tbuckley/cabot-search huggingface dataset:
Immune Deficiency and Cancer: Epstein-Barr Virus and Lymphoproliferative Malignancies.
Authors: David T. Purtilo
Journal: Annals of Internal Medicine (1985)

Immune Deficiency, Epstein-Barr Virus (EBV) and Lymphoproliferative Disorders.- Classical Epstein-Barr Virus Associated Disorders.- Infectious Mononucleosis and Complications.- Nasopharyngeal Carcinoma.- Burkitt's Lymphoma.- Inherited Immune Deficiency and Lymphoproliferative Malignancies.- Hematopathology of X-Linked Lymphoproliferative Syndrome.- Responses to Epstein-Barr Virus in Immune Deficient Patients.- Immunodeficiency to Epstein-Barr Virus in Chediak-Higashi Syndrome.- Model Systems for Epstein-Barr Virus-Target Cell Interaction.- Expression of Virus-Associated Functions in Cells Transformed In Vitro by Epstein-Barr Virus: Epstein-Barr Virus Cell Surface Antigen and Virus-Release From Transformed Cells.- In Vitro Modulation of Epstein-Barr Virus-Carrying Lymphoblastoid Cell Lines.- Epstein-Barr Virus in New Host Cells.- Biology of Epstein-Barr Virus.- Herpesvirus-Induced Lymphoproliferative Diseases in Non-Human Primates.- Relationship of Immune Deficiency and Oncogenic Viruses to Malignant B Cell Lymphomas: Mouse and Man.- Acquired Immune Deficiency and Lymphoproliferative Disorders.- Allograft Transplant Cancer Registry.- Lymphoma in Cardiac Transplant Recipients Associated with Cyclosporin A, Prednisone, and Anti-Thymocyte Globulin (ATG).- Lymphoproliferative Diseases in Renal Allograft Recipients.- Chronic Mononucleosis.- The Syndrome of Acquired Immunodeficiency Among a Subset of Homosexual Men.- Lymphoproliferative Diseases and Kaposi's Sarcoma in Homosexual Males.- Genetic Factors in Lymphomagenesis.- Mendelian Predisposition to Lymphomagenesis.- Chromosomal Defects and Their Role in Lymphomagenesis.- Prevention of Epstein-Barr Induced Diseases in Immunodeficient Individuals.- Interferon Therapy in Herpes Virus Infections.- Epstein-Barr Virus and Marrow Transplantation Recipients.- Immunoreconstitution by Bone Marrow Transplantation Decreases Lymphoproliferative Malignancies in Wiskott-Aldrich and Severe Combined Immune Deficiency Syndromes.- Contributors.
The Pregnant Therapist
Authors: CAROL NADELSON, MALKAH NOTMAN, ELISSA ARONS, JUDITH FELDMAN
Journal: American Journal of Psychiatry (1974)

The authors discuss the relevance of a therapist`s pregnancy to the therapeutic interaction, presenting case histories to illustrate the issues that arise. The therapist must deal with increased vulnerability, role integration, and dependency issues with colleagues. In the patient, the pregnancy may evoke infantile feelings, intensified maternal transference, and internal sexual conflicts. The authors recommend that the therapist deal with her pregnancy openly and realistically; they believe that working through the reactions of both therapist and patient may be an effective aspect of therapy.
Prospective evaluation of the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample
Authors: Xu Yang, Xiao‐peng Tang, Yong‐hong Zhang, Kai‐zhong Luo, Yong‐fang Jiang, Hong‐yu Luo, Jian‐hua Lei, Wen‐long Wang, Ming‐ming Li, Han‐chun Chen, Shi‐lin Deng, Li‐ying Lai, Jun Liang, Min Zhang, Yi Tian, Yun Xu
Journal: Hepatology (2015)

Hepatic copper determination is an important test for the diagnosis of Wilson's disease (WD). However, the method has not been standardized, the diagnostic accuracy has not been evaluated prospectively, and the optimal cut‐off value remains controversial. Accordingly, we aimed to prospectively evaluate the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample. Patients for whom a liver biopsy was indicated were consecutively enrolled. Hepatic copper content was determined with atomic absorption spectroscopy. All assays were performed using careful quality control by a single technician. WD diagnosis was based on WD score or its combination with clinical follow‐up results. A total of 3,350 consecutive patients underwent liver biopsy. Six hundred ninety‐one patients, including 178 with WD, underwent two passes of liver biopsy with hepatic copper determination. Mean hepatic content in WD patients was 770.6 ± 393.2 μg/g dry weight (wt). Sensitivity, specificity, and positive and negative predictive values of hepatic copper content for WD diagnosis in the absence of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis at the cut‐off value of 250 μg/g dry wt. were 94.4%, 96.8%, 91.8%, and 97.8%, respectively. The most useful cut‐off value was 209 μg/g dry wt, with a sensitivity and specificity of 99.4% and 96.1%, respectively. A total of 23.3% of patients without WD and PBC had hepatic copper content &gt;75 μg/g dry wt. Conclusion: A liver biopsy sample of more than 1 mg dry wt may reliably reflect hepatic copper content and should be used for hepatic copper determination. Hepatic copper determination is a very valid procedure for the diagnosis of WD, and the most useful cut‐off value is 209 μg/g dry wt.(H epatology 2015;62:1731–1741)
A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC).
Authors: J. O'Shaughnessy, D. Miles, R. J. Gray, V. Dieras, E. A. Perez, R. Zon, J. Cortes, X. Zhou, S. Phan, K. Miller
Journal: Journal of Clinical Oncology (2010)

1005 Background: E2100, AVADO, and RIBBON-1, three randomized trials in patients with MBC evaluating BV plus first-line chemotherapy regimens (taxane-, anthracycline-, or capecitabine-based), each demonstrated improvement in the primary endpoint of progression-free survival (PFS). Although the trials were not designed to show an overall survival (OS) benefit, it was a secondary endpoint in all trials. We present a meta-analysis of OS in 2,447 patients from these trials using complete survival data for each study. Methods: Kaplan—Meier methodology was used to estimate the median duration of PFS and OS. Stratified log-rank test was used to assess the difference in PFS and OS between treatment arms (control vs. BV+chemo). Stratified hazard ratio (HR) was estimated using the Cox regression model. Each individual study was included as a stratification factor in the stratified analysis. 1-year survival rate was compared using normal approximation method. All p-values were two-sided and tested at the type I error rate of 0.05. Results: 2,447 patients were included (1,008 control; 1,439 BV+chemo). Patient characteristics were well- balanced between the arms (overall median age, 56; hormone receptor-positive, 73%; prior adjuvant chemo, 62%; ≥3 metastatic sites, 40%). Duration of follow-up ranged from 29 (AVADO) to 36 (E2100) months. In the pooled analysis, median PFS improved from 6.7 to 9.2 mo (HR=0.64, p<0.0001) in the BV arms. Pooled results for OS showed no statistically significant difference between the arms (median OS control 26.4 mo, BV+chemo 26.7 mo; HR=0.97, (95% CI, 0.86–1.08, p=0.56). 1 yr survival rate was greater in the BV+chemo arms (control, 76.5%; BV+chemo, 81.6%, p=0.003). Results were consistent across key subgroups. Conclusions: Results from the exploratory analysis of the pooled PFS data show that BV, when combined with first-line chemotherapy (taxane-, anthracycline-, or capecitabine-based regimens), results in clinically meaningful and statistically significant improvements in PFS. Though no statistically significant difference in median OS was seen, the pooled OS data from these trials suggest an early benefit at 1 year. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, NICRC CCOP-NCI Genentech, Roche Roche Genentech, Roche Genentech
An empirical literature review of definitions of severe and persistent mental illness
Authors: A P Schinnar, A B Rothbard, R Kanter, Y S Jung
Journal: American Journal of Psychiatry (1990)

Seventeen definitions of the severely and persistently mentally ill have appeared in the literature over the past decade. These definitions have been used by 13 authors to formulate service programs and to estimate the prevalence of serious mental illness in the population. To test the applicability of these definitions, the authors operationalized each definition and applied it to a representative sample of 222 patients receiving services in one of Philadelphia's inner-city neighborhoods. The analysis showed estimates of prevalence of serious mental illness ranging from 4% to 88% of the treated population, depending on the definition applied. The NIMH (1987) definition was representative of the middle-range estimates of 45% to 55% arrived at by eight authors.
Exhaled breath condensate hydrogen peroxide in obstructive airways disease
Authors: Prasanna Sankaran, Ajay Kamath, Andrew Wilson
Journal: European Respiratory Journal (2014)

Background   Non-Invasive assessment of inflammation and oxidative stress has been of interest in the past two decades. Exhaled breath hydrogen peroxide (H202) is a marker of oxidative lung injury but is a highly unstable chemical and difficult to measure. We have performed a real-time assessment of H202 and wished to assess its utility in patients with stable and exacerbated airways disease.   Methods   We recruited 23 (10 male) patients, with stable airways disease (asthma or COPD) and 37 (16 male) patients with acute exacerbation admitted to hospital. Measurements were made of H202 using a handheld collector and analysed using a new biosensor based, real-time analyser (Exhalation Technology Limited, Dereham Norfolk) that gives immediate result. Exhaled Nitric oxide (FENO) was measured using a NIOX MINO (Aerocrine, Sweden). Spirometry was attempted in all patients.   Results   In exacerbation of airways disease (37), only 2 were able to perform spirometry, 26 were able to performed FENO and all 37 were able to do H202. H202 was higher in exacerbated airways disease(p=0.04) but FENO was not significant. H202 and FENO were higher (non significant) in exacerbations of asthma and COPD.   Conclusion   Our study demonstrates that EBC H202 measurement can be applied in a clinical setting using newer sensors that provide a real-time analyses. We have demonstrated higher H202 in exacerbated airways disease suggesting its utility in patient assessment.
Clinical analysis of patients treated with mechanical ventilation in an emergency respiratory ward
Authors: Valentina Dimitrova, Marinka Peneva, Kamen Yankov
Journal: European Respiratory Journal (2012)

Aim:  To make analysis of indications, duration, complications and outcome of the mechanical ventilation in patients treated in the Emergency Respiratory Ward.   Data and methods:    A retrospective analysis of the patients in the Emergency Respiratory Ward treated with mechanical ventilation during the last 5 years (2007-2011) has been made. 191 patients (10,33%) from the total number of patients (1848) needed mechanical ventilation.   Results:   The percentage of patients, treated with mechanical ventilation, does not differ substantially during the studied years – from 10,81% in 2007 to 11,68% in 2011.  The most common reason for heavy respiratory insufficiency, demanding mechanical ventilation, is pulmonary pathology (81,67%) as the greatest percentage belongs to COPD exacerbation and its complications (pneumonia) – 134 patients (85,90%). The most common reasons from the non-pulmonary pathology are alveolar hypoventilation in case of extreme obesity, chest deformations, left - side cardiac insufficiency.  The usual duration of mechanical ventilation is 15 days as there are no significant differences in the studied years – from 77,14 % to 87,10 %.  7 of the patients (3,66 %) have a verified diagnosis ventilator – associated pneumonia.  The total number of patients with lethal outcome is 66 (34,50 %) as there are no significant differences in the studied years.   Conclusion:    About 10 % of the patients, treated in Emergency Respiratory Ward, need mechanical ventilation as the most common pulmonary pathology is COPD. Problematic microbial flora, most often Gram /-/ strains are isolated in tube secrets, which significantly deteriorates the prognosis and leads to lethality in 34,50 % of the cases.
Abstract 594: DNAJB6a as tumor suppressor in esophageal squamous cell carcinoma
Authors: Valentine Zhuoyou YU, Victor Chun Lam WONG, Kwok Wah CHAN, Maria Li LUNG
Journal: Cancer Research (2014)

Abstract Esophageal squamous cell carcinoma (ESCC) has an especially high incidence in China, with five-year survival rates in Hong Kong being of ∼14%. Functional impact and molecular mechanisms of DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) in ESCC were examined. Tissue microarray (TMA) analysis was performed to investigate the clinical relevance of DNAJB6 in ESCC. In vivo and in vitro functional and molecular studies were performed to verify the TMA results and elucidate the mechanisms for DNAJB6 function. Nuclear but not cytoplasmic DNAJB6 staining was found to correlate significantly with survival in metastasis-free patients by Kaplan-Meier analysis. Expression of nuclear DNAJB6 was down-regulated in tumors compared to normal tissues. In ESCC cell lines, over-expression of the nuclear isoform (DNAJB6a) suppresses in vivo tumor growth in a localization-dependent manner. DNAJB6a over-expression suppresses G1/S transition through inhibiting the key oncogenic Akt signaling pathway and impairs proliferation, by recruiting protein phosphatase 2A through the N-terminal HPD motif. DNAJB6a silencing results in the opposite effect in both cancer cells and immortalized normal esophageal epithelial (NE) cells. DNAJB6a silencing in NE cells also results in senescence-like alterations. DNAJB6a also regulates Akt phosphorylation in other cancers. In summary, nuclear DNAJB6 staining is associated with survival in ESCC patients. DNAJB6a regulates AKT1 phosphorylation in ESCC to suppress tumorigenicity. DNAJB6a may be a useful biomarker for detecting early ESCC tumor initiation and its role in Akt signaling may yet provide opportunities for therapeutic intervention. Note: This abstract was not presented at the meeting. Citation Format: Valentine Zhuoyou YU, Victor Chun Lam WONG, Kwok Wah CHAN, Maria Li LUNG. DNAJB6a as tumor suppressor in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 594. doi:10.1158/1538-7445.AM2014-594
Hearing loss is important in dementia
Authors: Ted Leverton
Journal: BMJ (2015)

The useful clinical review on timely diagnosis and early intervention in dementia misses one important point—hearing loss1—which complicates dementia in three ways. It confuses diagnosis and interferes with support, and evidence shows that people whose hearing loss has been treated have reduced levels of dementia.

By the age of 70 years, 70% of people have hearing loss,2 and many refuse hearing aids. Hearing loss …
Asthma, upper airway disease and systemic inflammation in patients with Churg Strauss syndrome and severe chronic asthma
Authors: Manuela Latorre, Federica Novelli, Veronica Seccia, Chiara Baldini, Paolo Iannicelli, Federico Dente, Maria Laura Bartoli, Stefano Bombardieri, Pier Luigi Paggiaro
Journal: European Respiratory Journal (2012)

Background : the bronchial and systemic eosinophilic inflammation is a well-known distinctive tract in patients with SCA (severe chronic asthma) and with CSS (Churg Strauss syndrome), where the upper airways disease is a comorbidity which strongly influences the respiratory symptoms.

Aims : to compare the functional and biological characteristics of patients with SCA and CSS in relation to systemic asset and level of therapy; to define the upper airways diseases and to characterize nasal inflammation.

Methods : 35 patients with CSS and 21 with SCA were enrolled. All patients were assessed for lung function and bronchial iperreactivity. Asthma control was established according to GINA guidelines and by ACT questionnaire, the quality of life by AQLQ. Sputum eosinophil percentages, exhaled nitric oxide, peripheral blood eosinophil counts and nasal disease and cytology were assessed.

Result : the two groups of patients were similar in lung function, asthma control and quality of life. While CSS patients showed higher sputum eosinophil percentages (38[91] vs 15[94], p<0.05) SCA patients had higher peripheral eosinophil counts (895±740 vs 592±579, p<0.05), depending probably by the different therapy (higher systemic therapy in CSS vs higher ICS dose in SCA).The majority of patients presented upper airway involvement, with eosinophilic inflammation evidence (nasal eosinophilic %: 0.5[38] CSS vs 0.6[10] CSA).

Conclusions : both groups of patients showed partially controlled eosinophilic airway inflammation. The ICS dose in CSS patients seems not appropriate to the asthma severity. Eosinophilic upper airway inflammation may represent a limit to achieve a good asthma control.
Abstract 3572: Copy number detection using genomics technologies: A comparison between aCGH and NGS
Authors: George Vasmatzis, Andrew L. Feldman, Sarah H. Johnson, Erik C. Thorland, Rafael Fonseca, Esteban Braggio, Troy J. Gliem
Journal: Cancer Research (2014)

Abstract Introduction: Identification of causal DNA copy number variations (CNVs) is critical to the understanding of cancer development and progression, and is important clinically for accurate prognosis and efficient treatment. T-cell lymphomas are replete with amplifications and deletions that result in over- and under-expression of genes. Array comparative genomic hybridization (aCGH) has been the technology of choice to detect CNVs but recently, it has been proposed that mate-pair Next Generation Sequencing (mpNGS) can produce similar results. Here, we report a comparison between the two techniques. Methods: We have developed an algorithm based on extreme value theory to identify CNVs across the genome at high resolution from mate-pair NGS data. The algorithm is based on plotting the distribution of read-counts in windows across the genome, and detecting deletions and gains by finding the windows that differ significantly from the distribution of the normal part of the genome. We compared this algorithm with aCGH data to detect CNVs. We ran five cases of T-cell lymphoma with both techniques and compared the results using concordance statistics. Results: With 50kb lower cutoff for a CNV, mpNGS detected 98% of the cumulative deleted genome and 94% of the amplified/gained genome that were called by aCGH. Most of the discordant CNVs that were detected by only aCGH were in regions of repetitive areas where mapping fails. Conversely, aCGH detected 75% of the cumulative deleted genome and 74% of the amplified/gained genome that were called by mpNGS. Conclusion: A detailed comparison of these techniques showed that both have pros and cons. In general, mpNGS can detect most CNVs detected by aCGH, as long as they are more than 50KB. Additionally, mpNGS offers confirmatory data, particularly for deletions, based on detection of aberrant mate pairs that map to the rejoined ends of deleted regional. Finally, the mate-pair technology can also detect balanced translocations and can also predict fusion genes. Citation Format: George Vasmatzis, Andrew L. Feldman, Sarah H. Johnson, Erik C. Thorland, Rafael Fonseca, Esteban Braggio, Troy J. Gliem. Copy number detection using genomics technologies: A comparison between aCGH and NGS. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3572. doi:10.1158/1538-7445.AM2014-3572
Myocardial Fibrosis in Hypertrophic Cardiomyopathy
Authors: David M Kaye, Leah Iles, Andrew J Taylor
Journal: New England Journal of Medicine (2010)

Hypertrophic cardiomyopathy (HCM) is characterised by myocardial hypertrophy, fibrosis and abnormal vascular pathology and is usually caused by mutations in sarcomeric protein genes.Histological studies and in vivo imaging with cardiac magnetic resonance imaging (CMRI) have shown that myocardial fibrosis is an important entity that contributes to disease progression.However, little is known about the regulation of genes involved in collagen synthesis and metabolism, the pathways that contribute to the development of myocardial fibrosis and whether this is an early pathological process which ultimately leads to the development of the overt phenotype in genetic mutation carriers.Furthermore, the contribution of fibrosis on myocardial function has been poorly defined.In this thesis, I identified that myocardial genetic expression of collagen is upregulated in patients with HCM and this is paralleled by elevated levels of procollagen in plasma.The genetic expression of transforming growth factor beta (TGF-β) and its downstream mediator connective tissue growth factor was also enhanced in HCM and correlated with collagen I and III RNA levels, suggesting a central role of TGF-β in mediating fibrosis.Plasma markers of collagen synthesis and metabolism were also increased in sarcomeric mutation carriers without hypertrophy, suggesting that fibrosis may be an early process that contributes to the development of the overt phenotype.Plasma levels of procollagen I were higher in patients with non-sustained ventricular tachycardia and focal fibrosis identified by CMRI was associated with impaired systolic deformation.Diffuse fibrosis beyond that seen in healthy controls also correlated with a reduction in systolic function.Together, the findings of this thesis support the hypothesis that myocardial fibrosis is an active process in HCM that precedes clinical phenotype.Myocardial fibrosis is at least in part mediated by the TGF-β pathway and associated with impaired systolic performance and may contribute to arrhythmic risk in HCM.
Survival of patients (pts) with metastatic melanoma treated with the anti-CTLA4 monoclonal antibody (mAb) CP-675,206 in a phase I/II study
Authors: J. Gomez-Navarro, S. Antonia, J. Sosman, J. M. Kirkwood, B. Redman, T. F. Gajewski, D. Pavlov, C. Bulanhagui, A. Ribas, L. H. Camacho
Journal: Journal of Clinical Oncology (2007)

8524 Background: The fully human anti-CTLA4 mAb CP-675,206 has demonstrated clinical activity in pts with metastatic melanoma. Prolonged survival was observed in a prior single-dose phase I study, even in pts who did not achieve objective tumor responses. Methods: A multidose phase I/II trial was conducted in pts (N = 119) with histologically confirmed stage IIIc (unresectable) or stage IV recurrent metastatic melanoma and ECOG PS = 1. The study consisted of a phase I, open-label, multidose study (3, 6, and 10 mg/kg) and a phase I expansion cohort for HLA-A2.1+ pts (10 mg/kg monthly [Q1M]), followed by a phase II open-label study of 2 dosing regimens: 10 mg/kg Q1M and 15 mg/kg every 3 months (Q3M). The primary endpoint was safety in phase I, immune monitoring in the expansion cohort, and response in phase II. Survival was analyzed as a secondary endpoint. Results: In the phase I study, Kaplan-Meier estimates of median overall survival were 17.6 months for all dose groups combined (n = 28). In the phase II study, median survival was 10.3 months in the 10 mg/kg arm and 11.0 months in the 15 mg/kg arm. Survival outcomes were favorable, compared with historical median survival of 7 months, independent of whether pts achieved an objective response. Updated survival data will be presented. Conclusions: Patients participating in a multiple dose study of CP-675,206 showed a survival time that was greater than expected on historic controls. These observations support the endpoints of an ongoing randomized phase III study in melanoma to further evaluate survival in the frontline setting. [Table: see text] [Table: see text]