tbuckley/cabot-search huggingface dataset:
Effects on Upper Gastrointestinal Mucosa of Three Delivery Systems of Potassium as Supplement to Frusemide Administration
Authors: J C McLoughlin
Journal: Journal of the Royal Society of Medicine (1985)

Thirty healthy volunteers were recruited into a study to determine the effects on the gastrointestinal mucosa of 3 different delivery systems of oral potassium supplementation associated with diuretic therapy (Diumide-K Continus R tablets, Napp; Lasikal tablets, Hoechst; Lasix and Slow-K R tablets, Hoechst, Ciba). The volunteers were gastroscoped initially and after one week of treatment with one of the three therapies. There was a 60% incidence of erosions in the Lasix + Slow-K group, a 40% incidence in the Lasikal group, but no erosions in the group receiving Diumide-K Continus tablets. It is therefore concluded that Diumide-K Continus tablets incorporate the potassium in a delivery system which is unlikely to cause disruption to the gatrointestinal mucosa.
Adenovirus-Mediated Wild-Type p53 Gene Transfer in Patients Receiving Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Results of a Multicenter Phase II Study
Authors: Martin Schuler, Richard Herrmann, Jacques L.P. De Greve, A. Keith Stewart, Ulrich Gatzemeier, David J. Stewart, Leslie Laufman, Richard Gralla, Jürgen Kuball, Roland Buhl, Claus P. Heussel, Friedrich Kommoss, André P. Perruchoud, Frances A. Shepherd, Mary Ann Fritz, Jo Ann Horowitz, Christoph Huber, Christoph Rochlitz
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in patients undergoing first-line chemotherapy for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable NSCLC were enrolled in an open-label, multicenter phase II study of three cycles of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175 mg/m 2 , day 1), or regimen B, cisplatin (100 mg/m 2 , day 1) plus vinorelbine (25 mg/m 2 , days 1, 8, 15, and 22) in combination with intratumoral injection of 7.5 × 10 12 particles of SCH 58500 (rAd/p53, day 1). Responses of individual tumor lesions were assessed after each cycle, and gene transfer was examined in posttreatment tumor biopsies using reverse transcriptase polymerase chain reaction. RESULTS: There was no difference between the response rate of lesions treated with p53 gene therapy in addition to chemotherapy (52% objective responses) and lesions treated with chemotherapy alone (48% objective responses). Subgroup analysis according to the chemotherapy regimens revealed evidence for increased mean local tumor regressions in response to additional p53 gene therapy in patients receiving regimen B, but not in patients receiving regimen A. There was no survival difference between the two chemotherapy regimens, and the median survival of the cohort was 10.5 months (1-year survival, 44%). Transgene expression was confirmed in tumor samples from 68% of patients, and toxicities attributable to gene therapy were mild to moderate. CONCLUSION: Intratumoral adenoviral p53 gene therapy appears to provide no additional benefit in patients receiving an effective first-line chemotherapy for advanced NSCLC.
Abstract 17848: Evolving Iron Deficiency Confers Most of the Adversity Associated with a Temporal Rise in Red Cell Distribution Width, is More Ominous than a Falling Hemoglobin, and Blunts Left Ventricular Long Axis Function in Chronic Heart Failure
Authors: Klio Konstantinou, Nay Aung, Karl Norrington, Richard Jabbour, Mihir Kelshiker, Hazel K Turner, Mohamad F Barakat, Hua Zen Ling, Suneil Aggarwal, Julia Flint, Jamil Mayet, Darrel P Francis, Martin Thomas, Simon Woldman, Darlington O Okonko
Journal: Circulation (2012)

Background: Whilst a progressive rise in the red cell distribution width (RDW) can reflect many aberrations that exacerbate chronic heart failure (CHF), the combination of a rising RDW and falling ...
Risk of Hospitalized Infection Among Rheumatoid Arthritis Patients Concurrently Treated With a Biologic Agent and Denosumab
Authors: Jeffrey R. Curtis, Fenglong Xie, Huifeng Yun, Kenneth G. Saag, Lang Chen, Elizabeth Delzell
Journal: Arthritis & Rheumatology (2015)

Denosumab is a biologic agent used to treat osteoporosis. Its safety profile given concurrently with biologic drugs for rheumatoid arthritis (RA) has not been well studied. We evaluated hospitalized infections among patients treated with biologic agents for RA who initiated denosumab or zoledronic acid (ZA), a parenteral bisphosphonate without known associations with infection. We hypothesized that the rate of hospitalized infection with denosumab would be noninferior to ZA.We identified RA patients enrolled in Medicare in 2006-2012 treated with biologic agents who initiated denosumab or ZA. Cox proportional hazards models compared the risk for hospitalized infection, comparing denosumab users to ZA users and adjusting for potentially confounding factors. A noninferiority margin was specified a priori to demonstrate that denosumab had no greater infection risk than ZA if the upper bound of the 95% confidence interval (95% CI) of the hazard ratio (HR) was <1.5.Eligible RA patients receiving biologic agents initiated denosumab (n = 1,354) or ZA (n = 4,460). Characteristics of the denosumab users were as follows: mean ± SD age 73.0 ± 8.9, 98.2% women, with a majority receiving infliximab (35.7%) or abatacept (18.6%). Denosumab users had a higher prevalence of prior infections (11.5% hospitalized and 48.3% outpatient) and infection-related risk factors. The crude rate of hospitalized infections for denosumab (14.9/100 person-years [95% CI 12.2-18.1]) was comparable to that for ZA (13.9/100 person-years [95% CI 12.5-15.4]). After adjustment, the HR of hospitalized infection for denosumab users was noninferior to that for ZA users (HR 0.89 [95% CI 0.69-1.15]).The rate of hospitalized infection among RA patients receiving denosumab concurrently with biologic agents for RA was not increased compared to those receiving zoledronate.
Acute and chronic systemic corticosteroid–related complications in patients with severe asthma
Authors: Patrick Lefebvre, Mei Sheng Duh, Marie-Hélène Lafeuille, Laurence Gozalo, Urvi Desai, Marie-Noëlle Robitaille, Frank Albers, Steve Yancey, Hector Ortega, Mark Forshag, Xiwu Lin, Anand A. Dalal
Journal: Journal of Allergy and Clinical Immunology (2015)
Recruiting 5000 more GPs will be tough, NHS chief tells MPs
Authors: Adrian O’Dowd
Journal: BMJ (2015)

Half of the efficiency savings expected of the NHS in England by 2020 should come from improving productivity, alongside savings from prices paid by the NHS, preventing ill health, and moderating demand, MPs have been told.

In a wide ranging evidence session of the House of Commons Health Committee’s inquiry into current issues relating to NHS England, held on 21 July, the head of the NHS also admitted that pressure on GP surgeries was just as intense as pressure in hospitals and that it would be tough to recruit 5000 more GPs in the next five years.

The committee’s chair, Sarah Wollaston, the Conservative MP for Totnes, asked what problems were keeping NHS England’s chief executive, Simon Stevens, awake at night. Stevens replied, “We’ve got to keep current services running well while also redesigning what a …
Gemcitabine, Dexamethasone, and Cisplatin (GDP) As Secondary Chemotherapy In Relapsed/Refractory Peripheral T-Cell Lymphoma
Authors: Stephen Parkin, Joseph M. Connors, Laurie H. Sehn, Diego Villa, Richard Klasa, Alina S. Gerrie, Randy D. Gascoyne, Tamara Shenkier, Cynthia L. Toze, John D. Shepherd, Kevin Song, Kerry J. Savage
Journal: Blood (2013)
IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity
Authors: Philipp Starkl, Thomas Marichal, Nicolas Gaudenzio, Laurent Lionel Reber, Riccardo Sibilano, Mindy Tsai, Stephen Joseph Galli
Journal: Journal of Allergy and Clinical Immunology (2015)
Systemic sclerosis patients9 sera recognize collagen V in experimental scleroderma lung fibrosis
Authors: Natália Borsonello, Ana Paula Velosa, Patricia Martin, Roberta Marangoni, Solange Carrasco, Edwin Parra, Vera Capelozzi, Natalino Yoshinari, Walcy Teodoro
Journal: European Respiratory Journal (2011)

Background:  Type V collagen (COLV) has been recognized as an auto antigen involved in lung transplantation rejection and may be involved in systemic sclerosis pathogenesis (SSc), since immunization of healthy rabbits with this collagen induced an experimental model with similar characteristic of SSc patients.   Objective:  To investigate if SSc patient9s sera recognize COLV present in pulmonary tissue from this model and collagen isolated from supernatant culture of pulmonary fibroblasts from these patients.   Methods:  Immunofluorescence using collagen type I, III and IV adsorved sera from 8 SSc treatment naive patients and from 8 controls was performed to evaluate COLV reactivity in lung tissue from experimental model. These sera were also tested by immunoblotting to evaluate COLV reactivity in collagen isolated from SSc patient9s lung fibroblasts supernatants.   Results:  Positive immunofluorescence reaction was observed when the sera of SSc patients recognized epitopes of COLV in the experimetal model vessels walls and pulmonary interstitium contrasting with the negative reaction observed in the control. Morphometric analysis confirmed these findings, demonstrating a higher COLV reactivity to sera from SSc patients when compared to the control (p=0.0028). Immunoblotting showed that SSc patients sera strongly reacted to COLV standard and to the high molecular weight fragments of COLV isolated from SSc lung fibroblasts culture supernatants, different from control sera reactivity (p=0,02).   Conclusions:  SSc patient9s sera recognize COLV epitopes in experimental model lung tissue and SSc patient9s lung fibroblasts culture suggesting that this protein is an antigen involved in SSc pathogenesis.
Metabolic Characterization of Human Prostate Cancer with Tissue Magnetic Resonance Spectroscopy
Authors: Leo L. Cheng, Melissa A. Burns, Jennifer L. Taylor, Wenlei He, Elkan F. Halpern, W. Scott McDougal, Chin-Lee Wu
Journal: Cancer Research (2005)

Diagnostic advancements for prostate cancer have so greatly increased early detections that hope abounds for improved patient outcomes. However, histopathology, which guides treatment, often subcategorizes aggressiveness insufficiently among moderately differentiated Gleason score (6 and 7) tumors (>70% of new cases). Here, we test the diagnostic capability of prostate metabolite profiles measured with intact tissue magnetic resonance spectroscopy and the sensitivity of local prostate metabolites in predicting prostate cancer status. Prostate tissue samples (n = 199) obtained from 82 prostate cancer patients after prostatectomy were analyzed with high-resolution magic angle spinning proton magnetic resonance spectroscopy, and afterwards with quantitative pathology. Metabolite profiles obtained from principal component analysis of magnetic resonance spectroscopy were correlated with pathologic quantitative findings by using linear regression analysis and evaluated against patient pathologic statuses by using ANOVA. Paired t tests show that tissue metabolite profiles can differentiate malignant from benign samples obtained from the same patient (P < 0.005) and correlate with patient serum prostate-specific antigen levels (P < 0.006). Furthermore, metabolite profiles obtained from histologically benign tissue samples of Gleason score 6 and 7 prostates can delineate a subset of less aggressive tumors (P < 0.008) and predict tumor perineural invasion within the subset (P < 0.03). These results indicate that magnetic resonance spectroscopy metabolite profiles of biopsy tissues may help direct treatment plans by assessing prostate cancer pathologic stage and aggressiveness, which at present can be histopathologically determined only after prostatectomy.
Hypoxia and the hypoxia-regulated transcription factor HIF-1α suppress the host defense of the respiratory epithelium
Authors: Markus Polke, Philipp Lepper, Andreas Kamyschnikow, Frank Langer, Dominik Monz, Christian Herr, Robert Bals, Christoph Beisswenger
Journal: European Respiratory Journal (2014)

Acute and chronic infectious diseases of the respiratory tract, such as pneumonia and cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of respiratory epithelial cells are required to prevent and control infections of the lung. The transcription factor HIF-1α regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1α regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs).Exposure of HBECs to hypoxia or the hypoxia-mimetic agent cobalt chloride (CoCl 2 ) resulted in a significantly decreased expression and release of inflammatory mediators (e.g. IL-6, IP-10) and the antimicrobial peptide hBD-2 in response to bacterial infection with  P. aeruginosa and ligands for Toll-like receptors (flagellin, polyI:C). Small interfering RNA–mediated knockdown of the hypoxia-inducible factor 1α (HIF-1α) in HBECs resulted in increased expression of these factors under normoxic and hypoxic conditions. Hypoxia reduced the antimicrobial activity of HBECs against  P. aeruginosa . The inflammatory response was decreased in lungs of mice infected with inactivated  P. aeruginosa  under hypoxia. These data suggest that hypoxia suppresses the innate immune response of respiratory epithelial cells via HIF-1 α.
Median follow-up in clinical trials.
Authors: J J Shuster
Journal: Journal of Clinical Oncology (1991)

AbstractJanuary 01, 1991 Share on Median follow-up in clinical trials.Author: J J ShusterAuthors Info & AffiliationsPublication: Journal of Clinical OncologyVolume 9, Number 1https://doi.org/10.1200/JCO.1991.9.1.191 Get Access
Sunitinib therapy for patients (pts) with metastatic renal cell carcinoma (mRCC): Updated results of two phase II trials and prognostic factor analysis for survival
Authors: J. E. Rosenberg, R. J. Motzer, M. D. Michaelson, B. G. Redman, G. R. Hudes, R. M. Bukowski, D. J. George, S. T. Kim, C. M. Baum, G. Wilding
Journal: Journal of Clinical Oncology (2007)

5095 Background: Two single-arm phase 2 trials reported a 42% objective response rate (ORR) with sunitinib as second-line therapy in mRCC pts (JAMA 2006;295:2516–24). Efficacy results were updated and an analysis of prognostic factors for survival was performed on pooled data. Methods: Eligibility criteria and treatment plan were nearly identical for both trials. Pts with mRCC who failed =1 prior cytokine-based therapy received sunitinib in repeated 6-week cycles of 50 mg/day orally for 4 weeks, followed by 2 weeks off treatment. Response was assessed by investigators according to RECIST. Pretreatment clinical and biochemical features were examined for prognostic factors by univariate and multivariate analysis (p&lt;0.05 significance level was used in the backward stepwise selection procedure). Results: Updated efficacy data for 168 evaluable pts showed an ORR of 45% (95% CI: 39%, 54%), median progression-free survival (PFS) of 8.4 months (95% CI: 7.9, 10.7), and median overall survival (OS) of 22.3 months (95% CI: 14.8, 36.0). Twenty pts remain on treatment with sunitinib with the longest pt on the drug for &gt;3.5 years with partial response for &gt;3 years. The median duration of response was 11.6 months (95% CI: 9.9, 15.2), and included 1 pt with a complete response for &gt;2 years. The proportion of pts alive at 2 years is 48%. Final prognostic factors for survival in the multivariate model were ECOG PS 0 vs. =1 (p=0.0034); time interval from diagnosis to sunitinib treatment =1 yr vs. &lt;1 yr (p=0.0002); hemoglobin =13 vs. &lt;13 g/dL for males and =11.5 vs. &lt;11.5 g/dL for females (p=0.0002). Conclusions: Median survival is nearly 2 years, which compares favorably to the historical experience (12.7 months) in second-line therapy with other agents (JCO 2004;22:454–63). The influence of sunitinib therapy on patient survival is being investigated in a randomized phase 3 trial compared to interferon-a in first-line therapy for mRCC. Further study of prognostic factors to sunitinib therapy is warranted in the first-line setting. No significant financial relationships to disclose.
Regional ventilation quantified by multi-volume computed tomography (CT): Comparison with 3-helium magnetic resonance imaging (3He-MRI)
Authors: Francesca Pennati, Caterina Salito, James Quirk, Mario Castro, Jason Woods, Andrea Aliverti
Journal: European Respiratory Journal (2014)

Maps of Specific Gas Volume variations (ΔSVg) between different lung volumes have been proposed to identify and quantify the extent and severity of trapped gas in severe emphysema (Aliverti et al, ERJ 2013). The aim of this study was to compare ΔSVg maps to the corresponding  3 He ventilation images.  Five asthmatic subjects were scanned at total lung capacity (TLC) and residual volume (RV) through high-resolution CT. Images at TLC were registered onto the RV scans (Thirion, MedImageAnal 1998),and maps of ΔSVg were obtained by subtracting voxel-by-voxel the two lung volumes. On the same subjects,  3 He ventilation imaging was performed at FRC+1L. ΔSVg and  3 He data were compared per patient by computing the linear correlation between the median values of ΔSVg and  3 He in thirty corresponding regions, selected in ventral, intermediate and dorsal areas at five equally-spaced lung levels between aortic arch (AA) and top diaphragm (TD).  Fig. 1 shows ΔSVg maps (top), the corresponding  3 He-MR images (middle) and their correlation (bottom, R 2 =0.56, p 2 =0.54±0.09 (p  In conclusion, CT-based and  3 He-MRI ventilation imaging show a reasonable correlation in asthmatic subjects, suggesting that ΔSVg maps can be used to identify ventilation defects.
Cloning and sequencing of bovine apolipoprotein A-I cDNA and molecular evolution of apolipoproteins A-I and B-100.
Authors: C O'hUigin, L Chan, W H Li
Journal: Molecular Biology and Evolution (1990)

We have cloned and sequenced bovine apoA-I cDNA. Comparison with the apoA-I sequences of six other vertebrates shows the bovine gene to be most similar to that of the dog. Estimates of substitution rates show that apoA-I evolves approximately 25% faster than an average gene in mammalian lineages. All portions of the coding region evolve at roughly similar rates, suggesting that global conformation is conserved. However, a region of the rat protein has evolved rapidly both relative to other portions of the rat sequence and relative to homologous regions in other mammals. To extend our analysis to other apolipoproteins, we compared four vertebrate apoB-100 sequences. Conserved regions were found to include two putative LDL receptor binding domains, in addition to several regions of unidentified function. Comparison of the apoA-I sequences and the apoB-100 sequences indicates that the latter evolve approximately 40% faster than the former and at twice the average rate for mammalian proteins.
Does azithromycin modify viral load during severe respiratory syncytial virus bronchiolitis?
Authors: Avraham Beigelman, Leonard B. Bacharier, Jack Baty, Richard Buller, Sheila Mason, Kenneth B. Schechtman, Geneline Sajol, Megan Isaacson-Schmid, Mario Castro, Gregory A. Storch
Journal: Journal of Allergy and Clinical Immunology (2015)
In vitro assessment of elastance unloading and work of breathing during proportional assist ventilation
Authors: Olie Chowdhury, Gerrard Rafferty, Simon Hannam, Silke Lee, Anthony Milner, Anne Greenough
Journal: European Respiratory Journal (2012)

Proportional assist ventilation (PAV) is a patient-triggered mode in which the elastic and resistive work of breathing (WOB) can be unloaded. The unloading level is set with the aim of achieving an optimal balance of the WOB between the ventilator and the patient. In vitro studies, however, have shown that during PAV, there are trigger delays and the pressure wave forms of the ventilator and lung models differ which may influence the relationship between the level of unloading and the WOB of the patient and ventilator.   Aim:  To assess the WOB of the ventilator and a lung model with increasing amounts of elastance unloading.   Methods:  A dynamic lung model, with a compliance of 0.4ml/cmH 2 O, was connected to a Stephanie ventilator in PAV mode. Elastance unloading was applied in stepwise increments and pressure, flow and tidal volume were recorded. Pressure/volume loops were constructed, from which the WOB was calculated for the ventilator and the lung model.   Results:  The median tidal volume of breaths analysed was 3.75 (range 3.1 to 4.4) ml. As the elastance unloading was increased, the lung model showed a greater reduction in the elastic WOB than the increase of WOB of the ventilator.  The WOB in the lung model, however, was underestimated by the distortion of the inflation pressure waveform due to the trigger delay.   Conclusion:  Although elastance unloading during PAV enables transfer of the WOB from the patient to ventilator, the infant has no support during the trigger delay, thus the benefit is over-estimated.
A single arm, multicenter, open-label phase II study of orally administered GW572016 as single-agent, second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract. Interim analysis
Authors: J.-P. Machiels, C. Wülfing, D. J. Richel, P. Beuzeboc, X. Garcia Del Muro, M.-O. Grimm, J. Farrell, J. R. Colman, I. A. El-Hariry
Journal: Journal of Clinical Oncology (2004)

4615 Background: GW572016 is an oral, reversible, dual inhibitor of ErbB1 and ErbB2 receptors. This multicenter, phase II trial assessed GW572016 as a single-agent in relapsed urothelial tumors. Objective response rate (RECIST criteria) and toxicity were primary endpoints. Methods: Fifty-eight patients with locally advanced or metastatic urothelial tumors, who had progressed after platinum-based therapy, received 1250 mg GW572016 once daily until disease progression or withdrawal. Safety and efficacy assessments (independent review) were carried out at 4 and 8-week intervals respectively. Patients were also assessed at withdrawal, and followed every 2 months until death. Data from 30 patients were reviewed at an interim analysis (16 weeks on study), and are presented below. Results: The median age was 62 years. Most patients (67%) had visceral metastases. All patients had confirmed expression of ErbB1 and/or ErbB2 (1+, 2+ or 3+ by immunohistochemistry). Only 19 patients (63%) received GW572016 as intended second-line therapy. Three patients (10%) had tumour reduction that was qualified as partial responses (PR) at the initial assessment; however, only one PR was confirmed at 8 weeks. Eight patients (27%) had stable disease (SD), 5 with noted cytoreduction. Clinical benefit (>=6 months SD) was seen in 3 patients (10%). Five patients (17%) had progressive disease, 11 patients (37%) withdrew prior to week 8, and 3 patients (10%) were not evaluable. Disease progression was the most frequent reason for withdrawal. Survival data are not mature at this time. Six patients (20%) experienced serious adverse events of which one, G3 diarrhea, was drug-related as assessed by the investigator. Conclusions: Second-line treatment with oral GW572016 has promising activity and is generally well tolerated in patients with locally advanced or metastatic urothelial tumors. On the basis of these preliminary data, additional trials of GW572016 in urothelial tumors, as mono- or combination therapy, are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline