tbuckley/cabot-search huggingface dataset:
Timed stair climbing to 20 m altitude identifies lung resection candidates with high exercise capacity
Authors: Maurizio Bernasconi, David Maree, Coenraad Koegelenberg, Florian von Groote-Bidlingmaier, Andreas Diacon, Chris Bolliger
Journal: European Respiratory Journal (2011)

Background:  Clinical evaluation for lung resection includes assessment of pulmonary function and maximum oxygen uptake (VO2max). A VO2max of 20ml/kg/min is considered sufficient for pneumonectomy. Stair climbing as a low-cost alternative to formal treadmill cardiopulmonary exercise testing (CPET), is attractive but lacks standardisation.   Methods:  We asked 40 lung resection candidates (bronchiectasis or aspergilloma, n=31; lung cancer, n=7; hydatid cyst, n=2) with FEV1 and/or DLCOc    Results:  Mean elevation reached was 17.2m. Mean peak VO2 during stair climbing was very similar to that during CPET (23.5 vs. 23.6ml/min/kg, p=0.87). Twenty-four patients (60%) reached 20m. There was a good linear correlation between speed of ascent and peak VO2 (r=0.63 for stair climbing and 0.67 for CPET), but 4 of those patients (17%) remained below a peak VO2 of 20ml/kg/min. However, all 16 patients (67%) who reached 20m and climbed with a speed of >15m/min had a VO2 peak of >20ml/min/kg during stair climbing and CPET. No patient with a FEV1  15m/min.   Conclusions:  Speed of ascent of >15m/min accurately identifies patients with a peak VO2 of >20ml/min/kg, thereby obviating the need for CPET in those patients.
Gynaecomastia associated with cimetidine.
Authors: R W Spence, L R Celestin
Journal: Gut (1979)

Gynaecomastia has occurred unilaterally or bilaterally in five out of 25 male duodenal ulcer patients after more than four months treatment with cimetidine 1.6 g daily. All elected to continue treatment to 12 months and their breast enlargement regressed rapidly and disappeared after stopping treatment. During treatment all patients were found to have normal concentrations of plasma testosterone and oestradiol, and serum prolactin was normal in the two patients measured. Excision biopsy of the subareolar tissue in one patient revealed histology typical of the florid stage of gynaecomastia. Blockade of androgen-responsive receptors receptors in the target organ appears to be the most likely mechanism involved.
Peginterferon -2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response
Authors: S M Kamal
Journal: Gut (2005)

<b>Background:</b> The response rates and duration of peginterferon alpha (PEG-IFN-α) and ribavirin combination therapy in chronic hepatitis C genotype 4, the prevalent genotype in the Middle East and Africa, are poorly documented. <b>Aims:</b> To compare the efficacy and safety of 24, 36, or 48 weeks of PEG-IFN-α-2b and ribavirin therapy in chronic hepatitis C genotype 4. <b>Methods:</b> In this prospective, randomised, double blind study, 287 patients with chronic hepatitis C genotype 4 were randomly assigned to PEG-IFN-α-2b (1.5 μg/kg) once weekly plus daily ribavirin (1000–1200 mg) for 24 weeks (group A, n = 95), 36 weeks (group B, n = 96), or 48 weeks (group C, n = 96) and followed for 48 weeks after completion of treatment. Early viral kinetics and histopathological evaluation of pre- and post treatment liver biopsies were performed. The primary end point was viral clearance 48 weeks after completion of treatment. <b>Results:</b> Sustained virological response was achieved in 29%, 66%, and 69% of patients treated with PEG-IFN-α-2b and ribavirin for 24, 36, and 48 weeks, respectively, by intention to treat analysis. No statistically significant difference in sustained virological response rates was detected between 36 and 48 weeks of therapy (p = 0.3). Subjects with sustained virological response showed greater antiviral efficacy (ε) and rapid viral load decline from baseline to treatment week 4 compared with non-responders and improvement in liver histology. The incidence of adverse events was higher in the group treated for 48 weeks. <b>Conclusion:</b> PEG-IFN-α-2b and ribavirin for 36 or 48 weeks was more effective in the treatment of chronic hepatitis C genotype 4 than treatment for 24 weeks. Thirty six week therapy was well tolerated and produced sustained virological and histological response rates similar to the 48 week regimen.
CXC Receptor-1 Silencing Inhibits Androgen-Independent Prostate Cancer
Authors: Nagarajarao Shamaladevi, Dominic A. Lyn, Diogo O. Escudero, Bal L. Lokeshwar
Journal: Cancer Research (2009)

Abstract The CXC receptor-1 (CXCR1) is a coreceptor for interleukin-8 (IL-8) and is expressed on both normal and tumor cells. The function of CXCR1 in prostate cancer was investigated by silencing its expression, using RNA interference. We established stable cell colonies of PC-3 cells, depleted of CXCR1, using lentiviral plasmids (pLK0.1puro) generating small hairpin RNA (shRNA) against CXCR1 mRNA. Stable shRNA transfectants (PLK1–PLK5) that express significantly reduced CXCR1 mRNA (≥90% down) and protein (≥43% down) or vector-only transfectants (PC-3V) were characterized. PLK cells showed reduced cell proliferation (down, ≥66%), due to cell cycle arrest at G1-S phase, decreases in Cyclin D1, CDK4, phosphorylated Rb, and extracellular signal-regulated kinase 1/2 levels compared with those in PC-3V cells. CXCR1 depletion lead to increases in spontaneous apoptosis by mitochondria-mediated intrinsic mechanism and increases in proapoptotic proteins (BAD, 40%; BAX, 12%), but decreases in antiapoptotic proteins (BCL2, down 38%; BCLxL, 20%). PLK2 cells grew as slow-growing tumors (decrease of 54%), compared with that of PC3V tumors in athymic mice. Ex vivo analyses of PLK2 tumor tissues showed reduced expression of Cyclin D1 and vascular endothelial growth factor, and increased apoptosis activity. Other IL-8–expressing prostate cancer cell lines also exhibited similar phenotypes when CXCR1 was depleted by CXCR1 shRNA transfection. In contrast to these cells, CXCR1 depletion had little effect on IL-8 ligand–deficient LNCaP cells. RNA interference rescue using mutated CXCR1 plasmids reversed the silencing effect of PLK2, thus demonstrating the specificity of phenotypic alteration by CXCR1 shRNA. These studies establish that CXCR1 promotes IL-8–mediated tumor growth. [Cancer Res 2009;69(21):8265–74]
Inhibition of Tumor Growth and Progression of LNCaP Prostate Cancer Cells in Athymic Mice by Androgen and Liver X Receptor Agonist
Authors: Chih-pin Chuu, Richard A. Hiipakka, John M. Kokontis, Junichi Fukuchi, Rou-Yu Chen, Shutsung Liao
Journal: Cancer Research (2006)

Abstract Androgen-dependent human LNCaP 104-S tumor xenografts progressed to androgen-independent relapsed tumors (104-Rrel) in athymic mice after castration. The growth of 104-Rrel tumors was suppressed by testosterone. However, 104-Rrel tumors adapted to androgen and regrew as androgen-stimulated 104-Radp tumors. Androgen receptor expression in tumors and serum prostate-specific antigen increased during progression from 104-S to 104-Rrel but decreased during transition from 104-Rrel to 104-Radp. Expression of genes related to liver X receptor (LXR) signaling changed during progression. LXRα, LXRβ, ATP-binding cassette transporter A1 (ABCA1), and sterol 27-hydroxylase decreased during progression from 104-S to 104-Rrel. These coordinated changes in LXR signaling in mice during progression are consistent with our previous findings that reduction of ABCA1 gene expression stimulates proliferation of LNCaP cells. To test if attenuation of LXR signaling may enhance prostate cancer progression from an androgen-dependent state to an androgen-independent state, castrated mice carrying 104-S tumors were given the synthetic LXR agonist T0901317 by gavage. T0901317 delayed progression from 104-S to 104-Rrel tumors. Based on our in vivo model, androgen is beneficial for the treatment of androgen-independent androgen receptor–rich prostate cancer and modulation of LXR signaling may be a potentially useful therapy for prostate cancer. (Cancer Res 2006; 66(13): 6482-6)
Critically ill obstetric patients in an American and an Indian public hospital: comparison of case-mix, organ dysfunction, intensive care requirements, and outcomes
Authors: Uma Munnur, Dilip R. Karnad, Venkata D. P. Bandi, Vijay Lapsia, Maya S. Suresh, Priya Ramshesh, Michael A. Gardner, Stephen Longmire, Kalpalatha K. Guntupalli
Journal: Intensive Care Medicine (2005)
PREDICTORS OF 1-MONTH AND 1-YEAR READMISSION FOR WORSENING OF HEART FAILURE IN AMBULATORY PATIENTS
Authors: Jesus Álvarez-Garcia, Andreu Ferrero, Teresa Puig, Rafael Vazquez, Juan Delgado, Domingo Pascual Figal, Luis Alonso-Pulpon, Jose Ramon Gonzalez Juanatey, Miguel Rivera, Fernando Worner, Alfredo Bardaji Ruiz, Juan Cinca
Journal: Journal of the American College of Cardiology (2014)
The Use of Pulse Oximetry During Conscious Sedation
Authors: Yank D. Coble
Journal: JAMA (1993)

SINCE its introduction in the early 1980s, pulse oximetry has been one of the most rapidly diffusing electronic monitoring technologies in medicine.<sup>1</sup>Use of pulse oximetry during procedures requiring general anesthesia quickly became standard practice in the United States because it is noninvasive, requires no special training, gives continuous realtime estimates of arterial oxygen saturation (SaO<sub>2</sub>) in the range of 70% to 100%, and gives early warning of loss of pulse.<sup>1-3</sup>This report provides background information concerning the development of oximetry technology and its use during "conscious sedation," a state of minimally depressed consciousness elicited by sedating agents used during certain procedures. <h3>HISTORY</h3> Oximetry originated in Germany in the 1930s with the work of Nicolai, Kramer, and Matthes.<sup>4</sup>They studied the kinetics of tissue oxygenation and applied the Beer Lambert law, which relates the concentration of a solute to the intensity of light transmitted through the
Epidemiology of pleural mesothelioma in Northern Sardinia (Italy) from 2000 to 2012
Authors: Valentina Spada, Alessia Azzu, Alessandro Giuseppe Fois, Antonella Arcadu, Paolo Cossu Rocca, Lorenzo Cordero, Marras Teresa, Pirina Pietro
Journal: European Respiratory Journal (2013)

Introduction. Pleural mesothelioma (80% of all forms) has a documented asbestos exposure in 70% of cases. It’s characterized by poor short term prognosis and its incidence is still high in developing countries, while in Italy it’s 3,5-1,3/100000 in males and in females respectively. Incidence and survival rates in Sardinia aren’t yet available.  Aim. To calculate incidence and survival rates of pleural mesothelioma in Northern Sardinia from 2000 to 2012.  Materials and methods. We examined: Health Districts data on discharge diagnosis and death cause (ICD-9-CM codes and subcodes); medical records of Northern Sardinia Health Centers patients. Incidence was calculated on current population of Sassari and Olbia-Tempio provinces and standardized by sex and age on regional population.  Results. Total cases were 60: 78,3% males (M/F: 3,6); mean age 67,6 years. Occupational asbestos exposure was determined/highly probable in 55% of cases. Epithelial forms were 68,3%. Incidence: less than 1 case/100000 from 2000 to 2004, less than 2 from 2005 to 2010, again less than 1 in 2011 and 2012, steadily higher in males than in females (max rates: 2,8 and 0,6 respectively). Survival: 60% up to 1 year after diagnosis, while it falls to 28%, 22%, 20%, 18%, 12% up to 2, 3, 4, 5, more than 5 years respectively; median survival: 13 months (18 in epithelial forms) and not significantly related either with TNM staging or with a specific treatment.  Conclusions. Incidence in Northern Sardinia is lower than at national level and much lower than in provinces that were asbestos industry based until 1992. Other differences compared to national data: median survival (13 vs 9 months) and percentage of epithelial forms (68% vs 51%).
Interferon induction treatment with and without amantadine HCl (AHCl) in patients with chronic hepatitis C
Authors: F.A. Jorge, H. Tanno, E.B. Igartua, L. Pinchuk, J.A. Sorda, J. Curciarello, A. Findor, R. Isla, E. Manero, G. Bianchi, J. Daruich
Journal: Journal of Hepatology (2001)
Cervical gastrostomy in the surgical treatment of oesophageal cancer by reconstruction with the stomach.
Authors: J L Barros
Journal: Thorax (1981)

A technique of cervical gastrostomy is described. Cervical gastrostomy as an alternative to the use of an indwelling nasogastric tube after cervical oesophagogastrostomy after resection for cancer has been used in six patients and appears to have certain advantages in terms of effective gastric decompression, avoiding discomfort to the patient, and simplification of postoperative nursing. It may play a significant role in reducing postoperative mortality from aspiration pneumonitis and other pulmonary complications.
Etanercept combined with methotrexate for high-need psoriasis
Authors: R.J.B. Driessen, P.C.M. van de Kerkhof, E.M.G.J. de Jong
Journal: British Journal of Dermatology (2008)

For some high-need psoriatic patients, the efficacy of etanercept monotherapy is insufficient. In these cases it might be indicated to combine etanercept with other conventional treatments. Objectives To provide daily practice safety and efficacy data for etanercept and methotrexate combination therapy.Data were extracted from an existing database, which contains prospective safety and efficacy data of all patients who were treated with etanercept in clinical practice. A case was defined as a patient using etanercept and methotrexate simultaneously for an indefinite period during follow-up. For all cases, baseline data, Psoriasis Area and Severity Index (PASI) scores, adverse events and laboratory values were investigated. Furthermore, the influence of introduction and discontinuation of methotrexate on these parameters was analysed.Fourteen patients with simultaneous use of etanercept and methotrexate were selected. In six patients, methotrexate was introduced after etanercept to avoid further psoriasis deterioration, which resulted in an improvement of psoriasis in four of these patients. Eight patients were on methotrexate therapy before start of etanercept. Discontinuation of methotrexate in six of these patients resulted in a decrease in PASI improvement in five patients. Etanercept combined with methotrexate was well tolerated, and only mild adverse events were reported. No clinically significant changes in laboratory parameters occurred.Results show that combining etanercept with methotrexate is reasonable when efficacy of etanercept monotherapy is insufficient, or when rapid deterioration of psoriasis after abrupt discontinuation of methotrexate is expected. Laboratory values and adverse events were not different from what would have been expected when using methotrexate alone.
Mutations in pattern recognition receptor genes modulate seroreactivity to microbial antigens in patients with inflammatory bowel disease
Authors: L. Henckaerts, M. Pierik, M. Joossens, M. Ferrante, P. Rutgeerts, S. Vermeire
Journal: Gut (2007)

<h3>Background and aims:</h3> A number of antibodies against microbial epitopes or self-antigens have been associated with Crohn's disease. The development of antibodies reflects a loss of tolerance to intestinal bacteria that underlies Crohn's disease, resulting in an exaggerated adaptive immune response to these bacteria. It was hypothesised that the development of antimicrobial antibodies is influenced by the presence of genetic variants in pattern recognition receptor genes. The aim of this study was therefore to investigate the influence of mutations in these innate immune receptor genes (nucleotide oligomerisation domain (NOD) 2/caspase recruitment domain (CARD) 15, NOD1/CARD4, TUCAN/CARDINAL/CARD8, Toll-like receptor (TLR) 4, TLR2, TLR1 and TLR6) on the development of antimicrobial and antiglycan antibodies in inflammatory bowel disease (IBD). <h3>Materials and methods:</h3> A cohort of 1163 unrelated patients with IBD (874 Crohn's disease, 259 ulcerative colitis, 30 indeterminate colitis) and 312 controls were analysed for anti-<i>Saccharomyces cerevisiae</i> antibodies (gASCA) IgG, anti-laminaribioside antibodies (ALCA) IgG, anti-chitobioside antibodies (ACCA) IgA, anti-mannobioside antibodies (AMCA) IgG and outer membrane porin (Omp) IgA and were genotyped for variants in NOD2/CARD15, TUCAN/CARDINAL/CARD8, NOD1/CARD4, TLR4, TLR1, TLR2 and TLR6. <h3>Results:</h3> When compared with Crohn's disease patients without CARD15 mutations, the presence of at least one CARD15 variant in Crohn's disease patients more frequently led to gASCA positivity (66.1% versus 51.5%, p &lt; 0.0001) and ALCA positivity (43.3% versus 34.9%, p = 0.018) and higher gASCA titers (85.7 versus 51.8 ELISA units, p &lt; 0.0001), independent of ileal involvement. A gene dosage effect, with increasing gASCA and ALCA positivity for patients carrying none, one and two CARD15 variants, respectively, was seen for both markers. Similarly, Crohn's disease patients carrying NOD1/CARD4 indel had a higher prevalence of gASCA antibodies than wild-type patients (63.8% versus 55.2%, p = 0.014), also with a gene dosage effect. An opposite effect was observed for the TLR4 D299G and TLR2 P631H variants, with a lower prevalence of ACCA antibodies (23.4% versus 35%, p = 0.013) and Omp antibodies (20.5% versus 34.6%, p = 0.009), respectively. <h3>Conclusion:</h3> Variants in innate immune receptor genes were found to influence antibody formation against microbial epitopes. In this respect, it is intriguing that an opposite effect of CARD15 and TLR4 variants was observed. These findings may contribute to an understanding of the aetiology of the seroreactivity observed in IBD.
MHC class II genes of a marsupial, the red-necked wallaby (Macropus rufogriseus): identification of new gene families.
Authors: S Schneider, V Vincek, H Tichy, F Figueroa, J Klein
Journal: Molecular Biology and Evolution (1991)

In placental mammals, the class II region of the major histocompatibility complex (Mhc) consists of several gene families which show orthologous relationships in the different species. As these families are not orthologous with the Mhc class II beta-chain-encoding gene families of birds, the different mammalian families must have diverged after the separation of birds and mammals approximately 250 Mya but before the radiation of placental mammals (60-80 Mya). To obtain further information about the origin of the class II genes in mammals, we studied the beta-chain-encoding genes of the wallaby as a representative of marsupials, which split from placental mammals approximately 125 Mya. Three beta-chain-encoding genes were isolated from a red-necked wallaby (Macropus rufogriseus) cDNA library by using a chimpanzee DRB probe, and their nucleotide sequences were determined. The genes are not orthologous to any of the genes in mammals studied thus far but belong to two new families which we designated Maru-DAB and Maru-DBB. One of the three sequences (DAB2) seems to be derived from a transcribed pseudogene; it lacks the codons specifying the first 51 amino acid residues of the beta 2 domain. The fact that the DAB and DBB families have thus far not been found in placental mammals and that none of the DOB, DPB, DQB, or DRB genes seems to be expressed in the one representative marsupial species can be interpreted as suggesting that class II gene families of eutherian and metatherian mammals evolved from different ancestral genes.
Central GLP-2 Enhances Hepatic Insulin Sensitivity via Activating PI3K Signaling in POMC Neurons
Authors: Xuemei Shi, Fuguo Zhou, Xiaojie Li, Benny Chang, Depei Li, Yi Wang, Qingchun Tong, Yong Xu, Makoto Fukuda, Jean J. Zhao, Defa Li, Douglas G. Burrin, Lawrence Chan, Xinfu Guan
Journal: Cell Metabolism (2013)
GS-9219—A Novel Acyclic Nucleotide Analogue with Potent Antineoplastic Activity in Dogs with Spontaneous Non–Hodgkin's Lymphoma
Authors: Hans Reiser, Jianying Wang, Lee Chong, William J. Watkins, Adrian S. Ray, Riri Shibata, Gabriel Birkus, Tomas Cihlar, Sylvia Wu, Bei Li, Xiaohong Liu, Ilana N. Henne, Grushenka H.I. Wolfgang, Manoj Desai, Gerald R. Rhodes, Arnold Fridland, William A. Lee, William Plunkett, David Vail, Douglas H. Thamm, Robert Jeraj, Daniel B. Tumas
Journal: Clinical Cancer Research (2008)

GS-9219, a novel prodrug of the nucleotide analogue 9-(2-phosphonylmethoxyethyl)guanine (PMEG), was designed as a cytotoxic agent that preferentially targets lymphoid cells. Our objective was to characterize the antiproliferative activity, pharmacokinetics, pharmacodynamics, and safety of GS-9219.GS-9219 was selected through screening in proliferation assays and through pharmacokinetic screening. The activation pathway of GS-9219 was characterized in lymphocytes, and its cytotoxic activity was evaluated against a panel of hematopoietic and nonhematopoietic cell types. To test whether the prodrug moieties present in GS-9219 confer an advantage over PMEG in vivo, the pharmacokinetics, pharmacodynamics (lymph node germinal center depletion), and toxicity of equimolar doses of GS-9219 and PMEG were evaluated after i.v. administration to normal beagle dogs. Finally, proof of concept of the antitumor efficacy of GS-9219 was evaluated in five pet dogs with spontaneous, advanced-stage non-Hodgkin's lymphoma (NHL) following a single i.v. administration of GS-9219 as monotherapy.In lymphocytes, GS-9219 is converted to its active metabolite, PMEG diphosphate, via enzymatic hydrolysis, deamination, and phosphorylation. GS-9219 has substantial antiproliferative activity against activated lymphocytes and hematopoietic tumor cell lines. In contrast, resting lymphocytes and solid tumor lines were less sensitive to GS-9219. GS-9219, but not PMEG, depleted the germinal centers in lymphoid tissues of normal beagle dogs at doses that were tolerated. In addition, GS-9219 displayed significant in vivo efficacy in five dogs with spontaneous NHL after a single administration, with either no or low-grade adverse events.GS-9219 may have utility for the treatment of NHL.
Reversal of γ-Radiation-Induced Leukemogenesis in Mice by Immunomodulation with Thiabendazole and Dinitrofluorobenzene&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: S A Elgebaly, R Barton, F Forouhar
Journal: JNCI Journal of the National Cancer Institute (1985)

The effect of thiabendazole (TBZ) and dinitrofluorobenzene (DNFB) on radiation-induced leukemogenesis was investigated in the C57BL/6 mouse model. Administration of TBZ-DNFB during, post, or during and post irradiation successfully blocked leukemogenesis, as indicated by the absence of leukemia blast cells in thymus and peripheral blood, as well as prevented thymic lymphoma. TBZ-DNFB treatment prevented the development of leukemia when studies were terminated both after 7 months of last irradiation (disease fully developed) and after 5 months of last irradiation (disease in the process of development). This TBZ-DNFB treatment also resulted in a significant increase in survival.