tbuckley/cabot-search huggingface dataset:
Reduction of Surgical Mortality and Morbidity in Diabetic Patients Undergoing Cardiac Surgery With a Combined Intravenous and Subcutaneous Insulin Glucose Management Strategy
Authors: Lowell R. Schmeltz, Anthony J. DeSantis, Vinaya Thiyagarajan, Kathleen Schmidt, Eileen O'Shea-Mahler, Diana Johnson, Joseph Henske, Patrick M. McCarthy, Thomas G. Gleason, Edwin C. McGee, Mark E. Molitch
Journal: Diabetes Care (2007)

To determine if glucose management in postcardiothoracic surgery patients with a combined intravenous (IV) and subcutaneous (SC) insulin regimen reduces mortality and morbidity in patients with diabetes and stress-induced hyperglycemia.Retrospective review of 614 consecutive patients who underwent cardiothoracic (CT) surgery in 2005 was performed to evaluate the incidence and treatment of postoperative hyperglycemia and operative morbidity and mortality. Hyperglycemic patients (glucose >6.05 mmol/l) were treated with IV insulin in the intensive care unit (ICU) followed by SC insulin (outside ICU). Subgroup analysis was performed on 159 coronary artery bypass grafting (CABG)-only patients.Among all CT surgeries, patients with a preoperative diagnosis of diabetes had higher rates of postoperative mortality (7.3 vs. 3.3%; P = 0.03) and pulmonary complications (19.5 vs. 11.6%; P = 0.02) but had similar rates of infections and cardiac, renal, and neurological complications on univariate analysis. However, on multivariate analysis, a preoperative diagnosis of diabetes was not a significant factor in postoperative mortality or pulmonary complications. In CABG-only patients, no significant differences were seen in outcomes between diabetic and nondiabetic patients. Independent of diabetic status, glucose > or =11 mmol/l on ICU admission was predictive of higher rates of mortality and renal, pulmonary, and cardiac postoperative complications.A combination of IV insulin (in the ICU) and SC insulin (outside the ICU), a less costly and less nursing-intensive therapy than 3 days of IV insulin postoperatively, results in a reduction of the increased surgical morbidity and mortality in diabetic patients after CT surgery.
Challenges and Possible Solutions to Colorectal Cancer Screening for the Underserved
Authors: S. Gupta, D. A. Sussman, C. A. Doubeni, D. S. Anderson, L. Day, A. R. Deshpande, B. Joseph Elmunzer, A. O. Laiyemo, J. Mendez, M. Somsouk, J. Allison, T. Bhuket, Z. Geng, B. B. Green, S. H. Itzkowitz, M. E. Martinez
Journal: JNCI Journal of the National Cancer Institute (2014)

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide.CRC incidence and mortality can be reduced through screening.However, in the United States, screening participation remains suboptimal, particularly among underserved populations such as the uninsured, recent immigrants, and racial/ethnic minority groups.Increasing screening rates among underserved populations will reduce the US burden of CRC.In this commentary focusing on underserved populations, we highlight the public health impact of CRC screening, list key challenges to screening the underserved, and review promising approaches to boost screening rates.We identify four key policy and research priorities to increase screening among underserved populations: 1) actively promote the message, "the best test is the one that gets done"; 2) develop and implement methods to identify unscreened individuals within underserved population groups for screening interventions; 3) develop and implement approaches for organized screening delivery; and 4) fund and enhance programs and policies that provide access to screening, diagnostic follow-up, and CRC treatment for underserved populations.This commentary represents the consensus of a diverse group of experts in cancer control and prevention, epidemiology, gastroenterology, and primary care from across the country who formed the Coalition to Boost Screening among the Underserved in the United States.The group was organized and held its first annual working group meeting in conjunction with the World Endoscopy Organization's annual Colorectal Cancer Screening Committee meeting during Digestive Disease Week 2012 in San Diego, California.
Compartment-Specific Expression and Function of the Chemokine IP-10/CXCL10 in a Model of Renal Endothelial Microvascular Injury
Authors: Ulf Panzer, Oliver M. Steinmetz, Rüdiger R. Reinking, Tobias N. Meyer, Susanne Fehr, André Schneider, Gunther Zahner, Gunter Wolf, Udo Helmchen, Patrick Schaerli, Rolf A.K. Stahl, Friedrich Thaiss
Journal: Journal of the American Society of Nephrology (2005)

The recruitment of inflammatory cells into renal tissue, mainly T cells and monocytes, is a typical feature of various renal diseases such as glomerulonephritis, thrombotic angiopathies, allograft rejection, and vasculitis. T cells predominantly infiltrate the tubulointerstitium, whereas monocytes are present in the tubulointerstitial and glomerular compartment. Because chemokines play a pivotal role in leukocyte trafficking under inflammatory conditions, this study investigated whether a differential expression of chemokines contributes to the precise coordination of leukocyte subtype trafficking in a rat model of renal microvascular endothelial injury. Renal microvascular endothelial injury was induced in rats by selective renal artery perfusion with an anti-endothelial antibody. Induction of the disease led to severe glomerular and tubulointerstitial endothelial injury with subsequent upregulation of chemokines followed by inflammatory cell recruitment. Among the analyzed chemokine mRNA, IP-10/CXCL10 (119-fold), acting via CXCR3 on activated T cells, and MCP-1/CCL2 (65-fold), acting via CCR2 on monocytes, were by far the most strongly upregulated chemokines. In situ hybridization revealed that IP-10/CXCL10 mRNA was selectively expressed by endothelial cells in the tubulointerstitial area, co-localizing with infiltrating T cells. Despite extensive damage of glomerular vasculature, no IP-10/CXCL10 expression by glomerular endothelial cells was detected. MCP-1/CCL2 mRNA in contrast was detectable in the glomerulus and the tubulointerstitium. Treatment with a neutralizing anti-IP-10/CXCL10 antibody significantly reduced the number of infiltrating tubulointerstitial T cells without affecting monocyte migration and led to an improved renal function. Our study demonstrates a role of IP-10/CXCL10 on T cell recruitment in a rat model of renal endothelial microvascular injury. Furthermore, a differential chemokine expression profile by endothelial cells in different renal compartments was found. These findings are consistent with the hypothesis that functional heterogeneity of endothelial cells from different vascular sites exists and provide an insight into the molecular mechanisms that may mediate compartment-specific T cell and monocyte recruitment in inflammatory renal disease.
The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A
Authors: Ana Paula Moreira, Karen A. Cavassani, Ugur B. Ismailoglu, Rikki Hullinger, Michael P. Dunleavy, Darryl A. Knight, Steven L. Kunkel, Satoshi Uematsu, Shizuo Akira, Cory M. Hogaboam
Journal: Journal of Clinical Investigation (2011)

TLRs are a family of receptors that mediate immune system pathogen recognition. In the respiratory system, TLR activation has both beneficial and deleterious effects in asthma. For example, clinical data indicate that TLR6 activation exerts protective effects in asthma. Here, we explored the mechanism or mechanisms through which TLR6 mediates this effect using mouse models of Aspergillus fumigatus-induced and house dust mite antigen-induced (HDM antigen-induced) chronic asthma. Tlr6-/- mice with fungal- or HDM antigen-induced asthma exhibited substantially increased airway hyperresponsiveness, inflammation, and remodeling compared with WT asthmatic groups. Surprisingly, whole-lung levels of IL-23 and IL-17 were markedly lower in Tlr6-/- versus WT asthmatic mice. Tlr6-/- DCs generated less IL-23 upon activation with lipopolysaccharide, zymosan, or curdlan. Impaired IL-23 generation in Tlr6-/- mice also corresponded with lower levels of expression of the pathogen-recognition receptor dectin-1 and expansion of Th17 cells both in vivo and in vitro. Exogenous IL-23 treatment of asthmatic Tlr6-/- mice restored IL-17A production and substantially reduced airway hyperresponsiveness, inflammation, and lung fungal burden compared with that in untreated asthmatic Tlr6-/- mice. Together, our data demonstrate that TLR6 activation is critical for IL-23 production and Th17 responses, which both regulate the allergic inflammatory response in chronic fungal-induced asthma. Thus, therapeutics targeting TLR6 activity might prove efficacious in the treatment of clinical asthma.
Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis
Authors: C. Hutchinson, C. A Geissler, J. J Powell, A. Bomford
Journal: Gut (2007)

<h3>Abstract</h3> Vertebrate limb morphology often reflects the environment, due to variation in locomotor requirements and other ecological traits. However, proximal and distal limb segments may evolve differently to each other, reflecting an anatomical gradient of functional specialization that has been suggested to be impacted by the timing of bone condensation during ontogeny. Here we explore whether the temporal sequence of bone condensation predicts variation in the capacity of evolution to generate morphological diversity between proximal and distal forelimb segments across more than 600 species of mammals. Our findings are consistent with the hypothesis that late developing distal limb elements should display greater morphological variation than more proximal limb elements, which condense earlier during morphogenesis. Distal limb elements, belonging to the autopod, not only exhibit higher diversity of form, but are also more integrated and, on average, show greater evolutionary versatility than intermediate and upper limb segments. Our findings indicate that the macroevolutionary patterns of proximal and distal limb segments are not the same, suggesting that strong functional selection, combined with the higher potential of development to generate variation in more distal limb structures, facilitate the evolution of high autopodial disparity in mammals.
Joint surgery in the Utrecht Rheumatoid Arthritis Cohort: the effect of treatment strategy
Authors: S M M Verstappen, J N Hoes, E J ter Borg, J W J Bijlsma, A A M Blaauw, G A van Albada-Kuipers, C van Booma-Frankfort, J W G Jacobs
Journal: Annals of the Rheumatic Diseases (2006)

To investigate the prevalence and prognostic factors of joint surgery in a large cohort of patients with rheumatoid arthritis, whose treatment, clinical and radiographic data have been assessed at predefined points in time since disease onset.Data on surgical interventions were retrospectively obtained from 482 patients with rheumatoid arthritis whose follow-up data for at least 2 years were available, including treatment and response to treatment during the first 2 years. Survival time until the first surgical intervention and until the first major surgical intervention was determined for the total study population by Kaplan-Meier survival curves. Three separate Cox regression analyses were carried out to determine which variables measured at baseline, during the first year and during the first 2 years were predictors for joint surgery.27% of the patients underwent surgical interventions. Mean survival time until the first surgical intervention was 10.4 years. The percentage of patients with a surgical intervention was 10% lower in the group with response to treatment when compared with the non-response group. Next to a delayed start with disease-modifying antirheumatic drugs, fast radiographic progression during the first year and first 2 years was a predictor of joint surgery in the multivariate regression analyses.Treatment with disease-modifying antirheumatic drugs immediately after diagnosis results in less joint surgery when compared with a delayed start. Furthermore, joint surgery is carried out more often in patients who do not respond to treatment.
Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation
Authors: Falk Martin, Tobias Linden, Dörthe M. Katschinski, Felix Oehme, Ingo Flamme, Chinmay K. Mukhopadhyay, Katrin Eckhardt, Juliane Tröger, Sandra Barth, Gieri Camenisch, Roland H. Wenger
Journal: Blood (2005)
The effects of isotretinoin on follicular and sebaceous gland differentiation
Authors: K. DALZIEL, S. BARTON, R. MARKS
Journal: British Journal of Dermatology (1987)

Follicular and sebaceous gland cell differentiation was investigated during treatment of acne patients with isotretinoin. Sebaceous glands were significantly reduced in volume and showed decreased metabolic activity as measured by glucose‐6‐phosphate dehydrogenase and succinic dehydrogenase enzyme activities. There was no measurable change in the volume of follicular duct epithelium or in its metabolic activity during treatment. Metabolic activity was also unchanged in the interfollicular epidermis, contrasting with the effects of another retinoid, etretinate. These findings provide no support for the proposition that alteration in the process of follicular keratinization forms a substantial part of the mode of action of isotretinoin.
Low-Dose Therapy With the Long-Acting Erythropoietin Analogue Darbepoetin Alpha Persistently Activates Endothelial Akt and Attenuates Progressive Organ Failure
Authors: Ferdinand H. Bahlmann, Rong Song, Sascha M. Boehm, Michael Mengel, Reinhard von Wasielewski, Carsten Lindschau, Torsten Kirsch, Kirsten de Groot, Robert Laudeley, Eva Niemczyk, Faikah Güler, Jan Menne, Hermann Haller, Danilo Fliser
Journal: Circulation (2004)

The hematopoietic cytokine erythropoietin has cytoprotective effects in endothelial cells in vitro that are mediated through direct activation of the pro-survival Akt tyrosine kinase signaling pathway. We tested the hypothesis that low-dose therapy with the long-acting recombinant human erythropoietin analogue darbepoetin alpha protects vascular endothelium in vivo in a classic remnant kidney rat model characterized by severe endothelial damage, progressive vascular sclerosis, and ischemia-induced tissue fibrosis.Using a parallel group study design, we randomly assigned animals after 5/6 nephrectomy to treatment with either saline (n=36) or 0.1 microg/kg body wt darbepoetin (n=24) subcutaneously once weekly. We monitored hematocrit, blood pressure, and serum creatinine regularly and obtained renal tissue 6 weeks after nephrectomy for morphological and immunohistochemical analysis. Darbepoetin-treated animals had significantly improved survival compared with saline-treated controls (63% versus 33%; P<0.05), although hematocrit levels were similar in both groups. Darbepoetin treatment ameliorated endothelial damage; attenuated the composite tissue injury score (saline 1.9+/-0.4; darbepoetin 0.4+/-0.2; P<0.001), which included vascular sclerosis, glomerulosclerosis, and tubulointerstitial damage; and preserved renal function. We found persistent activation of the pro-survival Akt signaling pathway in endothelial and epithelial glomerular cells in darbepoetin-treated animals, accompanied by a significant reduction of apoptotic cell death in renal tissue.Low-dose darbepoetin treatment confers vascular and tissue protection that is associated with persistent stimulation of the pro-survival Akt signaling pathway. The use of recombinant human erythropoietin or analogues may have utility in preventing ischemia-related progressive vascular injury and organ failure.
Hypoxia Increases Androgen Receptor Activity in Prostate Cancer Cells
Authors: Soo-Yeon Park, Yun-Jeong Kim, Allen C. Gao, James L. Mohler, Sergio A. Onate, Alejandro A. Hidalgo, Clement Ip, Eun-Mi Park, Sun Young Yoon, Young-Mee Park
Journal: Cancer Research (2006)

Abstract Recent studies show that prostate cancer cells are able to survive in a hypoxic tumor environment, and the extent of tumor hypoxia correlates with poor clinical outcome. Androgen deprivation, the most common form of prostate cancer therapy, was itself shown to induce a state of transient hypoxia at the microenvironmental level. Because androgen receptor (AR) signaling plays a critical role in prostate cancer, we investigated the effect of hypoxia in regulating AR function. We found that in LNCaP prostate cancer cells, AR binding to the androgen-responsive element (ARE), prostate-specific antigen accumulation, and ARE-reporter gene activity were increased after hypoxia treatment. Hypoxia-enhanced AR function was also observed when AR was exogenously introduced into AR-null DU145 cells. Confocal microscopy and chromatin immunoprecipitation assays showed that AR translocation to the nucleus and AR recruitment to the prostate-specific antigen promoter were facilitated after hypoxia treatment. The AR stimulatory effect seemed to be ligand-dependent because it was abrogated when cells were cultured in an androgen-depleted medium, but was restored with the addition of R1881, a synthetic androgen. The sensitivity of AR activation to R1881 was also increased after hypoxia treatment. Although concentrations of &amp;lt;1 nmol/L R1881 did not induce ARE reporter activity under normoxic conditions, exposure to hypoxia greatly potentiated the AR response to low levels of R1881. Collectively, our results provide compelling evidence that changes in hypoxia/reoxygenation stimulate AR trans-activation and sensitization. The AR-stimulatory effect of an unstable tissue oxygenation milieu of a tumor is likely to contribute to treatment resistance and the emergence of recurrent prostate cancer. (Cancer Res 2006; 66(10): 5121-9)
The Results of Insulin Therapy in Diabetes Mellitus
Authors: H. MacLean
Journal: BMJ (1927)

OURNLs 1015 or roasted.Potatoes, mashed or in their jackets.Turnips.Spinach.Artichokes.Mild cheese.Fruit after three months.*Forbidden.-Fat and eggs.Stewed and fried foods.Sweetbreads.Liver.Duck.Kidneys.Pork.Black puddings.Game.High or spiced dishes
The ECGs that will be read around the world—and save lives of sportspeople
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2013)

‘Having a heart attack? There's an iPhone App for that!’ is a true story. We congratulate its inventor Dr David Albert. This issue of BJSM contains advances that are equally exciting and which deserve as much media attention. Sports cardiology is one defining element of the sport and exercise medicine specialty (http://bjsm.bmj.com/content/46/Suppl_1/i2.full). Every one of us has seen an athlete drop dead on film—if not in real life. Whose heart has not stopped on each such occasion? “There but for the grace of God go I” as physician, athlete, or parent. “Houston, we have buy in.”

Sports cardiology is a BJSM ‘priority topic’. We cover priority topics in each of our three ‘pillars’—research, education and implementation. Another way of labelling the ‘pillars’ is innovation, education and knowledge translation. We use BJSM and partner ‘platforms’ (eg, see Partnering with BMJ Learning section) to deliver the content. Think of pages such as this one you are reading, the education tab on the BJSM home …
Subcortical Ca <sup>2+</sup> Waves Sneaking Under the Plasma Membrane in Endothelial Cells
Authors: Masashi Isshiki, Akiko Mutoh, Toshiro Fujita
Journal: Circulation Research (2004)

Subplasmalemmal Ca 2+ , dynamically equilibrated with extracellular Ca 2+ , affects numerous signaling molecules, effectors, and events within this restricted space. We demonstrated the presence of a novel Ca 2+ wave propagating beneath the plasma membrane in response to acute elevation of extracellular [Ca 2+ ], by targeting a Ca 2+ sensor, cameleon, to the endothelial plasmalemma. These subcortical waves, spatially distinct from classical cytosolic Ca 2+ waves, originated in localized regions and propagated throughout the subplasmalemma. Translocation of an expressed GFP fused with a PH domain of PLCδ from the plasma membrane to the cytosol accompanied these subcortical waves, and U73122 attenuated not only the GFP-PHδ translocation, but also the peak amplitude of the subcortical Ca 2+ waves; this finding suggests the involvement of local IP 3 production through PLC-mediated PIP 2 hydrolysis in the initiation of these waves. Changes in NO production as well as PKCβ-GFP translocation from the cytosol to the plasma membrane, but not of GFP-PLA 2 to perinuclear endomembranes, were associated with the subplasmalemmal Ca 2+ changes. Thus, extracellular Ca 2+ maintains the basal PLC activity of the plasma membrane, is involved in the initiation of compartmentalized subcortical Ca 2+ waves, and regulates Ca 2+ -dependent signaling molecules residing in or translocated to the plasma membrane. The full text of this article is available online at http://circres.ahajournals.org.
Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial
Authors: X Chevalier, J Jerosch, P Goupille, N van Dijk, F P Luyten, D L Scott, F Bailleul, K Pavelka
Journal: Annals of the Rheumatic Diseases (2009)

The primary objective was to compare a single, 6 ml, intra-articular injection of hylan G-F 20 with placebo in patients with symptomatic knee osteoarthritis. The safety of a repeat injection of hylan G-F 20 was also assessed. Patients with primary osteoarthritis knee pain were randomly assigned to arthrocentesis plus a 6 ml intra-articular injection of either hylan G-F 20 or placebo in a prospective, double-blind (one injector/one blinded observer) study. were evaluated at 4, 8, 12, 18 and 26 weeks post-injection. The primary outcome criterion was change from baseline over 26 weeks in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index A pain. Secondary outcome measures included WOMAC A1 and C, patient global assessment (PGA) and clinical observer global assessment (COGA) and Outcome Measures in Rheumatology, Osteoarthritis Research Society International responder rates. A 4-week, open, repeat treatment phase evaluated safety only. Results: A total of 253 patients (Kellgren-Lawrence grade II or III) was randomly assigned. Patients receiving hylan G-F 20 experienced statistically significantly greater improvements in WOMAC A pain scores (-0.15, SE 0.076, p = 0.047), and several of the secondary outcome measures (WOMAC A1, PGA and COGA), than patients receiving placebo. There was no difference between the safety results of the two groups. No increased risk of local adverse events was observed in the open, repeat treatment phase. This placebo-controlled study demonstrated that, in patients with knee osteoarthritis, a single 6 ml intra-articular injection of hylan G-F 20 is safe and effective in providing statistically significant, clinically relevant pain relief over 26 weeks, with a modest difference versus placebo.