tbuckley/cabot-search huggingface dataset:
Allergic rhinitis is associated with poor asthma control in children with asthma
Authors: Eric P de Groot, Anke Nijkamp, Eric J Duiverman, Paul L P Brand
Journal: Thorax (2012)

<h3>Background</h3> Asthma and allergic rhinitis are the two most common chronic disorders in childhood and adolescence. To date, no study has examined the impact of comorbid allergic rhinitis on asthma control in children. <h3>Objective</h3> To examine the prevalence of allergic rhinitis in children with asthma, and the impact of the disease and its treatment on asthma control. <h3>Methods</h3> A cross-sectional survey in 203 children with asthma (5–18 years) using validated questionnaires on rhinitis symptoms (stuffy or runny nose outside a cold) and its treatment, and the paediatric Asthma Control Questionnaire (ACQ). Fraction of nitric oxide in exhaled air (FeNO) was measured with a Niox Mino analyser; total and specific IgE levels were assessed by the Immunocap system. <h3>Results</h3> 157 children (76.2%) had symptoms of allergic rhinitis but only 88 of these (56.1%) had been diagnosed with the condition by a physician. ACQ scores were worse in children with allergic rhinitis than in those without the condition (p=0.012). An ACQ score ≥1.0 (incomplete asthma control) was significantly more likely in children with allergic rhinitis than in those without (OR 2.74, 95% CI 1.28 to 5.91, p=0.0081), also after adjustment for FeNO levels and total serum IgE. After adjustment for nasal corticosteroid therapy, allergic rhinitis was no longer associated with incomplete asthma control (OR 0.72, 95% CI 0.47 to 1.12, p=0.150). <h3>Conclusion</h3> Allergic rhinitis is common in children with asthma, and has a major impact on asthma control. The authors hypothesise that recognition and treatment of this condition with nasal corticosteroids may improve asthma control in children, but randomised clinical trials are needed to test this hypothesis.
Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma: Southwest Oncology Group–Directed Intergroup Trial S0205
Authors: Philip A. Philip, Jacqueline Benedetti, Christopher L. Corless, Ralph Wong, Eileen M. O'Reilly, Patrick J. Flynn, Kendrith M. Rowland, James N. Atkins, Barry C. Mirtsching, Saul E. Rivkin, Alok A. Khorana, Bryan Goldman, Cecilia M. Fenoglio-Preiser, James L. Abbruzzese, Charles D. Blanke
Journal: Journal of Clinical Oncology (2010)

Purpose Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. Patients and Methods Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. Results A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. Conclusion In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.
Diagnostic and Prognostic Information in Prostate Cancer with the Help of a Small Set of Hypermethylated Gene Loci
Authors: Patrick J. Bastian, Jörg Ellinger, Axel Wellmann, Nicolas Wernert, Lukas C. Heukamp, Stefan C. Müller, Alexander von Ruecker
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Our study was designed to evaluate promoter CpG island hypermethylation in the diagnosis and prognosis of prostate cancer. Experimental Design: Primary prostate cancers from 53 patients, pelvic lymph nodes, noncancerous prostate tissues, and prostate cell lines were analyzed. Real-time methylation-specific PCR was used to identify CpG island hypermethylation at five promising gene loci (i.e., GSTP1, APC, PTGS2, MDR1, and RASSF1a). Results: At three gene loci (GSTP1, APC, and PTGS1) and CpG island, hypermethylation was highly prevalent in prostate cancers (71-91%), and analysis of receiver operator curves showed that hypermethylation at these three gene loci can distinguish between prostate cancer and noncancerous prostatic tissue (i.e., benign hyperplasia) with a sensitivity of 71.1% to 96.2% and a specificity of 92.9% to 100%. Using sensitive SYBR green methylation-specific PCR technology, we observed a respective 28% and 71% hypermethylation rate at the RASSF1a and MDR1 loci in benign prostate hyperplasia, which may represent early nonaggressive carcinogenesis. Methylation characteristics in prostate cancer metastases (i.e., pelvic lymph nodes) were comparable to the respective primary cancer. Statistical analysis showed no correlation between the methylation status of a single gene locus and clinicopathologic variables (e.g., preoperative prostate specific antigen levels, Gleason score, capsular penetration, involvement of seminal vesicle, and age). In contrast, the methylation of two (GSTP1/APC; GSTP1/PTGS2) or three (GSTP1/APC/PTGS2) gene loci correlated with prognostic indicators (i.e., pathologic stage, extraprostatic extension, and Gleason score, but not with prostate specific antigen levels). Conclusions: Our data suggest that the evaluation of DNA hypermethylation at three gene loci (i.e., GSTP1, APC, and PTGS2) is of diagnostic and prognostic value in prostate cancer.
Prognostic Role of <i>KRAS</i> and <i>BRAF</i> in Stage II and III Resected Colon Cancer: Results of the Translational Study on the PETACC-3, EORTC 40993, SAKK 60-00 Trial
Authors: Arnaud D. Roth, Sabine Tejpar, Mauro Delorenzi, Pu Yan, Roberto Fiocca, Dirk Klingbiel, Daniel Dietrich, Bart Biesmans, György Bodoky, Carlo Barone, Enrique Aranda, Bernard Nordlinger, Laura Cisar, Roberto Labianca, David Cunningham, Eric Van Cutsem, Fred Bosman
Journal: Journal of Clinical Oncology (2009)

Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting.Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models.KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P = .0016), while BRAF mutation was significantly associated with female sex (P = .017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10(-4)). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P = .0003).In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.
Immunological studies before and during interferon therapy in chronic HBV infection: Identification of factors predicting response
Authors: Linda J. Scully, David Brown, Chris Lloyd, Ruvan Shein, Howard C. Thomas
Journal: Hepatology (1990)

Lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis B virus infection. To assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, CD4/CD8 ratio, natural killer cell activity, IgM anti-HBc antibody levels and concanavalin A-induced lymphocyte proliferative response in 30 patients before treatment. In addition, to investigate the mechanisms of action of interferon in promoting hepatitis B virus clearance, we serially measured the CD4/CD8 ratios, natural killer activity and lymphocyte proliferative response at wk 4, 8 and 12 of treatment. A beneficial response to therapy was defined as the sustained clearance of HBeAg and serum hepatitis B virus DNA within 1 yr of commencing therapy. Elevated IgM anti-HBc levels were associated with a beneficial response to therapy, but there was no correlation observed between response and pretreatment CD4/CD8 ratio, natural killer activity or lymphocyte proliferative response. Six of seven human leukocyte antigen DR3-positive patients responded. No measurable changes in the immunological parameters studied were observed in the nonresponder group, whereas a significant rise in CD4/CD8 ratio, associated with a fall in peripheral CD8 number and a decline in measurable NK activity, was seen in the responder group. These changes were maximal at the time of hepatitis B virus DNA clearance, which was associated with a transient increase in hepatic inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
Basic science for the chest physician:<i>Pseudomonas aeruginosa</i>and the cystic fibrosis airway: Figure 1
Authors: Huw D Williams, Jane C Davies
Journal: Thorax (2012)

Pseudomonas aeruginosa is the most frequently encountered lung pathogen in patients with cystic fibrosis (CF). Following initial, often intermittent, episodes of infection, it becomes a permanently established component of the chronically infected lung in more than 80% of patients and confers an adverse prognosis. The predisposition of the CF airway to P aeruginosa is incompletely understood but our current concept of the sequence of events leading from initial acquisition of infection through to the chronic state with severe but often ineffective inflammation is becoming clearer.

The defect in ion transport resulting from abnormal CF transmembrane conductance regulator protein leads to a dehydrated airway surface. Mucociliary clearance suffers and either shed bacterial components, such as flagella, or, more controversially, the bacteria themselves, trigger inflammatory responses via direct contact with cell surface glycoproteins. Increased expression of pro-inflammatory cytokines leads to neutrophil influx from the systemic circulation. Although at early stages of infection P aeruginosa can be successfully eradicated from the airway, the CF inflammatory response has been shown to be both exaggerated (out of proportion with the bacterial load) and prolonged (failing to be successfully regulated by the usual ‘switch-off’ signals such as lipoxins); both likely contribute to the destructive changes in the airway wall characteristic of the disease. If the initial infecting bacteria survive, they lose their flagella, becoming thereby less detectable to the host immune system. They enter a sessile state and reproduce making use of the high concentrations of amino acids in the sputum to extremely high bacterial densities (often ≥109 colony-forming units ml−1). They appear to be attracted to the hypoxic environment in CF mucus plugs and this hypoxia, and other environmental conditions, may encourage a number of genetic and phenotypic switches as the bacteria adapt to the chronically infecting state.

Phagocytosis, long considered the major …
Quality of life measurement in patients with oesophageal cancer.
Authors: J M Blazeby, M H Williams, S T Brookes, D Alderson, J R Farndon
Journal: Gut (1995)

Quality of life (QOL) measurement may aid decision making in the treatment of patients with oesophageal cancer but must be clinically valid to be useful. This study considered if the European Organisation for Research and Treatment of Cancer QOL questionnaire, the QLQ-C30, showed differing results in two clinically distinct groups of patients with oesophageal cancer and also investigated the correlation between dysphagia grade and various scales of QOL. Patients treated by oesophagectomy reported significantly better physical, emotional, cognitive, and global health scores than those in the palliative treatment group. Patients who received palliative treatment had significantly worse pain, fatigue, appetite loss, constipation, and dysphagia. The correlations between dysphagia grade and each of the QOL scales and items in both groups of patients were poor. This questionnaire differentiates clearly between the two clinically distinct groups of patients, but to be an entirely appropriate indicator of QOL in patients with oesophageal cancer, an additional specific oesophageal module including a dysphagia scale is required.
T Lymphocyte Sensitization to Hbcag and T Cell–Mediated Unresponsiveness to Hbsag in Hepatitis B Virus–Related Chronic Liver Disease
Authors: Sandro Vento, John E. Hegarty, Alfredo Alberti, Charles J. O'brien, Graeme J.M. Alexander, Adrian L.W.F. Eddleston, Roger Williams
Journal: Hepatology (1985)

Using a newly developed indirect T lymphocyte migration inhibition test, cell–mediated immunity to HBsAg and HBcAg was directly and simultaneously examined in a total of 21 patients with HBsAg–positive chronic liver disease (CLD), and in seven subjects whose sera contained anti–HBs (2 previous acute hepatitis B; 4 hepatitis B vaccine recipients and 1 chronic active hepatitis). T cell sensitization to HBcAg was invariably detected in the HBsAg–positive CLD patients tested (12/12), whereas T cell sensitization to HBsAg was not present in any of the patients (0/21). In contrast, T cell sensitization to HBsAg was present in all anti–HBs–positive subjects. These results support the hypothesis that the cellular immune response to HBcAg, rather than to HBsAg, is implicated in the pathogenesis of HBsAg–positive CLD. Moreover, the observation that the addition of T cells from patients with HBsAg–positive CLD to T cells from anti–HBs positive subjects in a ratio of 1 to 9 reversed their sensitization to HBsAg, suggests that a hyperactivity of HBsAg–specific suppressor T cell population may be responsible for persistent HBs antigenemia.
DNMT3b overexpression contributes to a hypermethylator phenotype in human breast cancer cell lines
Authors: J Devon Roll, Ashley G Rivenbark, Wendell D Jones, William B Coleman
Journal: Molecular Cancer (2008)

Abstract Background DNA hypermethylation events and other epimutations occur in many neoplasms, producing gene expression changes that contribute to neoplastic transformation, tumorigenesis, and tumor behavior. Some human cancers exhibit a hypermethylator phenotype, characterized by concurrent DNA methylation-dependent silencing of multiple genes. To determine if a hypermethylation defect occurs in breast cancer, the expression profile and promoter methylation status of methylation-sensitive genes were evaluated among breast cancer cell lines. Results The relationship between gene expression (assessed by RT-PCR and quantitative real-time PCR), promoter methylation (assessed by methylation-specific PCR, bisulfite sequencing, and 5-aza-2'deoxycytidine treatment), and the DNA methyltransferase machinery (total DNMT activity and expression of DNMT1, DNMT3a, and DNMT3b proteins) were examined in 12 breast cancer cell lines. Unsupervised cluster analysis of the expression of 64 methylation-sensitive genes revealed two groups of cell lines that possess distinct methylation signatures: (i) hypermethylator cell lines, and (ii) low-frequency methylator cell lines. The hypermethylator cell lines are characterized by high rates of concurrent methylation of six genes ( CDH1, CEACAM6, CST6, ESR1, LCN2, SCNN1A ), whereas the low-frequency methylator cell lines do not methylate these genes. Hypermethylator cell lines coordinately overexpress total DNMT activity and DNMT3b protein levels compared to normal breast epithelial cells. In contrast, most low-frequency methylator cell lines possess DNMT activity and protein levels that are indistinguishable from normal. Microarray data mining identified a strong cluster of primary breast tumors that express the hypermethylation signature defined by CDH1 , CEACAM6, CST6, ESR1, LCN2 , and SCNN1A . This subset of breast cancers represents 18/88 (20%) tumors in the dataset analyzed, and 100% of these tumors were classified as basal-like, suggesting that the hypermethylator defect cosegregates with poor prognosis breast cancers. Conclusion These observations combine to strongly suggest that: (a) a subset of breast cancer cell lines express a hypermethylator phenotype, (b) the hypermethylation defect in these breast cancer cell lines is related to aberrant overexpression of DNMT activity, (c) overexpression of DNMT3b protein significantly contributes to the elevated DNMT activity observed in tumor cells expressing this phenotype, and (d) the six-gene hypermethylator signature characterized in breast cancer cell lines defines a distinct cluster of primary basal-like breast cancers.
Molecular phylogeny of symbiotic dinoflagellates from planktonic foraminifera and radiolaria
Authors: R. J. Gast, D. A. Caron
Journal: Molecular Biology and Evolution (1996)

Recent analyses of the small subunit ribosomal DNA (srDNA) from dinoflagellate symbionts of cnidaria have confirmed historical descriptions of a diverse but well-defined clade, Symbiodinium, as well as several other independent symbiont lineages (Rowan 1991; Rowan and Powers 1992; Sadler et al. 1992; McNally et al 1994). Dinoflagellates also occur as intracellular symbionts in a number of pelagic protistan taxa, but the srDNA of these symbionts has not been examined. We analyzed the srDNA sequences of the symbiotic dinoflagellates from four planktonic foraminiferal species and six radiolarian species. The symbionts from these sarcodines formed two distinct lineages within the dinoflagellates. Within each lineage, symbionts obtained from different host species showed few, if any, srDNA sequence differences. The planktonic foraminiferal symbionts were most closely related to Gymnodinium simplex and the Symbiodinium clade, whereas the radiolarian symbionts were most closely related to the dinoflagellate symbiont from the oceanic chondrophore, Velella velella. Therefore, although the dinoflagellate symbionts of foraminifera appear to be a sister taxon of the symbionts from benthic foraminifera and invertebrates, the symbionts of radiolaria are distinct and arose from an independent lineage of dinoflagellate symbionts that shares common ancestry with the symbiont of at least one pelagic metazoan. The lack of srDNA variability within the sarcodine symbiont lineages suggests that coevolution of host and symbiont has not occurred.
Arteriovenous Aneurysm of Phrenic Vessels Simulating Cardiac Fistula
Authors: IAN R. GRAY, H. PARRY WILLIAMS
Journal: Circulation (1962)

A child is described with an arteriovenous communication between the left phrenic artery and the left pericardio-phrenic vein. The differential diagnosis of continuous murmurs in the chest is discussed in the light of this case. The hemodynamic consequences of arteriovenous communications and indications for their surgical treatment are briefly outlined.
Acute Pancreatitis in Association With Type 2 Diabetes and Antidiabetic Drugs
Authors: Antonio Gonzalez-Perez, Raymond G. Schlienger, Luis A. García Rodríguez
Journal: Diabetes Care (2010)

Previous observational studies have found an increased risk of acute pancreatitis among type 2 diabetic patients. However, limited information is available on this association and specifically on the role of antidiabetic treatment. Our aim, therefore, was to further assess the risk of acute pancreatitis in adult patients with type 2 diabetes.We performed a population-based case-control analysis nested in a cohort of 85,525 type 2 diabetic patients and 200,000 diabetes-free individuals from the general population using data from The Health Improvement Network database. Subjects were followed up to ascertain incident cases of acute pancreatitis.We identified 419 cases of acute pancreatitis, 243 in the general population and 176 in the diabetes cohort. Incidence rates were 30.1 and 54.0 per 100,000 person-years in the general population and the diabetes cohort, respectively. In the cohort analysis, the adjusted incidence rate ratio of acute pancreatitis in diabetic patients versus that in the general population was 1.77 (95% CI 1.46-2.15). The magnitude of this association decreased with adjustment for multiple factors in the nested case-control analysis (adjusted odds ratio 1.37 [95% CI 0.99-1.89]). Furthermore, we found that the risk of acute pancreatitis was decreased among insulin-treated diabetic patients (0.35 [0.20-0.61]).Type 2 diabetes may be associated with a slight increase in the risk of acute pancreatitis. We also found that insulin use in type 2 diabetes might decrease this risk. Further research is warranted to confirm these associations.
Prognostic Value of Site SYNTAX Score and Rationale for Combining Anatomic and Clinical Factors in Decision Making
Authors: Yao-Jun Zhang, Javaid Iqbal, Carlos M. Campos, David V. Klaveren, Christos V. Bourantas, Keith D. Dawkins, Adrian P. Banning, Javier Escaned, Ton de Vries, Marie-Angèle Morel, Vasim Farooq, Yoshinobu Onuma, Hector M. Garcia-Garcia, Gregg W. Stone, Ewout W. Steyerberg, Friedrich W. Mohr, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2014)