tbuckley/cabot-search huggingface dataset:
S90 ‘Chronic cough, cause unknown’: a qualitative study of patient perspectives of idiopathic cough
Authors: K Hulme, S Dogan, SM Parker, V Deary
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Idiopathic chronic cough patients have symptoms that persist despite trials of empirical treatment with no underlying cause found. Higher-order brain processes are involved in modulating the cough reflex, but very little is known about the psychological processes underlying idiopathic cough. As the first step in the development of a complex intervention, we sought to elicit an in-depth understanding of patient experience of this condition. <h3>Methods</h3> Fourteen patients (12 females, mean age = 59 years) participated in qualitative interviews theoretically based upon the comprehensive cognitive-behavioural model. Interviews were thematically analysed and cross-validated using the guidelines outlined by Braun and Clark (2006). <h3>Results</h3> Eight key themes emerged illustrating the complex, all-encompassing nature of idiopathic cough. ‘Individual vulnerability’ described precipitating factors possibly linked with cough onset. ‘More than just a cough’ highlighted the co-occurrence of severe physical and emotional experiences. ‘Cough in the social sphere’ highlighted the effort of dealing with others’ reactions and concerns about the contagious image. ‘Cough and Identity’ described how the cough often defines the person. The occurrence of ‘Vicious circles’ became apparent, contributing to cough maintenance. ‘The battle for control’ highlighted the unpredictable nature of the cough, its subsequent impact and the management strategies employed to counter this. Framing the ‘Cough in relation to other health conditions’ provided coughers with a point of reference and some coherence to an otherwise confusing condition. The theme ‘‘At the end of the line’: the cough healthcare journey’ described the care experienced and the continuing search for answers. <h3>Conclusions</h3> The onset and persistence of idiopathic cough is complex, involving many interlinking factors. Experiential evidence confirmed previous findings of the involvement of biological (e.g. urge-to-cough sensations) and psychological (e.g. attention) mechanisms. Importantly, it also highlighted the role of the social dimension in how the cough is perceived and managed. These insights suggest a valuable target for future interventions, which accordingly need to take a multi-disciplinary and integrative approach. <h3>Reference</h3> 1 Braun V, Clarke V. Using thematic analysis in psychology. <i>Qual Res Psychol</i>. 2006;<b>3</b>:77–101
PTU-182 Can response to pharyngeal stimulation in dysphagic stroke be predicted by bdnf genetic polymorphisms?
Authors: H Essa, D Vasant, A Raginis-Zborowska, A Payton, E Michou, S Hamdy
Journal: Gut (2015)

<h3>Introduction</h3> Pharyngeal electrical stimulation (PES) has shown promise as a novel treatment option for dysphagia after stroke. Furthermore, we have shown that the BDNF Val66Met polymorphism is strongly associated with cortical plasticity to neurostimulation in the pharyngeal motor system (Gastroenterology 2011;141:827–836). However, the ability to predict response outcome and the factors associated with stimulation driven dysphagia recovery are unclear. This study aims to elucidate the role of common genetic polymorphisms in influencing response to PES. <h3>Method</h3> 38 dysphagic stroke patients were recruited for a single blinded randomised control trial of active or sham PES over a 4 year period. Swallowing outcome was assessed by a validated dysphagia severity rating scale, recorded at baseline, 2 weeks and 3 months post recruitment. Saliva samples were obtained during the recruitment phase for DNA extraction and genotyped for the BDNF polymorphism Val66Met rs76265. Response to PES was correlated with BDNF status. Statistical analysis was performed using a linear regression model adjusting for stroke severity (based on NIHSS score) and patient’s age. <h3>Results</h3> Of the 38 patients recruited, 20 patients provided quantifiable saliva samples, of which 16 (8 in the active group and 8 in the sham group) were clean enough for DNA extraction. Analysis revealed that in the active stimulation group the presence of the BDNF Met allele demonstrated significantly greater improvements at the 3 months stage as compared to non-Met allele counterparts (F(2, 4) 23.89, p = . 009). No associations were seen in the sham group. <h3>Conclusion</h3> This novel study has found intriguing associations between BDNF polymorphisms and stimulation related swallowing recovery that warrant further research. <h3>Disclosure of interest</h3> H. Essa: None Declared, D. Vasant: None Declared, A. Raginis-Zborowska: None Declared, A. Payton: None Declared, E. Michou: None Declared, S. Hamdy Conflict with: Provide scientific advice to Phagenesis Ltd.
Noninvasive Measures of Ventricular-Arterial Coupling and Circumferential Strain Predict Cancer Therapeutics–Related Cardiac Dysfunction
Authors: Hari K. Narayan, Benjamin French, Abigail M. Khan, Theodore Plappert, David Hyman, Akinyemi Bajulaiye, Susan Domchek, Angela DeMichele, Amy Clark, Jennifer Matro, Angela Bradbury, Kevin Fox, Joseph R. Carver, Bonnie Ky
Journal: JACC. Cardiovascular imaging (2016)
Androgen-Induced Increase in Red-Cell 2,3-Diphosphoglycerate
Authors: John P. Parker, Gregory J. Beirne, Jitendra N. Desai, Peter C. Raich, Nasrollah T. Shahidi
Journal: New England Journal of Medicine (1972)

The administration of testosterone enanthate to six patients with chronic renal failure on biweekly hemodialysis increased erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in all patients. Whereas the value was 5670 ± 550 (mean ± S.E.) nmoles per milliliter of red blood cells before treatment, it was 9097 ± 760 after 12 weeks of androgen therapy. This increase was statistically significant (p less than 0.01). None of a group of seven similarly affected patients who did not receive androgens and were followed within the same period showed any increase in red-cell 2,3-DPG. The shift in oxygen equilibrium curve to the right that results from testosterone enanthate should greatly enhance the unloading of oxygen to the tissues.
Localization of Parathyroid Adenomas by Selective Venous Catheterization and Radioimmunoassay
Authors: Richard E. Reitz, James J. Pollard, Chiu-An Wang, Donald J. Fleischli, Oliver Cope, Timothy M. Murray, Leonard J. Deftos, John T. Potts
Journal: New England Journal of Medicine (1969)

We have successfully applied the radioimmunoassay for parathyroid hormone (PTH) to the localization of parathyroid adenomas by measurements of hormone concentration in multiple blood samples obtained by selective catheterization of the major veins draining the neck and thorax. During venous catheterization, blood samples collected from the left and right jugular, left and right subclavian and left and right innominate veins and superior and inferior vena cava showed a definite localized increase in PTH concentration in six patients. In five patients the increase was found in either the right or the left jugular vein; in the sixth patient a mediastinal location of the adenoma was indicated. The location of the tumor was in agreement with findings at surgery in all patients. The application of these technics can greatly facilitate efforts to remove all abnormal parathyroid tissue at a single operation.
Diagnostic categorization of psychiatric disturbance in Cushing's syndrome
Authors: R F Haskett
Journal: American Journal of Psychiatry (1985)

The author obtained a longitudinal psychiatric history from 30 patients with proven Cushing's syndrome. Twenty-five (83%) of the patients met strict diagnostic criteria for an episode of affective disorder during the course of their endocrine disturbance. Twenty patients met criteria for endogenous depression and eight patients also reported an episode of mania or hypomania. Schizophrenic syndromes were not evident, although two patients met criteria for a psychotic depression. Patients frequently attempted to minimize or conceal serious psychiatric disturbance, including a suicide attempt. Typical affective syndromes occurred in patients with adrenocortical tumors as well as in those with ACTH-dependent Cushing's syndrome.
Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines
Authors: Özlem Türeci, Mathias Vormehr, Mustafa Diken, Sebastian Kreiter, Christoph Huber, Ugur Sahin
Journal: Clinical Cancer Research (2016)

Somatic mutations binding to the patient's MHC and recognized by autologous T cells (neoepitopes) are ideal cancer vaccine targets. They combine a favorable safety profile due to a lack of expression in healthy tissues with a high likelihood of immunogenicity, as T cells recognizing neoepitopes are not shaped by central immune tolerance. Proteins mutated in cancer (neoantigens) shared by patients have been explored as vaccine targets for many years. Shared ("public") mutations, however, are rare, as the vast majority of cancer mutations in a given tumor are unique for the individual patient. Recently, the novel concept of truly individualized cancer vaccination emerged, which exploits the vast source of patient-specific "private" mutations. Concurrence of scientific advances and technological breakthroughs enables the rapid, cost-efficient, and comprehensive mapping of the "mutanome," which is the entirety of somatic mutations in an individual tumor, and the rational selection of neoepitopes. How to transform tumor mutanome data to actionable knowledge for tailoring individualized vaccines "on demand" has become a novel research field with paradigm-shifting potential. This review gives an overview with particular focus on the clinical development of such vaccines.
Abstract P1-04-01: Breast milk exosomes promote breast cancer progression
Authors: ER Sauter, W Qin, S Dasgupta
Journal: Cancer Research (2016)

Abstract Background: The stimulation of extant neoplastic cells vs. their inhibition during breast involution is a key concept in whether pregnancy and lactation decrease or increase breast cancer risk. The time of weaning, a period of breast involution and remodeling, appears critical to future breast cancer risk, as during involution the breast microenvironment becomes tumor promotional. Both matrix metalloproteinases (MMPs) and transforming growth factor (TGF)β isoforms have been implicated in this process. We previously reported that TGFβ2 (but not TGFβ1) expression was significantly higher in milk collected from the cancer containing (vs. matched clinically normal) breast of women diagnosed with cancer during lactation. Hypothesis: TGFβ2 in milk exosomes from healthy lactating women modulates the development and progression of breast cancer. Methods: Matched (early, mature and wean-early involution) milk samples were collected from 13 lactating women, exosomes isolated and the levels of five (MMP2, 3, 9; TGFβ1, 2) proteins measured. Based on the results, additional wean samples were analyzed for TGFβ2 expression and samples divided based on their TGFβ2 expression. The highest and lowest TGFβ2 expressing milk exosome samples were co-cultured with MCF-7 breast cancer cells grown in exosome-depleted media. Cell proliferation was measured after 24h. Confocal microscopy was performed after 72h to evaluate epithelial to mesenchymal transition (EMT) in the cells. A TGFβ2 neutralizing blocking antibody was applied after 72 h co-culture. Results: The greatest increase in expression (four-fold) at the time of involution was in TGFβ2. Confocal microscopy performed 24h after co-culture confirmed the uptake of the exosomes (both those expressing hi and lo TGFβ2) in the MCF-7 cells. There was a significant increase in cell proliferation compared to control (p&amp;lt;0.001) in cells treated with hi TGFβ2 milk exosomes. 72h after co-culture, bright field microscopy demonstrated that MCF-7 cells treated with hi TGFβ2 underwent EMT including the formation of filopodia, whereas those treated with low TGFβ2 did not. A TGFβ2 blocking antibody reversed the EMT phenotype and filopodia formation. Impact: Pregnancy has a lasting influence on breast cancer risk, and pregnancy associated breast cancers (PABCs) diagnosed after delivery are generally aggressive, with a poor prognosis. Part of the reason for the development of PABCs, and the aggressive nature of PABCs may be the influence of high-expressing TGFβ2 exosomes in the milk on the breast ductal epithelium. Citation Format: Sauter ER, Qin W, Dasgupta S. Breast milk exosomes promote breast cancer progression. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-04-01.
Phase 2 Trial to Evaluate the Efficacy and Safety of Dovitinib in Patients (Pts) with Gastrointestinal Stromal Tumor (Gist) Refractory and/or Intolerant to Imatinib (Im)
Authors: H. Joensuu, J-Y. Blay, A. Comandone, J. Martin Broto, E. Fumagalli, G.E. Grignani, X. Garcia Del Muro, A. Adenis, C. Valverde Morales, A. Lopez Pousa, O. Bouché, B. Bui, S. Bauer, C. Barone, C. Weiss, S. Crippa, M. Camozzi, R. Castellana, A. Le Cesne
Journal: Annals of Oncology (2014)
Expression of multiple cancer stem cell markers by triple-negative breast carcinomas.
Authors: A. Behdad, S. Bose
Journal: Journal of Clinical Oncology (2010)

e21108 Background: Breast carcinomas lacking expression of ER, PR, and HER2 (triple-negative [TN] carcinomas), are characterized by aggressive behavior, distinct pattern of metastasis, and lack of targeted therapy. In this study we sought to evaluate the presence of cancer stem cells (CSC) in this group of cancers. CSC are pluripotential cells with tumor-initiating properties capable of driving tumor growth and progression and are believed to be responsible for treatment failures and recurrences. Methods: Eleven TN, five ER/PR positive and four HER-2 positive cases of invasive breast carcinoma, diagnosed in 1999 with median follow-up of 90 months, were randomly selected from our files. Immunohistochemical stains for cytokeratins using ADH-5 cocktail (composed of CK5, CK14, p63, CK7, CK18 antibodies), EGFR and CSC markers including CD44, CD24, CD133, ALDH1, and EZH2 were performed. Results of immunohistochemical stains were correlated with conventional prognostic biomarkers. Results: 9 (45%) of the cases expressed basal cytokeratins, while the remaining 11 (55%) expressed luminal cytokeratins with the ADH-5 cocktail. EZH2 was the most frequently expressed CSC marker, noted in 14 (70%) of the cases. 12 (60%) of the breast cancers were CD 44+/CD24±, while CD 133 and ALDH1 were positive in 4 (20%) and 2 (10%) cases respectively. EGFR was overexpressed in half of our cases. 9/11 TN cancers expressed basal cytokeratins while two expressed luminal cytokeratins. The expression of each CSC marker in TN, ER+ and Her-2 + tumors is shown in the Table. Expression of multiple stem cell markers (2-4) was observed in 82% of TN in contrast to 20% of ER+, and 25% of HER2+ tumors. All nine basal tumors and only two (18%) of the luminal ones, expressed multiple (2-4) CSC markers. Conclusions: Expression of multiple cancer stem cell markers is highly associated with triple negative breast carcinomas and in carcinomas expressing basal cytokeratins. Additional studies to develop therapies targeting stem cell markers may be warranted. Expression of CSC markers in various types of breast carcinoma ER/PR/HER2 status 0-1 CSC markers (%) 2-4 CSC markers (%) CD44+/CD24- (%) CD 133 (%) ALDH 1(%) EZH2 (%) TN 18 82 72 27 9 100 ER+/HER2– 80 20 60 0 0 20 HER2+ 50 25 25 25 25 75 No significant financial relationships to disclose.
Hemoglobin a Synthesis in the Developing Fetus
Authors: Haig H. Kazazian, Andrea P. Woodhead
Journal: New England Journal of Medicine (1973)

To determine when synthesis of hemoglobin A (composed of 2 α and 2 β chains and the hemoglobin predominant in the human adult) begins in the fetus, hemoglobin synthesis was measured in fetuses of various gestational ages. Synthesis of hemoglobin A by reticulocytes obtained from 42 embryos and fetuses 3.5 to 20.0 cm in crown-to-rump length accounted for 4.3 to 13.0 per cent of total hemoglobin synthesis, and varied directly with fetal crown-to-rump length. Since the smallest embryo was estimated to be 55 days old, β-chain synthesis has begun by that gestational age. Furthermore, since β thalassemia is characterized by decreased β-chain synthesis, the accurate diagnosis of this condition in fetuses depends on knowledge of the values for hemoglobin A synthesis in normal fetuses of variousgestational ages. (N Engl J Med 289:58–62, 1973)
Senile Cardiac Amyloidosis with Myocardial Dysfunction
Authors: Lyle J. Olson, Morie A. Gertz, William D. Edwards, Chin-Yang Li, Patricia A. Pellikka, David R. Holmes, A.Jamil Tajik, Robert A. Kyle
Journal: New England Journal of Medicine (1987)

Senile cardiac amyloid discovered at autopsy is usually regarded as an incidental finding. However, in immunohistochemical studies of autopsy material, three distinct forms of senile cardiovascular amyloid have been characterized, including a systemic form that diffusely infiltrates the cardiac ventricles. The systemic form can be identified immunohistochemically with use of antiserum to human prealbumin. We diagnosed senile systemic amyloidosis causing cardiac dysfunction in five men (57 to 72 years old) by using antiserum to prealbumin in myocardial biopsy tissue. Clinically, the five patients were indistinguishable from patients with nonsecretory immunoglobulin-derived primary amyloidosis with cardiac involvement; only immunohistochemical staining of myocardial tissue distinguished between the two entities. This distinction is important, because the treatment and prognosis of the two disorders are different. We recommend immunohistochemical staining of myocardial tissue for prealbumin in patients with biopsy-proved cardiac amyloid in whom no monoclonal immunoglobulin light chain is detectable in the serum or urine.
Apo2L/TRAIL pharmacokinetics in a phase 1a trial in advanced cancer and lymphoma
Authors: J. Ling, R. S. Herbst, D. S. Mendelson, S. G. Eckhardt, P. O’Dwyer, S. Ebbinghaus, R. Osborne, M. Cheu, G. Lieberman, B. L. Lum
Journal: Journal of Clinical Oncology (2006)

3047 Background: Apo2L/TRAIL (Apo2L ligand/tumor necrosis factor-related apoptosis-inducing ligand) is the first recombinant human protein that selectively induces apoptosis or programmed cell death in cancer cells while sparing normal cells. The molecule used in this joint clinical development between Genentech, Inc. and Amgen, Inc., is an optimized recombinant human Apo2L/TRAIL protein produced in E. coli. It displays broad activity in preclinical models of a variety of solid and hematologic cancers. This is the first report of the pharmacokinetics of Apo2L/TRAIL in humans. Methods: Thirty-nine patients enrolled in a phase 1a study had PK assessments at dose levels ranging from 0.5–15 mg/kg in two cohorts, those with and those without liver metastases. Recombinant human Apo2L/TRAIL was administered as a 1-hr IV infusion for 5 consecutive days over a 21-day cycle. Serum concentrations were determined using a sensitive ELISA assay. PK calculations were performed using Non-compartmental analyses. Results: Currently Apo2L/TRAIL PK data are available for 27 patients, 15 in cohort 1 (no liver metastases) and 12 in cohort 2 (liver metastases). Mean (± SD) PK data for patients in cohort 1 and cohort 2 did not differ. PK data for cohort 1 are outlined in the table below. Apo2L/TRAIL clearance appeared proportional to dose and consistent with that predicted from nonclinical models. Cmax achieved at doses ≥ 4 mg/kg are equivalent to or greater than those displaying activity in preclinical models. There was no evidence of drug accumulation between day 1 and day 5 of treatment. Conclusions: Apo2L/TRAIL at doses which can be safely administered in humans produces serum concentrations consistent with those demonstrating efficacy in tumor xenograft models. Hepatic metastases with or without mild liver dysfunction do not appear to influence the PK of Apo2L/TRAIL. [Table: see text] [Table: see text]
A 14q+ Marker and a Late Replicating Chromosome #22 in a Brain Tumor: Brief Communication
Authors: Kiyomi Yamada, Masumi Yoshioka, Hiroshi Oami
Journal: JNCI Journal of the National Cancer Institute (1977)

Chromosome studies of a malignant lymphoma of the brain were made by G-, Q-, and C-banding techniques and by autoradiography. The tumor had a modal chromosome number of 47 and contained 4 markers: 1q-, 6p+, 11q+, and 14q+. A 14q+ marker chromosome frequently seen in malignant lymphomas was identified as a translocation between chromosomes No. 1 and 14 in this case. Although the banding pattern did not reveal abnormalities in chromosomes No. 22, the late replication of one chromosome No. 22 was detected by autoradiography. The abnormality of chromosomes No. 14 and 22 was discussed in relation to its occurrence in brain tumors, and the application of autoradiography in addition to banding techniques was stressed as necessary in cytogenetic studies of tumor chromosomes.
Hypomagnesemia with Tetany in Nontropical Sprue
Authors: J. A. Balint, B. I. Hirschowitz
Journal: New England Journal of Medicine (1961)

INTEREST in magnesium has been greatly stimulated by the introduction of simpler and more reliable methods for its estimation.1 A number of reports have appeared recently describing the clinical features of the magnesium-deficiency syndrome.1 2 3 We have recently seen 3 patients with nontropical sprue in whom hypomagnesemia presented a significant clinical problem. It is the purpose of this paper to report our observations in these patients.Case ReportsCase 1. B.R., a 52-year-old housewife, was first admitted to the hospital on July 13, 1960, with a 6-week history of 10 watery stools per day, worse after meals. The stools contained undigested . . .
P816 MERTK rs4374383 AA GENOTYPE IS ASSOCIATED WITH A LOWER PREVALENCE OF SEVERE HEPATIC STEATOSIS IN NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: S. Petta, L. Valenti, S. Grimaudo, C. Tripodo, C. Cammà, V. Di Marco, P. Dongiovanni, S. Fargion, C. Guarnotta, A. Gulino, E. Mozzi, E. Orlando, R.M. Pipitone, R. Rametta, A. Craxì
Journal: Journal of Hepatology (2014)
A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease
Authors: Tulio B. Abud, Francisco Amparo, Ujwala S. Saboo, Antonio Di Zazzo, Thomas H. Dohlman, Joseph B. Ciolino, Pedram Hamrah, Reza Dana
Journal: Ophthalmology (2016)
Genetic Variability of Adiponectin Gene Defines the Biosynthesis Rate of Adiponectin in Adipose Tissue and Regulates Superoxide Generation in Human Arteries in vivo
Authors: Charalambos Antoniades, Alexios Antonopoulos, Dimitris Tousoulis, Constantinos Bakogiannis, Antigoni Miliou, Nikolaos Sfyras, Michael Demosthenous, Kyriakoula Marinou, Keith M Channon, Christodoulos Stefanadis
Journal: Circulation (2010)