tbuckley/cabot-search huggingface dataset:
Utility and validity of NO Vario Analyser® equipment for the determination of nitric oxide in exhaled air (FeNO)
Authors: Luis Fernandez de Rota Garcia, Alicia Padilla Galo, Pilar Fuentes Gala, Yolanda Sanchez Garcia, Maria del Mar Sanchez Jimenez, Francisco Rivas Ruiz, Jose Joaquin Cebrian Gallardo
Journal: European Respiratory Journal (2014)

Introduction:  Determination of FeNO is traditionally performed with chemiluminescence equipments that are not always available. Other devices are appearing lately, portable, simple and less expensive, but in many cases there are no reference values.   Aims: : Determine the cutoffs in FeNO levels by using the NO Vario Analyser® equipment, and determine its correlation with the already-validated Niox-Mino®.   Methods:  A group of healthy controls and patients from our asthma consultation were selected. All subjects underwent a determination of FeNO with both devices in random order.   Results:  42 subjects were included. Its main features and findings are described in Table 1. A direct and statistically significant correlation between FeNO determinations with both devices were observed (p    Conclusions:  NO Vario Analyser equipment has demonstrated validity in determining levels of FeNO with a very good correlation with the already-validated Niox-Mino device, establishing cutoffs of 18.6 and 38.6 to rate FeNO levels in low, intermediate or high.
Nano-antidotes for drug overdose and poisoning
Authors: Vincent Forster, Jean-Christophe Leroux
Journal: Science Translational Medicine (2015)

The number of intoxications from xenobiotics--natural or synthetic foreign chemicals, or substances given in higher doses than typically present in humans--has risen tremendously in the last decade, placing poisoning as the leading external cause of death in the United States. This epidemic has fostered the development of antidotal nanomedicines, which we call "nano-antidotes," capable of efficiently neutralizing offending compounds in situ. Although prototype nano-antidotes have shown efficacy in proof-of-concept studies, the gap to clinical translation can only be filled if issues such as the clinical relevance of intoxication models and the safety profile of nano-antidotes are properly addressed. As the unmet medical needs in resuscitative care call for better treatments, this Perspective critically reviews the recent progress in antidotal medicine and emerging nanotechnologies.
Impaired cardiac output responses to incremental exercise measured by signal-morphology impedance cardiography in advanced COPD
Authors: Luiza Costa, Gabriela Siqueira, Daniela Bravo, Mayron Oliveira, Miguel Rodrigues, J. Alberto Neder
Journal: European Respiratory Journal (2012)

Background : There is renewed interest in the continuous evaluation of cardiac output (Q´T) during exercise in patients with chronic obstructive pulmonary disease (COPD). Signal-morphology impedance cardiography (SMICG) has some advantages over previous impedance approaches and it might be useful to track relative changes in exercise Q´T in this patient population. Objective : To contrast the dynamic changes (Δ) in Q´T as a function of metabolic demand (O2 uptake, ΔV´O2) in patients with advanced COPD and healthy controls. Methods : 15 males with COPD (11 GOLD stages III-IV) and 9 gender-matched controls underwent a ramp-incremental test with Q´T being measured by a commercially-available SMICG system (Physioflow™ PF-05, Manatec, France). ΔQ´T/ΔV´O2 relationship was calculated by linear regression. Results : Patients were significantly younger than controls (61 ± 6 yrs vs. 72 ± 5 yrs, respectively; p 0.05). Interestingly, however, both parameters were lower in patients than controls when Q´T was expressed as fold-changes (0.90 ± 0.30 vs. 1.22 ± 0.18 and 0.43 ± 0.17 vs. 0.61 ± 0.10, respectively; p<0.05). ΔQ´T at maximal exercise was associated with peak V´O2 in controls (r= 0.73; p<0.05) but not in patients (r= 0.12). Conclusions : Semi-quantitative SMICG measurements indicated blunted Q´T adjustments to rapidly-incremental exercise in patients with advanced COPD - even when compared to older healthy controls.
Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer.
Authors: M Rozencweig, W ten Bokkel Huinink, F Cavalli, U Bruntsch, P Dombernowsky, H Høst, V Bramwell, G Renard, M Van Glabbeke, G Decoster
Journal: Journal of Clinical Oncology (1984)

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.
Morbidity of Simple Cholecystectomy and Cholecystectomy with Transduodenal Sphincteroplasty
Authors: Ralph M Antrum, Robert Hall
Journal: Journal of the Royal Society of Medicine (1985)

Exploration of the common bile duct via transduodenal sphincteroplasty is thorough and provides an opportunity for the natural passage of retained calculi. However, this procedure destroys both the sphincter ampulla and sphincter choledochus, the sequelae of which are unknown. Fifty patients who had a transduodenal sphincteroplasty performed between 1970 and 1980 were randomly selected and compared with 50 patients who only had cholecystectomy. They were all seen in the outpatient department, assessed on a modified Visick scale and had liver function tests performed. There was no statistical difference in the subjective quality of result or in the liver function of the sphincteroplasty group when compared with the cholecystectomy patients, which suggests that destruction of the sphincters does not appear to be harmful to the patient.
Efficacy of Combined Pi3K and Angiogenesis Inhibition in Dedifferentiated Liposarcoma (Ddlps)
Authors: P. Schöffski, H. Li, A. Wozniak, J. Cornillie, J. Wellens, T. Van Looy, D. Hompes, L. Friedman, R. Sciot, M. Debiec-Rychter
Journal: Annals of Oncology (2014)
Canakinumab for the Treatment of Children With Colchicine‐Resistant Familial Mediterranean Fever: A 6‐Month Open‐Label, Single‐Arm Pilot Study
Authors: Riva Brik, Yonatan Butbul‐Aviel, Sari Lubin, Eliad Ben Dayan, Tamar Rachmilewitz‐Minei, Lillian Tseng, Philip J. Hashkes
Journal: Arthritis & Rheumatology (2014)
External multicentric validation of a COPD detection questionnaire
Authors: Miguel Bergna, Gabriel Garcia, Ramon Alchapar, Hector Altieri, Oscar Caberlotto, Juan Figueroa Casas, Luis Larrateguy, Luis Nannini, Pedro Grabre, Gustavo Zabert, Daniel Paskansky, Sebastian Fucile
Journal: European Respiratory Journal (2012)

Introduction: Chronic obstructive pulmonary disease (COPD) is a preventable disease. The development of a simple questionnaire can help to improve the diagnosis. Objective: External validation of the questionnaire to detect COPD in Argentina. Material and Methods: We were performed a questionnaire in subjects with over 40 years old and history of smoking ≥ 10 or more pack / year. Demographic data and pre and post bronchodilator spirometry were performed. Subjects with previous diagnosis of COPD or asthma were excluded.  Results. 468 subjects were evaluated.100 (21.1%) had spirometric diagnosis of COPD. In univariate analysis patients with COPD had higher median age (58 years vs 54 years, p   Conclusion This simple questionnaire for demographic and clinical data can be useful for detection of COPD.
N-Acetylcysteine and disease progression in COPD
Authors: K Satkunam
Journal: Thorax (2005)

▴ Decramer M, Rutten-van Molken M, Dekhuijzen PR, et al . Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomized placebo-controlled trial. Lancet2005;365:1552–60

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



It is known that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study the anti-oxidant N-acetylcysteine (NAC) was used to assess whether this drug could …

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In vivo kinetic approach reveals slow SOD1 turnover in the CNS
Authors: Matthew J. Crisp, Kwasi G. Mawuenyega, Bruce W. Patterson, Naveen C. Reddy, Robert Chott, Wade K. Self, Conrad C. Weihl, Jennifer Jockel-Balsarotti, Arun S. Varadhachary, Robert C. Bucelli, Kevin E. Yarasheski, Randall J. Bateman, Timothy M. Miller
Journal: Journal of Clinical Investigation (2015)

Therapeutic strategies that target disease-associated transcripts are being developed for a variety of neurodegenerative syndromes. Protein levels change as a function of their half-life, a property that critically influences the timing and application of therapeutics. In addition, both protein kinetics and concentration may play important roles in neurodegeneration; therefore, it is essential to understand in vivo protein kinetics, including half-life. Here, we applied a stable isotope-labeling technique in combination with mass spectrometric detection and determined the in vivo kinetics of superoxide dismutase 1 (SOD1), mutation of which causes amyotrophic lateral sclerosis. Application of this method to human SOD1-expressing rats demonstrated that SOD1 is a long-lived protein, with a similar half-life in both the cerebral spinal fluid (CSF) and the CNS. Additionally, in these animals, the half-life of SOD1 was longest in the CNS when compared with other tissues. Evaluation of this method in human subjects demonstrated successful incorporation of the isotope label in the CSF and confirmed that SOD1 is a long-lived protein in the CSF of healthy individuals. Together, the results of this study provide important insight into SOD1 kinetics and support application of this technique to the design and implementation of clinical trials that target long-lived CNS proteins.
A Pseudo-Outbreak of Skin Disease in British Troops
Authors: Ashley Croft, Harvey Smith, Ian Creamer
Journal: Journal of the Royal Society of Medicine (1996)

When a newspaper report claimed that a serious outbreak of skin disease had occurred in British Army troops stationed at the Bočac Dam, in western Bosnia, all troops at the Bočac Dam location (n=96), followed by a matched control group of troops (n=91) at a nearby location, were examined by two investigators. 14% of the study population and 21% of the control group were found to have skin disorders. Most were complaints that are commonly encountered in general medical practice. There was a striking absence of skin infestations. The historical consultation rate for skin disorders had not increased. It was concluded that an outbreak of skin disease had not occurred in British troops guarding the dam. This epidemiological study shows that, even under conditions of modern field hygiene, up to one in five soldiers will have skin disease. Skin infestations, however, have become progressively less common during military campaigns this century, probably because of better personal hygiene, good preventive medicine practices and better access to effective health care.
Rivaroxaban for treatment of venous thromboembolism. A real-life perspective in 103 patients
Authors: Raquel Sanchez-Oro-Gomez, Luis Jara-Palomares, Raquel Morillo-Guerrero, Teresa Elias-Hernandez, Marta Ferrer-Galvan, Maribel Asensio-Cruz, Remedios Otero-Candelera
Journal: European Respiratory Journal (2014)

Background: Rivaroxaban is an oral, active direct Factor Xa inhibitor and may be used in patients with venous thromboembolism (VTE).  Objective:To evaluate tolerance, recurrence, bleeding and adverse events in outpatients VTE in treatment with rivaroxaban.  Methods: Prospective study from 2011 to 2013. Inclusion criteria: 1) Above 18 years old, 2) Diagnosis of pulmonary embolism (PE) or Deep vein thrombosis (DVT). Exclusion criteria: 1) creatinine clearance   Results: 103 patients were treated with rivaroxaban, with a mean age of 58+/-17 (Mean +/- standard deviation), and 56% male. There was DVT (64.1 %), EP (18.4 %) and DVT + PE (17.5 %). Rivaroxaban was initial treatment in 30% of patients. In 70% rivaroxaban was initiated after low molecular weight heparin (56%) or vitamin K antagonist (43%) whose the median time of anticoagulant previous rivaroxaban was 16 months [range:1-124 months].  The median time of rivaroxaban treatment was 5 months. There were no deaths or recurrences. There were 6 bleeding, one mayor (acute hemoperitoneum). We had to withdraw treatment in one patient  Conclusions: In our study, rivaroxaban efficacy and safety is consistent with the published randomized clinical trials. The convenience of the dosage, the absence of requirements for periodic controls and few interactions with another drugs regarding VKA requires us to consider rivaroxaban in selected group of VTE.
How much of a role does immunohistochemistry have in reaching a final diagnosis of pleural malignancy in routine clinical practice
Authors: Kerry Woolnough
Journal: European Respiratory Journal (2012)

Introduction   Pleural fluid immunohistochemistry is not recommended in the routine pathological work up of a suspected malignant pleural effusion due to its low sensitivity. However, research has demonstrated its usefulness in diagnosing the primary site of a malignancy, particularly in adenocarcinomas.  We wished to ascertain the frequency of its use and the contribution immunohistochemistry made to identifying the source of metastatic pleural deposits.   Methods   We retrospectively examined all pleural specimens sent for analysis over a 12 month period in patients with confirmed pleural malignancy. We noted the proportion of specimens stained for tumour markers and evaluated the contribution immunohistochemistry made to localising the primary source of the malignancy. These were grouped into three different categories: (i) undiagnostic, (ii) confirmatory and (iii) diagnostic.   Results   A total of 101 pleural specimens were sent for cytological and histological examination. Analysis revealed: 37 adenocarcinomas, 4 squamous cell carcinomas, 1 small cell cancer, 19 malignant mesotheliomas, 1 lymphoma and 1 schwanoma. 10 specimens were reported as malignant cells and 28 samples had no malignant cells present.  42 specimens had additional immunohistochemistry performed. In 2 specimens immunohistochemistry was undiagnostic. It was a confirmatory test in 38% (n=16) and diagnostic in 47.6% (n=20).   Conclusion   We found that immunohistochemistry was underutilised, particularly when cytological analysis revealed malignant cells or adenocarcinoma. In the specimens where these tumour markers were used it was mostly diagnostic in localising the primary for adenocarcinomas.
A low-cost method of managing pleural effusions
Authors: Tiyas Sen Dutt, Syed Tousheed, Kedar Hibare, Murali Mohan, Vipin Gupta
Journal: European Respiratory Journal (2013)

Introduction  Pleural effusions have always been a challenge to manage. In India, lymphocyte-dominant exudative pleural effusions are usually empirically treated as tubercular, largely because medical pleuroscopy is unavailable; diagnosis of malignant pleural effusions can be delayed. We discuss a cost effective way of managing pleural effusions using a fibreoptic bronchoscope (FOB).  Objectives  1) To demonstrate that pleuroscopy can be done successfully with a FOB through an intercostal drain (ICD).  Materials and methods  Eleven consecutive patients with undiagnosed pleural effusions, have undergone FOB pleuroscopy. In the FOB suite, under local anaesthesia and sedation, an intercostal chest drain (ICD) no 32 was introduced into the intercostal space. The FOB was inserted through the ICD and the entire parietal pleura, lung surface and diaphragm were visualised. Multiple parietal pleural biopsies were taken. Where malignancy was confirmed, the same procedure was repeated for pleurodesis.  Results  Among six patients showing a hyperaemic, nodular pleura, and 2 with an apparently normal pleural surface, histopathology showed adenocarcinoma. 6 of these 8 later underwent pleurodesis. In 3 patients with a nodular pleura, the biopsy showed caseating tuberculous granulomas. One patient developed re-expansion pulmonary edema; there were no mortality due to the procedure. The overall diagnostic yield was 91.9 %.  Conclusions  FOB can be used for pleural biopsy and pleurodesis instead of a semi-rigid pleuroscope. There are previous reports of this technique, but this is the first report from India. In resource-limited settings we can adapt low cost, available technology to new uses.
β Hexosaminidase isozymes in human colonic carcinoma
Authors: Michael G. Brattain, Pamela M. Kimball, Thomas G. Pretlow
Journal: Cancer Research (1977)

Isoelectric focusing of crude extracts demonstrated that human colonic carcinomas contained a higher proportion of β-hexosaminidase B than β-hexosaminidase A, while normal human colonic mucosa contained a higher proportion of the A form of the enzyme. Studies of the isolated isozymes showed that β-hexosaminidase B was more stable to heat and more active at low pH than β-hexosaminidase A. Kinetic studies revealed that the A and B forms of β-hexosaminidase had essentially the same Km and Vmax for ρ-nitrophenyl- N -acetyl-β-d-glucosaminide.
Fluorescence In Situ Hybridization on Peripheral-Blood Specimens Is a Reliable Method to Evaluate Cytogenetic Response in Chronic Myeloid Leukemia
Authors: Steven Le Gouill, Pascaline Talmant, Noël Milpied, Axelle Daviet, Michèle Ancelot, Philippe Moreau, Jean-Luc Harousseau, Régis Bataille, Hervé Avet-Loiseau
Journal: Journal of Clinical Oncology (2000)

To evaluate the usefulness of fluorescence in situ hybridization (FISH) on peripheral-blood specimens to evaluate the cytogenetic response to treatment in patients with chronic myeloid leukemia (CML).In a first attempt, we analyzed 62 bone marrow specimens using interphase FISH and compared the results with those of conventional cytogenetics. In a second step, we analyzed 60 paired sets of bone marrow and peripheral-blood specimens with interphase FISH.The results of interphase FISH agreed with conventional cytogenetics on bone marrow for most patients, and only minor differences were found (r =.98). The comparison of interphase FISH on bone marrow versus peripheral-blood specimens showed a strong correlation between these two specimen sources (r =.97).Our results confirmed that FISH is a sensitive technique for the evaluation of response to treatment in patients with CML. Moreover, our study suggests that follow-up of cytogenetic response to therapy can be evaluated on peripheral-blood specimens, thus enabling an easier and more frequent evaluation of patients. The next step will be to evaluate this technique in a large prospective trial to define the prognostic value of complete remissions evaluated by FISH.
Effect of cell type and drug lipophilicity on the extravascular transport of small molecule anticancer drugs: tirapazamine analogs
Authors: Kevin O. Hicks, Kashyap Patel, Frederik B. Pruijn, Michael P. Hay, William R. Wilson
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4107 

Many anticancer drugs must diffuse large distances to reach their target cells. This is potentially an important limitation in anticancer drug development, but the effect of drug physicochemical properties and tumor cell type on extravascular transport of low MW drugs is not well understood. This study investigates the influence of drug lipophilicity (log P7.4) and tumor cell type on the extravascular diffusion of a ‘cassette’ of tirapazamine (TPZ) analogs, by measuring their diffusion coefficients in multicellular layers (MCL) as an in vitro model of the tumor extravascular compartment. Tandem mass spectrometry (Agilent LC/MSD Trap SL) was used to simultaneously measure the concentrations of 6 TPZ analogs and acridan-9(10 H )-one in diffusion chambers separated by an MCL under 95% O2 to suppress any bioreductive metabolism. Diffusion of 3H-mannitol was also measured. The 8 compounds spanned a range of logP7.4 values from -2.62 to 2.97. The data were fitted using Fick’s second law to estimate the diffusion coefficients in the MCL ( DMCL ). In all 4 human cell lines investigated, a sigmoid dependence of DMCL on log P7.4 was observed. In HT29 MCL, the asymptote for DMCL of the more lipophilic compounds (log P7.4 > 1.5) was 15-fold higher than for hydrophilic compounds (log P7.4 < -1) [individual values ranged from 1.8 - 35 × 10-7 cm2 s-1]. Similar log P7.4 dependence was observed in SiHa MCL, but DMCL values [(4.8 - 56) × 10-7 cm2 s-1] were ca. 4 fold greater than in HT29. In well differentiated epithelial HCT8-Sa MCL, the asymptotes differed by 50-fold [individual values (0.32 - 55) × 10-7 cm2 s-1] while a much narrower range [(14 - 59) × 10-7 cm2 s-1] was observed in a variant HCT-8 line (HCT8-Ra) which lacks tight junctions and is histologically poorly differentiated. This study confirmed the usefulness of LC-MS to measure DMCL values simultaneously for a cassette of compounds, and demonstrated significant differences between MCL grown from different cell lines. These differences appear to be related to histological features which affect the relative importance of paracellular versus transcellular diffusion routes (cell packing density and presence of tight junctions). Despite these quantitative differences, increasing analog lipophilicity improved extravascular transport through MCL grown from all four cell lines, suggesting that maximising lipophilicity (within the constraints of other pharmacological processes) has the potential to improve extravascular drug transport in human tumors.