tbuckley/cabot-search huggingface dataset:
Limited resection of pancreatic cancer in high-risk patients can result in a second primary: Table 1
Authors: T P Potjer, D K Bartsch, E P Slater, E Matthäi, B A Bonsing, H F A Vasen
Journal: Gut (2015)

15%) had abdominal bloating in Gp-L, while 3 (5%) patients experienced abdominal pain and nausea in rifaximin, but no patient was withdrawn from the trial due to these adverse effects.Baseline MELD score, Child-Turcotte-Pugh score, bilirubin, arterial ammonia, heart rate, mean arterial pressure and total leucocyte count significantly correlated with development of HE.On multivariate analysis, only baseline arterial ammonia and blood transfusion requirement during hospital stay were the predictors of development of HE (table 3).The results of two recently published meta-analyses which compared the efficacy of oral non-absorbable disaccharides versus rifaximin in the management HE showed that both lactulose and rifaximin are equally effective and rifaximin is better tolerated. 6 7In our study, rifaximin was not superior to lactulose for prophylaxis of HE in patients of cirrhosis with AVB and well tolerated.It will be worthwhile to give rifaximin or lactulose as a standard treatment in the management of AVB in patients with cirrhosis to prevent HE considering the prognosis, burden and associated cost in the management of HE.
The effect of a single inhaled dose of a VLA‐4 antagonist on allergen‐induced airway responses and airway inflammation in patients with asthma
Authors: A. J. Ravensberg, B. Luijk, P. Westers, P. S. Hiemstra, P. J. Sterk, J. W. Lammers, K. F. Rabe
Journal: Allergy (2006)

Adhesion molecule very late antigen‐4 (VLA‐4) is implicated in the recruitment and activation of inflammatory cells in asthma, including eosinophils, T cells and mast cells. VLA‐4 antagonists have been proposed as a new anti‐inflammatory treatment modality for asthma. Therefore, we investigated whether a single inhaled dose of VLA‐4 antagonist GW559090X could protect against allergen‐induced changes in airway responses and airway inflammation in patients with asthma. We performed a randomized, double‐blind, three‐way crossover study with single inhaled doses of 3 mg of GW559090X, 500 μ g of fluticasone propionate (FP) or placebo in 15 patients with mild intermittent asthma, controlled with short‐acting β 2 ‐agonists only. All patients developed a late asthmatic response (LAR) after allergen inhalation during screening. Study medication was administered 30 min prior to allergen challenge. Pre‐dose and 24 h post‐dose PC 20 methacholine and levels of exhaled nitric oxide (eNO) were determined. At the given dose, VLA‐4 antagonist GW559090X did not attenuate the early asthmatic response (EAR) when compared with placebo: mean AUC 0−2h (± SEM) (%fall h): 27.2 ± 3.7 and 21.9 ± 3.0 respectively ( P = 0.33); nor the LAR: mean AUC 3−8h (± SEM) (%fall h): 98.8 ± 12.9 and 94.8 ± 6.8 respectively ( P = 0.84). However, pretreatment with FP did attenuate both EAR and LAR when compared with placebo: mean AUC 0−2h 11.6 ± 3.3 ( P = 0.024) and mean AUC 3−8h 6.3 ± 7.6 ( P &lt; 0.001). None of these treatments had an effect on allergen‐induced changes in airway hyper‐responsiveness or eNO levels. These findings suggest that VLA‐4 may not play a major role in allergen‐induced airway responses and inflammation in asthma.
Zinc Intake and Biochemical Markers of Bone Turnover in Type 1 Diabetes
Authors: Raelene E. Maser, John N. Stabley, M. James Lenhard, Phyllis Owusu-Griffin, Michelle A. Provost-Craig, William B. Farquhar
Journal: Diabetes Care (2008)

To examine the relationship between Zn nutritive status and biochemical markers of bone turnover in type 1 diabetes.Serum osteocalcin, urine N-telopeptides, and dietary intake data, obtained by 3-day food records, were assessed for 66 individuals with type 1 diabetes.Zn intake correlated with osteocalcin in the group overall (r = 0.48; P < 0.001) but not with N-telopeptides. Examined by sex, both Zn and osteocalcin correlated for men (r = 0.57; P < 0.001), but the correlation did not reach statistical significance for women (r = 0.34; P = 0.09). A direct-entry linear regression model with osteocalcin as the dependent variable was performed. Duration, sex, A1C, insulin use per kilogram, total calorie intake, and Zn intake were entered as potential independent variables. The model was statistically significant (R(2) = 0.32; P < 0.01). Zn intake (P < 0.001), however, was the only independent correlate of osteocalcin.This study provides evidence of a positive relationship between Zn intake and osteocalcin in type 1 diabetes.
Incidence of inhibitors in patients with severe and moderate hemophilia a treated with factor VIII concentrates
Authors: Iise Schwarzinger, Ingrid Pabinger, Christian Korninger, Ferdinand Haschke, Michael Kundi, Herwig Niessner, Klaus Lechner
Journal: American Journal of Hematology (1987)

Abstract Recent data published on the prevalence of inhibitors to factor VIII in hemophiliacs on treatment show great variations, with prevalence rates ranging from 3.6 to 14.2%. We have studied the cumulative risk of inhibitor development in a cohort of 62 patients with hemophilia A. All patients were born after 1960, were natives of the Vienna area, had a factor VIII activity of less than 5%, and were treated at least once. Using the method of Cutler and Ederer, the cumulative risk of inhibitor development was found to be 24% at the age of 25 years. Most inhibitors developed between the ages of 3 and 7 years. The current prevalence of F VIII inhibitors in the group of patients studied is 17.5%. It is concluded that prevalence data underestimate the true risk of inhibitor development.
Evidence that binding site occupancy is necessary and sufficient for effective major histocompatibility complex (MHC) class II transport through the secretory pathway redefines the primary function of class II-associated invariant chain peptides (CLIP).
Authors: G Zhong, F Castellino, P Romagnoli, R N Germain
Journal: The Journal of Experimental Medicine (1996)

Invariant chain (Ii) associates with newly synthesized class II molecules in the endoplasmic reticulum (ER), an interaction that has been shown to interfere with peptide binding to class II molecules. The class II-associated invariant chain peptide (CLIP) region (residues 81-104) of Ii is believed to mediate this inhibition by engaging the binding domain of class II like an antigenic peptide. Together, these findings have given rise to a model in which CLIP association with the class II groove acts to prevent inappropriate presentation of peptides imported into the ER for association with major histocompatibility complex class I molecules. However, the properties of class II molecules synthesized by cells lacking coexpressed Ii are at least superficially inconsistent with this paradigm in that they do not show clear evidence of peptide acquisition. At the same time, we have previously shown the shortest form of Ii still containing CLIP to play an essential role in regulation of early class II molecule assembly and transport in the secretory pathway. Using covalent peptide technology, we now show that occupancy of the class II binding site in the ER regulates class II trafficking to the Golgi complex, an event that is the locus of the major defect in cells of Ii-deficient mice. These data argue that CLIP occupies the class II binding site, not to prevent interaction with short peptides meant for class I, but rather to maintain the structural integrity of class II molecules that are labile without engaged binding regions, and that would also associate with intact proteins in the ER if left unoccupied. By these means, CLIP occupancy of the class II binding site promotes effective export of useful class II molecules for endocytic peptide acquisition.
Power and Color Doppler Ultrasound Settings for Inflammatory Flow: Impact on Scoring of Disease Activity in Patients With Rheumatoid Arthritis
Authors: Søren Torp‐Pedersen, Robin Christensen, Marcin Szkudlarek, Karen Ellegaard, Maria Antonietta D'Agostino, Annamaria Iagnocco, Esperanza Naredo, Peter Balint, Richard J. Wakefield, Arendse Torp‐Pedersen, Lene Terslev
Journal: Arthritis & Rheumatology (2014)

Objective To determine how settings for power and color Doppler ultrasound sensitivity vary on different high‐ and intermediate‐range ultrasound machines and to evaluate the impact of these changes on Doppler scoring of inflamed joints. Methods Six different types of ultrasound machines were used. On each machine, the factory setting for superficial musculoskeletal scanning was used unchanged for both color and power Doppler modalities. The settings were then adjusted for increased Doppler sensitivity, and these settings were designated study settings. Eleven patients with rheumatoid arthritis (RA) with wrist involvement were scanned on the 6 machines, each with 4 settings, generating 264 Doppler images for scoring and color quantification. Doppler sensitivity was measured with a quantitative assessment of Doppler activity: color fraction. Higher color fraction indicated higher sensitivity. Results Power Doppler was more sensitive on half of the machines, whereas color Doppler was more sensitive on the other half, using both factory settings and study settings. There was an average increase in Doppler sensitivity, despite modality, of 78% when study settings were applied. Over the 6 machines, 2 Doppler modalities, and 2 settings, the grades for each of 7 of the patients varied between 0 and 3, while the grades for each of the other 4 patients varied between 0 and 2. Conclusion The effect of using different machines, Doppler modalities, and settings has a considerable influence on the quantification of inflammation by ultrasound in RA patients, and this must be taken into account in multicenter studies.
Vaccination Against Leprosy
Authors: J. A. K. Brown
Journal: BMJ (1966)

One and a half hours later the right testicle was explored under local anaesthesia.At opera- uon it was found to be very oedematous and congested, and rotated through 180°.There was no evidence of a haematoma.The cord was untwisted and the testicle anchored to the scrotal wall.The wound was drained.The patient made an uneventful recovery, apart from post- operative retention of urine, for which he had to be catheterized on one occasion.He was seen subsequently on 30 April 1965 at follow-up when he was found to have a normal-sized testicle.
Matrix Metalloproteinase-2 in a Murine Model of Infantile-Type Polycystic Kidney Disease
Authors: CAROLYN A. RANKIN, YOSHIFUMI ITOH, CHUNQIAO TIAN, DONNA M. ZIEMER, JAMES P. CALVET, VINCENT H. GATTONE
Journal: Journal of the American Society of Nephrology (1999)

Abstract. It was previously found that elevated levels of matrix metalloproteinase (MMP)-2 (gelatinase A) and -9 (gelatinase B) were synthesized and secreted into the medium by cultured kidney tubules derived from cystic C57BL/6J- cpk mice. To determine whether increased synthesis and secretion occur in vivo in this mouse model of polycystic kidney disease, kidney protein extracts, mRNA, and tissue sections were compared for expression and activity of MMP-2 and -9. Although both MMP were detected in tissue extracts, the differences in expression levels and activity in normal and cystic kidneys were far greater for MMP-2. High levels of MMP-2 seemed to result from increased expression by the cystic kidneys predominantly in the second and third postnatal weeks (a time when the kidneys are undergoing rapid cystic enlargement). Much of the increased MMP was present in the inactive zymogen form, although active enzyme was readily detected by sodium dodecyl sulfate-polyacrylamide gel zymography and in situ zymography. MMP-2 was abnormally localized to the interstitium and to foci between cysts, suggesting that MMP-2 may regulate collagen accumulation at those sites, thus allowing cyst enlargement and limiting the severity of interstitial fibrosis.
A Role for Glial Cell–Derived Neurotrophic Factor–Induced Expression by Inflammatory Cytokines and RET/GFRα1 Receptor Up-regulation in Breast Cancer
Authors: Selma Esseghir, S. Katrina Todd, Toby Hunt, Richard Poulsom, Ivan Plaza-Menacho, Jorge S. Reis-Filho, Clare M. Isacke
Journal: Cancer Research (2007)

By screening a tissue microarray of invasive breast tumors, we have shown that the receptor tyrosine kinase RET (REarranged during Transfection) and its coreceptor GFR alpha 1 (GDNF receptor family alpha-1) are overexpressed in a subset of estrogen receptor-positive tumors. Germ line-activating oncogenic mutations in RET allow this receptor to signal independently of GFR alpha 1 and its ligand glial cell-derived neurotrophic factor (GDNF) to promote a spectrum of endocrine neoplasias. However, it is not known whether tumor progression can also be driven by receptor overexpression and whether expression of GDNF, as has been suggested for other neurotrophic factors, is regulated in response to the inflammatory microenvironment surrounding many epithelial cancers. Here, we show that GDNF stimulation of RET(+)/GFR alpha 1(+) MCF7 breast cancer cells in vitro enhanced cell proliferation and survival, and promoted cell scattering. Moreover, in tumor xenografts, GDNF expression was found to be up-regulated on the infiltrating endogenous fibroblasts and to a lesser extent by the tumor cells themselves. Finally, the inflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta, which are involved in tumor promotion and development, were found to act synergistically to up-regulate GDNF expression in both fibroblasts and tumor cells. These data indicate that GDNF can act as an important component of the inflammatory response in breast cancers and that its effects are mediated by both paracrine and autocrine stimulation of tumor cells via signaling through the RET and GFR alpha 1 receptors.
Long-term efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. An Italian multicenter, randomized trial
Authors: Giuseppe Barbaro, Franco Zechini, Adriano M. Pellicelli, Ruggiero Francavilla, Gaetano Scotto, Donato Bacca, Marcello Bruno, Sergio Babudieri, Mauro Annese, Filippo Matarazzo, Gabriele Di Stefano, Giorgio Barbarini
Journal: Journal of Hepatology (2001)
Stent Thrombosis After Successful Sirolimus-Eluting Stent Implantation
Authors: Allen Jeremias, Brett Sylvia, Jonathan Bridges, Ajay J. Kirtane, Brian Bigelow, Duane S. Pinto, Kalon K.L. Ho, David J. Cohen, Lawrence A. Garcia, Donald E. Cutlip, Joseph P. Carrozza
Journal: Circulation (2004)

Stent thrombosis (ST) is a rare but devastating complication of coronary stent implantation, occurring in 0.5% to 1.9% of patients with bare metal stents. The incidence of ST with drug-eluting stents is less well studied, particularly among patients outside of clinical trials.The aim of this study was to evaluate the incidence and potential risk factors for ST in patients receiving sirolimus-eluting stents (SES) in the "real world" after commercial release in the United States in April 2003. All 652 patients who underwent SES implantation (776 lesions treated) at our institution between April and October 2003 were followed up prospectively after the procedure (median follow-up 100 days). During that period, 7 patients (1.1%, 95% CI 0.4% to 2.2%) developed ST within a range of 2 to 13 days, and 1 patient had an ST-elevation myocardial infarction on day 39 with evidence of thrombus within the SES at angiography. Patients with an ST had significantly smaller final nominal balloon diameters (2.75 versus 3.00 mm, P=0.04), and in 4 (57%) of the 7 patients with ST versus 1.7% of patients without ST (P<0.001), antiplatelet therapy had been discontinued after the procedure. Among the ST patients, 1 died and 5 had myocardial infarctions.In this single-center experience, the incidence of ST after SES implantation was approximately 1%, which is within the expected range of bare metal stents. The discontinuation of antiplatelet therapy was strongly associated with the development of ST in this patient population.
Bone Conduction in Otosclerosis
Authors: E. R. G. Passe
Journal: BMJ (1948)

Disk Lesions and Osteopathy SIR,-Dr.G. Macdonald's partisan letter (April 3, p. 663) really cannot be allowed to stand unchallenged.A. T. Still (the founder of osteopathy) postulated that all diseases arose from pressure on arteries and nerves as the result of vertebral dis- placements.If medical research has led to the recognition of spinal disk protrusion, and if this is now claimed as the "vindication of osteopathy, it must prove the opposite of Dr.Macdonald's contention.Surely it shows that the whole of osteopathic doctrine, except in that small particular, is false.-Iam, etc., London, W.1.
Cancer risk in primary biliary cirrhosis: A population-based study from Sweden
Authors: Lars Lööf, Hans-Olov Adami, Pär Sparén, Åke Danielsson, Ljusk Siw Eriksson, Rolf Hultcrantz, Stefan Lindgren, Rolf Olsson, Hanne Prytz, Bengt-Olof Ryden, Hanna Sandberg-Gertzen, Sven Wallerstedt
Journal: Hepatology (1994)

ABSTRACT A cohort of 559 patients in Sweden who satisfied predetermined criteria for the diagnosis of primary biliary cirrhosis was followed with respect to the incidence of cancer during the period of 1958 to 1988. The mean follow–up time from the time of primary biliary cirrhosis diagnosis was 9.0 ± 54 yr. During the follow–up period, 148 patients died and the primary cause of death was liver insufficiency. An overall excess risk for cancer, standardized incidence ratio 1.6; 95% confidence interval, 1.1 to 2.2, was found in the cohort. In contrast to previous reports, we found no excess risk for breast cancer (standardized incidence ratio, 0.9; 95% confidence interval, 0.3 to 2.1). The number of hepatocellular cancers in the primary biliary cirrhosis cohort did not significantly differ from expected (standardized incidence ratio, 2.91; 95% confidence interval, 0.4 to 10.5). (Hepatology 1994;20:101-104.)
Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus
Authors: Joshua D. Ramsay, Ryan Evanoff, Tom E. Wilkinson, Thomas J. Divers, Donald P. Knowles, Robert H. Mealey
Journal: Hepatology (2015)

Equine hepacivirus (EHCV; nonprimate hepacivirus) is a hepatotropic member of the Flaviviridae family that infects horses. Although EHCV is the closest known relative to hepatitis C virus (HCV), its complete replication kinetics in vivo have not been described, and direct evidence that it causes hepatitis has been lacking. In this study, we detected EHCV in 2 horses that developed post-transfusion hepatitis. Plasma and serum from these horses were used to experimentally transmit EHCV to 4 young adult Arabian horses, two 1-month-old foals (1 Arabian and 1 Arabian-pony cross), and 2 foals (1 Arabian and 1 Arabian-pony cross) with severe combined immunodeficiency (SCID). Our results demonstrated that EHCV had infection kinetics similar to HCV and that infection was associated with acute and chronic liver disease as measured by elevations of liver-specific enzymes and/or by histopathology. Although most of these animals were coinfected with equine pegivirus (EPgV), also a flavivirus, EPgV viral loads were much lower and often undetectable in both liver and blood. Three additional young adult Arabian-pony crosses and 1 SCID foal were then inoculated with plasma containing only EHCV, and evidence of mild hepatocellular damage was observed. The different levels of liver-specific enzyme elevation, hepatic inflammation, and duration of viremia observed during EHCV infection suggested that the magnitude and course of liver disease was mediated by the virus inoculum and/or by host factors, including breed, age, and adaptive immune status.This work documents the complete infection kinetics and liver pathology associated with acute and chronic EHCV infection in horses and further justifies it as a large animal model for HCV.
Collagen-induced Arthritis Is Reduced in 5-Lipoxygenase-activating Protein-deficient Mice
Authors: Richard J. Griffiths, MaryAlice Smith, Marsha L. Roach, Jeffrey L. Stock, Ethan J. Stam, A.J. Milici, Deborah N. Scampoli, James D. Eskra, Robert S. Byrum, Beverly H. Koller, John D. McNeish
Journal: The Journal of Experimental Medicine (1997)

Collagen-induced arthritis in the DBA/1 mouse is an experimental model of human rheumatoid arthritis. To examine the role of leukotrienes in the pathogenesis of this disease, we have developed embryonic stem (ES) cells from this mouse strain. Here, we report that DBA/1 mice made deficient in 5-lipoxygenase-activating protein (FLAP) by gene targeting in ES cells develop and grow normally. Zymosan-stimulated leukotriene production in the peritoneal cavity of these mice is undetectable, whereas they produce substantial amounts of prostaglandins. The inflammatory response to zymosan is reduced in FLAP-deficient mice. The severity of collagen-induced arthritis in the FLAP-deficient mice was substantially reduced when compared with wild-type or heterozygous animals. This was not due to an immunosuppressive effect, because anti-collagen antibody levels were similar in wild-type and FLAP-deficient mice. These data demonstrate that leukotrienes play an essential role in both the acute and chronic inflammatory response in mice.
A pilot study of autologous tumor lysate-loaded dendritic cell vaccination combined with sunitinib for metastatic renal cell carcinoma
Authors: Hirokazu Matsushita, Yutaka Enomoto, Haruki Kume, Tohru Nakagawa, Hiroshi Fukuhara, Motofumi Suzuki, Tetsuya Fujimura, Yukio Homma, Kazuhiro Kakimi
Journal: Journal for ImmunoTherapy of Cancer (2014)

Sunitinib, a tyrosine kinase inhibitor currently in use for the treatment of metastatic renal cell carcinoma (mRCC), has been reported to modulate immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in addition to exerting anti-angiogenic effects. We conducted a clinical trial of dendritic cell (DC)-based immunotherapy together with sunitinib in mRCC patients in an effort to enhance immunotherapeutic efficacy by inhibiting immunosuppressive cells.Patients aged ≥20 years with advanced or recurrent mRCC who underwent nephrectomy were eligible for this study. Autologous tumor samples were obtained by surgery under aseptic conditions and used for preparing autologous tumor lysate. About 4 weeks after surgery, leukapheresis was performed to isolate peripheral blood mononuclear cells (PBMCs). DCs were generated from adherent PBMCs in the presence of recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) (500 IU/ml) and recombinant human IL-4 (500 IU/ml). Autologous tumor lysate was loaded into mature DC by electroporation. Eight patients were enrolled in the study and received sunitinib at a dose of 50 mg p.o. daily for 28 days followed by 14 days of rest. Tumor lysate-loaded DCs were administered subcutaneously every two weeks, with concomitant sunitinib.No severe adverse events related to vaccination were observed. Sunitinib decreased the frequencies of MDSCs in peripheral blood of 5 patients and of Tregs in 3. Tumor lysate-reactive CD4 or CD8 T cell responses were observed in 5 patients, 4 of whom showed decreased frequencies of Tregs and/or MDSCs. The remaining 3 patients who failed to develop tumor-reactive T cell responses had high levels of IL-8 in their sera and did not show consistent reductions in MDSCs and Tregs.DC-based immunotherapy combined with sunitinib is safe and feasible for patients with mRCC.UMIN000002136.