tbuckley/cabot-search huggingface dataset:
P133 A Single Centre Retrospective Survival Analysis of Patients with Interstitial Lung Disease
Authors: T Bradshaw, A Roychoudhury, SM Bianchi
Journal: Thorax (2012)

<h3>Introduction</h3> Idiopathic pulmonary fibrosis is a chronic, progressive condition. BTS guidelines indicate that the ‘triple therapy’ - Prednisolone, Azathioprine, N-acetylcysteine (NAC) – can be considered in the management of UIP (usual interstitial pneumonitis) pattern disease based on the outcome of the IFIGENIA study (Demedts NEJM 2005). Recent data from the PANTHER study (Raghu NEJM 2012) has led to reversal of this recommendation due to concerns of increased adverse events, deaths and hospitalisation in the triple therapy arm as compared with placebo controls and those receiving NAC alone. This retrospective review examines the survival outcome of patients with UIP and UIP/COPD in a single centre (Sheffield Teaching Hospitals NHS Foundation Trust) where triple therapy was used over a five year period. <h3>Methodology</h3> All patients with a UIP or UIP/COPD diagnosis managed within the interstitial lung disease clinic were identified through review of clinical notes and correspondence. Therapy, survival and demographic details were collected. Cox regression analysis was conducted using covariates of age at diagnosis, gender, occupational risk factors, COPD comorbidity and life limiting comorbidities. <h3>Results</h3> 73 patients with UIP alone were identified; 16 patients had a UIP/COPD diagnosis. 8 patients received prednisolone alone, 2 NAC alone, 7 Pred/NAC, 3 Pred/Aza, 14 triple therapy and 11 received other immunosuppressive regimens (due to Azathioprine intolerance). 44 patients received no immunosuppressive therapy. Median survival, as derived from Kaplan-Meier curves, for those on no active therapy was 632 days (IQ range 485), 555 (IQ range 723) days for those on Prednisolone alone, 873 (IQ range 577)days for those on Pred/Aza and 869 (IQ range 918) days for those on triple therapy. No increase in hospitalisation was noted in the triple therapy group as compared with ‘untreated’ patients. <h3>Conclusions</h3> In a cohort of 89 patients treated over a 5 year period triple therapy has been associated with an improved survival as compared to any other treatment regimen. No increase in hospitalisation has been identified and serious untoward events including blood abnormalities have been rare and manageable. Further Cox analysis using the covariates discussed above allied with smoking history, FVC and TLCO at diagnosis and rate of decline in FVC and TLCO at ‘decision to treat’ as covariates is awaited. We hope this data may enlighten practitioners to the progression of UIP over time, the reasons adopted by clinicians in selection of various (often unproven) therapies and the safety and utility of these treatments in a real life population.
Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial
Authors: Maria-Victoria Mateos, Paul G. Richardson, Rudolf Schlag, Nuriet K. Khuageva, Meletios A. Dimopoulos, Ofer Shpilberg, Martin Kropff, Ivan Spicka, Maria T. Petrucci, Antonio Palumbo, Olga S. Samoilova, Anna Dmoszynska, Kudrat M. Abdulkadyrov, Rik Schots, Bin Jiang, Dixie L. Esseltine, Kevin Liu, Andrew Cakana, Helgi van de Velde, Jesús F. San Miguel
Journal: Journal of Clinical Oncology (2010)

The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies.Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338).With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide- (41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months.VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse.
Differential Expression of Voltage-Gated K <sup>+</sup> Channel Subunits in Adult Rat Heart
Authors: Dianne M. Barry, James S. Trimmer, John P. Merlie, Jeanne M. Nerbonne
Journal: Circulation Research (1995)

Abstract Polyclonal antibodies against each of the K + channel subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) shown previously to be expressed in adult rat heart at the mRNA level were used to examine the distributions of these K + channel subunits in adult rat atrial and ventricular membranes. Immunohistochemistry on isolated adult rat ventricular myocytes revealed strong labeling with the anti-Kv4.2 and anti-Kv1.2 antibodies. Although somewhat weaker (than with anti-Kv1.2 or anti-Kv4.2), positive staining was also observed with the anti-Kv1.5 and anti-Kv2.1 antibodies. Ventricular myocytes exposed to the anti-Kv1.4 antibody, in contrast, did not appear significantly different from background. Qualitatively similar results were obtained on isolated adult rat atrial myocytes. Western blots of atrial and ventricular membrane proteins confirmed the presence of Kv1.2, Kv1.5, Kv2.1, and Kv4.2 and revealed differences in the relative abundances of these subunits in the two membrane preparations. Kv4.2, for example, is more abundant in ventricular than in atrial membranes, whereas Kv1.2 and Kv2.1 are higher in atrial membranes; Kv1.5 levels are comparable in the two preparations. In contrast to these results, nothing was detected in Western blots of atrial or ventricular membrane proteins with the anti-Kv1.4 antibody at concentrations that revealed intense labeling of a 97-kD protein in adult rat brain membranes. A very faint band was detected at 97 kD in the atrial and ventricular preparations when the anti-Kv1.4 antibody was used at a 5- to 10-fold higher concentration. The simplest interpretation of these results is that Kv1.4 is not an abundant protein in adult rat atrial or ventricular myocytes. Therefore, it seems unlikely that Kv1.4 plays an important role in the formation of functional depolarization-activated K + channels in these cells. The relation(s) between the (other four) K + channel subunits and the depolarization-activated K + channels identified electrophysiologically in adult rat atrial and ventricular myocytes is discussed in the present study.
Left axis deviation: a reassessment.
Authors: J K Perloff, N K Roberts, W R Cabeen
Journal: Circulation (1979)

This report deals with the ramifications of the concept of left axis deviation. In early life, the leftward shift of the frontal plane QRS axis is determined chiefly, if not solely, by the relative weights of the ventricles. Once adult ventricular weight ratios are reached, there is a long period of axis stability, then a gradual leftward drift of the QRS, governed principally by left anterior fascicular conduction. Thus, the normal QRS axis is age-dependent, and left axis deviation must be considered accordingly.
Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke
Authors: John D. Carroll, Jeffrey L. Saver, David E. Thaler, Richard W. Smalling, Scott Berry, Lee A. MacDonald, David S. Marks, David L. Tirschwell
Journal: New England Journal of Medicine (2013)

Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age.In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated.We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased.In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.).
The hypocretin/orexin system
Authors: I O Ebrahim, R S Howard, M D Kopelman, M K Sharief, A J Williams
Journal: Journal of the Royal Society of Medicine (2002)

The hypocretins (orexins) are recently described hypothalamic neuropeptides thought to have an important role in the regulation of sleep and arousal states1. Their discovery was reported independently by two groups using different techniques. de Lecea et al.2 identified the pro-hormone pre-prohypocretin, and its peptide products hypocretin-1 (Hcrt-1) and hypocretin-2 (Hcrt-2), by nucleotide sequencing. The discovery of the orexins, orexin-A (Orx-A) and orexin-B (Orx-B), was reported almost simultaneously by Sakurai et al.3 who used the technique of orphan receptor cloning. The terms orexin and hypocretin are synonymous and in this article we will use hypocretin (Hcrt). The finding that cerebrospinal fluid (CSF) levels of these peptides were abnormal in patients with narcolepsy has stimulated research on the potential role of these peptides in human disease. We present here an overview of the pertinent findings from animal studies and a review of the published data from human studies, with a particular emphasis on narcolepsy. Finally, we consider the possible roles of these peptides in neurological and psychiatric disorders.
Preferential coreceptor utilization and cytopathicity by dual-tropic HIV-1 in human lymphoid tissue ex vivo
Authors: Svetlana Glushakova, Yanjie Yi, Jean-Charles Grivel, Anjali Singh, Dominique Schols, Erik De Clercq, Ronald G. Collman, Leonid Margolis
Journal: Journal of Clinical Investigation (1999)

Many HIV-1 isolates at the late stage of disease are capable of using both CXCR4 and CCR5 in transfected cell lines, and are thus termed dual-tropic. Here we asked whether these dual-tropic variants also use both coreceptors for productive infection in a natural human lymphoid tissue microenvironment, and whether use of a particular coreceptor is associated with viral cytopathicity. We used 3 cloned dual-tropic HIV-1 variants, 89.6 and its chimeras 89-v345.SF and 89-v345.FL, which use both CCR5 and CXCR4 in transfected cell lines. In human lymphoid tissue ex vivo, one variant preferentially used CCR5, another preferentially used CXCR4, and a third appeared to be a true dual-tropic variant. The 2 latter variants severely depleted CD4(+) T cells, whereas cytopathicity of the virus that used CCR5 only in lymphoid tissue was mild and confined to CCR5(+)/CD4(+) T cells. Thus, (a) HIV-1 coreceptor usage in vitro cannot be unconditionally extrapolated to natural microenvironment of human lymphoid tissue; (b) dual-tropic viruses are not homogeneous in their coreceptor usage in lymphoid tissue, but probably comprise a continuum between the 2 polar variants that use CXCR4 or CCR5 exclusively; and (c) cytopathicity toward the general CD4(+) T cell population in lymphoid tissue is associated with the use of CXCR4.
LONG-TERM OUTCOMES OF MODERATE TO SEVERE MITRAL REGURGITATION SEEN IN PATIENTS REFERRED FOR STRESS ECHOCARDIOGRAPHY
Authors: Azhar Supariwala, Seth Uretsky, Kavit Desouza, Amit Correa, Ahmed Otokiti, Eric Bader, Martin Tabaksblat, Farooq Chaudhry
Journal: Journal of the American College of Cardiology (2013)
Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial
Authors: Jean-Philippe Collet, Johanne Silvain, Olivier Barthélémy, Grégoire Rangé, Guillaume Cayla, Eric Van Belle, Thomas Cuisset, Simon Elhadad, François Schiele, Nicolas Lhoest, Patrick Ohlmann, Didier Carrié, Hélène Rousseau, Pierre Aubry, Jacques Monségu, Pierre Sabouret, Stephen A O'Connor, Jérémie Abtan, Mathieu Kerneis, Christophe Saint-Etienne, Farzin Beygui, Eric Vicaut, Gilles Montalescot
Journal: The Lancet (2014)
Evaluation of Primary Care Patients with Chronic Stable Angina: Guidelines from the American College of Physicians
Authors: Vincenza Snow, Patricia Barry, Stephan D. Fihn, Raymond J. Gibbons, Douglas K. Owens, Sankey V. Williams, Kevin B. Weiss, Christel Mottur-Pilson
Journal: Annals of Internal Medicine (2004)

In 1999, the American College of Physicians (ACP), then the American College of Physicians–American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which the ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the first of 2 that will provide guidance on the management of patients with chronic stable angina. This document will cover diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on history or on electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A future guideline will cover pharmacologic therapy and follow-up. * This paper, written by Vincenza Snow, MD; Patricia Barry, MD, MPH; Stephan D. Fihn, MD, MPH; Raymond J. Gibbons, MD; Douglas K. Owens, MD; Sankey V. Williams, MD; Kevin B. Weiss, MD, MPH; and Christel Mottur-Pilson, PhD, was developed for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (ACP): Kevin B. Weiss, MD (Chair); Mark Aronson, MD; Patricia Barry, MD; Thomas Cross Jr., MD, MPH; Nick Fitterman, MD; E. Rodney Hornbake, MD; Douglas K. Owens, MD; and Katherine D. Sherif, MD. Approved by the ACP Board of Regents in January 2004.
Diagnosis of occupational asthma from time point differences in serial PEF measurements
Authors: C B S G Burge, V C Moore, C F A Pantin, A S Robertson, P S Burge
Journal: Thorax (2009)

<h3>Background:</h3> The diagnosis of occupational asthma requires objective confirmation. Analysis of serial measurements of peak expiratory flow (PEF) is usually the most convenient first step in the diagnostic process. A new method of analysis originally developed to detect late asthmatic reactions following specific inhalation testing is described. This was applied to serial PEF measurements made over many days in the workplace to supplement existing methods of PEF analysis. <h3>Methods:</h3> 236 records from workers with independently diagnosed occupational asthma and 320 records from controls with asthma were available. The pooled standard deviation for rest day measurements was obtained from an analysis of variance by time. Work day PEF measurements were meaned into matching 2-hourly time segments. Time points with mean work day PEF statistically lower (at the Bonferroni adjusted 5% level) than the rest days were counted after adjusting for the number of contributing measurements. <h3>Results:</h3> A minimum of four time point comparisons were needed. Records with ⩾2 time points significantly lower on work days had a sensitivity of 67% and a specificity of 99% for the diagnosis of occupational asthma against independent diagnoses. Reducing the requirements to ⩾1 non-waking time point difference increased sensitivity to 77% and reduced specificity to 93%. The analysis was only applicable to 43% of available records, mainly due to differences in waking times on work and rest days. <h3>Conclusion:</h3> Time point analysis complements other validated methods of PEF analysis for the diagnosis of occupational asthma. It requires shorter records than are required for the Oasys score and can identify smaller changes than other methods, but is dependent on low rest day PEF variance.
Increased Endoplasmic Reticulum Stress in Atherosclerotic Plaques Associated With Acute Coronary Syndrome
Authors: Jeffrey G. Dickhout, Stephen M. Colgan, Šárka Lhoták, Richard C. Austin
Journal: Circulation (2007)

A cute coronary syndrome (ACS) represents a series of indications of sudden cardiac ischemia that involve a variety of causes, including acute myocardial infarction and unstable angina. 1 ACS usually is associated with thrombus formation in the coronary artery or coronary artery vasospasm, resulting in myocardial ischemia. 2Thrombus formation may involve platelet adhesion and degranulation on damaged or dysfunctional endothelium overlying the intact or ruptured atherosclerotic plaque, as well as microthrombi. 3therosclerotic plaque rupture represents a series of deleterious events linked to the breakdown of the fibrous cap.This process may occur as a result of the increased secretion of matrix metalloproteinases by lesion resident macrophages or enhanced apoptotic cell death within the fibrous cap.However, viable smooth muscle cells (SMCs) within the fibrous cap synthesize interstitial collagen fibers that enhance the structural integrity of the plaque and prevent its rupture.
Comparison of clinical and self reported diagnosis for rheumatology outpatients.
Authors: I Rasooly, A C Papageorgiou, E M Badley
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To examine the sensitivity of patient self reported diagnoses compared with physician diagnoses in a rheumatology outpatient population. METHODS--A mailed survey to 472 rheumatology outpatients (81% response rate) asked about joint symptoms, disabilities, and underlying rheumatic conditions. The self-reported diagnoses were linked with physician diagnoses in the rheumatology clinic computer based diagnostic registry. RESULT--Overall there was an 87% sensitivity for self reported compared with physician diagnoses when the matching criteria included compatible yet different diagnoses such as rheumatoid arthritis (RA) and osteoarthritis (OA). The sensitivity for exact match was 65%, and it varied with the underlying clinical diagnosis, and was greatest for RA (90%) and ankylosing spondylitis (AS) (100%), and intermediate for OA (52%) and psoriatic arthritis (50%). The sensitivity of self report was primarily related to the type of diagnosis (RA or AS v other rheumatic conditions; odds ratio = 16.3, 95% confidence interval (CI) 9.0 to 29.5), and also to difficulty in activities of daily living (odds ratio = 2.3, 95% CI 1.1 to 4.6) but not age, gender, duration of disease, or clinic attendance, as shown by multivariate analysis. CONCLUSIONS--This study in a rheumatology outpatient population indicated that most patients report a diagnosis which is compatible with the clinical diagnosis. These findings give an upper limit to the sensitivity of self reported diagnoses, though further research is needed to assess the extent to which our results may be generalised to other settings.
Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people.
Authors: E Husebye, V Skar, T Hoverstad, K Melby
Journal: Gut (1992)

Fifteen healthy old people mean age 84 years (range 80-91 years), were examined to assess the effect of advanced age on the microecology of the upper gastrointestinal tract. Twelve of 15 (80%) were hypochlorhydric with pH 6.6 (0.3) (mean (SEM) and a mean bacterial count of 10(8) colony forming units (CFU) per ml (range 10(5)-10(10)) in fasting gastric aspirate. Normochlorhydric subjects had low counts (< or = 10(1) CFU/ml). The microbial flora was dominated by viridans streptococci, coagulase negative staphylococci, and Haemophilus sp. Only one subject harboured significant concentrations of Gram negative bacilli with Escherichia coli (10(4-5) CFU/ml) and Klebsiella (10(4-5)). Strict anaerobes were not found. The total concentration of short chain fatty acids in gastric aspirate was 10.6 (2.9) mmol/l (mean (SEM). Absence of significant, intraluminal fermentation of xylose to CO2 was shown by the 14C-d Xylose breath test, and ambulatory manometry showed preserved fasting motility pattern of the small intestine. Serum immunoglobulins were normal. Advanced age is accompanied by fasting hypochlorhydria and colonisation with mainly Gram positive flora in the upper gut. Other factors than old age and fasting hypochlorhydria are required for colonisation with Gram negative bacilli.