tbuckley/cabot-search huggingface dataset:
The relationship of sex and treatment modality to neuropsychologic outcome in childhood acute lymphoblastic leukemia.
Authors: D P Waber, N J Tarbell, C M Kahn, R D Gelber, S E Sallan
Journal: Journal of Clinical Oncology (1992)

PURPOSE Long-term adverse neurobehavioral sequelae frequently are observed in pediatric patients treated for acute lymphoblastic leukemia (ALL). To clarify the relative contribution of cranial irradiation (CRT) therapy and drug therapy to these outcomes, we evaluated neuropsychologic outcomes associated with different doses of CRT and intravenous (IV) methotrexate (MTX) in long-term survivors. PATIENTS AND METHODS Fifty-one patients treated for ALL on Dana-Farber Cancer Institute protocol 81-01 were evaluated by standardized cognitive and academic achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received 1,800 cGy or 2,800 cGy CRT, respectively. A subgroup of these patients was randomized to receive MTX during remission induction, either as a single low dose (LD; 40 mg/m2) or a single high dose (HD; 4 g/m2) with leucovorin rescue. RESULTS Sex and MTX randomization jointly predicted the intelligence quotient (IQ). Fifty percent of girls versus 14% of boys exhibited low IQ (less than 90; P = .01); 80% of girls who received HD MTX versus 25% of girls who received LD MTX exhibited low IQ (P = .03). In contrast, risk group better predicted performance on tasks sensitive to verbal memory and/or coding. CONCLUSIONS We conclude that (1) significant neurotoxicity occurred principally in girls; (2) increased dose intensity of IV MTX was associated with lower IQ, but only in girls; and (3) increased dose of CRT may have been associated with impairment of verbal memory and coding.
Viral infection land lung function decline following lung transplantation
Authors: Kathleen Jahn, Peter Grendelmeier, John David Aubert, Hans Hirsch, Daiana Stolz, Michael Tamm
Journal: European Respiratory Journal (2014)

Viral infections are very common in immunocompromised patients. The potential association of viral infection with the development of bronchiolitis obliterans syndrome is under dabate. New diagnostic methods such as viral multiplex PCR allow to better diagnose and characterise viral infections in lung transplant recipients. In this study we evaluated wheter viral infection, documented in the lower respiratory tract are associated with a decline in lung function.  From October 2010 till December 2013 236 lung transplant recipients underwent bronchoscopy with BAL with bacterial, fungal, cytological and viral work up including multiplex viral PCR for 13 respiratory viruses.  Respiratory viruses were detected in 105 cases ( Rhinovirus 44; RSV 14; Coronavirus 10; Influenza A and B 6; Parainfluenza 6; human Metapneumovirus 3; Adenovirus 1; HSV 7; CMV > 109000 copies 24). A total of 24 patients experienced an acute decline in FEV1, observed in 14 out of 105 cases with viral infection (13.3%) as compared to 10 out of 131 patients without evidence of viral pathogens ( 7.7%). Documented viruses in the 14 cases were: Entero-/ Rhinovirus 7, Coronavirus 2, Parainfluenza 2, Influenza B 1, hMPV 1, RSV B 1. In two cases there were also bacteria grown (MOTT ; pseudomonas).Three patients with no viral infection but an acute decline in lung function showed bacterial or fungal infection (Staph aureus; enterobacteriaceae, aspergillus).   Conclusion : Following lung transplantation an acute drop of lung function is only observed in a minority of cases with documented viral infection in the lower respiratoty tract.
Late-breaking abstract: Predictors of restrictive spirometry pattern in large population based studies. Is there a role for occupational exposures?
Authors: Giulia Paolocci, Nicola Murgia, Jonas Brisman, Anna.Carin Olin, Giacomo Muzi, Kjell Torén
Journal: European Respiratory Journal (2014)

Background:Epidemiological studies have found that 7-13% of adults have FVC values   Aims:the objective of this study is to evaluate predictors of restrictive pattern, including several potential occupational risk factors.  Methods:A general population sample of 3645 subjects was selected from the population register in Goteborg, Sweden.Restrictive pattern was defined as having FVC values   Results:71 subjects (2%) had a restrictive ventilatory defect. Risk factors for a restrictive pattern were male gender, BMI, low birth weight, being non-swedish born.Among subjects overweight, alongside the before mentioned risk factors, occupational exposure to textile fibres and leather dust was associated with a restrictive pattern (OR 3.4, 95%CI 1.05-11).  Conclusions: A restrictive ventilatory defect in spirometry is not a common finding.In our study overweight blue-collar workers, exposed to textile and leather dust, are at higher risk of restricitive pattern.This interesting finding needs to be confirmed in studies considering also lung volumes.
Efficacy and safety of vancomycin constant-rate infusion in the treatment of chronic Gram-positive bone and joint infections
Authors: E. Bernard, I. Perbost, M. Carles, A. Michiels, H. Carsenti-Etesse, R.M. Chichmanian, B. Dunais, P. Dellamonica
Journal: Clinical Microbiology and Infection (1997)
Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study
Authors: C M Moore, J D Christensen, B Lafer, M Fava, P F Renshaw
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to evaluate whether the concentration of beta-nucleoside triphosphate is lower in the basal ganglia of depressed subjects.In vivo 31P magnetic resonance spectra were acquired from a 45-cm3 region surrounding the basal ganglia of 35 unmedicated depressed subjects and 18 comparison subjects.beta-Nucleoside triphosphate, which arises primarily from beta-ATP, was 16% lower in the depressed subjects than in the comparison subjects.The low level of beta-nucleoside triphosphate is consistent with an abnormality of high-energy phosphate metabolism in the basal ganglia of subjects with major depression.
Successful treatment of meningeal leukemia using systemic high-dose cytosine arabinoside.
Authors: J Frick, P S Ritch, R M Hansen, T Anderson
Journal: Journal of Clinical Oncology (1984)

Conventional therapy for leukemic meningitis includes cranial irradiation and intrathecal chemotherapy administered by repeated lumbar punctures or direct intraventricular instillation via an Ommaya reservoir. Several clinical reports have indicated that high doses of cytosine arabinoside (ara-C) are effective in the treatment of acute leukemia refractory to standard induction therapy. Pharmacokinetic studies have demonstrated that high doses of ara-C given intravenously obtain sustained therapeutic drug concentrations in the cerebrospinal fluid, suggesting that this approach may be useful in the treatment of systemic disease associated with meningeal involvement. Five consecutive patients with overt meningeal leukemia were treated using only systemic chemotherapy containing high-dose ara-C. In all patients there was prompt resolution of neurologic symptoms and signs accompanied by cytologic clearing of leukemic cells from the cerebrospinal fluid.
Topotecan: Weekly intravenous (IV) schedule similar to standard 5-day IV schedule as second-line therapy for relapsed small cell lung cancer (SCLC)—A Minnie Pearl Cancer Research Network phase II trial
Authors: D. L. Shipley, J. D. Hainsworth, D. R. Spigel, J. R. Gray, J. H. Barton, A. Switzer, M. Nicolau, T. Marsland, G. Joseph, F. A. Greco
Journal: Journal of Clinical Oncology (2006)

7083 Background: Topotecan IV weekly produces significantly less myelotoxicity than the standard 5-day IV schedule and appears as active as the 5-day schedule in patients (pts) with relapsed ovarian cancer. Topotecan 5-day IV schedule is the standard for second-line therapy for sensitive relapse SCLC. Methods: The primary endpoints of this phase II trial were to determine the response rate and toxicity of topotecan IV weekly as second-line therapy in patients with sensitive relapse (SR) and resistant relapse (RR) SCLC. Topotecan 4mg/m 2 IV over 30 minutes for 12 consecutive weeks was planned. Dose modifications were made based on toxicity. Pts were evaluated for response after 4 weeks; at least 3 weekly treatments were required to be evaluable. Results: A total of 103 pts (59 SR; 44 RR) were enrolled: 56 men, 48 women; age range 42–86 (median 65); performance status 0=18, 1=69, 2=16, 3=1. 47 pts with SR and 34 pts with RR were evaluable for response by WHO criteria. For SR, 3 pts had partial response (6.4%, 95% CI 1.3%-17.5%), 17 pts had stable disease (7 had minor responses with tumor shrinkage of 39%, 27%, 21%, 20%, 20%, 7%, and 3%, respectively). Using RECIST criteria 5 pts had PR (13%, 95% CI 6%-25%). For RR, 1 pt had a CR (3%, 95% CI 0.1%-15.3%), 6 pts had stable disease (2 had minor responses with 36%, 5% tumor shrinkage). Grade 3/4 neutropenia/thrombocytopenia was seen in 17 and 22pts, grade 3 infection 6 pts; grade 3/4 fatigue 16 pts. There was 1 treatment-related death. Median and 1-year survival for all patients was 4.5 months (SR = 5.6 months; RR 3.2 months, p = 0.05) and 19% (SR = 22%; RR = 10%). There was no difference in survival for PR versus stable pts, and PR/stable had 1-year survival of 46% compared to PD of 9% (p &lt; 0.0001). Conclusions: Topotecan IV weekly has similar activity to the standard 5-day IV schedule in SR SCLC, and considerably less myelotoxicity. These data support the weekly schedule for standard therapy of SR SCLC, and further study of weekly topotecan as a component of combination therapy for SCLC. [Table: see text]
Microfluidic Sample Preparation for Medical Diagnostics
Authors: Francis Cui, Minsoung Rhee, Anup Singh, Anubhav Tripathi
Journal: Annual Review of Biomedical Engineering (2015)

Fast and reliable diagnoses are invaluable in clinical care. Samples (e.g., blood, urine, and saliva) are collected and analyzed for various biomarkers to quickly and sensitively assess disease progression, monitor response to treatment, and determine a patient's prognosis. Processing conventional samples entails many manual time-consuming steps. Consequently, clinical specimens must be processed by skilled technicians before antigens or nucleic acids are detected, and these are often present at dilute concentrations. Recently, several automated microchip technologies have been developed that potentially offer many advantages over traditional bench-top extraction methods. The smaller length scales and more refined transport mechanisms that characterize these microfluidic devices enable faster and more efficient biomarker enrichment and extraction. Additionally, they can be designed to perform multiple tests or experimental steps on one integrated, automated platform. This review explores the current research on microfluidic methods of sample preparation that are designed to aid diagnosis, and covers a broad spectrum of extraction techniques and designs for various types of samples and analytes.
The results of automated data capture following introduction of electronic patient record (EPR) in a specialist bronchiectasis clinic
Authors: Rizwan Ahmed, Ben Mercer, Ian Clifton, Miles Denton, Daniel Peckham
Journal: European Respiratory Journal (2012)

We have piloted EPR in a specialist bronchiectasis clinic in Leeds with an aim to combine e-consultation with high quality live coded data for audit, service development and clinical trials. We report a preliminary snapshot of 12 months data.

Method The software used was a primary care web based solution from Egton Medical Information Systems. Key functions include demographics, alerts, coded history, e-consultations, automated letter generation and e-prescribing. New local, Read and snowmed codes were developed to ensure detail capture of previously un-coded information. Data was entered using templates.

Results A total of 110 patients (68 F) had a diagnosis of bronchiectasis with a median(range) age of 62(17-87)yrs and median(range) %predicted FEV1 of 65%(12%-133%). Investigations carried out are shown in table 1 & underlying aetiology in table 2.

View this table:

Investigations carried out





View this table:

Underlying Aetiology of Bronchiectasis





Sputum microbiology was positive for P. aeruginosa, A. fumigatus and Methicillin-resistant S. aureus in 38%, 21% & 9% of cases respectively.

Conclusion Early experience has highlighted the successful implementation of EPR. The approach has been shown to work smoothly and provides a strong basis for audit and research for any chronic disease.
Liraglutide improves weight loss in people who are overweight or obese, study shows:
Authors: Susan Mayor
Journal: BMJ (2015)

Liraglutide significantly reduces body weight and improves metabolic control in people who are obese or overweight and have dyslipidaemia or hypertension, a randomised trial reported in the New England Journal of Medicine has shown.1

The study randomised 3731 people who were obese, had a body mass index (BMI) of at least 30, or were overweight (BMI>27), and who had treated or untreated dyslipidaemia or hypertension, to treatment with once daily injections of liraglutide (3.0 mg) or placebo in addition to counselling on lifestyle changes.

Liraglutide …
Factors associated with exacerbation in a general practitioners'-based Swiss chronic obstructive pulmonary disease (COPD) cohort
Authors: Nebal Abu Hussein, Pierre-Olivier Bridevaux, Prashant Chhajed, Jean-William Fitting, Thomas Geiser, Ladina Joos Zellweger, Malcolm Kohler, Sabrina Maier, David Miedinger, Salome Schafroth Török, Robert Thurnheer, Michael Tamm, Jörg Daniel Leuppi
Journal: European Respiratory Journal (2013)

Background: Patients with COPD often suffer from acute exacerbations, which can require hospitalization. Frequent COPD exacerbations are related with higher mortality.  Aim: Our objective was to investigate predictors for exacerbation in a general practitioners’ (GP’s) based Swiss COPD cohort.  Methods: COPD patients from 23 Swiss cantons were screened and enrolled into our cohort. Demographic data, medical treatment, spirometric parameters and exacerbation history were collected and recorded for 24 months. Patients with presumed mild to very severe COPD (GOLD stages I-IV) were seen by their GPs at least twice a year during the study period.  Results: Among 139 GPs, 413 patients (64% male, mean age 68 years), (No COPD 26%, GOLD Stage I 1%, II 23%, III 38%, IV 12%) were analyzed. During the study period of two years, 239 exacerbations occurred (57 patients with > 3 exacerbations, 182 patients with 1-2 exacerbations and 235 patients with no exacerbations. Chronic cough (Hazard Ratio HR 2.29, p =0), sputum production (HR 3.28, p =0) and severe to very severe dyspnea (HR 2.89, 3.96, p =0) were associated with high risk of exacerbation. Cardiovascular diseases (HR 1.45 p =0.02), previous rehabilitation (HR 2.96, p =0), hospitalization (HR 1,709, p = 0.09) and a history of exacerbation at baseline (HR 7.66 p =0) were significantly associated with a future exacerbation.  Conclusion: Exacerbations in the past and symptoms such as sputum production, dyspnea and cough seem to be predictors for future exacerbations in patients with COPD treated in primary–care settings.
Survey of the provision of supportive care services at National Cancer Institute-designated cancer centers.
Authors: P H Coluzzi, M Grant, J H Doroshow, M Rhiner, B Ferrell, L Rivera
Journal: Journal of Clinical Oncology (1995)

The purpose of this survey was to determine the scope of supportive care services (SCS) designed to promote quality of life during cancer therapies at National Cancer Institute (NCI)-designated cancer centers.A survey was mailed to the medical directors and nursing directors of 52 NCI-designated comprehensive (n = 26), clinical (n = 11), and planning cancer centers (n = 15) in the United States. Only one survey was completed from each institution. Survey questions identified services provided such as pain management, terminal care, psychosocial programs, and spiritual care.Thirty-nine questionnaires were received for a total response rate of 75%. Of the respondents, 45% were comprehensive cancer centers, 24% clinical cancer centers, and 29% planning centers. One center did not identify their NCI designation. Sixty-one percent of the centers reported research programs in supportive care. Outside funding was reported in 51% of the respondents, with 39% having American Cancer Society (ACS) or National Institutes of Health (NIH) funding and 28% having private industry funding. Overall SCS self-ratings improved from a 21% rating of excellent to very good 5 years ago to the current 54% rating.Survey results provide data on SCS across a representative sample of NCI cancer centers and can be used to develop standards for future cancer control programs.
Neurohormonal Axis in Patients with Pulmonary Arterial Hypertension
Authors: Frances S. de Man, M. Louis Handoko, Christophe Guignabert, Harm J. Bogaard, Anton Vonk-Noordegraaf
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Despite its description some 25 years ago, neurohormonal activation has long been neglected as an important factor in the pathophysiology of pulmonary arterial hypertension (PAH). Neurohormonal activation was interpreted as a necessary compensatory response to maintain cardiac contractility and systemic blood pressure. Therefore, inhibitors of neurohormonal activity (like β-blockers or angiotensin-converting enzyme inhibitors) are considered contraindicated in current PAH management guidelines. However, recent data revealed that sympathetic overstimulation is strongly related to mortality, and blockade of neurohormonal activity in experimental PAH improved survival and cardiac function. These novel insights shed new light on the role of neurohormonal activity in PAH.
Correlation of 18F-FDG PET/CT with inflammatory biomarkers in sarcoidosis
Authors: Nadja Koren Pucelj, Matevz Harlander, Marko Grmek, Barbara Salobir, Mirjana Zupancic, Marjeta Tercelj
Journal: European Respiratory Journal (2014)

INTRODUCTION  The positive association between 18F-FDG PET/CT (PET/CT) and inflammatory biomarkers of sarcoidosis such as angiotensin converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R) were already described but there is no data on relationship with chitotriosidase (CTO). The aim of our study was to test the correlation of PET/CT with CTO, sIL-2R, ACE.  METHODS  We studied 24 sarcoidosis patients with symptoms of active lung sarcoidosis, who were not treated for sarcoidosis for at least three months. Patients underwent PET/CT (Siemens Biograph mCT). Simultaneously CTO (Perkin-Elmer fluorimeter), sIL-2R, ACE were obtained. Maximal standardized uptake value (SUVmax) was measured in thoracic lymph nodes (LN) and in pulmonary parenchyma (PP).  RESULTS  PET/CT detected inflammation in all patients. Mean value of SUVmax±SD at any location was 17.2±12.5, in LN 15.5±13.8 and in PP 5.9±6.8. There was significant positive relationship (1) of SUVmax at any location with sIL-2R (rho=0.49, p=0.03) and CTO (rho=0.54, p=0.007) but not ACE; (2) of SUVmax in LN with sIL-2R (rho=0.47, p=0.04) and CTO (rho=0.42, p=0.04), but not ACE; (3) and of SUVmax in PP with sIL-2R (rho=0.59, p=0.008) but not CTO nor ACE.  CONCLUSION  The results show for the first time positive correlation of SUVmax with sIL-2R and CTO at any location and in thoracic lymph nodes, while SUVmax in PP correlates only with sIL-2R. These findings could be accounted due to different sources of both biomarkers, since sIL-2R derives mainly from lymphocytes and CTO from macrophages. So both biomarkers could be used to detect active disease and thus reduce the number of radiologic examinations in sarcoidosis patient.
England's chief medical officer asks for review of drug evaluation in wake of statins controversy
Authors: J. Wise
Journal: BMJ (2015)

Pathological hallmarks of Alzheimer9s disease (AD) include amyloid-β (Aβ) plaques, neurofibrillary tangles, and reactive gliosis. Glial cells offer protection against AD by engulfing extracellular Aβ peptides, but the repertoire of molecules required for glial recognition and destruction of Aβ are still unclear. Here, we show that the highly conserved glial engulfment receptor Draper/MEGF10 provides neuroprotection in an AD model of <i>Drosophila</i> (both sexes). Neuronal expression of human Aβ42<sup>arc</sup> in adult flies results in robust Aβ accumulation, neurodegeneration, locomotor dysfunction, and reduced lifespan. Notably, all of these phenotypes are more severe in <i>draper</i> mutant animals, whereas enhanced expression of glial Draper reverses Aβ accumulation, as well as behavioral phenotypes. We also show that the signal transducer and activator of transcription (Stat92E), c-Jun N-terminal kinase (JNK)/AP-1 signaling, and expression of matrix metalloproteinase-1 (Mmp1) are activated downstream of Draper in glia in response to Aβ42<sup>arc</sup> exposure. Furthermore, Aβ42-induced upregulation of the phagolysosomal markers Atg8 and p62 was notably reduced in <i>draper</i> mutant flies. Based on our findings, we propose that glia clear neurotoxic Aβ peptides in the AD model <i>Drosophila</i> brain through a Draper/STAT92E/JNK cascade that may be coupled to protein degradation pathways such as autophagy or more traditional phagolysosomal destruction methods. <b>SIGNIFICANCE STATEMENT</b> Alzheimer9s disease (AD) and similar dementias are common incurable neurodegenerative disorders in the aging population. As the primary immune responders in the brain, glial cells are implicated as key players in the onset and progression of AD and related disorders. Here we show that the glial engulfment receptor Draper is protective in a <i>Drosophila</i> model of AD, reducing levels of amyloid β (Aβ) peptides, reversing locomotor defects, and extending lifespan. We further show that protein degradation pathways are induced downstream of Draper in AD model flies, supporting a model in which glia engulf and destroy Aβ peptides to reduce amyloid-associated toxicity.
Sarcoidosis in India: Investigation into vitamin D and calcium metabolism
Authors: Sagar Chandrashekariah, Deepak Rosha
Journal: European Respiratory Journal (2014)

Introduction: 

Sarcoidosis has been found to be associated with hypervitaminosis D, hypercalcemia and hypercalciuria in Western population( James DG et al . Ann NY Acad Sci 1976;278:321-34 ). However Indian studies( Rosha D et al. Lung India 2000;18(3):70-73 ) have shown lower prevalence of hypercalcemia. Till date no study has analyzed Vitamin D and calcium metabolism in Indian sarcoid patients, for which this study was performed.

Aims and Objectives: 

To study serum Vitamin D levels and Calcium metabolism in Indian Sarcoid patients

Method :

A cross-sectional study was performed in Indraprastha Apollo Hospitals,New Delhi, from July2012 to May2013. 53 Sarcoid patients were enrolled based on cyto/histopathology results. Those on steroids or vitamin D supplements were excluded. Vitamin D and Calcium levels were noted and analyzed by appropriate statistical methods and compared for Vitamin D levels against a control group of 53 non sarcoid subjects.

Result :

Mean Vitamin D level(normal:30–100 ng/ml) was 13.2 ng/ml. Vitamin D deficiency (<30ng/ml) was seen in 51 (96.2%). Hypervitaminosis D was not observed. Mean S.calcium level(normal:8.4-10.2 mg/dl)was 9.05mg/dl. Hypocalcemia was seen in 5(9.4%), normocalcemia in 48(90.6%)and hypercalcemia in none. Control group(n=53) showed a mean Vitamin D levels of 15.07ng/ml with deficiency in 50(94.33%) subjects.

Conclusions :

Our study shows hypovitaminosis D in both cases and controls. Although these patients escape the brunt of hypercalcemia, they may suffer from adverse effects of hypovitaminosis D which can be attributed to inherent prevalence of Vitamin D deficiency in Indian population.Hence, they may rather need calcium and vitamin D supplementation under close monitoring.