tbuckley/cabot-search huggingface dataset:
Phase II Trial of Cetuximab in Patients With Previously Treated Non–Small-Cell Lung Cancer
Authors: Nasser Hanna, Rogerio Lilenbaum, Rafat Ansari, Thomas Lynch, Ramaswamy Govindan, Pasi A. Jänne, Philip Bonomi
Journal: Journal of Clinical Oncology (2006)

Purpose To determine the efficacy of cetuximab in patients with recurrent or progressive non–small-cell lung cancer (NSCLC) after receiving at least one prior chemotherapy regimen. Patients and Methods This was an open-label, phase II study of patients with epidermal growth factor receptor (EGFR) –positive and EGFR-negative advanced NSCLC with Eastern Cooperative Oncology Group performance status 0 to 1. Patients received cetuximab 400 mg/m 2 intravenously (IV) during 120 minutes on week 1 followed by weekly doses of cetuximab 250 mg/m 2 IV during 60 minutes. A cycle was considered as 4 weeks of treatment and therapy was continued until disease progression or intolerable toxicities. The primary end point was to assess response rate. Secondary end points included an estimation of time to progression and survival. Results Patient and disease characteristics (n = 66) included EGFR-positive status (n = 60); EGFR-negative status (n = 6); number of prior regimens (one, n = 28; two, n = 27; ≥ three, n = 11); male (n = 41); female (n = 25); adenocarcinoma (n = 36); and smoking status (never, n = 13; former, n = 45; current, n = 8). Grade 3/4 toxicities included acne-like rash (6.1%), anaphylactic reactions (1.5%), and diarrhea (1.5%). The response rate for all patients (n = 66) was 4.5% (95% CI, 0.9% to 12.7%) and the stable disease rate was 30.3% (95% CI, 19.6% to 42.9%). The response rate for patients with EGFR-positive tumors (n = 60) was 5% (95% CI, 1.0% to 13.9%). The median time to progression for all patients was 2.3 months (95% CI, 2.1 to 2.6 months) and median survival time was 8.9 months (95% CI, 6.2 to 12.6 months). Conclusion Although the response rate with single-agent cetuximab in this heavily pretreated patient population with advanced NSCLC was only 4.5%, the disease control rates and overall survival seem comparable to that of pemetrexed, docetaxel, and erlotinib in similar groups of patients.
Diphenylhydantoin in Neurotic Anxiety
Authors: WARREN G. CASE, KARL RICKELS, STANFORD BAZILIAN
Journal: American Journal of Psychiatry (1969)

Anxious-neurotic psychiatric clinic outpatients in social classes IV and V were treated over a four-week period with diphenylhydantoin, 100 mg., twice daily. While some improvement was observed in this patient group, no significant difference was noted between the diphenylhydantoin and a comparable placebo group.
Clinical Experience With Primary Percutaneous Transluminal Coronary Angioplasty Compared With Alteplase (Recombinant Tissue-Type Plasminogen Activator) in Patients With Acute Myocardial Infarction
Authors: Alan J Tiefenbrunn, Nisha C Chandra, William J French, Joel M Gore, William J Rogers
Journal: Journal of the American College of Cardiology (1998)

Objectives. We sought to compare outcomes after primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for acute myocardial infarction (MI). Background. Primary PTCA and thrombolytic therapy are alternative means of achieving reperfusion in patients with acute MI. The Second National Registry of Myocardial Infarction (NRMI-2) offers an opportunity to study the clinical experience with these modalities in a large patient group. Methods. Data from NRMI-2 were reviewed. Results. From June 1, 1994 through October 31, 1995, 4,939 nontransfer patients underwent primary PTCA within 12 h of symptom onset, and 24,705 patients received alteplase (recombinant tissue-type plasminogen activator [rt-PA]). When lytic-ineligible patients and patients presenting in cardiogenic shock were excluded, baseline characteristics were similar. The median time from presentation to initiation of rt-PA in the thrombolytic group was 42 min; the median time to first balloon inflation in the primary PTCA group was 111 min (p < 0.0001). In-hospital mortality was higher in patients in shock after rt-PA than after PTCA (52% vs. 32%, p < 0.0001). In-hospital mortality was the same in lytic-eligible patients not in shock: 5.4% after rt-PA and 5.2% after PTCA. The stroke rate was higher after lytic therapy (1.6% vs. 0.7% after PTCA, p < 0.0001), but the combined end point of death and nonfatal stroke was not significantly different between the two groups (6.2% after rt-PA and 5.6% after PTCA). There was no difference in the rate of reinfarction (2.9% after rt-PA and 2.5% after PTCA). Conclusions. These findings suggest that in lytic-eligible patients not in shock, PTCA and rt-PA are comparable alternative methods of reperfusion when analyzed in terms of in-hospital mortality, mortality plus nonfatal stroke and reinfarction.
Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts
Authors: Yutong Cai, Tamara Schikowski, Martin Adam, Anna Buschka, Anne-Elie Carsin, Benedicte Jacquemin, Alessandro Marcon, Margaux Sanchez, Andrea Vierkötter, Zaina Al-Kanaani, Rob Beelen, Matthias Birk, Bert Brunekreef, Marta Cirach, Françoise Clavel-Chapelon, Christophe Declercq, Kees de Hoogh, Audrey de Nazelle, Regina E Ducret-Stich, Virginia Valeria Ferretti, Bertil Forsberg, Margaret W Gerbase, Rebecca Hardy, Joachim Heinrich, Gerard Hoek, Debbie Jarvis, Dirk Keidel, Diana Kuh, Mark J Nieuwenhuijsen, Martina S Ragettli, Andrea Ranzi, Thierry Rochat, Christian Schindler, Dorothea Sugiri, Sofia Temam, Ming-Yi Tsai, Raphaëlle Varraso, Francine Kauffmann, Ursula Krämer, Jordi Sunyer, Nino Künzli, Nicole Probst-Hensch, Anna L Hansell
Journal: Thorax (2014)

This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project.Annual average particulate matter (PM(10), PM(2.5), PM(absorbance), PM(coarse)), NO(2), nitrogen oxides (NO(x)) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis.15 279 and 10 537 participants respectively were included in the main NO(2) and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO(2) and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PM(coarse) OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM(10) with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM(2.5abs) (black carbon) exposures.Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations.
Distinct functional phenotypes of cloned Ia-restricted helper T cells.
Authors: J Kim, A Woods, E Becker-Dunn, K Bottomly
Journal: The Journal of Experimental Medicine (1985)

Analysis of activation of phosphorylcholine (PC)-specific B cells by a large number of different cloned, self Ia-specific helper T cell (Th) clones has permitted the classification of such T cells into four distinct functional types. Types 1 and 2 induce B cells to secrete anti-PC antibody in an antigen-specific, Ia-restricted fashion. Type 3 cells induce antigen-specific, Ia-restricted B cell proliferation, but do not lead to specific antibody formation, and have been shown previously to have suppressor functions. Type 4 cells are autoreactive, and induce antigen-independent B cell activation and antibody secretion. The distinction between type 1 and type 2 Th clones was analyzed in detail. In bulk cultures, type 1 cloned lines generate an idiotypically heterogeneous anti-PC antibody response, whereas type 2 cloned lines induce a larger response that is dominated by the T15 idiotype. In limiting-dilution analyses, type 2 cells induce fourfold more T15+, PC-specific precursor B cells than do type 1 cells, and in addition, induce larger burst sizes for T15+, PC-specific B cells. Type 4 clones can also be subdivided into cells that are type 1-like, and cells that are type 2-like. These differences in functional phenotype are seen over a broad range of antigen and cell doses. Detailed analysis of the behavior of these distinct functional types of Th should allow a better understanding of the functional properties of mixed populations of antigen-primed, Ia-restricted Th cells.
Reply to M. Sun et al
Authors: Dmitry A. Nosov, William J. Slichenmyer
Journal: Journal of Clinical Oncology (2012)

Sun et al 1 provide a concise overview of renal cell carcinoma (RCC), current treatment options for the disease, and some of the findings from our recently published randomized discontinuation phase II clinical study of tivozanib, an investigational agent in development for this indication. 2In the phase II study, 2 tivozanib-a potent, selective inhibitor of vascular endothelial growth factor receptors (VEGFRs)-was active and well-tolerated in the patient population evaluated.Although Sun et al 1 point out the statistically significant improvement in progression-free survival (PFS) for patients treated with tivozanib during the randomized phase of the trial, we believe it is important to clarify for readers that the median PFS in the intent-totreat population for the entire study was 11.7 months for patients treated with tivozanib.The median PFS of 10.3 months cited by Sun et al pertains to the double-blinded phase of the trial, which included only a subset of the study population over a defined interval after a 16-week run-in phase of treatment with tivozanib.Sun et al 1 also comment on the positive findings from a phase III trial of tivozanib versus sorafenib in patients with advanced RCC.The results of this study were recently presented at the 2012 Annual Meeting of the American Society of Clinical Oncology 3 and have not yet been published fully.As mentioned by Sun et al, 1 when compared with sorafenib, tivozanib demonstrated superior efficacy, including a median PFS of 12.7 months in the subset of patients who were treatmentnaive for metastatic disease.In addition, tivozanib was well-tolerated, had lower rates of certain off-target adverse events, and required fewer dose adjustments.Sun et al 1 inquire about the choice of sorafenib as comparator in that trial.It should be noted that other agents recently approved for use as first-line treatment for patients with RCC were compared in phase III studies to either placebo or interferon.The tivozanib versus sorafenib study is the first head-to-head trial that has shown superiority of one contemporary tyrosine kinase inhibitor over another in an anti-VEGFR-naive population with RCC.We agree with Sun et al 1 that future trials will be important in guiding the selection of optimal treatments from among the various alternatives.One such study that is currently being initiated is a comparison of tivozanib with sunitinib to assess patient-reported outcomes.This study will use a design similar to the PISCES study, which was presented at the 2012 Annual Meeting of the American Society of Clinical Oncology. 4We also agree with Sun et al 1 that future trials may consider other comparator agents including the VEGFR and mammalian target of rapamycin antagonists that they listed.
Functional Anatomy of Aortic Regurgitation
Authors: Jean-Benoît le Polain de Waroux, Anne-Catherine Pouleur, Céline Goffinet, David Vancraeynest, Michel Van Dyck, Annie Robert, Bernhard L. Gerber, Agnès Pasquet, Gébrine El Khoury, Jean-Louis J. Vanoverschelde
Journal: Circulation (2007)

Background— For patients with aortic regurgitation (AR), aortic valve sparing or repair surgery is an attractive alternative to valve replacement. In this setting, accurate preoperative delineation of aortic valve pathology and potential repairability is of paramount importance. The aim of the present study was to assess the diagnostic value of preoperative transesophageal echocardiography (TEE) in defining the mechanisms of AR, as identified by surgical inspection, and in predicting repairability, by using the final surgical approach as reference. Methods and Results— One hundred and sixty-three consecutive patients (117 males, mean age: 58±14 years) undergoing AR surgery were included. Mechanisms of AR were categorized by TEE and surgical inspection as follows: type 1, aortic dilatation; type 2, cusp prolapse; and type 3, restrictive cusp motion or endocarditis. At surgery, mechanisms of AR were type 1 in 41 patients, type 2 in 62, and type 3 in 60. Agreement between TEE and surgical inspection was 93% (κ=0.90). Valve sparing or repair was performed in 125 patients and valve replacement in 38 patients. TEE correctly predicted the final surgical approach in 108/125 (86%) patients undergoing repair and in 35/38 (93%) patients undergoing replacement. The gross anatomic classification of AR lesions by TEE was determinant of valve repairability and postoperative outcome (4-year freedom from &gt; grade 2 AR, reoperation, or death, P =0.04). Conclusions— TEE provides a highly accurate anatomic assessment of all types of AR lesions. In addition, the functional anatomy of AR defined by TEE is strongly and independently predictive of valve repairability and postoperative outcome.
Amylase gene structures in primates: retroposon insertions and promoter evolution
Authors: L. C. Samuelson, R. S. Phillips, L. J. Swanberg
Journal: Molecular Biology and Evolution (1996)

Amylase transcription in the human salivary gland results from the evolutionary juxtaposition of two inserted elements, a gamma-actin pseudogene and an endogenous retrovirus, to create an unusual salivary-specific promoter. We utilized these structures as molecular tags to characterize the amylase genes in extant primates by polymerase chain reaction amplification of promoter fragments from genomic DNA. Six distinct amylase promoter structures were identified, which allowed us to infer the structures of common ancestors and trace the evolution of the modern human amylase promoters. Our data show that integration of the pseudogene and retrovirus were evolutionarily recent events. The gamma-actin pseudogene integrated after the divergence of the New World monkeys from the primate ancestral tree, and the retrovirus integrated later, after the divergence of the Old World monkeys. The New World monkey amylase promoter represents the mammalian amylase precursor structure before integration of the two retroposons. Two distinct amylase genes were identified in the Old World monkeys, one with a complete gamma-actin pseudogene insert and another novel structure with a truncation of the gamma-actin sequences. We demonstrated abundant amylase expression in the saliva of an Old World monkey, indicating that the endogenous retrovirus is not required for amylase transcription in the primate salivary gland.
Feasibility of progressive knee-extension strength training using ankle weight cuffs in patients hospitalized with COPD for acute exacerbation
Authors: Linette Marie Kofod, Martin Døssing, Johnna Steentoft, Morten Tange Kristensen
Journal: European Respiratory Journal (2013)

Introduction   Muscle weakness in COPD is associated with increased morbidity and mortality. It is desirable to develop an easily applicable method of training to prevent patients with COPD from losing strength and function    Objective   To examine the feasibility of progressive strength training using ankle weight cuffs in patients hospitalized with COPD in acute exacerbation    Methods   Twenty patients with COPD (12 men and 8 women – mean (SD) age of 71.6 (10.1) years) with a mean FEV1 33% (16.2) and a MRC 4.3 (0.6) conducted daily unilateral knee-extension strength training. The patient was seated on the bedside using ankle weights cuffs in 3 sets of 10 repetition maximum loadings (adjusted on a set-by-set basis). The Sit-to-stand (STS) and Timed Up and Go (TUG) tests were assessed before and after the strength program    Results   Weight loads increased progressively by an average of 33% (P  20 kg (n=1). Patients who conducted more than two training sessions (n=11) increased weight loads with 57% after a mean of 6 (2.9) days. The TUG and STS improved (n=11, P≤0.001) by 15% and 56% respectively    Conclusions   Progressive knee-extension strength training using ankle weight cuffs seems feasible and may be effective in improving function and preventing loss of strength in patients hospitalized with severe COPD. Confirmation in a randomized design is needed.
Are we missing an epidemic of HIV-associated nephropathy?
Authors: J A Winston, P E Klotman
Journal: Journal of the American Society of Nephrology (1996)

HIV-associated nephropathy is infrequently cited as a common cause of ESRD. It is likely, however, that by the end of the decade, HIV-associated nephropathy will be the third leading cause of ESRD in African Americans between the ages of 20 and 64. Underreporting for reasons of confidentiality and a failure to track this specific diagnostic category nationally may account for the nephrology community's inattention. As a result of this community's failure to define this issue, national agencies are poorly prepared to recognize and anticipate the changing demographics of the AIDS epidemic as it affects the practice of nephrology. The study presented here concluded: that a national registry should be created to track the incidence of HIV-associated nephropathy as a cause of ESRD; that renal biopsies should be routinely performed to confirm the clinical diagnosis of HIV-associated nephropathy; that anonymous serological screening of all patients and health care providers in dialysis units be reconsidered in order to maintain vigilance for potential unit outbreaks; that the National Institutes of Health and the Office of AIDS Research be better appraised of the importance of this issue by the nephrology community; and that special attention be directed toward the underlying cause(s) of HIV-associated nephropathy and the cofactor(s) that determine the predilection of this disease in blacks.
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
Authors: Nicole Soranzo, Tim D Spector, Massimo Mangino, Brigitte Kühnel, Augusto Rendon, Alexander Teumer, Christina Willenborg, Benjamin Wright, Li Chen, Mingyao Li, Perttu Salo, Benjamin F Voight, Philippa Burns, Roman A Laskowski, Yali Xue, Stephan Menzel, David Altshuler, John R Bradley, Suzannah Bumpstead, Mary-Susan Burnett, Joseph Devaney, Angela Döring, Roberto Elosua, Stephen E Epstein, Wendy Erber, Mario Falchi, Stephen F Garner, Mohammed J R Ghori, Alison H Goodall, Rhian Gwilliam, Hakon H Hakonarson, Alistair S Hall, Naomi Hammond, Christian Hengstenberg, Thomas Illig, Inke R König, Christopher W Knouff, Ruth McPherson, Olle Melander, Vincent Mooser, Matthias Nauck, Markku S Nieminen, Christopher J O'Donnell, Leena Peltonen, Simon C Potter, Holger Prokisch, Daniel J Rader, Catherine M Rice, Robert Roberts, Veikko Salomaa, Jennifer Sambrook, Stefan Schreiber, Heribert Schunkert, Stephen M Schwartz, Jovana Serbanovic-Canic, Juha Sinisalo, David S Siscovick, Klaus Stark, Ida Surakka, Jonathan Stephens, John R Thompson, Uwe Völker, Henry Völzke, Nicholas A Watkins, George A Wells, H-Erich Wichmann, David A Van Heel, Chris Tyler-Smith, Swee Lay Thein, Sekar Kathiresan, Markus Perola, Muredach P Reilly, Alexandre F R Stewart, Jeanette Erdmann, Nilesh J Samani, Christa Meisinger, Andreas Greinacher, Panos Deloukas, Willem H Ouwehand, Christian Gieger
Journal: Nature Genetics (2009)
Metabolic phenotype and adipose tissue inflammation in patients with chronic obstructive pulmonary disease
Authors: Pavol Joppa, Jozef Ukropec, Peter Skyba, Barbara Ukropcova, Pavol Pobeha, Katarina Stroffekova, Miroslav Brusik, Daniela Gasperikova, Ruzena Tkacova
Journal: European Respiratory Journal (2011)

Rationale: Potential links between metabolic derangements and adipose tissue inflammation in patients with chronic obstructive pulmonary disease (COPD) are unexplored. We investigated adipose tissue expressions of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, CD68 (macrophage cell surface receptor), caspase-3 and Bax, and their relationships to the metabolic phenotype in nine cachectic, 12 normal-weight, 12 overweight, and 11 obese patients with stable COPD (age 62.3±7.2 years).

Methods: Body composition was assessed by Dual Energy X-Ray Absorptiometry, and insulin sensitivity by euglycemic hyperinsulinemic clamp. Subcutaneous adipose tissue samples were analyzed using real-time PCR.

Results: With increasing body mass index, increases in adipose tissue expressions of IL-6, TNF-alpha and CD68 were observed (p<0.001; p=0.005; p<0.001, respectively), in association with reduced insulin sensitivity (p<0.001). No differences were observed between cachectic and normal-weight patients in adipose tissue expressions of inflammatory or proapoptotic markers. Adipose tissue CD68 and TNF-alpha expressions predicted insulin sensitivity independently of known confounders (p=0.005; p=0.025; R 2=0.840).

Conclusions: Our results suggest that adipose tissue inflammation in obese COPD patients relates to insulin resistance. Cachectic patients remained insulin sensitive, with no significant upregulation of inflammatory or proapoptotic markers in the adipose tissue.

Support: APVV-0122-06, VEGA-1/0348/09 and VVGS 36/10-11.
Mechanisms of Hypoxia Responses in Renal Tissue
Authors: Volker H. Haase
Journal: Journal of the American Society of Nephrology (2013)

pO2 in the kidney is maintained at relatively stable levels by a unique and complex functional interplay between renal blood flow, GFR, O2 consumption, and arteriovenous O2 shunting. The fragility of this interplay makes the kidney susceptible to hypoxic injury. Cells in the kidney utilize various molecular pathways that allow them to respond and adapt to changes in renal oxygenation. This review provides an integrative perspective on the role of molecular hypoxia responses in normal kidney physiology and pathophysiology, and discusses their therapeutic potential for the treatment of renal diseases.
Chronic lyme disease: psychogenic fantasy or somatic infection?
Authors: Phyllis Mervine
Journal: Environmental Health Perspectives (2003)

Sigal and Hassett published an article about Lyme disease in the EHP Supplements (Sigal and Hassett 2002), suggesting that chronic Lyme disease is "psychogenic." I do not think that Sigal and Hassett, non-psychiatrists, are qualified to speak about psychiatric matters. I, however, actually have had the disease, which they characterize as "medically unexplained," for over 25 years and have 15 years of experience as a patient advocate and educator. I beg to differ.
Abstract 3348: TAXUS Liberte Inhibits the Effect of Diabetes on Restenosis: A Pooled Analysis of the TAXUS ATLAS Program
Authors: John A Ormiston, Ehtisham Mahmud, Lazar Mandinov, Jeffrey J Popma, Neil J Weissman, Charles D O'Shaughnessy, Tift Mann, Jack J Hall, Thomas F McGarry, Louis A Cannon, Mark W Webster, Joerg Koglin, Donald S Baim
Journal: Circulation (2007)

Background: Diabetics suffer from accelerated atherosclerosis, co-morbidities and an increased risk of restenosis. Paclitaxel is hypothesized to inhibit restenosis even in the presence of insulin r...