tbuckley/cabot-search huggingface dataset:
Mortality and prognosis related to the amyloidosis of Still's disease.
Authors: M.E Smith, B.M Ansell, E.G Bywaters
Journal: Annals of the Rheumatic Diseases (1968)

Amyloidosis in adult rheumatoid arthritis is well documented (Table I).Rosenberg, Baggenstoss, and Hench (1944) reported an incidence of 6-6 per cent. in a study of thirty post mortem cases and Unger, Zuckerbrod, Beck, and Steele (1948a) re- corded a similar incidence (6 -9 per cent. in 58 cases), but Teilum and Lindahl (1954) found it in 60-7 per cent. of 28 post mortem cases.Missen and Taylor (1956), reporting 47 cases from the Royal Post- graduate Medical School of London, and reviewing other large series in the literature, found a total of 385 cases and suggested 14-7 per cent.as a conserva- tive estimate of the incidence of amyloidosis post mortem in adult rheumatoid arthritis.Fearnley and Lackner (1955) reported an incidence of 3 -8 per cent. in 181 cases, using a modified Congo red test and *The criteria for definite Still's disease comprise an onset of poly- arthritis before the age of 16 years involving four or more joints for a minimum of 3 months; when less than four joints are involved, a biopsy of synovial membrane showing histology compatible with the diagnosis of rheumatoid arthritis (in the absence of other similar diseases such as polyarteritis nodosa, systemic lupus erythematosus, ankylosing spondylitis, psoriasis, or ulcerative colitis) may be regarded as diagnostic (Ansell and Bywaters, 1959).
Rapid diagnosis of tuberculosis using<i>ex vivo</i>host biomarkers in sputum
Authors: Martin O.C. Ota, Joseph F. Mendy, Simon Donkor, Toyin Togun, Mohammed Daramy, Marie P. Gomez, Novel N. Chegou, Abdou K. Sillah, Olumuyiwa Owolabi, Beate Kampmann, Gerhard Walzl, Jayne S. Sutherland
Journal: European Respiratory Journal (2014)

To the Editor: 

Tuberculosis continues to be a major public health problem in developing countries [1]. One of the roadblocks in reducing tuberculosis transmission is the lack of accurate laboratory-free diagnostic tests for use at the point of care. If tuberculosis is to be eliminated, we need a robust, low-cost and safe point-of-care diagnostic test, which in turn requires identification of appropriate biomarkers [2]. Rapid tests based on microfluidics (lateral flow tests) hold great promise for tuberculosis diagnostics. They are easy to use, cheap, provide an answer within minutes, do not require specialised equipment and are stable at room temperature, making them ideal for use in high tuberculosis burden, resource-poor settings. To date, however, no such test has been developed for tuberculosis due to lack of sensitivity related to the markers and/or sample type. Development of tests based on host biomarkers requires evaluation of different sample types [3]–[5] and markers other than interferon (IFN)-γ [5] to provide differential diagnosis of active tuberculosis, latent infection and other respiratory disorders. We have previously shown that a combination of three host factors in pleural fluid resulted in 96% correct classification of tuberculosis among other respiratory diseases (ORD) (including bacterial pneumonia) regardless of HIV status [6]. However, this sample type is not easy to obtain and we therefore wanted to determine if we could use ex vivo sputum, which is noninvasive and easy to obtain in adult pulmonary tuberculosis patients.

Subjects were consecutively recruited from the outpatient clinic and ward at the Medical Research Council Unit, Fajara, the Gambia. All subjects were adults (≥18 years of age) with symptoms suggestive of tuberculosis. Subjects were subsequently classified into two groups: those with culture-confirmed tuberculosis and those with ORD. 75% of the tuberculosis and …
Patient-Specific Predictions of Outcomes in Myocardial Infarction for Real-Time Emergency Use: A Thrombolytic Predictive Instrument
Authors: H P Selker, J L Griffith, J R Beshansky, C H Schmid, R M Califf, R B D'Agostino, M M Laks, K L Lee, C Maynard, R H Selvester, G S Wagner, W D Weaver
Journal: Annals of Internal Medicine (1997)

Background: Thrombolytic therapy can be life-saving in patients with acute myocardial infarction. However, if given too late or insufficiently selectively, it may provide little benefit but still cause serious complications and incur substantial costs. Objective: To develop a thrombolytic predictive instrument for real-time use in emergency medical service settings that could 1) identify patients likely to benefit from thrombolysis and 2) facilitate the earliest possible use of this therapy. Design: Creation and validation of logistic regression-based predictive instruments based on secondary analysis of clinical data. Patients: 4911 patients who had acute myocardial infarction and ST-segment elevation on electrocardiogram; 3483 received thrombolytic therapy. Measurements: Data were obtained from 13 major clinical trials and registries and directly from medical records, including electrocardiograms obtained at presentation. Input variables include presenting clinical and electrocardiographic features; predictive models generate probabilities for acute (30-day) mortality if and if not treated with thrombolysis, 1-year mortality rates if and if not treated with thrombolysis, cardiac arrest if and if not treated with thrombolysis, thrombolysis-related intracranial hemorrhage, and thrombolysis-related major bleeding episode requiring transfusion. Together, these models constitute the thrombolytic predictive instrument. Results: The predictive models generated the following mean predictions for patients in the Thrombolytic Predictive Instrument Database: 30-day mortality rate, 7.1%; 1-year mortality rate, 10.9%; rate of cardiac arrest, 3.7%; rate of thrombolysis-related intracranial hemorrhage, 0.6%; and rate of other thrombolysis-related major bleeding episodes, 5.0%. They discriminated well between persons having and those not having the predicted outcome; areas under the receiver-operating characteristic (ROC) curve were between 0.77 and 0.84 for the five outcomes. Calibration between each instrument's predicted and observed rates was excellent. Validation of the predictive instruments for 30-day and 1-year mortality, done on a separate test dataset, yielded areas under the ROC curve of 0.76 for each. Conclusions: After the basic features of a clinical presentation are entered into a computerized electrocardiograph, the predictions of the thrombolytic predictive instrument can be printed on the electrocardiogram report. This decision aid may facilitate earlier and more appropriate use of thrombolytic therapy in patients with acute myocardial infarction.
Dual Ca2+ requirement for optimal lipid peroxidation of low density lipoprotein by activated human monocytes.
Authors: Q Li, A Tallant, M K Cathcart
Journal: Journal of Clinical Investigation (1993)

The oxidative modification of LDL seems a key event in atherogenesis and may participate in inflammatory tissue injury. Our previous studies suggested that the process of LDL oxidation by activated human monocytes/macrophages required O2- and activity of intracellular lipoxygenase. Herein, we studied the mechanisms involved in this oxidative modification of LDL. In this study, we used the human monocytoid cell line U937 to examine the role of Ca2+ in U937 cell-mediated lipid peroxidation of LDL. U937 cells were activated by opsonized zymosan. Removal of Ca2+ from cell culture medium by EGTA inhibited U937 cell-mediated peroxidation of LDL lipids. Therefore, Ca2+ influx and mobilization were examined for their influence on U937 cell-mediated LDL lipid peroxidation. Ca2+ channel blockers nifedipine and verapamil blocked both Ca2+ influx and LDL lipid peroxidation by activated U937 cells. The inhibitory effects of nifedipine and verapamil were dose dependent. TMB-8 and ryanodine, agents known to prevent Ca2+ release from intracellular stores, also caused a dose-dependent inhibition of LDL lipid peroxidation by activated U937 cells while exhibiting no effect on Ca2+ influx. Thus, both Ca2+ influx through functional calcium channels and Ca2+ mobilization from intracellular stores participate in the oxidative modification of LDL by activated U937 cells. 45Ca2+ uptake experiments revealed profound Ca2+ influx during the early stages of U937 cell activation, however, the Ca2+ ionophore 4-bromo A23187 was unable to induce activation of U937 cells and peroxidation of LDL lipids. Release of intracellular Ca2+ by thapsigargin only caused a suboptimal peroxidation of LDL lipids. Our results indicate that although increases in intracellular Ca2+ levels provided by both influx and intracellular Ca2+ mobilization are required, other intracellular signals may be involved for optimal peroxidation of LDL lipids by activated human monocytes.
Barriers to the Use of Breast Cancer Risk Reduction Therapies
Authors: Arvind Bambhroliya, Mariana Chavez-MacGregor, Abenaa M. Brewster
Journal: Journal of the National Comprehensive Cancer Network (2015)

Evidence from randomized clinical trials supports the use of tamoxifen, raloxifene, exemestane, and anastrozole for the reduction of risk of invasive breast cancer, predominately estrogen receptor-positive tumors. Revised clinical guidelines now strongly recommend that physicians offer high-risk women medication for breast cancer risk reduction. Although only a small portion of eligible women receive risk reduction medication, evidence suggests higher acceptance among women with atypical hyperplasia or lobular carcinoma in situ. Among physicians, barriers for prescribing risk reduction medications include inadequate training in risk assessment, lack of reimbursement for prevention counseling, and the unavailability of easily accessible and user-friendly prediction tools for estimating risk/benefit profiles. Strategies to improve uptake among women have focused on providing education about breast cancer risk and information that accurately conveys the risks and benefits of risk reduction medications. Priority areas of research that have been identified to improve the use of risk reduction medications are the (1) development of risk assessment tools that more accurately identify women most likely to benefit, (2) identification of circulating or tissue biomarkers that can predict and monitor responsiveness of treatment, and (3) better understanding of patient-related barriers, including patients' subjective beliefs and experiences.
Impressive Response With Imatinib in a Heavily Pretreated Patient With Metastatic <i>c-KIT</i> Mutated Thymic Carcinoma
Authors: Sebastiano Buti, Maddalena Donini, Pietro Sergio, Lorella Garagnani, Laura Schirosi, Rodolfo Passalacqua, Giulio Rossi
Journal: Journal of Clinical Oncology (2011)
Six minute walk distance is a useful predictor of survival in lung transplant recipients
Authors: V Ganagaram
Journal: Thorax (2008)

Six minute walk distance (6MWD) is routinely used as part of the assessment process for lung transplant recipients. However, there is a paucity of data supporting the impact of baseline 6MWD on transplant outcomes in advanced lung diseases.

In this study, clinical information was prospectively collected over a 28-month period from 376 patients with diverse lung diseases …
Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia
Authors: Hideyuki Hyogo, Susumu Tazuma, Koji Arihiro, Keiko Iwamoto, Yoshitaka Nabeshima, Motoki Inoue, Tomokazu Ishitobi, Michihiro Nonaka, Kazuaki Chayama
Journal: Metabolism (2008)
Mechanisms governing the postural response and baroreceptor abnormalities in chronic congestive heart failure: effects of acute and long-term converting-enzyme inhibition.
Authors: R J Cody, K W Franklin, J Kluger, J H Laragh
Journal: Circulation (1982)

We assessed the hemodynamic and hormonal response to tilt and the baroreceptor response in 12 patients in sinus rhythm with severe chronic congestive heart failure. We also assessed the response to acute (n = 12) and chronic (n = 8) converting-enzyme inhibition with captopril. The control tilt was characterized by high cardiac filling pressures, absence of significant peripheral pooling and apparent absence of afferent stimuli for hemodynamic and hormonal response. After acute captopril, the hemodynamic response to tilt was improved, but not normalized. The chronic response was characterized by the absence of a reflex increase of systemic vascular resistance on tilt despite peripheral pooling. Five patients developed orthostatic hypotension, but responded to acute infusion of 0.9% sodium chloride. Efferent sympathetic activity (response to cold pressor) was abnormal during the control study, but indistinguishable from normal subjects by the time of chronic captopril therapy. This paralleled an improved responsiveness of plasma catecholamines during chronic tilt. The Valsalva maneuver remained abnormal. There was a distinct absence of the normally anticipated heart rate increase on tilt, suggesting a parasympathetic abnormality.
Comparative phosphoproteomics reveals evolutionary and functional conservation of phosphorylation across eukaryotes
Authors: Jos Boekhorst, Bas van Breukelen, Albert JR Heck, Berend Snel
Journal: Genome biology (2008)

Abstract Background Reversible phosphorylation of proteins is involved in a wide range of processes, ranging from signaling cascades to regulation of protein complex assembly. Little is known about the structure and evolution of phosphorylation networks. Recent high-throughput phosphoproteomics studies have resulted in the rapid accumulation of phosphopeptide datasets for many model organisms. Here, we exploit these novel data for the comparative analysis of phosphorylation events between different species of eukaryotes. Results Comparison of phosphoproteomics datasets of six eukaryotes yields an overlap ranging from approximately 700 sites for human and mouse (two large datasets of closely related species) to a single site for fish and yeast (distantly related as well as two of the smallest datasets). Some conserved events appear surprisingly old; those shared by plant and animals suggest conservation over the time scale of a billion years. In spite of the hypothesized incomprehensive nature of phosphoproteomics datasets and differences in experimental procedures, we show that the overlap between phosphoproteomes is greater than expected by chance and indicates increased functional relevance. Despite the dynamic nature of the evolution of phosphorylation, the relative overlap between the different datasets is identical to the phylogeny of the species studied. Conclusion This analysis provides a framework for the generation of biological insights by comparative analysis of high-throughput phosphoproteomics datasets. We expect the rapidly growing body of data from high-throughput mass spectrometry analysis to make comparative phosphoproteomics a powerful tool for elucidating the evolutionary and functional dynamics of reversible phosphorylation.
Asthma protection with bacteria - science or fiction?
Authors: H. Renz
Journal: Thorax (2011)

What is the role of bacterial exposure in asthma protection and prevention? This topic is receiving increasing attention, particularly based on epidemiological findings relating to the ‘hygiene hypothesis’. More than a decade ago the observation was made that infants living in a microbial-rich environment show a high degree of protection, particularly against respiratory allergies and allergic sensitisation.1 The model situation of the farming environment offers the opportunity to investigate the context of environmental exposures, the effect on immune responses and development of disease phenotypes. That microbes are indeed relevant in triggering the protective immune response was epidemiologically shown initially for exposure to lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria. In that study, an inverse relationship was observed between the natural microbial load (endotoxin load in mattress dust) and the prevalence of asthma, allergic rhinitis and atopic sensitisation. Subsequently, several groups employed models of experimental asthma to study the mechanisms of protection in this regard.2–4 These studies provided important information for the context of microbial exposure and asthma protection. First, it was shown that timing of exposure is relevant. If LPS was delivered well before the first contact with the allergen, the immune system was able …
Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction
Authors: S D Anderson, G J Argyros, H Magnussen, K Holzer
Journal: British Journal of Sports Medicine (2001)

The International Olympic Committee Medical Commission (IOC-MC) requires notification for use of a β 2 agonist at the Winter Olympic Games in Salt Lake City. This notification will be required seven days before the event and must be accompanied by objective evidence that justifies the need to use one. The IOC-MC has expressed the viewpoint that, at present, eucapnic voluntary hyperpnoea (EVH) is the optimal laboratory challenge to confirm that an athlete has exercise induced bronchoconstriction (EIB). The EVH test recommended was specifically designed to identify EIB. EVH has been performed in thousands of subjects in both the laboratory and the field. The test requires the subject to hyperventilate dry air containing 5% carbon dioxide at room temperature for six minutes at a target ventilation of 30 times the subject's forced expiratory volume in one second (FEV 1 ). The test conditions can be modified to simulate the conditions that give the athlete their symptoms with exercise. A reduction in FEV 1 of 10% or more of the value before the test is considered positive.
Cystic fibrosis and estrogens: a perfect storm
Authors: Pamela L. Zeitlin
Journal: Journal of Clinical Investigation (2008)

Irreversible destruction and widening of the airways due to acquired infections or genetic mutations as well as those of unknown cause are more severe in females. Differences between male and female anatomy, behavior, and hormonal state have been proposed to explain the increased incidence and severity in females with airway disease such as cystic fibrosis (CF); however, a mechanism to explain a sex-related difference has remained elusive. In this issue of the JCI, Coakley et al. report that elevations in the major estrogen hormone in humans--17beta-estradiol--reduce Ca2+-activated Cl- secretion by airway epithelial cells in culture, thereby disrupting ion and water balance (see the related article beginning on page 4025). They measure a similar diminution of nasal epithelial Ca2+-activated Cl- secretion in women with CF during the menstrual cycle phase at which 17beta-estradiol level is at its highest. These data suggest that for about one week of a four-week menstrual cycle, women with CF will have a reduced ability to efficiently clear airway secretions, the buildup of which is a hallmark of CF. The authors suggest that these data warrant the testing of antiestrogen therapy in females with CF and propose an alternative avenue for CF therapeutic development.
Combined pulmonary fibrosis and emphysema syndrome associated with ABCA3 mutations
Authors: Ralph Epaud, Céline Delestrain, Malek Louha, Stéphanie Simon, Pascale Fanen, Abdellatif Tazi
Journal: European Respiratory Journal (2013)

The next step for our study will be direct determination, such as faecal H. pylori antigens or H. pylori determination in BAL (i.e.DNA PCR or culture), in a wide population of IPF patients.The effects of IPF pharmacological treatments on H. pylori infection remain to be established.
Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture.
Authors: L Wong, G Yamasaki, R J Johnson, S L Friedman
Journal: Journal of Clinical Investigation (1994)

A consistent response to liver injury is the activation of resident mesenchymal cells known as lipocytes (Ito, fat-storing cells) into a proliferating cell type. In cultured lipocytes, platelet-derived growth factor (PDGF) is the most potent proliferative cytokine, but requires the activation-dependent expression of its receptor protein (Friedman, S. L., and M. J. P. Arthur. 1989. J. Clin. Invest. 84:1780-1785); the role of PDGF receptor (PDGFR) in liver injury is unknown. We have examined PDGFR gene expression in freshly isolated lipocytes during liver injury and correlated these findings with a culture model of cellular activation. Whereas lipocytes from normal rats had no detectable transcript for the beta-PDGFR subunit, this mRNA was induced within 1 h after a dose of carbon tetrachloride (CCl4). In contrast, alpha subunit mRNA was detected in normal cells, but was unchanged after liver injury. Similar results were observed in lipocytes from bile duct-obstructed rats, although beta-PDGFR induction was less marked. By immunoblot, induction of beta-PDGFR protein in lipocytes isolated from CCl4-treated animals correlated with mRNA increases. In contrast to lipocytes, endothelial cells from normal liver expressed low levels of alpha- and beta-receptor subunit mRNA, which did not increase with injury. Using a beta-PDGFR antibody, receptor protein could be identified within fibrotic septa in CCl4-treated animals in regions where cells expressed proliferating cell nuclear antigen (PCNA). In cultured lipocytes activated by growth on uncoated plastic, beta-PDGFR transcripts appeared within 3 d after plating, which coincided with the onset of cellular proliferation. In contrast, quiescent cells in suspension culture had no detectable beta-PDGFR mRNA. These results indicate that beta-PDGF receptor induction by lipocytes is an early event during hepatic injury in vivo and in primary culture.
First and second line treatment pattern among pulmonary hypertension patients enrolled in a managed care health plan
Authors: Vijay Joish, David Muccino, Charles Krelick
Journal: European Respiratory Journal (2011)

Purpose:  To describe first and second line treatment pattern among PH patients enrolled in managed care health plan.   Methods:  Data were derived from the MarketScan claims database. PH patients were identified anytime during 4/1/2006 to 3/31/2009 using the ICD-9 claim of 416.X. First line therapy was defined as the first PH-related pharmacy claim within ±12 months of the diagnosis claim. Second line treatment was defined as separate PH-related pharmacy claim post the first line PH-related pharmacy claim. PH-related treatment included prescriptions for high-dose calcium channel blockers (CCBs), endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5s), or prostacyclin analogues (PAs). CCB users had no diagnosis claim of essential hypertension anytime during the study period.   Results:  Final study sample was 2,252, with a mean age of 61.2 years (SD+16.41), and 57% females. 46% of PH-patients had CCB as the first line treatment followed by PDE5s (38%), ERAs (13%), and PAs (3%). 16% of the sample had some second line treatment over a 12-month follow-up. Combination therapy was only observed in the CCB-cohort, where 39 patients added an ERA/PDE5/PA to their current treatment. Switching was most common among ERA (61%) and PA (50%) first line users, with majority switching to PDE5. Total average treatment days for first-line PH-prescription varied from a low of 21 (SD=81.44) days among PA-users to 266 (SD=131.39) among ERA-users, respectively.   Conclusions:  CCBs and PDE5 were the most prescribed first line treatment among PH-patients. Future research would need to explore the choice of first line treatment on clinical and economic outcomes.