tbuckley/cabot-search huggingface dataset:
Antibiotic prescription in asthma exacerbations in the admitting and emergency (A&E) department
Authors: Caroline Gouder, Justine Farrugia Preca, Rachelle Asciak, Josef Micallef, Stephen Montefort
Journal: European Respiratory Journal (2011)

Aim:  To assess the appropriateness of antibiotic prescription in patients diagnosed with asthma exacerbations in the A&E department.   Method:  All adult patients presenting at the A&E department over 10 consecutive months (January to October 2010) were included in a prospective study. Comparative statistical analysis was carried out using the t-test.   Results:  A total of 244 patients were included. Forty-eight patients (19.7%) had been prescribed antibiotics by their general practitioner prior to presentation to A&E. A chest X-ray was done in 201 patients (82.4%). A radiological infiltrate suggestive of pneumonia was reported in 12 patients (6%). A white cell count (WCC) was available in 165 patients (67.6%). Antibiotics were prescribed in 65.9% of admitted patients (n=126). Of these patients 9.5% had a radiological pneumonia, 30.2% had a raised WCC (mean 10.42×10 9 /L), 23% were febrile at presentation and 73% had symptoms of a respiratory tract infection including a cough and/or sputum. Antibiotics were administered to 28 patients (11.5%) at the A&E Department, 3 (10.7%) of whom had a radiological pneumonia. Antibiotics were prescribed to 39.7% of discharged patients (n=118). Of these, 11% had a fever at presentation, 46.6% had symptoms of a respiratory tract infection, and 12.7% had a raised WCC (mean 9.01×10 9 /L). None had evidence of pneumonia. There was no significant correlation in the WCC and antibiotic prescription in admitted and discharged patients (p=0.013).   Conclusion:  There is a tendency towards unnecessary antibiotic prescription in asthma exacerbations as few patients have evidence of radiological pneumonia or concomitant bacterial infection of the respiratory tract.
Dopamine Gene Therapy for Parkinson’s Disease in a Nonhuman Primate Without Associated Dyskinesia
Authors: Béchir Jarraya, Sabrina Boulet, G. Scott Ralph, Caroline Jan, Gilles Bonvento, Mimoun Azzouz, James E. Miskin, Masahiro Shin, Thierry Delzescaux, Xavier Drouot, Anne-Sophie Hérard, Denise M. Day, Emmanuel Brouillet, Susan M. Kingsman, Philippe Hantraye, Kyriacos A. Mitrophanous, Nicholas D. Mazarakis, Stéphane Palfi
Journal: Science Translational Medicine (2009)

A gene therapy approach for the treatment of Parkinson’s disease.
Chronic inhibition of Na/H-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure
Authors: A BAARTSCHEER, C SCHUMACHER, M VANBORREN, C BELTERMAN, R CORONEL, T OPTHOF, J FIOLET
Journal: Cardiovascular Research (2004)

Objective: In patients with heart disease, the transition from compensatory hypertrophy to heart failure (HF) is associated with altered calcium handling. Up-regulated Na+/H+-exchanger (NHE-1) activity underlies increased [Na+]i and disturbance of cellular calcium handling in HF. We hypothesize that chronic inhibition of NHE-1 activity prevents the hypertrophic response, cellular remodeling, and development of HF.
Imatinib Inhibits Proliferation of Ewing Tumor Cells Mediated by the Stem Cell Factor/KIT Receptor Pathway, and Sensitizes Cells to Vincristine and Doxorubicin-Induced Apoptosis
Authors: Iranzu González, Enrique J. Andreu, Angel Panizo, Susana Inogés, Ana Fontalba, José Luis Fernández-Luna, Mirella Gaboli, Luis Sierrasesúmaga, Salvador Martín-Algarra, Javier Pardo, Felipe Prósper, Enrique de Alava
Journal: Clinical Cancer Research (2004)

Abstract Purpose and Experimental Design: The stem cell factor/KIT receptor loop may represent a novel target for molecular-based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. Results: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. KIT expression was stronger in Ewing tumors showing EWS-FLI1 nontype 1 fusions. Despite absence of c-kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. Treatment with KIT tyrosine kinase inhibitor imatinib (0.5–20 μm) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC50, 12–15 μm). However, imatinib administered alone at doses close to IC50 for growth inhibition (10 μm) did not induce a significant increase in apoptosis. We then analyzed if blockade of KIT loop through imatinib (10 μm) was able to increase the antitumor in vitro effect of doxorubicin (DXR) and vincristine (VCR), drugs usually used in Ewing tumor treatment. Addition of imatinib decreased in 15–20 and 15–36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. Conclusions: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Inhibition of KIT increases sensitivity of these cells to DXR and VCR. This study supports a potential role for imatinib in the treatment of Ewing tumor.
Advantage of a Residualizing Iodine Radiolabel in the Therapy of a Colon Cancer Xenograft Targeted with an Anticarcinoembryonic Antigen Monoclonal Antibody
Authors: Rhona Stein, Serengulam V. Govindan, Marianne Hayes, Gary L. Griffiths, Hans J. Hansen, Ivan D. Horak, David M. Goldenberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: A disadvantage of conventionally radioiodinated monoclonal antibodies (mAb) for cancer therapy is the short retention time of the radionuclide within target cells. To address this issue, we recently developed a method in which radioiodine is introduced onto antibodies using an adduct consisting of a nonmetabolizable peptide attached to the aminopolycarboxylate diethylenetriaminepentaacetic acid, designated IMP-R4. This adduct causes the radioiodine to become trapped in lysosomes following antibody catabolism. Clinical-scale production of 131I-IMP-R4-labeled antibodies is possible using a recently developed facile method. Experimental Design: The properties of 131I-IMP-R4-labeled anticarcinoembryonic antigen (CEA) humanized mAb hMN-14 were compared with the directly radioiodinated hMN-14 (131I-hMN-14) in CEA-expressing human colon cancer cell lines, LoVo and LS174T, and in nude mice bearing established LoVo tumor xenografts. Results: 125I-IMP-R4-hMN-14 retention in the cell lines was significantly increased (61.5% after 3 days) compared with 125I-hMN-14. In vivo, a significant improvement in tumor accretion of radiolabel was obtained using 131I-IMP-R4-hMN-14, which led to a marked improvement in therapeutic efficacy. Eight weeks post-treatment, mean tumor volumes were 0.16 ± 0.19 and 1.99 ± 1.35 cm3 in mice treated with 131I-IMP-R4-hMN-14 and 131I-hMN-14, respectively, with complete remissions observed in 27% of mice treated with 131I-IMP-R4-hMN-14 and none using 131I-hMN-14. Conclusion: 131I-IMP-R4-hMN-14 provides a significant therapeutic advantage in comparison to the conventionally 131I-labeled antibody. The ability of this labeling method to lend itself to clinical-scale labeling, the broad applicability of a humanized anti-CEA mAb for CEA-expressing cancers, and the clinical benefits of radioimmunotherapy with anti-CEA mAb shown recently for small-volume and minimal residual disease combine to make 131I-IMP-R4-hMN-14 a promising new agent for radioimmunotherapy.
Does Violence Breed Violence? Contributions from a Study of the Child Abuse Syndrome
Authors: LARRY B. SILVER, CHRISTINA C. DUBLIN, REGINALD S. LOURIE
Journal: American Journal of Psychiatry (1969)

A study covering three generations of families of abused children supports the themes that violence breeds violence and that a child who experiences violence as a child has the potential of becoming a violent member of society in the future. The authors believe that the physician has a critical role and responsibility in interrupting this cycle of violence.
Mechanistic Rationale for Inhibition of Poly(ADP-Ribose) Polymerase in ETS Gene Fusion-Positive Prostate Cancer
Authors: J. Chad Brenner, Bushra Ateeq, Yong Li, Anastasia K. Yocum, Qi Cao, Irfan A. Asangani, Sonam Patel, Xiaoju Wang, Hallie Liang, Jindan Yu, Nallasivam Palanisamy, Javed Siddiqui, Wei Yan, Xuhong Cao, Rohit Mehra, Aaron Sabolch, Venkatesha Basrur, Robert J. Lonigro, Jun Yang, Scott A. Tomlins, Christopher A. Maher, Kojo S.J. Elenitoba-Johnson, Maha Hussain, Nora M. Navone, Kenneth J. Pienta, Sooryanarayana Varambally, Felix Y. Feng, Arul M. Chinnaiyan
Journal: Cancer Cell (2011)
Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy
Authors: A K Simonds, F Muntoni, S Heather, S Fielding
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Respiratory failure is the commonest cause of death in patients with Duchenne muscular dystrophy (DMD). Life expectancy is less than one year once diurnal hypercapnia develops. This study examines the effects of nasal intermittent positive pressure ventilation (NIPPV) on survival in symptomatic Duchenne patients with established ventilatory failure. <h3>METHODS</h3> Nocturnal NIPPV was applied in 23 consecutive patients with DMD of mean (SD) age 20.3 (3.4) years who presented with diurnal and nocturnal hypercapnia. <h3>RESULTS</h3> One year and five year survival rates were 85% (95% CI 69 to 100) and 73% (95% CI 53 to 94), respectively. Early changes in arterial blood gas tensions following NIPPV occurred with mean (SD) Po<sub>2</sub> increasing from 7.6 (2.1) kPa to 10.8 (1.3) kPa and mean (SD) Pco<sub>2</sub> falling from 10.3 (4.5) kPa to 6.1 (1.0) kPa. Improvements in arterial blood gas tensions were maintained over five years. Health perception and social aspects of SF-36 health related quality of life index were reported as equivalent to other groups with non-progressive disorders using NIPPV. <h3>CONCLUSION</h3> Nasal ventilation is likely to increase survival in hypercapnic patients with Duchenne muscular dystrophy and should be considered as a treatment option when ventilatory failure develops.
Patterns of Variation Within Self-Incompatibility Loci
Authors: N. Takebayashi
Journal: Molecular Biology and Evolution (2003)

Diverse self-incompatibility (SI) mechanisms permit flowering plants to inhibit fertilization by pollen that express specificities in common with the pistil. Characteristic of at least two model systems is greatly reduced recombination across large genomic tracts surrounding the S-locus, which regulates SI. In three angiosperm families, including the Solanaceae, the gene that controls the expression of gametophytic SI in the pistil encodes a ribonuclease (S-RNase). The gene that controls pollen SI expression is currently unknown, although several candidates have recently been proposed. Although each candidate shows a high level of polymorphism and complete allelic disequilibrium with the S-RNase gene, such properties may merely reflect tight linkage to the S-locus, irrespective of any functional role in SI. We analyzed the magnitude and nature of nucleotide variation, with the objective of distinguishing likely candidates for regulators of SI from other genes embedded in the S-locus region. We studied the S-RNase gene of the Solanaceae and 48A, a candidate for the pollen gene in this system, and we also conducted a parallel analysis of the regulators of sporophytic SI in Brassica, a system in which both the pistil and pollen genes are known. Although the pattern of variation shown by the pollen gene of the Brassica system is consistent with its role as a determinant of pollen specificity, that of 48A departs from expectation. Our analysis further suggests that recombination between 48A and S-RNase may have occurred during the interval spanned by the gene genealogy, another indication that 48A may not regulate SI expression in pollen.
Prevalence of a shortened prostacyclin half‐life in plasma in healthy adults: Results of a screening investigation
Authors: H. Sinzinger, F. Rauscha, P. Fitscha, Susanne Granegger
Journal: American Journal of Hematology (1990)

Abstract Out of a total of 1,981 adults (956 males, 1,025 females; aged 16‐71 yr) undergoing a screening investigation for elevated cholesterol only 3 healthy participants with pathologically enhanced prostaglandin 12 (PG12) degradation in plasma in vitro were discovered. The PG12 half‐life in these three screenings was shorter than 60 sec and persisted during several follow‐up checks. In one patient a familial defect was discovered. Diseases known to be associated with this disturbance in PG12 metabolism have been excluded. The mean half‐life of PG12 in 1,978 people amounted to 10.71 ± 1.93 min. It still needs to be clarified whether this rare disturbance in PG12 metabolism is causally related to, or only associated with, thromboembolic events. A possible predisposition should be elucidated by regular monitoring of affected persons.
Changing profile of joint disorders with age: findings from a postal survey of the population of Calderdale, West Yorkshire, United Kingdom.
Authors: E M Badley, A Tennant
Journal: Annals of the Rheumatic Diseases (1992)

A survey of the age-sex specific prevalence of joint problems in a population and associated features such as disablement and use of treatment was carried out in 1986 in Calderdale, West Yorkshire, United Kingdom. A postal questionnaire was sent to 25,168 households; 87% were returned, representing households containing 42,826 people aged 16 years and over. Positive answers to a question about pain, swelling, or stiffness in the joints, neck, or back were given by 10,246 subjects, 24% of the population aged 16 years and older, of whom 6181 (60.3%) were women. The rate of reporting of joint problems increased markedly with age, from 5% for subjects aged 16-24 years to 54% for those aged 85 years and older. The joint sites most often reported as affected were the knee and the back, with a frequency in the population of about 10%. The increase in joint problems with age was accompanied by an increase in reported morning stiffness of more than half an hour, taking drugs, and disability, but not in reporting seeing a specialist for these conditions. Of those aged 85 years and older who reported joint problems, most also had difficulty or dependence in activities of daily living. The increasing prevalence of joint problems with age has implications for the provision of care, both in the community and in hospitals, especially in view of the aging of the population as a whole. The planning of health services for those with rheumatic disorders needs to take into account the high incidence of joint problems in the population.
Assessment of fitness in patients with cystic fibrosis and mild lung disease
Authors: P. McLoughlin, D. McKeogh, P. Byrne, G. Finlay, J. Hayes, M. X. FitzGerald
Journal: Thorax (1997)

Maximal exercise testing is used in patients with cystic fibrosis to assess functional status and prognosis. The lactate threshold is an index of aerobic fitness with significant advantages over maximal exercise tests. This study was undertaken to determine if the lactate threshold might be identified, non-invasively, in adult patients with cystic fibrosis and mild lung disease by measurement of ventilatory and gas exchange parameters.Ten subjects with mild cystic fibrosis (forced vital capacity (FVC) > 70% predicted) and 10 healthy controls undertook an incremental exercise test on a bicycle ergometer. Ventilation and gas exchange parameters were measured continually and arterialised venous blood pH, carbon dioxide tension (PCO2), and lactate concentrations were measured at intervals throughout the tests.In subjects with cystic fibrosis there was no significant difference between the mean gas exchange and lactate thresholds (mean difference 1.0 (95% confidence interval (CI) of the mean -1.5 to 3.44) ml/kg/min). In contrast, there was a significant difference between the mean ventilatory and lactate thresholds (3.8 (95% CI 0.9 to 6.7) ml/kg/min). Arterialised venous PCO2 increased significantly during the exercise tests. In healthy subjects the mean differences between these thresholds were not significantly different from zero and PCO2 fell significantly during the tests.The ventilatory threshold significantly overestimates the lactate threshold in subjects with cystic fibrosis induced lung disease because of impaired carbon dioxide excretion during exercise. However, the gas exchange threshold may be used to determine the lactate threshold in this patient group.
Longitudinal Follow-Up of Bipolar Disorder in Women With Premenstrual Exacerbation: Findings From STEP-BD
Authors: Rodrigo S Dias, Beny Lafer, Cibele Russo, Alessandro Del Debbio, Andrew A Nierenberg, Gary S Sachs, Hadine Joffe
Journal: American Journal of Psychiatry (2011)

Objective: The impact of hormonal fluctuation during the menstrual cycle on the course of bipolar disorder is poorly understood. The authors determined the course of illness and time to relapse of bipolar disorder in prospectively followed women with premenstrual exacerbation. Method: Participants were 293 premenopause-age women with bipolar disorder who were followed prospectively for 1 year as part of the Systematic Treatment Enhancement Program for Bipolar Disorder. Frequency of mood episodes was compared between 191 women with premenstrual exacerbation (65.2%) and 102 women without. Among 129 women who were in recovered status at baseline, time to relapse was compared between 66 women with premenstrual exacerbation (51.2%) and 63 without. Results: During follow-up, the group with premenstrual exacerbation had more episodes (primarily depressive) than did the group without, but they were not more likely to meet criteria for rapid cycling during this period. In contrast, they were more likely to report rapid cycling retrospectively. Women with premenstrual exacerbation had a shorter time to relapse and were at greater risk for relapse, but this association was not significant after adjustment for retrospectively reported rapid cycling. Women with premenstrual exacerbation had more depressive and mood elevation symptoms overall. Conclusions: Women with bipolar disorder and premenstrual exacerbation have a worse course of illness, a shorter time to relapse, and greater symptom severity, but they are not more likely to meet criteria for rapid cycling. Premenstrual exacerbation may be a clinical marker predicting a more symptomatic and relapse-prone phenotype in reproductive-age women with bipolar disorder.
Interpretation of ERCP with associated digital imaging correlation
Authors: D MARTIN
Journal: Gut (1997)

Interpretation of ERCP with associated digital imaging correlation. Andrew J Taylor and Anthony G Bohorfoush. (Pp 372; illustrated; £73.00.) Philadelphia: Lippincott- Raven Publishers, 1996. ISBN 0-397- 51579-0.

The Royal College of Radiologists is very keen that x -ray departments should be called Departments of …
Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats
Authors: Marc Mejias, Laura Coch, Annalisa Berzigotti, Ester Garcia-Pras, Javier Gallego, Jaime Bosch, Mercedes Fernandez
Journal: Gut (2014)

<h3>Objective</h3> Antiangiogenic strategies have been proposed as a promising new approach for the therapy of portal hypertension and chronic liver disease. Pigment epithelium-derived factor (PEDF) is a powerful endogenous angiogenesis inhibitor whose role in portal hypertension remains unknown. Therefore, we aimed at determining the involvement of PEDF in cirrhotic portal hypertension and the therapeutic efficacy of its supplementation. <h3>Design</h3> PEDF expression profiling and its relationship with vascular endothelial growth factor (VEGF), neovascularisation and fibrogenesis was determined in bile duct-ligated (BDL) rats and human cirrhotic livers. The ability of exogenous PEDF overexpression by adenovirus-mediated gene transfer (AdPEDF) to inhibit angiogenesis, fibrogenesis and portal pressure was also evaluated in BDL rats, following prevention and intervention trials. <h3>Results</h3> PEDF was upregulated in cirrhotic human and BDL rat livers. PEDF and VEGF protein expression and localisation in mesentery and liver increased in parallel with portal hypertension progression, being closely linked in time and space with mesenteric neovascularisation and liver fibrogenesis in BDL rats. Furthermore, AdPEDF increased PEDF bioavailability in BDL rats, shifting the net balance in the local abundance of positive (VEGF) and negative (PEDF) angiogenesis drivers in favour of attenuation of portal hypertension-associated pathological neovascularisation. The antiangiogenic effects of AdPEDF targeted only pathological angiogenesis, without affecting normal vasculature, and were observed during early stages of disease. AdPEDF also significantly decreased liver fibrogenesis (through metalloproteinase upregulation), portosystemic collateralisation and portal pressure in BDL rats. <h3>Conclusions</h3> This study provides compelling experimental evidence indicating that PEDF could be a novel therapeutic agent worthy of assessment in portal hypertension and cirrhosis.
Rare and aggressive metastatic, axial multifocal local epithelioid sarcoma associated with paraneoplastic granulocytosis and hypoglycaemia
Authors: George P Tsakonas, Manolis S Kallistratos, Eugenia K Balamoti, Argyris Gassiamis, Adamadia Zizi-Sermpetzoglou, Nicolas Mylonakis, Athanasios Karabelis, Christos Kosmas
Journal: The Lancet Oncology (2006)
Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells
Authors: Rangsima Reantragoon, Alexandra J. Corbett, Isaac G. Sakala, Nicholas A. Gherardin, John B. Furness, Zhenjun Chen, Sidonia B.G. Eckle, Adam P. Uldrich, Richard W. Birkinshaw, Onisha Patel, Lyudmila Kostenko, Bronwyn Meehan, Katherine Kedzierska, Ligong Liu, David P. Fairlie, Ted H. Hansen, Dale I. Godfrey, Jamie Rossjohn, James McCluskey, Lars Kjer-Nielsen
Journal: The Journal of Experimental Medicine (2013)

Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell receptor (TCR) α-chain, TRAV1-2–TRAJ33, and are activated by vitamin B metabolites bound by the major histocompatibility complex (MHC)–related class I–like molecule, MR1. Understanding MAIT cell biology has been restrained by the lack of reagents to specifically identify and characterize these cells. Furthermore, the use of surrogate markers may misrepresent the MAIT cell population. We show that modified human MR1 tetramers loaded with the potent MAIT cell ligand, reduced 6-hydroxymethyl-8-d-ribityllumazine (rRL-6-CH2OH), specifically detect all human MAIT cells. Tetramer+ MAIT subsets were predominantly CD8+ or CD4−CD8−, although a small subset of CD4+ MAIT cells was also detected. Notably, most human CD8+ MAIT cells were CD8α+CD8β−/lo, implying predominant expression of CD8αα homodimers. Tetramer-sorted MAIT cells displayed a TH1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1–rRL-6-CH2OH tetramers detected CD4+, CD4−CD8− and CD8+ MAIT cells in Vα19 transgenic mice. Both human and mouse MAIT cells expressed a broad TCR-β repertoire, and although the majority of human MAIT cells expressed TRAV1-2–TRAJ33, some expressed TRAJ12 or TRAJ20 genes in conjunction with TRAV1-2. Accordingly, MR1 tetramers allow precise phenotypic characterization of human and mouse MAIT cells and revealed unanticipated TCR heterogeneity in this population.