tbuckley/cabot-search huggingface dataset:
Respiratory syncytial viral infections in lung transplant recipients: Treatment with aerolised ribavirin
Authors: Simona Soresi, Haifa Lyster, Anne Hall, Anna Reed, Andre Simon, Martin Carby
Journal: European Respiratory Journal (2013)

Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in lung transplant recipients (LTRs). RSV is a well recognised risk factor for the development of bronchiolitis obliterans syndrome (BOS). Ribavirin has been administered intravenously and orally in the treatment of RSV in adult lung transplantation but reports of its use aerolised is limited. We performed a retrospective analysis of LTRs who received aerolised ribavirin to treat RSV during the period December 2010-12, outcomes included respiratory function tests (RFTs) and adverse drug reactions (ADRs).  8 LTRs (2 male) were treated with aerolised Ribavirin for RSV infection, all presented with a drop in RFTs and viral symptoms. 3 patients with histological and/or radiological evidence of interstitial pneumonitis also received intravenous immunoglobulin (500mg/kg daily for 5 days) and high dose corticosteroids. Aerolised Ribavirin was administered as 6g/day at a concentration of 60mg/ml running at 17.5ml/hour for 2 hours every 8 hours until 2 consecutive negative nasopharyngeal aspirate samples were achieved. RFTs were repeated at the end of the treatment course.  8 patients (9 treatment episodes) were treated for a mean of 10.6 days (range: 6-22 days). In 6 of the 9 treatment episodes the respiratory symptoms resolved completely, with RFTs returning to baseline. 2 patients died post-treatment (81 and 184 days) and 1 patient developed BOS. There were minor ADRs in 4 patients: sore throat (1), headache (3) and nausea (1), none necessitated treatment discontinuation.  In adult LTRs with RSV infections, aerolised ribavirin is a safe and promising treatment option with minimal systemic ADRs.
Abstract 4629: Long-Term Open Label Extension of the Prevention of Embolic and Thrombotic Events on Dabigatran in Atrial Fibrillation (PETRO- Ex study)
Authors: Rangadham Nagarakanti, Michael D Ezekowitz, Kambiz Parcham-Azad, Paul A Reilly, Gerhard Nehmiz, Dominick A Lionetti, Lars Wallentin
Journal: Circulation (2008)

Dabigatran is an oral direct thrombin inhibitor (DTI), which has a rapid onset of action and can be given twice daily (b-i-d) without anticoagulation monitoring. To determine the long term safety and efficacy of dabigatran in patients with atrial fibrillation (AF). AF patients (n=502) from 53 centers in Denmark, the Netherlands, Sweden and the United States were enrolled in the PETRO study, a 12 week comparison between dabigatran (50, 150, and 300 mg b-i-d) and warfarin (INR 2–3). 361 dabigatran patients were rolled over into a long term extension trial (PETRO-Ex). The warfarin patient arm (n=70) was discontinued. All patients were initially maintained on the same dabigatran doses as in PETRO except the 50 mg b-i-d dose group who were switched to 150 mg once daily (qd). At entry, patients were 70 years old (mean age), 19% female, median AF duration of 4.2 years, and had a median of 3 stroke risk factors. Maximum and mean follow-up times were 51 and 29 months respectively. Due to higher frequency of major bleeding events in 300 mg b-i-d group and thromboembolic events in 150 mg qd group, they were switched to dabigatran 300 mg qd or 150 mg b-i-d groups. PETRO and PETRO-Ex results: Events reported as absolute number of patients (per 100 patient-years) Thromboembolic event rates were lowest in the dabigatran 150 and 300 mg b-i-d groups. Major bleeding was most frequent in the 300 mg b-i-d group. No significant liver function abnormalities were noted in any of the dabigatran groups. The balance between stroke and bleeding risk supported dabigatran doses between 100 and 150 mg b-i-d for the ongoing phase 3 Randomized Evaluation of Longterm anticoagulation therapY (RELY) trial.
Evidence-Based Medicine
Authors: J. N Rao, J D Middleton
Journal: BMJ (1996)

erence ranges.We therefore suggest that the problems of standardising the reporting of results for anticoagulation clinics would be reduced by use of the proportion of patients achieving therapeutic international normalised ratios, the percentage of time for which the ratios are within the therapeutic reference range, and the mean (±1 SD) ratio.The model of care reported by Macgregor and colleagues may have a place in anticoagulant treat- ment, but their small observational study cannot draw the broad conclusion that ifwe "are willing to devolve management to pharmacists then good therapeutic control is achievable in the surgery."
Skin Oxygen Tension in Venous Insufficiency of the Lower Leg
Authors: H J Dodd, P M Gaylarde, I Sarkany
Journal: Journal of the Royal Society of Medicine (1985)

Tissue anoxia has for long been invoked as a cause of venous leg ulcers, and recently it has been suggested that pericapillary fibrin prevents the diffusion of oxygen in the skin. In the present study direct measurements of skin oxygen levels on the lower leg were made using a transcutaneous oxygen monitor. In the recumbent position mean oxygen tensions were higher in patients than in controls, thus disproving the existence of any block to oxygen diffusion. In both groups there was a fall in oxygen tension to low levels on standing as a result of the normal reflex vasoconstrictor response to increased venous pressure. Exercise produced a marked rise in skin oxygen tension in normal legs but not in those affected by venous insufficiency. In normal subjects exercise reduces venous pressure, thus removing the stimulus for reflex vasoconstriction. In patients with defective valves, the venous pressure remains high during exercise and reflex vasoconstriction persists. It is concluded from this study that the sustained low skin oxygen tension in the upright position even during exercise is responsible for leg ulcer formation associated with venous insufficiency. Normal legs are protected by a rise in skin oxygenation during exercise.
Effect of auto servo-ventilation (ASV) and continuous positive airway pressure (CPAP) on B-type natriuretic peptide (NT-proBNP) in patients with co-existing obstructive (OSA) and central sleep apnea (CSA) in heart failure (HF)
Authors: Winifried Randerath, G. Nothofer, N. Anduleit, M. Treml, C. Priegnitz, W. Galetke
Journal: European Respiratory Journal (2011)

Introduction:  The optimal ventilatory mode for patients with co-existing OSA and CSA in HF is unclear. We investigated the effects of ASV and CPAP therapy on NT-proBNP, a marker of HF severity.   Methods:  70 patients (66.3±9.1 y., 31.3±6.0 kg/m 2 ) with    Results:  AHI significantly improved in both groups (ASV: 48.0±25.0 vs. 6.9±6.8/h, p   Conclusions:  Effective treatment of co-existing OSA and CSA with ASV improves NT-proBNP levels, suggesting a relief of cardiac load. This may be related to a more efficient reduction of central disturbances in this group of patients compared to CPAP.
Review of Jonathan Kahn,<i>Race in a Bottle: The Story of BiDil and Racialized Medicine in the Post-Genomic Age</i><sup>1</sup>
Authors: Nathan Nobis
Journal: The American Journal of Bioethics (2015)

"Review of Jonathan Kahn, Race in a Bottle: The Story of BiDil and Racialized Medicine in the Post-Genomic Age1." The American Journal of Bioethics, 15(10), pp. W4–W5
Prenosological diagnosis of respiratory function abnormalities in smokers
Authors: Marina Segizbaeva, Mikhail Pogodin, Nina Aleksandrova
Journal: European Respiratory Journal (2012)

Chronic tobacco poisoning leads to the gradual development of various pathological processes at the cellular, tissue, organ and system levels, but their clinical manifestations may have delayed effect. Prenosological diagnosis of respiratory function disorders in smokers is very important in order to promote an effective behavioral intervention for smoking cessation. The study was performed for evaluation of simple and noninvasive diagnostic methods of respiratory disorders in smokers. Maximal inspiratory pressure (MIP), peak inspiratory flow (PIF) and peak expiratory flow (PEF), as well as the measurement of the fall in pulse oximetry saturation caused by 20-s breath-holding (dSaO2) at the end of expiration (Inoue H. et al, 2009) was studied in 20 young nonsmokers and smokers. Our results showed significant reduction of PEF and PIF in a group of men and women smokers compared with nonsmokers. MIP had a trend to decrease in smokers, especially in women9s group. It was found that a temporary reduction in hemoglobin oxygen saturation caused by 20-sec apnea is significantly higher in smokers than non-smokers. Violation of ventilation-perfusion relationships during apnea because of the typical smoker disorders of the peripheral airway patency can be a major cause of severe oxygen desaturation. Smokers are at greater risk of hypoxemia during any apnea than nonsmokers. Our results showed that the measurement of PIF, PEF, MIP and dSO2 may be adequate diagnostic methods for early detection of respiratory pathology in smokers. These methods can be used in routine clinical practice.
A hierarchy of drug use in adolescene: behavioral and attitudinal correlates of substantial drug use
Authors: B A Hamburg, H C Kraemer, W Jahnke
Journal: American Journal of Psychiatry (1975)

The authors studied drug use in a representative sample of suburban junior and senior high school students. They found high levels of drug use overall and a substantial amount of drug involvement among junior high school students. They also found that drugs were used in clusters, that there was a distinctive age-related pattern of drug use, and that the progressive-step therory of drug use was not confirmed. A number of behavioral and attitudinal variables correlated with a tendency toward a high level of drug use. The implications of these findings include the need for targeted drug education and prevention programs and a differentiated approach to the study of drug use among adolescents.
Abstract 856: Renal Tissue Perfusion Increases After Interventional Therapy In Patients With Unilateral Renal Artery Stenosis
Authors: Erdal Safak, Wolfgang Utz, Steffen Bohl, Wolfgang Derer, Ralf Wassmuth, christian M Gross, Friedrich C Luft, Jeannette Schulz-Menger, Rainer Dietz, Ralf Dechend
Journal: Circulation (2008)
Staphylococcal Diarrhoea
Authors: J. Cook, C. Elliott, A. Elliot-Smith, B. R. Frisby, A. M. N. Gardner
Journal: BMJ (1957)

During the years 1953-5, 31 cases of diarrhoea following antibiotic therapy were investigated in the Radcliffe Infirmary.Staphylococcus aureus was cultured from the
Phagocytosis by blood monocytes in differentiation between sarcoidosis and tuberculosis
Authors: Anna Dubaniewicz, Monika Wybieralska, Katarzyna Rogoza, Marlena Typiak, Adam Sternau, Jan M. Slominski, Piotr Trzonkowski
Journal: European Respiratory Journal (2012)

Due to clinical and histopathological similarities between sarcoidosis (SA) and tuberculosis TB), we try to find some biomarker(s), which allow to a differential diagnosis between these disorders. We recently revealed increased frequencies of receptors for Fc fragment of IgG (FcγR) FcγRI+ and FcγRII+ monocytes in both SA and TB but in contrast to TB, sarcoid monocytes had increased FcγRIII occurrence with receptors for fragment of complement (CR) CR1 and CR4 deficiency. Abnormal expression of FcγR and CR may cause of a disorder of the phagocytosis by monocytes and clearance of immune complexes (CIs) with following immunocomlexemia, which concentration was higher in SA than in TB. Therefore, we have evaluated the percentage of phagocitizing blood monocytes from 22 patients with SA, 20 patients with TB, and 20 healthy volunteers using the PHAGOTEST® kit by flow cytometry. Our study revealed increased percentage of monocytes in SA than in TB and the controls (p=0.003, p=0.002, respectively), but there was no difference between TB and healthy individuals. The percentage of phagocitizing monocytes was increased in SA than in the controls (p=0.03) and it was slightly elevated compared to TB. There was no difference between TB and the controls. In summary, current study revealed increased of phagocytic activity of monocytes in SA than TB and explained previously obtained results regarding higher frequency of FcγR and CR deficiency on sarcoid than on tuberculoid monocytes. The increased phagocytosis of CIs and high antigen load with following persistent antigenemia may explain the presence persistent complexemia in our patients with SA. This study may be useful for differentiation of both diseases.
Direct‐acting antiviral drug approvals for treatment of chronic hepatitis C virus infection: Scientific and regulatory approaches to clinical trial designs
Authors: Poonam Mishra, Jeffrey Murray, Debra Birnkrant
Journal: Hepatology (2015)

Therapeutic options for treatment of chronic hepatitis C have improved substantially since the approval of direct‐acting antiviral agents (DAAs). Several interferon (IFN)‐free or IFN‐ and ribavirin (RBV)‐free treatment regimens with shorter durations and improved efficacy and safety profiles are now available. The U.S. Food and Drug Administration (FDA) used several scientific approaches and regulatory mechanisms, such as (1) use of a “validated” surrogate (sustained virological response) for a primary endpoint, (2) shortening the time point for measuring the surrogate by 12 weeks, (3) use of historical controls when clinically appropriate, and (4) use of modeling when scientifically sound to extend treatment indications to subpopulations not fully evaluated in clinical trials, which had an impact on DAA development and subsequent approvals. This article intends to provide increased transparency about the FDA's scientific approaches and regulatory processes that supported drug development and marketing approval of DAAs for treatment of hepatitis C, a serious, life‐threatening infection. (H epatology 2015;62:1298‐1303)
Home mechanical ventilation in chronic respiratory diseases: An experience from a pediatric semi-intensive respiratory care unit
Authors: Francesco Paolo Rossi, Martino Pavone, Elisabetta Verrillo, Alessandra Schiavino, Maria Beatrice Chiarini Testa, Maria Giovanna Paglietti, Serena Soldini, Renato Cutrera
Journal: European Respiratory Journal (2011)

Mechanical, invasive and non invasive ventilation represents an important therapeutic tool for many acute and chronic respiratory diseases in childhood.  We retrospectively analyzed clinical history of children receiving home mechanical ventilation (HMV) in our Pediatric Semi-Intensive Respiratory Care Unit from 2003 to 2010.  From 2003 to 2010 we treated with HMV 153 children (M/F 80/73 girls, mean age 10.5years). Most of the patients (138) were treated with non-invasive ventilation (C-PAP or BiPAP). In this group, the most frequent diagnosis were Spinal Muscular Atrophy, followed by Prader Willi syndrome, obstructive sleep apnoea, myopathies, Cystic Fibrosis, encephalopathy, cerebral palsy, muscular dystrophy, metabolic or genetic diseases and others diseases such as congenital heart disease, brain tumors and othorinolaryngohiatric diseases. Fifteen patients were treated with invasive HMV through trachestomy. In this group the most frequent diagnoses were Cerebral Palsy, followed by Spinal Muscular Atrophy, Encephalopathies and others chronic respiratory disorders (Congenital central hypoventilation syndrome, bronchopulmonary dysplasia, etc).  Sixtyone percent of the patients are still in follow-up in our Unit, 17% stopped mechanical ventilation, 14% were lost to follow-up, while 8% is died. Of the 95 patients followed at our unit, only 53 (56%) has an adequate home care.  Home mechanical ventilation, invasive or non-invasive, is a valid tool for the management of children with chronic respiratory diseases. In our experience home care of these patients must be improved in terms of family support (nursing, technical support, psychological support).
Familial Jejunal Atresia with ‘Apple-Peel’ Variant<sup>1</sup>
Authors: S A Al-Awadi, K Naguib, T I Farag, A Cuschieri, M Issa
Journal: Journal of the Royal Society of Medicine (1981)

We report two siblings who had jejunal atresia which we believe to be familial. The parents of these siblings were first cousins. The first child had jejunal atresia with mesenteric agenesis and ‘apple-peel’ configuration; the second child had jejunal atresia with a V-shaped mesenteric defect. Other reported cases of familial atresia of the small intestine are reviewed.
Impact of QRS Duration and Morphology on the Risk of Sudden Cardiac Death in Asymptomatic Patients With Aortic Stenosis
Authors: Anders M. Greve, Eva Gerdts, Kurt Boman, Christa Gohlke-Baerwolf, Anne B. Rossebø, Richard B. Devereux, Lars Køber, Simon Ray, Ronnie Willenheimer, Kristian Wachtell
Journal: Journal of the American College of Cardiology (2012)
Propylthiouracil inhibits the conversion of l-thyroxine to l-triiodothyronine
Authors: Jack H. Oppenheimer, Harold L. Schwartz, Martin I. Surks
Journal: Journal of Clinical Investigation (1972)

6-n-propylthiouracil (PTU) administered to male Sprague-Dawley rats maintained on 2 and 5 mug L-thyroxine (T(4))/100 g body weight resulted in a marked reduction in the rate of conversion of L-thyroxine to L-triiodothyronine (T(3)). These effects could not be ascribed to induced hypothyroidism since the group maintained on 5 mug T(4)/day had normal levels of liver mitochondrial alpha glycerophosphate dehydrogenase. In confirmation of previous studies, PTU also reduced the fractional rate of deiodination of T(3). These observations provide a possible explanation of the many published observations indicating that PTU antagonizes the tissue effects of T(4) but not of T(3). The data suggest that monodeiodination of T(4) but not of T(3) is essential before hormonal effects can be manifested at the cellular level.
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis
Authors: Matthew J. Armstrong, Diana Hull, Kathy Guo, Darren Barton, Jonathan M. Hazlehurst, Laura L. Gathercole, Maryam Nasiri, Jinglei Yu, Stephen C. Gough, Philip N. Newsome, Jeremy W. Tomlinson
Journal: Journal of Hepatology (2015)

Graphical abstractAbstractBackground & AimsInsulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.MethodsFourteen patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomised, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.ResultsLiraglutide reduced BMI (−1.9 vs. +0.04kg/m2; p<0.001), HbA1c (−0.3 vs. +0.3%; p<0.01), cholesterol-LDL (−0.7 vs. +0.05mmol/L; p<0.01), ALT (−54 vs. −4.0IU/L; p<0.01) and serum leptin, adiponectin, and CCL-2 (all p<0.05). Liraglutide increased hepatic insulin sensitivity (−9.36 vs. −2.54% suppression of hepatic endogenous glucose production with low-dose insulin; p<0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (−24.9 vs. +54.8pmol/L insulin required to ½ maximally suppress serum non-esterified fatty acids; p<0.05), and specifically within subcutaneous adipose tissue (p<0.05). In addition, liraglutide decreased hepatic de novo lipogenesis in vivo (−1.26 vs. +1.30%; p<0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p<0.01).ConclusionsLiraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH.
Cisplatin-induced atrial fibrillation.
Authors: O Menard, Y Martinet, P Lamy
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.1.192 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1985170 Cisplatin-induced atrial fibrillation. O MenardxO MenardSearch for articles by this author , Y MartinetxY MartinetSearch for articles by this author , P LamyxP LamySearch for articles by this author https://doi.org/10.1200/JCO.1991.9.1.192 PDF "Cisplatin-induced atrial fibrillation.." Journal of Clinical Oncology, 9(1), pp. 192–193© 1991 by American Society of Clinical Oncology
Late-breaking abstract: Short term improvement in 6 minute walk distance predicts long term survival in incident idiopathic pulmonary arterial hypertension. Results from the Pulmonary Hypertension Registry of the United Kingdom and Ireland
Authors: Yi Ling, Martin Johnson, David Kiely, Robin Condliffe, Charlie Elliot, Simon Gibbs, Luke Howard, Joanna Pepke-Zaba, Karen Sheares, Paul Corris, Andrew Fisher, Jim Lordan, Sean Gaine, Gerry Coghlan, John Wort, Michael Gatzoulis, Andrew Peacock
Journal: European Respiratory Journal (2011)

Background: Improvement in 6 minute walk distance (6MWD) after 12-16 weeks of treatment has been used as the primary end point in many pivotal pulmonary arterial hypertension (PAH) clinical trials. However, the consensus view is that although baseline 6MWD predicts survival, change in 6MWD (Δ6MWD) does not.

Aim: To determine whether Δ6MWD after 3 months of disease targeted therapy predicts long term survival in patients from the Pulmonary Hypertension Registry of the UK and Ireland.

Methods: Retrospective observational study of all incident cases of idiopathic (IPAH), heritable and anorexigen-associated PAH diagnosed in the UK and Ireland between 1st January 2001 and 31st December 2009. Patients were divided into low and high baseline 6MWD by the median 6MWD (295 m).

Results: Total of 646 patients were diagnosed. After 3 months of disease targeted therapy, patients with absolute 6MWD >353 m (corresponding to the median value at 3 months) had better survival than those with 6MWD   37.5 m had better survival compared to those with Δ6MWD at 3 months of < 37.5 m (Log-rank, p=0.03). This is not seen in patients with high baseline 6MWD.

Conclusion: Change in 6MWD after 3 months of treatment predicts long term survival in patients with low baseline 6MWD.