tbuckley/cabot-search huggingface dataset:
Regulatory B10 Cells Are Decreased in Patients With Rheumatoid Arthritis and Are Inversely Correlated With Disease Activity
Authors: Claire I. Daien, Sarah Gailhac, Thibault Mura, Rachel Audo, Bernard Combe, Michael Hahne, Jacques Morel
Journal: Arthritis & Rheumatology (2014)

Regulatory interleukin-10 (IL-10)-producing B cells (B10 cells) have been shown to prevent and cure collagen-induced arthritis in mice. In humans, very little is known about B10 cells in rheumatoid arthritis (RA). Several B cell subsets, such as CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells, were suggested to be precursors of B10 cells. We aimed to analyze these B cell subsets and B10 cells in RA patients and healthy controls.B10 cells were generated from peripheral blood mononuclear cells stimulated for 24 hours with CpG and for 4 hours with phorbol 12-myristate 13-acetate/ionomycin/brefeldin A. Intracellular B cell IL-10 was assessed by flow cytometry. Thirty-one controls and 99 RA patients were included.After multiple adjustments, levels of CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells were found to be similar in RA patients and controls. Levels of B10 cells were lower in RA patients than in controls, especially in patients with RA of ≤5 years' duration. Levels of B10 cells correlated inversely with the Disease Activity Score in 28 joints. This was more pronounced in patients with RA of ≤5 years' duration, in whom B10 cells also correlated inversely with C-reactive protein levels. Moreover, B10 cells correlated inversely with rheumatoid factor levels. CD24(high) CD38(high) and CD24(high) CD27+ B cells induced more Treg cells than did CD24(low) B cells in controls but not in RA patients.The ability of B cells to produce IL-10 was altered in RA, and this impairment influenced disease activity, biologic inflammation, and autoantibody levels, especially in patients with RA of ≤5 years' duration. This strongly suggests a role of B10 cells in RA initiation.
Pathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer: a prospective assessment.
Authors: F Saliba, R Hagipantelli, J L Misset, G Bastian, G Vassal, M Bonnay, P Herait, C Cote, M Mahjoubi, D Mignard, E Cvitkovic
Journal: Journal of Clinical Oncology (1998)

PURPOSE Irinotecan (CPT-11), a camptothecin derivative, has shown efficacy against colorectal cancer. Delayed-onset diarrhea is its main limiting toxicity. The aim of this study was to determine the pathophysiology of CPT-11-induced delayed-onset diarrhea and assess the efficacy of combined antidiarrheal medication in a phase II, prospective, successive-cohorts, open study. PATIENTS AND METHODS Twenty-eight patients with advanced colorectal cancer refractory to fluorouracil (5-FU) therapy received CPT-11 350 mg/m2 every 3 weeks. The first cohort of 14 consecutive patients explored for the mechanism of diarrhea received acetorphan (a new enkephalinase inhibitor) 100 mg three times daily; the second 14-patient cohort received, in addition to acetorphan, loperamide 4 mg three times daily. Before treatment, and if late diarrhea occurred, patients underwent colon mucosal biopsies for CPT-11 and topoisomerase I levels; intestinal transit time; fecalogram; fat and protein excretion; alpha1-antitrypsin clearance; D-xylose test; blood levels for vasoactive intestinal polypeptide, glucagon, gastrin, somatostatin, prostaglandin E2, and carboxylesterase; CPT-11/SN-38 and SN-38 glucuronide pharmacokinetics; and stool cultures. RESULTS Delayed-onset diarrhea occurred during the first three treatment cycles in 23 patients (82%). Electrolyte fecal measurements showed a negative or small osmotic gap in nine of nine patients and an increased alpha1-antitrypsin clearance in six of six patients. There were no modifications in stool cultures or hormonal dysfunction. Four of 11 patients (36%) with delayed-onset diarrhea in the first cohort responded to acetorphan, whereas nine of 10 patients (90%) responded to the combination of acetorphan and loperamide (P &lt; .02). CONCLUSION CPT-11-induced delayed-onset diarrhea is caused by a secretory mechanism with an exudative component. Early combined treatment with loperamide and acetorphan seems effective in controlling the diarrheal episodes.
The role of increased airway microvascular permeability and plasma exudation in asthma
Authors: KF Chung, DF Rogers, PJ Barnes, TW Evans
Journal: European Respiratory Journal (1990)

Airway oedema and inflammation are recognized as cardinal features of asthma, resulting from increase microvascular permeability of the bronchial circulation with the exudation of plasma and inflammatory cells into the airway lumen. Resistance to airflow is increased and the epithelium is disrupted either directly or by cytotoxic proteins derived from migrating inflammatory cells. Such mediators include bradykinin, platelet-activating factor (PAF), leukotrienes and histamine. Antigen-induced and neurogenic inflammation, generated by immunoglobulin E (IgE) and neuropeptides respectively, may also contribute to oedema generation. Assessment of increased bronchial vascular permeability in animals has largely involved measurement of the extravasation of radiolabelled albumin or protein-bound dyes. Non-invasive techniques are less reliable in humans, but measurement of the rate of clearance of inhaled particles labelled with isotope may prove successful. Airway oedema appears to be an important feature of asthma and future research may be aimed at developing drugs that specifically prevent airway microvascular leakage.
Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomised controlled trial
Authors: Gregory L Calligaro, Grant Theron, Hoosain Khalfey, Jonathan Peter, Richard Meldau, Brian Matinyenya, Malika Davids, Liezel Smith, Anil Pooran, Maia Lesosky, Aliasgar Esmail, Malcolm G Miller, Jenna Piercy, Lancelot Michell, Rodney Dawson, Richard I Raine, Ivan Joubert, Keertan Dheda
Journal: The Lancet Respiratory Medicine (2015)
Statistics notes: Multiple significance tests: the Bonferroni method
Authors: J M. Bland, D. G Altman
Journal: BMJ (1995)

<h3>Abstract</h3> Recent studies have shown that p53 contributes to poor survival during immune checkpoint blockade (ICB) therapy. Lung cancer patients with p53 mutations have significantly improved response rates to PD-1 ICB therapy. While previous studies have shown that tumor-derived IL-33 is required for the anti-tumor immune response and efficacy of ICB therapies, the relationship between p53 and IL-33 during ICB therapy is unknown. In this study, we characterized the role of the p53/IL-33 axis in regulating the tumor microenvironment (TME) in response to ICB therapy. CRISPR-Cas9-mediated deletion of Trp53 in tumor cells combined with PD-1 ICB therapy synergistically inhibited tumor growth in a murine MC38 colon adenocarcinoma model. We observed increased CD4+ and CD8+ T cell infiltration, as well as reduced Treg infiltration. IL-33 was upregulated and its expression increased with time and response to treatment. Simultaneous deletion of Il33 in the MC38 tumor cells reversed the efficacy of PD-1 ICB therapy. ST2<sup>-/-</sup>(IL-33 receptor) mice with Trp53-deficient MC38 tumors also showed no response to PD-1 ICB. Our findings depict a novel mechanism by which the loss of p53 in tumors treated with ICB therapy induces upregulation of tumoral IL-33 and host ST2 signaling. p53 mutations may be a double-edged sword for cancer, i.e. loss of the tumor suppressor initially facilitates tumorigenesis, but also leads to upregulation of danger signals in the tumor. These danger signals, such as IL-33, mediate the anti-tumor effect of ICB.
73.6 Gy and Beyond: Hyperfractionated, Accelerated Radiotherapy for Non–Small-Cell Lung Cancer
Authors: Patrick D. Maguire, Lawrence B. Marks, Gregory S. Sibley, James E. Herndon II, Robert W. Clough, Kim L. Light, Maria L. Hernando, Philip A. Antoine, Mitchell S. Anscher
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To assess results with twice-daily high-dose radiotherapy (RT) for non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between 1991 and 1998, 94 patients with unresectable NSCLC were prescribed ≥ 73.6 Gy via accelerated fractionation. Fifty were on a phase II protocol (P group); 44 were similarly treated off-protocol (NP group). The clinical target volume received 45 Gy at 1.25 Gy bid (6-hour interval). The gross target volume received 1.6 Gy bid to 73.6 to 80 Gy over 4.5 to 5 weeks using a concurrent boost technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated by the Kaplan-Meier method. Median follow-up durations for surviving P and NP patients were 67 and 16 months, respectively. RESULTS: Total doses received were ≥ 72 Gy in 97% of patients. The median OS by stage was 34, 13, and 12 months for stages I/II, IIIa, and IIIb, respectively. LPFS was significantly longer for patients with T1 lesions (median, 43 months) versus T2-4 (median, 7 to 10 months; P = .01). Results were similar in the P and NP groups. Acute grade ≥ 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade ≥ 3 late toxicity in 86 assessable patients included esophagus (three patients; 3%), lung (15 patients; 17% [three grade 5]), skin (five patients; 6%), heart (two patients; 2%), and nerve (one patient; 1%). CONCLUSION: This regimen yielded favorable survival results, particularly for T1 lesions. Acute grade ≥ 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade ≥ 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses ≥ 86 Gy.
Spontaneous Reticular Neoplasms in (CBA × DBA/2)F&lt;sub&gt;1&lt;/sub&gt; Mice, With Special Emphasis on the Occurrence of Plasma Cell Neoplasms&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ragna Rask-Nielsen, Peter Ebbesen
Journal: JNCI Journal of the National Cancer Institute (1969)

Ninety-six spontaneous reticular neoplasms developing in 213 (CBA × DBA/2)F1 mice are described. Most neoplasms occurred in mice more than 18 months old. Thirty-five were classified as immature plasma cell, grade III, 15 as plasma cell, grade IV, 11 as definite reticulosarcomas, 6 as stem cell leukemias, and 25 as lymphatic leukemias; 4 were not classified. Paper and immunoelectrophoresis revealed γG paraproteinemia in 16 mice, γM in 2, and γA in 2 of the 35 mice with plasma cell neoplasms, grade III; 2 of the 15 neoplasms, grade IV, showed γG immunoglobulin production. On transplantation of the tumors, production of a certain type of paraprotein was usually retained for all generations or, in a few lines only, for some generations. Bence Jones protein was never observed. Malignancies producing immunoglobulin γM showed some lymphocytic differentation, whereas those producing γA immunoglobulin had “flaming” plasma cells. The high incidence of plasmacytoid neoplasms in mice of this particular genetic constitution is discussed in light of previously published evidence for the presence of a latent leukemogenic virus and the possible importance of an age-dependent decrease in immunologic capacity.
The in Vitro Chromosome Constitution of Cells from Human Tumors
Authors: Takaaki Ishihara, George E. Moore, Avery A. Sandberg
Journal: Cancer Research (1962)

Summary  The chromosome constitution was determined in nine established, long-term cultures of cells obtained from the effusions or excised tissues of cancer patients. The cultures were characterized by chromosome modes near the triploid range (66–75), with a considerable spread of the chromosome number about the mode. Analysis of the karyotypes revealed that most of the chromosomes could be grouped superficially into the various groups described for the normal human karyotype. The heteroploidy of the cells was due to extrasomy of all groups, with the exception of group G, which was usually in the diploid range. New, marker chromosomes were present in most of the cell lines examined.
High prevalence of sleep disordered breathing (SDB) in patients with systemic AL amyloidosis
Authors: Shameem Mahmood, Leena George, Milind Sovani, Peter Smith, Philip Hawkins, Sajitha Sachchithanantham, Thirusha Lane, Lisa Rannigan, Darren Foard, Rabya Sayed, Ketna Patel, Marianna Fontana, Carol Whelan, Helen Lachmann, Julian D. Gillmore, Ashutosh Wechalekar
Journal: European Respiratory Journal (2014)

Background: Patients with systemic amyloidosis with Oropharyngeal soft tissue abnormalities and/or heart failure are likely to have increased prevalence of sleep disordered breathing (SDB) and obstructive sleep apnoea (OSA) yet little data exist on this topic.  Aims: To explore the incidence of SDB in patients diagnosed with cardiac and or soft tissue involvement with macroglossia,  Methods: Between July 2013 and February 2014 Fifty three patients with either cardiac or macroglossia with clinical suspicion of SDB completed the Epworth Sleepiness Score (ESS) and STOP BANG questionnaire for OSA and underwent overnight Pulse Oximetry in addition to the standard protocol at the UK National Amyloidosis Centre.  Results: Data for 46 patients analysed: (Median Age 66, 58% male, median BMI 26). Twenty three patients had macroglossia and 30 had cardiac involvement. Fifteen,11, and 22 patients reported snoring, witnessed apnoeas and had neck circumference g 40cm respectively. 21 and 8 patients had STOP Bang score ≥3, ESS score more than 10 respectively. High risk of OSA was present in 20 (43%) by STOP BANG questionnaire score of ≥ 3. Overnight oximetry was abnormal in 32 (68%) patients. 32, 18, 13 patients had 4% Oxygen Desaturation Index (ODI) more than 5, 10, 15/hour respectively.  Conclusion: There is a high prevalence of SDB in Amyloidosis. Most patients are tired but not sleepy. There was no difference in any parameters between patients with macroglossia and cardiac involvement. STOP BANG questionnaire likely to miss out those with central SDB due to heart failure. Sleep Polygraphy and longitudinal studies are needed to characterise this further and to assess effects on cardiac mortality.
Patients will challenge doctors more, says study
Authors: Roger Dobson
Journal: BMJ (2000)

The rise of consumerism in health care has brought a decline in deference, as patients are less willing to trust the opinion of doctors and managers, according to a report based on a study of a series of cases involving disputes over care. Health authorities and primary care groups must expect that their decisions will be increasingly challenged in future and will need to develop efficient decision-making processes to maintain confidence and sustain patient trust, says the report.

The study was co-authored by Professor Chris Ham, director of the health services management centre at Birmingham University, who is currently on secondment to the Department of Health on health …
Regulation of ghrelin on appetite in patients with acute exacerbations of chronic obstructive pulmonary disease
Authors: Ye Wang, Fuqiang Wen
Journal: European Respiratory Journal (2012)

Background: Patients with COPD are usually complicated with malnutrition, which is partly caused by reductions of appetite and food intake, especially in acute exacerbations. Recent studies reported the key roles of ghrelin in appetite stimulation and energy homeostasis. However, the association between the orexigenic function of ghrelin and appetite reduction in AECOPD remains unclear.  Objectives: To investigate the secretion, acylation of ghrelin, and its association with appetite reduction in patients with AECOPD.  Methods: Thirty-six patients with AECOPD and 23 healthy adults were enrolled. Total and acylated ghrelin, obestatin, simplified nutritional appetite questionnaire (SNAQ) scoring, and calorie intake were compared in patients between in exacerbations and in remissions. Further more, the same indexes were also compared between AECOPD patients and healthy controls.  Results: Total ghrelin level in patients was significantly higher in exacerbations than remissions (627.2±234.9 vs. 500.8±181.0 pg/ml, p=0.001), while the SNAQ score and calorie intake were significantly lower (10.8±2.3 vs. 14.3±1.8, p  Conclusions: A higher ghrelin level in AECOPD indicated increased secretion of ghrelin, but its role in stimulating appetite was compromised. Moreover, the decreased acylation of ghrelin was noted in patients, which might be a cause for appetite reduction in AECOPD.
Abstract 31: Comparison between Mechanical Active Chest Compression/Decompression and Standard Mechanical Chest Compression
Authors: Giuseppe Ristagno, Wanchun Tang, Hao Wang, Shijie Sun, Max H Weil
Journal: Circulation (2007)

Introduction. After cardiac arrest, uninterrupted chest compressions with restoration of myocardial blood flow facilitate defibrillation. Accordingly, decreases in intrathoracic pressure (ITP), fol...
Foodborne transmission of sorbitol-fermenting Escherichia coli O157:[H7] via ground beef: an outbreak in northern France, 2011
Authors: L.A. King, E. Loukiadis, P. Mariani-Kurkdjian, S. Haeghebaert, F.-X. Weill, C. Baliere, S. Ganet, M. Gouali, V. Vaillant, N. Pihier, H. Callon, R. Novo, O. Gaillot, D. Thevenot-Sergentet, E. Bingen, P. Chaud, H. de Valk
Journal: Clinical Microbiology and Infection (2014)
Acute respiratory failure and severe sepsis may identify different clinical phenotypes in community-acquired pneumonia
Authors: Stefano Aliberti, Anna Maria Brambilla, James D. Chalmers, Catia Cilloniz, Angelo Bignamini, Elena Prina, Alice D'Adda, Marco Mantero, Alberto Pesci, Julio Ramirez, Antoni Torres, Francesco Blasi, Roberto Cosentini
Journal: European Respiratory Journal (2013)

The aim of the study was to evaluate the impact of acute respiratory failure (ARF) and severe sepsis (SS) on outcomes of patients with community-acquired pneumonia (CAP). This was a multicenter, observational, prospective study of immunocompetent CAP patients admitted to three hospitals in Italy, Spain and Scotland between 2008 and 2010. ARF was defined as the presence of at least one among: PaO2
Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection.
Authors: Monica C Panelli, Mitchell E Stashower, Herbert B Slade, Kina Smith, Christopher Norwood, Andrea Abati, Patricia Fetsch, Armando Filie, Shelley-Ann Walters, Calvin Astry, Eleonora Aricó, Yingdong Zhao, Silvia Selleri, Ena Wang, Francesco M Marincola
Journal: Genome biology (2007)

Imiquimod is a Toll-like receptor-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection. We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (n = 22) or vehicle cream (n = 14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hours for 4 or 8 days). RNA was amplified and hybridized to 17.5 K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 × 4 days regimen, associated with highest effectiveness, induced the most changes, with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-α involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity. This study, based on a powerful and reproducible model of cancer eradication by innate immune mechanisms, provides the first insights in humans into the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction.
Consolidation with intraperitoneal cisplatin in first-line therapy of advanced ovarian cancer.
Authors: U Beller, J Speyer, N Colombo, J Sorich, J Wernz, H Hochster, A Zeleniuch-Jacquotte, R Porges, E M Beckman
Journal: Journal of Clinical Oncology (1991)

Seventy-five patients with advanced epithelial ovarian cancer were treated with a combined modality regimen of systemic, induction chemotherapy followed by intraperitoneal therapy (IPT). All patients underwent initial surgery for staging and/or cytoreduction followed by cisplatin 20 mg/m2 intravenously (IV) for 5 days and cyclophosphamide 600 mg/m2 on day 4 every 3 to 4 weeks for two to four cycles. Patients were then evaluated for IPT and, if eligible, had an intraperitoneal (IP) catheter placed. IPT consisted of cisplatin 60 mg/m2 in 2 L on day 1 and IV cyclophosphamide 600 mg/m2 on day 2 every 3 weeks for three to six cycles. Patients who demonstrated a clinical complete response (CCR) were then referred for second-look laparotomy (SLL). Of 71 patients who completed the induction phase, 53 (75%) were eligible for IPT, and 49 patients entered the therapy phase. Toxicity of the combined modality approach was acceptable and did not differ from our previous experience using the same drugs systemically. Thirty-two of the 49 patients who completed IPT achieved a CCR, which was confirmed by SLL in 20 patients. Twenty recurrences were documented in the 32 CCR patients, 13 occurred in patients after SLL. Projected median survival of all patients is 38 months. Median survival correlated with amount of residual disease following initial surgery (23 months for bulky v 45 months for minimal residual; P less than .001) and with performance status ([PS]; 24 months for PS 2, 3 v greater than 46 months for PS O; P less than .001). Patients who presented with bulky tumors were less likely to reach the consolidation IPT phase. Incorporation of IP cisplatin into the first-line regimen for treatment of ovarian cancer does not appear to have major impact on the survival of all treated patients when compared with our historical control series. Combined IV and IPT cisplatin and cyclophosphamide is feasible with acceptable toxicity. Its impact on response and survival may be limited to only "good-prognosis" patients.
Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe
Authors: R. Cantón, M. Akóva, Y. Carmeli, C.G. Giske, Y. Glupczynski, M. Gniadkowski, D.M. Livermore, V. Miriagou, T. Naas, G.M. Rossolini, Ø. Samuelsen, H. Seifert, N. Woodford, P. Nordmann
Journal: Clinical Microbiology and Infection (2012)