tbuckley/cabot-search huggingface dataset:
Agglutination of Haemolytic Streptococci (Group A) in Serum from Patients with Rheumatoid Arthritis
Authors: K. Kalbak
Journal: Annals of the Rheumatic Diseases (1947)

The theory of a streptococcal causation of rheumatoid arthritis continues to be of great importance, and since it was first advanced it has been supported by serological and bacteriological investigations, including agglutination tests, more especially in the United States.Table 1 summarizes a number of these investigations.The writer (Kalbak, 1946) obtained 79 per cent. of positive reactions among rheumatoid arthritis patients.In the control material the positives represented a very low percentage.In the same year Cecil and de Gara reported finding positive agglutination reactions in 60 per cent. of 268 patients with rheumatoid arthritis.The number of positive reactions among scarlatina patients was only 25 per cent., and in a control material there were none, or only very few.In their opinion the test was more often positive in patients with a severe joint affection, whereas the reaction became weaker and gradually quite negative as the disease improved or was cured.Edstrom and Winblad (1947) had 76 per cent. of positive reactions among fifty patients with rheumatoid arthritis.They claimed that the reaction did not become positive until four or six months after the commencement of the strepto- coccal infection.Using a somewhat altered technique, Thulin (1947) obtained over 90 per cent. of positive reactions, and Hedlund (1947) 55 per cent., among patients with rheumatoid arthritis.The article by Angevine and others (1942) should also be consulted.The conclusions to be drawn from these investigations appear to be: 1.The agglutination test is best made with haemolytic streptococci of Lance- field's Group A.2. Among polyarthritis patients there are between 50 and 75 per cent.positive agglutination reactions.3. The percentage of positives in the control materials is very low.
UK government puts children at centre of plans to improve the country's health
Authors: Kristina Fišter
Journal: BMJ (2005)

A sound ethical framework for research in developing countries is crucial for ensuring that participants are safe from exploitation, says a report from the Nuffield Council on Bioethics.But some of the measures introduced to try to offer such protection-such as arguing that participants should have access to the same standards of care made available in developed countries-are impractical and can undermine potential research opportunities, it says.The conclusions follow a discussion paper issued by the council in 2002 and a subsequent meeting in Cape Town, South Africa, in February 2004, attended by 58 participants from 28 countries, including India, China, Kenya, and Botswana.The discussion paper published by the council looks at the current laws governing research in developing countries, including the 1964 Declaration of Helsinki, which has since been amended five times by the World Medical Association and clarified by the Council for International Organizations of Medical Sciences.Research in developing countries is crucial, the paper says, for improving health care.But researchers in these countries often cannot conduct their own research, making partnership with more developed countries essential.
A Phase I Trial to Determine the Optimal Biological Dose of Celecoxib when Combined with Erlotinib in Advanced Non–Small Cell Lung Cancer
Authors: Karen L. Reckamp, Kostyantyn Krysan, Jason D. Morrow, Ginger L. Milne, Robert A. Newman, Christopher Tucker, Robert M. Elashoff, Steven M. Dubinett, Robert A. Figlin
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Overexpression of cyclooxygenase-2 (COX-2) activates extracellular signal-regulated kinase/mitogen-activated protein kinase signaling in an epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI)–resistant manner. Because preclinical data indicated that tumor COX-2 expression caused resistance to EGFR TKI, a phase I trial to establish the optimal biological dose (OBD), defined as the maximal decrease in urinary prostaglandin E-M (PGE-M), and toxicity profile of the combination of celecoxib and erlotinib in advanced non–small cell lung cancer was done. Experimental Design: Twenty-two subjects with stage IIIB and/or IV non–small cell lung cancer received increasing doses of celecoxib from 200 to 800 mg twice daily (bid) and a fixed dose of erlotinib. Primary end points included evaluation of toxicity and determination of the OBD of celecoxib when combined with erlotinib. Secondary end points investigate exploratory biological markers and clinical response. Results: Twenty-two subjects were enrolled, and 21 were evaluable for the determination of the OBD, toxicity, and response. Rash and skin-related effects were the most commonly reported toxicities and occurred in 86%. There were no dose-limiting toxicities and no cardiovascular toxicities related to study treatment. All subjects were evaluated on intent to treat. Seven patients showed partial responses (33%), and five patients developed stable disease (24%). Responses were seen in patients both with and without EGFR-activating mutations. A significant decline in urinary PGE-M was shown after 8 weeks of treatment, with an OBD of celecoxib of 600 mg bid. Conclusions: This study defines the OBD of celecoxib when combined with a fixed dose of EGFR TKI. These results show objective responses with an acceptable toxicity profile. Future trials using COX-2 inhibition strategies should use the OBD of celecoxib at 600 mg bid.
Asthma, airflow limitation and mortality risk in the general population
Authors: Shuang Huang, Monica M. Vasquez, Marilyn Halonen, Fernando D. Martinez, Stefano Guerra
Journal: European Respiratory Journal (2014)

Asthma and chronic obstructive pulmonary disease co-exist in a significant proportion of patients. Whether asthma increases mortality risk among subjects with airflow limitation remains controversial. We used data from 2121 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease cohort. At enrolment (1972–1973), participants completed questionnaires and lung function tests. Participants were categorised into four groups based on the combination of airflow limitation (AL; forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) &lt;70%) and physician-confirmed asthma at baseline. Vital status as of January 2011 was assessed through the National Death Index. Cox proportional hazards models were used to test differences in mortality risk across the four airflow limitation/asthma groups. In multivariate Cox models, the AL+/asthma+ group had a 114% increased mortality risk during follow-up compared with the AL-/asthma- group (adjusted HR 2.14; 95% CI 1.64–2.79). The corresponding hazard ratios were 1.09 (95% CI 0.89–1.34) and 1.34 (95% CI 1.14–1.57) for the AL-/asthma+ and AL+/asthma- groups, respectively. Among subjects with airflow limitation, asthma was associated with increased mortality risk (HR 1.58, 95% CI 1.17–2.12). However, this increased risk was substantially reduced and no longer significant after further adjustment for baseline FEV 1 levels. Similar results were obtained when airflow limitation was defined as FEV 1 /FVC less than the lower limit of normal. In a population-based cohort, subjects with concomitant airflow limitation and asthma had an increased risk of dying, which was mainly related to their baseline lung function deficits.
Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease
Authors: Y. Atsuta, R. Suzuki, T. Yamashita, T. Fukuda, K. Miyamura, S. Taniguchi, H. Iida, T. Uchida, K. Ikegame, S. Takahashi, K. Kato, K. Kawa, T. Nagamura-Inoue, Y. Morishima, H. Sakamaki, Y. Kodera
Journal: Annals of Oncology (2014)

The number of long-term survivors after hematopoietic stem cell transplantation (HSCT) showed steady increase in the past two decades. Second malignancies after HSCT are a devastating late complication. We analyzed the incidence of, risk compared with that in the general population, and risk factors for secondary solid cancers.Patients were 17 545 adult recipients of a first allogeneic stem cell transplantation between 1990 and 2007 in Japan. Risks of developing secondary solid tumors were compared with general population by using standard incidence ratios (SIRs).Two-hundred sixty-nine secondary solid cancers were identified. The cumulative incidence was 0.7% [95% confidence interval (CI), 0.6%-0.9%] at 5 years and 1.7% (95% CI, 1.4%-1.9%) at 10 years after transplant. The risk was significantly higher than that in the general population (SIR=1.8, 95% CI, 1.5-2.0). Risk was higher for oral cancer (SIR=15.7, 95% CI, 12.1-20.1), esophageal cancer (SIR=8.5, 95% CI, 6.1-11.5), colon cancer (SIR=1.9, 95% CI, 1.2-2.7), skin cancer (SIR=7.2, 95% CI, 3.9-12.4), and brain/nervous system cancer (SIR=4.1, 95% CI, 1.6-8.4). The risk of developing oral, esophageal, or skin cancer was higher at all times after 1-year post-transplant. Extensive-type chronic graft-versus-host disease (GVHD) was a significant risk factor for the development of all solid tumors (RR=1.8, P<0.001), as well as for oral (RR=2.9, P<0.001) and esophageal (RR=5.3, P<0.001) cancers. Limited-type chronic GVHD was an independent risk factor for skin cancers (RR=5.8, P=0.016).Recipients of allogeneic HSCT had a significantly higher ∼2-fold risk of developing secondary solid cancers than the general population. Lifelong screening for high-risk organ sites, especially oral or esophageal cancers, is important for recipients with active, or a history of, chronic GVHD.
Bidirectional regulation of Ca2+ sparks by mitochondria-derived reactive oxygen species in cardiac myocytes
Authors: Yuan Yan, Jie Liu, Chaoliang Wei, Kaitao Li, Wenjun Xie, Yanru Wang, Heping Cheng
Journal: Cardiovascular Research (2007)

AimsThe cardiac ryanodine receptor (RyR) Ca2+ release channel homotetramer harbours ∼21 potentially redox-sensitive cysteine residues on each subunit and may act as a sensor for reactive oxygen species (ROS), linking ROS homeostasis to the regulation of Ca2+ signalling. In cardiac myocytes, arrayed RyRs or Ca2+ release units are packed in the close proximity of mitochondria, the primary source of intracellular ROS production. The present study investigated whether and how mitochondria-derived ROS regulate Ca2+ spark activity in intact cardiac myocytes.
A role for inflammation in irritable bowel syndrome?
Authors: G Barbara, R De Giorgio, V Stanghellini, C Cremon, R Corinaldesi
Journal: Gut (2002)

Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.
One-Hit Effects in Cancer: Altered Proteome of Morphologically Normal Colon Crypts in Familial Adenomatous Polyposis
Authors: Anthony T. Yeung, Bhavinkumar B. Patel, Xin-Ming Li, Steven H. Seeholzer, Renata A. Coudry, Harry S. Cooper, Alfonso Bellacosa, Bruce M. Boman, Tao Zhang, Samuel Litwin, Eric A. Ross, Peggy Conrad, James A. Crowell, Levy Kopelovich, Alfred Knudson
Journal: Cancer Research (2008)

Abstract We studied patients with Familial Adenomatous Polyposis (FAP) because they are virtually certain to develop colon cancer, and because much is known about the causative APC gene. We hypothesized that the inherited heterozygous mutation itself leads to changes in the proteome of morphologically normal crypts and the proteins that changed may represent targets for preventive and therapeutic agents. We determined the differential protein expression of morphologically normal colon crypts of FAP patients versus those of individuals without the mutation, using two-dimensional gel electrophoresis, mass spectrometry, and validation by two-dimensional gel Western blotting. Approximately 13% of 1,695 identified proteins were abnormally expressed in the morphologically normal crypts of APC mutation carriers, indicating that a colon crypt cell under the one-hit state is already abnormal. Many of the expression changes affect pathways consistent with the function of the APC protein, including apoptosis, cell adhesion, cell motility, cytoskeletal organization and biogenesis, mitosis, transcription, and oxidative stress response. Thus, heterozygosity for a mutant APC tumor suppressor gene alters the proteome of normal-appearing crypt cells in a gene-specific manner, consistent with a detectable one-hit event. These changes may represent the earliest biomarkers of colorectal cancer development, potentially leading to the identification of molecular targets for cancer prevention. [Cancer Res 2008;68(18):7579–86]
A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12
Authors: David J Klinke
Journal: Molecular Cancer (2010)

Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales.
Gene Expression Profiling of Breast Cancer
Authors: Maggie C.U. Cheang, Matt van de Rijn, Torsten O. Nielsen
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

DNA microarray platforms for gene expression profiling were invented relatively recently, and breast cancer has been among the earliest and most intensely studied diseases using this technology. The molecular signatures so identified help reveal the biologic spectrum of breast cancers, provide diagnostic tools as well as prognostic and predictive gene signatures, and may identify new therapeutic targets. Data are best presented in an open access format to facilitate external validation, the most crucial step in identifying robust, reproducible gene signatures suitable for clinical translation. Clinically practical applications derived from full expression profile studies already in use include reduced versions of microarrays representing key discriminatory genes and therapeutic targets, quantitative polymerase chain reaction assays, or immunohistochemical surrogate panels (suitable for application to standard pathology blocks). Prospective trials are now underway to determine the value of such tools for clinical decision making in breast cancer; these efforts may serve as a model for using such approaches in other tumor types.
Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma
Authors: P. Macchiaverni, A. Rekima, M. Turfkruyer, L. Mascarell, S. Airouche, P. Moingeon, K. Adel-Patient, A. Condino-Neto, I. Annesi-Maesano, S. L. Prescott, M. K. Tulic, V. Verhasselt
Journal: Allergy (2013)

There is an urgent need to identify environmental risk and protective factors in early life for the prevention of allergy. Our study demonstrates the presence of respiratory allergen from house dust mite, Der p 1, in human breast milk. Der p 1 in milk is immunoreactive, present in similar amounts as dietary egg antigen, and can be found in breast milk from diverse regions of the world. In a mouse model of asthma, oral exposure to Der p through breast milk strongly promotes sensitization rather than protect the progeny as we reported with egg antigen. These data highlight that antigen administration to the neonate through the oral route may contribute to child allergic sensitization and have important implications for the design of studies assessing early oral antigen exposure for allergic disease prevention. The up-to-now unknown worldwide presence of respiratory allergen in maternal milk allows new interpretation and design of environmental control epidemiological studies for allergic disease prevention.
Effect of intrarenal angiotensin II blockade on renal function in conscious dogs.
Authors: H M Kimbrough, E D Vaughan, R M Carey, C R Ayers
Journal: Circulation Research (1977)

The effects of intrarenal infusion of 1-sar-8-ala angiotension II (P 113) and a converting enzyme inhibitor, SQ 20881, at doses that did not affect systemic blood pressure (2.0 mug/kg per min) were studied in conscious, uninephrectomized dogs. In dogs receiving approximately equal to 5 mEq/day of sodium, intrarenal infusion of P 113 increased renal blood flow (RBF) from 219.8 +/- 32.3 to 282.7 +/- 20.0 ml/min (P less than 0.004), and with intrarenal SQ 20881 infusion from 215.3 +/- 14.2 to 278.0 +/- 22.2 ml/min (p less than 0.005). In sodium-restricted dogs (approximately equal to 5 mEq/day), glomerular filtration rate (GFR) also increased with intrarenal P 113 infusion from 57.9 +/- 5.7 to 66.3 +/- 6.6 ml/min (P less than 0.05), and with SQ 20881 infusion from 43.1 +/- 2.1 to 55.7 +/- 4.5 ml/min (P less than 0.01). Dogs on approximately equal to 5 mEq/day of sodium showed significant increases in plasma renin activity (PRA) with intrarenal infusion of the peptides, unmasking a negative feedback inhibition of renin release by angiotensin II. No increases in RBF, GFR, or PRA were seen with infusion without inhibitors, or in dogs give P 113 or SQ 20881 while on approximately equal to 80 mEq/day of sodium. In addition, angiotensin II inhibition increased sodium excretion during sodium restriction. These findings suggest that intrarenal angiotensin II is intimately involved in renal responses to sodium restriction which result in conservation of sodium and water.
The Computer and the Clinical Decision Process: II
Authors: BERNARD C. GLUECK, CHARLES F. STROEBEL
Journal: American Journal of Psychiatry (1969)

The computer poses intriguing challenges about the ways patient data may best be presented to aid clinicians. The authors present a classification approach which depends heavily on the clinician's unique ability to make meaningful hypotheses, based partly on hunches. After he sets up guidelines for establishing categories, the computer provides him with information about previous cases; if the optimal weights appear to possess reasonable validity he asks for a prediction about potential decisions concerning a current patient.
Afatinib (A) Followed By a + Paclitaxel (P) or Investigator'S Choice of Single-Agent Chemotherapy (Ic) in Patients (Pts) with Advanced Squamous Cell Carcinoma (Scc) of the Lung: Subgroup Analysis of Lux-Lung 5 (Ll5)
Authors: K. Park, J. Kim, M. Schuler, D. Planchard, F. De Marinis, Y. Chen, C. Zhou, J. Bennouna, L. Xiaoqing, J. Feng, P. Bidoli, J. Strausz, C. Chouaid, M. Huang, L. Ho, B. Wang, V. Chand, J. Yang
Journal: Annals of Oncology (2014)
Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement
Authors: D. Husereau, M. Drummond, S. Petrou, C. Carswell, D. Moher, D. Greenberg, F. Augustovski, A. H. Briggs, J. Mauskopf, E. Loder
Journal: BMJ (2013)

Economic evaluations of health interventions pose a particular challenge for reporting. There is also a need to consolidate and update existing guidelines and promote their use in a user friendly manner. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines efforts into one current, useful reporting guidance. The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication. The need for new reporting guidance was identified by a survey of medical editors. A list of possible items based on a systematic review was created. A two round, modified Delphi panel consisting of representatives from academia, clinical practice, industry, government, and the editorial community was conducted. Out of 44 candidate items, 24 items and accompanying recommendations were developed. The recommendations are contained in a user friendly, 24 item checklist. A copy of the statement, accompanying checklist, and this report can be found on the ISPOR Health Economic Evaluations Publication Guidelines Task Force website (www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to better reporting, and ultimately, better health decisions. To facilitate dissemination and uptake, the CHEERS statement is being co-published across 10 health economics and medical journals. We encourage other journals and groups, to endorse CHEERS. The author team plans to review the checklist for an update in five years.
THE PREDICTIVE VALUE OF BASELINE WHITE CELL COUNTS ON MORTALITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Gabriel Maluenda, Itsik Ben-Dor, Michael Mahmoudi, Michael A. Gaglia, Kohei Wakabayashi, Manuel Gonzalez, Gabriel Sardi, Rafael Romaguera, Ana Laynez, Rebecca Torguson, Zhenyi Xue, William O. Suddath, Kenneth M. Kent, Lowell F. Satler, Augusto D. Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2011)