tbuckley/cabot-search huggingface dataset:
Osteoporosis treatment effectiveness in patient with idiopathic pulmonary fibrosis (IPF)
Authors: Yulia Ilkovich, Dali Dzadzua, Lubov Novikova
Journal: European Respiratory Journal (2012)

Aim: to assess effectiveness of osteoporosis treatment by Calcium, Vitamin D3 (VD3), Bisphosphonates (BPN), Calcitonin (CTN) in patients with IPF.

Subjects: 95 Caucasian patients with IPF, 18 male, 77 female, 55.4±10.9 y.o., treated with glucocorticoids.

Materials, methods. Bone Mineral Density was measured by DEXA. Patients were categorized according to T-criterion value. 19 patients (1st group) had T-criterion > -1.5 SD. In this group only Calcium and VD3 were recommended. 24 patients (2nd group) had T-criterion value from -1.5 SD to -2.0 SD. In this group Calcium, VD3 and BPN were prescribed. 20 patients (3rd group) had T-criterion value from -2.0 SD to -2.5 SD. In these cases Calcium, VD3 and CTN were prescribed. 32 persons (4th group) had T-criterion lower than -2.5 SD. These patients received Calcium, VD3, CTN, BPN.

Results were assessed in a year. The main criteria were: T-criterion change (ΔT), fractures incidence, presence of bone pain (BP). In the 1st group ΔT was -0.07 SD, 10.5% patients had manifestation of BP. In the 2nd group ΔT was -0.25 SD; one hip fracture occurred; the number of patients with BP decreased from 66.7 % to 25.0 % (p<0.001). In the 3rd group ΔT was +0,04 SD, no fractures were registered, the number of patients with BP increased from 20.0% to 30.0%. In the 4th group ΔT was +0.11 SD; no fractures were registered, the number of patients with BP decreased from 25.0 % to 6.3 % (p <0.01).

Combination of Calcium and VD3 with antiresorptive agents (both CTN and BPN) is an essential way to prevent and treat osteoporosis in patients with IPF. CTN has an advantage due to its analgesic effect in osteoporotic patients with bone pain.
Complement receptors regulate differentiation of bone marrow plasma cell precursors expressing transcription factors Blimp-1 and XBP-1
Authors: Dominique Gatto, Thomas Pfister, Andrea Jegerlehner, Stephen W. Martin, Manfred Kopf, Martin F. Bachmann
Journal: The Journal of Experimental Medicine (2005)

Humoral immune responses are thought to be enhanced by complement-mediated recruitment of the CD21-CD19-CD81 coreceptor complex into the B cell antigen receptor (BCR) complex, which lowers the threshold of B cell activation and increases the survival and proliferative capacity of responding B cells. To investigate the role of the CD21-CD35 complement receptors in the generation of B cell memory, we analyzed the response against viral particles derived from the bacteriophage Qbeta in mice deficient in CD21-CD35 (Cr2(-/-)). Despite highly efficient induction of early antibody responses and germinal center (GC) reactions to immunization with Qbeta, Cr2(-/-) mice exhibited impaired antibody persistence paralleled by a strongly reduced development of bone marrow plasma cells. Surprisingly, antigen-specific memory B cells were essentially normal in these mice. In the absence of CD21-mediated costimulation, Qbeta-specific post-GC B cells failed to induce the transcriptional regulators Blimp-1 and XBP-1 driving plasma cell differentiation, and the antiapoptotic protein Bcl-2, which resulted in failure to generate the precursor population of long-lived plasma cells residing in the bone marrow. These results suggest that complement receptors maintain antibody responses by delivery of differentiation and survival signals to precursors of bone marrow plasma cells.
Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease
Authors: F Krombach, JT Gerlach, C Padovan, A Burges, J Behr, T Beinert, C Vogelmeier
Journal: European Respiratory Journal (1996)

This flow cytometric study was designed to identify, characterize and quantify alveolar monocyte-like cells in healthy volunteers and in patients with chronic inflammatory lung disease. Cells were obtained by bronchoalveolar lavage (BAL) from 19 patients with sarcoidosis, 29 with idiopathic pulmonary fibrosis, 10 with extrinsic allergic alveolitis, 19 with collagen vascular disease, and from 10 healthy volunteers. By taking advantage of the distinct electro-optical features of alveolar macrophages (AMs) and monocyte-like cells, the numbers of alveolar monocyte-like cells were counted, the cell dimensions calculated, and the densities of antigens on the surface of alveolar monocyte-like cells and AMs were compared. By using a panel of monoclonal antibodies detecting CD11b, CD14, CD16, and human leucocyte antigen-DR (HLA-DR), the immunophenotypes of these cells were selectively characterized. In the BAL fluid of patients with chronic inflammatory lung disease, significantly increased numbers of alveolar monocyte-like cells were detected that exhibited an immunophenotype intermediate between blood monocytes and mature AMs. Positive correlations were found between numbers of monocyte-like cells and expression of the monocyte-associated surface antigens CD11b and CD14 on total AMs; in contrast, an inverse relationship existed between monocyte numbers and expression of the macrophage-associated surface antigens CD16 and HLA-DR. When the patients were assigned to two groups according to the percentage of BAL monocyte-like cells being lower or higher than 13% (= mean value of the controls +2SD), it could be demonstrated that a high percentage of BAL monocyte-like cells was associated with significantly reduced lung function parameters. In summary, our flow cytometric data strongly support the view that considerable numbers of blood monocytes are recruited to the bronchoalveolar space in patients with chronic inflammatory lung disease.
Metacognition, mindreading, and insight in schizophrenia
Authors: Ben Wiffen, Anthony David
Journal: Behavioral and Brain Sciences (2009)

Abstract Mindreading in schizophrenia has been shown to be impaired in a multitude of studies. Furthermore, there is increasing evidence to suggest that metacognition is damaged as well. Lack of insight, or the inability to recognise one's own disorder, is an example of such a failure. We suggest that mindreading and metacognition are linked, but separable.
Uses of Electronic Health Records for Public Health Surveillance to Advance Public Health
Authors: Guthrie S. Birkhead, Michael Klompas, Nirav R. Shah
Journal: Annual Review of Public Health (2015)

Public health surveillance conducted by health departments in the United States has improved in completeness and timeliness owing to electronic laboratory reporting. However, the collection of detailed clinical information about reported cases, which is necessary to confirm the diagnosis, to understand transmission, or to determine disease-related risk factors, is still heavily dependent on manual processes. The increasing prevalence and functionality of electronic health record (EHR) systems in the United States present important opportunities to advance public health surveillance. EHR data have the potential to further increase the breadth, detail, timeliness, and completeness of public health surveillance and thereby provide better data to guide public health interventions. EHRs also provide a unique opportunity to expand the role and vision of current surveillance efforts and to help bridge the gap between public health practice and clinical medicine.
Hereditary tyrosinemia type I: A new clinical classification with difference in prognosis on dietary treatment
Authors: Francjan J. Van Spronsen, Yolande Thomasse, Peter G.A. Smit, James V. Leonard, Peter T. Clayton, Vaclav Fidler, Ruud Berger, Hugo S.A. Heymans
Journal: Hepatology (1994)

Hereditary tyrosinemia type I (McKusick 27670) is a heterogeneous disease with poor prognosis, yet there are few reports of the long-term prognosis. It is therefore difficult to decide on the treatment for individual patients. We have conducted an international survey of patients with tyrosinemia type I and examined the probability of survival on dietary treatment and the causes of death in 108 patients with tyrosinemia type I. The survival after the onset of symptoms varied with the age at onset; the earlier the symptoms developed the poorer the outlook. Liver failure and recurrent bleeding (67%), hepatocellular carcinoma (17%) and the porphyria-like syndrome with respiratory failure (10%) were the most common causes of death. The 1- and 2-yr survival probability after the onset of symptoms in patients in whom symptoms developed before 2 mo, between 2 and 6 mo and after 6 mo were 38%/29%, 74%/74% and 96%/96%, respectively. On the basis of these survival rates, a new classification--which is important with respect to choices in treatment--is proposed: very early (onset of symptoms < 2 mo), early (2 to 6 mo) and late presenting form (> 6 mo).
Long-term Temporal Patterns of Ventricular Tachyarrhythmias
Authors: Mark A. Wood, Pippa M. Simpson, Bruce S. Stambler, John M. Herre, Robert C. Bernstein, Kenneth A. Ellenbogen
Journal: Circulation (1995)

Background Technological limitations have precluded investigation of long-term temporal patterns of ventricular tachyarrhythmia recurrences. Newer implantable cardioverter-defibrillators permit such analyses by accurately recording the time and date of tachycardia detections during long-term follow-up. This study tests the hypothesis that ventricular tachycardia occurrences are randomly distributed over time in individual patients. Methods and Results The time and date of 727 episodes of ventricular tachyarrhythmias were recorded from the data logs of 31 patients with implantable cardioverter-defibrillators followed for a median of 177 days (range, 7 to 782 days). All patients had three or more ventricular tachycardia detections and no detections from causes other than ventricular arrhythmias. In 28 of 31 patients, the distribution of the interdetection time intervals during follow-up differed significantly (all P &lt;.01) from an exponential model distribution of interdetection intervals that assumed that detections were equally likely to occur at any time during follow-up (random). The Kolmogorov-Smirnov goodness-of-fit test was used to compare sample and model distributions. In each patient, the nonrandom distributions resulted from a preponderance of interdetection time intervals that were shorter than predicted by the random model, resulting in a temporal clustering of arrhythmic events. The interdetection interval was ≤1 hour and ≤91 hours for 55% and 78% of all intervals, respectively. When only those episodes receiving shock or antitachycardia pacing therapy were analyzed, 25 of 29 patients still manifested nonrandom distributions (all P &lt;.01). When only episodes with tachycardia rates &gt;240 beats per minute were analyzed, 11 of 13 patients manifested nonrandom distributions (all P &lt;.01). Conclusions Ventricular tachycardia detections and delivered antitachycardia therapies by implantable cardioverter-defibrillators are nonrandomly distributed throughout long-term follow-up in the majority of patients. The temporal clustering of these arrhythmic events may allow preemptive antiarrhythmic therapy and should be considered in the design of therapy based on suppression of spontaneous ventricular arrhythmias to statistically derived end points.
Effects of insulin and exercise on muscle lipoprotein lipase activity in man and its relation to insulin action.
Authors: B Kiens, H Lithell, K J Mikines, E A Richter
Journal: Journal of Clinical Investigation (1989)

The effects of exercise and a physiological increase in plasma insulin concentration on muscle lipoprotein lipase activity (mLPLA), leg exchange of glucose, and serum lipoprotein levels were investigated in healthy young men. During euglycemic hyperinsulinemia (n = 7) at 44 mU.liter-1, m-LPLA in non-exercised muscle decreased from 30 +/- 7.4 mU.g-1 wet weight (w.w.) (mean +/- SE) to 19 +/- 3.3 (P less than 0.05). Furthermore, the decrease in m-LPLA correlated closely (r = 0.97, P less than 0.05) with the increase in leg glucose uptake. Moreover, basal m-LPLA correlated with the insulin-induced increase in leg glucose uptake (r = 0.93, P less than 0.05). In the control group (n = 6) in which saline was infused in place of insulin and glucose, m-LPLA in nonexercised muscle did not change with time. No change in m-LPLA was observed immediately after one-legged knee extension exercise, but 4 h after exercise m-LPLA was higher (P less than 0.05) in the exercised thigh (47 +/- 17.8 mU.g-1 w.w.) compared with the contralateral nonexercised thigh (29 +/- 6.3 mU.g-1 w.w.). This difference was not found 8 h after exercise. The triacylglycerol content of serum lipoproteins decreased during insulin infusion. It is concluded that in contrast to the effect on adipose tissue, physiological concentrations of insulin decrease m-LPLA in proportion to the effect of insulin on muscle glucose uptake, while muscle contractions cause a local, delayed, and transient increase in m-LPLA. Further-more, basal m-LPLA is an indicator of muscle insulin sensitivity.
Radiotherapy With Concurrent Carbogen and Nicotinamide in Bladder Carcinoma
Authors: Peter J. Hoskin, Ana M. Rojas, Søren M. Bentzen, Michele I. Saunders
Journal: Journal of Clinical Oncology (2010)

Phase II clinical studies suggest that hypoxic modification with carbogen and nicotinamide (CON) may increase the efficacy of radiotherapy (RT).Three hundred thirty-three patients with locally advanced bladder carcinoma were randomly assigned to RT alone versus RT with CON. A schedule of either 55 Gy in 20 fractions in 4 weeks or 64 Gy in 32 fractions in 6.5 weeks was used. The primary end point was cystoscopic control at 6 months (CC(6m)) and secondary end points were overall survival (OS), local relapse-free survival (RFS), urinary and rectal morbidity.CC(6m) was 81% for RT + CON and 76% for RT alone (P = .3); however, just more than half of patients underwent cystoscopy at that time. Three-year estimates of OS were 59% and 46% (P = .04) and 3-year estimates of RFS were 54% and 43% (P = .06) for RT + CON versus RT alone. Risk of death was 14% lower with RT + CON (P = .04). In multivariate comparison, RT + CON significantly reduced the risk of relapse (P = .05) and death (P = .03). There was no evidence that differences in late urinary or GI morbidity between treatment groups or between fractionation schedules were significant.RT + CON produced a small nonsignificant improvement in CC(6m). Differences in OS, risk of death, and local relapse were significantly in favor of RT + CON. Late morbidity was similar in both trial arms. Results indicate a benefit of adding CON to radical RT.
Adoptively Transferable Tolerance Induced by CD45RB Monoclonal Antibody
Authors: ZUHUA GAO, ROBERT ZHONG, JIFU JIANG, BERTHA GARCIA, JING JING XING, MARTIN J. WHITE, ANDREW I. LAZAROVITS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The phenomenon of rejection remains the most serious problem in transplantation. The ultimate goal in transplant immunology is to develop therapeutic strategies that lead to tolerance. It has been shown that two injections of a monoclonal antibody to CD45RB leads to indefinite acceptance of renal allografts in mice. Moreover, the CD45RB monoclonal antibody reverses acute rejection and still induces tolerance. The purpose of this study was to assess mechanisms that could underlie this therapeutic benefit. It was shown that splenic lymphocytes from tolerant animals augmented proliferation in allogeneic mixed lymphocyte reactions against donor alloantigens, and the serum of tolerant mice contained donor-specific antibodies, mainly of the IgG1 isotype, suggesting the presence of TH2 cytokines. Tolerance could not be broken by interleukin-2 infusion, but tolerance could be adoptively transferred by transfusion of tolerant mouse CD4 + splenic lymphocytes into naive allografted animals. These data suggest that an active immunoregulatory mechanism is partly responsible for the therapeutic effect. CD45RB-directed therapy may find clinical application in organ transplantation in human patients.
Prognostic Implication of FLT3 and N- RAS Gene Mutations in Acute Myeloid Leukemia
Authors: Hitoshi Kiyoi, Tomoki Naoe, Yasuyuki Nakano, Shohei Yokota, Saburo Minami, Shuichi Miyawaki, Norio Asou, Kazutaka Kuriyama, Itsuro Jinnai, Chihiro Shimazaki, Hideki Akiyama, Kenji Saito, Hakumei Oh, Toshiko Motoji, Eijiro Omoto, Hidehiko Saito, Ryuzo Ohno, Ryuzo Ueda
Journal: Blood (1999)
Extravascular necrotizing palisaded granulomas as the presenting skin sign of systemic lupus erythematosus
Authors: G. Obermoser, B. Zelger, R. Zangerle, N. Sepp
Journal: British Journal of Dermatology (2002)

Journal Article Extravascular necrotizing palisaded granulomas as the presenting skin sign of systemic lupus erythematosus Get access G. Obermoser, G. Obermoser Department of Dermatology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria G.Obermoser. E‐mail: gerlinde.obermoser@uibk.ac.at Search for other works by this author on: Oxford Academic Google Scholar B. Zelger, B. Zelger Department of Dermatology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar R. Zangerle, R. Zangerle Department of Dermatology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar N. Sepp N. Sepp Department of Dermatology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 2, 1 August 2002, Pages 371–374, https://doi.org/10.1046/j.1365-2133.2002.04790.x Published: 01 August 2002 Article history Accepted: 07 January 2002 Published: 01 August 2002
High prevalence of NSAID enteropathy as shown by a simple faecal test
Authors: J A Tibble, G Sigthorsson, R Foster, D Scott, M K Fagerhol, A Roseth, I Bjarnason
Journal: Gut (1999)

BACKGROUND The diagnosis of non-steroidal anti-inflammatory drug (NSAID) induced enteropathy is difficult, requiring enteroscopy or the use of four day faecal excretion of 111 In labelled white cells. AIMS To assess faecal calprotectin (a non-degraded neutrophil cytosolic protein) as a method for diagnosing NSAID enteropathy. METHODS Single stool faecal calprotectin concentrations were compared with the four day faecal excretion of 111 In labelled white cells in 47 patients taking NSAIDs. The prevalence and severity of NSAID enteropathy was assessed using this method in 312 patients (192 with rheumatoid arthritis, 65 with osteoarthritis, 55 with other conditions) taking 18 different NSAIDs. RESULTS The four day faecal excretion of 111 In white cells correlated significantly with faecal calprotectin concentrations. In the group of 312 patients on NSAIDs faecal calprotectin concentrations were significantly higher than in controls, the prevalence of NSAID enteropathy being 44%. The prevalence and severity of NSAID enteropathy was independent of the particular type or dose of NSAID being taken or other patient variables. CONCLUSIONS Assay of faecal calprotectin provides a simple practical method for diagnosing NSAID enteropathy in man. Forty four per cent of patients receiving these drugs had NSAID induced enteropathy when assessed by this technique; 20% of these had comparable levels of inflammation to that previously reported in patients with inflammatory bowel disease.
Intranodal Vaccination with Naked Antigen-Encoding RNA Elicits Potent Prophylactic and Therapeutic Antitumoral Immunity
Authors: Sebastian Kreiter, Abderraouf Selmi, Mustafa Diken, Michael Koslowski, Cedrik M. Britten, Christoph Huber, Özlem Türeci, Ugur Sahin
Journal: Cancer Research (2010)

Abstract Although naked antigen-encoding RNA has entered clinical testing, basic knowledge on how to apply this promising novel vaccine format is still pending. By comparing different administration routes, we observed surprisingly potent antigen-specific T-cell immunity upon intranodal injection of naked antigen-encoding RNA. RNA was selectively uptaken by resident dendritic cells, propagated a T-cell attracting and stimulatory intralymphatic milieu, and led to efficient expansion of antigen-specific CD8+ as well as CD4+ T cells. By intranodal treatment of mice with repeated cycles of RNA, we achieved de novo priming of naïve T cells, which became potent cytolytic effectors capable of homing to primary and secondary lymphatic tissues as well as memory T cells. In tumor-bearing mice intralymphatic RNA vaccination elicited protective and therapeutic antitumor immune responses, resulting in a remarkable survival benefit as compared with other treatment regimens. This is the first report of strong systemic antigen-specific Th1-type immunity and cancer cure achieved with naked antigen-encoding RNA in preclinical animal models. Cancer Res; 70(22); 9031–40. ©2010 AACR.
Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor.
Authors: C Weber, T A Springer
Journal: Journal of Clinical Investigation (1997)

We have studied the pathways that lead to arrest and firm adhesion of rolling PMN on activated, surface-adherent platelets. Stable arrest and adhesion strengthening of PMN on thrombin-stimulated, surface-adherent platelets in flow required distinct Ca2+- and Mg2+-dependent regions of Mac-1 (alphaMbeta2), and involved interactions of Mac-1 with fibrinogen, which was bound to platelets via alphaIIbbeta3. Mac-1 also bound to other unidentified ligands on platelets, which were not intracellular adhesion molecule-2 (ICAM-2), heparin, or heparan-sulfate proteoglycans. This was shown by inhibition with mAbs or peptides, by treatment of platelets with heparitinase, and by using platelets with defective alphaIIbbeta3 from a patient with Glanzmann thrombasthenia. Tethering of PMN on platelet ICAM-2 via LFA-1 (alphaLbeta2) was observed, which may facilitate the transition between rolling on selectins and Mac-1-dependent arrest. Arrest and adhesion strengthening was pertussis toxin sensitive and in flow was mainly induced by platelet-activating factor but not through activation of the chemokine receptor CXCR2. In stasis, spreading occurred and the CXCR2 contributed to firm adhesion.
Missing Data in Clinical Studies: Issues and Methods
Authors: Joseph G. Ibrahim, Haitao Chu, Ming-Hui Chen
Journal: Journal of Clinical Oncology (2012)

Missing data are a prevailing problem in any type of data analyses. A participant variable is considered missing if the value of the variable (outcome or covariate) for the participant is not observed. In this article, various issues in analyzing studies with missing data are discussed. Particularly, we focus on missing response and/or covariate data for studies with discrete, continuous, or time-to-event end points in which generalized linear models, models for longitudinal data such as generalized linear mixed effects models, or Cox regression models are used. We discuss various classifications of missing data that may arise in a study and demonstrate in several situations that the commonly used method of throwing out all participants with any missing data may lead to incorrect results and conclusions. The methods described are applied to data from an Eastern Cooperative Oncology Group phase II clinical trial of liver cancer and a phase III clinical trial of advanced non-small-cell lung cancer. Although the main area of application discussed here is cancer, the issues and methods we discuss apply to any type of study.