tbuckley/cabot-search huggingface dataset:
Characteristics of Polyclonal Endemicity of<i>Pseudomonas aeruginosa</i> Colonization in Intensive Care Units
Authors: MARC J. M. BONTEN, DENNIS C. J. J. BERGMANS, HAN SPEIJER, ELLEN E. STOBBERINGH
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We investigated the endemicity of Pseudomonas aeruginosa in intensive care units (ICUs) through analyses of surveillance cultures (from the rectum, stomach, oropharynx, and trachea; n = 1,089), and clinical cultures (n = 2,393) from 297 consecutive patients. Multiple isolates of P. aeruginosa (n = 353) were genotyped. Variables associated with acquisition of respiratory tract colonization (RTC) were tested in a risk factor analysis. The mean daily prevalence of colonization was 34%. On admission, 22 patients had intestinal colonization and 13 had RTC. Twenty patients acquired colonization in the intestinal and 24 in the respiratory tract. Forty-four different genotypes were found; 38 (86%) were isolated from individual patients only. In all, 37 patients had RTC with a total of 38 genotypes: 13 (34%) were colonized on admission, 9 (24%) acquired RTC with a novel genotype during a stay in the ICU, five (13%) acquired colonization from their intestinal tract and three (8%) were colonized via cross-acquisition. In eight patients (21%), no route could be demonstrated for colonization. Antibiotics providing P. aeruginosa with a selective growth advantage were associated with acquired RTC. Endemicity of colonization with P. aeruginosa is characterized by polyclonality, and seems to be maintained by continuous admittance of colonized patients and selection pressure from antibiotics rather than by cross-acquisition.
Predisposing factors of multi drug resistant tuberculosis (MDR-TB) in Sardjito Hospital, Yogyakarta, Indonesia in 2009-2012
Authors: Antonia Iswari, Aida Hartono, Tjip van der Werf
Journal: European Respiratory Journal (2014)

Background:  The emergence of MDR-TB challenges global TB control. Treatment of MDR-TB is complicated:toxic drugs need to be administered for 20 months, and outcome is generally poor compared to drug-susceptible TB. One determinant of poor outcome may be late detection, and if detection is delayed, transmission may continue in the community. By unveiling the predisposing factors of MDR-TB, new prevention strategies may become available.   Objectives:  To determine predisposing factors of MDR-TB in Sardjito Hospital, Yogyakarta, Indonesia.   Methods:  A retrospective cohort study was carried out, involving 249 medical records of TB patients in Sardjito Hospital.The variables used in this study were patient9s age, gender, comorbidity (Diabetes Mellitus/DM and HIV), socioeconomic status, previous TB treatment status, organ involvement, history of illicit drug use, and unsafe sex among MSM.The data was analyzed with the Chi-square test and simple logistic regression method.   Results: MDR-TB prevalence among all TB cases in Sardjito General Hospital was 5,2%. MDR-TB development was associated with a history of DM (p=0.038) and age >35 years (p=0.003). Individuals with DM had 5.98 times higher risk (95% CI: 1.1-32), while individuals aged >35 had 5.92 times higher risk to develop MDR-TB (95% CI: 1.6-22.1).   Conclusions:  Age>35 and DM emerged as risk factors for MDR-TB among this Indonesian TB population, in this retrospective chart review; if resources are limited to test for MDR-TB we suggest to target these risk groups for testing. Prospective cohort studies should be conducted to confirm these preliminary findings.
Frontal Lobe Dysfunction in Schizophrenia and Parkinson's Disease-a Meeting Point for Neurology, Psychology and Psychiatry: Discussion Paper
Authors: P J Reading
Journal: Journal of the Royal Society of Medicine (1991)

The psychotic features of schizophrenia and the motor problems of Parkinson's disease, respectively, allow striking contrasts to be made between the two disorders. However, it has recently become apparent that the two groups of patients share problems of mentation that are best explained by some dysfunction of the prefrontal cortical areas of the brain. These commonalities are addressed in terms of neurobiological fact and psychological theory, providing possible insight into the neuropsychology of schizophrenia and its dichotomous nature. In particular, the putative role of abnormal frontostriatal interactions in the two disease states is emphasized.
A phase I clinical trial of 2-chlorodeoxyadenosine in pediatric patients with acute leukemia.
Authors: V M Santana, J Mirro, F C Harwood, J Cherrie, M Schell, D Kalwinsky, R L Blakley
Journal: Journal of Clinical Oncology (1991)

To evaluate its toxicity and clinical efficacy in children with relapsed or refractory leukemia, we performed a phase I trial of 2-chloro-2'-deoxy-adenosine (2-chlorodeoxyadenosine; 2-CDA) given as a continuous 5-day infusion at doses of 3 to 10.7 mg/m2/d. In this study of 31 children with acute leukemia, the only dose-limiting toxicity was myelosuppression. At the highest dose level, three of seven patients developed fatal systemic bacterial or fungal infections. At dose levels above 6.2 mg/m2/d, significant oncolytic responses occurred in all patients. In addition, there was a significant correlation between both the responsiveness by cell type and dose of 2-CDA, such that more oncolytic responses were noted in acute myeloid leukemia (AML) patients than acute lymphoblastic leukemia (ALL) patients (P = .02). Although this was a phase I trial in heavily pretreated patients with refractory disease, two AML patients treated at 5.2 and 10.7 mg/m2/d, respectively, had complete hematologic responses, and one patient treated at 10.7 mg/m2/d had a partial response. In addition, there was a dose-response relationship in all patients with improved cytoreduction of peripheral blast cells at higher doses of 2-CDA. In vitro evaluation of 2-CDA uptake and anabolism by leukemic blast cells from 22 patients demonstrated that 2-chloro-2'-deoxyadenosine (Cld-AMP) and 2-chloro-2'-deoxyadenosine 5'-striphosphate (CldATP) reached concentrations close to steady-state levels within 1 hour. Intracellular nucleotide disappearance rates were high with half-lives of 1.29 and 2.47 hours for CldAMP and CldATP, respectively. This suggests that continuous infusion is necessary to maintain the desired plasma concentration. The results of this study confirm the antileukemic activity of 2-CDA and the lack of prohibitive nonhematologic toxicity. Phase II trials in patients with AML and ALL are warranted.
Elevated serum levels of oxidized low-density lipoprotein in COPD patients
Authors: Yongchun Shen, Ting Yang, Tao Wang, Lei Chen, Xiao'ou Li, Fuqiang Wen
Journal: European Respiratory Journal (2013)

Background/Objective   Recent studies suggested oxidized low density lipoprotein (ox-LDL) is involved in oxidative stress and inflammation, which are the key characteristics of chronic obstructive pulmonary disease (COPD). This study aimed to investigate the serum levels of ox-LDL in COPD patients and their correlations with lung function, systematic inflammation and oxidative stress.   Method   48 COPD patients and 32 healthy controls were recruited. Serum ox-LDL and C-reactive protein (CRP) levels were analyzed by enzyme-linked immunosorbent assay, oxidative stress was analyzed by measurement of Reactive Oxygen Species (ROS) with a colorimetric kit.   Results   The clinical summary of included subjects was listed in  Table 1.   The levels of serum ox-LDL were significantly elevated in COPD patients when compared to controls (18.62±7.56 mU/L vs. 12.57±5.90 mU/L, p    Conclusion   Serum ox-LDL levels are increased in COPD patients, and are associated with lung function, systematic inflammation and oxidative stress in COPD.
Accuracy in assessment of acute asthma needs improved to avoid potential adverse outcomes
Authors: Selina Tsim, Lorraine Bridges, Grace Murphy, Peter Kewin
Journal: European Respiratory Journal (2012)

Introduction  Despite comprehensive BTS Asthma Guidelines (2011 revision), there are up to 1200 deaths annually in the UK, 90% due to identifiable and preventable disease, management and psychosocial factors. We retrospectively compared management of acute asthma admissions in a city centre hospital for 1 year (2010) with BTS guidelines to identify key areas for service improvement.   Results  Data was obtained for 72/106 admissions. The majority of admissions were female (70.8%), during winter months (63.9%), and outside normal working hours (65.3%; fig 1A). Initial peak expiratory flow rate (PEFR) and severity guide management decisions. While 79.2% had a best previous PEFR documented, pre- and post treatment PEFR were recorded in only 65.3% and 36.1% respectively. No severity was recorded in 68.1% and there was a tendency to underestimate it (fig 1B). In spite of this 91.7% of admissions were appropriate according to BTS criteria (fig 1C) and there were no subsequent deteriorations resulting in death. Magnesium sulphate is often used to treat severe asthma, and was used appropriately in 75% of patients (fig 1D).   Conclusions  In keeping with previous data (Heaney, BTS adult asthma audit 2010) initial PEFR and severity, key aids to decision making in acute asthma, were routinely not recorded or underestimated. The importance of accurate initial assessment in acute asthma needs to be reinforced to avoid potential adverse outcomes.
Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction
Authors: Nikhil Pal, Nadiya Sivaswamy, Masliza Mahmod, Arash Yavari, Amelia Rudd, Satnam Singh, Dana K. Dawson, Jane M. Francis, Jeremy S. Dwight, Hugh Watkins, Stefan Neubauer, Michael Frenneaux, Houman Ashrafian
Journal: Circulation (2015)

Background— Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF. Methods and Results— We conducted a randomized, crossover study comparing selective heart rate reduction with the I f blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [ o 2 peak] &lt;80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in o 2 peak. Secondary outcomes included tissue Doppler–derived E/e′ at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P &lt;0.0001) and hypertensive (127 versus 145 bpm; P =0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in o 2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg −1 ·min −1 ; P =0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable. Conclusion— Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02354573.
Smoking-induced changes in epithelial lining fluid volume, cell density and protein
Authors: WM Burke, CM Roberts, DH Bryant, D Cairns, M Yeates, GW Morgan, BJ Martin, H Blake, R Penny, JJ Zaunders, al. et
Journal: European Respiratory Journal (1992)

Bronchoalveolar lavage has proved a useful research technique for recovering cellular and molecular contents of the lower respiratory tract. Because the recovered fluid is variably diluted, an accurate estimation of molecular and cellular concentrations can only be made if the epithelial lining fluid volume recovered is also known. It has been suggested that smoking may alter epithelial lining fluid volume by reducing clearance or by stimulating production and, thus, affect the interpretation of bronchoalveolar lavage studies. In this study, urea was used as an endogenous marker of epithelial lining fluid volume in a comparison of 26 smokers and 31 nonsmokers. The mean epithelial lining fluid volume recovered from smokers was significantly greater than that of nonsmokers (2.4 +/- 1.40 ml vs 1.2 +/- 0.75 ml, p less than 0.005). The total cellular concentration in the bronchoalveolar lavage fluid in smokers was also greater (94.2 +/- 46 x 10(6) vs 33.9 +/- 21.5 x 10(6) cells per 300 ml lavage), even when corrected for bronchoalveolar lavage volume recovered (63.1 +/- 32.5 x 10(6) vs 24.9 +/- 13.3 x 10(6) cells per 100 ml recovered lavage fluid). This was true for macrophage, lymphocyte and neutrophil cell numbers. However, when corrected for the apparent epithelial lining fluid volume, only the macrophage count remained significantly higher in the smokers compared with nonsmokers (30.66 +/- 20.7 x 10(6) vs 18.21 +/- 8.6 x 10(6) macrophages.ml-1 ELF). In addition, concentrations of albumin and immunoglobulin M (IgM) were significantly lower in smokers after correction for epithelial lining fluid volume. These results highlight smoking as a confounding factor in the interpretation of bronchoalveolar lavage data.(ABSTRACT TRUNCATED AT 250 WORDS)
Rhinovirus-C infection in children presenting with acute respiratory infection to hospital in Brazil
Authors: David Fawkner-Corbett, Katie Rose, Angela Fonceca, Jailson Correia, Mark Hopkins, Siew-Kim Khoo, Peter N. Le Souef, Paul Stephen McNamara
Journal: European Respiratory Journal (2011)

Introduction:  Human Rhinovirus (HRV) is a common cause of acute respiratory infection (ARI) in children. A new group of Rhinoviruses (Rhinovirus C (HRV-C)) have recently been reported. We aimed to assess the frequency of HRV groups, including HRV-C, in preschool children presenting to a paediatric emergency department with different clinical manifestations and severities of ARI.   Methods:  Children    Results:  630 children were recruited, of whom 54% were hospitalised. Bronchiolitis, pneumonia, viral induced wheeze and upper respiratory tract infection were the commonest clinical diagnoses. HRV was detected in 118 samples (19%), the 4th most common infection after Respiratory Syncytial virus (32%), Adenovirus (29%) and Bocavirus (24%). Preliminary data shows 35% of HRV samples are HRV-C positive. Relationships between clinical manifestation/severity scorings will be examined once sub-typing analysis is complete.   Conclusions:  This study underlines the importance of Rhinovirus infection in preschool children presenting to hospital with ARI. Preliminary data indicates HRV-C subtype is highly prevalent, further analysis will show whether this subtype is associated with particular clinical manifestations and severities of disease.
Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas.
Authors: M Mohiuddin, W F Regine, J Stevens, F Rosato, D Barbot, W Biermann, R Cantor
Journal: Journal of Clinical Oncology (1995)

To evaluate the effectiveness of combined intraoperative radiation therapy (IORT) and perioperative chemotherapy in the management of unresectable pancreatic cancer.Forty-nine patients with localized unresectable adenocarcinoma of the pancreas were treated in a multimodality program of initial IORT and perioperative chemotherapy (fluorouracil [5-FU]/leucovorin) followed by combined external-beam radiation (40 to 55 Gy) and continued chemotherapy. Patients were evaluated for toxicity, pattern of failure, and survival. The follow-up times of these patients range from a minimum of 12 months to a maximum of 62 months, with a median of 28 months.The incidence of perioperative mortality was 0%. Early postsurgical morbidity (grade 3/4) was observed in seven of 49 patients (14%) and late treatment-related morbidity (grade 3/4) in eight of 43 patients (19%) alive beyond 6 months. Morbidity was primarily gastrointestinal (GI), with no hematologic toxicities observed. The median survival time in the total group of patients is 16 months, with a 2-year survival rate of 22% and a 4-year survival rate of 7%. Freedom from local progression of disease was achieved in 71% of patients.The patients who undergo IORT with electrons and treated with perioperative chemotherapy (5-FU leucovorin) followed by additional external-beam radiation and chemotherapy appear to have improved survival, with few early or late complications. Dose escalation of external-beam radiation and chemotherapy may further improve local control of disease and survival of patients.
Neisseria gonorrhoeae population in Arkhangelsk, Russia: phenotypic and genotypic heterogeneity
Authors: M. Unemo, V. Vorobieva, N. Firsova, T. Ababkova, I. Leniv, B.C. Haldorsen, H. Fredlund, V. Skogen
Journal: Clinical Microbiology and Infection (2007)
A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via activation of protein phosphatase PP2A
Authors: Yoshiki Kobayashi, Rossios Christos, Peter Barnes, Kazuhiro Ito
Journal: European Respiratory Journal (2011)

Introduction:  Activation of PI3 kinase causes oxidative stress-induced corticosteroid (CS) insensitivity via HDAC2 reduction. We have recently demonstrated that a novel macrolide/fluoroketolide, solithromycin (Soli, CEM-101) restores CS sensitivity via HDAC up-regulation due to PI3K signaling inhibition (ATS2010). However, the mechanism of this effect has not been elucidated.   Aims:  To investigate the role of a serine/threonine phosphatase PP2A on regulation of the PI3K pathway as the target of Soli.   Methods:  CS sensitivity was determined by IC 50  of dexamethasone (Dex) on TNFα-induced IL-8 production in U937 monocytic cell. Activities of HDAC2 and PP2A were measured by fluorescence-based activity assay. Phosphorylation levels of Akt as a marker of PI3K activation were determined by Western blotting. Okadaic acid (OA) was used to inhibit PP2A as needed.   Results:  OA enhanced H 2 O 2 -induced Akt phosphorylation and HDAC2 reduction in U937 cells, and recombinant PP2A reduced Akt phosphorylation levels. Soli restored Dex sensitivity under H 2 O 2  exposure, but pretreatment with OA abrogated Soli-mediated restoration of Dex sensitivity, inhibition of Akt phosphorylation, and HDAC2 activation. In addition, PP2A immunoprecipitates from the membrane fraction and recombinant PP2A were directly activated by Soli.   Conclusions:  PP2A might be a negative regulator of PI3K signalling. Soli activates PP2A directly, inhibits Akt phosphorylation, then restores HDAC2 activity, resulting in the restoration of CS sensitivity under oxidative stress. Thus, Soli may be a potential treatment for steroid insensitive diseases such as COPD and severe asthma.
Biology of TACE inhibition
Authors: R C Newton, K A Solomon, M B Covington, C P Decicco, P J Haley, S M Friedman, K Vaddi
Journal: Annals of the Rheumatic Diseases (2001)

Studies conducted over the past decade have demonstrated a central role for tumour necrosis factor alpha (TNFalpha) in inflammatory diseases. As a result of this work, a number of biological agents that neutralise the activity of this cytokine have entered the clinic. The recent clinical data obtained with etanercept and infliximab highlight the relevance of this strategy. TNFalpha converting enzyme (TACE) is the metalloproteinase that processes the 26 kDa membrane bound precursor of TNFalpha (proTNFalpha) to the 17 kDa soluble component. Although a number of proteases have been shown to process proTNFalpha, none do so with the efficiency of TACE. A series of orally bioavailable, selective, and potent TACE inhibitors are currently in clinical development. These inhibitors effectively block TACE mediated processing of proTNFalpha and can reduce TNF production by lipopolysaccharide stimulated whole blood by >95%. Through a series of studies it is shown here that >80% of the unprocessed proTNFalpha is degraded intracellularly. The remainder appears to be transiently expressed on the cell surface. Although, in vitro, TACE inhibition has also been implicated in shedding of p55 and p75 surface TNFalpha receptors, the in vivo data cast doubt on the consequences of this finding. In a mouse model of collagen-induced arthritis, the inhibitors are efficacious both prophylactically and therapeutically. The efficacy seen is equivalent to strategies that neutralise TNFalpha. In many studies greater efficacy is observed with the TACE inhibitors, presumably owing to greater penetration to the site of TNFalpha production.
Adjuvant-dependent immune response to malarial transmission-blocking vaccine candidate antigens.
Authors: D J Rawlings, D C Kaslow
Journal: The Journal of Experimental Medicine (1992)

Immune responses in major histocompatibility complex (MHC)-disparate congenic mouse strains immunized with sexual stage malaria parasites or purified recombinant protein were adjuvant dependent. Whereas mice exhibited a limited antibody response to immunization with newly emerged Plasmodium falciparum gametes in Freund's adjuvant, all five congenic mouse strains responded to several transmission-blocking vaccine candidate antigens, when parasites were emulsified in a monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) adjuvant. The humoral response in those animals immunized with the antigen in a MPL/TDM adjuvant was helper T cell dependent, as evident by boosting of the antibody response after a second immunization. If the immunogen consisted of purified recombinant protein, then the immune response was not MHC class II limited in mice immunized with either complete Freund's adjuvant or TDM/MPL. The potential role of adjuvants in overcoming apparent immune nonresponsiveness and the implications for development of a malaria transmission-blocking vaccine are discussed.
Solubilization and Degradation of Extracellular Matrix by Various Metastatic Cell Lines Derived From a Rat Rhabdomyosarcoma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M Becker, M Moczar, M F Poupon, E Moczar
Journal: JNCI Journal of the National Cancer Institute (1986)

Examination by use of WAG syngeneic female rats was made on 4 rat rhabdomyosarcoma sublines expressing different metastatic potentials for their abilities to degrade proteoglycans and glycoproteins of the extracellular matrix (ECM), deposited by corneal endothelial cells and metabolically labeled with [3H]glycosamine and [35S]sulfate. Of the label incorporated in ECM, 10-20% was released in the culture medium in 3 days by the cell lines studied. The proteoglycans, glycosaminoglycans, and glycoproteins released by the cells from ECM were separated and partially characterized. Most of the ECM glycoproteins were recovered in the region of 200,000 (200K) on gel chromatography. Glycopeptides of 10K-20K apparent molecular weight were minor components. The glycosaminoglycan chains of the proteoheparan sulfate were partially hydrolyzed to 20K fragments. Tumor cells increased also the solubilization of the nondegraded matrix macromolecules. About 5-8% of the radioactivity of the ECM remained associated with the tumor cells detached from the ECM. ECM degrading activity of the sublines did not correlate with their ability to colonize the lungs after iv injection but did correlate with their ability to metastasize to the lungs from the primary subcutaneous site.