tbuckley/cabot-search huggingface dataset:
Abstract 1739: Alcohol Septal Ablation of Hypertrophic Cardiomyopathy Produces a Distinctive ECG Pattern
Authors: Erin Coakley, Daniel H Steinberg, Amit Tibrewala, Federico Asch, Augusto D Pichard, Kenneth M Kent, Joseph Lindsay
Journal: Circulation (2007)

Alcohol septal ablation (ASA) of patients with hypertrophic cardiomyopathy (HCM) produces necrosis limited to the base of the interventricular septum. Atherothrombotic occlusion of the left anterio...
Use of circulating tumor cells (CTC) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy to predict risk for relapse: The SUCCESS trial.
Authors: B. K. Rack, C. Schindlbeck, U. Andergassen, A. Schneeweiss, T. Zwingers, W. Lichtenegger, M. Beckmann, H. L. Sommer, K. Pantel, W. Janni
Journal: Journal of Clinical Oncology (2010)

1003 Background: The prognostic significance of CTCs in MBC has been demonstrated. We evaluated whether the presence of CTC before and after adjuvant chemotherapy increases the risk of subsequent relapse and death. Methods: We analyzed 23 mL of peripheral blood from 1,489 N+ and high risk N- breast cancer pts before and after adjuvant taxane based chemotherapy. CTC were assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-Ck8/18/19 and anti-CD45 antibodies to distinguish between epithelial cells and leukocytes. Pts were followed for a median of 32 months. Results: In 9.4% of pts (n > 140) > 1 CTC was detected before the start of systemic treatment (median 1, range 1-827), while 8.7% (n > 129) presented with > 1 CTC (median 1, range 1-124) after chemotherapy. Pts with CTC before treatment had significantly more lymphnodes involved (p < 0.01), but no correlation to tumor size, grading and HR-Status could be found. 85 recurrences occurred and 33 pts died of their disease. The presence of > 1 CTC before treatment was a significant prognostic factor with respect to poor DFS (p < 0.0001) and OAS (p > 0.023), whereas the persistence of > 1 CTC after chemotherapy only predicted reduced DFS (p > 0.054; p > 0.154 for OAS). A significantly better DFS and OAS was detected between the groups with persistently negative CTC status compared to those with persistently positive CTC status (p > 0.0031 and p > 0.0187). More than 5 CTC were a significant indicator of poor prognosis for DFS and OAS at all time points. In multivariate analysis, > 1CTC before treatment was an independent predictor for OAS, > 1 CTC after treatment for DFS, while tumor size, lymph node involvement, grading and HR-status were relevant for both time points. Conclusions: We demonstrated the prognostic relevance of CTC in peripheral blood of early breast cancer pts before and after chemotherapy. Therefore, CTC detection could serve as clinically useful prognostic marker and treatment monitoring tool and should be tested as indicator for additional secondary adjuvant treatment intervention within clinical trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Chugai Pharma, Lilly, Novartis, sanofi-aventis AstraZeneca, Chugai Pharma, Johnson & Johnson, Lilly, Novartis, sanofi-aventis
Tumor Radiosensitization by Antiinflammatory Drugs: Evidence for a New Mechanism Involving the Oxygen Effect
Authors: Nathalie Crokart, Kim Radermacher, Bénédicte F. Jordan, Christine Baudelet, Gregory O. Cron, Vincent Grégoire, Nelson Beghein, Caroline Bouzin, Olivier Feron, Bernard Gallez
Journal: Cancer Research (2005)

Abstract We hypothesized that nonsteroidal antiinflammatory drugs (NSAIDs) might enhance tumor radiosensitivity by increasing tumor oxygenation (pO2), via either a decrease in the recruitment of macrophages or from inhibition of mitochondrial respiration. The effect of four NSAIDs (diclofenac, indomethacin, piroxicam, and NS-398) on pO2 was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO2 (tmax, 30 minutes after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO2 measurements were done using electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging. The oxygen consumption rate of tumor cells after in vivo NSAID administration was measured using high-frequency electron paramagnetic resonance. Tumor-infiltrating macrophage localization was done with immunohistochemistry using CD11b antibody. All the NSAIDs tested caused a rapid increase in pO2. At tmax, tumor perfusion decreased, indicating that the increase in pO2 was not caused by an increase in oxygen supply. Also at tmax, global oxygen consumption decreased but the amount of tumor-infiltrating macrophages remained unchanged. Our study strongly indicates that the oxygen effect caused by NSAIDs is primarily mediated by an effect on mitochondrial respiration. When irradiation (18 Gy) was applied at tmax, the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7). These results show the potential utility of an acute administration of NSAIDs for radiosensitizing tumors, and shed new light on the mechanisms of NSAID radiosensitization. These results also provide a new rationale for the treatment schedule when combining NSAIDs and radiotherapy.
Downregulation of class II molecules on epidermal Langerhans cells in Lyme borreliosis
Authors: M. Silberer, F. Koszik, G. Stingl, E. Aberer
Journal: British Journal of Dermatology (2000)

Borrelia burgdorferi can be isolated from the skin of patients with acrodermatitis chronica atrophicans (ACA), a late-stage manifestation of Lyme borreliosis; despite a marked T-cell infiltrate in lesional skin and high antibody titres in patients' sera.To determine whether antigen-presenting Langerhans cells (LCs), which reportedly show signs of injury in erythema chronicum migrans (ECM), the early stage of disease, are altered in ACA.We studied the immunophenotype of cutaneous leucocytes on cryostat sections of lesional skin from both ECM and ACA patients.The total number of CD1a+ cells evaluated by semiautomatic image analysis was lower in ECM (594 +/- 263 cells mm(-2) epidermis) than in ACA (835 +/- 317 cells mm(-2) epidermis). HLA-DR expression was remarkably downregulated on CD1a+ LCs to 29% in ECM and 18% in ACA, whereas in normal skin, most of the epidermal CD1a+ dendritic cells were HLA-DR+. The inflammatory infiltrate was mainly composed of CD68+ macrophages and CD45RO+ memory T cells, with a predominance of CD4+ helper T cells.It is conceivable that the downregulation of major histocompatibility complex class II molecules on LC in both the early and late skin manifestations of Lyme borreliosis is indicative of a poorly effective anti-B. burgdorferi immune response and thus at least partly responsible for the insufficient elimination of this micro-organism from ACA skin.
Cardiac Hypertrophy, Accessory Pathway, and Conduction System Disease in an Adolescent
Authors: Enrico Fabris, Francesca Brun, Andrea Giuseppe Porto, Pasquale Losurdo, Laura Vitali Serdoz, Massimo Zecchin, Giovanni Maria Severini, Luisa Mestroni, Antonio Di Chiara, Gianfranco Sinagra
Journal: Journal of the American College of Cardiology (2013)
Dose-response study of alendronate sodium for the treatment of cancer-associated hypercalcemia.
Authors: S R Nussbaum, R P Warrell, R Rude, J Glusman, J P Bilezikian, A F Stewart, M Stepanavage, J F Sacco, S D Averbuch, B J Gertz
Journal: Journal of Clinical Oncology (1993)

PURPOSE A randomized, double-blind, dose-ranging study of single-dose intravenous (IV) therapy with alendronate sodium (aminohydroxybutylidene bisphosphonate) was performed in patients with cancer-associated hypercalcemia. PATIENTS AND METHODS Patients with hypercalcemia who had not received antitumor therapy in the preceding 7 days were treated with 48 hours of IV hydration. Patients with persistent hypercalcemia (albumin-corrected serum calcium concentration [CSCC] &gt; or = 11.5 mg/dL) were randomly assigned to receive 2.5, 5, 10, or 15 mg of alendronate infused over 2 hours, or 10 mg of alendronate infused over 24 hours. Fifty-nine patients were treated and 50 patients were assessable for the dose-response relationship. RESULTS Normalization of CSCC (&lt; or = 10.5 mg/dL) was achieved in 22%, 82%, 75%, and 90% of assessable patients in the 2.5-, 5-, 10- (2- and 24-hour groups pooled), and 15-mg dose groups, respectively, within 8 days of therapy. Doses &gt; or = 5 mg were significantly superior to the 2.5-mg dose level (P &lt; .05). There was no significant difference in the minimum CSCC achieved between the 2- and 24-hour infusions of the 10-mg dose. Based on an intent-to-treat analysis of all randomized patients, the overall complete response rate was 74% for dose levels greater than 2.5 mg. For assessable patients who responded to &gt; or = 5 mg of alendronate, the estimated median duration of normocalcemia was 10 days (range, 1 to 25). The estimated median time to relapse (CSCC &gt; 11.5 mg/dL) was 15 days from initial treatment and 12 days from initial response, respectively. Adverse events included a transient febrile response in 34% of patients and eight episodes of reversible elevations in serum transaminase levels among treated patients. CONCLUSION While a statistically significant dose-response relationship was not clearly evident at doses greater than 5 mg, single doses of &gt; or = 5 mg alendronate sodium effectively lowered serum calcium concentrations and were well tolerated in the treatment of cancer-associated hypercalcemia.
CD8+ T cells, dendritic cells, mast cells and FOXP3 in the lungs of patients with severe influenza A (H1N1) infection
Authors: Monique Buttignol, Ruy Pires-Neto, Marina Ballarin, Marisa Dolhnikoff, Thais Mauad
Journal: European Respiratory Journal (2014)

Backgroud : Influenza A (H1N1) infection can induce acute respiratory distress syndrome (ARDS) in some patients. There are still few reports on the immunophenotype of the inflammatory cells present in lung infiltrates of patients that died due to H1N1 infection when compared to other causes of ARDS.  Aim : Quantify CD8+T cells, Dendritic Cells (CD83), Natural Killer cells (NK–CD57), Mast Cells (chymase/tryptase) and Foxp3 regulatory T cells in the lungs of patients who died of H1N1.  Methods : We analyzed autopsy lung tissue of 46 subjects (48±16 years, 55% male), divided in 3 groups according to cause of death: Control (non-pulmonary cause of death, n=16); ARDS (ARDS due to non viral infection, n=14) and H1N1 (H1N1 infection, n=16). Using immunohistochemistry and image analysis we quantified the density of CD8+T, chymase, tryptase, CD83, CD57+ and Foxp3 in the lung parenchyma. Data are expressed as cells/alveolar septum length (median [IQR]).  Results : We found an increase of CD8+T cell density in H1N1 group when compared to ARDS and control groups (3.7[2.3] x 3.7[1.7] x 6.3[3.3] 10 3 cels/μm, p=0.019). There was also an increase of CD83 cell density in H1N1 group compared to control (0.5[0.4] x 1.4[1] 10 3 cels/μm, p=0.007). Finally, compared to ARDS group, H1N1 showed an increase of CD57 cell density (2[1] x 3.3[3] 10 3 cels/μm, p=0.007). The expression of tryptase, chymase and Foxp3 was not different between groups.  Conclusion : ARDS induced by H1N1 infection is associated with an inflammatory phenotype that is different from other causes of ARDS, with increased recruitment of cytotoxic, dendritic cells and NK cells to the lungs.
Validation of the G8 screening tool in geriatric oncology: The ONCODAGE project.
Authors: P. Soubeyran, C. Bellera, J. Goyard, D. Heitz, H. Cure, H. Rousselot, G. Albrand, V. Servent, O. Saint Jean, C. Roy, S. Mathoulin-Pelissier, M. Rainfray
Journal: Journal of Clinical Oncology (2011)

9001 Background: The risk of treatment-related toxicity increases with age and may even lead to toxic death. Comprehensive Geriatric Assessment (CGA) is an appropriate but time-consuming method. The development of a screening tool appears adequate. Based on a multicenter prospective cohort of 364 cancer patients > 70, we developed the G8 (8 items; range 0 [poor] to 17 [good prognosis]). Results suggested 14 as threshold, equivalent to 90% sensitivity, and 60% specificity. Methods: We have set up a national multicenter prospective cohort study to validate the G8, a quick and easy-to-use screening tool that can be performed routinely by oncologists. G8 and VES13 were evaluated to predict for at least one abnormal CGA test among CIRS-G, ADL, IADL, MMSE, MNA, GDS-15 and Timed Get up and Go. We estimated the necessary accrual to 1,650 patients (project funded by a French National Cancer Institute grant). Results: 1,668 patients have been included in 23 French cancer and geriatric centers (18 months). 1,590 patients were eligible and 1,425 evaluable: mean age 78.2 (70 to 98); 69.6% females; 75.9% PS 0-1; 53.7% breast, 14.2% colon, 10.5% lung, 8.6% prostate, 5.1% head and neck cancer and 7.9% lymphomas. Overall, abnormal CGA, G8 and VES13 were respectively 80.1%, 68.4% and 60.1%. Mean time to fill in G8 and VES13 were respectively 4.4’ and 4.3’. Reproducibility of the two questionnaires was good (kappa = 0.65, 95%CI [0.61; 0.69] vs 0.64, 95%CI [0.54; 0.73]). Sensitivity of G8 was superior to VES13 (76.6%, 95%CI [74.0%; 79.0%] vs 68.7%, 95%CI [65.9%; 71.4%]) although its specificity was inferior (64.4%, 95%CI [58.6%; 70.0%] vs 74.3%, 95%CI [68.8%; 79.3%]). When G8 and VES13 were used together (at least one abnormal test), sensitivity increased to 86.6% but specificity decreased to 53.2%. All results were confirmed in subgroup analyses (according to tumor type, extension, or previous treatment). Conclusions: These results validate G8 as a screening tool for patients older than 70 with cancer before therapy. Patients screened abnormal with G8 should benefit from at least increased medical attention or CGA followed by geriatric intervention when indicated.
Pulmonary complications of pneumococcal community-acquired pneumonia: incidence, predictors, and outcomes
Authors: C. Cillóniz, S. Ewig, E. Polverino, C. Muñoz-Almagro, F. Marco, A. Gabarrús, R. Menéndez, J. Mensa, A. Torres
Journal: Clinical Microbiology and Infection (2011)
Implantation in Coronary Circulation Induces Morphofunctional Transformation of Radial Grafts From Muscular to Elastomuscular
Authors: Mario Gaudino, Francesco Prati, Eugenio Caradonna, Carlo Trani, Francesco Burzotta, Giovanni Schiavoni, Franco Glieca, Gianfederico Possati
Journal: Circulation (2005)

Background— The purpose of this research was to investigate the in vivo morphofunctional changes induced in the radial artery (RA) by its use as coronary artery bypass conduit by comparing the morphological features and vasoreactivity of the native RA versus the coronary RA graft in the same patient. Methods and Results— Ten years after surgery, 10 patients were submitted to intravascular ultrasound examination of the RA graft of the controlateral (in situ) RA and of the internal thoracic artery (ITA) graft and to vasoactive challenges with acetylcholine and serotonin. Quantitative angiographic assessment showed that the mean diameter of the RA coronary grafts was significantly larger than that of the in situ RA and of the ITA (2.89±0.40 mm RA grafts, 2.14±0.52 mm in situ RA, 2.25±0.53 mm ITA grafts; P &lt;0.001). The in situ RA demonstrated a typical muscular architecture, whereas RA coronary grafts showed a clear reduction of the thickness of the medial layer and had a less well-defined muscular component of the media with interposition of elastic tissue. Serotonin endovascular infusion elicited a strong spastic reaction in in situ RAs; the same challenge induced only moderate constriction in RA and ITA coronary grafts. Conclusions— Implantation in the coronary circulation leads to major anatomic and vasoreactive modifications of the RAs that tend to lose the morphofunctional features of a muscular conduit and assume those of an elastomuscular artery, such as the ITA.
Measurement of estrogen and progesterone receptors in human breast tumors: enzyme immunoassay versus binding assay.
Authors: F A Holmes, H A Fritsche, J W Loewy, A M Geitner, R C Sutton, A U Buzdar, G N Hortobagyi
Journal: Journal of Clinical Oncology (1990)

To determine whether we could replace our current binding assay (BA) method for measurement of estrogen receptors (ERs) and progesterone receptors (PRs) with the recently developed enzyme immunoassay (EIA) method, we compared simultaneous measurements of ERs and PRs in frozen breast tumor samples by both methods. A value of greater than or equal to 10 fmol/mg cytosol protein was defined as positive. There was agreement between the BA and EIA on whether the sample was positive or negative in 75 of 91 (82%) samples measured for ERs and in 74 of 93 (80%) for PRs. When the threshold value for a positive assay was redefined as greater than or equal to 20 fmol/mg protein, there was agreement in 85 of 91 (93%) samples for ERs and 85 of 93 (91%) for PRs. The numerical value for ERs by EIA was not consistently greater or less than ERs by BA, but the difference between the EIA and BA measurement increased as the size of the measurement increased. We did not see an excess of premenopausal patients whose ERs by BA were negative and whose ERs by EIA were positive. Although we performed a linear regression analysis and determined the Pearson correlation coefficient to compare the BA and EIA as reported by others, we show that this analysis may be misleading when the objective is to demonstrate similarities between these methods. Our study shows that the EIA can be confidently used in place of the BA. However, a threshold value for a positive EIA should be confirmed clinically in future studies.
Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone
Authors: E de Beurs, A J van Balkom, A Lange, P Koele, R van Dyck
Journal: American Journal of Psychiatry (1995)

The purpose of this comparative outcome study was to investigate whether the effects of exposure in vivo treatment for panic disorder with agoraphobia could be enhanced by adding interventions specifically for panic attacks before the start of exposure treatment. The additional effect of two types of treatment for panic attacks--pharmacological (fluvoxamine) and psychological (repeated hyperventilation provocations and respiratory training)--was examined. Thus, the combined treatment of panic interventions with exposure in vivo could be compared to exposure in vivo alone.Ninety-six patients were randomly assigned to four treatment conditions: double-blind, placebo-controlled fluvoxamine followed by exposure in vivo, psychological panic management followed by exposure, and exposure in vivo alone. Outcome was assessed by self-report measures, a standardized multitask behavioral avoidance test, and continuous monitoring of panic attacks. Seventy-six patients completed the study.All four treatments were effective and resulted in a significant decrease of agoraphobic avoidance. Moreover, the combination of fluvoxamine and exposure in vivo demonstrated efficacy superior to that of the other treatments and had twice as large an effect size (difference between pre- and posttreatment scores) on self-reported agoraphobic avoidance. The other treatments did not differ among each other in effectiveness.Results of the study indicate that the short-term outcome of exposure in vivo treatment can be enhanced by adding fluvoxamine treatment. Psychological panic management combined with exposure was not superior to exposure alone of equal duration.
AntagomiR directed against miR-20a restores BMP signaling in hypoxia-induced pulmonary hypertension in vivo
Authors: Matthias Brock, Michelle Trenkmann, Colin Schwarzwald, Silvia Ulrich, Max Gassmann, Louise Ostergaard, Rudolf Speich, Lars Huber
Journal: European Respiratory Journal (2011)

Introduction:  Dysregulated expression of the bone morphogenetic protein (BMP) receptor type II (BMPR2) is a pathogenetic hallmark in the development of pulmonary hypertension (PH). We recently demonstrated that microRNA 20a (miR-20a) represses the expression of BMPR2. Here we investigated the therapeutic potential of antagonizing miR-20a in an in vivo model of PH.   Methods:  For in vivo inhibition of miR-20a, antagomiR-20a (A-20a) was injected intraperitoneally into mice with hypoxia-induced PH. After three weeks of hypoxia, morphometry and blood gas analysis were performed. RNA levels of miR-20a, BMPR2, Smad5, and Id2 were assessed by real-time PCR in hearts and lungs.   Results:  Intraperitoneal injection of A-20a resulted in significant down regulation of miR-20a in lungs. When exposed to hypoxia, animals treated with A-20a developed less right ventricular hypertrophy as evidenced by relative heart weight. Treatment with A-20a reduced the hemoglobin levels and, moreover, the acid-base status (base deficit) approached the baseline values of normoxic animals. Molecular analysis showed down regulation of BMPR2 mRNA levels in lung tissue by hypoxia (0.79±0.24 fold, p=0.039). A-20a abrogated the hypoxia induced down regulation of BMPR2 and led to significant up regulation of BMPR2 (1.62±0.18 fold, p   Conclusion:  Our data underpin the importance of miR-20a in the BMP signaling and emphasize the need for further studies to address the therapeutic potential of antagomiRs for the human disease.
Defining target antigens in linear IgA disease using skin from subjects with inherited epidermolysis bullosa as a substrate for indirect immunofluorescence microscopy
Authors: None Harman, None Bhogal, None Eady, None Mcgrath, None Black
Journal: British Journal of Dermatology (1999)

Identification of target antigens in immunobullous disorders usually involves laborious techniques such as immunoblotting and immunoprecipitation, which do not always provide conclusive data. This is particularly true of linear IgA disease (LAD) in which the target antigen has often proved difficult to identify. As an alternative means of antigen identification in five adult patients with LAD, we performed indirect immunofluorescence (IIF) microscopy on a panel of skin samples taken from subjects with different forms of inherited epidermolysis bullosa (EB). Skin samples were selected that showed a complete absence of immunostaining for a specific basement membrane zone (BMZ) molecule (type VII collagen, laminin 5 or the 180-kDa bullous pemphigoid antigen BP180). In each case, the underlying genetic mutations had been defined and shown to consist of premature termination codons on both alleles of the particular gene, resulting in total ablation of the encoded protein. Two epidermal-binding LAD sera showed BMZ fluorescence on all substrates except BP180-deficient skin, suggesting that the target antigen was BP180, or a closely related molecule. In contrast, two dermal-binding LAD sera were positive on all substrates except the type VII collagen-deficient skin, suggesting that the target antigen was likely to be type VII collagen. One LAD serum sample, which showed combined dermal and epidermal fluorescence on normal salt-split skin, was also positive on all substrates tested, suggesting a target antigen other than type VII collagen, laminin 5 or BP180. The study confirms that LAD is a heterogeneous disorder and illustrates that IIF using a panel of skin samples which lack specific BMZ molecules, taken from subjects with inherited EB, is a relatively simple and useful tool to help identify target antigens in immunobullous disorders.