tbuckley/cabot-search huggingface dataset:
Coronary calcium and epicardial adipose tissue in patients with chronic obstructive pulmonary disease
Authors: Jorge Zagaceta, Javier Zulueta, Gorka Bastarrika, Inmaculada Colina, Ana B. Alcaide, Arantza Campo, Bartolome Celli, Juan P. de Torres
Journal: European Respiratory Journal (2013)

Rationale: Coronary Artery Calcium (CAC) and Epicardial Adipose Tissue (EAT) volume as determined by CT is an independent marker of cardiovascular events in the general population.   Objectives:  To assess CAC and EAT volume in COPD and explore its association with clinical and physiological variables of disease severity. Methods:  We measured EAT and CAC using CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI.  The variables studied are shown in Table 1. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables.  Results : COPD patients had a higher EAT volume (p=0.02) but found no difference in CAC (p=0.062). In COPD patients, EAT volume was associated with (Table 2): age, pack-years, BMI, gender, FEV 1 %, 6MWD, MMRC and HTN.  Multivariate analysis showed that only pack-years, BMI and 6MWD, predicted EAT volume.  Conclusions:  EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events.
Effect of Dietary Menhaden Oil on Tumor Cell Loss and the Accumulation of Mass of a Transplantable Mammary Adenocarcinoma in BALB/c Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: H Gabor, S Abraham
Journal: JNCI Journal of the National Cancer Institute (1986)

A reduction in the size of transplantable mammary adenocarcinoma IX was achieved when female BALB/c mice were fed isocaloric 10% fat diets containing either hydrogenated cottonseed oil (HCTO) or menhaden oil (MO) as opposed to those mice fed corn oil (CO). Indeed, CO increased the size of the neoplasms when fed alone at 5 or 1% of the diet, although such diets contained less fat calories than did the 10% fat diets containing the other two oils. At the 10% level of dietary fat, enhanced accumulation of tumor mass was observed even when 7.5, 5.0, and 2.5% CO was administered in combination with either HCTO or MO. Although this effect of CO could not be inhibited when nine times as much HCTO was added to the diet, such growth enhancement was abolished when the diet contained nine times as much MO. Hence these experiments emphasized the importance of the type rather than the amount of dietary fat. Whereas MO contained polyunsaturated fatty acids (PUFA's) [approximately 1% as linoleic acid, approximately 16% as 5,8,11,14,17-eicosapentaenoic acid (EPA), approximately 11% as 4,7,10,13,16,19-docosahexaenoic acid (DHA)], HCTO contained none and CO had about 60% of its constituent fatty acids in the form of linoleic acid. The rate of tumor cell loss, determined by the [125I]5-iodo-2'-deoxyuridine method, in the 10% MO-fed or the 10% HCTO-fed mice (54 or 45%, respectively) was more than twice that observed for tumors from the 10% CO-fed mice (22%). These observations were discussed in terms of the influence of the dietary PUFA linoleic acid [C 18:2 (No. of carbons:No. of double bonds), n-6], the PUFA EPA (C 20:5, n-3), and the PUFA DHA (C 22:6, n-3) on the size of mammary tumors and on the involvement of prostaglandins in this process.
High peripheral blast count in adult acute myelogenous leukemia is a primary risk factor for CNS leukemia.
Authors: P A Cassileth, L S Sylvester, J M Bennett, C B Begg
Journal: Journal of Clinical Oncology (1988)

The lengthening remission duration achievable in acute myelogenous leukemia (AML) places patients at risks for CNS leukemic relapse. We reviewed the data on two Eastern Cooperative Oncology Group (ECOG) trials in acute nonlymphocytic leukemia to determine the incidence of CNS leukemia (CNSL). The incidence of CNSL was 5% (30 of 569 patients) overall, and 3% (ten of 331) in patients in complete remission (CR). A number of factors were evaluated for association with increased risk of CNSL. Men more frequently developed CNSL than women at a three to one ratio, and median presenting WBC counts were higher in affected than unaffected patients (44,200/microL v 17,000/microL, P = .01). The low incidence of CNSL in AML supports the view that CNS prophylaxis is unnecessary. However, because 68% of patients (13 of 19) who developed CNSL early in the course of disease had presenting WBC counts greater than 40,000/microL, screening lumbar punctures should be routinely obtained during induction therapy in patients presenting with high circulating blast cell counts.
Extended CSF cytarabine exposure following intrathecal administration of DTC 101.
Authors: S Kim, E Chatelut, J C Kim, S B Howell, C Cates, P A Kormanik, M C Chamberlain
Journal: Journal of Clinical Oncology (1993)

PURPOSE The aims of the present study were to determine ventricular and lumbar CSF pharmacokinetics and the maximum-tolerated dose (MTD) of DTC 101 (DepoFoam; DepoTech Corp, La Jolla, CA) following intraventricular administration. PATIENTS AND METHODS Twelve patients with neoplastic meningitis were treated with escalating doses of DTC 101. CSF samples were obtained from the right lateral ventricle or from the lumbar subarachnoid space and cytarabine concentrations were determined by high-performance liquid chromatography. RESULTS Therapeutic ventricular CSF concentrations were maintained for 9 +/- 2 days following administration of a single dose of DTC 101 into the lateral ventricle. Lumbar cytarabine concentrations became equal to those in the ventricle within the first 6 hours after intraventricular injection, and the subsequent decay in concentrations of free and total cytarabine were the same at both sites. Following intralumbar administration, the peak ventricular concentration of free cytarabine was reached within 1 day, and therapeutic ventricular CSF levels were maintained for several days. Therapeutic intralumbar concentration of free cytarabine was maintained for up to 14 days. The MTD was 75 mg of DTC 101, and seven of nine patients manifested cytologic responses. CONCLUSION Extended CSF exposure to therapeutic cytarabine concentrations was achieved after a single intraventricular or intralumbar dose of DTC 101, permitting drug administration once every 2 weeks.
Pleural ultrasound & the pulmonologist's toolkit
Authors: Burhan Khan
Journal: European Respiratory Journal (2013)

Background: 

The timely and safe investigation,intervention and management of pleural effusions remains discrepant with varying practices; possibly impacting upon quality of care and patient safety.

Following the National Patient Safety Agency 2008 report highlighting 12 deaths from intercostal chest drain, the BTS recommended using ultrasound guidance when inserting chest drains. Moreover,patients with a pleural effusion conventionally have either diagnostic/therapeutic thoracentesis without any image guidance or an “X mark the spot” in the radiology department and then transferred back to the wards for the actual procedure; also posing potential for patient harm.

Methods: 

A retrospective analysis of 3 years experience in a DGH of providing a chest physician deliver inpatient pleural service with bedside pleural ultrasound.

Results: 

Since 2010 over 600 pleural ultrasounds have been performed; with only 3 dry taps and 2 clinically insignificant iatrogenic pneumothoraces. 43% were therapeutic thoracentesis,25% diagnostic,18% ultrasound only with no intervention,and 14% pre chest drain insertion or thoracoscopy, and X” marks the spot are now obsolete.

Conclusions: 

Pleural ultrasound is becoming an essential component in the pulmonologist's armanentarium, enabling prompt assessment and management of pleural effusions. Though it requires work planning and resources it does result in substantial qualitative and quantitative improvements in patient care.Though not all pleural effusions need be aspirated under ultrasound guidance, it is not an exact science to ascertain which effusions can be safely aspirated without imaging. Not infrequently, with the benefit of pleural ultrasound, an invasive pleural intervention may be avoided altogether.
Smoking History and Response to Nivolumab in Patients with Advanced Nsclcs
Authors: M.D. Hellmann, B.C. Creelan, K. Woo, C.S. Sima, W.T. Iams, S.J. Antonia, L. Horn, J.R. Brahmer, S. Gettinger, C. Harbison, N. Rizvi
Journal: Annals of Oncology (2014)
Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines
Authors: Barbara Gerratana
Journal: Medicinal Research Reviews (2010)

Abstract Pyrrolobenzodiazepines (PBDs) are sequence selective DNA alkylating agents with remarkable antineoplastic activity. They are either naturally produced by actinomycetes or synthetically produced. The remarkable broad spectrum of activities of the naturally produced PBDs encouraged the synthesis of several PBDs, including dimeric and hybrid PBDs yielding to an improvement in the DNA‐binding sequence specificity and in the potency of this class of compounds. However, limitation in the chemical synthesis prevented the testing of one of the most potent PBDs, sibiromycin, a naturally produced glycosylated PBDs. Only recently, the biosynthetic gene clusters for PBDs have been identified opening the doors to the production of glycosylated PBDs by mutasynthesis and biosynthetic engineering. This review describes the recent studies on the biosynthesis of naturally produced pyrrolobenzodiazepines. In addition, it provides an overview on the isolation and characterization of naturally produced PBDs, chemical synthesis of PBDs, mechanism of DNA alkylation, and DNA‐binding affinity and cytotoxic properties of both naturally produced and synthetic pyrrolobenzodiazepines. © 2010 Wiley Periodicals, Inc. Med Res Rev
How long does it take for supine gas transfer to become stable after sitting upright
Authors: Liam O'Reilly, Helen Ward, Brendan Cooper
Journal: European Respiratory Journal (2011)

Introduction:  We are interested in using the change in gas transfer from sitting to supine in patients with various lung diseases, but were unable to find any published studies showing how long a subject should be supine before a stable representative measurement could be made. We looked at this in healthy subjects first.   Method:  We measured single breath gas transfer (TLCO & KCO) using a MasterScreen lung function system (Jaeger Ltd, Hochburg, Germany) 3 times sitting at rest and then after approximately 10, 15, 20, 25 & 30 minutes respectively, lying supine in 14 healthy subjects (11F:3M; Ages: 22-51 years).   Results:  The results (Table 1) show that TLCO and KCO increase by about 9% and 15% respectively and VAeff decreases by 5% from sitting to supine. Stability is reached after 15 minutes.   Discussion:  We have shown that changes in gas transfer when supine stabilise after 15 minutes. Unexpectedly, not all subjects showed an increase gas transfer, with 6 showing no increase or a slight decrease when supine. This result needs further explanation.   Conclusion:  Supine gas transfer should be measured after 15minutes lying supine. Not all subjects produced an increase in gas tarnsfer when supine.
Evaluation of inhaler devices device usage skills among the medical personnels (pulmonologist, family physician, nurse), pharmacist and assistant pharmacist
Authors: Didem Gorgun, Filiz Yilmaz, Cigdem Gamze Özkan, Aysin Durmaz, Feyza Nazik
Journal: European Respiratory Journal (2013)

Treatment failure is usually related of improper use of devices. Education of patient is a critical component of treatment and requirs cooperative effort of doctor, nurse and pharmacist. We aimed to evaluate inhaler device usage skills of doctors,nurses, pharmacist and assistant pharmacist who trains patients.  A total number of 120 doctors,nurses, pharmacist and assistant pharmacist included the study. We asked to demostrate the use of each device which are widely used, metered dose inhaler(MDI), diskus, turbuhaler, aerolizer and easyhaler. Correct use of each devices was assessed in ten steps over 10 points.  Mean demostration score for meter dose inhaler 6.5, discus 6.8, turbuhaler 5.8, aerolizer 7.4 and easyhaler 2.9. Mean demostration score for meter dose inhaler, discus, turbuhaler ,aerolizer, easyhaler 6.3, 7.3, 6.6, 7.7, 3.5 in assistant pharmacist, 6.3, 6.8 ,5.5, 6.7, 3.5 in pharmacist, 6.0, 4.8, 7.8, 3.1 in nurses, 6.4, 6.4 ,4.3 ,6.2, 1.4 in family physician, 9.0, 9.5, 9.2, 9.6 in pulmonologist (p  In conclusion we determined high incidence of incorrect usage of inhaler devices among the all groups. We suggest that medical personnel and pharmacist should have adequate and periodically education to increase patient compliance and treatment success.
Recombinant adeno‐associated virus–mediated inhibition of microRNA‐21 protects mice against the lethal schistosome infection by repressing both IL‐13 and transforming growth factor beta 1 pathways
Authors: Xing He, Jun Xie, Dongmei Zhang, Qin Su, Xue Sai, Ruipu Bai, Chao Chen, Xufeng Luo, Guangping Gao, Weiqing Pan
Journal: Hepatology (2014)

Schistosomiasis is a serious parasitic disease in humans, which can lead to liver fibrosis and death. Accumulating evidence indicated that targeting the deregulated microRNAs (miRNAs) could mitigate disease outcomes. Here, we showed that progressive hepatic schistosomiasis caused elevation of miR‐21 and efficient and sustained inhibition of miR‐21 by using highly hepatic tropic adeno‐associated virus serotype 8 (rAAV8), which protected mice against lethal schistosome infection through attenuation of hepatic fibrosis (HF). We demonstrated an additive role of interleukin (IL)−13 and transforming growth factor beta 1 (TGF‐β1) in up‐regulating miR‐21 expression in hepatic stellate cells (HSCs) by activation of mothers against decapentaplegic (SMAD) proteins. Furthermore, down‐regulation of miR‐21 in HSCs reversed HF by enhancing SMAD7 expression, thus repressing TGF‐β1/Smad and IL‐13/Smad pathways. Conclusion : This study suggests the mechanism of IL‐13‐mediated schistosomiasis HF by up‐regulation of miR‐21 and highlights the potential of rAAV8‐mediated miR‐21 inhibition as a therapeutic intervention for hepatic fibrotic diseases, such as schistosomiasis. (H epatology 2015;61:2008–2017)
Prevalence of high risk population for obstructive sleep apnea using STOP-BANG questionnaire in a large urban population
Authors: Farzane Saeidifard, Parisa Adimi, Moein Foroughi, Majid Malekmohammad
Journal: European Respiratory Journal (2014)

Objective:  Obstructive Sleep Apnea (OSA) is the commonest sleep-related breathing disorder. While it is associated with significant morbidities and increased mortality, the majority of people suffering from OSA are left undiagnosed. Epidemiology of OSA is well studied in Western nations, while data on epidemiology of OSA is scarce in other countries. We researched prevalence of OSA in a large urban area (Tehran) in Iran.   Methods:  We randomly selected a total of 4021 individuals above 18 years of age in clusters from different districts of Tehran and surveyed by STOP-BANG questionnaire. Our study questionnaire also inquired about demographic characteristics, education level, history of coronary artery disease and diabetes, and women9s menopausal status. Score of 3 or higher is considered high risk for OSA.   Results:  The study population consisted of 2075 (51.6%) females with the mean age of 40.88(SD=15.4) and mean BMI 26.18(SD=4.43). 51.4% of males and 26.5% of females (a total of 1513 individuals (36.8%)) were labeled as high risk group for OSA according to STOP-BANG. The degree of risk is directly correlated with BMI, older age, history of cardiovascular diseases and diabetes.   Conclusion:  The STOP-BANG classified about 1 out of 3 Tehran9s inhabitants to be at high risk of having OSA. Given the morbidity and mortality of this disorder, it is considered as a major health problem. Further detailed studies with confirmatory tests are recommended in order to plan strategies for detection, treatment and rehabilitation of affected individuals.
Obstructive sleep apnoea is associated with the increased prothrombotic state
Authors: Maria Wilczynska, Keir E. Lewis, P. Rhodri Williams, Sophie Stanford, Matthew Lawrence, Phillip A. Evans
Journal: European Respiratory Journal (2014)

Introduction: Obstructive sleep apnoea (OSA) appears to be an independent factor for arterial and venous thrombosis. Fibrinogen (FBG) and thrombin interactions result in the fibrin clot formation. In a healthy state excessive thrombosis is limited by the activation of fibrinolytic pathway of which tissue plasminogen activator/plasminogen activator inhibitor-1 (TPA/PAI-1) complex is a marker. The aim of this study was to compare morning and afternoon levels of thrombin generation (TG), FBG and TPA/PAI-1 complex in controls and subjects with a newly diagnosed OSA.  Methods: Nineteen patients with newly diagnosed moderate/severe OSA and ten controls with similar symptoms but negative sleep studie were enrolled. Whole blood was collected at 4pm and after sleep the following morning. Tests were performed using the TG Assay (Technoclone Diagnostics, Vienna, Austria), Zymutest TPA/PAI-1 complex assay (Hyphen Biomed, Epsom, UK) and Clauss Fibrinogen assay (Sysmex, Kyoto, Japan).  Results: There were no significant differences in the measured haemostatic factors levels within and between groups (all p>0.05).  Conclusions: Despite lack of significant differences in haemostatic markers levels between and within groups, there was a trend for a higher TG levels in the OSA indicating increased prothrombotic predisposition. Furthermore we observed increased levels of TPA/PAI-1 complex in both groups reflecting impaired fibrinolysis.
Serum adiponectin in hospitalised patients with COPD: Relationship with peripheral muscle function, physical performance and readmissions
Authors: Samantha Kon, Sarah Jones, Bruce Miller, Ruth Tal-Singer, Brigitte Haselden, Jane Canavan, Claire Nolan, Susie Schofield, Paul Cullinan, Michael Polkey, William Man
Journal: European Respiratory Journal (2014)

Background: Adiponectin (APN) is the most abundant systemic adipokine and exerts potent metabolic effects upon skeletal muscle. Skeletal muscle dysfunction is particularly marked in patients hospitalised with acute exacerbation of COPD (AECOPD).

Aims: To determine if APN is associated with muscle strength, muscle mass, physical performance and disease severity in hospitalised patients with AECOPD and if APN at hospital discharge is associated with risk of readmission.

Methods: 100 patients hospitalised with AECOPD were recruited. Measurements made at hospital discharge included APN, handgrip strength (HG), quadriceps maximum voluntary contraction (QMVC), fat free mass (FFM), 4-metre gait speed (4MGS), Short Physical Performance Battery (SPPB) and ADO score. Readmission rates at 90 days were recorded.

Results: Median length of stay was 2.5days. Patient characteristics:mean(SD) age 70(11); 58%male;BMI 26.7(7.1);FEV1%pred 39(19);MRC dyspnoea score 4.0(1.2);HG 25.4kg (11.0);FFM 42.8kg (7.5);4MGS 0.64m/s (0.29);SPPB 6.8(3.0) and ADO 6.2(1.8); median(IQR) QMVC 15.7kg (10.9–21.9) and APN 13500ng/ml (7710-23675). APN was associated with HG (r=-0.30;p=0.002),QMVC (r=-0.40;p<0.001),FFM (r=-0.31;p=0.002),SPPB (r=-0.26;p=0.008) and ADO(r=0.20;p<0.05). There was no association with FEV1%pred. When stratified by quartiles of APN, there were increasing rates of readmission at 90 days with higher levels of APN (Q1 8%;Q2 20%;Q3 28%;Q4 40%;Χ2 for trend p=0.007).

Conclusions: Higher levels of APN in hospitalised patients with AECOPD at discharge are associated with muscle weakness, loss of muscle mass, poor physical performance and increased risk of readmission.
Neutrophil gelatinase-associated lipocalin (NGAL) is a prognostic marker in human primary breast cancer
Authors: M. Bauer, J. Eickhoff, M. Gould, C. Mundhenke, N. Maass, W. Jonat, A. Friedl
Journal: Journal of Clinical Oncology (2008)

22068 Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a small, secreted glycoprotein with proposed functions in cell proliferation, survival and morphogenesis. NGAL is expressed in a variety of tumor types including breast carcinomas, but it is not known whether NGAL contributes directly to breast cancer progression. This study examines the relationship between NGAL expression in breast carcinomas and established clinical prognostic markers as well as clinical outcome. Methods: Tissue microarrays were constructed from tumor samples from 207 patients with primary invasive breast cancer. Immunhistochemistry was used to evaluate NGAL expression. Primary endpoints were disease-specific survival (DSS) and disease-free survival (DFS). The associations between NGAL expression and various clinicopathological markers were assessed via cross-tabulation, χ2-test, and Fisher's exact test. The Kaplan-Meier method was used to analyze DSS and DFS. Cox proportional hazard models were used to determine the prognostic significance of the variables for predictive value for DSS and DFS. Results: The median follow-up time was 6.2 years. NGAL labelling was detected in 33% of the breast carcinomas in a cytoplasmic location. NGAL expression correlated strongly with negative steroid receptor status (p=0.001), HER- 2/neu overexpression (p=0.002), poor histologic grade (p=0.022), the presence of lymph node metastases (p<0.0001) and a high Ki-67 proliferation index (p=0.02). In univariate survival analysis, NGAL expression was associated with decreased disease-specific survival (p=0.015) and decreased disease-free survival (p=0.001) in the entire cohort. In multivariate analysis, NGAL remained an independent prognostic marker for disease-free survival (p=0.02). In a subset of patients with estrogen receptor positive tumors, NGAL was significantly associated with decreased disease-free survival (p=0.037). Conclusions: The results show that NGAL expression is a predictor of poor prognosis in primary human breast cancer and suggest that NGAL detection may provide information for risk assessment and identify a subset of patients requiring more aggressive adjuvant therapy. No significant financial relationships to disclose.