tbuckley/cabot-search huggingface dataset:
Elder abuse: Do general practitioners know or care?
Authors: Claudine Mccreadie, Gerry Bennett, Mark S Gilthorpe, Guy Houghton, Anthea Tinker
Journal: Journal of the Royal Society of Medicine (2000)

A pilot survey in Tower Hamlets, London, indicated that many general practitioners (GPs) might not be recognizing abuse of elderly patients through lack of training. The survey was replicated on a large scale in Birmingham, to allow further analysis. 561 Birmingham GPs were mailed questionnaires and responses from 291 were analysed, providing data from 95% of the practices. The findings were similar to those in Tower Hamlets: just under half had diagnosed elder abuse in the previous year. Regression analysis of the combined data-sets (n = 363) indicated that the strongest factor predicting GP diagnosis of abuse was knowledge of 5 or more risk situations (odds ratio 6.77, 95% confidence interval 4.19, 10.93). The findings of these surveys suggest that research-based education and training would help GPs to become better at identifying and managing elder abuse.
No Improvement Of Overall Survival After Extended Follow-Up Of Donor Versus No Donor Analysis Of Newly Diagnosed Myeloma Patients Included In The HOVON 50/54 Study
Authors: Henk Lokhorst, Bronno van der Holt, Jan Cornelissen, Marie José Kersten, Marinus H.J. Van Oers, Reinier Raymakers, Monique C. Minnema, Sonja Zweegman, Jeroen JWM Janssen, Mark Zijlmans, Gerard M.J. Bos, Nicolaas PM Schaap, Okke de Weerdt, Shulamiet Wittebol, Rianne Ammerlaan, Pieter Sonneveld
Journal: Blood (2013)
The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies
Authors: John B. Buse, Ralph A. DeFronzo, Julio Rosenstock, Terri Kim, Colleen Burns, Sharon Skare, Alain Baron, Mark Fineman
Journal: Diabetes Care (2015)

OBJECTIVE Delayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediate-release metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. RESEARCH DESIGN AND METHODS Study 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference). RESULTS The bioavailability of 1,000 mg Met DR b.i.d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information. CONCLUSIONS Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action.
Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7.
Authors: M M Le Beau, K S Albain, R A Larson, J W Vardiman, E M Davis, R R Blough, H M Golomb, J D Rowley
Journal: Journal of Clinical Oncology (1986)

Clinical, histologic, and cytogenetic features in 63 patients with a therapy-related myelodysplastic syndrome (t-MDS) or acute nonlymphocytic leukemia (t-ANLL) following cytotoxic chemotherapy or radiotherapy for a previous disease were analyzed. Eleven patients had received only radiotherapy for the primary disorder. In most cases, high doses had been administered to treatment ports that included the pelvic or spinal bone marrow. Twenty-one patients had received only chemotherapy for their primary disease, all for more than 1 year and all but one with an alkylating agent, either alone or in combination with other drugs. Thirty-one patients had received both radiotherapy and chemotherapy, either concurrently or sequentially. A clonal chromosomal abnormality was observed in marrow or blood cells from 61 of the 63 patients (97%). Fifty-five patients (87%) had a clonal abnormality of chromosomes no. 5 and/or 7 consisting of loss of all or part of the long arm of the chromosome. The critical chromosome region that was consistently deleted in all 17 patients with del(5q) comprised bands q23 to q32. In addition to nos. 5 and 7, five other chromosomes (no. 1, 4, 12, 14, and 18) were found to be nonrandomly involved. Both t-MDS and t-ANLL are late complications of cytotoxic therapies that have distinctive clinical and histologic features and are associated with characteristic aberrations of chromosomes no. 5 and 7. It seems likely that these two chromosomes contain genes involved in the pathogenesis of these hematopoietic neoplasms.
Results of a survey on the communication between COPD patients and their health care providers in Germany
Authors: Michael Köhler, Dietmar J. Hecker, Darja Schendel, Robert Bals
Journal: European Respiratory Journal (2014)

Background : The age-specific death rate from COPD in Germany is approximately 17.55 per 100,000 (ERS White Book 2013) per year. Only a few patient based studies that include data on disease education and the self-management of COPD are available.   Methods : Aim of the investigation was to describe the knowledge of COPD-patients about their disease and the implementation of therapy. 760 questionnaires with 10 items were distributed to more than 20 local patient groups in Germany. The items referred to the general knowledge about COPD, handling of the inhalation devices, efficacy of the prescribed therapy, smoking behaviour and contacts with physicians.   Results : 262 evaluable questionnaires were obtained. Mean age of the COPD patients participating in our study was 68 years (+/- 8.4). 54% were female. The patients received their diagnosis at the age of 59. COPD was in 47% considered to be severe or very severe. Only 41% of the patients felt to be adequately informed about COPD by their physician. Sufficient instructions how to handle the prescribed devices was only given to 55% of the participants. Dyspnea was the dominant symptom in 28% of the patients and reported often to occur in the morning or during physical activity. Therefore 90% of the patients judged the rapid onset of bronchodilation to be very important or important. 46% of the patients terminated smoking after or before (13%) the diagnosis COPD was provided.   Conclusion : Patients often feel to be not adequately informed about the diagnosis and the use of inhalation devices by their physicians. There is a need to improve communication between patients and health care professionals.
Endothelial modulation of pulmonary vascular tone
Authors: AT Dinh-Xuan
Journal: European Respiratory Journal (1992)

Pulmonary endothelial cells normally synthesize prostacyclin (PGI2) and nitric oxide (NO), which are both potent vasodilators. Although PGI2 is largely used to treat patients with severe pulmonary hypertension, its role in the physiology and pathophysiology of the pulmonary circulation is still debated. NO, which is now considered as the endogenous nitrovasodilator, is perhaps more involved than PGI2 in the mechanisms that modulate pulmonary vascular tone in health and disease. There is evidence to suggest that background release of NO contributes to the normally low pulmonary vascular tone in normoxia. Although there are theoretical grounds to hypothesize that hypoxia reduces the synthesis of NO, lack of the latter does not seem to account for the acute hypoxic pulmonary vasoconstriction. Instead, there is evidence to suggest that NO activity is increased in order to modulate the pulmonary vasopressor response to acute alveolar hypoxia. However, more consistent, concerning the role of NO, are data gathered from studies performed in chronic hypoxic conditions. Both experimental data and studies performed in man demonstrate impairment of NO synthesis and/or release in chronic hypoxic pulmonary hypertension. The impaired NO production, whilst reducing the ability of the pulmonary vasculature to relax, also favours the occurrence of excessive pulmonary vasoconstriction. Lack of NO synthesis might also permit mitogenesis and proliferation of various cell types within the vascular wall. We hypothesize that functional alterations of pulmonary endothelium are likely to affect both reactivity and growth of pulmonary vessels. In this respect, NO probably has a pivotal role in modulating pulmonary vascular tone and controlling pulmonary vascular remodelling in health and disease.
Pneumonia in H1N1 influenza infection
Authors: Judith Brebner, Chirag Dave, Dhruv Parekh
Journal: European Respiratory Journal (2011)

Introduction:  As we entered the post 2009 H1N1 influenza pandemic period, the Centres for Disease Control and Prevention reported that a third of H1N1 deaths were attributed to co-infection with common pneumonia causing bacteria.We performed a study of all the H1N1 positive admissions to a large teaching hospital during the most recent flu season in 2010/11 with the aim of looking at radiological diagnosis of pneumonia and its relation to morbidity and mortality.   Methods:  We retrospectively analysed the electronic records and radiology for all patients admitted with H1N1 infection between 1st November 2010 and 31st January 2011.Complications and respiratory support (invasive or non-invasive) were used as markers of morbidity.   Results:  280 (mean age 39.5) patients had laboratory confirmed H1N1 infection. 96 (34.3%; mean age 44.5) had radiological pneumonia (48 unilateral, 48 bilateral);mortality 8.3%. 36 (37.5%) had no co-morbidities. Of all those that died with H1N1 8/37 (21.6%) had pneumonia. 11.5% had complications:5 effusion/empyemas,4 ARDS and 2 pneumothorax.31.3% required respiratory support.Bilateral radiological pneumonia conferred higher risk of death (7/8) and respiratory support (22/30; invasive 63.6%, non-invasive 36.4%).All those that had both bilateral pneumonia and complications (n=8) required respiratory support of which 3 died. 26% had positive sputum cultures-most common pathogens being haemophilus influnzae, streptococcus pneumonia, klebsiella and candida.50% of those requiring respiratory support had positive sputum cultures.   Conclusion:  Pneumonia in H1N1 infection is common. Bilateral pneumonia is a risk factor for the need for respiratory support and death. Development of respiratory complications confers further risk of morbidity.
Cognitive, behavioral, and emotional problems among school-age children of alcoholic parents
Authors: L A Bennett, S J Wolin, D Reiss
Journal: American Journal of Psychiatry (1988)

Sixty-four children from 37 families with an alcoholic parent were compared with 80 children from 45 families that did not have an alcoholic parent on measures of intelligence, cognitive achievement, psychological and physical disorders, impulsivity-hyperactivity, social competence, learning problems, behavior problems, and self-esteem. On nine of 17 tests, the children of alcoholic parents scored less well than did the children of nonalcoholic parents, although both were within normal ranges. Factor analysis yielded significant differences between the two samples in emotional functioning and cognitive abilities and performance; marginally significant differences were found with respect to behavior problems.
Authors overestimate role of barefoot doctors in China
Authors: T. Jewell
Journal: BMJ (1996)

EDITOR,—Paul Johnstone and Isobel McConnan are right to draw readers' attention to primary care in developing countries and its relevance for our “primary care led NHS.”1 I wish to make three points.

In drawing attention to the appreciable reduction in childhood mortality in mainland China the authors overestimate the contribution that the barefoot doctors made in the late 1960s and the ‘70s (including the period of the Cultural Revolution). The …
Mycoplasma pneumoniae infection affects total eosinophil count, the serum level of ECP, and interleukin-5 in atopic children
Authors: Jae-Won Oh, Joo-Hwa Kim, Ha-Baik Lee
Journal: European Respiratory Journal (2012)

Background:  A number of studies have outlined mechanisms by which mycoplasma infection may promote allergic lung inflammation. In addition, there is increasing evidence from human studies suggesting that mycoplasma infection contribute to asthma exacerbations, and severity with the change of cytokines. The present study evaluated the change of serum levels of eosinophil count, eosinophil cationic protein, and interleukin-5 in atopic children with Mycoplasma pneumonia infection.   Method:  We recruited 137 children including 44 atopic children with mycoplasma pneumonia (Group 1), 34 non-atopic children with mycoplasma pneumonia (Group 2), 25 children with viral pneumonia (group 3), 34 non-atopic children with viral pneumonia with mycoplasma infection (Group 4). The change of total eosinophil count, serum levels of interleukin (IL)-5, eosinophil cationic protein were measured at admission and at recovery for each group by using commercial ELISA.   Results:  The serum level of IL-5 at admission was increased at recovery in group 1 (114±51.1 pg/mL at admission, 143.2±68.4 pg/mL at recovery). However, Buserum eosinophil cationic protein concentrations were increased at clinical recovery compared to the mean serum concentration at admission(49.5 pg/mL at admission, 37.9 pg/mL at recovery in group 1; 38.2 pg/mL at admission, 27.8 pg/mL at recovery).   Conclusion:  The outcomes of the present study implied changes of eosinophil and its mediators during  Mycoplasma  infection may be associated with the mechanism by which the  Mycoplasma pneumoniae  contribute to the development of airway hypersensitivity.
The Anti-fibrotic and Anti-inflammatory Potentials of Purified Human Muscle-derived Perivascular Cells for the Treatment of Myocardial Infarction
Authors: Chien-Wen Chen, Mirko Corselli, Masaho Okada, Mihaela Crisan, Kimimasa Tobita, Bruno Peault, Johnny Huard
Journal: Circulation (2010)
Abstract 1588: Midkine Gene Transfer Ameliorates Ischemic Cardiomyopathy through Enhancements of Neovascularization via Akt/PI3 Kinase and ERK Pathways and Anti-Apoptosis by Regulating Bcl-2 and Bax
Authors: Arihiro Sumida, Mitsuru Horiba, Hisaaki Ishiguro, Hiroharu Takenaka, Norihiro Ueda, John-Kook Lee, Toyoaki Murohara, Kenji Kadomatsu, Itsuo Kodama
Journal: Circulation (2008)

Midkine (MK) is a heparin-binding growth factor involved in diverse biological phenomena, e.g. neural survival, carcinogenesis and tissue repair. We have demonstrated recently that MK ameliorates acute myocardial injury by ischemia/reperfusion through prevention of apoptotic reactions. Chronic effects of MK on the ventricular remodeling after myocardial infarction (MI) remain to be confirmed. MI was created in Wistar rat by ligation of the left anterior discending coronary artery. Rats of MK overexpression were prepared by intramyocardial injection of adenoviruses encoding MK (AdMK, n=12) at the onset of MI. Control rats were injected with adenoviruses encoding beta-galactosidase (AdLacZ, n=12). In echocardiography 4w after MI, AdMK showed smaller LVESD and LVEDD than AdLacZ (LVESD: 6.7±0.7 vs. 9.3±0.7mm, LVEDD: 8.7±0.7 vs. 10.7±0.7mm, p&lt;0.01). AdMK had better FS than AdLacZ (FS: 23.0±2.8 vs. 12.4±2.1%, p&lt;0.01). Better preservation of systolic/diastolic function in AdMK than AdLacZ was also recognized in the LV catheterization 6w after MI (dP/dt max : 3092±619 vs. 2171±763mmHg/s, dP/dt min : −2525±878 vs. −1700±722mmHg/s, LVEDP: 3.3±0.9 vs. 8.3±2.2mmHg, p&lt;0.01). Morphological study on AdMK 6w after MI revealed less fibrosis (collagen deposition area: 10.2±5.3 vs. 15.3±4.5%, p&lt;0.05) and a higher vWF-positive capillary density in the perinfarct zone (32±11 vs. 21±5/mm 2 , p&lt;0.01) compared with AdLacZ. In Western blotting, the levels of Akt and ERK phosphorylation and PI3K were elevated in AdMK compared with AdLacZ (pAkt; 2.08-fold increase, pERK; 1.43-fold increase, PI3K; 2.36-fold increase, relative to AdLacZ, p&lt;0.05). In addition, the level of Bcl-2 increased and the level of Bax decreased in AdMK compared with AdLacZ (Bcl-2; 2.15-fold increase, Bax; 3.63-fold decrease, relative to AdLacZ, p&lt;0.01). Overexpression of MK has long-term beneficial effects to reduce the progression of LV remodeling and dysfunction after MI. This amelioration is attributable in part to an enhancement of neovascularization via PI3K/Akt and ERK pathways, and in part to anti-apoptotic actions regulating Bcl-2 and Bax. MK gene transfer might be a new therapeutic strategy for treatment of ischemic heart disease.
Erythropoiesis‐driven regulation of hepcidin in human red cell disorders is better reflected through concentrations of soluble transferrin receptor rather than growth differentiation factor 15
Authors: Kleber Yotsumoto Fertrin, Carolina Lanaro, Carla Fernanda Franco‐Penteado, Dulcinéia Martins de Albuquerque, Mariana Rezende Bandeira de Mello, Flávia Rubia Pallis, Marcos André Cavalcanti Bezerra, Betania Lucena Domingues Hatzlhofer, Gordana Olbina, Sara Terezinha Olalla Saad, Aderson da Silva Araújo, Mark Westerman, Fernando Ferreira Costa
Journal: American Journal of Hematology (2013)

Growth differentiation factor 15 (GDF-15) is a bone marrow-derived cytokine whose ability to suppress iron regulator hepcidin in vitro and increased concentrations found in patients with ineffective erythropoiesis (IE)suggest that hepcidin deficiency mediated by GDF-15 may be the pathophysiological explanation for nontransfusional iron overload. We aimed to compare GDF-15 production in anemic states with different types of erythropoietic dysfunction. Complete blood counts, biochemical markers of iron status, plasma hepcidin, GDF-15, and known hepcidin regulators [interleukin-6 and erythropoietin (EPO)] were measured in 87 patients with red cell disorders comprising IE and hemolytic states: thalassemia, sickle cell anemia, and cobalamin deficiency. Healthy volunteers were also evaluated for comparison. Neither overall increased EPO,nor variable GDF-15 concentrations correlated with circulating hepcidin concentrations (P = 0.265 and P = 0.872). Relative hepcidin deficiency was found in disorders presenting with concurrent elevation of GDF-15 and soluble transferrin receptor (sTfR), a biomarker of erythropoiesis, and sTfR had the strongest correlation with hepcidin (r(s) = 0.584, P < 0.0001). Our data show that high concentrations of GDF-15 in vivo are not necessarily associated with pathological hepcidin reduction, and hepcidin deficiency was only found when associated with sTfR overproduction. sTfR elevation may be a necessary common denominator of erythropoiesis-driven mechanisms to favor iron absorption in anemic states and appears a suitable target for investigative approaches to iron disorders.
Successful Outcome of Severe Unilateral Pulmonary Interstitial Emphysema after Bi-Lobectomy in a Very Low Birthweight Infant
Authors: J S Ahluwalia, J M Rennie, F C Wells
Journal: Journal of the Royal Society of Medicine (1996)

Extubation of ventilated infants with severe unilateral pulmonary interstitial emphysema is difficult because the function of normal lung tissue is impaired. Continued positive pressure ventilation worsens hyperinflation on the side with interstitial emphysema, leading to cardiorespiratory compromise. Resection of affected single lobes is well described, but there are no reported cases of multiple lobectomies in very low birthweight infants. We describe a case where resection of both right upper and middle lobes was successful, allowing extubation within a few days of surgery. Computed tomography (CT) of the chest was helpful in making the decision to treat this infant by surgery.
Long-term metabolic correction of Wilson’s disease in a murine model by gene therapy
Authors: Oihana Murillo, Daniel Moreno Luqui, Cristina Gazquez, Debora Martinez-Espartosa, Iñigo Navarro-Blasco, Jose Ignacio Monreal, Laura Guembe, Armando Moreno-Cermeño, Fernando J. Corrales, Jesus Prieto, Ruben Hernandez-Alcoceba, Gloria Gonzalez-Aseguinolaza
Journal: Journal of Hepatology (2015)
A phase IIa pharmacokinetic and efficacy study of amonafide (AS1413) in combination with cytarabine in patients with acute myeloid leukemia.
Authors: A. S. Lundberg, S. L. Allen
Journal: Journal of Clinical Oncology (2010)

TPS278 Background: Amonafide is a novel DNA intercalator that is not affected by multidrug resistance mechanisms, a common cause of treatment failure in AML. Amonafide has previously been studied in combination with cytarabine in patients with secondary AML in a phase I dose- escalation study and a phase II safety and efficacy study. The phase III ACCEDE study is comparing amonafide + cytarabine to daunorubicin + cytarabine in previously untreated secondary AML (sAML). The pharmacokinetics (PK) of amonafide when given at lower doses and as monotherapy has been extensively studied. This study is designed to further determine the amonafide PK in the combination antileukemic regimen being evaluated clinically and to facilitate the development of a population PK model for further clinical studies. Methods: This is a multicenter, single-arm, fixed-dose phase IIa study of amonafide + cytarabine in with newly diagnosed, relapsed, or refractory adult patients with AML. The objectives of the study are to define the plasma PK profile and urinary excretion of amonafide and metabolite(s) and to evaluate the safety, tolerability, and remission rate of amonafide in combination with cytarabine. Patients will receive therapy with amonafide 600 mg/m2/day IV over 4 hours daily on days 1-5 in combination with cytarabine 200 mg/m2 IV CI daily on days 1-7, with a second course for persistent leukemia on day 14. Up to 30 patients are expected to be enrolled and treated in this study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisoma Antisoma