tbuckley/cabot-search huggingface dataset:
Avian influenza A(H5N1) in humans: lessons from Egypt
Authors: F O Fasina, V I Ifende, A A Ajibade
Journal: Eurosurveillance (2010)

Highly pathogenic avian influenza A(H5N1) has ravaged the Egyptian poultry population. Ninety human cases, including 27 fatalities have been recorded by 30 December, 2009. However, epidemiological information on the infection in humans in Egypt is scarce. We analysed the first three years of highly pathogenic avian influenza A(H5N1) in Egypt between 20 March 2006 and 31 August 2009) and found that more cases occurred in females than males, especially in 2006 and 2007. Women in the age group 20-39 years had the greatest tendency to be infected. It took an average of one day and 18 hours to seek medical assistance in patients who recovered and of six days in fatal cases. Children sought treatment much earlier than adults. On average, a patient died 11 days after the onset of symptoms. Exposure to infected poultry remained the most important risk factor.
SAT0547 Sequential Diagnosis of Sarcoidosis and Malignancy: A close But Complex Association with Four Differential Clinical Scenarios
Authors: P. Brito Zeron, J. Sellarés, X. Bosch, F. Hernández, C. Lopez-Casany, M. Sanchez, J. Ramírez, H. Gheitasi, B. Kostov, J. Santos, A. Sisό Almirall, C. Agustí, M. Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> The aim of this study was to evaluate the temporal association between the diagnosis of neoplasia and sarcoidosis in a large cohort of Spanish sarcoidosis patients. <h3>Methods</h3> We included 170 patients consecutively diagnosed with sarcoidosis. The diagnosis of sarcoidosis was based on clinical criteria and imaging studies, together with the histopathological demonstration of non-necrotizing granulomas, and excluding other granulomatous diseases. The diagnosis of neoplasia was recorded before and after the diagnosis of sarcoidosis. Hematological neoplasias were classified according to the 2008 WHO Classification. <h3>Results</h3> There were 111 (65%) women and 59 (35%) men (mean age at diagnosis, 47 years); 23 (13.5%) patients developed 25 neoplasias (two patients developed 2 neoplasias, before and after the diagnosis of sarcoidosis). There were 13 (52%) solid neoplasias, including pulmonary (n=3), thyroid (n=2), breast (n=2), melanoma (n=2) and cervix, testicular, renal and gastric cancer (1 case each). The remaining 12 (48%) were hematological neoplasias, mainly mature B-cell neoplasms (3 chronic lymphocytic leukemia, 3 extranodal MALT lymphomas and 2 diffuse large B-cell lymphoma), but also 2 acute leukemias (1 acute promyelocytic PML-PARA, 1 acute myeloid leukemia), 1 mature T-cell neoplasia (mycosis fungoide) and 1 myeloid neoplasia (essential thrombocytopenia). No significant differences were found in the main epidemiological, clinical or radiological features of sarcoidosis in patients with or without associated neoplasia, except for a statistical trend to a higher frequency of extrathoracic sarcoidosis in patients with associated cancer (70% vs 50%, p=0.11). Of the 23 patients with cancer, 5 were diagnosed before sarcoidosis and 16 after the diagnosis of sarcoidosis (10 solid and 6 hematological neoplasia); the 2 remaining patients developed a second neoplasia after the diagnosis of sarcoidosis. <h3>Conclusions</h3> We identified four states of association between sarcoidosis and malignancy: i) patients with sarcoidosis who develop solid tumors (43%); ii) development of hematologic malignancies, mainly sarcoidosis-lymphoma syndrome (26%); iii) development of sarcoidosis in patients with neoplasia, including paraneoplastic sarcoidosis (cancer discovered concurrently ±1 year of the diagnosis of sarcoidosis) in 3 patients (22%); iv) patients with sarcoidosis and previous cancer who developed a second and different neoplasia (9%). <h3>Disclosure of Interest</h3> None declared
Normal Reference Laboratory Values
Authors: Alexander Kratz, Kent B. Lewandrowski
Journal: New England Journal of Medicine (1998)

The following is a table of reference values, methods, and conversion factors for tests commonly ordered at the Massachusetts General Hospital (MGH) and recorded in the Case Records. The table revises the most recently published data (Normal Reference Laboratory Values. N Engl J Med 1992;327:718-24). Laboratory values are expressed in the units used at MGH (MGH units) and the units of the Systeme International d'Unites (SI units), with a factor to convert MGH units to SI units by multiplication. This table is not intended to provide a comprehensive review of reference values, since this information is widely available in standard . . .
Pharmacological Elimination of Tumor Cells Contaminating Normal Human Bone Marrow Using PTT-119
Authors: Roberto M. Lemoli, Subhash C. Gulati, Amaury Perez, Bayard D. Clarkson
Journal: Cancer Communications (1990)

In this study, we evaluated the inhibitory effects of PTT-119, a new tripeptide which is known to be a bifunctional alkylating agent, on two tumor cell lines with different origins: SK-DHL-2 (B-cell diffuse histiocytic lymphoma cell line) and RPMI 8226 (Multiple myeloma patient cell line) and compared the toxicity of PTT-119 toward normal human bone marrow granulocyte macrophage (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEM) progenitors. Reduction of at least four logs was achieved on clonogenic myeloma cells after 1 hr of treatment with 25 micrograms/mL of PTT-119 either in the presence or absence of irradiated bone marrow (BM) cells. More than three and at least four logs of lymphoma cell kill were found after 1 hr of incubation with 25 and 40 micrograms/mL of the tripeptide, respectively. PTT-119 antitumor effects on SK-DHL-2 were only slightly affected in the presence of an excess of BM cells. BM cells treated for 1 hr with 25 micrograms/mL of PTT-119 showed a mean recovery of 4.5, 3.8, and 13.8% of CFU-GM, BFU-E, and CFU-GEM, respectively. The addition of 5- and 10-fold excesses of red blood cells (RBC) produced a slightly higher recovery of these hematopoietic progenitors. These results suggest that PTT-119 may be useful as a chemotherapeutic agent for the ex vivo treatment of bone marrow grafts.
Monitoring the Effect of Immunotherapy in Autoimmune Limbic Encephalitis Using 18F-FDG PET
Authors: Cristina Trevino-Peinado, Javier Arbizu, Pablo Irimia, Mario Riverol, Eduardo Martínez-Vila
Journal: Clinical Nuclear Medicine (2015)

A 70-year-old woman with a history of autoimmune hepatitis and renal cell carcinoma presented with subacute cognitive impairment. A brain MRI revealed mild leukoaraiosis, whereas brain F-FDG PET/CT showed diffuse cerebral hypometabolism that resembled some of the patterns described in limbic encephalitis and neurodegenerative diseases. With the suspicion of autoimmune encephalitis, the patient received immunotherapy with dramatic improvement of cognitive function and metabolic normalization at the 2-month follow-up on brain F-FDG PET/CT. Our results demonstrate that brain F-FDG PET/CT might be a useful tool in the assessment of patients with autoimmune encephalitis.
11. Biodegradable electrospun fibers as drug delivery system for local cancer treatment: A rugged path to the bright future
Authors: Nicholas A. Peppas, Ruth Duncan, Gary E. Wnek, Allan S. Hoffman, Guang Hui Gao, Sung Wan Kim, Doo Sung Lee, Michael Hadjiargyrou, Elka Touitou, Denize Ainbinder, Russell Mumper, Alain Rolland, Takuro Niidome, Vinod Labhasetwar, Shi Liu, Guangyuan Zhou, Yubin Huang, Zhigang Xie, Xiabin Jing, Noemi Csaba
Journal: Journal of Controlled Release (2014)
Gamete activation: basic knowledge and clinical applications
Authors: Elisabetta Tosti, Yves Ménézo
Journal: Human Reproduction Update (2016)

The first clues to the process of gamete activation date back to nearly 60 years ago. The mutual activation of gametes is a crucial event during fertilization. In the testis and ovaries, spermatozoa and oocytes are in a state of meiotic and metabolic quiescence and require reciprocal signals in order to undergo functional changes that lead to competence for fertilization. First, the oocyte activates sperm by triggering motility, chemoattraction, binding and the acrosome reaction, culminating with the fusion of the two plasma membranes. At the end of this cascade of events, collectively known as sperm capacitation, sperm-induced oocyte activation occurs, generating electrical, morphological and metabolic modifications in the oocyte. The aim of this review is to provide the current state of knowledge regarding the entire process of gamete activation in selected specific animal models that have contributed to our understanding of fertilization in mammals, including humans. Here we describe in detail the reciprocal induction of the two activation processes, the molecules involved and the mechanisms of cell interaction and signal transduction that ultimately result in successful embryo development and creation of a new individual. We carried out a literature survey with no restrictions on publication date (from the early 1950s to March 2016) using PubMed/Medline, Google Scholar and Web of Knowledge by utilizing common keywords applied in the field of fertilization and embryo development. We also screened the complete list of references published in the most recent research articles and relevant reviews published in English (both animal and human studies) on the topics investigated. Literature on the principal animal models demonstrates that gamete activation is a pre-requisite for successful fertilization, and is a process common to all species studied to date. We provide a detailed description of the dramatic changes in gamete morphology and behavior, the regulatory molecules triggering gamete activation and the intracellular ions and second messengers involved in active metabolic pathways in different species. Recent scientific advances suggest that artificial gamete activation may represent a novel technique to improve human IVF outcomes, but this approach requires caution. Although controversial, manipulation of gamete activation represents a promising tool for ameliorating the fertilization rate in assisted reproductive technologies. A better knowledge of mechanisms that transform the quiescent oocyte into a pluripotent cell may also provide new insights for the clinical use of stem cells.
Brief versus standard hospitalization: the families
Authors: M I Herz, J Endicott, R L Spitzer
Journal: American Journal of Psychiatry (1976)

A total of 175 newly admitted inpatients who lived with families were randomly assigned to three treatment groups: standard inpatient care (discharge at the therapist's discretion), brief hospitalization (one week or less) with transitional day care available, and brief hospitalization without day care. Outpatient aftercare was offered to all patients. There was no major differential family burden as a function of length of hospitalization. Generally, brief hospitalization had several positive effects on family functioning, primarily earlier resumtption of occupational roles and less financial burden, with few significant deleterious effects.
Immunomodulatory effects of OX40 agonists in a defined antigen challenge in cynomolgus macaques.
Authors: Stacie L Lambert, Darren Heeke, Kathryn Patton, Rui Lin, Cindy Shambaugh, Shahin Aslam, Li Yu, Fengrong Zuo, Andrew Pierce, Xavier Paliard
Journal: Journal of Clinical Oncology (2015)

3086 Background: Immunomodulatory antibodies targeting specific T cell costimulatory pathways have shown great potential as cancer therapeutics. OX40 agonists can enhance T cell proliferation and survival and cause tumor regressions in mouse models. While initial evaluations of pharmacodynamic activity of these compounds in non-human primate models have relied on non-specific T cell proliferation readouts (Ki67), additional sensitive biomarkers of pharmacodynamic activity would add value in evaluating optimal dosing and timing of candidate therapeutics. Methods: In this study, we compared the in vivo activity in cynomolgus macaques of intravenously infused OX40 agonist MEDI6469 (9B12, a murine IgG1 antibody) and MEDI6383, a human OX40 ligand fusion protein consisting of a dimer of OX40L trimers held together by Fcγ domains that also agonizes the OX40 receptor. Antigen-specific responses were evaluated to respiratory syncytial virus soluble F (sF) protein, which was administered intramuscularly on the same day as OX40 agonist treatment. Ki67 proliferation was additionally measured in whole blood. Results: Enhancement of F-specific T cell responses, serum anti-F IgG responses and functional antibodies was observed in animals that received the OX40 agonists. In addition, OX40 agonism resulted in a temporal enhancement of cellular proliferation (Ki67 staining) in CD4 and CD8 T cell memory subsets, as well as in NK cells and B cells. The strongest antigen-specific and Ki67 responses were observed in response to MEDI6383, with the exception of responses observed for NK cell proliferation which were similar between MEDI6469 and MEDI6383. Conclusions: Our study indicates that antigen-specific cellular and humoral responses may be useful biomarkers of OX40 agonist activity. Additionally, our study confirms that Ki67 readouts are informative in cynomolgus macaques, which was also demonstrated in separate studies using rhesus macaques.
Radiosurgery: a new application?
Authors: C B Wilson, D A Larson, P H Gutin
Journal: Journal of Clinical Oncology (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.9.1373 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1517780 Radiosurgery: a new application? C B WilsonxC B WilsonSearch for articles by this author , D A LarsonxD A LarsonSearch for articles by this author , P H GutinxP H GutinSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.9.1373 PDF "Radiosurgery: a new application?." Journal of Clinical Oncology, 10(9), pp. 1373–1374© 1992 by American Society of Clinical Oncology
Gastric Carcinoma; Can an Increased Diagnostic Accuracy Greatly Improve Survival Rates?
Authors: Templeton, Frederic E.
Journal: JNCI Journal of the National Cancer Institute (1947)

Journal Article Gastric Carcinoma; Can an Increased Diagnostic Accuracy Greatly Improve Survival Rates? Get access Frederic E. Templeton, M. D. Frederic E. Templeton, M. D. Seattle Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 7, Issue 5, April 1947, Pages 385–386, https://doi.org/10.1093/jnci/7.5.385 Published: 01 April 1947
AB0456 Good Response on Tocilizumab for Patients with Rheumatoid Arthritis Persists for 3 Years
Authors: I.M. Visman, E. Kneepkens, I. van den Oever, S. Turk, M. van Beers-Tas, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> With the advent of biological therapy a range of new drugs have come available for patients with rheumatoid arthritis (RA). Tocilizumab (TCZ) was registered more recently for patients with RA. Obviously, data on long-term efficacy and safety in daily clinical practice is important as results obtained in short-term clinical registration trials might differ from those observed in long-term daily clinical practice. <h3>Objectives</h3> To ascertain the efficacy of long- term TCZ treatment for RA <h3>Methods</h3> From May 2009 to August 2014, 40 consecutive patients have been included in the TCZ RA cohort Patients were eligible for inclusion if disease activity was high despite previous treatment with TNF-inhibitor and in the absence of contraindications for the start of TCZ. TCZ was given, intravenously, in a dose of 8 mg/kg once every 4 weeks. Visits were performed regularly based on a fixed protocol. At every visits, disease activity was measured using Disease Activity Score of 28 joints (DAS28). Improvement after baseline as measured using the ΔDAS28. In addition, the Health Assessment Questionnaire was performed at baseline and half yearly thereafter. To investigate the course of DAS28 and improvement over time a t-test was used. <h3>Results</h3> The mean age was 53 years (SD:18), and 29 (73%) were female. At baseline, the median disease duration was 9 (5-18) years, 29 (74%) were rheumatoid factor positive, 25 (66) had erosive disease, 29 (76%) were anti-CCP positive. At baseline, 22 (56%) used methotrexate (MTX), 24 (62%) used prednisolone, and 11 (28%) a DMARD other than MTX. On average patients had used 3.4 (SD:1.3) DMARDs, and 2.0 (0-3.0) biologicals. The maximum follow-up duration was 4.7 years, during which a total of 23 (58%) patients were stillon drug, and 17 (43%) patients have dropped out 8 patients (47%) due to adverse events, 7 patients (41%) stopped due to inefficacy, and 2 patients (12%) stopped for other reasons. The median follow-up duration was 0.48 (IQR:0.23-1.97) years for patients currently on TCZt, and 1.02 (0.25-1.96) years for drop-outs. The mean DAS-28 dropped significantly from 5.3 (SD: 1.7) at baseline to 3.2 (1.3) at 12 weeks. This improvement sustained and increased further over 3 years, see figure. The mean score on the health assessment questionnaire (HAQ) dropped from 1.6 (0.7) to 1.3 (0.8) at 12 weeks of treatment, and remained stable after that, see figure. <h3>Conclusions</h3> This cohort of RA patients treated with TCZ intravenously followed long term showed that the initial good response on tocilizumab persists for at least 3 years of follow-up based on DAS28 and HAQ, in patients who remained on TCZ treatment. 43% of patients dropped out during 5 years of follow-up. <h3>Disclosure of Interest</h3> None declared
SP0004 The Therapeutic Landscape in RA – Bdmards, Biosimilars and Beyond
Authors: J.E. Fonseca
Journal: Annals of the Rheumatic Diseases (2015)

The use of biologic disease modifying anti rheumatic drugs (bDMARDs) has revolutionized the treatment of rheumatoid arthritis (RA). Innovation in this filed is continuous and several innovative bDMARDs that are currently on clinical trials will be reviewed. In addition, data coming from national registries has helped to fine tune the use of bDMARDs and this information will be also updated. Biological therapies are large, highly complex molecules derived from living cells or organisms. Biological therapies have intrinsic variability, creating differences even between subsequent batches of the same product. In contrast to the traditional chemical medicines, which are simple molecules of low molecular weight, synthesized by chemical means that can be precisely reproduced after the expiring of the patent, biologics cannot. In addition, after expiring the patent access to the manufacturing conditions used in producing the originator therapy, including, for example, the relevant cell line clone and growth medium, is not granted. Therefore it cannot be guaranteed that biosimilar products are identical to their reference product on a molecular level. Thus, while conventional generic drugs require only a limited comparison and demonstration of identity to the reference product, biosimilars require a thorough comparison of structural and functional characteristics and a detailed preclinical testing, preceding phase I and phase III trials. Biosimilars offer a highly attractive strategy for reducing medical costs and increase accessibility to targeted biologic therapies. A landmark event for the future widespread use of biosimilars was the European Medicines Agency (EMA) approval of infliximab biosimilars. The post marketing surveillance, with special emphasis for the role of national registries, will be crucial for the confidence on the use of these biosimilars and will pave the way for the approval in the near future of other biosimilar candidates of biologics, such as rituximab, adalimumab and etanercept. Another field of future opportunities for RA treatment are the inhibitors of intracellular signalling pathways, allowing oral administration, potentially less expensive and exploring new mechanisms of action that offer the promise of controlling an additional fraction of patients who still have persistent disease. Issues related to toxicity have limited its widespread use and this will be also detailed in this session. <h3>Disclosure of Interest</h3> J. Fonseca Grant/research support from: Abbvie, Amgen, Celtrion, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbvie, Amgen, Celtrion, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB
Phase I/II trial of gemcitabine (Gem) plus irinotecan (CPT-11) for metastatic pancreatic cancer (MPC).
Authors: Takuo Yamai, Tatsuya Ioka, Hironari Sueyoshi, Ryoji Takada, Nobuyasu Fukutake, Reiko Ashida, Kazuhiro Katayama
Journal: Journal of Clinical Oncology (2014)

301 Background: Treatment options for patients with metastatic pancreatic cancer are still limited. Recently, new strategies to prolong disease control are reported. We conducted phase I/II trial of GEM+CPT-11 combination chemotherapy for MPC to evaluate the effectiveness and safety. Methods: As phase I study, traditional 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose. Four escalating dose levels of GEM/CPT-11 (800/60 mg/m 2 , 1000/60 mg/m 2 , 1000/80 mg/m 2 , and 1000/100 mg/m 2 ) were studied. As results of this investigation, the recommended phase II dose was GEM 1000 mg/m2 and CPT-11 100 mg/m2, biweekly. Phase II eligibility included naïve MPC, PS0-2, Pathological diagnosis, no refractory ascites and pleural effusion, and adequate organ function. Primary endpoint was overall survival. Results: Eighteen patients were entered phase I study. The DLTs were anorexia, and nausea/vomiting. Severe neutropenia was rare. MTDs were determined GEM 1000 and CPT-11 100 mg/m 2 . After that, we investigated phase II trial in 40 patients. There were 6 partial response, 14 stable disease, 18 progressive disease and 2 in-evaluable. Response rate was 16%. The median overall survival was 7.5 months; progressive disease 4.0 months. Grade 3 to 4 toxicity included neutropenia (7%), anemia (7%), diarrhea (7%), ALT elevation (10%), pneumonitis(7%). There was no treatment-related death. Conclusions: This combination chemotherapy is not effective as first-line chemotherapy for metastatic pancreatic cancer. But this is safe and generally well tolerated. This chemotherapy could be effective of salvage chemotherapy with low toxicity after standard chemotherapy such as FOLFIRINOX.
Mycophenolate mofetil as an alternative treatment for autoimmune hepatitis
Authors: Seung Woon Park, Soon Ho Um, Han Ah Lee, Sang Hyun Kim, Yura Sim, Sun Young Yim, Yeon Seok Seo, Ho Sang Ryu
Journal: Clinical and Molecular Hepatology (2016)

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.