tbuckley/cabot-search huggingface dataset:
Switching From Morphine to Methadone to Improve Analgesia and Tolerability in Cancer Patients: A Prospective Study
Authors: Sebastiano Mercadante, Alessandra Casuccio, Fabio Fulfaro, Liliana Groff, Roberto Boffi, Patrizia Villari, Vittorio Gebbia, Carla Ripamonti
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the clinical benefits of switching from morphine to oral methadone in patients who experience poor analgesia or adverse effects from morphine. PATIENTS AND METHODS: Fifty-two consecutive cancer patients receiving oral morphine but with uncontrolled pain and/or moderate to severe opioid adverse effects were switched to oral methadone administered every 8 hours using different dose ratios. Intensity of pain and adverse effects were assessed daily, and the symptom distress score (DS) was calculated before and after switching. RESULTS: Data were analyzed for 50 patients. Switching was considered effective in 80% of the patients; results were achieved in an average of 3.65 days. In the 10 patients who switched to methadone because of uncontrolled pain, a significant reduction in pain intensity (P &lt; .005) and an average of a 33% increase in methadone doses necessary (P &lt; .01) were found after an average of 3.5 days. DS significantly decreased from an average of 8.4 to 4.5 (P &lt; .0005). In the 32 patients switching because of uncontrolled pain and morphine-related adverse effects, significant improvement was found in pain intensity (P &lt; .0005), nausea and vomiting (P &lt; .03), constipation (P &lt; .001), and drowsiness (P &lt; .01), but a significant increase in the methadone dose of an average of 20% (P &lt; .004) was required. CONCLUSION: In most patients with cancer pain referred for poor pain control and/or adverse effects, switching to oral methadone is a valid therapeutic option. In the clinical setting of poor pain control, higher doses of methadone are necessary with respect to the equianalgesic calculated dose ratios previously published.
<i>PHOX2B</i> Is a Novel and Specific Marker for Minimal Residual Disease Testing in Neuroblastoma
Authors: Janine Stutterheim, Annemieke Gerritsen, Lily Zappeij-Kannegieter, Ilona Kleijn, Rob Dee, Lotty Hooft, Max M. van Noesel, Marc Bierings, Frank Berthold, Rogier Versteeg, Huib N. Caron, C. Ellen van der Schoot, Godelieve A.M. Tytgat
Journal: Journal of Clinical Oncology (2008)

Polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) in neuroblastoma can be used to monitor therapy response and to evaluate stem cell harvests. Commonly used PCR markers, tyrosine hydroxylase (TH) and GD2 synthase, have expression in normal tissues, thus limiting MRD detection. To identify a more specific MRD marker, we tested PHOX2B.To determine PHOX2B, TH, and GD2 synthase expression in normal tissues, it was measured by real-time quantitative PCR in samples of normal bone marrow (BM; n = 51), peripheral blood (PB; n = 37), and peripheral-blood stem cells (PBSCs; n = 24). Then, 289 samples of 101 Dutch patients and 47 samples of 43 German patients were tested for PHOX2B and TH; these samples included 52 tumor, 214 BM, 32 BM, and 38 PBSC harvests. Of the 214 BM samples, 167 were compared with cytology, and 47 BM samples were compared with immunocytology (IC).In contrast to TH and GD2 synthase, PHOX2B was not expressed in any of the normal samples. In patient samples, PHOX2B was detected in 32% cytology-negative and in 14% IC-negative samples and in 94% of cytology-positive and in 90% of IC-positive BM samples. Overall, PHOX2B was positive in 43% compared with 31% for TH. In 24% of all samples, TH expression was inconclusive, which is similar to expression found in normal tissues. In 42% of these samples, PHOX2B expression was positive.PHOX2B is superior to TH and GD2 synthase in specificity and sensitivity for MRD detection of neuroblastoma by using real-time quantitative PCR. We propose to include PHOX2B in additional prospective MRD studies in neuroblastoma alongside TH and other MRD markers.
Human papillomavirus type 6-induced condylomata: an unusual complication of intertrigo
Authors: J.A. YELL, R. SINCLAIR, S. MANN, K. FLEMING, T.J. RYAN
Journal: British Journal of Dermatology (1993)

A 79-year-old virgo intacta presented with a 20-year-history of intertrigo, and a 3-month history of superimposed warty masses beneath both breasts and in the groin and perianal areas. There was no evidence of immunosuppression. Histology of the warty lesions showed squamous papillomata, with evidence of wart virus infection. Human papillomavirus (HPV) type 6 was identified by in situ DNA hybridization, in the submammary lesions. This is an unusual manifestation of both intertrigo and wart virus infection. HPV-6 is classically found in anogenital warts. We assume that these warts were acquired by a non-venereal route and/or by congenital infection some 78 years ago. We suggest that it is the warm, moist environment, rather than the specific site, which encourages HPV-6 to flourish.
Diabetes Is an Independent Predictor for Severe Osteoarthritis
Authors: Georg Schett, Arndt Kleyer, Carlo Perricone, Enijad Sahinbegovic, Annamaria Iagnocco, Jochen Zwerina, Rolando Lorenzini, Franz Aschenbrenner, Francis Berenbaum, Maria-Antonietta D’Agostino, Johann Willeit, Stefan Kiechl
Journal: Diabetes Care (2012)

To evaluate if type 2 diabetes is an independent risk predictor for severe osteoarthritis (OA).Population-based cohort study with an age- and sex-stratified random sample of 927 men and women aged 40-80 years and followed over 20 years (1990-2010).Rates of arthroplasty (95% CI) were 17.7 (9.4-30.2) per 1,000 person-years in patients with type 2 diabetes and 5.3 (4.1-6.6) per 1,000 person-years in those without (P < 0.001). Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard ratios (95% CI), 3.8 (2.1-6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1-3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA. The probability of arthroplasty increased with disease duration of type 2 diabetes and applied to men and women, as well as subgroups according to age and BMI. Our findings were corroborated in cross-sectional evaluation by more severe clinical symptoms of OA and structural joint changes in subjects with type 2 diabetes compared with those without type 2 diabetes.Type 2 diabetes predicts the development of severe OA independent of age and BMI. Our findings strengthen the concept of a strong metabolic component in the pathogenesis of OA.
Patterns of Positive Selection in Seven Ant Genomes
Authors: Julien Roux, Eyal Privman, Sébastien Moretti, Josephine T. Daub, Marc Robinson-Rechavi, Laurent Keller
Journal: Molecular Biology and Evolution (2014)

The evolution of ants is marked by remarkable adaptations that allowed the development of very complex social systems. To identify how ant-specific adaptations are associated with patterns of molecular evolution, we searched for signs of positive selection on amino-acid changes in proteins. We identified 24 functional categories of genes which were enriched for positively selected genes in the ant lineage. We also reanalyzed genome-wide data sets in bees and flies with the same methodology to check whether positive selection was specific to ants or also present in other insects. Notably, genes implicated in immunity were enriched for positively selected genes in the three lineages, ruling out the hypothesis that the evolution of hygienic behaviors in social insects caused a major relaxation of selective pressure on immune genes. Our scan also indicated that genes implicated in neurogenesis and olfaction started to undergo increased positive selection before the evolution of sociality in Hymenoptera. Finally, the comparison between these three lineages allowed us to pinpoint molecular evolution patterns that were specific to the ant lineage. In particular, there was ant-specific recurrent positive selection on genes with mitochondrial functions, suggesting that mitochondrial activity was improved during the evolution of this lineage. This might have been an important step toward the evolution of extreme lifespan that is a hallmark of ants.
Granular cell tumour of the bronchus: bronchoscopic and clinical features.
Authors: O G Hernandez, E F Haponik, W R Summer
Journal: Thorax (1986)

Granular cell tumours are uncommon, generally benign neoplasms of uncertain origin that occasionally affect the tracheobronchial tree. Their incidence seems to be increasing, despite the fact that such tumours are rarely suspected on clinical grounds or bronchoscopic appearance. Here we describe three cases of endobronchial granular cell tumours, one of which regressed spontaneously after biopsy, and review previous accounts of their bronchoscopic and clinical features.
Prospective Randomized Controlled Trial to Evaluate Effectiveness of Registered Dietitian–Led Diabetes Management on Glycemic and Diet Control in a Primary Care Setting in Taiwan
Authors: Meng-Chuan Huang, Chih-Cheng Hsu, Huan-Sen Wang, Shyi-Jang Shin
Journal: Diabetes Care (2009)

OBJECTIVE In this randomized controlled trial we evaluated the effect of registered dietitian–led management of diabetes on glycemic control and macronutrient intake in type 2 diabetic patients in primary care clinics in Taiwan and studied the association between changes in macronutrient intake and glycemic measures. RESEARCH DESIGN AND METHODS We recruited 154 adult patients with type 2 diabetes and randomly assigned them to a routine care control group (n = 79) or a registered dietitian–led intervention group (n = 75) who received on-site diabetic self-management education every 3 months over 12 months. RESULTS Over the 1-year period, neither the intervention group (n = 75) nor the control group (n = 79) had significant changes in A1C, whereas the intervention patients with poorly controlled baseline A1C (≥7%) (n = 56) had significantly greater improvements in A1C and fasting plasma glucose than the control subjects (n = 60) (−0.7 vs. −0.2%, P = 0.034; −13.4 vs. 16.9 mg/dl, P = 0.007) during the same period. We also found significant net intervention-control group differences in overall energy intake (−229.06 ± 309.16 vs. 56.10 ± 309.41 kcal/day) and carbohydrate intake (−31.24 ± 61.53 vs. 7.15 ± 54.09 g/day) (P &amp;lt; 0.001) in patients with poorly controlled A1C. Multivariable adjusted modeling revealed an independent association between changes in carbohydrate intake and A1C in the intervention group (n = 56; β = 0.10, SEM = 0.033, P = 0.004). CONCLUSIONS On-site registered dietitian–led management of diabetes can improve glycemic control in patients with poorly managed type 2 diabetes in primary care clinics in Taiwan. A reduction in carbohydrate intake may improve glycemic status.
VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents
Authors: David F Stojdl, Brian D Lichty, Benjamin R tenOever, Jennifer M Paterson, Anthony T Power, Shane Knowles, Ricardo Marius, Jennifer Reynard, Laurent Poliquin, Harold Atkins, Earl G Brown, Russell K Durbin, Joan E Durbin, John Hiscott, John C Bell
Journal: Cancer Cell (2003)
Fibulin-5 Is a Novel Binding Protein for Extracellular Superoxide Dismutase
Authors: Andrew D. Nguyen, Shinichi Itoh, Viktoria Jeney, Hiromi Yanagisawa, Mitsuaki Fujimoto, Masuko Ushio-Fukai, Tohru Fukai
Journal: Circulation Research (2004)

The extracellular superoxide dismutase (ecSOD) plays an important role in atherosclerosis and endothelial function by modulating levels of the superoxide anion (O2*-) in the extracellular space. Although heparan sulfate proteoglycan is an important ligand for ecSOD, little is known about other biological binding partners of ecSOD. The goal of this study was to identify novel proteins that interact with ecSOD. A yeast two-hybrid screening of a human aorta cDNA library using ecSOD as bait identified fibulin-5 as a predominant binding protein for ecSOD. Further analysis showed that the binding domain of ecSOD within fibulin-5 mapped to its C-terminal domain. In vitro pulldown assays and coimmunoprecipitation analysis further confirmed that ecSOD interacts with fibulin-5 in vitro and in vivo. Studies using fibulin-5-/- mice indicated that fibulin-5 is required for binding of ecSOD to vascular tissue. Importantly, the decrease in tissue-bound ecSOD levels in aortas from fibulin-5-/- mice was associated with an increase in vascular O2*- levels. Furthermore, immunohistochemical analysis using ApoE-/- mice suggested a codistribution of ecSOD and fibulin-5 in atherosclerotic vessels. In summary, we provide in this study the first evidence that the ecSOD-fibulin-5 interaction is required for ecSOD binding to vascular tissues, thereby regulating vascular O2*- levels. This interaction may represent a novel mechanism for controlling vascular redox state in the extracellular space in various cardiovascular diseases such as atherosclerosis and hypertension in which oxidative stress is increased.
Why Does Airway Inflammation Persist? Is It Failure to Treat Early?
Authors: SØREN PEDERSEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

At present there is no direct evidence to demonstrate that early use of antiinflammatory therapy will reduce the persistence of airway inflammation. However, there is evidence that early treatment with inhaled corticosteroids is associated with better clinical effects, including a modification of the course of asthma so that it becomes easier to treat. Exactly how or if this relates to differences in control of airway inflammation is not known.
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Authors: Bolormaa Vandanmagsar, Yun-Hee Youm, Anthony Ravussin, Jose E Galgani, Krisztian Stadler, Randall L Mynatt, Eric Ravussin, Jacqueline M Stephens, Vishwa Deep Dixit
Journal: Nature Medicine (2011)
Predictive value of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injections in patients with rheumatoid arthritis.
Authors: R Luukkainen, M Hakala, E Sajanti, H Huhtala, U Yli-Kerttula, R Hameenkorpi
Journal: Annals of the Rheumatic Diseases (1992)

The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement.
RECTAL PARALDEHYDE BEFORE OPERATION
Authors: J. D. Stewart
Journal: BMJ (1932)

administered per rectum every four hours.This treat- ment seemed to act extremely well in the five cases in which it was tried by the writer.In the Mayo Clinics, 1929, Alvarez suggests the use of choline, which is said to be a normal constituent of intestinal muscle and concerned with maintaining peristalsis.TABLE VII.-Use of Bile Eneinata o.Nof igeNg.Hfours' ative Findings Post-operative Case Years i and Treatment Treatment Result 1 11 72 G e n e r a 1 peritonitis Distension persisted; Cured from ruptured appen-1 oz.bile run into dix; ileus-entero-bowel through stoiny; B. welchii enterostomy tube antitoxin 2 14 38 Localized pelvic peri-Marked post-operative Cured tonitis from ruptured distension and vomit- appendix-local ingdarkbrownfluid; drainage 1 oz.bile in fourhourly enema 3 48 48 Ruptured appendix; Post-operative disten-Cured general peritonitis; sion; vomiting; 2 oz. 2 free concretions bile in saline, fourhourly enemata 4 14 78 General peritonitis; Post-operative disten-Cured ruiptured appendixsion; vomiting; B. enterostomy welcbii; 2 oz.bile in four-hourly enemata 5 15 72 Ruptured appendix; Post-operative vomit-Cured general peritonitis-ing and marked disenterostomy tension; 2 oz.bile in four-hourly enemata SUMMARYIn the treatment of general peritonitis discussed above, successes have been obtained from the use of: (1) operative measures-namely, enterostomy ; (2) B. welchii antitoxin injections; and (3) bile enemata.
Stratification of Health Risk Posed By Allergic Responses at Peanut Threshold Doses: A Pilot Study
Authors: Stefano Luccioli, Jianmei Zhu, David Mark Fleischer, Whitney Hiemstra, Edwin H. Kim, Susan B. Leung, Robert W. Lindblad, Kim E. Mudd, Rene Reames, Pamela H. Steele, Hugh A. Sampson, Scott H. Sicherer, Brian P. Vickery, Ernest K. Kwegyir-Afful
Journal: Journal of Allergy and Clinical Immunology (2015)
Sterol synthesis and low density lipoprotein clearance in vivo in the pregnant rat, placenta, and fetus. Sources for tissue cholesterol during fetal development.
Authors: W M Belknap, J M Dietschy
Journal: Journal of Clinical Investigation (1988)

Whereas the greatest relative increase in body mass occurs during the third trimester of fetal life, the source of the cholesterol that supports this growth is uncertain. These studies used [3H]water and 125I-cellobiose-labeled low density lipoproteins to quantitate absolute rates of cholesterol acquisition in vivo by the fetus of the rat. Preliminary studies demonstrated that [3H]water administered intravenously to the mother rapidly equilibrated with the body pool of water in the fetus and that 22-microgram atoms of H from the water pool were incorporated into each micromole of newly synthesized cholesterol. After administration of [3H]water to pregnant rats, the rates of sterol synthesis per 100 g of whole body weight were severalfold higher in the fetus than in the dams. Individual organs of the dam such as the liver, however, had much higher synthetic rates than those in the fetus. When maternal hepatic cholesterol synthesis was suppressed by cholesterol feeding, newly synthesized cholesterol disappeared from the maternal blood yet there was essentially no change in the rate of appearance of newly synthesized sterol in the fetus, placenta, and fetal membranes. The placenta did take up low density lipoproteins at rates equal to about one-third of that seen in the maternal liver, but none of the apolipoprotein or cholesterol was transferred to the fetus. These studies indicate that the rat fetus receives little or no cholesterol from the mother but, rather, satisfies its need for cholesterol during fetal development through local synthesis. Furthermore, the fetal membranes appear to be an important site for sterol synthesis in the fetal compartment.
Structure of the Kinase Domain of an Imatinib-Resistant Abl Mutant in Complex with the Aurora Kinase Inhibitor VX-680
Authors: Matthew A. Young, Neil P. Shah, Luke H. Chao, Markus Seeliger, Zdravko V. Milanov, William H. Biggs, Daniel K. Treiber, Hitesh K. Patel, Patrick P. Zarrinkar, David J. Lockhart, Charles L. Sawyers, John Kuriyan
Journal: Cancer Research (2006)

Abstract We present a high-resolution (2.0 Å) crystal structure of the catalytic domain of a mutant form of the Abl tyrosine kinase (H396P; Abl-1a numbering) that is resistant to the Abl inhibitor imatinib. The structure is determined in complex with the small-molecule inhibitor VX-680 (Vertex Pharmaceuticals, Cambridge, MA), which blocks the activity of various imatinib-resistant mutant forms of Abl, including one (T315I) that is resistant to both imatinib and BMS-354825 (dasatinib), a dual Src/Abl inhibitor that seems to be clinically effective against all other imatinib-resistant forms of BCR-Abl. VX-680 is shown to have significant inhibitory activity against BCR-Abl bearing the T315I mutation in patient-derived samples. The Abl kinase domain bound to VX-680 is not phosphorylated on the activation loop in the crystal structure but is nevertheless in an active conformation, previously unobserved for Abl and inconsistent with the binding of imatinib. The adoption of an active conformation is most likely the result of synergy between the His396Pro mutation, which destabilizes the inactive conformation required for imatinib binding, and the binding of VX-680, which favors the active conformation through hydrogen bonding and steric effects. VX-680 is bound to Abl in a mode that accommodates the substitution of isoleucine for threonine at residue 315 (the “gatekeeper” position). The avoidance of the innermost cavity of the Abl kinase domain by VX-680 and the specific recognition of the active conformation explain the effectiveness of this compound against mutant forms of BCR-Abl, including those with mutations at the gatekeeper position. (Cancer Res 2006; 66(2): 1007-14)
Treatment recommendations for psoriatic arthritis
Authors: C T Ritchlin, A Kavanaugh, D D Gladman, P J Mease, P Helliwell, W-H Boehncke, K de Vlam, D Fiorentino, O FitzGerald, A B Gottlieb, N J McHugh, P Nash, A A Qureshi, E R Soriano, W J Taylor
Journal: Annals of the Rheumatic Diseases (2008)

To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion.Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire.Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective.Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.