tbuckley/cabot-search huggingface dataset:
Inability of Potassium Canrenoate to Convert Experimentally Induced Ouabain Arrhythmias in the Canine Heart
Authors: CARL J. NIELSEN, BENEDICT R. LUCCHESI
Journal: Circulation Research (1974)

The antiarrhythmic effects of potassium canrenoate were examined in 20 closed-chest, pentobarbital-anesthetized dogs with ouabain-induced ventricular tachycardia. In a group of 8 dogs, a mean dose of ouabain of 64.4 ± 3.7 µg/kg induced sustained ventricular tachycardia. Subsequent administration of potassium canrenoate (30 mg/kg, iv) caused ventricular fibrillation in 1 dog and sinus tachycardia in 3 dogs. Stimulation of the distal end of the cut right vagus in the latter 3 dogs slowed the sinus rhythm enough to permit the ventricular focus to become the dominant pacemaker. In the other 4 dogs, potassium canrenoate did not alter the ouabain-induced ventricular tachycardia. In a second group of 12 dogs, ventricular tachycardia was also induced by administering a toxic dose of ouabain (65.5 ± 2.9 µg/kg, iv). After ouabain intoxication, atrial overdrive suppression of the ventricular rhythm was initiated by electrically pacing the right atrium at a mean frequency of 184.5 ± 7.9 beats/min. Subsequent administration of potassium canrenoate (30 mg/kg, iv) to these dogs restored sinus rhythm in 4 of the dogs; however, stimulation of the distal end of the cut right vagus caused a reappearance of the ventricular ectopic focus. After potassium canrenoate administration, the minimum atrial pacing rate required to capture the ventricular rhythm was 160.9 ± 9.4 beats/min. This rate represents a significant reduction ( P &lt; 0.005) in the rate of the ouabain-induced ventricular ectopic focus, but in no instance was the focus directly suppressed by potassium canrenoate. Propranolol, in contrast to potassium canrenoate, restored normal sinus rhythm in all 20 ouabain-intoxicated dogs and suppressed the ouabain-induced ectopic pacemaker during the period of vagally induced sinoatrial arrest. The results of this study show that potassium canrenoate fails to exert an antiarrhythmic effect against digitalis-induced arrhythmias and that any apparent restoration of sinus rhythm in response to potassium canrenoate is due to overdrive suppression of the ouabain-induced ventricular ectopic pacemaker.
All-Cause Mortality in the Canterbury (New Zealand) Insulin-Treated Diabetic Registry Population
Authors: Laurie J. Brown, Russell S. Scott, Cameron L. Moir
Journal: Diabetes Care (2001)

OBJECTIVE— To establish all-cause death rates and life expectancies of and risk factors for mortality in insulin-treated diabetic individuals living in Canterbury, New Zealand. RESEARCH DESIGN AND METHODS— Insulin-treated diabetic subjects(n = 1,008) on the Canterbury Diabetes Registry were tracked over 9 years, and their vital status was determined. Death rates were standardized using direct and indirect methods. Cox proportional hazard regression was used to model the effects of demographic and clinical covariates on survival time. RESULTS— At study entry, age ranged from 2.9 to 92.7 years,with mean 48.7 ± 20.4 years; age at diagnosis was 0.2-88.9 years, mean 34.5 ± 20.0 years; and duration of diabetes was 0.1-58.5 years, mean 14.0 ± 10.6 years. There were 303 deaths in 7,372 person-years of follow-up with a standardized mortality ratio (SMR) of 2.6 (95% CI 2.4-3.0). Relative mortality was greatest for those aged 30-39 years (SMR 9.2[4.8-16.2]). The death rate for the diabetic cohort standardized against the Segi world standard population was 16.2 per 1,000. Attained age, sex, and clinical subtype were significant predictors of mortality. The SMR for subjects with type 1 diabetes and age at onset &amp;lt;30 years was 3.7 (CI 2.7-5.0), 2.2 (1.8-2.6) for those with onset ≥30 years, and 3.1 (2.5-3.7)for subjects suspected of having latent autoimmune diabetes in adulthood or insulin-treated type 2 diabetes. Life expectancy was reduced for both sexes at all ages. CONCLUSIONS— Mortality rates for insulin-treated diabetic individuals remain high, resulting in shortened life spans relative to the general population. Marked differences in mortality exist between clinical groups of subjects. Further research is needed to improve diabetes classification and to clarify differences in health outcomes.
FURTHER STUDIES ON THE REVERSIBILITY OF SERUM SICKNESS CHOLESTEROL-INDUCED ATHEROSCLEROSIS
Authors: M. Van Winkle, L. Levy
Journal: The Journal of Experimental Medicine (1970)

Rabbits were induced to form atheromatous cardiovascular lesions by subjecting them to treatments of a single BSA injection plus a 2-wk period of cholesterol diet, or to the diet alone. Microscopic examination of the hearts at the end of the 2-wk induction period, or after having been returned to regular diet for 5 or 8 wk, showed that lesion incidence in the cholesterol-only animall decreased markedly during the 8-wk rest period, while little change in incidence occurred in animals with lesions from the combined treatment. This finding was taken to mean that the latter type of lesion was less reversible, and therefore perhaps more pathologically significant, than the former type. It was felt that lipid deposition was not solely responsible for this prolongation, since it was present in diet-only lesions which disappeared with time, and also seemed to be disappearing from the prolonged lesions in all treatment groups. On the other hand, elastic tissue was demonstrated only in lesions arising from the combined treatment, and it is hypothesized that this feature is implicated in the prolongation of these lesions.
Boosting Cancer Immunotherapy with Anti-CD137 Antibody Therapy
Authors: Atsushi Yonezawa, Suparna Dutt, Cariad Chester, Jeewon Kim, Holbrook E. Kohrt
Journal: Clinical Cancer Research (2015)

Abstract In the past 5 years, immunomodulatory antibodies have revolutionized cancer immunotherapy. CD137, a member of the tumor necrosis factor receptor superfamily, represents a promising target for enhancing antitumor immune responses. CD137 helps regulate the activation of many immune cells, including CD4+ T cells, CD8+ T cells, dendritic cells, and natural killer cells. Recent studies indicate that the antitumor efficacy of therapeutic tumor-targeting antibodies can be augmented by the addition of agonistic antibodies targeting CD137. As ligation of CD137 provides a costimulatory signal in multiple immune cell subsets, combination therapy of CD137 antibody with therapeutic antibodies and/or vaccination has the potential to improve cancer treatment. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched. In this review, we discuss the recent advances and clinical promise of agonistic anti-CD137 monoclonal antibody therapy. Clin Cancer Res; 21(14); 3113–20. ©2015 AACR.
Effectiveness of Leech Therapy in Osteoarthritis of the Knee
Authors: Andreas Michalsen, None Stefanie Klotz, Rainer Ldtke, Susanne Moebus, Gnther Spahn, Gustav J. Dobos
Journal: Annals of Internal Medicine (2003)

Background: Leech therapy was commonly used in traditional medicine for treating localized pain. Clinically significant pain relief after leech therapy for osteoarthritis of the knee has been demonstrated by preliminary data. Objective: To evaluate the effectiveness of leech therapy for symptomatic relief of osteoarthritis of the knee. Design: Randomized, controlled trial. Setting: Outpatient department for integrative medicine of an academic teaching hospital. Patients: 51 patients with osteoarthritis of the knee (leech therapy: 24 patients, mean age [SD], 62.5 10.2 years; topical diclofenac therapy: 27 patients, mean age [SD], 65.5 6.7 years). Intervention: A single treatment with 4 to 6 locally applied leeches (leech therapy group) or a 28-day topical diclofenac regimen (control group). Measurements: Mean of the pain, function, and stiffness subscores of the Western Ontario and McMaster Universities Osteoarthritis Index and physical sum score of the Medical Outcomes Study 36-Item Short-Form Health Survey with group comparisons at days 3, 7, 28, and 91. Results: The primary end point, pain at day 7, was reduced from a mean (SD) of 53.5 13.7 to 19.3 12.2 after leech therapy compared with 51.5 16.8 to 42.4 19.7 with topical diclofenac (estimated group difference, 23.9 [95% CI, 32.8 to 15.1]; P < 0.001). Although the difference between group pain scores was no longer significant after day 7, differences for function, stiffness, and total symptoms remained significant in favor of leech therapy until the end of study and for quality of life until day 28. Results were not affected by outcome expectation. Conclusions: Leech therapy helps relieve symptoms in patients with osteoarthritis of the knee. The potential of leech therapy for treating osteoarthritis and the pharmacologic properties of leech saliva remain to be clarified.
Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIα gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab
Authors: M. Tanner, M. Hollmén, T.T. Junttila, A.I. Kapanen, S. Tommola, Y. Soini, H. Helin, J. Salo, H. Joensuu, E. Sihvo, K. Elenius, J. Isola
Journal: Annals of Oncology (2005)
Rewired ERK-JNK Signaling Pathways in Melanoma
Authors: Pablo Lopez-Bergami, Conway Huang, James S. Goydos, Dana Yip, Menashe Bar-Eli, Meenhard Herlyn, Keiran S.M. Smalley, Alka Mahale, Alexey Eroshkin, Stuart Aaronson, Ze'ev Ronai
Journal: Cancer Cell (2007)
The Antigenic Structure of Proteins: A Reappraisal
Authors: David C. Benjamin, Jay A. Berzofsky, Iain J. East, Frank R. N. Gurd, Charles Hannum, Sydney J. Leach, Emanuel Margoliash, J. Gabriel Michael, Alexander Miller, Ellen M. Prager, Morris Reichlin, Eli E. Sercarz, Sandra J. Smith-Gill, Pam E. Todd, A. C. Wilson
Journal: Annual Review of Immunology (1984)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Get a kick out of this: the spectrum of knee extensor mechanism injuries
Authors: Betty Tuong, Jeremy White, Luck Louis, Robyn Cairns, Gordon Andrews, Bruce B Forster
Journal: British Journal of Sports Medicine (2010)

At the end of this article, the reader should be able to (1) recognise normal anatomy and anatomical variants of the extensor mechanism of the knee on various imaging modalities, including plain film, ultrasound and MRI; (2) diagnose a broad spectrum of EM injuries in adult and paediatric patients including patellar and quadriceps tendinopathy, Osgood-Schlatter disease, Sindig-Larsen-Johansson syndrome, chondromalacia patellae and patellar fractures on various imaging modalities; and (3) appreciate the important role of imaging in the diagnosis of musculoskeletal injuries.
Impaired Autophagosome Clearance Contributes to Cardiomyocyte Death in Ischemia/Reperfusion Injury
Authors: Xiucui Ma, Haiyan Liu, Sarah R. Foyil, Rebecca J. Godar, Carla J. Weinheimer, Joseph A. Hill, Abhinav Diwan
Journal: Circulation (2012)

Background— In myocardial ischemia, induction of autophagy via the AMP-induced protein kinase pathway is protective, whereas reperfusion stimulates autophagy with BECLIN-1 upregulation and is implicated in causing cell death. We examined flux through the macroautophagy pathway as a determinant of the discrepant outcomes in cardiomyocyte cell death in this setting. Methods and Results— Reversible left anterior descending coronary artery ligation was performed in mice with cardiomyocyte-restricted expression of green fluorescent protein–tagged microtubule–associated protein light chain-3 to induce ischemia (120 minutes) or ischemia/reperfusion (30–90 minutes) with saline or chloroquine pretreatment (n=4 per group). Autophagosome clearance, assessed as the ratio of punctate light chain-3 abundance in saline to chloroquine-treated samples, was markedly impaired with ischemia/reperfusion compared with sham controls. Reoxygenation increased cell death in neonatal rat cardiomyocytes compared with hypoxia alone, markedly increased autophagosomes but not autolysosomes (assessed as punctate dual fluorescent mCherry-green fluorescent protein tandem-tagged light chain-3 expression), and impaired clearance of polyglutamine aggregates, indicating impaired autophagic flux. The resultant autophagosome accumulation was associated with increased reactive oxygen species and mitochondrial permeabilization, leading to cell death, which was attenuated by cyclosporine A pretreatment. Hypoxia-reoxygenation injury was accompanied by reactive oxygen species–mediated BECLIN-1 upregulation and a reduction in lysosome-associated membrane protein-2, a critical determinant of autophagosome-lysosome fusion. Restoration of lysosome-associated membrane protein-2 levels synergizes with partial BECLIN-1 knockdown to restore autophagosome processing and to attenuate cell death after hypoxia-reoxygenation. Conclusion— Ischemia/reperfusion injury impairs autophagosome clearance mediated in part by reactive oxygen species–induced decline in lysosome-associated membrane protein-2 and upregulation of BECLIN-1, contributing to increased cardiomyocyte death.
Increased H1N1 Infection Rate in Children with Asthma
Authors: Kirsten M. Kloepfer, Jaime P. Olenec, Wai Ming Lee, Guiyan Liu, Rose F. Vrtis, Kathy A. Roberg, Michael D. Evans, Ronald E. Gangnon, Robert F. Lemanske, James E. Gern
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: The 2009 H1N1 flu appeared to cause more severe cold symptoms during the 2009–2010 flu season.Objectives: We evaluated H1N1 infections during peak viral season in children with and without asthma to determine whether the H1N1 infectivity rate and illness severity were greater in subjects with asthma.Methods: One hundred and eighty children, 4–12 years of age, provided eight consecutive weekly nasal mucus samples from September 5 through October 24, 2009, and scored cold and asthma symptoms daily. Viral diagnostics were performed for all nasal samples.Measurements and Main Results: One hundred and sixty-one children (95 with asthma, 66 without asthma) completed at least 6 of the 8 nasal samples. The incidence of H1N1 infection was significantly higher in children with asthma (41%) than in children without asthma (24%; odds ratio, 4; 95% confidence interval, 1.8–9; P < 0.001), but rates of human rhinovirus infection (90% each) and other viral infections (47 vs. 41%) were similar. In children with asthma, there was a nonsignificant trend for increased loss of asthma control during H1N1 infections compared with human rhinovirus infections (38 vs. 21%; odds ratio, 2.6; 95% confidence interval, 0.9–7.2; P = 0.07).Conclusions: During peak 2009 H1N1 flu season, children with asthma were infected almost twice as often with H1N1 compared with other respiratory viruses. H1N1 infection also caused increased severity of cold symptoms compared with other viral infections. Given the increased susceptibility of children with asthma to infection, these findings reinforce the need for yearly influenza vaccination to prevent infection, and raise new questions about the mechanism for enhanced susceptibility to influenza infection in asthma.
Improved coverage and accuracy with strand-conserving sequence enrichment
Authors: Toumy Guettouche, Stephan Zuchner
Journal: Genome Medicine (2013)

Targeted next-generation sequencing is becoming a common tool in the molecular diagnostic laboratory. However, currently available methods to enrich for regions of interest in the DNA sequence suffer from drawbacks such as high cost, complex protocols, lack of clinical-level accuracy and uneven target coverage. A target-enrichment approach using complementary long padlock probes described in a recent article significantly improves on previous methods in most of these areas.http://genomemedicine.com/content/5/5/50.
Effectiveness of paramedic practitioners in attending 999 calls from elderly people in the community: cluster randomised controlled trial
Authors: Suzanne Mason, Emma Knowles, Brigitte Colwell, Simon Dixon, Jim Wardrope, Robert Gorringe, Helen Snooks, Julie Perrin, Jon Nicholl
Journal: BMJ (2007)

<b>Objective</b> To evaluate the benefits of paramedic practitioners assessing and, when possible, treating older people in the community after minor injury or illness. Paramedic practitioners have been trained with extended skills to assess, treat, and discharge older patients with minor acute conditions in the community. <b>Design</b> Cluster randomised controlled trial involving 56 clusters. Weeks were randomised to the paramedic practitioner service being active (intervention) or inactive (control) when the standard 999 service was available. <b>Setting</b> A large urban area in England. <b>Participants</b> 3018 patients aged over 60 who called the emergency services (n=1549 intervention, n=1469 control). <b>Main outcome measures</b> Emergency department attendance or hospital admission between 0 and 28 days; interval from time of call to time of discharge; patients9 satisfaction with the service received. <b>Results</b> Overall, patients in the intervention group were less likely to attend an emergency department (relative risk 0.72, 95% confidence interval 0.68 to 0.75) or require hospital admission within 28 days (0.87, 0.81 to 0.94) and experienced a shorter total episode time (235 <i>v</i> 278 minutes, 95% confidence interval for difference −60 minutes to −25 minutes). Patients in the intervention group were more likely to report being highly satisfied with their healthcare episode (relative risk 1.16, 1.09 to 1.23). There was no significant difference in 28 day mortality (0.87, 0.63 to 1.21). <b>Conclusions</b> Paramedics with extended skills can provide a clinically effective alternative to standard ambulance transfer and treatment in an emergency department for elderly patients with acute minor conditions. <b>Trial registration</b>ISRCTN27796329.
Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years
Authors: Mark H Drazner, J.Eduardo Rame, Emily K Marino, John S Gottdiener, Dalane W Kitzman, Julius M Gardin, Teri A Manolio, Daniel L Dries, David S Siscovick
Journal: Journal of the American College of Cardiology (2004)
THE USE OF AUTORADIOGRAPHY TO STUDY THE LOCALIZATION OF GERMICIDES IN SKIN
Authors: T. RUTHERFORD, J. G. BLACK
Journal: British Journal of Dermatology (1969)

SUMMARY.— An autoradiographic technique for studying skin deposition and localization is described and applied to a study of germicides in surfactants. The method involves the use of unfixed frozen sections exposed to dry emulsion‐coated slides. The radioactive germicides carboxy‐14C‐3,4,4′‐trichlorocarbanilide (TCC) in soap containing non‐soap detergent (NSD) and zinc or zirconium pyridine‐2‐thione‐1‐N‐oxide (PTO) in a shampoo were applied to the skin of guinea‐pigs. Auto‐radiograms of the skins showed that from soap, TGC was deposited on the stratum corneum, around the entrances to hair follicles, and was seen in the epidermis and dermis, but not in the follicles or sebaceous glands. From the NSD, TCC was seen in addition in the follicles and sebaceous glands. In one human subject, TCC from NSD was seen on the corneum, in the epidermis and dermis, hair follicles and sebaceous glands and also in the sweat glands. From the shampoo ZnPTO and ZrPTO were seen in guinea‐pig skin on the corneum and in the follicles but whereas ZrPTO was in the epidermis and dermis, ZnPTO was not. In all vehicles the largest proportion of germicide was deposited on the corneum. ZnPTO was shown to be soluble in sebum and to penetrate from sebum into only the hair follicles of guinea‐pigs. Scintillation counting of sections of guinea‐pig skin treated with TCC, ZnPTO and ZrPTO supported the autoradiographic evidence that most of the germicide remained on the corneum.
Football blades: a cause for concern
Authors: M J Hall, P Riou
Journal: British Journal of Sports Medicine (2004)

Sporting injuries have always contributed a significant proportion of the workload of the emergency department.1 The number is increasing considerably2 for several reasons. A burgeoning range of sporting activities combined with increased disposable income and leisure time has led to greater participation.2 Consequently research and development aimed at enhancing performance has escalated.

One such development is the use of “blades” instead of the more traditional studs on football boots. Unlike the traditional round peg-like studs, the new blades measure up to 3 cm long and are shaped to contour the foot (fig 1), providing enhanced stability to the standing foot when kicking. Since they were first endorsed by high profile figures such as …
Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α production by interaction with its soluble E-cadherin ligand in chronically inflamed joints
Authors: Lode Melis, Liesbet Van Praet, Hanspeter Pircher, Koen Venken, Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Killer cell lectin-like receptor G1 (KLRG1) is an NK cell marker also expressed on T cells showing an immunosenescent phenotype. KLRG1 binding to its ligand E-cadherin inhibits functional responses. It was recently shown that soluble E-cadherin (sE-cadherin) also influences KLRG1 signalling, although its involvement in arthritis is unknown. Our goal was to evaluate the contribution of KLRG1<sup>+</sup> T cells to synovitis. <h3>Methods</h3> Paired peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 21 patients with spondyloarthritis (SpA) or rheumatoid arthritis (RA), eight with crystal-induced arthritis and 10 controls were obtained. T cells were characterised for KLRG1 expression directly ex vivo, while TNF-α/IFN-γ production was assessed after polyclonal stimulation. Assays of chemotaxis response towards SF were conducted. Additionally, sE-cadherin levels in our paired samples were determined. Moreover, TNF-α/IFN-γ production by antigen-specific T cells was evaluated in the presence of sE-cadherin. <h3>Results</h3> KLRG1<sup>+</sup> T cells were enriched in SF as opposed to PB of SpA and RA patients, which contrasts with results obtained in crystal-induced arthritides. KLRG1<sup>+</sup> T cells were more functionally active as opposed to KLRG1<sup>−</sup> T cells and migrated preferentially towards SpA and RA SF. sE-cadherin levels were higher in SF versus plasma. The presence of sE-cadherin enhanced the number of KLRG1<sup>+</sup> CD4<sup>+</sup> T cells able to produce TNF-α but not IFN-γ. <h3>Conclusions</h3> sE-cadherin contributes to the local proinflammatory environment in the joint by favouring TNF-α production by KLRG1<sup>+</sup> CD4<sup>+</sup> T cells. This pathway seems to be operational in both SpA and RA, but not in crystal-induced arthritis.
1042-82 White blood cell count predicts higher risk of intermediate-term outcomes in patients stabilized after acute coronary syndromes: Observations from the SYMPHONY and 2ndSYMPHONY trials
Authors: Gustavo B.F Oliveira, L Kristin Newby, Lauren Lindblad, Leopoldo S Piegas, Freek W Verheught, Robert A Harrington, Judith S Hochman, Harvey D White, Frans Van de Werf, Christopher B Granger
Journal: Journal of the American College of Cardiology (2004)