tbuckley/cabot-search huggingface dataset:
Opioids, Reward and Addiction: An Encounter of Biology, Psychology, and Medicine
Authors: Jan M. van Ree, Mirjam A.F.M. Gerrits, Louk J.M.J. Vanderschuren
Journal: Pharmacological Reviews (1999)

If the entire materia medica at our disposal were limited to the choice and use of only one drug, I am sure that a great many, if not the majority, of us would choose opium ([Macht, 1915][1]).

### A. Early History

Opium is the dried milky juice of the unripe seed capsule of the poppy, the Papaver
The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy
Authors: Brian C. Callaghan, Raymond S. Price, Kevin S. Chen, Eva L. Feldman
Journal: JAMA Neurology (2015)

<h3>Importance</h3> Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination but has limited diagnostic evaluation. However, rare localizations of peripheral neuropathy often require more extensive diagnostic testing and different treatments. <h3>Objective</h3> To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. <h3>Evidence Review</h3> References were identified from PubMed searches conducted on May 29, 2015, with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the authors' own files. Search terms included common rare neuropathy localizations and their causes, as well as<i>epidemiology</i>,<i>pathophysiology</i>,<i>diagnosis</i>, and<i>treatment</i>. <h3>Findings</h3> Diffuse, nonlength-dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, nonlength-dependent neuropathies are Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying therapies exist for many diffuse, nonlength-dependent neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is lacking. <h3>Conclusions and Relevance</h3> Recognition of rare localizations of peripheral neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important early step in the diagnostic evaluation and provide information on the localization and pathophysiology of nerve injury.
Molecular cancer prevention: Current status and future directions
Authors: Karen Colbert Maresso, Kenneth Y. Tsai, Powel H. Brown, Eva Szabo, Scott Lippman, Ernest T. Hawk
Journal: CA A Cancer Journal for Clinicians (2015)

Answer questions and earn CME/CNE The heterogeneity and complexity of advanced cancers strongly support the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer‐predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (eg, aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the US Food and Drug Administration for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet it has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, several challenges to the field must be addressed. Here, the authors provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results from major randomized controlled trials. CA Cancer J Clin 2015;65:345–383. © 2015 American Cancer Society .
Rate of completion of forms should have been analysed by age
Authors: W R Primrose, D G Seymore, A E Ball, E M Russell
Journal: BMJ (1996)

EDITOR,—Charlotte Paterson compares her patient generated measure, the “measure yourself medical outcome profile” (MYMOP) with the short form health survey, the SF-36.1 Although she states that 7% of the MYMOP …
NOD-like receptors in the human upper airways: a potential role in nasal polyposis
Authors: A. Månsson, J. Bogefors, A. Cervin, R. Uddman, L. O. Cardell
Journal: Allergy (2011)

To cite this article: Månsson A, Bogefors J, Cervin A, Uddman R, Cardell LO. NOD-like receptors in the human upper airways: a potential role in nasal polyposis. Allergy 2011; 66: 621–628. Background: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are newly discovered cytosolic receptors belonging to the pattern-recognition receptor family. They detect various pathogen-associated molecular patterns, triggering an immune response. The knowledge about these receptors, and their role in health and disease, is limited. The aim of the present study was to characterize the expression of NOD1, NOD2, and NALP3 in the human upper airways. Methods: Surgical samples were obtained from patients with tonsillar disease (n = 151), hypertrophic adenoids (n = 9), and nasal polyposis (n = 24). Nasal biopsies were obtained from healthy volunteers (n = 10). The expression of NOD1, NOD2, and NALP3 was analyzed using real-time PCR and immunohistochemistry. Results: Expression of NOD1, NOD2, and NALP3 mRNA and protein were seen in all tissue specimens. The NLR mRNA was found to be higher in nasal polyps than in normal nasal mucosa, and local steroid treatment reduced the NLR expression in polyps. In contrast, tonsillar infection with Streptococcus pyogenes or Haemophilus influenzae did not affect the NLR expression. Conclusions: The present study demonstrates the presence of NLRs in several upper airway tissues and highlights a potential role of NLRs in chronic rhinosinusitis with polyps.
Ongoing multi-strain food-borne hepatitis A outbreak with frozen berries as suspected vehicle: four Nordic countries affected, October 2012 to April 2013
Authors: S Gillesberg Lassen, B Soborg, S  E Midgley, A Steens, L Vold, K Stene-Johansen, R Rimhanen-Finne, M Kontio, M Löfdahl, L Sundqvist, M Edelstein, T Jensen, H T Vestergaard, T K Fischer, K Mølbak, S Ethelberg
Journal: Eurosurveillance (2013)

Binary file ES_Abstracts_Final_ECDC.txt matches
A novel localized co-delivery system with lapatinib microparticles and paclitaxel nanoparticles in a peritumorally injectable in situ hydrogel
Authors: Hongxiang Hu, Zhiqiang Lin, Bing He, Wenbing Dai, Xueqing Wang, Jiancheng Wang, Xuan Zhang, Hua Zhang, Qiang Zhang
Journal: Journal of Controlled Release (2015)
New methodology for specific inhalation challenges with occupational agents in powder form
Authors: Y Cloutier, F Lagier, R Lemieux, MC Blais, C St-Arnaud, A Cartier, JL Malo
Journal: European Respiratory Journal (1989)

Numerous agents in powder form (wood dust, flour, antibiotics, drugs, etc.) can cause occupational asthma. The diagnosis is generally confirmed by specific inhalation challenges in a special challenge room. There are several pitfalls to the procedure: 1) subjects may be exposed to high concentrations of particles; the concentrations of particles may be higher than the threshold limit value-short term exposure level (TLV-STEL), possibly resulting in severe or irritant reactions; 2) the exposure is erratic. To overcome these problems, a new device for aerosolization of powders has been developed. This apparatus consists of three parts: a particles generator, an aerosol delivery system connected to an orofacial mask, and monitors - a photometer and a cascade impactor. Information on the concentration and size distribution of inhaled particles can therefore be obtained. We performed specific inhalation challenges with this apparatus on 20 subjects suspected of having occupational asthma. The concentration of particles was generally below or close to the TLV-STEL and information was obtained on the proportion of particles with a diameter less than 10 mu. Falls in forced expiratory volume in one second (FEV1) were progressive with each increase in the duration of exposure. The five subjects who had negative reactions to exposure were asked to tip the relevant product from one tray to another in the traditional realistic way. All had negative responses. We conclude that this new procedure offers advantages over the traditional method as it gives information on the concentration and size distribution of inhaled particles and makes the drawing of a dose-response curve possible, both of which may improve the safety and accuracy of the test.
Abstract A08: CADM1 is a TWIST1 regulated suppressor of melanoma invasion
Authors: Edward J. Hartsough, Michele B. Weiss, Sheera R. Rosenbaum, Andrew E. Aplin
Journal: Cancer Research (2015)

Abstract Melanoma is the deadliest form of skin cancer; however, with early detection prior to metastatic dissemination, patients generally have a good prognosis. Recently, our lab has implicated the transcription factor TWIST1 in the progression of melanoma towards metastasis. In melanoma cells, we found that RAS-RAF-MEK-ERK (ERK1/2 pathway) signaling increases TWIST1 expression, which promotes invasive properties in the dermal microenvironment, at least in part by enhancing levels of the matrix metalloproteinase, MMP1. Other TWIST1-regulated targets are poorly described. In this study, we compared expression-profiling data from cells expressing shRNA against TWIST1 or cells overexpressing TWIST1 in order to identify TWIST1-regulated genes. KEGG and GO analysis revealed that TWIST1 is responsible for regulating a number of genes involved in cellular adhesion. We found that TWIST1 levels inversely correlate with levels of cell adhesion molecule 1 (CADM1, also known as NECL-2, IGSF4, TSLC1, SynCAM). Chromatin immunoprecipitation (ChIP) studies and promoter assays demonstrated that TWIST1 physically interacts with the CADM1 promoter and this is associated with reduced CADM1 levels. Additionally, CADM1 expression is inversely associated with ERK1/2 signaling and TWIST1 expression. Modulation of cellular CADM1 levels did not affect proliferation rates; however, overexpression of CADM1 augmented cell-cell interaction, cell aggregation, and reduced trans-endothelial invasion. Furthermore, exogenous CADM1 inhibited serum-directed migration and invasion through Matrigel-coated Boyden chambers, whereas knockdown of CADM1 was associated with enhanced migratory and invasive properties. Taken together, these data provide evidence that CADM1 is negatively regulated by TWIST1 and may act as a suppressor of melanoma invasion. Citation Format: Edward J. Hartsough, Michele B. Weiss, Sheera R. Rosenbaum, Andrew E. Aplin. CADM1 is a TWIST1 regulated suppressor of melanoma invasion. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A08.
Activity of the T-type calcium channel antagonist Mibefradil in pancreatic cancer xenografts
Authors: Ignacio Garrido-Laguna, Aik Choon Tan, Maria Cristina Villarroel, N.V. Rajeshkumar, Belen Rubio-Viqueira, Lloyd Gray, Manuel Hidalgo
Journal: Clinical Cancer Research (2008)

B49    Background:  Pancreatic cancer is the forth leading cancer death in US. More than 80% of pancreatic adenocarcinomas are unresectable on diagnosis. The standard treatment in this setting is gemcitabine. Response rates are lower than 10%. Novel therapies are urgently needed. Mibefradil is a T-type calcium channel inhibitor that exerts a cytostatic effect on cancer cells. Here we explored the activity of Mibefradil in a direct pancreatic cancer xenografts model using a molecular mimicry approach to select tumors more likely to be sensitive to the drug.  Methods:  We first normalized the activity of Mibefradil across the NCI-60 cell lines and defined cell lines as sensitive and resistant if the normalized GI50   -1, respectively. We used a molecular mimicry approach to predict Mibefradil sensitivity of seven xenografts based on their pathway expression similarity to NCI-60 cell lines. We treated these selected xenografts with Mibefradil 65mg/Kg PO bid for 28 days.  Results:  Xenograft Panc 219 was predicted as the most sensitive to Mibefradil based on its molecular mimicry with ME2, the top cell line sensitive to Mibefradil. The TGI for Panc 219 was 12%. Xenograft Panc 215 was predicted to be resistant based on its connection to NSCLC4, the top cell line resistant to Mibefradil. The TGI for 215 was 145%. The rest of the xenografts were connected to resistant cell lines and were found to be resistant when treated with the drug.  Conclusions:  Mibefradil was very effective in treating a patient derived pancreas xenograft model and this activity was correctly predicted based on the activity of the drug against a reference set of cancer cell lines. This approach may help to identify patients for clinical trials with Mibefradil.
Phase IIa trial of cilengitide (EMD121974) single-agent therapy in patients (pts) with recurrent glioblastoma (GBM): EMD 121974-009
Authors: D. Reardon, K. Fink, B. Nabors, T. Cloughesy, S. Plotkin, D. Schiff, J. Raizer, S. Krueger, M. Picard, T. Mikkelsen
Journal: Journal of Clinical Oncology (2007)

2002 Background: Our phase IIa study evaluated the safety, toxicity, and clinical activity of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, as a single agent at doses of 500 and 2000 mg in pts with recurrent GBM. Methods: In this multicenter, open-label, randomized, uncontrolled study, pts with GBM and measurable disease that had relapsed after previous temozolomide and radiotherapy were randomized to receive cilengitide at either 500 mg or 2000 mg i.v., 2x/week, until progression. Neurologic exams were performed after every cycle (4 weeks) and MRIs were performed every other cycle. Central, blinded pathology and radiology reviews were performed. The primary endpoint was Progression Free Survival (PFS) at 6 months (6-mth PFS). Secondary endpoints included response, survival, time to disease progression, safety, tolerability and pharmacokinetics (PK). Results: 81 pts accrued (median Karnofsky Performance Status 80%; median age 57 yrs) at 15 sites including 41 at the 500 mg and 40 at the 2000 mg dose levels. Demographic and pretreatment variables were comparable between dose level cohorts. The median number of infusions was 16 [range, 4–179]. PK studies revealed significantly greater exposures among the 2000 mg cohort. Treatment related NCI CTC grade 3 adverse events (AEs) included elevated transaminases (at 500 mg), arthralgia/ myalgia (at 500 mg), and weight increase/ edema (at 2000 mg) in 1 patient, respectively. No grade 4 therapy related AEs were reported. One CTC grade 2 cerebral hemorrhage was reported in a pt at progression. The 6- mth PFS was 16.1% (n=13/81 pts). 10 pts (12.3 %, n=4 with 500 mg, n=6 with 2000 mg) received 12 or more cycles. Six pts (7.4%) remain progression-free and on treatment. Median Overall Survival (mOS) was 6.5 mths [95% CI: 5.2–9.3 mths] in the 500 mg arm and 9.9 mths [95% CI, 6.3–15.7 mths] in the 2000 mg arm. Although not statistically significant, there was a trend towards better tumor control in pts receiving 2000 mg 2x/week. Conclusions: Cilengitide was well tolerated and demonstrated single agent activity in recurrent GBM, with long term disease stabilization in a subset of pts. [Table: see text]
Stimulation of Monovalent Cation Active Transport by Low Concentrations of Cardiac Glycosides
Authors: Thomas J. Hougen, Nancy Spicer, Thomas W. Smith
Journal: Journal of Clinical Investigation (1981)

The stimulatory effect of low concentrations of ouabain on the Na-K pump in isolated guinea pig left atria was studied in vitro by assessing active transport of the K+ analog Rb+. Active transport of Rb+ was stimulated 20±8% (SEM, P < 0.05) above control values by 3 nM ouabain, but was inhibited by concentrations >10 nM. Preincubation with the β-adrenergic antagonist propranolol (1 μM) completely blocked stimulation of active transport of Rb+ by 3 nM ouabain. Norepinephrine, 10 nM, increased Rb+ active transport 29±10% (P < 0.02) above control values. The β-adrenergic agonist l-isoproterenol, 10 nM, increased active transport of Rb+ by 33±10% (P < 0.01) above control levels. This stimulatory effect was abolished if tissues were first exposed to propranolol. Tyramine (0.1 μM), a stimulator of endogenous catecholamine release, increased active transport of Rb+ 26±12% (P < 0.05) above control values. Rb+ active transport was not significantly changed when left atrial tissues were incubated with α-adrenergic agonists or antagonists. Ouabain stimulation of Rb+ active transport was prevented by in vivo depletion of myocardial endogenous catecholamines by either reserpine or 6-hydroxydopamine. These findings indicated that in myocardial tissue, Na-K pump stimulation by low concentrations of ouabain is mediated at least in part through β-adrenergic effects of endogenous catecholamines.
Omalizumab in asthmatics with IgE levels > 700 IU/ml
Authors: Diego Maselli, Joseph Diaz, Jay Peters
Journal: European Respiratory Journal (2011)

Introduction:  Omalizumab, a monoclonal antibody against IgE, has been effectively used to control symptoms and reduce steroid requirements in asthmatics with serum IgE levels between 30-700 IU/ml and positive testing for perennial allergens. Its use when IgE levels are > 700 IU/ml is unclear.   Aim:  To evaluate the response of asthmatics treated with omalizumab with IgE levels > 700 IU/ml.   Methods:  A retrospective, case-controlled study was performed in an allergy referral clinic. Consecutive asthmatics treated with omalizumab ≥ 6 months with elevated IgE levels were identified, and demographic variables recorded. Systemic corticosteroid requirements, emergency room visits, hospitalizations, FEV1, Asthma Control Test (ACT) scores, medications and allergen responses were recorded for a period of 6 months pre and post treatment.   Results:  Twenty-six patients with an IgE >700 IU/ml (Group 1) and 26 with an IgE of 30 to 700 IU/ml (Group 2) were identified. The mean IgE level was 2371 IU/ml (786-10979) vs. 221 IU/ml (30-578) respectively (p   Conclusions:  Omalizumab was effective in controlling asthma symptoms and reducing the need for systemic corticosteroids in patients with IgE levels > 700 IU/ml and produced clinical improvement similar to patients with IgE levels between 30-700 IU/ml.
Detection of platelet associated IgG in immune thrombocytopenia: A new assay employing protein a and peroxidase anti‐peroxidase (PROA‐PAP)
Authors: Douglas Y. Tate, Gregory T. Carlton, Mark E. Nesbit, James G. White, William Krivit, Robert L. Sorenson
Journal: American Journal of Hematology (1980)

Abstract Immune thrombocytopenia is frequently encountered in medical practice and is generally accepted as being caused by an IgG antibody. The capability of detecting platelet‐bound IgG as a diagnostic and therapeutic modality is critical for appropriate care and management of patients with idiopathic thrombocytopenic purpura (ITP), as well as other immune thrombocytopenias We have modified our previous assay (Br J Haematol 37:265, 1977) by employing protein A and PAP as a labeled antibody. Surface bound platelet IgG was quantitated by phase contrast microscopy after incubation with PAP, graded per 100 platelets and expressed as a reactive index (RI). Controls (n=13) had RIs ranging from 0.49 to 0.72 (mean 0.63 ± 0.02 SE). The nonimmune thrombocytopenic group (n=7) had an RI ranging from 0.58 to 0.72 (mean 0.64 ± 0.01 SE). In contrast, the immune thrombocytopenic group (n=28) had RIs ranging from 1.04 to 1.75 (mean 1.43 ± 0.03 SE). Platelet‐associated IgG was evaluated further by absorbing representative sera samples from each group against washed granulocytes, red cells and platelets Only when sera from the immune thrombocytopenic group were absorbed against platelets did the reactive indices of pre‐ and postabsorption samples change significantly. These findings suggest that our assay is clinically applicable in detecting platelet‐associated IgG in immune thrombocytopenia and has the advantage of being rapid, reproducible and easy to perform in a clinical laboratory.
Accuracy of the Eosinophilic Esophagitis Endoscopic Reference Score in Diagnosis and Determining Response to Treatment
Authors: Evan S. Dellon, Cary C. Cotton, Jessica H. Gebhart, Leana L. Higgins, RoseMary Beitia, John T. Woosley, Nicholas J. Shaheen
Journal: Clinical Gastroenterology and Hepatology (2015)
Using results of new laboratory test for tuberculosis infection in children
Authors: Zhanna Kryvasheyeva, Andrey Astrovko, Natalia Emeljanova, Irina Babchenok, Natalya Morozkina, Galina Baradzina, Pavel Krivonos, Valeriy Pylishev, Elena Bobrukevich, Anna Belko
Journal: European Respiratory Journal (2013)

Aim. To evaluate skin test efficiency using new reagent for tuberculosis infection diagnostics – DIASKINTEST.

Methods. We analyzed results of DIASKINTEST (DST) in 105 patients: 53 children with active tuberculosis (TB), 20 – with treated TB; 12 – with non-tuberculosis process and 20 children with BCG vaccination complications. Making method and interpretation of examination test is analogous to Mantoux sample.

Results. Patients with active TB in various stages of chemotherapy had positive reaction in 88.7%, in the beginning of treatment – 94.0% cases. 4 children with lung TB and 2 children with TB peripheral lymphadenitis had negative reaction to DST (11.3%). 88.5% children had descent reaction to DST and its reversion to negative during chemotherapy; 7.7% patients had invariable negative reactions. patients with clinical treated TB and positive Mantoux test had negative DST in 65.0% and positive in 35.5% cases. All the children with non-tuberculosis process and BCG vaccination complications with positive Mantoux test – had negative DST reaction.

Conclusion. Positive DST sample is marker of active tuberculosis infection. Skin test with preparation DIASKINTEST had high specificity: frequency of negative reactions in children with non-tuberculosis and BCG complications was 100%; also had high sensitivity: frequency of positive reactions in children with non-treated TB was 94.0%. DST sample is safe to use in children practice – it was no unusual reactions (3 cases of rise temperature in 1908 samples).