tbuckley/cabot-search huggingface dataset:
Association Study of Functional Polymorphisms in Genes Involved in Histamine Homeostasis and Multiple NSAID–Triggered Urticaria and/or Angioedema and Anaphylaxis in Patients without Pre-Existing Chronic Urticaria (MNSAID-UA)
Authors: Pedro Ayuso Parejo, Jose Augusto García-Agúndez, Jose A. Cornejo-Garcia, Miguel Blanca, María José Torres, Inmaculada Doña, Maria Salas, Natalia Blanca-López, Gabriela Canto, Carmen Rondon, Paloma Campo, Jose Julio Laguna, F. Javier Fernandez, Carmen Martínez, Elena García-Martín
Journal: Journal of Allergy and Clinical Immunology (2013)
Synaptic Plasticity in the Mammalian Central Nervous System
Authors: N Tsukahara
Journal: Annual Review of Neuroscience (1981)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593.
Authors: M P Mehta, S P Tannehill, S Adak, L Martin, D G Petereit, H Wagner, J F Fowler, D Johnson
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.
A comparison of mitoxantrone and doxorubicin in breast cancer.
Authors: J A Neidhart, D Gochnour, R Roach, D Hoth, D Young
Journal: Journal of Clinical Oncology (1986)

Ninety patients with breast cancer refractory to cyclophosphamide/fluorouracil/methotrexate (CMF) have been randomized in their treatment, receiving either doxorubicin or mitoxantrone. Seventy-nine have received two full courses of therapy. Twelve of the 40 (30%) who initially received doxorubicin responded, whereas eight of the 47 (17%) who received mitoxantrone responded. These rates are not statistically different. The degree of myelosuppression was equivalent. Patients who received mitoxantrone had less nausea, vomiting, alopecia, and fatigue. Controllable clinical congestive heart failure developed in seven patients, and four others had a deterioration of noninvasive measures of cardiac function without clinical failure. One patient with clinical heart failure developing received only doxorubicin and one, only mitoxantrone, whereas the others received both agents. The duration of remission and time lapsed before disease progression were almost identical for the two regimens. This study included a crossover design. Two of 22 (10%) patients receiving doxorubicin and five of 24 (21%) receiving mitoxantrone as secondary therapy responded. This suggests that there is not absolute cross-resistance between these agents. We conclude that the efficacy of these two drugs is comparable in patients refractory to CMF, though the nonhematologic side effects of mitoxantrone are less.
Nociceptive Sensitizers Are Regulated in Damaged Joint Tissues, Including Articular Cartilage, When Osteoarthritic Mice Display Pain Behavior
Authors: Clare Driscoll, Anastasios Chanalaris, Chancie Knights, Heba Ismail, Pradeep K. Sacitharan, Clive Gentry, Stuart Bevan, Tonia L. Vincent
Journal: Arthritis & Rheumatology (2015)

Pain is the most common symptom of osteoarthritis (OA), yet where it originates in the joint and how it is driven are unknown. The aim of this study was to identify pain-sensitizing molecules that are regulated in the joint when mice subjected to surgical joint destabilization develop OA-related pain behavior, the tissues in which these molecules are being regulated, and the factors that control their regulation.Ten-week-old mice underwent sham surgery, partial meniscectomy, or surgical destabilization of the medial meniscus (DMM). Pain-related behavior as determined by a variety of methods (testing of responses to von Frey filaments, cold plate testing for cold sensitivity, analgesiometry, incapacitance testing, and forced flexion testing) was assessed weekly. Once pain-related behavior was established, RNA was extracted from either whole joints or microdissected tissue samples (articular cartilage, meniscus, and bone). Reverse transcription-polymerase chain reaction analysis was performed to analyze the expression of 54 genes known to regulate pain sensitization. Cartilage injury assays were performed using avulsed immature hips from wild-type or genetically modified mice or by explanting articular cartilage from porcine joints preinjected with pharmacologic inhibitors. Levels of nerve growth factor (NGF) protein were measured by enzyme-linked immunosorbent assay.Mice developed pain-related behavior 8 weeks after undergoing partial meniscectomy or 12 weeks after undergoing DMM. NGF, bradykinin receptors B1 and B2, tachykinin, and tachykinin receptor 1 were significantly regulated in the joints of mice displaying pain-related behavior. Little regulation of inflammatory cytokines, leukocyte activation markers, or chemokines was observed. When tissue samples from articular cartilage, meniscus, and bone were analyzed separately, NGF was consistently regulated in the articular cartilage. The other pain sensitizers were also largely regulated in the articular cartilage, although there were some differences between the 2 models. NGF and tachykinin were strongly regulated by simple mechanical injury of cartilage in vitro in a transforming growth factor β-activated kinase 1-, fibroblast growth factor 2-, and Src kinase-dependent manner.Damaged joint tissues produce proalgesic molecules, including NGF, in murine OA.
Long-term Outcomes of Thalidomide Therapy for Adults With Refractory Crohn’s Disease
Authors: Marion Simon, Benjamin Pariente, Jérôme Lambert, Jacques Cosnes, Yoram Bouhnik, Philippe Marteau, Matthieu Allez, Jean-Frédéric Colombel, Jean-Marc Gornet
Journal: Clinical Gastroenterology and Hepatology (2015)
Risk stratification of normotensive pulmonary embolism: prognostic impact of copeptin
Authors: Kristian Hellenkamp, Johanna Schwung, Heidi Rossmann, Anja Kaeberich, Rolf Wachter, Gerd Hasenfuß, Stavros Konstantinides, Mareike Lankeit
Journal: European Respiratory Journal (2015)

The prognostic value of copeptin, the C-terminal fragment of the precursor protein of vasopressin which is released upon stress, and hypotension in pulmonary embolism is unknown, especially if combined with biomarkers reflecting different pathophysiological axes such as myocardial injury (high-sensitivity troponin T (hsTnT)) and stretch (N-terminal pro-brain natriuretic peptide (NT-proBNP)). We prospectively studied 268 normotensive pulmonary embolism patients included in a single-centre cohort study. Patients with an adverse 30-day outcome (5.6%) had higher copeptin levels than patients with a favourable course (median (interquartile range) 51.8 (21.6–90.8) versus 13.2 (5.9–39.3) pmol·L −1 ; p=0.020). Patients with copeptin levels above the calculated optimal cut-off value of 24 pmol·L −1 had a 5.4-fold increased risk for an adverse outcome (95% CI 1.68–17.58; p=0.005). We developed a strategy for risk stratification based on biomarkers. None of 141 patients (52.6%) with hsTnT &lt;14 pg·mL −1 or NT-proBNP &lt;600 pg·mL −1 had an adverse outcome (low risk). Copeptin ≥24 pmol·L −1 stratified patients with elevated hsTnT and NT-proBNP as intermediate–low and intermediate–high risk (5.6% and 20.0% adverse outcome, respectively). Compared to the algorithm proposed by the 2014 European Society of Cardiology guideline, more patients were classified as low risk (52.8% versus 17.5%, p&lt;0.001) and more patients in the intermediate–high risk group had an adverse outcome (20.0% versus 11.6%). Copeptin might be helpful for risk stratification of normotensive patients with pulmonary embolism, especially if integrated into a biomarker-based algorithm.
Effect of Dermatophagoides Pteronyssinus Allergens On Expression of Genes Involved in Inflammation and Tissue Remodeling by Peripheral Blood Mononuclear Cells of Allergic Asthma Patients
Authors: Krzysztof Kowal, Pawel Bernatowicz, Lech Chyczewski, Anna Bodzenta Lukaszyk
Journal: Journal of Allergy and Clinical Immunology (2013)
Part 10: Special Circumstances of Resuscitation
Authors: Eric J. Lavonas, Ian R. Drennan, Andrea Gabrielli, Alan C. Heffner, Christopher O. Hoyte, Aaron M. Orkin, Kelly N. Sawyer, Michael W. Donnino
Journal: Circulation (2015)

Suspected Pulmonary EmbolismNo evidence is available to support or refute the effectiveness of empiric thrombolysis in suspected but unconfirmed PE. Recommendations-New and Updated ALS Modification: Confirmed Pulmonary EmbolismIn patients with confirmed PE as the precipitant of cardiac arrest, thrombolysis, surgical embolectomy, and mechanical embolectomy are reasonable emergency treatment options (Class IIa, LOE C-LD).Comparative data are not available to recommend one strategy over another.Patient location, local intervention options, and patient factors (including thrombolysis contraindications) are recognized elements to be considered.Thrombolysis can be beneficial even when chest compressions have been provided (Class IIa, LOE C-LD).Given the poor outcomes associated with fulminant PE in the absence of clot-directed therapy, standard contraindications to thrombolysis may be superseded by the need for potentially lifesaving intervention. ALS Modifications: Suspected Pulmonary EmbolismThrombolysis may be considered when cardiac arrest is suspected to be caused by PE (Class IIb, LOE C-LD).There is no consensus on inclusion criteria (eg, risk factors, signs, or symptoms that constitute suspected PE), thrombolytic timing, drug, or dose in this situation.There are insufficient data on surgical and mechanical embolectomy to evaluate these therapies for cardiac arrest associated with suspected but unconfirmed PE.
Improved survival duration with combination chemotherapy induction for multiple myeloma: a Southwest Oncology Group Study.
Authors: B G Durie, D O Dixon, S Carter, R Stephens, S Rivkin, J Bonnet, S E Salmon, L Dabich, J C Files, J J Costanzi
Journal: Journal of Clinical Oncology (1986)

Four hundred forty previously untreated patients with active multiple myeloma were entered into a randomized trial (Southwest Oncology Group [SWOG] study 7927/28) comparing vincristine, melphalan, Cytoxan (Mead Johnson &amp; Company, Evansville, Ind), and prednisone (VMCP) alternating with vincristine, BCNU, Adriamycin (Adria Laboratories, Columbus, Ohio) and prednisone (VBAP) with or without levamisole with vincristine, Cytoxan, and prednisone (VCP) with or without levamisole for induction therapy. The treatment groups were well balanced for all of the known major prognostic factors. Patients receiving VMCP-VBAP responded (greater than or equal to 75% regression) more frequently to induction therapy, both without (54%) and with (44%) levamisole v VCP without (28%) or with (28%) levamisole (P less than .001). In addition, patients receiving VMCP-VBAP (+/- levamisole) had a survival duration determined to be significantly increased by all forms of analysis: 48 and 33 months for VMCP-VBAP without and with levamisole v 29 and 26 months for VCP without and with levamisole (P = .011 overall). Levamisole did not improve response rates or survival duration (P greater than or equal to .1), nor did it prolong remission in the maintenance phase (P = .85). Analysis of SWOG study 7704/05 (updated April 1985) confirmed improved survival for combination therapy v MP, but no benefit for levamisole. The overall findings support the use of VMCP-VBAP as an excellent treatment option for remission induction in patients with active myeloma of all stages and prognostic categories.
Moving beyond journals
Authors: A. Bienkowski, L. Finegold
Journal: BMJ (1999)

Editor—Too much attention has been given to the dissemination function of journals and its improvement through the application of electronic publishing methods. I see little, actually nothing, that refers to the other important functions performed by the current scheme of journal publication. Preservation of the scholarly record is one such function, and it is not addressed at all in the BMJ’s proposal.1 Librarians are not forgetting it, though—and we must remind the academic community not to forget it either. No amount of handwaving or references to “advanced technology” which will solve this problem “somehow” alters the fact that there is no electronic equivalent to print on acid free paper. Electronic signatures decay; equipment becomes obsolete and disappears; companies merge or dissolve, and their promises of access “in perpetuity” may vanish too. Some serious discussion of this matter is necessary.
Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction: a 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA)
Authors: K Hørslev-Petersen, M L Hetland, L M Ørnbjerg, P Junker, J Pødenphant, T Ellingsen, P Ahlquist, H Lindegaard, A Linauskas, A Schlemmer, M Y Dam, I Hansen, T Lottenburger, C G Ammitzbøll, A Jørgensen, S B Krintel, J Raun, J S Johansen, M Østergaard, K Stengaard-Pedersen
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy ( NCT00660647 ). Methods Disease-modifying antirheumatic drug (DMARD)-naive patients with eRA started methotrexate (20 mg/week) and intra-articular triamcinolone (20 mg/ml) for 2 years. In addition, they were randomised to receive placebo adalimumab (DMARD group, n=91) or adalimumab (40 mg/every other week) (DMARD+adalimumab group, n=89) during the first year. Sulfasalazine and hydroxychloroquine were added if disease activity persisted after 3 months. During year 2, synthetic DMARDs continued. Adalimumab was (re)initiated if active disease reoccurred. Clinical response, remission, disability, quality of life and radiographic changes were assessed. Results One year after adalimumab withdrawal, treatment profiles and clinical responses did not differ between groups. In the DMARD/DMARD+adalimumab groups, the median 2-year methotrexate dose was 20/20 mg/week (p=0.45), triple DMARD therapy had been initiated in 33/27 patients (p=0.49), adalimumab was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28&gt;3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were DAS28CRP&lt;2.6:69%/66%; Clinical Disease Activity Index ≤2.8:55%/57%; Simplified Disease Activity Index &lt;3.3:54%/49%; American College of Rheumatology/European League against Rheumatism (28 joints):44%/45% (p=0.66–1.00). Radiographic progression (Δtotal Sharp score/year) was similar 1.31/0.53 (p=0.12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). Conclusions An aggressive triamcinolone and synthetic DMARD treat-to-target strategy in eRA provided excellent 2-year clinical and radiographic disease control independent of adalimumab induction therapy. ES progression was slightly less during and following adalimumab induction therapy. Trial registration number NCT00660647.
Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients
Authors: Michael W. Deininger, J. Graeme Hodgson, Neil P. Shah, Jorge E. Cortes, Dong-Wook Kim, Franck E. Nicolini, Moshe Talpaz, Michele Baccarani, Martin C. Müller, Jin Li, Wendy T. Parker, Stephanie Lustgarten, Tim Clackson, Frank G. Haluska, Francois Guilhot, Hagop M. Kantarjian, Simona Soverini, Andreas Hochhaus, Timothy P. Hughes, Victor M. Rivera, Susan Branford
Journal: Blood (2015)
THE CLIMATES OF THE WORLD, IN REFERENCE TO THEIR EFFECTS ON MAN'S GENERAL WELFARE AND DESTINY
Authors: T. G. Hake
Journal: BMJ (1853)

Ai'm 8, the sinus for the left coronary artery, equal to the size of a walnut: augmented calibre of the aorta; two ulcers in the ascending aorta-one situated as inch and a half above the valves, extending in the long axis of the artery, and capa& ble of lodging two ordinary thimbles-the other commencing about two and a half inches above the valves, and capable of lodging one thimble (each ulcer being three times as long as its width).The edges of the ulcers were distinct to the touch; but red granulations nearly filled the cavities.The lining membrane of the aorta was smnooth.The aortic valves were incompetent when tested by water.Blood was found in only one cavity of the heart, viz, the left auricle, in which it was liquild.The right auricle was empty, and very small.The right ventricle was small, and enclosed as before statel.The coluiunaw carneaw were very strong, and the little finger could lbe inserted its whole length into a diverticului in the septum, between two such columnn.The total weight of the heart was probably not more than twelve ouinces.The mnuscular tissue was not visibly de- geinerated.Abdom.en.The liver was not enlarged.The spleen was turgidl.Both kitineys were very weighity, probably four times as much so as natural.The capsules separated easily, leavinig smiooth surfaces.A large amount of san- guincous serum cscaped on slicinig the organs.The cortical structure was packed with greyish-white deposit.
Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1.
Authors: E Jäger, M Heike, H Bernhard, O Klein, G Bernhard, D Lautz, J Michaelis, K H Meyer zum Büschenfelde, A Knuth
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the most effective dose of leucovorin (folinic acid [FA]) within a weekly bolus fluorouracil (FU) schedule, we conducted a randomized multicenter trial to compare therapeutic effects and toxicity of high-dose FA versus low-dose FA combined with FU at equal doses in both treatment groups. PATIENTS AND METHODS Patients with measurable inoperable or metastatic colorectal cancer were randomized to receive weekly FU 500 mg/m2 by intravenous (IV) bolus combined with high-dose FA 500 mg/m2 (group A) or low-dose FA 20 mg/m2 (group B) by 2-hour infusion. RESULTS Of 291 assessable patients (group A, n = 148; group B, n = 143), we observed, in group A, complete response (CR)/partial response (PR) in 32 (21.6%), no change (NC) in 64 (43.2%), and progressive disease (PD) in 52 (35.1%); and in group B, CR/PR in 25 (17.5%), NC in 63 (44.1%), and PD in 55 (38.5%). The median response duration was 24.8 weeks in group A and 23.1 weeks in group B. Median progression-free intervals were 29.3 weeks (group A) and 30 weeks (group B). The median survival time was 55.1 weeks in group A and 54.1 weeks in group B. Overall toxicity was moderate. Mild nausea and vomiting, and stomatitis were common side effects in both groups. The incidence of World Health Organization (WHO) grade III/IV diarrhea was significantly higher in group A (40 v 23 patients). Severe side effects were observed only in a minority of patients in both arms. WHO grade IV diarrhea was observed in seven patients: four in group A and three in group B. The rate of toxicity-related adjustments of dose and schedule was comparable in both groups. CONCLUSION High-dose FA/FU is not superior to low-dose FA/FU within a weekly treatment schedule. Response rates and survival were comparable in both treatment arms. Treatment-related toxicity was higher in group A (high-dose FA). Therefore, low-dose FA combined with weekly FU may be considered the preferred treatment for metastatic colorectal cancer.
Vitamin K and the Oral Anticoagulant Drugs
Authors: R A O'Reilly
Journal: Annual Review of Medicine (1976)

The evolution of vitamin K, from a dietary deficiency in birds to a postribosomal modifier of prothrombin in man, has been a fascinating scientific saga. Its antivitamin, the oral anticoagulant drugs, has been a powerful probe both of vitamin K action and of drug interactions. These agents have emerged from a limbo of clinical therapeutics to become a light of human pharmacology.
The Disposition and Effects of Sedatives and Analgesics in Liver Disease
Authors: A M Hoyumpa, R A Branch, S Schenker
Journal: Annual Review of Medicine (1978)

The aim of drug therapy is to deliver a drug concentration sufficient to affect the site of action. Whether the desired intensity and duration of action are attained or exceeded depends largely on the efficiency of drug disposition and on the sensitivity of the receptor site(s). The pharmacologic effects of sedatives and analgesics have been shown to be exaggerated in some patients with significant liver disease or portasystemic shunts, with coma as a potential outcome (1). In recent years a number of studies revealed impaired disposition and altered response to such widely used drugs as tranquilizers, sedatives, and analgesics in the presence of significant hepatic dysfunction (2). The purpose of the present discussion is to review the disposition and effects of drugs in hepatic dys­ function, and thus provide a rational approach to the management of liver disease.