updated existing meta-analyses that have evaluated the clinical effectiveness of viscoelastic point-of-care tests vs the current standard of care for the management of cardiac surgery patients at risk of coagulopathic bleeding. Randomized controlled trials comparing viscoelastic point-of-care diagnostic testing with standard care in cardiac surgery patients were sought. All-cause mortality, blood loss, reoperation, blood transfusion, major morbidity, and intensive care unit and hospital length of stay were analysed using random-effects modelling. Fifteen trials that randomized a total of 8737 participants were included for the analysis. None of the trials was classified as low risk of bias. The use of thromboelastography- (TEG®) or thromboelastometry (ROTEM®)-guided algorithms did not reduce mortality [risk ratio (RR) 0.55, 95% confidence interval (CI) 0.28-1.10] without heterogeneity (I2=1%), reoperation for bleeding, stroke, ventilation time, or hospital length of stay compared with standard care. Use of TEG® or ROTEM® resulted in reductions in the frequency of red blood cell (Risk Ratio 0.88, 95% Confidence Interval 0.79-0.97; I2=43%) and platelet transfusion (Risk Ratio 0.78, 95% Confidence Interval 0.66-0.93; I2=0%). Group Reading Assessment and Diagnostic Evaluation (GRADE) assessment demonstrated that the quality of the evidence was low or very low for all estimated outcomes. Routine use of viscoelastic point-of-care tests did not improve important clinical outcomes beyond transfusion in adults undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Despite many years of clinical and experimental research, the contribution of cardiopulmonary bypass (CPB) and cardioplegic arrest to morbidity and mortality following cardiac surgery remains unclear. This is due, in part, to lack of suitable control group against which bypass and cardioplegic arrest can be compared. The recent success of beating heart coronary artery bypass grafting has, however, for the first time, provided an opportunity to compare the same operation, in similar patient groups, with, or without CPB and cardioplegic arrest. CPB is associated with an acute phase reaction of protease cascades, leucocyte, and platelet activation that result in tissue injury. This is largely manifest as subclinical organ dysfunction that produces a clinical effect in those patients that generate an excessive inflammatory response or in those with limited functional reserve. The contribution of myocardial ischemia/reperfusion, secondary to aortic cross-clamping, and cardioplegic arrest, to the systemic inflammatory response and wider organ dysfunction is unknown, and requires further evaluation in clinical trials.(J Card Surg 2004;19:481-488) [ABSTRACT FROM AUTHOR]

Background: Allograft vasculopathy remains the leading cause of late allograft failure following transplantation and can be inhibited by the antiproliferative drug rapamycin. This study assessed the efficacy of combining rapamycin therapy with calcineurin inhibition. Methods: Male Sprague-Dawley rats received rapamycin 0.05 mg/kg daily and either tacrolimus 0.1 mg/kg or cyclosporin 5 mg/kg daily, and findings were compared with those in an untreated control group. Animals underwent left common carotid artery balloon angioplasty; the artery was explanted after 2 weeks. Morphometric analysis was performed on transverse sections and the intima: media ratio was calculated. Profibrotic gene expression was measured with competitive reverse transcriptase-polymerase chain reaction at 14 and 28 days. Proliferation was determined with proliferating cell nuclear antigen at 14 and 28 days. Extracellular matrix deposition was quantified with Sirius red. Results: The combination of rapamycin and tacrolimus was associated with the greatest reduction in intimal thickening. Furthermore, treatment with rapamycin and tacrolimus significantly attenuated extracellular matrix deposition compared with rapamycin and cyclosporin (P < 0.02). Conclusion: The effects of rapamycin in combination with tacrolimus were better than those observed with rapamycin and cyclosporin. [ABSTRACT FROM AUTHOR]

Background: Chronic allograft dysfunction (CAD), the leading cause of solid organ transplant failure, is characterized by histological evidence of extracellular matrix (ECM) accumulation (fibrosis). The aim of this study was to characterize the changes in fibrosis-associated gene expression in an experimental model of CAD and to measure the effect of the immunosuppressant cyclosporin on these changes. Methods: Lewis recipients of F344 rat thoracic to abdominal transplants were administered cyclosporin or no treatment. Vascular remodelling and ECM accumulation (picrosirius red) were measured using computerized histomorphometry. Fibrosis-associated gene expression was studied by semiquantitative reverse transcription–polymerase chain reaction. Results: Cyclosporin inhibited medial ECM accumulation and vascular remodelling in allografts. This was associated with an attenuation of the graft inflammatory infiltrate and a reduction in intragraft matrix metalloproteinase (MMP) 2 and MMP-9 messenger RNA (mRNA) levels. There was a significant negative correlation between neoadventitial ECM density and MMP-9 expression, as well as with vessel circumference. Neoadventitial ECM density was significantly higher in the cyclosporin-treated group than in animals with untreated allografts, as were mRNA levels of collagen 3 and tissue inhibitor of metalloproteinase 1. Conclusion: The alloimmune injury itself may contribute directly to vascular remodelling and fibrosis in allograft vasculopathy. Cyclosporin attenuated this component of the pathophysiology of CAD effectively. [ABSTRACT FROM AUTHOR]

Background: The success of infragenicular revascularisation for lower limb ischaemia is limited by the high proportion of patients without ipsilateral long saphenous vein (LSV) of adequate length or quality. The aim of this study was to report the results of an autogenous vein only policy for infragenicular revascularisation utilising contralateral LSV when ipsilateral LSV is inadequate. The treatment and outcome of infection of autogenous grafts with methicillin resistant Staphylococcus aureus (MRSA) is also reported.Patients and Methods: The vascular audit database and patient case notes were reviewed retrospectively for patients with arterial occlusive disease requiring infragenicular reconstruction. There were 68 critically ischaemic legs in 65 patients of whom 48 were male: median age (range) 74 years (41-94), over a three year period.Results: Thirty six patients (53%) underwent revascularisation (eight infragenicular femoropopliteal bypass, 28 femorodistal), 24 (35%) underwent primary amputation and a further eight (12%) were found to have unsuitable distal vessels for revascularisation after tibial vessel exploration and intraoperative angiography. Thirty three grafts (92%) utilised LSV and three (8%) were polytetrafluoroethylene grafts. Thirteen patients (39%) lacked adequate ipsilateral LSV of whom 12 had the contralateral leg explored providing suitable LSV in 10/12 (83%). Contralateral LSV was used as a single length conduit in two cases and as a venovenous composite graft in eight cases. Primary, primary assisted, and secondary patency rates at two years were 38%, 77%, and 81% respectively. Actuarial limb survival and patient survival rates at two years were 86% and 61% respectively. Eleven patients developed ipsilateral wound complications (30%) including seven (21%) who developed MRSA infection of the ipsilateral leg wound. MRSA wound infection was treated successfully in all cases by antibiotic therapy (intravenous vancomycin). No patient subsequently required saphenous vein harvesting for a secondary reconstruction or coronary artery bypass graft.Conclusion: Excellent long term results can be achieved using autogenous vein for infragenicular revascularisation and the contralateral LSV is an excellent alternative in the absence of suitable ipsilateral LSV. Autogenous vein may confer some protection against severe complications observed with MRSA infection seen in vascular patients and therefore its use is recommended. [ABSTRACT FROM AUTHOR]

Summary Background Primary thrombosis and chronic allograft nephropathy are important causes of early and late graft loss, respectively, following renal transplantation. This study examined the potential for aspirin therapy to reduce these complications. Methods A consecutive series of 105 cadaveric renal transplants treated with aspirin 150 mg daily for the first 3 months after transplantation was compared with an untreated historical control group (n = 121). Protocol needle-core biopsies were performed on all transplants in both groups at 1 week and 12 months after transplantation. Needle-core allograft biopsies were performed at 3, 6 and 12 months after transplantation, and serum creatinine was measured at each outpatient attendance for the duration of follow-up. Results There was a significantly lower rate of primary allograft thrombosis in patients treated with aspirin (none of 105) compared with that in the control group (six (5 per cent) of 121; P = 0·03). There were no differences in renal function or 2-year allograft survival between the two groups. Aspirin-treated patients had a lower incidence of chronic allograft nephropathy at 1 year than controls although this did not reach statistical significance (16 versus 26 per cent; P = 0·075). There were no major bleeding complications in either group in association with peptic ulcer disease or following renal transplant biopsy. Conclusion Aspirin reduced the rate of early graft thrombosis of renal transplants in this series but did not improve renal function or graft survival. A trend towards a lower rate of chronic allograft nephropathy was noted with aspirin treatment. These findings require confirmation in a prospective randomized trial. [ABSTRACT FROM AUTHOR]

Summary Background The recent expansion of renal replacement therapy programmes has been associated with an increase in the number and complexity of patients requiring permanent vascular access. The introduction of strategies designed to maximize secondary access patency is, therefore, increasingly important as a means of prolonging patient survival on dialysis, reducing morbidity and reducing the escalating cost of such programmes. Methods A review of the current literature on the planning of vascular access, access surveillance methods and treatment of the most common complications was performed. Results Multidisciplinary vascular access planning, increased use of preoperative imaging and the preferential use of autogeneous vein are essential to obtain the best long-term results. While vascular access surveillance, in particular protocols involving direct measurement of access flow, enables the prospective detection and treatment of venous stenosis, the precise indications for treating venous stenosis remain unclear. Surgical revision remains the gold standard for the treatment of failing arteriovenous fistulas, but recent advances in interventional radiological techniques along with the suitability of arteriovenous fistulas for percutaneous intervention may offer an effective alternative. The effect of both these interventions on access patency requires comparison in a randomized trial. Conclusion The introduction of strategies to improve access patency rates will change vascular access surgical practice away from the construction of new fistulas towards an increase in outpatient percutaneous intervention and surgical revisional procedures. The role of surgical interventions requires clearer definition. [ABSTRACT FROM AUTHOR]

Summary: In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre‐operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 μg.l−1; functional iron deficiency as ferritin 30–100 μg.l−1 or transferrin saturation < 20%; and the remainder as non‐iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co‐primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri‐operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one‐third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre‐operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l−1, 95%CI 5.3–12.5; moderate in functional iron deficiency, mean difference 2.8 g.l−1, 95%CI −0.1 to 5.7; and with little change seen in those patients who were non‐iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p = 0.33 for interaction), transferrin saturation (p = 0.13) or in combination (p = 0.45), or for the number of blood transfusions (p = 0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay. [ABSTRACT FROM AUTHOR]

Objectives: To inform the design of a clinical trial of a targeted screening programme for relatives of individuals affected by thoracic aortic disease, we performed a consensus exercise as to the acceptability of screening, the optimal sequence and choice of tests, long-term patient management, and choice of trial design.Methods: Working with the Aortic Dissection Awareness UK & Ireland patient association, we performed a Delphi exercise with clinical experts, patients, and carers, consisting of three rounds of consultation followed by a final multi-stakeholder face-to-face workshop.Results: Thirty-five experts and 84 members of the public took part in the surveys, with 164 patients and clinicians attending the final workshop. There was substantial agreement on the need for a targeted screening pathway that would employ a combined approach (imaging + genetic testing). The target population would include the first- and second-degree adult (> 15 years) relatives, with no upper age limit of affected patients. Disagreement persisted about the screening process, sequence, personnel, the imaging method to adopt, computed tomography (CT) scan vs magnetic resonance imaging (MRI), and the specifics of a potential trial, including willingness to undergo randomisation, and measures of effectiveness and acceptability.Conclusion: A Delphi process, initiated by patients, identified areas of uncertainty with respect to behaviour, process, and the design of a targeted screening programme for thoracic aortic disease that requires further research prior to any future trial. [ABSTRACT FROM AUTHOR]

Background: The aim was to investigate whether preoperative weight loss results in improved clinical outcomes in surgical patients with clinically significant obesity. Methods: This was a systematic review and aggregate data meta‐analysis of RCTs and cohort studies. PubMed, MEDLINE, Embase and CINAHL Plus databases were searched from inception to February 2018. Eligibility criteria were: studies assessing the effect of weight loss interventions (low‐energy diets with or without an exercise component) on clinical outcomes in patients undergoing any surgical procedure. Data on 30‐day or all‐cause in‐hospital mortality were extracted and synthesized in meta‐analyses. Postoperative thromboembolic complications, duration of surgery, infection and duration of hospital stay were also assessed. Results: A total of 6060 patients in four RCTs and 12 cohort studies, all from European and North American centres, were identified. Most were in the field of bariatric surgery and all had some methodological limitations. The pooled effect estimate suggested that preoperative weight loss programmes were effective, leading to significant weight reduction compared with controls: mean difference –7·42 (95 per cent c.i. –10·09 to –4·74) kg (P < 0·001). Preoperative weight loss interventions were not associated with a reduction in perioperative mortality (odds ratio 1·41, 95 per cent c.i. 0·24 to 8·40; I2 = 0 per cent, P = 0·66) but the event rate was low. The weight loss groups had shorter hospital stay (by 27 per cent). No differences were found for morbidity. Conclusion: This limited preoperative weight loss has advantages but may not alter the postoperative morbidity or mortality risk. Possible, but how much is enough? [ABSTRACT FROM AUTHOR]

Background and objectives: To review preclinical and clinical studies that have evaluated the effects of red cell rejuvenation in vivo and in vitro and to assess the potential risks and benefits from their clinical use. Materials and methods: A systematic review and narrative synthesis of the intervention of red cell rejuvenation using a red cell processing solution containing inosine, pyruvate, phosphate and adenine. Outcomes of interest in vitro were changes in red cell characteristics including adenosine triphosphate (ATP), 2,3‐diphosphoglycerate (2,3‐DPG), deformability and the accumulation of oxidized lipids and other reactive species in the red cell supernatant. Outcomes in vivo were 24‐h post‐transfusion survival and the effects on oxygen delivery, organ function and inflammation in transfused recipients. Results: The literature search identified 49 studies evaluating rejuvenated red cells. In vitro rejuvenation restored cellular properties including 2,3‐DPG and ATP to levels similar to freshly donated red cells. In experimental models, in vivo transfusion of rejuvenated red cells improved oxygen delivery and myocardial, renal and pulmonary function when compared to stored red cells. In humans, in vivo 24‐h survival of rejuvenated red cells exceeded 75%. In clinical studies, rejuvenated red cells were found to be safe, with no reported adverse effects. In one adult cardiac surgery trial, transfusion of rejuvenated red cells resulted in improved myocardial performance. Conclusion: Transfusion of rejuvenated red cells reduces organ injury attributable to the red cell storage lesion without adverse effects in experimental studies in vivo. The clinical benefits of this intervention remain uncertain. [ABSTRACT FROM AUTHOR]

Background: We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys.Methods: In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery.Results: The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n =98 patient-specific algorithm; n =106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups.Conclusions: These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery.Clinical Trial Registration: http://www.controlled-trials.com , ISRCTN 23557269. [ABSTRACT FROM AUTHOR]

Background: Experimental studies suggest that mechanical cell washing to remove pro-inflammatory components that accumulate in the supernatant of stored donor red blood cells (RBCs) might reduce inflammation and organ injury in transfused patients.Methods: Cardiac surgery patients at increased risk of large-volume RBC transfusion were eligible. Participants were randomized to receive either mechanically washed allogenic RBCs or standard care RBCs. The primary outcome was serum interleukin-8 measured at baseline and at four postsurgery time points. A mechanism substudy evaluated the effects of washing on stored RBCs in vitro and on markers of platelet, leucocyte, and endothelial activation in trial subjects.Results: Sixty adult cardiac surgery patients at three UK cardiac centres were enrolled between September 2013 and March 2015. Subjects received a median of 3.5 (interquartile range 2-5.5) RBC units, stored for a mean of 21 ( sd 5.2) days, within 48 h of surgery. Mechanical washing reduced concentrations of RBC-derived microvesicles but increased cell-free haemoglobin concentrations in RBC supernatant relative to standard care RBC supernatant. There was no difference between groups with respect to perioperative serum interleukin-8 values [adjusted mean difference 0.239 (95% confidence intervals -0.231, 0.709), P =0.318] or concentrations of plasma RBC microvesicles, platelet and leucocyte activation, plasma cell-free haemoglobin, endothelial activation, or biomarkers of heart, lung, or kidney injury.Conclusions: These results do not support a hypothesis that allogenic red blood cell washing has clinical benefits in cardiac surgery.Clinical Trial Registration: ISRCTN 27076315. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty regarding the safety of different volume replacement solutions. The aim of this study was systematically to review evidence of crystalloid versus colloid solutions, and to determine whether these results are influenced by trial design or clinical setting. Methods: PubMed, Embase and the Cochrane Central Register of Controlled Trials were used to identify randomized clinical trials (RCTs) that compared crystalloids with colloids as volume replacement solutions in patients with traumatic injuries, those undergoing surgery and in critically ill patients. Adjusted odds ratios (ORs) for mortality and major morbidity including renal injury were pooled using fixed-effect and random-effects models. Results: Some 59 RCTs involving 16 889 patients were included in the analysis. Forty-one studies (69 per cent) were found to have selection, detection or performance bias. Colloid administration did not lead to increased mortality (32 trials, 16 647 patients; OR 0.99, 95 per cent c.i. 0.92 to 1.06), but did increase the risk of developing acute kidney injury requiring renal replacement therapy (9 trials, 11 648 patients; OR 1.35, 1.17 to 1.57). Sensitivity analyses that excluded small and low-quality studies did not substantially alter these results. Subgroup analyses by type of colloid showed that increased mortality and renal replacement therapy were associated with use of pentastarch, and increased risk of renal injury and renal replacement therapy with use of tetrastarch. Subgroup analysis indicated that the risks of mortality and renal injury attributable to colloids were observed only in critically ill patients with sepsis. Conclusion: Current general restrictions on the use of colloid solutions are not supported by evidence. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to develop two novel risk prediction scores for transfusion and bleeding that would be used to inform treatment decisions, quality assurance, and clinical trial design in cardiac surgery. Methods. Clinical data prospectively collected from 26 UK cardiac surgical centres and a single European centre were used to develop two risk prediction models: one for any red blood cell (RBC) transfusion, and the other for large volume blood transfusion (⩾4 RBC units; LVBT), an index of severe blood loss. 'Complete case' data were available for 24 749 patients. Multiple imputation was used for missing covariate data (typically <5% per variable), with the imputed data set containing 39 970 patients. Risk models were developed in the complete case data set, with internal validation using leave-one-centre-out cross-validation. The final selected models were fitted to the imputed data set. Final risk scores were then compared with the performance of three existing scores: the Transfusion Risk and Clinical Knowledge score (TRACK), the Transfusion Risk Understanding Scoring Tool (TRUST), and the Papworth Bleeding Risk Score (BRiSc). Results. The area under the receiver operating characteristic curve (AUC) was 0.77 (95% confidence interval 0.77-0.77) for the any RBC transfusion score and AUC 0.80 (0.79-0.80) for the LVBT score in the imputed data set. The LVBT model also showed excellent discrimination (Hosmer-Lemeshow P=0.32). In the imputed data set, the AUCs for the TRACK and TRUST scores for any RBC transfusion were 0.71 and 0.71, respectively, and for LVBT the AUC for the BRiSc score was 0.69. Conclusions. Two new risk scores for any RBC transfusion or LVBT among cardiac surgery patients have excellent discrimination, and could inform clinical decision making. [ABSTRACT FROM AUTHOR]

Insulin resistance is of major pathogenic importance in several common human disorders, but the underlying mechanisms are unknown. The stroke-prone spontaneously hypertensive (SHRSP) rat is a model of human insulin resistance and is characterized by reduced insulin-mediated glucose disposal and defective fatty acid metabolism in isolated adipocytes (Collison et al. [Diabetes 49:2222-2226, 2000]). In this study, we have examined skeletal muscle and cultured skeletal muscle myoblasts for defects in insulin action in the male SHRSP rat model compared with the normotensive, insulin-sensitive control strain, Wistar-Kyoto (WKY). We show that skeletal muscle from SHRSP animals exhibits a marked decrease in insulin-stimulated glucose transport compared with WKY animals (fold increase in response to insulin: 1.4 +/- 0.15 in SHRSP, 2.29 +/- 0.22 in WKY; n = 4, P = 0.02), but the stimulation of glucose transport in response to activation of AMP-activated protein kinase was similar between the two strains. Similar reductions in insulin-stimulated glucose transport were also evident in myoblast cultures from SHRSP compared with WKY cultures. These differences were not accounted for by a reduction in cellular GLUT4 content. Moreover, analysis of the levels and subcellular distribution of insulin receptor substrates 1 and 2, the p85alpha subunit of phosphatidylinositol 3'-kinase, and protein kinase B (PKB)/cAKT in skeletal muscle did not identify any differences between the two strains; the insulin-dependent activation of PKB/cAKT was not different between the two strains. However, the total cellular levels of caveolin and flotillin, proteins implicated in insulin signal transduction/compartmentalization, were markedly elevated in skeletal muscles from SHRSP compared with WKY animals. Increased cellular levels of the soluble N-ethylmaleimide attachment protein receptor (SNARE) proteins syntaxin 4 and vesicle-associated membrane protein (VAMP)-2 were also observed in the insulin-resistant SHRSP strain. Taken together, these data suggest that the insulin resistance observed in the SHRSP is manifest at the level of skeletal muscle, that muscle cell glucose transport exhibits a blunted response to insulin but unchanged responses to activation of AMP-activated protein kinase, that alterations in key molecules in both GLUT4 trafficking and insulin signal compartmentalization may underlie these defects in insulin action, and that the insulin resistance of these muscles appears to be of genetic origin rather than a paracrine or autocrine effect, since the insulin resistance is also observed in cultured myoblasts over several passages. [ABSTRACT FROM AUTHOR]

Presents an abstract of the article 'Total Parathyroidectomy in Patients With Chronic Renal Failure,' published in the 2000 issue of the 'British Journal of Surgery.'

Insulin stimulation of adipose and muscle cells results in the translocation of GLUT4 from an intracellular location to the plasma membrane; this translocation is defective in insulin resistance. Studies have suggested an important role for synaptobrevin and syntaxin homologues in this event, particularly the v-soluble N-ethylmaleimide attachment protein receptors (SNAREs) cellubrevin and vesicle-associated membrane protein-2 (VAMP-2) and the t-SNARE syntaxin 4, but the expression of these proteins has not been studied in insulin-resistant tissues. Therefore, we examined SNARE protein content in skeletal muscle from Zucker diabetic fatty (ZDF) rats compared with lean controls and determined the effect of the thiazolidinedione insulin sensitizer rosiglitazone on these proteins. GLUT4 levels in skeletal muscle from ZDF rats were similar to those in lean control animals. In contrast, cellubrevin, VAMP-2, and syntaxin 4 protein levels were elevated (2.8-fold, P = 0.02; 3.7-fold, P = 0.01; and 2.2-fold, P < 0.05, respectively) in skeletal muscle from ZDF rats compared with lean controls. Restoration of normoglycemia and normoinsulinemia in ZDF rats with rosiglitazone (30 micromol/kg) normalized cellubrevin, VAMP-2, and syntaxin 4 protein to levels approaching those observed in lean control animals. These data show that elevated v- and t-SNARE protein levels are associated with insulin resistance in skeletal muscle and that these increases may be reversed by rosiglitazone treatment concomitant with a restoration of glycemic control. Such increases in SNARE protein levels were not observed in streptozotocin-induced diabetic rats, which suggests that hyperinsulinemia rather than hyperglycemia may be more important in modulating SNARE protein expression in rodent models of insulin resistance. Consistent with this hypothesis, elevated levels of SNARE proteins were also observed in 3T3-L1 adipocytes chronically treated with insulin (500 nmol/l for 24 h). These data argue that SNARE protein levels may be altered in insulin-resistant states and that the levels of these proteins are modulated by agents that increase insulin sensitivity. Moreover, these data demonstrate for the first time altered expression of proteins known to regulate GLUT4 translocation in a model of diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To develop a monoclonal antibody that recognises an epitope of the native β[sub 3]-adrenoceptor expressed on the extracellular surface of human cells and tissues. DESIGN: A high affinity monoclonal antibody, Mab72c, was raised against the human β[sub 3]-adrenoceptor expressed on a transfected mammalian cell line. RESULTS: In CHO (Chinese hamster ovary) cells transfected with β[sub 3]-adrenoceptor cDNA, antibody labelling was found to be proportional to receptor density measured by the binding of the radiolabelled β-adrenoceptor antagonist, [[sup 125]I]iodocyanopindolol. The use of Mab 72c has demonstrated the expression of the β[sub 3]-adrenoceptor in a variety of human tissues, including gall bladder, prostate and colon, where a mRNA signal had been detected previously. This study also provides the first direct demonstration of the expression of β[sub 3]-adrenoceptors in human skeletal muscle, atrium and adipose tissue. CONCLUSION: The development of this antibody represents an important addition to the armentarium of reagents that are available to study the localisation of β[sub 3]-adrenoceptors in human tissues. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Aprotinin Revisited," by S.M. DeSantis and C. Lazaridis, that was published in a 2013 issue of the journal "Intensive Care Medicine."