tbuckley/cabot-search huggingface dataset:
Does CT scanning predict the likelihood of a positive transbronchial biopsy in sarcoidosis?
Authors: S de Boer, D G Milne, I Zeng, M L Wilsher
Journal: Thorax (2009)

<h3>Background:</h3> Transbronchial lung biopsy (TBB) has a variable diagnostic yield in sarcoidosis. It was hypothesised that the extent and pattern of parenchymal disease on CT scanning would predict the likelihood of a positive TBB result. <h3>Methods:</h3> Patients with sarcoidosis (n = 77) were included if they had undergone a CT scan within 6 weeks of TBB. Ethnicity, symptoms, pulmonary function and site and results of TBB and bronchoalveolar lavage (BAL) were recorded. CT scans were scored quantitatively for patterns of parenchymal disease (nodular, reticular, consolidation and ground glass) on a lobar basis. <h3>Results:</h3> 39 patients (50.6%) had a positive TBB. Symptoms, ethnicity, treatment, lung volumes and chest radiographic stage were not predictors of a positive biopsy. Female gender, reduced percentage predicted carbon monoxide transfer factor and a higher percentage of lymphocytes in the BAL fluid were associated with a positive biopsy, as were higher total lung score, reticular pattern and ground-glass opacity. The associations were more significant for the total lobar score and the lobar ground-glass score of the lobe biopsied. On multivariate analysis gender, percentage of lymphocytes in the BAL fluid and total lung score were independent predictors of a positive TBB. <h3>Conclusion:</h3> The total extent of parenchymal disease on the CT scan in addition to the pattern and lobar distribution predicts the likelihood of a positive TBB at bronchoscopy.
A Phase II Study of Concurrent Chemoradiation with Weekly Docetaxel, Carboplatin, and Radiation Therapy Followed by Consolidation Chemotherapy with Docetaxel and Carboplatin for Locally Advanced Inoperable Non-small Cell Lung Cancer (NSCLC)
Authors: Anshu K. Jain, Randall S. Hughes, Alan B. Sandler, Afshin Dowlati, Lee S. Schwartzberg, Tracy Dobbs, Larry Schlabach, Jean Wu, Nancy J. Muldowney, Hak Choy
Journal: Journal of Thoracic Oncology (2009)
Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis
Authors: E-M Pfaff, S Becker, A Günther, M Königshoff
Journal: European Respiratory Journal (2010)

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with unknown pathogenesis. The WNT/β-catenin pathway has recently been reported to be operative in epithelial cells in IPF. Dickkopf (DKK) proteins are known to regulate WNT signalling <i>via</i> interaction with Kremen (KRM) receptors, yet their expression and role in the adult lung and in IPF has not been addressed. We analysed the expression, localisation and function of DKK and KRM proteins in IPF lungs using Western blotting, quantitative RT-PCR, immunohistochemistry, ELISA and functional <i>in vitro</i> studies. Enhanced expression of DKK1 and DKK4 and KRM1 was detected in lung homogenates of IPF patients compared with transplant donors. Immunohistochemistry revealed that DKK1 was predominantly localised in basal bronchial epithelial cells. Furthermore, prominent expression of all proteins was observed in hyperplastic alveolar epithelial cells in IPF. Quantitative measurement of DKK1 revealed enhanced protein expression in the bronchoalveolar lumen of IPF patients. Finally, functional studies using human bronchial and alveolar epithelial cell lines demonstrated that WNT-induced epithelial cell proliferation is regulated by DKK1 in a dose-dependent fashion. In summary, DKK proteins are expressed in the lung epithelium in IPF. DKK proteins influence epithelial cell proliferation and may, therefore, be suitable therapeutic targets for IPF.
The effects of galactosamine-induced hepatic failure upon blood-brain barrier permeability
Authors: Warren D. Lo, Steven R. Ennis, Gary W. Goldstein, David L. McNeely, Lorris A. Betz
Journal: Hepatology (1987)

The role of changes in blood-brain barrier permeability in the pathogenesis of hepatic encephalopathy remains uncertain. To test the hypothesis that brain microvessel permeability is nonselectively increased in hepatic encephalopathy we measured the blood-brain barrier permeability-surface area product in rats with acute liver failure induced by intraperitoneal injection of galactosamine. The permeability-surface area products to the diffusion-limited tracers, sucrose and methylaminoisobutyric acid, were determined as a measure of blood-brain barrier permeability. Animals were examined 24, 36 and 42 hr after injection, at times when they were stuporous, but not comatose. No significant elevations of the permeability-surface area products for either compound were detected in clinically affected experimental animals when compared to controls. Our results indicate there is no generalized increase in brain vascular permeability during hepatic insufficiency in precomatose animals.
Modifying Resilience Mechanisms in At-Risk Individuals: A Controlled Study of Mindfulness Training in Marines Preparing for Deployment
Authors: Douglas C. Johnson, Nathaniel J. Thom, Elizabeth A. Stanley, Lori Haase, Alan N. Simmons, Pei-an B. Shih, Wesley K. Thompson, Eric G. Potterat, Thomas R. Minor, Martin P. Paulus
Journal: American Journal of Psychiatry (2014)

Marines who had first received Mindfulness-Based Mind Fitness Training, which can affect brain structures integral to the body’s response to stress, experienced quicker heart rate and breathing rate recovery, improved sleep quality, and lower levels of neuropeptide Y after stressful combat training than a comparison group without the intervention.
Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis
Authors: A C Young, J W Wilson, T C Kotsimbos, M T Naughton
Journal: Thorax (2007)

The clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure PaCO2>45 mm Hg).In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and PaCO2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity.Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2-5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO2 (PtcCO2 mean difference -17 mm Hg; 95% CI -7 to -28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake PaCO2.6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival.
Abstract 4741: Development of a novel therapeutic agent for breast cancer based on a new pathway analysis of triple-negative breast cancer
Authors: Minoru Fujimori, Tomoyuki Fujita, Tamio Mizukami, Tadashi Okawara, Kengo Inoue
Journal: Cancer Research (2012)

Abstract We developed a novel method for drug discovery using active compounds as pharmacodynamic biomarkers in triple-negative breast cancer cell lines. [Materials and Methods] Compounds that selectively inhibit proliferation of triple-negative breast cancer were screened in triple-negative breast cancer cell lines (MDA-MB231, MDA-MB468 and HCC-38) and control MCF7 and HeLa cell lines. A small molecule library was designed to seek structural diversity by chemical informatics and a total of 30,000 synthetic compounds were assessed considering drug similarities. The differences in gene expression profiles in the cell lines between before and after the addition of the selected compounds were analyzed and compared with the control cells. [Results] Seven compounds that exhibited inhibitory effects on the triple-negative breast cancer cell lines were found in the compound library. These compounds exhibited inhibitory activity with IC50-values ranging from 1.2 to 10.8 μM. The results of the microarray analysis indicated several pathways including the irinotecan pathway that changed specifically in the triple-negative breast cancer cell lines by the addition of the compounds.[Conclusion] A research strategy to screen a compound library with structural diversity and develop a drug discovery system using active compounds as pharmacodynamic biomarkers can be widely applied as a new approach for developing innovative personalized medicine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4741. doi:1538-7445.AM2012-4741
Nifedipine-Induced Coronary Vasodilation in Ischemic Hearts Is Attributable to Bradykinin- and NO-Dependent Mechanisms in Dogs
Authors: Masafumi Kitakaze, Hiroshi Asanuma, Seiji Takashima, Tetsuo Minamino, Yasunori Ueda, Yasuhiko Sakata, Masanori Asakura, Shoji Sanada, Tsunehiko Kuzuya, Masatsugu Hori
Journal: Circulation (2000)

Background —Dihydropyridine calcium channel blockers protect endothelial cells against ischemia and reperfusion injury, suggesting that nifedipine may increase the in vivo cardiac NO level and thus coronary blood flow (CBF) in ischemic hearts. We tested this hypothesis. Methods and Results —In open-chest dogs, coronary perfusion pressure (CPP) was reduced in the left anterior descending coronary artery so that CBF decreased to one third of the control level, and thereafter CPP was maintained constant (103±8 to 43±3 mm Hg, n=9). We obtained fractional shortening (FS) and lactate extraction ratio (LER) as indices of regional myocardial contraction and metabolism. Both FS (26.4±2.1% to 6.7±2.0%, n=9, P &lt;0.001) and LER (32±6% to −37±5%, n=9, P &lt;0.001) showed a decrease when CPP was reduced. After intracoronary infusion of nifedipine (4 μg · kg −1 · min −1 ), CBF increased from 30±1 to 48±4 mL · 100 g −1 · min −1 ( P &lt;0.01) without a change of CPP (n=9). Both FS (14.0±1.9%, n=9) and LER (−9±7%, n=9) also increased ( P &lt;0.01). Nifedipine increased the difference in the level of metabolites of NO (nitrate+nitrite; 9±3 to 25±5 nmol/mL, n=9, P &lt;0.01) and bradykinin (22±5 to 58±4 pmol/mL, n=9, P &lt;0.01) between coronary venous and arterial blood. L-NAME (an NO synthase inhibitor) or HOE-140 (a bradykinin receptor antagonist) attenuated ( P &lt;0.05) the increase in CBF (29±3 and 35±2 mL · 100 g −1 · min −1 , n=5 each), FS (4.8±0.6% and 6.9±1.7%, n=5 each), LER (−47±8% and −35±9%, n=5 each), and nitrate+nitrite (3±2 and 8±4 nmol/mL, n=5 each) due to nifedipine infusion. Conclusions —These results indicate that the calcium channel blocker nifedipine mediates coronary vasodilation and improves myocardial ischemia through both bradykinin/NO-dependent and -independent mechanisms.
Vitamin D Inhibits the Formation of Prostatic Intraepithelial Neoplasia in<i>Nkx3.1; Pten</i>Mutant Mice
Authors: Whitney Banach-Petrosky, Xuesong Ouyang, Hui Gao, Kamyar Nader, Yan Ji, Nanjoo Suh, Robert S. DiPaola, Cory Abate-Shen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Epidemiologic studies have shown that reduced levels of vitamin D represent a major risk factor for prostate cancer. In this report, we have examined the efficacy of 1α,25-dihydroxyvitamin D3 (1,25 D3) as a chemopreventive agent using Nkx3.1; Pten mutant mice, which recapitulate stages of prostate carcinogenesis from prostate intraepithelial neoplasia (PIN) to adenocarcinoma. Experimental Design: 1,25 D3 (or vehicle) was delivered continuously to Nkx3.1; Pten mutant or control mice for a 4-month period beginning before (precancerous cohort) or after (cancerous cohort) these mice developed PIN. At the conclusion of the study, the mice were analyzed for the occurrence of PIN and/or cancer phenotypes by histologic analyses and immunostaining using known markers of cancer progression in these mice. Results: We found that sustained delivery of 1,25 D3 to the Nkx3.1; Pten mutant mice resulted in a significant reduction in the formation of PIN while having no apparent effect on the control mice. Furthermore, 1,25 D3 was maximally effective when delivered before, rather than subsequent to, the initial occurrence of PIN. We further show that this 1,25 D3–mediated inhibition of PIN was coincident with up-regulation of vitamin D receptor expression in the prostatic epithelium of the mutant mice, as well as in CASP prostate epithelial cell lines developed from these mice, while having no effect on androgen receptor expression or androgen receptor signaling. Conclusion: Our findings show the value of chemoprevention studies using Nkx3.1; Pten mutant mice, particularly for evaluating the efficacy and underlying mechanisms of potential agents and to gain insights about the optimal timing of their delivery. In particular, our study predicts that vitamin D may have differential effects during early-stage versus late-stage disease and that it is more likely to be beneficial if delivered either before the overt manifestation of clinically detectable disease or during the earliest disease stages, rather than in advanced disease. Thus, our findings support the assessment of vitamin D analogues for chemoprevention in clinical trials targeting patients with early-stage disease and also establish molecular markers that can be used in such trials to determine biological activity and to optimize further clinical trials.
Local anaesthetic thoracoscopy: British Thoracic Society pleural disease guideline 2010
Authors: N. M. Rahman, N. J. Ali, G. Brown, S. J. Chapman, R. J. O. Davies, N. J. Downer, F. V. Gleeson, T. Q. Howes, T. Treasure, S. Singh, G. D. Phillips
Journal: Thorax (2010)

Thoracoscopy under local anaesthetic and intravenous sedation, also known as local anaesthetic thoracoscopy, medical thoracoscopy or pleuroscopy, is increasingly being performed by chest physicians in the UK. In 1999, 11 centres across the UK offered a local anaesthetic thoracoscopy service, increasing to 17 centres in May 20041 and 37 centres in 2009 (Dr N Downer, personal communication). This document, which will use the term ‘local anaesthetic thoracoscopy’, aims to consider the following issues and to make appropriate recommendations on the basis of evidence where available:

Creation of this guideline followed the Appraisal of Guidelines Research and Evaluation/Scottish Intercollegiate Guidelines Network (AGREE/SIGN) methodology of evidence assessment and integration (see introduction to pleural disease guidelines).

Is there a need for a physician-based local anaesthetic thoracoscopy service in the UK? The majority of local anaesthetic thoracoscopy is carried out in the context of an undiagnosed exudative pleural effusion, the commonest cause of which is malignancy.2 This section of the document will therefore focus mainly on local anaesthetic thoracoscopy in the context of malignant disease.

### The increasing burden of pleural disease

Malignant pleural effusion is a common clinical problem. Although the incidence of lung cancer in the UK is falling, the incidence of other cancers is rising. With increasing life expectancy in an ageing population and at current cancer incidence rates, an additional 100 000 cases of cancer per year are expected by 2025.3 Up to 15% of patients who die with malignancy have a pleural effusion at autopsy.4 Studies suggest that exudative effusions are caused by malignancy …
Cuts in social care could put pressure on hospitals to care for dying patients
Authors: A. O'Dowd
Journal: BMJ (2010)

Hospitals in England could face a growing demand for care from patients near the end of their lives if social care budgets are cut, a health policy think tank has warned in a new report.

The Nuffield Trust studied the use and estimated costs of hospital and social care services by 16 479 people at the end of life.

Around half a million people in the United Kingdom die each year; but despite the costs of caring for people at the end of life there is currently a lack of information about care and gaps in knowledge of what services are appropriate.

The trust’s …
ON IMMUNOLOGICAL MEMORY
Authors: Rolf M. Zinkernagel, Martin F. Bachmann, Thomas M. Kündig, Stephan Oehen, Hanspeter Pirchet, Hans Hengartner
Journal: Annual Review of Immunology (1996)

▪ Abstract Immunological memory is a hallmark of the immune system. Evolution can teach us which effector arms of immunological memory are biologically relevant against which virus. Antibodies appear to be the critical protective mechanism against cytopathic viruses. Since these viruses cause cell damage and disease directly, particularly in the absence of an immune response, mothers protect their offspring during a critical immunoincompetent period (a consequence of MHC-restricted T cell recognition) by passive transfer of neutralizing antibodies. In contrast, CTL appear to be the crucial effector mechanism against noncytopathic viruses. Since MHC polymorphism has made vertical transmission of T cell memory impossible, immunoincompetent offspring are not, and need not be, protected against such noncytopathic viruses. During the primary response and again during secondary infection, the most important function of CTL is to eliminate noncytopathic viruses, which may otherwise cause lethal immunopathology. Increased precursor frequencies of B and T cells appear to remain in the host independent of antigen persistence. However, in order to protect against cytopathic viruses, memory B cells have to produce antibody to maintain protective elevated levels of antibody; B cell differentiation into plasma cells is driven by persisting antigen. Similarly, to protect against infection with a noncytopathic virus, CTL have to recirculate through peripheral organs. Activation and capacity to emigrate into solid tissues as well as cytolytic effector function are also dependent upon, and driven by, persisting antigen. Because no convincing evidence is available yet of the existence of identifiable B or T cells with specialized memory characteristics, the phenotype of immunological memory correlates best with antigen-driven activation of low frequency effector T cells and plasma cells.
Use of Nicotinic Acid in the Management of Recurrent Hypoglycemic Episodes in Diabetes
Authors: Fadil Hannan, Peter Davoren
Journal: Diabetes Care (2001)

Chronic administration of nicotinic acid (NA) has been shown to cause a deterioration in glycemic control in diabetic patients (1,2). Acute use of NA inhibits lipolysis in adipose tissue suppressing circulating nonesterfied fatty acid (NEFA) levels. Once the effect of NA abates, NEFA levels increase above baseline (3). According to the Randle cycle hypothesis, when NEFA availability increases, NEFA oxidation occurs at the expense of glucose oxidation with a resultant reduction in glucose uptake by skeletal muscle and an increase in blood glucose levels (4).

Some patients with type 1 diabetes have frequent and often unpredictable hypoglycemic episodes. We hypothesized that the addition of regular oral NA to deliberately …
Five Myths about the HIV Epidemic in Asia
Authors: Peter Godwin, Nigel O'Farrell, Knut Fylkesnes, Sujaya Misra
Journal: PLoS Medicine (2006)

It is widely recognised that the huge population sizes of many Asian countries mean that although national HIV prevalence levels are still very low, very large absolute numbers of people are being infected each year with HIV [1]. Urgent responses are required; the effective responses by countries such as Thailand and Cambodia have shown how much can be done.

As implementers who have worked with HIV/AIDS programmes in several countries in the region, we recognise the public health and welfare costs of the epidemic in Asia, and we respond to the need to “act now”. We are concerned, however, about a number of misinformed beliefs, or myths, about the epidemic—myths that are widely circulating in Asia, disseminated in both public and professional discourse, and often dominating policy and political debate. We believe that these myths, if allowed to underpin and influence policy and programming and guide immediate action, have the potential to seriously jeopardise exactly the kind of focused, coherent, evidence-based programme being called for in Asia and the Pacific.

In this Essay, we set out five myths that are commonly held with regard to HIV in Asia. We also suggest areas of policy that require greater clarity.
Extended-spectrum-beta-lactamase producing multidrug resistant nosocomial bacterial isolates causing lower respiratory tract infection in Tertiary Care Hospital, Nepal
Authors: Manoj Kumar Sah, Ram Krishna Shrestha, Shyam Kumar Mishra, J.B. Sherchand, Basista Rijal, Bharat Mani Pokharel
Journal: European Respiratory Journal (2014)

Introduction

Nosocomial lower respiratory tract infections (LRTI) caused by multi-drug resistant pathogens (MDR) are major threat to the hospitalized patients.Extended-Spectrum-beta-Lactamase (ESBL) producing pathogens are becoming a major concern to treat by medical practitioners now-a-days placing an extra burden on individual patients and on healthcare system.

Aims and objectives

The objectives of this study were to determine the aetiology of nosocomial LRTI along with multidrug resistant bacterial strains producing ESBL.

Methods

A total of 100 bacterial isolates from the patients diagnosed of nosocomial LRTI were studied over a period of one year from March 2011 to February 2012 at Department of Microbiology, Tribhuvan University Teaching Hospital (TUTH). A Combination disk method was done for the detection of ESBL-producing isolates according to guidelines of Clinical Laboratory Standard Institute (CLSI).

Results

Out of total bacterial isolates Acinetobacter calcoaceticus baumannii(Acb) complex was found to more predominant(37%) which were followed by Klebsiella pnemoniae (27%).Alarmingly, (31%) bacterial isolates were recovered ESBL producers in which P. aeruginosa was found to be more predominant(41.2%) followed by K. pnemoniae (29.6%).

Conclusions

We found a high prevalence of MDR bacterial strains producing ESBL in our hospital which prompts a special attention for the management of such patients as well as urgent need for implementation of infection control strategies to prevent the dissemination of such strains.
136 OVEREXPRESSION OF 2-OXOGLUTARATE CARRIER IN HEPATOCELLULAR CARCINOMA OVERCOMES CHOLESTEROL-MEDIATED MITOCHONDRIAL GSH DEPLETION TO EVADE CELL DEATH AND PROMOTE IN VIVO TUMOR GROWTH
Authors: N. Matias, J. Montero, M. Stefanovic, A. Morales, J. Prieto, C. Garcia-Ruiz, A. Colell, J. Fernandez-Checa
Journal: Journal of Hepatology (2011)