tbuckley/cabot-search huggingface dataset:
Adjuvant Therapy With Fluorouracil and Oxaliplatin in Stage II and Elderly Patients (between ages 70 and 75 years) With Colon Cancer: Subgroup Analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer Trial
Authors: Christophe Tournigand, Thierry André, Franck Bonnetain, Benoist Chibaudel, Gérard Lledo, Tamas Hickish, Josep Tabernero, Corrado Boni, Jean-Baptiste Bachet, Luis Teixeira, Aimery de Gramont
Journal: Journal of Clinical Oncology (2012)

Oxaliplatin combined with fluoropyrimidine improves survival in patients with stage III colon cancer. However, adjuvant chemotherapy with oxaliplatin is controversial in stage II and elderly patients.We performed subgroup analyses of stage II and elderly patients randomly assigned fluorouracil with leucovorin (FL) ± oxaliplatin (FOLFOX4) in the Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer study. Comorbidities, severe adverse events, second cancers, management of relapse and death as a result of causes than other colon cancer were studied.Two thousand two hundred forty-six patients were enrolled. Overall, 899 patients had stage II disease, including 330 low-risk and 569 high-risk patients. A total of 315 patients were ages 70 to 75 years. For stage II patients, the hazard ratio (HR) for comparing FOLFOX4 with FL was 0.84 (95% CI, 0.62 to 01.14) for disease-free survival (DFS), 0.70 (95% CI, 0.49 to 0.99) for time to recurrence (TTR), and 1.00 (95% CI, 0.70 to 1.41) for overall survival (OS). There was no interaction between treatment and stage or age. Low-risk stage II patients did not benefit from oxaliplatin. In high-risk stage II patients, the HR comparing FOLFOX4 with FL was 0.72 (95% CI, 0.51 to 1.01) for DFS, 0.62 (95% CI, 0.41 to 0.92) for TTR, and 0.91 (95% CI, 0.61 to 1.36) for OS. In elderly patients, the HR comparing FOLFOX4 with FL was 0.93 (95% CI, 0.64 to 1.35) for DFS, 0.72 (95% CI, 0.47 to 1.11) for TTR, and 1.10 (95% CI, 0.73 to 1.65) for OS.The results of these subset analyses show no statistically significant benefit (OS and DFS) for the addition of oxaliplatin to FL as adjuvant treatment for either stage II and elderly patients.
Radiotherapy enhances laser palliation of malignant dysphagia: a randomised study.
Authors: I R Sargeant, J S Tobias, G Blackman, S Thorpe, J R Glover, S G Bown
Journal: Gut (1997)

BACKGROUND/AIMS: A major drawback of laser endoscopy in the palliation of malignant dysphagia is the need for repeated treatments. This study was designed to test whether external beam radiotherapy would reduce the necessity for repeated laser therapy. PATIENTS/METHODS: Sixty seven patients with inoperable oesophageal or gastric cardia cancers and satisfactory swallowing after initial laser recanalisation were randomised to palliative external beam radiotherapy (30 Gy in 10 fractions) or no radiotherapy. All patients underwent a 9check9 endoscopy five weeks after initial recanalisation and were subsequently reendoscoped only for recurrent dysphagia, which occurred in 59 patients. RESULTS: Dysphagia was relieved equally well in both groups and the improvement was maintained with further endoscopic treatment. The initial dysphagia controlled interval and the duration between procedures required to maintain lifelong palliation (treatment interval) increased from five to nine weeks (median) in the radiotherapy group (p &lt; 0.01 both parameters). Radiotherapy was well tolerated in all but three patients. One perforation occurred and two fistulae opened after dilatation in patients who received radiotherapy. CONCLUSION: Additional radiotherapy reduces the necessity for therapeutic endoscopy for a patient9s remaining life. It has an important role in relatively well patients who are likely to survive long enough to benefit.
Characteristics of cerebrovascular accidents after percutaneous coronary interventions
Authors: Srinivas Dukkipati, William W O'Neill, Kishore J Harjai, William P Sanders, Datinder Deo, Judith A Boura, Beth A Bartholomew, Michael W Yerkey, H.Mehrdad Sadeghi, Joel K Kahn
Journal: Journal of the American College of Cardiology (2004)
Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis
Authors: Frederique Ponchel, Ann W. Morgan, Sarah J. Bingham, Mark Quinn, Maya Buch, Robert J. Verburg, Judy Henwood, Susan H. Douglas, Aurelie Masurel, Philip Conaghan, Moji Gesinde, Julia Taylor, Alexander F. Markham, Paul Emery, Jacob M. van Laar, John D. Isaacs
Journal: Blood (2002)
The effect of coingestion of aspirin and nsaids on paracetamol-induced liver failure: a single centre case controlled study
Authors: L. Salter, G. Masterton, J. Davidson, D. Craig, C. Bates, K. Simpson
Journal: Gut (2011)

<h3>Introduction</h3> Acute liver failure (ALF), which has a high risk of death or emergency liver transplantation, is most commonly caused by paracetamol overdose (POD) in the UK. A murine study suggested aspirin could improve survival following POD induced hepatotoxicity. The aim of this case control study was to determine if coingestion of aspirin or other non-steroidal drugs (NSAIDs) influenced outcome in humans with severe liver injury following POD. <h3>Methods</h3> Age, sex and year of admission matched cohort of 46 pairs of patients (15 aspirin, 28 NSAIDs and 3 NSAIDs and aspirin) with POD induced liver injury were identified from a prospectively collected database of patients with POD admitted to the Scottish Liver Transplantation Unit (SLTU). Statistical analysis including Kaplan–Meier (KM) survival analysis was performed using SPSS v14. <h3>Results</h3> Spontaneous survival trended towards significance for NSAID/aspirin coingestion (38/46, 82.6%, survived) compared with controls (28/46, 60.9%, p=0.08), when death and transplant were considered as a single outcome. Survival was significant for NSAIDs alone (NSAID 24/28, 85.7%; controls 14/28, 50%, p&lt;0.01) and wasn9t for aspirin alone. KM analysis produced similar results. Analysis of admission variables of potential prognostic significance revealed that in the NSAID alone cohort, hepatic encephalopathy frequency was significantly lower (NSAID 9/28, 33%; controls 22/28, 79%, p&lt;0.01) as was PT when presenting at SLTU (NSAID 54.0, 42.4 to 65.6 mean, 95% CI; controls 76.1, 64.0 to 88.2, p&lt;0.01). <h3>Conclusion</h3> Contrary to the murine study, this analysis demonstrated that co-ingestion of NSAIDs, not aspirin, improves outcome in severe liver injury following POD. This could be helpful therapeutically.
Increased resting bronchial tone in normal subjects acclimatised to altitude
Authors: C M Wilson, S E Bakewell, M R Miller, N D Hart, R C N McMorrow, P W Barry, D J Collier, S J Watt, A J Pollard
Journal: Thorax (2002)

Normal subjects frequently experience troublesome respiratory symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and full and partial flow-volume loops were measured before and after ascent to 5000 m altitude to determine if there are changes in resting bronchial tone and BHR that might explain the symptoms.BHR to histamine was measured using a turbine spirometer to record partial and full flow-volume curves and expressed as log dose slopes. Twenty one subjects were tested at sea level and after acclimatisation at 5000 m altitude.No significant change in log dose slope measurements of forced expiratory volume in 1 second occurred after acclimatisation, and the maximal expiratory flow with 30% of forced vital capacity remaining (MEF(30%)) rose on the full loop and fell on the partial loop. Their ratio (full divided by partial) rose on average by 0.28 (95% confidence limits 0.14 to 0.42) from the mean (SD) sea level value of 0.87 (0.20).There is no increase in BHR in normal subjects acclimatised to altitude but an increase in resting bronchial tone occurs that could be released by deep inspiration. This may be the result of increased cholinergic tone.
Fatal Reactivation of Chronic Hepatitis B
Authors: K. M. De Cock, S. Govindarajan, N. Sandford, A. G. Redeker
Journal: JAMA (1986)

THE NATURAL history of chronic hepatitis B virus (HBV) infection is one of progression from a replicative to a nonreplicative stage.<sup>1</sup>The former is characterized by high serum titers of hepatitis B surface antigen (HBsAg), DNA polymerase and HBV-DNA, and by the presence of hepatitis B e antigen (HBeAg). Patients in this stage of infection have significant inflammatory activity on liver biopsy specimen and usually demonstrate elevated serum aminotransferase levels. The nonreplicative stage is associated with low levels or absence of HBV-DNA, with the presence of antibody to HBeAg, and quiescent biochemical test values and liver histology. Conversion fromthe replicative to the nonreplicative phase of HBV infection is generally a function of time, HBeAg-positive patients losing HBeAg at the rate of about 5% per year.<sup>2</sup> It has recently been recognized that remission of active viral turnover in chronic hepatitis B need not be permanent, and that reactivation
Screening for TB by sputum culture in high-risk groups in Copenhagen, Denmark: a novel and promising approach
Authors: Sidse Graff Jensen, Nete Wrona Olsen, Niels Seersholm, Troels Lillebaek, Torgny Wilcke, Mathias Klok Pedersen, Axel Kok-Jensen
Journal: Thorax (2015)

<h3>Introduction</h3> Evidence on screening high-risk groups for TB by mobile X-ray in low-incidence countries is building, but knowledge on other possible screening methods is limited. In this retrospective study we report results from a community based programme screening for TB by spot sputum culture. <h3>Methods</h3> On seven occasions, from September 2012 through June 2014, we offered TB screening to all persons present at 11 locations where socially marginalised people gather in Copenhagen. Spot sputum samples from participants were examined by smear microscopy and culture. Genotype, nucleic acid amplification test and chest X-ray were done if TB was found. <h3>Results</h3> Among 1075 participants, we identified 36 cases of TB. Twenty-four cases (66.7%) were identified at the first screening of each participant, that is, the prevalence of TB was 2233/100 000. Thirty-five (97%) of the TB cases were culture-positive and seven (19.4%) were smear-positive. Twelve out of 21 (57.1%) cases tested were nucleic acid amplification test positive. Twenty-eight (77.8%) had chest X-ray suggestive of TB. All patients with TB started treatment, 30 (83.3%) had a successful outcome. <h3>Discussion</h3> Screening for TB by spot sputum culture is possible and a promising alternative to mobile X-ray in a community based screening programme. 22.2% did not have chest X-ray suggestive of TB and would not have been identified using mobile X-ray. Most of the TB cases were smear-negative, suggesting that they were identified at an early, less infectious stage, which is essential in order to prevent transmission and gain infection control.
Cholesterol depletion by methyl-β-cyclodextrin augments tamoxifen induced cell death by enhancing its uptake in melanoma
Authors: Naoshad Mohammad, Parmanand Malvi, Avtar Singh Meena, Shivendra Vikram Singh, Balkrishna Chaube, Garikapati Vannuruswamy, Mahesh J Kulkarni, Manoj Kumar Bhat
Journal: Molecular Cancer (2014)

Despite modern advances in treatment, skin cancer is still one of the most common causes of death in the western countries. Chemotherapy plays an important role in melanoma management. Tamoxifen has been used either alone or in- combination with other chemotherapeutic agents to treat melanoma. However, response rate of tamoxifen as a single agent has been comparatively low. In the present study, we investigated whether treatment with methyl-β-cyclodextrin (MCD), a cholesterol depleting agent, increases the efficacy of tamoxifen in melanoma cells. This was a two-part study that incorporated in vitro effects of tamoxifen and MCD combination by analyzing cell survival, apoptosis and cell cycle analysis and in vivo antitumor efficacy on tumor isografts in C57BL/6J mice. MCD potentiated tamoxifen induced anticancer effects by causing cell cycle arrest and induction of apoptosis. Sensitization to tamoxifen was associated with down regulation of antiapoptotic protein Bcl-2, up-regulation of proapoptotic protein Bax, reduced caveolin-1 (Cav-1) and decreased pAkt/pERK levels. Co-administration of tamoxifen and MCD caused significant reduction in tumor volume and tumor weight in mice due to enhancement of drug uptake in the tumor. Supplementation with cholesterol abrogated combined effect of tamoxifen and MCD. Our results emphasize a potential synergistic effect of tamoxifen with MCD, and therefore, may provide a unique therapeutic window for improvement in melanoma treatment.
Relationship between cardiomyopathy and liver disease in chronic alcoholism
Authors: Ramon Estruch, Joaquim Fernández-Solá, Emilio Sacanella, Carles Paré, Emanuel Rubin, Alvaro Urbano-Márquez
Journal: Hepatology (1995)

Based on anecdotal impressions, there is a common clinical perception that alcoholics with liver disease do not develop cardiomyopathy and that those with alcohol-induced cardiac disease are spared cirrhosis. To determine the relationship between alcoholic cardiomyopathy and cirrhosis, we carried out a prospective cross-sectional study that included: (1) 30 alcoholic men with cardiomyopathy; (2) 30 alcoholic men without cardiomyopathy (left ventricular ejection fraction > 55%); (3) 20 actively drinking alcoholics with cirrhosis; (4) 15 abstaining alcoholics with cirrhosis; and (5) 15 nonalcoholics with cirrhosis of other etiologies. Cirrhosis was observed in 13 of 30 patients with alcoholic cardiomyopathy (43%), compared with 2 of 30 alcoholics without cardiomyopathy (6%) (P < .001). Ten of the 20 active alcoholics with cirrhosis (50%) showed evidence of dilated cardiomyopathy. Actively drinking alcoholics with cirrhosis had a significantly lower mean ejection fraction and shortening fraction, as well as a greater mean end-diastolic diameter and left ventricular mass than abstaining alcoholics with cirrhosis. Cardiac studies of patients with nonalcoholic cirrhosis were normal. We conclude that a positive correlation exists between alcoholic cardiomyopathy and cirrhosis. Alcoholics admitted solely for cardiomyopathy have a higher prevalence of cirrhosis than unselected alcoholics without heart disease. Actively drinking alcoholics admitted only for cirrhosis show impaired cardiac performance, whereas abstaining alcoholics with liver disease tend to manifest normal cardiac function.
PTU-080 Polyunsaturated phosphatidilcholine and sibutramin decrease the liver fibrosis progress in patients with non-alcoholic liver disease
Authors: E Sas, V Grinevich, U Kravchuk
Journal: Gut (2012)

<h3>Introduction</h3> From 2009 to 2011 in our randomised prospective, blinded clinical trial we studied the effect of polyunsaturated phosphatidylcholine—PUPC (Essentiale® forte N, A. Nattermann &amp; Cie.GmbH) and Sibutramin in patients with obesity (BMI 30–35 kg/m<sup>2</sup>). We studied 80 patients with obesity mean age of 38±7 years and 40 were males. High resolution B mode ultrasonography was carried out twice for screening NAFL patients and after 6 months treatment. <h3>Methods</h3> Liver function markers ALT, AST and GGT were measured twice, before and after 6 months treatment. All patients followed the basic treatment scheme included dietary and physical regimen. 50 patients of investigational group (IG) additionally were treated by Sibutramin, daily dosage contained 15 mg and PUPC (daily dosage contained 1368 mg Phosphatidylcholine). 30 patients of control group (CG) were treated by Sibutramin, daily dosage contained 15 mg. <h3>Results</h3> All 50 patients of IG and 30 patients of CG were available for follow-up reliable decrease (12.8%) of BMI and leptin level. In IG patients BMI and leptin level (24.7±2.1%—16.2±1.2%) was registered compared to CG patients (BMI decrease—9.3%, leptin level 24.5±1.5% to 19.9±1.1%). Moreover after 6 months of treatment the mean value of disease activity evaluated by Metavir scale was A1 in IG and A3 in CG. The results of liver biopsy (histological examination) and Fibromax test showed, that in patients with ALD additionally treated by PUPC, the progress of hepatic fibrosis was significantly slowly, then in CG (Fibromax test result: F1 vs F3) (p&lt;0.05). In addition after 6 months of treatment we found significant increase of steatosis in CG, and its reduction in IG (p&lt;0.05). Ultrasound studies were performed on the basis of liver attenuation value assessment and revealed the hepatic echo-texture had become significantly improved after Sibutramin treatment in 46/50 (92%) of patients, while there was no change in 7/30 (23.3%) individuals. Also in patients additionally treated by polyunsaturated phosphatidylcholine and Sibutramin we found significant reduction of glucose, insulin levels and of insulin resistance index HOMA. The usage of Sibutramin itself did not reveal significant changes. <h3>Conclusion</h3> Study results suggest that Sibutramin combined with PUPC improves liver function and insulin-sensitivity, reduces steatosis and fibrosis in patients with obesity and effect of combined therapy is higher than of Sibutramin itself. <h3>Competing interests</h3> None declared.
Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score.
Authors: D M van der Heijde, M A van 't Hof, P L van Riel, L A Theunisse, E W Lubberts, M A van Leeuwen, M H van Rijswijk, L B van de Putte
Journal: Annals of the Rheumatic Diseases (1990)

An investigation of clinical and laboratory variables which might form the basis for judging disease activity in clinical practice was made by six rheumatologists in a prospective study of up to three years9 duration of 113 patients with early rheumatoid arthritis. Decisions to start treatment with slow acting antirheumatic drugs were equated with moments of high disease activity. If treatment with slow acting antirheumatic drugs was not started or if the slow acting antirheumatic drug remained unchanged for at least one year or if treatment was stopped because of disease remission, this was equated with periods of low disease activity. Two groups, one with high and one with low disease activity according to the above criteria, were formed. Factor analysis was performed to enable easy handling of the large number of clinical and laboratory variables without loss of information; this resulted in five factors. Next, discriminant analysis was done to determine to what extent each factor contributed to discrimination between the two groups of differing disease activity. Finally, a multiple regression analysis was carried out to determine which laboratory and clinical variables underlie the factors of the discriminant function, resulting in a 9disease activity score9. This score consisted of the following variables: Ritchie index, swollen joints, erythrocyte sedimentation rate, and general health, in declining importance. The rheumatologists9 decisions to prescribe slow acting antirheumatic drugs, or not, were mainly based on articular symptoms.
Protection against rheumatoid arthritis by HLA: nature and nurture
Authors: A L Feitsma, A H M van der Helm-van Mil, T W J Huizinga, R R P de Vries, R E M Toes
Journal: Annals of the Rheumatic Diseases (2008)

Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA region contributes most to the genetic risk. HLA-DRB1 molecules containing the amino acid sequence QKRAA/QRRAA/RRRAA (ie, HLA-DRB1*0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001 and *1402) at position 70–74 in the third hypervariable region of the DRB1 chain are associated with susceptibility to RA. HLA-DRB1 molecules containing the amino acids "DERAA" (ie, HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302 and *1304) at the same position are associated with protection from RA. Interestingly, not only inherited but also non-inherited HLA-antigens from the mother can influence RA susceptibility. A protective effect of "DERAA"-containing HLA-DRB1 alleles as non-inherited maternal antigen (NIMA) has recently been described. The underlying mechanism of this protective effect is currently unknown, although a possible explanation is covered below. In this review, an overview of the current knowledge on protection against RA is given and the inherited and NIMA effect of "DERAA"-containing HLA-DRB1 alleles are compared.
Toll-like receptor 9 inhibition confers protection from liver ischemia-reperfusion injury
Authors: Zubin M. Bamboat, Vinod P. Balachandran, Lee M. Ocuin, Hebroon Obaid, George Plitas, Ronald P. DeMatteo
Journal: Hepatology (2009)

Endogenous ligands such as high-mobility group box 1 (HMGB1) and nucleic acids are released by dying cells and bind Toll-like receptors (TLRs). Because TLR9 sits at the interface of microbial and sterile inflammation by detecting both bacterial and endogenous DNA, we investigated its role in a model of segmental liver ischemia–reperfusion (I/R) injury. Mice were subjected to 1 hour of ischemia and 12 hours of reperfusion before assessment of liver injury, cytokines, and reactive oxygen species (ROS). Wild-type (WT) mice treated with an inhibitory cytosine-guanosine dinucleotide (iCpG) sequence and TLR9−/− mice had markedly reduced serum alanine aminotransferase (ALT) and inflammatory cytokines after liver I/R. Liver damage was mediated by bone marrow–derived cells because WT mice transplanted with TLR9−/− bone marrow were protected from hepatic I/R injury. Injury in WT mice partly depended on TLR9 signaling in neutrophils, which enhanced production of ROS, interleukin-6 (IL-6), and tumor necrosis factor (TNF). In vitro , DNA released from necrotic hepatocytes increased liver nonparenchymal cell (NPC) and neutrophil cytokine secretion through a TLR9-dependent mechanism. Inhibition of both TLR9 and HMGB1 caused maximal inflammatory cytokine suppression in neutrophil cultures and conferred even greater protection from I/R injury in vivo . Conclusion: TLR9 serves as an endogenous sensor of tissue necrosis that exacerbates the innate immune response during liver I/R. Combined blockade of TLR9 and HMGB1 represents a clinically relevant, novel approach to limiting I/R injury. (Hepatology 2009.)
Guidelines for the management of adult lower respiratory tract infections - Full version
Authors: M. Woodhead, F. Blasi, S. Ewig, J. Garau, G. Huchon, M. Ieven, A. Ortqvist, T. Schaberg, A. Torres, G. van der Heijden, R. Read, T.J.M. Verheij
Journal: Clinical Microbiology and Infection (2011)
Functional diversity within the suppressor phenotype as defined by monoclonal antibody in T‐cell prolymphocytic leukemia
Authors: Kenneth W. Zamkoff, Bernard J. Poiesz, Francis W. Ruscetti, Janet L. Moore, Frederick R. Davey, Antonio T. Planas, Harold Lamberson
Journal: American Journal of Hematology (1984)

Abstract A patient with T‐cell prolymphocytic leukemia (T‐PLL) is described. The malignant T‐cells from the patient were predominantly Leu‐2‐positive, indicating a suppressor phenotype. The cells were then tested to determine their functional capabilities. The patient's Leu‐2‐positive cells initially suppressed B‐cell proliferation, as predicted by their phenotype but later functioned as T helper cells in the pokeweed mitogen system without a change in phenotype. The cells also responded inadequately to alloantigen and mitogen despite addition of exogenous T‐cell growth factor (TCGF). Leu‐2‐positive prolymphocytes from the spleen of the patient were constitutive producers of TCGF. Surface phenotype using monoclonal antibody was inadequate to predict T‐cell function of the cells from this patient with T‐PLL. In addition, these data suggest there may be functional subpopulations within the OKT8 + phenotype. Constitutive TCGF production by malignant post‐thymic T‐cells may represent a mechanism by which these cells sustain their own growth.