tbuckley/cabot-search huggingface dataset:
Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Authors: Robert J. Motzer, Brian I. Rini, Ronald M. Bukowski, Brendan D. Curti, Daniel J. George, Gary R. Hudes, Bruce G. Redman, Kim A. Margolin, Jaime R. Merchan, George Wilding, Michelle S. Ginsberg, Jennifer Bacik, Sindy T. Kim, Charles M. Baum, M. Dror Michaelson
Journal: JAMA (2006)

Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients.To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy.Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy.Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment).All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively.The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.clinicaltrials.gov Identifier: NCT00077974.
Hepatitis C virus genotypes in France: comparison of clinical features of patients infected with HCV type I and type II
Authors: Di Qu, Ji-Su Li, Ludmila Vitvitski, Samya Mechai, Françoise Berby, Shu-Ping Tong, François Bailly, Qing-Shen Wang, Jean-Louis Martin, Christian Trépo
Journal: Journal of Hepatology (1994)
Lymph Node Evaluation as a Colon Cancer Quality Measure: A National Hospital Report Card
Authors: Karl Y. Bilimoria, David J. Bentrem, Andrew K. Stewart, Mark S. Talamonti, David P. Winchester, Thomas R. Russell, Clifford Y. Ko
Journal: JNCI Journal of the National Cancer Institute (2008)

Examination of 12 or more regional lymph nodes for colon cancer is associated with improved staging and survival, and the National Quality Forum recently endorsed lymph node examination for colon cancer as a quality surveillance measure. However, information regarding the extent of hospital compliance with the 12-node measure in the United States is lacking.From the National Cancer Data Base, 1296 hospitals that performed 156 789 colectomies in 1996-1997 and 2004-2005 were identified, and rates of hospital-level compliance (defined as examination of >or=12 nodes in >or=75% of patients) in these two time periods were compared. Multivariable models were developed to determine if hospital type, volume, or differences in case mix were associated with 12-node measure compliance. All statistical tests were two-sided.In 1996-1997, 15% of hospitals were compliant with the 12-node measure; in 2004-2005 the percentage of compliant hospitals had increased to 38%. From 1996-1997 to 2004-2005, 12-node measure compliance increased at 980 hospitals, remained unchanged at 6 hospitals, and decreased at 310 hospitals. In 2004-2005, National Cancer Institute-designated Comprehensive Cancer Centers were more frequently compliant with the 12-node measure than other academic hospitals, Veterans' Administration hospitals, or community hospitals (78.1% versus 52.4%, 53.1%, and 33.7%, respectively, all P < .001), even after adjustment for differences in characteristics of the colon cancer patients at these hospitals.This study provides a national report card of nearly 1300 hospitals showing that more than 60% of institutions failed to achieve a compliance benchmark for the 12-node measure. Considerable improvement is needed in colon cancer nodal evaluation in the United States.
Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance)
Authors: Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Ellen M.L. Smith, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Nina D. Wagner-Johnston, Kathryn J. Ruddy, Shaker Dakhil, Nathan P. Staff, Axel Grothey, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2015)

Purpose Given that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation. Methods Acute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy. Results Three hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P &lt; .0001). Conclusion Acute oxaliplatin-induced neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies.
Not so fast! Sick sinus syndrome is a complex and incompletely understood disease that might prove hard to model in animals: reply
Authors: Stefan Herrmann, Andreas Ludwig
Journal: Cardiovascular Research (2011)

We thank Dr Morris et al. for their interest and comments regarding our recent report.1

First, we would like to clarify the assertion that we used ‘a ubiquitous Cre promoter’. This is not correct since we did not use the CAGG-Cre promoter2 in this mouse model. As mentioned by Morris et al ., this CAGG promoter was employed in a previous publication.3 However, the Cre transgene used in the recent report is under control of the HCN4 promoter enabling Cre-mediated recombination specifically in cells of …
H<sub>1</sub>‐antihistamines for primary mast cell activation syndromes: a systematic review
Authors: U. B. Nurmatov, E. Rhatigan, F. E. R. Simons, A. Sheikh
Journal: Allergy (2015)

Abstract Background Primary mast cell activation syndromes ( MCAS ) are a group of disorders presenting with symptoms of mast cell mediator release. Objectives To assess the effectiveness and safety of orally administered H 1 ‐antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments. Methods We systematically searched five databases and three trial repositories and contacted an international panel of experts to identify published and unpublished trials. Results A total of 36 potentially relevant studies were identified. Of these, five crossover trials, enrolling a total of 71 patients (63 adults), met the eligibility criteria. All five of these studies were judged to be at moderate or high risk of bias. Two studies compared an H 1 ‐antihistamine with placebo, two compared two different H 1 ‐antihistamines, and one study compared H 1 ‐ and H 2 ‐antihistamines with oral cromolyn sodium. Four of the five randomized controlled trials were historic (reported from 1983–1993), small (enrolling 8–15 patients), and used agents and/or dosing regimens that are now less commonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine, and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found 4 weeks of treatment with the second‐generation H 1 ‐antihistamine rupatadine, compared with placebo, resulted in significant improvements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and headache, but not gastrointestinal symptoms), and reduction in itching and whealing after standardized skin provocation to elicit Darier's sign. Conclusions There is an urgent need for large, well‐designed, double‐blind, placebo‐controlled randomized trials investigating the effectiveness, cost‐effectiveness, and safety of second‐generation H 1 ‐antihistamines in treatment of primary MCAS .
2012 outbreak of acute haemorrhagic conjunctivitis in Indian Ocean Islands: identification of Coxsackievirus A24 in a returned traveller
Authors: C Aubry, P Gautret, A Nougairede, A S Dussouil, E Botelho-Nevers, C Zandotti, X De Lamballerie, P Brouqui, P Parola
Journal: Eurosurveillance (2012)

In May 2012, a Coxsackievirus A24 haemorrhagic conjunctivitis was diagnosed in Marseille, France, in a traveller returning from the Comoros Islands. This case allowed identification of the cause of an ongoing outbreak of haemorrhagic conjunctivitis in Indian Ocean Islands, illustrating that returning travellers may serve as sentinels for infectious diseases outbreaks in tropical areas where laboratory investigation is limited.
Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever
Authors: Gabriella Giancane, Nienke M Ter Haar, Nico Wulffraat, Sebastiaan J Vastert, Karyl Barron, Veronique Hentgen, Tilmann Kallinich, Huri Ozdogan, Jordi Anton, Paul Brogan, Luca Cantarini, Joost Frenkel, Caroline Galeotti, Marco Gattorno, Gilles Grateau, Michael Hofer, Isabelle Kone-Paut, Jasmin Kuemmerle-Deschner, Helen J Lachmann, Anna Simon, Erkan Demirkaya, Brian Feldman, Yosef Uziel, Seza Ozen
Journal: Annals of the Rheumatic Diseases (2015)

Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of <i>MEFV</i> mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique and were accepted if more than 80% agreement was reached. The literature search yielded 3386 articles, of which 25 were considered relevant and scored for validity and level of evidence. In total, 17 articles were scored valid and used to formulate the recommendations. Eight recommendations were accepted with 100% agreement after the consensus meeting. Topics covered were clinical versus genetic diagnosis of FMF, genotype–phenotype correlation, genotype–age at onset correlation, silent carriers and risk of amyloid A (AA) amyloidosis, and role of the specialist in FMF diagnosis. The SHARE initiative provides recommendations for diagnosing FMF aimed at facilitating improved and uniform care throughout Europe.
EXPERIMENTAL INFECTION WITH MYCOPLASMA PNEUMONIAE (EATON'S AGENT)
Authors: Adnan S. Dajani, Wallace A. Clyde, Floyd W. Denny
Journal: The Journal of Experimental Medicine (1965)

The pathogenesis of Mycoplasma pneumoniae infection was studied in the Syrian hamster with qualitative and quantitative culture methods and special histopathologic techniques. The animals were readily infected with the mycoplasma, which multiplied throughout the respiratory tract. Sensitivity of this experimental host to infection was indicated by the 50 per cent infective dose, which was 10 colony-forming units of the organism. Inoculation consistently resulted in the production of peribronchial pneumonitis which was induced by the mycoplasma. The organisms were visualized in a superficial location in the mucosa of involved bronchi, by means of indirect fluorescent antibody staining and by a modification of the Brown and Brenn technique. The data indicate applicability of the hamster to the study of problems concerned with M. pneumoniae disease which are impractical or impossible to resolve in the human host.
The Runx transcriptional co-activator, CBFβ, is essential for invasion of breast cancer cells
Authors: Daniel Mendoza-Villanueva, Wensheng Deng, Cesar Lopez-Camacho, Paul Shore
Journal: Molecular Cancer (2010)

Abstract Background The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFβ is a transcriptional co-activator that is recruited to promoters by Runx transcription factors and there is considerable evidence that CBFβ is essential for the function of Runx factors. However, overexpression of Runx1 can partially rescue the lethal phenotype in CBFβ-deficient mice, indicating that increased levels of Runx factors can, in some situations, overcome the requirement for CBFβ. Since Runx2 is overexpressed in metastatic breast cancer cells, and there are no reports of CBFβ expression in breast cells, we sought to determine whether Runx2 function in these cells was dependent on CBFβ. Such an interaction might represent a viable target for therapeutic intervention to inhibit bone metastasis. Results We show that CBFβ is expressed in the metastatic breast cancer cells, MDA-MB-231, and that it associates with Runx2. Matrigel invasion assays and RNA interference were used to demonstrate that CBFβ contributes to the invasive capacity of these cells. Subsequent analysis of Runx2 target genes in MDA-MB-231 cells revealed that CBFβ is essential for the expression of Osteopontin, Matrixmetalloproteinase-13, Matrixmetalloproteinase-9, and Osteocalcin but not for Galectin-3. Chromatin immunoprecipitation analysis showed that CBFβ is recruited to both the Osteopontin and the Galectin-3 promoters. Conclusions CBFβ is expressed in metastatic breast cancer cells and is essential for cell invasion. CBFβ is required for expression of several Runx2-target genes known to be involved in cell invasion. However, whilst CBFβ is essential for invasion, not all Runx2-target genes require CBFβ. We conclude that CBFβ is required for a subset of Runx2-target genes that are sufficient to maintain the invasive phenotype of the cells. These findings suggest that the interaction between Runx2 and CBFβ might represent a viable target for therapeutic intervention to inhibit bone metastasis.
Nitric oxide synthase in cardiac nerve fibers and neurons of rat and guinea pig heart.
Authors: L Klimaschewski, W Kummer, B Mayer, J Y Couraud, U Preissler, B Philippin, C Heym
Journal: Circulation Research (1992)

Participation of nitric oxide (NO) in the autonomic innervation of rat and guinea pig hearts was investigated by applying the NADPH diaphorase technique and immunohistochemistry with NO synthase antiserum. We present evidence that NO synthase is localized in cardiac ganglion cells and nerve fibers innervating the sinuatrial and atrioventricular nodes, the myocardium, local neurons, coronary arteries, and pulmonary vessels, suggesting an involvement of NO in neurogenic heart rate regulation, myocardial cell function, neuronal transmission in cardiac ganglia, and coronary as well as pulmonary vasodilation.
Interferon (IFN)-α Activation of Human Blood Mononuclear Cells In Vitro and In Vivo for Nitric Oxide Synthase (NOS) Type 2 mRNA and Protein Expression: Possible Relationship of Induced NOS2 to the Anti–Hepatitis C Effects of IFN-α In Vivo
Authors: Ala I. Sharara, Douglas J. Perkins, Mary A. Misukonis, Stanley U. Chan, Jason A. Dominitz, J. Brice Weinberg
Journal: The Journal of Experimental Medicine (1997)

Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) γ and endotoxin, it has been difficult to demonstrate activation of human mononuclear phagocytes. The purpose of this study was to determine if IFN-α serves as an activator in vitro and in vivo in humans. Treatment of normal monocytes or mononuclear cells in vitro with IFN-α caused a dose-dependent increase in monocyte NOS2 activity and NO production, and increased expression of NOS2 protein and mRNA expression. To determine if in vivo administration of IFN-α also modulated NOS2, we studied blood cells from patients with hepatitis C before and after IFN-α therapy. Untreated patients with chronic hepatitis C virus infection had levels of NOS activity and NOS2 antigen in freshly isolated mononuclear cells similar to those of healthy subjects, and they expressed minimal or no NOS2 mRNA. However, IFN-α treatment of patients with hepatitis C infection was associated with a significant elevation in mononuclear cell NOS activity, NOS2 antigen content, and NOS2 mRNA content. IFN-α–treated patients had significant decreases in levels of serum alanine aminotransferase and plasma hepatitis C mRNA. The degree of IFN-α–enhanced mononuclear cell NOS2 antigen content correlated significantly with the degree of reduction in serum alanine aminotransferase levels. Thus, IFN-α treatment of cells in vitro or administration of IFN-α to hepatitis C patients in vivo increases expression of mononuclear cell NOS2 mRNA expression, NOS activity, NOS2 antigen expression, and NO production. Since NO has been reported to have antiviral activity for a variety of viruses, we speculate that induced NO production may be related to the antiviral action(s) of IFN-α in hepatitis C infection.
A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 14
Authors: P C Calder, M R Lindley, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2010)

Part 14 covers issues related to fats. General health messages tell us that we consume too much fat; thus it might seem strange to include it as a potential supplement for sports performance. But fat, in the form of our body stores, provides a relatively unlimited pool of energy: a critical adaptation to training is to enhance our ability to transport it, take it up into the muscle and oxidise it during exercise. However, even the most highly trained athletes have not reached maximal capacity for fat oxidation during exercise, since it can be increased even further by consumption of a high-fat diet prior to the exercise. Although fat oxidation has limited capacity as a fuel source for the high-intensity activities that underpin success in most sports, if fat supplements or other products could increase fat utilisation at more moderate exercise intensities, it might provide a way to ‘spare’ muscle glycogen stores for the high-intensity phases of sport. Another aspect is to consider the roles that fats play apart from their contribution to body fuel. The ω-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly known as fish oils because of their concentrated presence in some fatty fish, are of interest here because of a range of proposed physiological activities.

### P C Calder

Fatty acids are a major component of most diets and can be synthesised endogenously in the human body.1 They are found in all cells and tissues and are transported between tissues in the bloodstream. Fatty acids are usually linked to other structures, frequently but not exclusively by ester linkages, to form more complex lipids such as triglycerides, phospholipids and sphingolipids. Non-esterified fatty acids (NEFAs), often called ‘free fatty acids’, circulate in the bloodstream and are an important source of energy for skeletal muscle and heart cells. …
Identification of sleep disruption and sleep disordered breathing from the systolic blood pressure profile.
Authors: R J Davies, K Vardi-Visy, M Clarke, J R Stradling
Journal: Thorax (1993)

BACKGROUND--Respiratory sleep studies are frequently performed to identify sleep disruption resulting from upper airway obstruction. Traditional polysomnographic studies may not detect brief recurrent sleep disruption and thus fail to recognise a significant problem when apnoea, hypopnoea, or arterial desaturation are not present. Arousal from sleep causes a transient blood pressure rise, and each inspiration causes a transient blood pressure fall. This study assesses whether these blood pressure changes are a useful indirect marker of disturbed sleep, obstructed sleep apnoea, and snoring related sleep disturbance. METHODS--Computer algorithms were developed to identify blood pressure falls caused by inspiration and rises related to arousal from 286 sleeping blood pressure samples of a consistent respiratory state drawn from 51 polysomnographic studies. From these samples, normal ranges for the number of arousal related systolic rises and the average size of the inspiratory falls were established. These were then applied prospectively to all night unedited blood pressure recordings from a further 20 subjects. RESULTS--The size of the inspiratory falls in blood pressure progressively increased from normal sleep, through snoring, to frank obstructive sleep apnoea. The 95th centile of normal was 12.5 mm Hg. The number of arousal related blood pressure rises also increased during obstructive sleep apnoea and periods of snoring with associated arousals, compared with normal undisturbed sleep, and all these periods of disturbed sleep included more than 30 such rises per hour. When these blood pressure features were examined in the 20 subjects studied prospectively, the six with a sleep related breathing disorder could all have been identified from their systolic blood pressure profile alone. CONCLUSIONS--The systolic blood pressure profile may be helpful in identifying patients with obstructive sleep apnoea, snoring with arousals, or other sleep disruption syndromes.