tbuckley/cabot-search huggingface dataset:
Alveolar echinococcosis of the liver: A parasitic disease in search of a treatment
Authors: Dominique Vuitton
Journal: Hepatology (1990)

The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to <2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes, significantly more effective than mebendazole (p < 0.05), praziquantel (p < 0.01) or untreated controls (p < 0.01).
Transcutaneous electrical nerve stimulation as adjunct to primary care management for tennis elbow: pragmatic randomised controlled trial (TATE trial)
Authors: Linda S Chesterton, A Martyn Lewis, Julius Sim, Christian D Mallen, Elizabeth E Mason, Elaine M Hay, Daniëlle A van der Windt
Journal: British Journal of Sports Medicine (2014)

Can transcutaneous electrical nerve stimulation (TENS), as a patient controlled adjunct to primary care management for tennis elbow, provide superior pain relief to primary care management alone.TENS conferred no additional clinical benefit over primary care management consisting of information and advice on analgesia and exercise for patients with tennis elbow, probably partly owing to poor adherence to treatment recommendations.A need exists for safe, self administered interventions to provide pain relief for patients with tennis elbow. TENS as an adjunct to primary care management failed to show any additional pain relief compared with primary care management alone.
Phase II Study of the Antiangiogenic Agent SU5416 in Patients with Advanced Soft Tissue Sarcomas
Authors: John V. Heymach, Jayesh Desai, Judith Manola, Darren W. Davis, David J. McConkey, David Harmon, David P. Ryan, Geraldine Goss, Travis Quigley, Annick D. Van den Abbeele, Stuart G. Silverman, Susan Connors, Judah Folkman, Christopher D. M. Fletcher, George D. Demetri
Journal: Clinical Cancer Research (2004)

SU5416 (semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor (VEGF) receptor-2 and KIT receptor tyrosine kinases. This Phase II study was conducted to investigate the safety and efficacy of SU5416 for patients with soft tissue sarcomas.Thirteen patients with locally advanced or metastatic soft tissue sarcomas were treated with SU5416 via intravenous infusion at a dose of 145 mg/m(2) twice weekly. In selected cases tumor biopsies were taken before and after 2 months of treatment.The median progression-free survival was 1.8 months. Median overall survival was 22.8 months. No objective tumor responses were observed. There was evidence of shorter survival among patients with high baseline urine VEGF levels (P = 0.04). No grade 4 toxicities were observed. The most common grade 3 toxicities were headache and thrombosis. Other less serious toxicities included fatigue, nausea, and abdominal pain. The median systolic blood pressure increased from 118 mmHg at baseline to 133 after 1 month of treatment (P = 0.01). Post-treatment tumor biopsies showed no significant decreases in VEGF receptor phosphorylation compared with baseline in 3 evaluable patients. One patient with gastrointestinal stromal tumor who had rapid progression during SU5416 treatment was subsequently treated with another KIT inhibitor, imatinib mesylate, and had a partial response lasting >36 months.SU5416 was relatively well tolerated but did not demonstrate significant antitumor activity against advanced soft tissue sarcoma. Correlative studies suggest that VEGF receptor or KIT inhibition was incomplete in at least some cases, providing a possible explanation for the observed lack of activity.
Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination
Authors: Stephen P J Fancy, Emily P Harrington, Tracy J Yuen, John C Silbereis, Chao Zhao, Sergio E Baranzini, Charlotte C Bruce, Jose J Otero, Eric J Huang, Roel Nusse, Robin J M Franklin, David H Rowitch
Journal: Nature Neuroscience (2011)
Workgroup III: facilitating screening for colorectal cancer: quality assurance and evaluation. UICC International Workshop on Facilitating Screening for Colorectal Cancer, Oslo, Norway (29 and 30 June 2002)
Authors: J. Patnick, D. Ransohoff, W. Atkin, J. Ma Borras, M. Elwood, G. Hoff, M. Nadel, A. Russo, J. Simon, E. Weiderpass-Vaino, M. Zappa, R. Smith
Journal: Annals of Oncology (2004)
Oral Contraceptives and Breast Cancer Risk in the International <i>BRCA1/2</i> Carrier Cohort Study: A Report From EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group
Authors: Richard M. Brohet, David E. Goldgar, Douglas F. Easton, Antonis C. Antoniou, Nadine Andrieu, Jenny Chang-Claude, Susan Peock, Rosalind A. Eeles, Margaret Cook, Carol Chu, Catherine Noguès, Christine Lasset, Pascaline Berthet, Hanne Meijers-Heijboer, Anne-Marie Gerdes, Håkan Olsson, Trinidad Caldes, Flora E. van Leeuwen, Matti A. Rookus
Journal: Journal of Clinical Oncology (2007)

Purpose Earlier studies have shown that endogenous gonadal hormones play an important role in the etiology of breast cancer among BRCA1/2 mutation carriers. So far, little is known about the safety of exogenous hormonal use in mutation carriers. In this study, we examined the association between oral contraceptive use and risk of breast cancer among BRCA1/2 carriers. Patients and Methods In the International BRCA1/2 Carrier Cohort study (IBCCS), a retrospective cohort of 1,593 BRCA1/2 mutation carriers was analyzed with a weighted Cox regression analysis. Results We found an increased risk of breast cancer for BRCA1/2 mutation carriers who ever used oral contraceptives (adjusted hazard ratio [HR] = 1.47; 95% CI, 1.16 to 1.87). HRs did not vary according to time since stopping use, age at start, or calendar year at start. However, a longer duration of use, especially before first full-term pregnancy, was associated with an increased risk of breast cancer for both BRCA1 and BRCA2 mutation carriers (4 or more years of use before first full-term pregnancy: HR = 1.49 [95% CI, 1.05 to 2.11] for BRCA1 carriers and HR = 2.58 [95% CI, 1.21 to 5.49] for BRCA2 carriers). Conclusion No evidence was found among BRCA1/2 mutation carriers that current use of oral contraceptives is associated with risk of breast cancer more strongly than is past use, as is found in the general population. However, duration of use, especially before first full-term pregnancy, may be associated with an increasing risk of breast cancer among both BRCA1 and BRCA2 mutation carriers.
Fibrinogen-γ proteolysis and solubility dynamics during apoptotic mouse liver injury: Heparin prevents and treats liver damage
Authors: Sujith V. W. Weerasinghe, David S. Moons, Peter J. Altshuler, Yatrik M. Shah, M. Bishr Omary
Journal: Hepatology (2011)

Fas ligand (FasL)-mediated hepatocyte apoptosis occurs in the context of acute liver injury that can be accompanied by intravascular coagulation (IC). We tested the hypothesis that analysis of selected protein fractions from livers undergoing apoptosis will shed light on mechanisms that are involved in liver injury that might be amenable to intervention. Proteomic analysis of the major insoluble liver proteins after FasL exposure for 4-5 hours identified fibrinogen-γ (FIB-γ) dimers and FIB-γ–containing high molecular mass complexes among the major insoluble proteins visible via Coomassie blue staining. Presence of the FIB-γ–containing products was confirmed using FIB-γ–specific antibodies. The FIB-γ–containing products partition selectively and quantitatively into the liver parenchyma after inducing apoptosis. Similar formation of FIB-γ products occurs after acetaminophen administration. The observed intrahepatic IC raised the possibility that heparin therapy may ameliorate FasL-mediated liver injury. Notably, heparin administration in mice 4 hours before or up to 2 hours after FasL injection resulted in a dramatic reduction of liver injury—including liver hemorrhage, serum alanine aminotransferase, caspase activation, and liver apoptosis—compared with heparin-untreated mice. Heparin did not directly interfere with FasL-induced apoptosis in isolated hepatocytes, and heparin-treated mice survived the FasL-induced liver injury longer compared with heparin-untreated animals. There was a sharp, near-simultaneous rise in FasL-induced intrahepatic apoptosis and coagulation, with IC remaining stable while apoptosis continued to increase. Conclusion: Formation of FIB-γ dimers and their high molecular mass products are readily detectable within the liver during mouse apoptotic liver injury. Heparin provides a potential therapeutic modality, because it not only prevents extensive FasL-related liver injury but also limits the extent of injury if given at early stages of injury exposure. (HEPATOLOGY 2011;)
Complement abnormalities in diffuse plane xanthomatosis with paraproteinaemia
Authors: R. RUSSELL JONES, A.S.J. BAUGHAN, J.J. CREAM, A. LEVANTINE, J.T. WHICHER
Journal: British Journal of Dermatology (1979)

Paraproteinaemia may be associated with xanthomatous skin deposits and these can arise in the absence of elevated lipid levels. Two cases of benign monoclonal gammopathy with diffuse plane xanthomatosis are reported. Case 1 exhibited hypolipidaemia and a functional deficiency of C1 esterase inhibitor. Case 2 showed a normal lipoprotein profile, abnormal platelet aggregation, and a cutaneous vasculitis with evidence of complement consumption via the classical pathway. The significance of these abnormalities is discussed.
PTU-163 Urinary Volatile Organic Compound Analysis To Distinguish Coeliac Disease From Irritable Bowel Syndrome: A Pilot Study
Authors: J Covington, M McFarlane, R Harbord, E Westenbrink, S Chambers, A Dhaliwal, N O’Connell, C Bailey, C Nwokolo, K Bardhan, R Arasaradnam
Journal: Gut (2014)

<h3>Introduction</h3> Coeliac disease (CD), a T-cell-mediated gluten sensitive enteropathy, affects ~1% of the UK population, and in adults presents with a wide range of clinical features; often mistaken for irritable bowel syndrome (IBS). Heightened clinical awareness and serological screening identifies those likely to have CD; the diagnosis confirmed by histological features in small bowel/duodenal biopsies. Limitations to diagnosis are false negative serology (e.g., in IgA deficient patients, the young and the elderly) and reluctance to undergo biopsy. Examining the pattern of urinary volatiles offers a novel non-invasive approach. The gut microbiome is perturbed in several gastrointestinal disorders, resulting in altered gut fermentation patterns, and recognisable by analysis of volatile organic compounds (VOC) in urine, breath and faeces. The altered structure of the small intestinal mucosa, increased gut permeability and altered gluten peptide metabolism, we hypothesised, would change the microbiome creating a unique “fermentome” pattern, distinguishable from IBS. We investigated this by examining the urinary VOC pattern using Field Asymmetric Ion Mobility Spectrometry (FAIMS). <h3>Methods</h3> 47 patients were recruited, 27 with CD and 20 with diarrhoea-predominant IBS (D-IBS). Urine was collected and 10ml aliquots were stored frozen in universal containers. For assay, the containers were heated to 40 ± 0.1<sup>o</sup>C. The headspace above the sample was then analysed by FAIMS. Linear discriminant analysis (LDA) was used for statistical evaluation. <h3>Results</h3> LDA showed that FAIMS distinguishes the VOC pattern in CD vs D-IBS with a sensitivity and specificity of 85% respectively. <h3>Conclusion</h3> This pilot study suggests that FAIMS offers a novel non-invasive approach to identify those likely to have CD, and distinguishes from D-IBS. It may have the potential to non-invasively track the progress of CD when on a gluten-free diet, to monitor adherence and observe changes. <h3>Disclosure of Interest</h3> None Declared.
Genetic Association Analysis of Functional Impairment in Chronic Obstructive Pulmonary Disease
Authors: Craig P. Hersh, Dawn L. DeMeo, Ross Lazarus, Juan C. Celedón, Benjamin A. Raby, Joshua O. Benditt, Gerard Criner, Barry Make, Fernando J. Martinez, Paul D. Scanlon, Frank C. Sciurba, James P. Utz, John J. Reilly, Edwin K. Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Patients with severe chronic obstructive pulmonary disease (COPD) may have varying levels of disability despite similar levels of lung function. This variation may reflect different COPD subtypes, which may have different genetic predispositions.Objectives: To identify genetic associations for COPD-related phenotypes, including measures of exercise capacity, pulmonary function, and respiratory symptoms.Methods: In 304 subjects from the National Emphysema Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically plausible candidate genes. Regression models were used to test for association, using a test–replication approach to guard against false-positive results. For significant associations, effect estimates were recalculated using the entire cohort. Positive associations with dyspnea were confirmed in families from the Boston Early-Onset COPD Study.Results: The test–replication approach identified four genes—microsomal epoxide hydrolase (EPHX1), latent transforming growth factor-β binding protein-4 (LTBP4), surfactant protein B (SFTPB), and transforming growth factor-β1 (TGFB1)—that were associated with COPD-related phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (p ⩽ 0.03) and in LTBP4 (p ⩽ 0.03) were associated with maximal output on cardiopulmonary exercise testing. Markers in LTBP4 (p ⩽ 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were associated with carbon monoxide diffusing capacity (p ⩽ 0.04). Three SNPs in TGFB1 were associated with dyspnea (p ⩽ 0.002), one of which replicated in the family study (p = 0.02).Conclusions: Polymorphisms in several genes seem to be associated with COPD-related traits other than FEV1. These associations may identify genes in pathways important for COPD pathogenesis.
OUTCOME IN PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL DIALYSIS AND HAEMODIALYSIS: 4-YEAR ANALYSIS OF A PROSPECTIVE MULTICENTRE STUDY
Authors: R. Gokal, J. King, S. Bogle, F. Marsh, D. Oliver, C. Jakubowski, L. Hunt, R. Baillod, C. Ogg, M. Ward, R. Wilkinson
Journal: The Lancet (1987)
Identifying and Testing for Hereditary Susceptibility to Common Cancers
Authors: R. Sifri, S. Gangadharappa, L. S. Acheson
Journal: CA A Cancer Journal for Clinicians (2004)

Hereditary cancer syndromes account for an estimated 5% of breast, ovarian, and colon cancers. The rapid discovery of cancer-related genes in the last 15 years has propelled the field of cancer genetic risk assessment forward. With patients becoming increasingly aware of available genetic testing options, it is important that various health professionals become knowledgeable in identifying and advising patients at increased risk for a hereditary cancer syndrome. This article will outline the components of providing a hereditary cancer risk assessment with a focus on hereditary breast and ovarian cancer syndrome and hereditary colon cancer.
Myeloproliferative neoplasms: A decade of discoveries and treatment advances
Authors: Ayalew Tefferi
Journal: American Journal of Hematology (2015)

Myeloproliferative neoplasms (MPN) are clonal stem cell diseases, first conceptualized in 1951 by William Dameshek, and historically included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In 1960, Nowell and Hungerford discovered an invariable association between the Philadelphia chromosome (subsequently shown to harbor the causal BCR‐ABL1 mutation) and CML; accordingly, the term MPN is primarily reserved for PV, ET, and PMF, although it includes other related clinicopathologic entities, according to the World Health Organization (WHO) classification system. In 2005, William Vainchenker and others described a Janus kinase 2 mutation ( JAK2 V617F) in MPN and this was followed by a series of additional descriptions of mutations that directly or indirectly activate JAK‐STAT: JAK2 exon 12, myeloproliferative leukemia virus oncogene ( MPL ) and calreticulin ( CALR ) mutations. The discovery of these, mostly mutually exclusive, “driver” mutations has contributed to revisions of the WHO diagnostic criteria and risk stratification in MPN. Mutations other than JAK2 , CALR and MPL have also been described in MPN and shown to provide additional prognostic information. From the standpoint of treatment, over the last 50 years, Louis Wasserman from the Unites States and Tiziano Barbui from Italy had skillfully organized and led a number of important clinical trials, whose results form the basis for current treatment strategies in MPN. More recently, allogeneic stem cell transplant, as a potentially curative treatment modality, and JAK inhibitors, as palliative drugs, have been added to the overall therapeutic armamentarium in myelofibrosis. In the current review, I will summarize the important advances made in the last 10 years regarding the science and practice of MPN. Am. J. Hematol. 91:50–58, 2016. © 2015 Wiley Periodicals, Inc.
Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study
Authors: Jonathan Mermin, Willy Were, John Paul Ekwaru, David Moore, Robert Downing, Prosper Behumbiize, John R Lule, Alex Coutinho, Jordan Tappero, Rebecca Bunnell
Journal: The Lancet (2008)
Glycolysis Back in the Limelight: Systemic Targeting of HK2 Blocks Tumor Growth
Authors: Susana Ros, Almut Schulze
Journal: Cancer Discovery (2013)

In a recent issue of Cancer Cell, Patra and colleagues report findings that underscore the importance of Hexokinase 2 (HK2) in tumor initiation and maintenance. The authors also show that HK2 can be systemically deleted without adverse physiologic consequences. These findings provide attractive insights into HK2 deletion as a potential therapeutic intervention for cancer.
Movement of Labeled Cholesterol Between Plasma Lipoprotein and Normal Arterial Wall across the Intimal Surface
Authors: SEYMOUR DAYTON, SAM HASHIMOTO
Journal: Circulation Research (1966)

Normal rat aortas were incubated with their intimal surfaces in contact with a lipoprotein solution containing isotopically labeled free cholesterol. Uptake of cholesterol by the tissue increased with increasing concentration toward a plateau level. Maximum uptake of free cholesterol was estimated to be 13 µg/cm 2 per 24 hours, and uptake at physiological cholesterol concentration was 7.9 µg/cm 2 per 24 hours. Aortas containing labeled cholesterol were prepared by intragastric administration of cholesterol-7α- 3 H to normal rats. Experiments in vitro with these aortas demonstrated that efflux across the intimal surface was dependent upon presence of lipoprotein in the medium. This efflux was not retarded by prior boiling of the tissue. These results support suggestions that movement of labeled free cholesterol from plasma into the arterial wall may be largely the result of a physicochemical exchange between lipoprotein and endothelium.
Chlormethiazole inhibition of cytochrome P450 2E1 as assessed by chlorzoxazone hydroxylation in humans
Authors: A C Gebhardt, D Lucas, J Menez, H K Seitz
Journal: Hepatology (1997)

Chlormethiazole is a sedative and anticonvulsive drug used in the treatment of alcohol withdrawal. Because it had been reported that chlormethiazole inhibits the alcohol-inducible cytochrome P450 2E1 in rat liver, we investigated the in vivo and in vitro effect of this drug on cytochrome P450 2E1 in human beings. The activity of this cytochrome was assessed using chlorzoxazone as a probe. The 6-hydroxychlorzoxazone-chlorzoxazone blood concentration ratio, reflecting the cytochrome P450 2E1 activity, was determined in 10 controls and in 24 alcoholic patients who had entered a hospital for detoxification. Alcoholic patients were administered either chlormethiazole (1.3-2.3 g/d) or chlorazepate (100-300 mg/d) as a sedative. Cytochrome P450 2E1 activity was significantly increased in alcoholic patients treated with chlorazepate (1.16 +/- 0.40 vs. 0.27 +/- 0.03, P < .05). In contrast, chlormethiazole treatment inhibited chlorzoxazone hydroxylation almost totally (0.046 +/- 0.03, P < .001). After 7-14 days of ethanol withdrawal, alcoholic patients treated with chlorazepate had ratio values similar to those of controls (0.31 +/- 0.05), whereas values from alcoholic patients treated with chlormethiazole remained low (0.049 +/- 0.01) even though chlormethiazole doses were gradually decreased. Pharmacokinetic studies in controls showed that chlormethiazole-mediated inhibition was present even when chlormethiazole was not detectable in the blood. In addition, the effect of chlormethiazole on cytochrome P450 2E1 was studied in vitro using human liver microsomes. Dixon plot analyses showed a noncompetitive inhibition (Ki = 12 micromol/L). These data clearly show that chlormethiazole is an efficient inhibitor of chlorzoxazone metabolism and thus of cytochrome P450 2E1 activity in human beings. Because cytochrome P450 2E1 induction after chronic ethanol consumption has detrimental effects on the liver through free radical formation, treatment of alcohol detoxification with chlormethiazole may be beneficial.
Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients
Authors: T. Koike, M. Harigai, S. Inokuma, N. Ishiguro, J. Ryu, T. Takeuchi, S. Takei, Y. Tanaka, K. Ito, H. Yamanaka
Journal: Annals of the Rheumatic Diseases (2011)

An interim analysis of an all-patient postmarketing surveillance programme in Japan to investigate the safety of tocilizumab for the treatment of rheumatoid arthritis (RA) in the real world.This analysis included 3881 patients. Patients received 8 mg/kg of tocilizumab every 4 weeks, and were observed for 28 weeks. Data on baseline characteristics and adverse events (AE) were collected.Total and serious AE were reported as 167 and 27 events/100 patient-years, respectively. The most frequent AE and serious AE were infections. Logistic regression analysis identified the following risk factors for the development of serious infection: concurrent or medical history of respiratory disorders; prednisolone dose at baseline ≥5 mg/day; and age ≥65 years. Twenty-five patients died, and the standardised mortality ratio, with the Japanese general population in 2008 as reference, was 1.66, similar to the results from the Japanese cohort study for RA patients.Tocilizumab is acceptably safe in the real clinical setting. Tocilizumab needs to be used with consideration of the benefit-risk balance to avoid serious infections in elderly patients and those on high doses of corticosteroids or with a concurrent or medical history of respiratory disorders.