tbuckley/cabot-search huggingface dataset:
Atrial Electrogram Characteristics in Patients With and Without Atrioventricular Nodal Reentrant Tachycardia
Authors: Mark J. Niebauer, Emile Daoud, Brian Williamson, K. Ching Man, Adam Strickberger, John Hummel, Fred Morady
Journal: Circulation (1995)

Multicomponent atrial electrograms and "slow pathway potentials" are helpful in identifying target sites for radiofrequency catheter ablation of the slow pathway in patients with atrioventricular (AV) nodal reentrant tachycardia. The purpose of this study was to compare the atrial electrograms recorded at various locations in the right atrium in patients with and without AV nodal reentrant tachycardia to assess the specificity of multicomponent atrial electrograms and possible slow pathway potentials both for the posteroseptal right atrium and for patients with AV nodal reentrant tachycardia.In 25 patients with AV nodal reentrant tachycardia and 23 control patients without AV nodal reentrant tachycardia or dual AV nodal physiology, atrial electrograms with an AV ratio of < or = 1:2 were recorded at the posteroseptal right atrium near the coronary sinus ostium and in the right atrium near the posterior, lateral, and anterior aspects of the tricuspid annulus. Attempts were made to identify broad, multicomponent, and double atrial electrograms. There were no significant differences between the patients with and without AV nodal reentrant tachycardia in the mean number of deflections in the atrial electrograms or in the mean duration of the atrial electrograms recorded at any of the atrial sites. In all patients, the number of atrial electrogram deflections and the atrial electrogram duration were significantly greater at the posteroseptal position than at the other three atrial sites. The prevalence of potentials with the appearance of slow pathway potentials in the posterior septum was similar in patients with and without AV nodal reentrant tachycardia (68% and 70%, respectively). The prevalence of these potentials was 6% to 25% at the other three atrial sites (P < .005 compared with the posterior septum).The atrial electrogram characteristics that have been found to be useful in identifying effective posteroseptal slow pathway ablation sites in patients with AV nodal reentrant tachycardia are equally prevalent in patients without AV nodal reentrant tachycardia or dual AV nodal physiology. Atrial electrograms in the posteroseptal area are broader and contain more deflections than at other areas in the right atrium, possibly because of conduction properties of the posterior transitional zone that are independent of the presence of AV nodal reentrant tachycardia.
Injection treatments for patellar tendinopathy
Authors: Mathijs van Ark, Johannes Zwerver, Inge van den Akker-Scheek
Journal: British Journal of Sports Medicine (2011)

Objective Injection treatments are increasingly used as treatment for patellar tendinopathy. The aim of this systematic review is to describe the different injection treatments, their rationales and the effectiveness of treating patellar tendinopathy. Methods A computerised search of the Medline, Embase, CINAHL and Web of Knowledge databases was conducted on 1 May 2010 to identify studies on injection treatments for patellar tendinopathy. Results 11 articles on seven different injection treatments (dry needling, autologous blood, high-volume, platelet-rich plasma, sclerosis, steroids and aprotinin injections) were found: 4 randomised controlled trials (RCTs), 1 non-RCT, 4 prospective cohort studies and 2 retrospective cohort studies. All studies reported positive results. The Delphi scores of the four RCTs ranged from 5 to 8 out of 9. Different and sometimes contradictory rationales were used for the injection treatments. Conclusion All seven different injection treatments seem promising for treating patellar tendinopathy. Unlike the other injection treatments, steroid treatment often shows a relapse of symptoms in the long term. Results should be interpreted with caution as the number of studies is low, few high-quality studies have been conducted and the studies are hard to compare due to different methodology. More high-quality studies using the same cross-cultural reliable and valid outcome measure are needed, as well as further research into the pathophysiology. Finally, some implications are provided for clinicians who want to use injection treatments as a part of their treatment for patellar tendinopathy, distinguishing between reactive and degenerative phase of patellar tendinopathy.
Weight Control and Risk Factor Reduction in Obese Subjects Treated for 2 Years With Orlistat
Authors: Michael H. Davidson, Jonathan Hauptman, Mario DiGirolamo, John P. Foreyt, Charles H. Halsted, David Heber, Douglas C. Heimburger, Charles P. Lucas, David C. Robbins, Jain Chung, Steven B. Heymsfield
Journal: JAMA (1999)

increasing number of Americans, 1 poses a therapeutic challenge to the clinician.Conventional nonpharmacological interventions based on diet and exercise have limited long-term success in producing sustained weight loss. 2,3Obesity induces multiple metabolic abnormalities that contribute to the pathogenesis of diabetes mellitus and cardiovascular disease 4,5 and is associated with increased morbidity and mortality risk. 6,7A need therefore exists for new and effective therapeutic tools.A potentially promising approach is induction of negative energy balance and weight loss by drug-mediated inhibition of nutrient absorption.Orlistat (Xenical, Hoffman La Roche Inc, Nutley, NJ), a minimally absorbable (Ͻ1%) agent that inhibits activity of pancreatic and gastric lipases, blocks gastrointesti-nal uptake of approximately 30% of ingested fat. 8Assuming incomplete energy compensation, the treated subject consuming an average American diet should gradually lose weight and maintain weight loss.The primary aim of this investigation was to test this hypothesis in a large-scale, 2-year, randomized, double-blind, placebocontrolled study.
Enteral nutrition in intensive care patients: a practical approach
Authors: P. Jolliet, C. Pichard, G. Biolo, R. Chioléro, G. Grimble, X. Leverve, G. Nitenberg, I. Novak, M. Planas, J. -C. Preiser, E. Roth, A. -M. Schols, J. Wernerman
Journal: Intensive Care Medicine (1998)
P288 The Desensitisation Effect Of Graphic Health Warning Labels And Cross-cultural Differences In The Awareness Of Smoking Related Consequences: Comparing A London And Singapore Cohort
Authors: C. Ratneswaran, B. Chisnall, A. Douiri, M. Li, S. Tan, S. Tan, C. Chang, D. Anantham, J. Steier
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Graphic Health Warning Labels (GHWL) assist in primary and secondary smoking prevention. A lack of evidence exists regarding their desensitisation with increased exposure. Investigating knowledge and attitudes around GHWL may allow better implementation of future public health policies. Singapore introduced GHWL in 2004, five years before they were introduced in the UK; this study aims to investigate any potential desensitisation effect by direct comparison. <h3>Methods</h3> Data were collected from 266 smokers and non-smokers, 163 from London (54.6% smokers, 54.0% male, mean age 52.4 (17.8)) and 103 from Singapore (47.6% smokers, 77.7% male, mean age 57.7 (14.5)) between 2011 and 2013. A structured interview with fifty items, showing ten different GHWL, recorded demographics, smoking history, plans to quit and knowledge about the health-related consequences of smoking, as well as the emotional response, processing and impact of GHWL on behaviour. Participants further ranked hypothetical conditions that they could develop in terms of prevention and treatment. <h3>Results</h3> The London cohort experienced significantly higher levels of ‘disgust’ when viewing GHWL than their Singapore counterparts (smokers 74.1% vs 49.0%, p = 0.003; non-smokers 83.8% vs 57.4%, p &lt; 0.001), and felt GHWLs were a sufficient deterrent (smokers 33.7% vs 16.3%, p = 0.029; non-smokers 71.6% vs 50.0%, p = 0.013). London non-smokers had a higher awareness of heart disease (82.4% vs 32.0%, p = 0.007), stroke (72.3% vs 28.2%, p = 0.02), mouth and throat cancer (95.6% vs 35.0%, p &lt; 0.001) and lung cancer (98.7% vs 35.0%, p &lt; 0.001) as smoking-related diseases. London smokers reported an increased motivation to quit if they hypothetically developed smoking-related disease (85.2% vs 72.7%, p = 0.001). Blindness was the least well-known consequence overall (27.8%), despite provoking the highest levels of fear amongst Singaporeans. <h3>Conclusion</h3> A desensitisation effect of GHWL is observed in cohorts with an increased length of exposure, both in smokers and non-smokers. The socio-cultural background needs to be considered when running public health campaigns due to differences in perception and responses to GHWL. Investigating the awareness of risks such as blindness, that have a low knowledge score but a high deterring impact, provides the chance to create a tailored approach when addressing this desensitisation.
By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?
Authors: M R Law, N J Wald, S G Thompson
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. <b>Design</b>: Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). Main outcome measure - Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. <b>Results</b>: For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being lose to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. Conclusions - The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18 000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change,lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45 000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.
Clinical uses of antiprogestogens
Authors: P. Van Look
Journal: Human Reproduction Update (1995)

Antiprogestogens, which block the action of progesterone at the cellular level through binding to the progesterone receptor, are proving to be one of the most significant developments in endocrinology in recent years. Several hundreds of such compounds have been synthesized, but only a few of them have been evaluated to any significant extent in biological screening models and, to our knowledge, only three compounds, namely mifepristone, lilopristone (ZK 98.734) and onapristone (ZK 98.299) have been given to humans. Most of the clinical research to date has focused on the use of mifepristone given in combination with prosta-glandin for termination of early pregnancy, an indication for which the compound is being used routinely in four countries so far, i.e. China, France, the UK and Sweden. The gynaecological and obstetrical applications in which antiprogestogens have been shown to be of value to date include ripening of the pregnant cervix prior to pregnancy termination, sensitization of the uterus to prostaglandins in second-trimester abortion, and induction of labour. Available data suggest that antiprogestogens have no place in the conservative treatment of ectopic pregnancy or in the treatment of premenstrual tension. In fertility regulation, the sequential combination regimen of mifepristone plus prostaglandin as used for inducing abortion has proved to be effective also for menses induction and can be expected to be an efficacious once-a-month contraceptive. Mifepristone alone, without adjuvant prostaglandin, has yielded promising results as an anti-implantation agent and in emergency contraception. Other potential uses include once-a-week contraception, ovulation inhibition (in a sequential regimen with a progestogen), and as a daily mini-pill. Mifepristone, and other antiprogestogens for which biological data have been reported also bind to the cellular receptors for glucocorticoid hormones and, consequently, possess antiglucocorticoid in addition to their antipro-gestational activity. Because of this antiglucocorticoid effect, mifepristone has been employed successfully in the palliative treatment of hypercortisolism due to Cushing's syndrome, and its use has been proposed for treating certain forms of depression and of glaucoma, and in wound healing. However, for scientific and practical reasons, it would be preferable if molecules were developed that have only the antiprogestational or the antiglucocorticoid activity rather than both.
Clinical practice decision tree for the choice of the first disease modifying antirheumatic drug for very early rheumatoid arthritis: a 2004 proposal of the French Society of Rheumatology
Authors: X Le Loet
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months' duration. <b>Methods:</b> Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) inventory of the information available to guide DMARD choice; (3) selection of the most pertinent information by 12 experts using a Delphi method; and (4) choice of DMARDs in 12 clinical situations defined by items selected in step 3 (28 joint disease activity score (DAS 28): ⩽3.2; &gt;3.2 and ⩽5.1; &gt;5.1; rheumatoid factor status (positive/negative); structural damage (with/without)—that is, 3×2×2). Thus, multiplied by all the possible treatment pairs, 180 scenarios were obtained and presented to 36 experts, who ranked treatment choices according to the Thurstone pairwise method. <b>Results:</b> Among the 77 items identified, 41 were selected as pertinent to guide the DMARD choice. They were reorganised into five domains: rheumatoid arthritis activity, factors predictive of structural damage; patient characteristics; DMARD characteristics; physician characteristics. In the majority of situations, the two top ranking DMARD choices were methotrexate and leflunomide. Etanercept was an alternative for these agents when high disease activity was associated with poor structural prognosis and rheumatoid factor positivity. <b>Conclusions:</b> Starting with simple scenarios and using the pairwise method, a clinical decision tree could be devised for the choice of the first DMARD to treat very early rheumatoid arthritis.
TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand
Authors: Jonathan Lam, Sunao Takeshita, Jane E. Barker, Osami Kanagawa, F. Patrick Ross, Steven L. Teitelbaum
Journal: Journal of Clinical Investigation (2000)

While TNF-α is pivotal to the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are unknown. We find that a pure population of murine osteoclast precursors fails to undergo osteoclastogenesis when treated with TNF-α alone. In contrast, the cytokine dramatically stimulates differentiation in macrophages primed by less than one percent of the amount of RANKL (ligand for the receptor activator of NF-κB) required to induce osteoclast formation. Mirroring their synergistic effects on osteoclast differentiation, TNF-α and RANKL markedly potentiate NF-κB and stress-activated protein kinase/c-Jun NH2-terminal kinase activity, two signaling pathways essential for osteoclastogenesis. In vivo administration of TNF-α prompts robust osteoclast formation in chimeric animals in which β-galactosidase positive, TNF-responsive macrophages develop within a TNF-nonresponsive stromal environment. Thus, while TNF-α alone does not induce osteoclastogenesis, it does so both in vitro and in vivo by directly targeting macrophages within a stromal environment that expresses permissive levels of RANKL. Given the minuscule amount of RANKL sufficient to synergize with TNF-α to promote osteoclastogenesis, TNF-α appears to be a more convenient target in arresting inflammatory osteolysis.
Sp1 and c-Myc modulate drug resistance of leukemia stem cells by regulating survivin expression through the ERK-MSK MAPK signaling pathway
Authors: Yi Zhang, Hai-xuan Chen, Shu-yan Zhou, Shao-xiang Wang, Kai Zheng, Dan-dan Xu, Yu-ting Liu, Xiao-yan Wang, Xiao Wang, Hai-zhao Yan, Li Zhang, Qiu-ying Liu, Wan-qun Chen, Yi-fei Wang
Journal: Molecular Cancer (2015)

Acute myeloid leukemia (AML) is initiated and maintained by a subset of self-renewing leukemia stem cells (LSCs), which contribute to the progression, recurrence and therapeutic resistance of leukemia. However, the mechanisms underlying the maintenance of LSCs drug resistance have not been fully defined. In this study, we attempted to elucidate the mechanisms of LSCs drug resistance. We performed reverse phase protein arrays to analyze the expression of anti-apoptotic proteins in the LSC-enriched leukemia cell line KG-1a. Immuno-blotting, cell viability and clinical AML samples were evaluated to verify the micro-assay results. The characteristics and transcriptional regulation of survivin were analyzed with the relative luciferase reporter assay, mutant constructs, chromatin immuno-precipitation (ChIP), quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and western blotting. The levels of Sp1, c-Myc, phospho-extracellular signal-regulated kinase (p-ERK), phospho-mitogen and stress-activated protein kinase (p-MSK) were investigated in paired CD34+ and CD34- AML patient samples. Survivin was highly over-expressed in CD34 + CD38- KG-1a cells and paired CD34+ AML patients compared with their differentiated counterparts. Functionally, survivin contributes to the drug resistance of LSCs, and Sp1 and c-Myc concurrently regulate levels of survivin transcription. Clinically, Sp1 and c-Myc were significantly up-regulated and positively correlated with survivin in CD34+ AML patients. Moreover, Sp1 and c-Myc were further activated by the ERK/MSK mitogen-activated protein kinase (MAPK) signaling pathway, modulating survivin levels. Our findings demonstrated that ERK/MSK/Sp1/c-Myc axis functioned as a critical regulator of survivin expression in LSCs, offering a potential new therapeutic strategy for LSCs therapy.
Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis
Authors: A Gramenzi, P Andreone, S Fiorino, C Cammà, M Giunta, D Magalotti, C Cursaro, C Calabrese, V Arienti, C Rossi, G Di Febo, M Zoli, A Craxì, G Gasbarrini, M Bernardi
Journal: Gut (2001)

BACKGROUND The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate. AIM To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis. PATIENTS AND METHODS Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age, sex, and Child-Pugh's score were enrolled in a prospective non-randomised controlled trial. Treated patients received leucocytic interferon alfa, with an escalating schedule for 12 months. The incidence and risk (Cox regression analysis) of clinical complications (hepatocellular carcinoma, ascites, jaundice, variceal bleeding, and encephalopathy) and death were calculated. RESULTS Over median follow up periods of 55 months for treated and 58 for untreated subjects, seven and nine patients, respectively, died, and 20 and 32, respectively, developed at least one clinical complication (ns). Hepatocellular carcinoma developed in six treated and 19 untreated patients (p=0.018). Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications. Clinical complications were significantly associated with low albumin, bilirubin, and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon, oesophageal varices, and high α fetoprotein levels. By stratified analysis, the beneficial effect of interferon was statistically evident only in patients with baseline α fetoprotein levels ⩾20 ng/ml. CONCLUSIONS Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma. Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up.
Early diagnosis of lung cancer: evaluation of a community-based social marketing intervention
Authors: Victoria L Athey, Rupert J Suckling, Angela M Tod, Stephen J Walters, Trevor K Rogers
Journal: Thorax (2011)

<h3>Background</h3> Poor UK lung cancer survival rates may, in part, be due to late diagnosis. <h3>Objectives</h3> To evaluate the effectiveness of a mixed-method community-based social marketing intervention on lung cancer diagnoses. <h3>Methods</h3> A public awareness campaign in conjunction with brief intervention training in general practices was piloted in six localities with a high lung cancer incidence. End points were self-reported awareness of lung cancer symptoms; intention to seek healthcare; chest x-ray referral rates in primary care; secular trends in the incidence of lung cancer and stage at diagnosis, compared before and after the intervention. <h3>Results</h3> 21% (128/600) (95% CI 18% to 25%) of the targeted population recalled something about the campaign. Compared with a responder in the control area, the odds of a responder in the intervention area saying that they would visit their general practitioner and request a chest x-ray for a cough was 1.97 times (95% CI 1.18 to 3.31, p=0.01). Primary care chest x-ray referral rates increased by 20% in the targeted practices in the year following the intervention compared with a 2% fall in the control practices. The difference was highly significant, with an incidence rate ratio of 1.22 (95% CI 1.12 to 1.33, p=0.001). There was a 27% increase in lung cancer diagnoses in the intervention area compared with a fall in the control area. The incidence rate ratio was 1.42 (95% CI 0.83 to 2.44 p=0.199). <h3>Conclusion</h3> This is encouraging early evidence that an awareness and early recognition initiative may facilitate lung cancer diagnosis.