tbuckley/cabot-search huggingface dataset:
Compliance and side effects of prophylactic oseltamivir treatment in a school in South West England
Authors: A Wallensten, I Oliver, D Lewis, S Harrison
Journal: Eurosurveillance (2009)

School closure along with mass prophylactic oseltamivir treatment of pupils have been used in England and elsewhere to contain school outbreaks of influenza A(H1N1)v. We evaluated the protective effect, compliance with and side effects of oseltamivir chemoprophylactic treatment with a ten-day course of 1x 75mg given to 11-12-year-old pupils in one school year in a secondary school in South West England closed for ten days in response to a symptomatic laboratory-confirmed pupil. We distributed a questionnaire to pupils in the affected school year in class after the school had re-opened. Questions included symptoms of flu-like illness, compliance with chemoprophylaxis and side effects. All present on the day, 248 (93.2%) participated. Compliance with chemoprophylaxis was high, 77% took the full course, 91% took at least seven days. Fifty-one percent experienced symptoms such as feeling sick (31.2%), headaches (24.3%) and stomach ache (21.1%). Although some children were ill with flu-like symptoms, those tested did not have A(H1N1)v infection. Compliance with oseltamivir chemoprophylaxis was high, although likely side effects were common. The burden of side effects needs to be considered when deciding on mass oseltamivir chemoprophylaxis in children especially given that the symptoms of A(H1N1)v influenza are generally mild.
Abstract 1654: Prevalence and Correlates of Aortic Root Dilatation in Normotensive and Hypertensive Adults: The Family Blood Pressure Program
Authors: Richard B Devereux, Richard Cooper, Alan Weder, Todd B Seto, Craig Hanis, Thomas H Mosley, D C Rao, Donna K Arnett
Journal: Circulation (2009)

Background: Aortic root dilatation (ARD) has been shown to predispose to aortic regurgitation (AR) and aortic dissection in clinical studies, but few population-based data exist on the prevalence A...
Abstract 4877: Clinical Phenotypes and Outcome of 101 LMNA Gene Mutation Carriers
Authors: Michele Pasotti, Alessandra Serio, Andrea Pilotto, Elena Serafini, Maurizia Grasso, Nicola Marziliano, Marilena Tagliani, Pamela Cassini, Barbara Digiorgio, Manuela Agozzino, Carlo Campana, Fabiana Gambarin, Stefano Ghio, Mario Viganò, Luigi Tavazzi, Eloisa Arbustini
Journal: Circulation (2008)

Purpose To analyze the cardiac phenotype and long-term follow-up of dilated cardiolaminopathies. Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiologic setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrio-ventricular block (AVB) constitute the majority of reported cases. Methods This was a longitudinal retrospective observational study conducted in 32 consecutive families in which LMNA gene defects were identified in the probands, sharing DCM phenotype. Results Of the 171 family members, 101 were carriers of LMNA gene mutations. Sixty-five of 101 (64 %) were phenotypically affected while 36 (36 %) were only genotypically affected, including 5 with preclinical signs. The 65 patients had DCM with AVB (n=44), DCM with Ventricular Tachycardia/Fibrillation (VT/VF) (n=12), DCM with AVB and Emery-Dreifuss Muscle Dystrophy type 2 (EDMD2) (n=6), AVB plus EDMD2 (n=2), magnetic resonance imaging signs of arrhythmogenic right ventricular dysplasia associated with mild left ventricular dilation and VT (n=1). The disease was proven to be familial autosomal dominant (AD) in 23 of the 32 families; likely familial AD (based on pedigree and family history) in 8; and associated with a de novo mutation in 1. During a median follow-up of 57.4 months (interquartile range 26 –115 months) we observed 54 events in 47 DCM patients (7 had a later event excluded from the analysis) whereas no event was observed among the 36 non-affected carriers. The events were related to heart failure (HF) [15 heart transplants, 2 death from end-stage HF] and ventricular arrhythmias [17 sudden cardiac deaths (SCD) and 13 appropriate implantable cardioverter defibrillator (ICD) interventions]. By multivariable analysis, NYHA class III–IV and competitive sport ≥10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted SCD. Conclusions DCMs caused by LMNA gene defects are highly penetrant, adult-onset, malignant diseases characterized by high rate of HF and life-threatening arrhythmias predicted by NYHA class, competitive sport activity and type of mutation.
Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis
Authors: K. Rajender Reddy, Marc Bourlière, Mark Sulkowski, Masao Omata, Stefan Zeuzem, Jordan J. Feld, Eric Lawitz, Patrick Marcellin, Tania M. Welzel, Robert Hyland, Xiao Ding, Jenny Yang, Steven Knox, Phillip Pang, Hadas Dvory‐Sobol, G. Mani Subramanian, William Symonds, John G. McHutchison, Alessandra Mangia, Edward Gane, Masashi Mizokami, Stanislas Pol, Nezam Afdhal
Journal: Hepatology (2015)

Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon‐free regimens of direct‐acting antiviral agents, making it difficult to optimize therapy. We performed a post‐hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed‐dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment‐naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV‐SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease‐inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%‐98%) achieved SVR12, 98% of treatment‐naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV‐SOF alone and 97% of those who received LDV‐SOF plus RBV), although previously treated patients receiving 12 weeks of LDV‐SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV‐SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%‐19%), and asthenia (14%‐16%). One patient (&lt;1%) of those receiving LDV‐SOF alone, and 4 (2%) of those receiving LDV‐SOF plus RBV had treatment‐related serious AEs. Conclusions: This analysis suggests that 12 weeks of LDV‐SOF is safe and effective for treatment‐naïve patients with HCV genotype 1 and compensated cirrhosis. The relatively lower SVR in treatment‐experienced patients treated with 12 weeks of LDV‐SOF raises the question of whether these patients would benefit from adding RBV or extending treatment duration to 24 weeks. (H epatology 2015;62:79‐86)
Das28 correlates best with the physician's clinical judgment of response to infliximab therapy in rheumatoid arthritis patients
Authors: B. Vander Cruyssen, Patrick Durez, Jean-Pierre Devogelaer, S. Van Looy, Rene Westhovens, F. Van den Bosch, Emilie Veys, L. De Clerck, A. Peretz, Michel Malaise, L. Verbruggen, N. Vastesaeger, A. Geldhof, L Boulart, F. De Keyser
Journal: Annals of the Rheumatic Diseases (2005)
Cortactin Overexpression Inhibits Ligand-Induced Down-regulation of the Epidermal Growth Factor Receptor
Authors: Paul Timpson, Danielle K. Lynch, Daniel Schramek, Francesca Walker, Roger J. Daly
Journal: Cancer Research (2005)

Abstract Ligand-induced receptor down-regulation by endocytosis is a critical process regulating the intensity and duration of receptor tyrosine kinase signaling. Ubiquitylation of specific receptor tyrosine kinases, for example, the epidermal growth factor receptor (EGFR) by the E3 ubiquitin ligase c-Cbl, provides a sorting signal for lysosomal degradation and leads to termination of receptor signaling. Cortactin, which couples the endocytic machinery to dynamic actin networks, is encoded by EMS1, a gene commonly amplified in breast and head and neck cancers. One mechanism whereby cortactin overexpression contributes to tumor progression is by enhancing tumor cell invasion and metastasis. However, in this study, we show that overexpression of cortactin in HeLa cells markedly inhibits ligand-induced down-regulation of the EGFR. This is independent of alterations in receptor autophosphorylation and correlates with impaired c-Cbl phosphorylation and association with the EGFR, reduced EGFR ubiquitylation, and sustained EGF-induced extracellular signal-regulated kinase activation. Furthermore, analysis of a panel of head and neck squamous cell carcinoma (HNSCC) cell lines revealed that cortactin overexpression is associated with attenuated ligand-induced EGFR down-regulation. Importantly, RNAi-mediated reduction of cortactin expression in an 11q13-amplified HNSCC cell line accelerates EGFR degradation. This represents the first demonstration of modulation of growth factor receptor signaling by cortactin. Moreover, enhanced EGFR signaling due to cortactin overexpression may provide an alternative explanation for EMS1 gene amplification in human cancers.
Abstract 18051: High Prevalence of Active Myocarditis in Patients with Takotsubo Cardiomyopathy: A Magnetic Resonance-endomyocardial Biopsy Study
Authors: Maurizio Pieroni, Costantino Smaldone, Antonia Camporeale, Anna Severino, Antonella Ventrone, Andrea Macchione, Fulvio Bellocci, Filippo Crea
Journal: Circulation (2011)

Background: Tako-tsubo cardiomyopathy (TTC) was recently classified as a cardiomyopathy with distinct clinical and angiographic features, but mechanisms of cardiac dysfunction and histological substrate are still largely unclear. We evaluated cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) findings in patients with TTC. Methods: Twenty consecutive patients (19 F, 58±12 years) with clinical and angiographic features of TTC underwent CMR with edema (STIR images) and delayed enhancement (DE) studies. Of these, 15 patients also underwent EMB. Myocardial samples obtained from apical akinetic left ventricular segments were processed for histology, immunohistochemistry and polymerase chain reaction (PCR) for cardiotropic viruses. Results: All patients presented acute chest pain with ST-segment elevation in anterior leads and evidence of myocardial necrosis. Symptoms were precipitated by emotional stress in 12 (60%) cases. At CMR DE was observed in 11 patients (55%) in all cases with a subepicardial or midventricular pattern; edema was observed in 10 (50%) patients, associated with DE in 8 cases. Neither DE nor edema was observed in 7 patients. In 11 patients (73%) EMB showed an active lymphocytic myocarditis with evidence of activated T lymphocytes. In 4 patients (27%) contraction band necrosis was observed. PCR identified parvovirus B19 viral genome in 3 patients with myocarditis. Among patients with a histological diagnosis of myocarditis CMR showed DE in 10 and edema in 8 cases. One patient with myocarditis had neither DE nor edema at CMR. Patients with contraction-band necrosis showed no DE or edema at CMR. Three myocarditis virus-negative patients failing to recovery after 6 weeks from clinical presentation, received prednisone and azathioprine for 8 weeks with significant improvement of left ventricular contractility. Conclusions: Acute myocarditis represents a frequent substrate of TTC. CMR may help to identify myocardial inflammation in TTC patients. Immunohistochemical and virological diagnosis through EMB may affect both treatment and prognosis. Further studies are needed to clarify the prevalence of acute myocarditis among TTC patients and the possible association between emotional stress and viral infection.
Double Hit Lymphoma: M.D. Anderson Experience
Authors: Yasuhiro Oki, Mansoor Noorani, Richard Eric Davis, Sattva S. Neelapu, Alma Rodriguez, Fredrick B Hagemeister, Nathan Fowler, Michael Wang, Michelle A. Fanale, Felipe Samaniego, Bouthaina S. Dabaja, Chelsea Pinnix, Larry W. Kwak, Jorge E Romaguera, Issa Khouri, Jason R. Westin, Luis E Fayad
Journal: Blood (2013)
Letter from Cuba: Cuba: plenty of care, few condoms, no corruption
Authors: H. Veeken
Journal: BMJ (1995)

The health system in Cuba guarantees accessibility to the entire population, is free of charge, and covers the spectrum from vaccinations to sophisticated interventions. The results are impressive: Cuba's health figures are on a par with developed countries that have 20 times the budget. The country is experiencing a difficult period because of the collapse and loss of support from the Soviet Union; over 30 years' trade embargo by the United States; and the gradual change from a centrally planned economy towards more of a free market system. Shortages are experienced in every sector, and maintaining health care services at the current level is too expensive. Doctors and nurses continue to work towards the goal of health for all Cubans, even though their salaries are minimal. Signs of negligence or corruption, often seen in other socialist countries where incentives for output are lacking, are unknown. Topics such as family planning and AIDS deserve immediate attention.The health system in Cuba guarantees accessibility to the entire population, and it is free of charge. Cuba's health figures are on a par with developed countries that have 20 times the budget. Each year around 4000 students start their medical training at 23 different universities. Since 1980 there has been a training course for family doctors. By 1995 22,000 of them have been trained covering 90% of the population. Their main work is preventive: health promotion and offering basic curative care. The family doctors are backed up by 400 polyclinics, where specialists offer their services to about 30,000 people. Life expectancy is 77 years and infant mortality a mere 9 per 1000 live births. Malaria has been eradicated and dengue fever successfully reduced. Leading causes of mortality are cardiovascular diseases, neoplasms, accidents, and homicides. Up to now only 1089 people have been diagnosed as HIV positive. From a mere epidemiological point of view, strict isolation could contain the epidemic in a closed society. In practice, however, the island opened the doors to tourism, with a side effect of increasing prostitution. Condoms or any contraceptives are in short supply. Nevertheless, the number of abortions is low, less than 1 per 100 deliveries. The reason is that all women whose expected menstruation is late by two weeks are offered a microaspiration in the polyclinic. 700 regulations are performed for every 5000 fertile women. Pregnancy tests are not performed as they are not available. The country is experiencing a difficult period because of the collapse and loss of support from the Soviet Union; over 30 years' trade embargo by the United States and the gradual change from a centrally planned economy towards more of a free market system. Family planning and AIDS seem two topics that need further exploration. Even if their system is under strain, health indices do not show a deterioration in health yet.
Interleukin-7 (IL-7) Enhances Class Switching to IgE and IgG4 in the Presence of T Cells Via IL-9 and sCD23
Authors: Pascale Jeannin, Yves Delneste, Sybille Lecoanet-Henchoz, Denise Gretener, Jean-Yves Bonnefoy
Journal: Blood (1998)
Toll‐like Receptor 7–Stimulated Tumor Necrosis Factor α Causes Bone Marrow Damage in Systemic Lupus Erythematosus
Authors: Haoyang Zhuang, Shuhong Han, Yuan Xu, Yi Li, Hai Wang, Li‐Jun Yang, Westley H. Reeves
Journal: Arthritis & Rheumatology (2013)

To define the pathogenesis of bone marrow (BM) involvement in systemic lupus erythematosus (SLE).Tumor necrosis factor α (TNFα) levels, cell death, and cellular damage in BM from SLE patients, controls, and mice with pristane-induced lupus were analyzed using a morphometric technique and immunohistochemistry. The pathogenesis of BM abnormalities was studied in wild-type (WT), TNFα(-/-) , Toll-like receptor-deficient (TLR-7(-/-) ), interferon (IFN)-α/β/ω receptor-knockout (IFNAR(-/-) ), and B cell-deficient (μmt) mice treated with pristane. Flow cytometry was used to examine TNFα production (by intracellular staining) and plasma cell/plasmablast development. CXCL12 expression was determined by quantitative polymerase chain reaction.BM from SLE patients exhibited striking death of niche and hematopoietic cells associated with TNFα overproduction. BM from mice with a type I IFN-mediated lupus syndrome induced by pristane showed similar abnormalities. TNFα was produced mainly by BM neutrophils, many with phagocytosed nuclear material (lupus erythematosus cells). TNFα production was abolished in pristane-treated TLR-7(-/-) and μmt mice but was restored in μmt mice by infusing normal plasma. Pristane-treated WT and IFNAR(-/-) mice developed anemia, BM hypocellularity, and extramedullary hematopoiesis, which were absent in TLR-7(-/-) and TNFα(-/-) mice. Additionally, the expression of CXCL12, which is produced by stromal cells and mediates homing of hematopoietic cells and plasmablasts, was decreased in BM from pristane-treated WT mice but was normal in BM from pristane-treated TNFα(-/-) mice.Although autoantibodies and glomerulonephritis are type I IFN dependent, lupus-associated BM abnormalities were TLR-7 and TNFα driven but type I IFN independent, suggesting that lupus is a disorder of innate immunity in which TLR-7 activation by phagocytosed nuclei causes relentless type I IFN and TNFα production mediating glomerulonephritis and hematologic involvement, respectively.
Basal serum tryptase as risk assessment for severe Hymenoptera sting reactions in elderly
Authors: E. Guenova, T. Volz, M. Eichner, W. Hoetzenecker, U. Caroli, G. Griesinger, G. Burow, V. Mitev, T. Biedermann
Journal: Allergy (2010)

Epidemiologic studies suggest that elderly people are more prone to develop severe anaphylactic reactions. However, the exact cause for this phenomenon remains unclear.To study the role of the serum tryptase as a diagnostic parameter for individual risk evaluation and its impact on the severity of allergic reactions in elderly people.Two hundred and seventy-four consecutive patients visiting the Department of Dermatology, Tübingen, Germany, who were diagnosed with honeybee or wasp venom allergy, were included in the study.Sting reaction severity increased with increased age and tryptase levels (P = 0.001 and P = 0.0003, respectively). Furthermore, we find not only a general increment in tryptase levels in elderly people (P = 0.0001) but also a continuous increase in tryptase concentrations even below the cut-off (11.4 microg/l) with increasing age (P = 0.0026).Our data confirm serum tryptase as a risk factor for severe anaphylactic reaction to hymenoptera stings. Furthermore, we give first evidence that basal serum tryptase levels increase continuously with age and being an indicator for either increased mast cell load or reactivity this can at least partly be responsible for the observed aggravated allergic reactions in elderly people. As those patients are at increased risk for life-threatening anaphylactic reactions, it should be considered to adjust VIT especially in elderly patients with elevated tryptase levels as recommended for patients with mastocytosis by increasing venom doses during VIT and by considering its life-long continuation.
Anamnesis and clinical peculiarities of severe bronchial asthma in children
Authors: Olga Tyutina, Svetlana Smirnova, Natalja Ilienkova
Journal: European Respiratory Journal (2012)

Aim: To study anamnesis and clinical data on severe/ moderate severe atopic bronchial asthma with different level of control, determine the main risk factors of the formation of BA non-controlled course in infants.  Materials and Methods: We have examined 100 infants, severe/ moderate severe atopic BA patients, inhabitants of Krasnoyarsk territory in average ages of 10.9±1.1. We have studied allergy anamnesis, carried out physical and specific allergy examination, estimated the results of instrumental research. In order to determine the level of controlling the disease we had estimated the results of «Test on controlling asthma». We have formed 2 groups: with controlled BA (n=50) and non-controlled BA (n=50).  Results: Living under unfavorable living conditions (wooden homes with damp, mould, stove heating, overcrowding) had been marked in 34% cases in group with non-controlled BA course and in 28% in group with controlled BA (p=0.0012). One or two smoking parents had been marked in 36% cases in controlled BA course and in 48% in non-controlled BA (p=0.007). Analysis of family structure revealed that 48% children of group of good control and 74% of group of absence of control live in sole-parent families (p  Conclusions: We have determined anamnesis predictors of non-controlled BA course in children: living in home with stove heating with damp in living area, smoking inside and presence of domestic animals. When estimating social status of the families in BA children with non-controlled course we have stated frequent occurrence of sole-parent families with low income.
Congenital erythropoietic porphyria: a single-observer clinical study of 29 cases
Authors: R.P. Katugampola, M.N. Badminton, A.Y. Finlay, S. Whatley, J. Woolf, N. Mason, J.C. Deybach, H. Puy, C. Ged, H. de Verneuil, S. Hanneken, E. Minder, X. Schneider-Yin, A.V. Anstey
Journal: British Journal of Dermatology (2012)

Background Congenital erythropoietic porphyria (CEP) is an autosomal recessive cutaneous porphyria caused by decreased activity of uroporphyrinogen III synthase (UROS). Its predominant characteristics include bullous cutaneous photosensitivity to visible light from early infancy, progressive photomutilation and chronic haemolytic anaemia. Due to its rarity and genetic heterogeneity, clinical phenotypes are unclear and its impact on health-related quality of life (HRQoL) has not been previously assessed. Objectives To define comprehensively CEP phenotypes and assess their impact on HRQoL, and to correlate these factors with laboratory parameters. Methods A single observer assessed patients with CEP from four European countries. Results Twenty-seven unrelated patients with CEP, aged between 7·6 and 65 years, participated in the study. The patients came from the U.K. (17), France (4), Switzerland (4) and Germany (2). Additional data were obtained for two deceased patients. Newly characterized features of CEP include acute-onset cutaneous and noncutaneous symptoms immediately following sunlight exposure, and pink erythematous facial papules. There was a lack of consistent genotype–phenotype correlation in CEP. The main poor prognostic factors in CEP are the early age of disease onset and haematological complications. Conclusions CEP is a multisystem disease; cutaneous, ocular, oral and skeletal manifestations also contribute to disease severity and impact on HRQoL, in addition to the haematological complications. The rarity of the disease can lead to delayed diagnosis. The lack of consistent genotype–phenotype correlation in CEP suggests a contribution to phenotype from other factors, such as environment, patients' photoprotective behaviour and genes other than UROS. There is currently an unmet need for multidisciplinary management of patients with CEP.
Abstract 16277: Absence of Putative Long QT Syndrome (LQTS)-Causing Mutations in the KCNJ5-Encoded Kir3.4 Channel Among a Large Cohort of Unrelated Patients With LQT1-12 Genotype Negative/Phenotype Positive LQTS
Authors: Jaeger P Ackerman, David Tester, Argelia Mederios-Domingo, Michael J Ackerman
Journal: Circulation (2011)

Background: Long QT syndrome is a potentially lethal heritable arrhythmia disorder characterized by delayed cardiac repolarization and prolongation of QT interval on a 12-lead ECG. Approximately 75...