tbuckley/cabot-search huggingface dataset:
Cardiac Troponin and Outcome in Acute Heart Failure
Authors: W. Frank Peacock, Teresa De Marco, Gregg C. Fonarow, Deborah Diercks, Janet Wynne, Fred S. Apple, Alan H.B. Wu
Journal: New England Journal of Medicine (2008)

Cardiac troponin provides diagnostic and prognostic information in acute coronary syndromes, but its role in acute decompensated heart failure is unclear. The purpose of our study was to describe the association between elevated cardiac troponin levels and adverse events in hospitalized patients with acute decompensated heart failure.We analyzed hospitalizations for acute decompensated heart failure between October 2001 and January 2004 that were recorded in the Acute Decompensated Heart Failure National Registry (ADHERE). Entry criteria included a troponin level that was obtained at the time of hospitalization in patients with a serum creatinine level of less than 2.0 mg per deciliter (177 micromol per liter). A positive troponin test was defined as a cardiac troponin I level of 1.0 microg per liter or higher or a cardiac troponin T level of 0.1 microg per liter or higher.Troponin was measured at the time of admission in 84,872 of 105,388 patients (80.5%) who were hospitalized for acute decompensated heart failure. Of these patients, 67,924 had a creatinine level of less than 2.0 mg per deciliter. Cardiac troponin I was measured in 61,379 patients, and cardiac troponin T in 7880 patients (both proteins were measured in 1335 patients). Overall, 4240 patients (6.2%) were positive for troponin. Patients who were positive for troponin had lower systolic blood pressure on admission, a lower ejection fraction, and higher in-hospital mortality (8.0% vs. 2.7%, P<0.001) than those who were negative for troponin. The adjusted odds ratio for death in the group of patients with a positive troponin test was 2.55 (95% confidence interval, 2.24 to 2.89; P<0.001 by the Wald test).In patients with acute decompensated heart failure, a positive cardiac troponin test is associated with higher in-hospital mortality, independently of other predictive variables. (ClinicalTrials.gov number, NCT00366639 [ClinicalTrials.gov].).
Staphylococcal protein A–formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps
Authors: Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takenori Haruna, Takaya Higaki, Yasuyuki Noyama, Sei-ichiro Makihara, Kengo Kanai, Kazunori Nishizaki
Journal: Journal of Allergy and Clinical Immunology (2015)
Continuous inhibition of renin release in dogs by vagally innervated receptors in the cardiopulmonary region.
Authors: G Mancia, J C Romero, J T Shepherd
Journal: Circulation Research (1975)

Inhibition of the release of renin by vagal afferents from the heart and lungs was studied in 14 dogs with their aortic nerves cut and their carotid sinuses vascularly isolated. The release of renin from one kidney was calculated from the venous-arterial difference in plasma renin activity (radioimmunoassay) and the renal blood flow (electromagnetic flowmeter). Renin release was determined before and during temporary interruption of afferent vagal nerve traffic (bilateral cooling of the cervical vagi). With carotid sinus pressure maintained at 40 mm Hg, vagal cooling increased mean aortic blood pressure (24%), decreased renal blood flow (19%), and increased renin release (241%). With sinus pressure maintained at the mean aortic blood pressure existing during the control period, vagal cooling caused a lesser increase in mean aortic blood pressure (12%), little decrease in renal blood flow (7%), and a marked increase in renin release (522%). The changes in renal blood flow and renin release with vagal cooling were prevented by renal denervation. Thus, vagal afferents from the cardiopulmonary region exert a tonic restraint on the release of renin; this restraint occurs in circumstances in which these afferents cause little change in total renal blood flow.
Rheumatoid Arthritis Is Associated With Increased Aortic Pulse-Wave Velocity, Which Is Reduced by Anti–Tumor Necrosis Factor-α Therapy
Authors: Kaisa M. Mäki-Petäjä, Frances C. Hall, Anthony D. Booth, Sharon M.L. Wallace, None Yasmin, Philip W.P. Bearcroft, Srinivasan Harish, Anita Furlong, Carmel M. McEniery, John Brown, Ian B. Wilkinson
Journal: Circulation (2006)

Background— Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, which is not explained by traditional cardiovascular risk factors but may be due in part to increased aortic stiffness, an independent predictor of cardiovascular mortality. In the present study, our aim was to establish whether aortic stiffness is increased in RA and to investigate the relationship between inflammation and aortic stiffness. In addition, we tested the hypothesis that aortic stiffness could be reduced with anti–tumor necrosis factor-α (TNF-α) therapy. Methods and Results— Aortic pulse-wave velocity (PWV), augmentation index, and blood pressure were measured in 77 patients with RA and in 142 healthy individuals. Both acute and chronic inflammatory measures and disease activity were determined. The effect of anti-TNF-α therapy on PWV and endothelial function was measured in 9 RA patients at 0, 4, and 12 weeks. Median (interquartile range) aortic PWV was significantly higher in subjects with RA than in control subjects (8.35 [7.14 to 10.24] versus 7.52 [6.56 to 9.18] m/s, respectively; P =0.005). In multiple regression analyses, aortic PWV correlated independently with age, mean arterial pressure, and log-transformed C-reactive protein ( R 2 =0.701; P &lt;0.0001). Aortic PWV was reduced significantly by anti-TNF-α therapy (8.82±2.04 versus 7.94±1.86 versus 7.68±1.56 m/s at weeks 0, 4, and 12, respectively; P &lt;0.001); concomitantly, endothelial function improved. Conclusions— RA is associated with increased aortic stiffness, which correlates with current but not historical measures of inflammation, suggesting that increased aortic stiffness may be reversible. Indeed, anti-TNF-α therapy reduced aortic stiffness to a level comparable to that of healthy individuals. Therefore, effective control of inflammation may be of benefit in reducing cardiovascular risk in patients with RA.
Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial
Authors: P.E. Van Schil, P. Baas, R. Gaafar, A.P. Maat, M. Van de Pol, B. Hasan, H.M. Klomp, A.M. Abdelrahman, J. Welch, J.P. van Meerbeeck
Journal: European Respiratory Journal (2010)

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less). Induction chemotherapy consisted of three courses of cisplatin 75 mg·m −2 and pemetrexed 500 mg·m −2 . Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy (54 Gy, 30 fractions). Our primary end-point was “success of treatment” and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects’ median age was 57 yrs. The subjects’ TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3–4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6–32.9) and median progression-free survival was 13.9 months (95% CI 10.9–17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36–1.00). Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary.
Influence of Whole-Brain Radiotherapy on Remission of Brain Metastases
Authors: Carsten Nieder
Journal: Journal of Clinical Oncology (2006)

TO THE EDITOR: Schwab et al reported an intriguing therapeutic benefit in a female nonsmoker with multiple brain metastases from lung adenocarcinoma treated with gefitinib 250 mg daily 3 years after thoracic surgery and adjuvant chemotherapy. Gefitinib treatment was initiated 6 weeks after whole-brain radiotherapy (WBRT) with 36 Gy because of a lack of objective response on magnetic resonance imaging and worsening clinical symptoms. After 8 weeks on gefitinib, a major response was seen. Eventually the patient achieved a complete remission. The effects of gefitinib on brain metastases from non–small-cell lung cancer have been reported by several authors, suggesting that objective responses occur in 33% to 43% of patients (Taiwan, Japan) or 10% of patients (Europe). All of these series included less than 80 patients. In comparison, WBRT with 30 Gy to 40 Gy for brain metastases from non–small-cell lung cancer results in objective responses in 38% to 45% of patients (Europe). In the absence of randomized trials comparing WBRT to small receptor tyrosine kinase inhibitors, WBRT should still be considered the first-line treatment of choice for patients with multiple brain metastases. Whether gefitinib has a role in salvage treatment for patients progressing after WBRT should be studied prospectively in patients ineligible for local treatment such as radiosurgery. An important question is when to evaluate remission after WBRT. A previous series suggested that 43% of brain metastases continued to shrink between the first imaging, performed within 2 weeks after WBRT, and the second imaging after 3 months. We have recently confirmed that the best imaging result was evident on scans obtained between 66 days and 120 days after WBRT (median volume reduction 1.5 cm versus, for example, 0.6 cm if the scans were performed within 14 days; P .05). It is therefore important to notice that imaging after 6 weeks does not necessarily reflect the final outcome. In addition, transient demyelination might develop a few weeks after WBRT, leading to clinical symptoms that respond to corticosteroids. These symptoms do not indicate treatment failure.
Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus
Authors: PollyJ. Bingley, Ezio Bonifacio, EdwinA.M. Gale, Jaakko Tuomilehto, Eva Tuomilehto-Wolf, Paul Zimmet, Ian Mackay, Merril Rowley, RichardW. Orrell, RussellJ.M. Lane, John Maitland, R. David, G. Leslie
Journal: The Lancet (1994)
Contribution of hepatitis C virus to non-A, non-B fulminant hepatitis in Japan
Authors: Makoto Yoshiba, Kazuhiko Dehara, Kazuaki Inoue, Hiroaki Okamoto, Makoto Mayumi
Journal: Hepatology (1994)

To assess the contribution of hepatitis C virus to non-A, non-B fulminant hepatitis in Japan, we compared 10 major clinical features among 7 patients with type B fulminant hepatitis (type B group), 13 patients with non-A, non-B fulminant hepatitis with evidence of hepatitis C virus infection (type C group) and 10 patients without evidence of hepatitis C virus infection (NANB group). Duration from first symptom to coma and that from onset of jaundice to coma was significantly longer in the type C group (median = 39 and 25 days, respectively) and in the non-A, non-B group (median = 29 and 12 days, respectively) than in the type B group (median = 9 and 2 days, respectively) (p < 0.01). The maximum median AST level was significantly lower in the type C (1,689 U/L) and non-A, non-B groups (1,353 U/L) than in the type B group (5,780 U/L) (p < 0.05). Serum transaminase levels showed a single peak in six of seven of the type B patients, whereas they formed two or more peaks in all of the type C patients and in most of the non-A, non-B group (p < 0.05). Six of seven in the type B group, 6 of 13 in the type C group and 4 of 10 in the non-A, non-B group survived (p < 0.05). We found no significant difference in any of the 10 clinical features between the type C and non-A, non-B groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Glucose Control and Cardiovascular Disease
Authors: Ignacio Conget, Marga Giménez
Journal: Diabetes Care (2009)

There is a substantial amount of clinical data showing the relationship between diabetes and atherosclerosis and its clinical complications (1,2). Cardiovascular disease (CVD) is more common in people with diabetes than in subjects without the disease, and when it is present, it also has a more aggressive course and a worse prognosis (3). The bulk of epidemiological data has firmly established that type 2 diabetes is associated with more than a twofold increased risk for cardiovascular (CV) death. In the case of subjects with type 1 diabetes, in spite of the fact that the CVD rate is significantly lower compared with the population with type 2 diabetes, their relative risk for coronary heart mortality is sevenfold higher than in matched counterparts without the disease (4). Despite all of these data concerning the association of diabetes and CVD, the exact mechanism by which diabetes, and its alterations, is linked to atherosclerosis remains incompletely elucidated. This is especially true in the case of hyperglycemia. The role of nonglycemic factors that accompany the vast majority of patients with type 2 diabetes, such as high blood pressure, dyslipidemia, and hemorreological abnormalities, among others, is much better understood and seems to be independent of glycemia. In addition to this, there have been studies demonstrating that interventions addressed to control these other factors in patients with diabetes effectively reduce CV risk. There also have been data including the use of statins, aspirin, the aggressive management of hypertension, and the use of ACE inhibitors (5,6). Therefore, the positive effects that the control of other factors beyond hyperglycemia exert on CVD are, nowadays, unquestionable. In contrast, to date, the positive effect of intensive glucose management in comparison to nonintensive glucose control on CVD outcomes is still far from proven and seems unlikely to change …
Genetic Services for Familial Cancer Patients: A Follow-Up Survey of National Cancer Institute Cancer Centers
Authors: Meira Epplein, Ksenia P. Koon, Scott D. Ramsey, John D. Potter
Journal: Journal of Clinical Oncology (2005)

Anecdotal reports suggest that the volume of services offered to individuals concerned with hereditary cancer risk has increased substantially in recent years. As a follow-up to our 1993 survey, we sought to determine how the scope and volume of genetic services has changed between 1993 and 2002.We surveyed the 61 National Cancer Institute-designated cancer centers in operation in 2002 using an updated version of the questionnaire from 1993. Analysis included frequencies and summary statistics.The majority of cancer centers responding (46 of 56 centers; 82.1%) provided some genetic services for evaluation of familial cancer, which is a higher proportion than in 1993 (50%; P < .01). Almost all centers (42 of 46 centers; 91.3%) provided services not only to cancer patients and their families, but also to individuals concerned with risk, which is a change (P = .01) from 1993, when 64.7% of centers offered such services. In addition, increases have been found for most other measures of services rendered for familial genetic services.As public awareness of cancer susceptibility genes has grown markedly in recent years, the demand has also grown for genetic services to assess familial cancer risk. Major deleterious genetic mutations are rare, and much of the current research in genetic variation focuses on higher prevalence variants that carry lower risks. This may suggest that testing for mutations will move from genetics clinics to primary care and specialty practices. Thus, it is unclear whether the scope and volume of cancer center genetics services will continue to grow as rapidly as they have over the last decade.
Primary sarcoma of the lung.
Authors: E W Cameron
Journal: Thorax (1975)

Primary sarcoma of lung is defined to exclude sarcomata of lymphatic origin. A series of nine patients is presented, all of whom were seen in Edinburgh. In each case there is histological proof of the diagnosis or sarcoma. From the same population and during the same period of time, 6000 cases of bronchial carcinoma presented. Eight of the nine patients underwent resection of the tumour, and the pathological findings and clinical results are described. From a review of the literature and from the Edinburgh series, a general series of 59 cases of primary sarcoma of the lung has been selected. The criteria for selection were directed at the assessment of the results of surgery in the treatment of this lesion. The five-year survival rate after 9curative9 surgery is 52%, and the prognosis after surgery does not appear to depend on the radical nature of the operation.
Effect of frusemide on bradykinin- and capsaicin-induced contraction of the guinea-pig trachea
Authors: M Molimard, C Advenier
Journal: European Respiratory Journal (1993)

Frusemide, a loop diuretic, inhibits the bronchial response to various bronchoconstrictor stimuli in asthmatic subjects. The underlying mechanisms remain unclear. In order to determine whether frusemide inhibits pharmacologically induced C-fibre stimulation, we investigated the effect of frusemide on bradykinin-, capsaicin-, neurokinin A-, and substance P-induced contraction of the guinea-pig isolated trachea. Frusemide 10(-5) and 10(-4) M produced a significant inhibition of concentration-response curves to bradykinin, which was markedly reduced by indomethacin 10(-6) M. Frusemide significantly reduced capsaicin-induced contraction only in the presence of indomethacin 10(-6) M. Neurokinin A- and substance P-induced contractions were not affected by frusemide and/or indomethacin. Our data suggest that a cyclo-oxygenase pathway is involved in the inhibition by frusemide of the bradykinin-induced contraction, but not in the inhibition of the capsaicin-induced contraction.
Thoracic duct terminating on the right side associated with aberrant retro-oesophageal right subclavian artery and truncus bicaroticus
Authors: H. Nathan, G. Gitlin
Journal: Thorax (1968)

A case is described showing the following rare combination of anomalies: (<i>a</i>) the thoracic duct terminating on the right side at the junction of the internal jugular and subclavian veins; (<i>b</i>) the right subclavian artery arising as the last branch of the aortic arch, beyond the left subclavian artery, and passing behind the oesophagus on its way to the upper limb; and (<i>c</i>) the right and left common carotid arteries arising by a common stem (`truncus bicaroticus9) from the aortic arch. The literature on the subject is reviewed and the embryological basis for the development of these variations is discussed briefly. It is suggested that special attention be directed to the course of the thoracic duct whenever an anomaly of the branches of the aortic arch is observed.
Mammalian Tumor Xenografts Induce Neovascularization in Zebrafish Embryos
Authors: Stefania Nicoli, Domenico Ribatti, Franco Cotelli, Marco Presta
Journal: Cancer Research (2007)

Abstract The zebrafish (Danio rerio)/tumor xenograft model represents a powerful new model system in cancer. Here, we describe a novel exploitation of the zebrafish model to investigate tumor angiogenesis, a pivotal step in cancer progression and target for antitumor therapies. Human and murine tumor cell lines that express the angiogenic fibroblast growth factor (FGF) 2 and/or vascular endothelial growth factor (VEGF) induce the rapid formation of a new microvasculature when grafted close to the developing subintestinal vessels of zebrafish embryos at 48 h postfertilization. Instead, no angiogenic response was exerted by related cell clones defective in the production of these angiogenic growth factors. The newly formed blood vessels sprout from the subintestinal plexus of the zebrafish embryo, penetrate the tumor graft, and express the transcripts for the zebrafish orthologues of the early endothelial markers Fli-1, VEGF receptor-2 (VEGFR2/KDR), and VE-cadherin. Accordingly, green fluorescent protein–positive neovessels infiltrate the graft when tumor cells are injected in transgenic VEGFR2:G-RCFP zebrafish embryos that express green fluorescent protein under the control of the VEGFR2/KDR promoter. Systemic exposure of zebrafish embryos immediately after tumor cell injection to prototypic antiangiogenic inhibitors, including the FGF receptor tyrosine kinase inhibitor SU5402 and the VEGFR2/KDR tyrosine kinase inhibitor SU5416, suppresses tumor-induced angiogenesis without affecting normal blood vessel development. Accordingly, VE-cadherin gene inactivation by antisense morpholino oligonucleotide injection inhibits tumor neovascularization without affecting the development of intersegmental and subintestinal vessels. These data show that the zebrafish/tumor xenograft model represents a novel tool for investigating the neovascularization process exploitable for drug discovery and gene targeting in tumor angiogenesis. [Cancer Res 2007;67(7):2927–31]
Predicting recovery from acute severe asthma.
Authors: P F Jenkins, G F Benfield, A P Smith
Journal: Thorax (1981)

Fifty-two patients admitted to hospital with acute severe asthma took part in a prospective study investigating the rate and pattern of their subsequent recovery. Clinical assessment of the severity of the acute attack on admission (according to pulse rate, degree of pulsus paradoxus, and peak expiratory flow rate) did not reliably predict the results of arterial blood gas analysis. Subjects were divided into three groups according to the speed of recovery of peak expiratory flow rate. Historical features associated with slow recovery were: age over 40 years, non-atopic asthma, a longer duration of the acute attack before hospital admission, poor long-term control of asthma, and the use of maintenance oral corticosteroids. The degree of pulsus paradoxus on admission and the improvement in PEFR at six hours and arterial oxygen tension (PaO2) at 48 hours were also useful in predicting speed of recovery. The severity of the attack, assessed on admission by arterial blood gas analysis and PEFR, did not differ between the three groups of recovering patients. Hyperinflation was still present in 15 out of 44 patients investigated five days after admission even though PEFR had returned to mre than 80% of predicted normal in seven of these 15 subjects. The recovery of hypoxia was also commonly delayed with 12 out of 52 patients having PaO2 values of less than 80 mmHg at five days. Persistent hypoxia was more common in those with delayed delayed recovery PEFR.
Molecular Engineering of Viral Gene Delivery Vehicles
Authors: David V. Schaffer, James T. Koerber, Kwang-il Lim
Journal: Annual Review of Biomedical Engineering (2008)

Viruses can be engineered to efficiently deliver exogenous genes, but their natural gene delivery properties often fail to meet human therapeutic needs. Therefore, engineering viral vectors with new properties, including enhanced targeting abilities and resistance to immune responses, is a growing area of research. This review discusses protein engineering approaches to generate viral vectors with novel gene delivery capabilities. Rational design of viral vectors has yielded successful advances in vitro, and to an extent in vivo. However, there is often insufficient knowledge of viral structure-function relationships to reengineer existing functions or create new capabilities, such as virus-cell interactions, whose molecular basis is distributed throughout the primary sequence of the viral proteins. Therefore, high-throughput library and directed evolution methods offer alternative approaches to engineer viral vectors with desired properties. Parallel and integrated efforts in rational and library-based design promise to aid the translation of engineered viral vectors toward the clinic.