tbuckley/cabot-search huggingface dataset:
Prediction of Serious Complications in Patients With Seemingly Stable Febrile Neutropenia: Validation of the Clinical Index of Stable Febrile Neutropenia in a Prospective Cohort of Patients From the FINITE Study
Authors: Alberto Carmona-Bayonas, Paula Jiménez-Fonseca, Juan Virizuela Echaburu, Maite Antonio, Carme Font, Mercè Biosca, Avinash Ramchandani, Jerónimo Martínez, Jorge Hernando Cubero, Javier Espinosa, Eva Martínez de Castro, Ismael Ghanem, Carmen Beato, Ana Blasco, Marcelo Garrido, Yaiza Bonilla, Rebeca Mondéjar, María Ángeles Arcusa Lanza, Isabel Aragón Manrique, Aránzazu Manzano, Elena Sevillano, Eduardo Castañón, Mercé Cardona, Elena Gallardo Martín, Quionia Pérez Armillas, Fernando Sánchez Lasheras, Francisco Ayala de la Peña
Journal: Journal of Clinical Oncology (2015)

To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections.We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE.We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC).CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes.
Interleukin-30 Expression in Prostate Cancer and Its Draining Lymph Nodes Correlates with Advanced Grade and Stage
Authors: Serena Di Meo, Irma Airoldi, Carlo Sorrentino, Alessia Zorzoli, Silvia Esposito, Emma Di Carlo
Journal: Clinical Cancer Research (2013)

The interleukin (IL)-27 cytokine subunit p28, also called IL-30, has been recognized as a novel immunoregulatory mediator endowed with its own functions. These are currently the subject of discussion in immunology, but completely unexplored in cancer biology. We set out to investigate the role of IL-30 in prostate carcinogenesis and its effects on human prostate cancer (hPCa) cells.IL-30 expression, as visualized by immunohistochemistry and real-time reverse transcriptase PCR on prostate and draining lymph nodes from 125 patients with prostate cancer, was correlated with clinicopathologic data. IL-30 regulation of hPCa cell viability and expression of selected gene clusters was tested by flow cytometry and PCR array.IL-30, absent in normal prostatic epithelia, was expressed by cancerous epithelia with Gleason ≥ 7% of 21.3% of prostate cancer stage I to III and 40.9% of prostate cancer stage IV. IL-30 expression by tumor infiltrating leukocytes (T-ILK) was higher in stage IV that in stage I to III prostate cancer (P = 0.0006) or in control tissue (P = 0.0011). IL-30 expression in prostate draining lymph nodes (LN)-ILK was higher in stage IV than in stage I to III prostate cancer (P = 0.0031) or in control nodes (P = 0.0023). The main IL-30 sources were identified as CD68(+) macrophages, CD33(+)/CD11b(+) myeloid cells, and CD14(+) monocytes. In vitro, IL-30 stimulated proliferation of hPCa cells and also downregulated CCL16/LEC, TNFSF14/LIGHT, chemokine-like factor (CKLF), and particularly CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) and greatly upregulated ChemR23/CMKLR.We provide the first evidence that IL-30 is implicated in prostate cancer progression because (i) its expression by prostate cancer or T- and LN-ILK correlates with advanced disease grade and stage; and (ii) IL-30 exerts protumor activity in hPCa cells.
Role of the Tricuspid Annulus and the Eustachian Valve/Ridge on Atrial Flutter
Authors: Hiroshi Nakagawa, Ralph Lazzara, Terrance Khastgir, Karen J. Beckman, James H. McClelland, Shinobu Imai, Jan V. Pitha, Anton E. Becker, Mauricio Arruda, Mario D. Gonzalez, Lawrence E. Widman, Michael Rome, Jeffrey Neuhauser, Xunzhang Wang, James D. Calame, Maurice D. Goudeau, Warren M. Jackman
Journal: Circulation (1996)

Background Typical atrial flutter (AFL) results from right atrial reentry by propagation through an isthmus between the inferior vena cava (IVC) and tricuspid annulus (TA). We postulated that the eustachian valve and ridge (EVR) forms a line of conduction block between the IVC and coronary sinus (CS) ostium and forms a second isthmus (septal isthmus) between the TA and CS ostium. Methods and Results Endocardial mapping in 30 patients with AFL demonstrated atrial activation around the TA in the counterclockwise direction (left anterior oblique projection). Double atrial potentials were recorded along the EVR in all patients during AFL. Pacing either side of the EVR during sinus rhythm also produced double potentials, which indicated fixed anatomic block across EVR. Entrainment pacing at the septal isthmus and multiple sites around the TA produced a Δ return interval ≤8 ms in 14 of 15 patients tested. Catheter ablation eliminated AFL in all patients by ablation of the septal isthmus in 26 patients and the posterior isthmus in 4. AFL recurred in 2 of 12 patients (mean follow-up, 33.9±16.3 months) in whom ablation success was defined by the inability to reinduce AFL, compared with none of 18 patients (mean follow-up, 10.3±8.3 months) in whom success required formation of a complete line of conduction block between the TA and the EVR, identified by CS pacing that produced atrial activation around the TA only in the counterclockwise direction and by pacing the posterior TA with only clockwise atrial activation. Conclusions ( 1) The EVR forms a line of fixed conduction block between the IVC and the CS; (2) the EVR and the TA provide boundaries for the AFL reentrant circuit; and (3) verification of a complete line of block between the TA and the EVR is a more reliable criterion for long-term ablation success.
Sleep apnoea and snoring: potential links with vascular disease
Authors: C. E Sullivan, S. G McNamara
Journal: Thorax (1998)

2‐7 Also emerging from these varied studies is a picture in which snoring and sleep apnoea appear to be linked to the common vascular diseases. This association, however, is not universally accepted. One view held by some commentators in this field questions the presence of any such link; instead it is proposed that any relative increase in cardiovascular disease among patients with sleep apnoea reflects an overlap of certain common risk factors, such as obesity, within the patient population. The broad question which this symposium proposes to discuss is what links, if any, exist between snoring, sleep apnoea and vascular disease, with a particular emphasis on the potential associations with heart disease. Furthermore, the strength of these scientific and epidemiological associations will be considered. The purpose of this brief review is to set the background against which the other contributions to this symposium are made. Snoring and sleep apnoea: Pathophysiology Whatever controversy there may be about the significance of snoring and sleep apnoea, there remains little doubt that both conditions are extremely common. The first large scale epidemiological study that looked at the prevalence of snoring was that of Lugaresi et al 8 in which a questionnaire was used to estimate the prevalence of snoring in a population of 2858 people in San Marino in Italy. About 24% of men and 14% of the women included in this study were reported to snore habitually. Several subsequent studies, again using a questionnaire approach, proceeded to estimate the diVerences in the prevalence of snoring between women and men and across age groups. 9‐14
Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.
Authors: N Khalil, O Bereznay, M Sporn, A H Greenberg
Journal: The Journal of Experimental Medicine (1989)

A rat model of bleomycin-induced pulmonary inflammation and fibrosis was used to examine the relationship between collagen synthesis and transforming growth factor beta (TGF-beta) production, and cellular distribution. Total lung TGF-beta was elevated within 2 h of intratracheal bleomycin administration and peaked 7 d later at levels 30-fold higher than controls. This was followed by a gradual decline with lower but persistent levels of production in the late phase of the response between 21 and 28 d later. The peak TGF-beta levels preceded the maximum collagen and noncollagen protein synthesis measured by [3H]proline incorporation into lung fibroblast explants of bleomycin-treated rats. The pattern of immunohistochemical staining localized TGF-beta initially in the cytoplasm of bronchiolar epithelium cells and subepithelial extracellular matrix. The peak of lung TGF-beta levels at 7 d coincided with intense TGF-beta staining of macrophages dispersed in the alveolar interstitium and in organized clusters. Later in the course of the response. TGF-beta was primarily associated with extracellular matrix in regions of increased cellularity and tissue repair, and coincided with the maximum fibroblast collagen synthesis. This temporal and spatial relationship between collagen production and TGF-beta production by macrophages suggests an important if not primary role for TGF-beta in the pathogenesis of the pulmonary fibrosis.
Determinants of 24-H Blood Pressure in IDDM Patients
Authors: Klavs W Hansen, Per L Poulsen, Jens S Christiansen, Carl Erik Mogensen
Journal: Diabetes Care (1995)

OBJECTIVE To assess the influence of basic clinical data on ambulatory blood pressure (AMBP) in insulin-dependent diabetes mellitus (IDDM) patients and to evaluate the reproducibility of the method. RESEARCH DESIGN AND METHODS AMBP was measured in 66 IDDM patients with urinary albumin excretion (UAE) &amp;lt;20 μg/min and in 53 healthy subjects. Determinants of AMBP were identified in a stepwise multiple regression model. In addition, 14 diabetic patients were monitored on two days of the same type, and 14 patients were monitored on one work day and one day off. RESULTS In healthy subjects, sex was the most important determinant of 24-h blood pressure (BP), whereas UAE and age were the main covariates in diabetes patients. The male-female difference in 24-h diastolic BP (dBP) was 5.6 mmHg lower in diabetic patients than in healthy control subjects (P &amp;lt; 0.05). In patients with long diabetes duration, nighttime dBP (69 ± 7 mmHg) was higher than in patients with medium diabetes duration (63 ± 8 mmHg, P &amp;lt; 0.05; after matching for age and sex). Daytime dBP was 5 mmHg higher on a work day than on a day off (P &amp;lt; 0.02). Standard deviation of the difference for repeated measurement of 24-h systolic/diastolic BP in the same subject was 5.7/2.5 mmHg. CONCLUSIONS The male-female difference in 24-h dBP was attenuated in diabetes. The influence of UAE on AMBP was noticed even in normoalbuminuric diabetic patients. Standardized AMBP was highly reproducible.
Effect of Ras Inhibition in Hematopoiesis and BCR/ABL Leukemogenesis
Authors: Karina J Baum, Ruibao Ren
Journal: Journal of Hematology & Oncology (2008)

Ras small GTPases are activated in many hematopoietic growth factor signaling and in hematological malignancies, but their role in hematopoiesis and leukemogenesis is not completely known. Here we examined the effect of Ras inhibition by a dominant negative mutant of Ras, N17 H-Ras, in adult hematopoiesis and in BCR/ABL leukemogenesis using the mouse bone marrow transduction and transplantation approach. We found that N17 H-Ras expression suppressed B- and T-lymphopoiesis and erythropoiesis. Interestingly, N17 H-Ras did not suppress myelopoiesis in the bone marrow, yet it greatly attenuated BCR/ABL-induced chronic myelogenous leukemia (CML)-like myeloproliferative disease. Most BCR/ABL + N17 H-Ras mice eventually developed pro-B lymphoblastic leukemia/lymphoma (B-ALL). These results suggest that Ras activation is essential for the development of lymphoid and erythroid cells but not myeloid cells and that Ras is a critical target of BCR/ABL in the pathogenesis of CML, but not B-ALL.
Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis
Authors: M. Toyoda, M. Nakamura, T. Makino, T. Hino, M. Kagoura, M. Morohashi
Journal: British Journal of Dermatology (2002)

Neurogenic components, such as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis (AD) via the neuroimmunocutaneous system. Numerous in vitro and in vivo studies have shown that nerve growth factor (NGF), the best-characterized member of the neurotrophin family, modulates the synthesis of the neuropeptide substance P (SP), both of which may be associated with the pathogenesis of human allergic diseases.To evaluate the levels of NGF and SP in the plasma of patients with AD and to examine their possible correlation with disease activity.We measured plasma levels of NGF by an immunoenzymatic assay and of SP by aradioimmunoassay in 52 patients with AD, and compared them with 35 normal non-atopic controls. The severity of the disease in AD patients was evaluated using validated clinical scoring systems.Patients with AD had significant increases in plasma levels of NGF and SP compared with controls (P < 0.0005 and P < 0.0001, respectively). A positive correlation between the plasma levels of NGF and SP was found in AD patients (correlation coefficient, Cc = 0.920, P < 0.0001). There was a significant correlation of plasma NGF and SP levels with disease activity evaluated using three different scoring systems: the grading system of Rajka and Langeland (P < 0.001 and P < 0.01, respectively), the objective Severity Scoring of AD (Cc = 0.656, P < 0.005 and Cc = 0.752, P < 0.0005, respectively) and the Eczema Area and Severity Index (Cc = 0.740, P < 0.001 and Cc = 0.765, P < 0.005, respectively).These data represent the first reported evidence of increased plasma levels of NGF and SP in an allergic human skin disease. They suggest that these neurogenic factors systemically modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. In addition, NGF and SP may be useful markers of disease activity in patients with AD.
Calcium release units in heart failure: that's about the size of it
Authors: F. Swift, G. Christensen
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Ultrastructural remodelling of Ca2+ signalling apparatus in failing heart cells’ by H.-D. Wu et al ., pp. 430–438, this issue. 

Cardiac remodelling, often defined as changes in the mass and shape of the whole heart,1 has been a focus of research over several decades. Despite considerable efforts, the cellular and molecular mechanisms that lead to contractile dysfunction of the remodelled heart are still not clear. Remodelling may also occur at the level of the cardiomyocyte and is then termed ultrastructural remodelling. Studies have revealed substantial ultrastructural alterations in several parts of the cardiomyocytes during cardiac disease, including the sarcoplasmic reticulum (SR)2 and transverse (T)-tubules,3,4 and in the positioning of ion channels and pumps that are crucial in regulating myocardial contraction and relaxation. Thus, it is likely that ultrastructural remodelling can explain several important aspects of systolic and diastolic heart failure of various aetiologies.

The machinery that couples the electrical activation of the cardiomyocyte to mechanical contraction is set to control transient rises of [Ca2+] in the cytosol. Research in the past decades has revealed that the global rise of [Ca2+] in the cytosol that activates myofilaments is regulated by mechanisms that are confined within spatially constrained microdomains in the cardiomyocyte. These microdomains occur at sites where Ca2+ channels in the T-tubule membrane come very close to Ca …
Randomized Phase III Study of Cisplatin With or Without Raltitrexed in Patients With Malignant Pleural Mesothelioma: An Intergroup Study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada
Authors: Jan P. van Meerbeeck, Rabab Gaafar, Christian Manegold, Rob J. Van Klaveren, Eric A. Van Marck, Mark Vincent, Catherine Legrand, Andrew Bottomley, Channa Debruyne, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2005)

Purpose We conducted a phase III trial to determine whether first-line treatment with raltitrexed, a thymidine synthase inhibitor, and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma (MPM). Patients and Methods Eligible patients with histologically proven advanced MPM, not pretreated with chemotherapy, WHO performance status (PS) 0 to 2, and adequate hematological, renal, and hepatic function were randomly assigned to receive cisplatin 80 mg/m 2 IV on day 1, alone (arm A) or combined with raltitrexed 3 mg/m 2 (arm B). In patients with measurable disease, response was monitored using the Response Evaluation Criteria in Solid Tumors criteria. Health related quality of life (HRQOL) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module (QLQ-LC13). Results Two hundred fifty patients were randomized: 80% male; median age, 58 years; and WHO PS, 0, 1, 2 in 25, 62, and 13% of cases, respectively. There were no toxic deaths. The main grade 3 or 4 toxicities observed were neutropenia and emesis, reported twice as often in the combination arm. Among 213 patients with measurable disease, response rate was 13.6% (arm A) versus 23.6% (arm B; P = .056). No difference in HRQOL was observed on any of the scales. Median overall and 1-year survival in arms A and B were 8.8 (95% CI, 7.8 to 10.8) v 11.4 months (95% CI, 10.1 to 15), respectively, and 40% v 46%, respectively (P = .048). Conclusion A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone. This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM, without harmful effect on HRQOL.
Global incidence of serogroup B invasive meningococcal disease: a systematic review
Authors: Shruti Sridhar, Brian Greenwood, Christopher Head, Stanley A Plotkin, Marco A Sáfadi, Samir Saha, Muhamed-Kheir Taha, Oyewale Tomori, Bradford D Gessner
Journal: The Lancet Infectious Diseases (2015)
Pro12Ala Polymorphism in the<i>PPARG</i>Gene Contributes to the Development of Diabetic Nephropathy in Chinese Type 2 Diabetic Patients
Authors: Limei Liu, Taishan Zheng, Feng Wang, Niansong Wang, Yanyan Song, Ming Li, Lifang Li, Jiamei Jiang, Weijing Zhao
Journal: Diabetes Care (2009)

OBJECTIVE Oxidative stress is a major contributing factor in the development of diabetic nephropathy. Peroxisome proliferator–activated receptor γ heterozygous mice and Pro12Ala polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Pro12Ala polymorphism, alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 760 Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Among patients, 532 had diabetic nephropathy with microalbuminuria (n = 245) or overt albuminuria (n = 287), and 228 did not show either of these symptoms but had had diabetes for ≥10 years and were not undergoing antihypertension treatment. RESULTS After adjustment for confounders, the Pro/Pro genotype was significantly associated with diabetic nephropathy (odds ratio 2.30 [95% CI 1.18–4.45], P = 0.014); smoking was also an independent risk factor for diabetic nephropathy (1.99 [1.08–3.68], P = 0.029). In addition, we identified possible synergistic effects; i.e., the high-risk group (smokers with the Pro/Pro genotype) showed 4.52 times higher risk (1.78–11.48, P = 0.002) of diabetic nephropathy than the low-risk group (nonsmokers with the Pro/Ala genotype) in a multiple logistic regression analysis controlled for the confounders. CONCLUSIONS Our results indicated that the Pro/Pro genotype and smoking were significant independent risk factors for diabetic nephropathy. The possible synergistic effects of genotype and smoking may aggravate oxidative stress and contribute to the development of diabetic nephropathy.
Characterization of a Novel Human Tumor Antigen Interleukin-13 Receptor α2 Chain
Authors: Koji Kawakami, Masaki Terabe, Mariko Kawakami, Jay A. Berzofsky, Raj K. Puri
Journal: Cancer Research (2006)

Abstract The interleukin (IL)-13 receptor α2 (IL-13Rα2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13Rα2 chain are expressed on a variety of human tumor cells and specimens, its precise role in tumor immunology has not been defined. To investigate the role of IL-13Rα2 in tumor immunity, we used D5 melanoma cells stably transfected with the human IL-13Rα2 gene (D5α2) to assess the effect of an IL-13Rα2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13Rα2 DNA vaccine resulted in protection against D5α2 tumor development. In vivo depletion experiments in C57BL/6 and RAG-2 knockout mice indicated that both T and B cells, but not natural killer cells, were required for the tumor protection. In addition, antibody induced by the IL-13Rα2 DNA vaccine showed a modest but significant inhibitory effect on D5α2 cells in vitro, suggesting that the antibody is biologically functional. The IL-13Rα2 DNA vaccine also exhibited antitumor activity against established D5α2 tumors in mice. Histologic analysis of regressing tumors identified infiltration of CD4+ and CD8+ T cells and the expression of CXCL9 chemokine in tumors. Taken together, our results identify the human IL-13Rα2 chain as a novel tumor rejection antigen. (Cancer Res 2006; 66(8): 4434-42)
Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial
Authors: Philip A Poole-Wilson, Karl Swedberg, John GF Cleland, Andrea Di Lenarda, Peter Hanrath, Michel Komajda, Jacobus Lubsen, Beatrix Lutiger, Marco Metra, Willem J Remme, Christian Torp-Pedersen, Armin Scherhag, Allan Skene
Journal: The Lancet (2003)