tbuckley/cabot-search huggingface dataset:
Prognostic Role of <i>Interleukin-1β</i> Gene and <i>Interleukin-1 Receptor Antagonist</i> Gene Polymorphisms in Patients With Advanced Gastric Cancer
Authors: Francesco Graziano, Annamaria Ruzzo, Daniele Santini, Bostjan Humar, Giuseppe Tonini, Vincenzo Catalano, Rossana Berardi, Francesca Pizzagalli, Federica Arduini, Italo Bearzi, Mario Scartozzi, Stefano Cascinu, Enrica Testa, Rita Ficarelli, Mauro Magnani
Journal: Journal of Clinical Oncology (2005)

A high interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-RN) ratio underlies an unfavorable proinflammatory status. Also, it seems to be involved in the mechanisms of cancer cachexia and tumor angiogenesis and metastasis. Two single nucleotide polymorphisms in IL-1B gene (IL-1B-511C/T,IL-1B-31T/C) and a variable number of tandem repeat polymorphisms in IL-RN gene (IL-1RNlong/2) enhance the circulating levels of the two cytokines. The prognostic role of IL-1B/IL-1RN genotypes was investigated in patients with relapsed and metastatic gastric cancer treated with palliative chemotherapy.Before starting palliative chemotherapy, 123 prospectively enrolled patients supplied peripheral-blood samples for DNA extraction. Survival data were analyzed according to IL-1RN/IL-1B genotypes.Forty-two patients showed wild-type genotypes (IL-1RNlong/long, IL-1B-511C/C, and IL-1B-31T/T; group A). Forty-five patients showed the IL-1RN2 polymorphism, with wild-type IL-1B genotypes in seven patients and with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms in 38 patients (group B). The remaining 36 patients demonstrated wild-type IL-1RN, with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms (group C). In group A and B patients, the median progression-free survival (PFS) was 25 and 26 weeks, respectively, and median overall survival (OS) was 42 and 43 weeks, respectively. Group C patients showed worse PFS (median, 16 weeks) and OS (median, 28 weeks) than group A (P = .006 for PFS; P = .0001 for OS) and group B patients (P = .01 for PFS; P = .0001 for OS). The long/T/C haplotype was overrepresented in patients with shortened PFS (P = .001) and OS (P = .0005).In patients with advanced gastric cancer, IL-1B polymorphisms showed adverse prognostic influence when coupled with wild-type IL-1RN genotype. These findings deserve further investigation for potential anticancer activity of recombinant IL-RN.
A phase I, pharmacokinetic and biologic correlative study of oblimersen sodium (Genasense™, G3139) and irinotecan in patients with metastatic colorectal cancer
Authors: M.M. Mita, L. Ochoa, E.K. Rowinsky, J. Kuhn, G. Schwartz, L.A. Hammond, A. Patnaik, I.-T. Yeh, E. Izbicka, K. Berg, A.W. Tolcher
Journal: Annals of Oncology (2005)
GPs and patients clash over use of premium rate phone lines
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Poor communication between primary care trusts and GPs is seriously compromising the safety of patients in England, a group of MPs said this week.In its latest report the House of Commons Committee of Public Accounts also warns that 96% of GPs are failing to report dangerous incidents to the National Patient Safety Agency.For its report, which examines the Department of Health's progress in implementing clinical governance in primary care, the committee had taken evidence from the chief executive of the NHS, the deputy chief medical officer, and the NHS's director general of commissioning.Committee chairman Edward Leigh said, "Too many primary care organisations are paying lip service to the principles of the Department of Health's clinical governance agenda.The lines of communication between the primary care trusts, on the one hand, and their GPs and other healthcare contractors, on the other, are defective."He added: "How can we be confident in the NHS's ability to share learning locally and nationally about what can go wrong in health care when only a tiny proportion of GPs-4%-routinely report patient safety events and incidents to the National Patient Safety Agency?"In response to a series of high profile problems in the 1990s, including the Shipman murders and events at the Bristol Royal Infirmary, the health department introduced its 10 year programme to boost patient safety.The centrepiece was the clinical governance system.The new report suggests, however, that clinical governance is not as well established in primary care as in secondary care.The committee says that this is due largely to the complexity of the role of primary care trusts in commissioning and providing care and to the independence of contractors delivering health care, particularly GPs.The Committee of Public Accounts' 47th report of the current session can be found at www. parliament.uk/pac.Primary� care pay�s only� "lip service" to clinical governance, MPs say� UK NEWS Regulator gives green light to research using human-animal embryos, p 531 WoRld NEWS US me�ical authorities are accuse� o�� ��ailing to act over �octors in �uantanamo, p 53� US me�ical authorities are accuse� o�� ��ailing to act over �octors in �uantanamo, p 53� , p 53� bmj.comNumber o�� bipolar �isor�er �iagnoses leaps among US young people Number o�� bipolar �isor�er �iagnoses leaps among US young people
Immuno-oncology Combinations: A Review of Clinical Experience and Future Prospects
Authors: Scott J. Antonia, James Larkin, Paolo A. Ascierto
Journal: Clinical Cancer Research (2014)

Immuno-oncology is an evolving treatment modality that includes immunotherapies designed to harness the patient's own immune system. This approach is being studied for its potential to improve long-term survival across multiple tumor types. It is now important to determine how immunotherapies may be most effectively used to achieve the best possible patient outcomes. Combining or sequencing immunotherapies that target distinct immune pathways is a logical approach, with the potential to further enhance the magnitude of the antitumor immune response over single agents. Early clinical data in patients with melanoma treated with two immune checkpoint inhibitors, ipilimumab and nivolumab, suggest support for this combination approach. Numerous other combination approaches are being evaluated in early-phase clinical trials; however, their clinical activity remains unknown. Clinical experience to date has shown that when combining an immuno-oncology agent with an existing therapeutic modality, it is important to determine the optimal dose, schedule, and sequence.
Increased production of nitric oxide in coronary arteries during congestive heart failure.
Authors: B O'Murchu, V M Miller, M A Perrella, J C Burnett
Journal: Journal of Clinical Investigation (1994)

Experiments were designed to determine whether a heterogeneity of endothelium-dependent relaxations in arteries from different vascular beds exists in experimental congestive heart failure (CHF) and to determine the mediators of those responses. CHF was produced in dogs by rapid ventricular pacing for 15 d. Rings of coronary, femoral, and renal arteries with and without endothelium from control and CHF dogs were suspended in organ chambers for measurement of isometric force. In arteries contracted with prostaglandin F2 alpha, endothelium-dependent relaxations to BHT 920 (an alpha 2-adrenergic agonist) were increased in coronary arteries from dogs with CHF (maximal relaxation: control -15 +/- 9% vs CHF -92 +/- 5%; n = 5-6; P < 0.05), with a modest enhancement in renal arteries. Relaxations to adenosine diphosphate and the calcium ionophore were unchanged. Relaxations to BHT 920 in CHF were reduced by NG monomethyl-L-arginine (L-NMMA) and pertussis toxin but not by indomethacin. These data suggest that endothelium-dependent relaxations are affected heterogeneously in CHF. The enhanced response to alpha 2-adrenergic agonists in the coronary artery is mediated by nitric oxide through a mechanism sensitive to inhibition by pertussis toxin. This selective increase in endothelium-dependent relaxations in the coronary artery may contribute to preserving coronary blood flow during CHF.
Autophagy in Pulmonary Diseases
Authors: Kiichi Nakahira, Maria Angelica Pabon Porras, Augustine M. K. Choi
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The pathogenesis of pulmonary diseases is often complex and characterized by multiple cellular events, including inflammation, cell death, and cell proliferation. The mechanisms by which these events are regulated in pulmonary diseases remain poorly understood. Autophagy is an essential process for cellular homeostasis and stress adaptation in eukaryotic cells. This highly conserved cellular process involves the sequestration of cytoplasmic components in double-membrane autophagosomes, which are delivered to lysosomes for degradation. The critical roles of autophagy have been demonstrated in a wide range of pathophysiological conditions. Emerging studies have identified that autophagy plays important roles in the pathogenesis of various lung diseases. In addition, autophagy has been shown to selectively degrade subcellular targets, including proteins, organelles, and pathogens. Here, we highlight the recent advances in the molecular regulation and function of autophagy in lung diseases.
Magnetic Resonance Imaging in Multiple Myeloma: Diagnostic and Clinical Implications
Authors: Ronald Walker, Bart Barlogie, Jeffrey Haessler, Guido Tricot, Elias Anaissie, John D. Shaughnessy, Joshua Epstein, Rudy van Hemert, Eren Erdem, Antje Hoering, John Crowley, Ernest Ferris, Klaus Hollmig, Frits van Rhee, Maurizio Zangari, Mauricio Pineda-Roman, Abid Mohiuddin, Shmuel Yaccoby, Jeffrey Sawyer, Edgardo J. Angtuaco
Journal: Journal of Clinical Oncology (2007)

Magnetic resonance imaging (MRI) permits the detection of diffuse and focal bone marrow infiltration in the absence of osteopenia or focal osteolysis on standard metastatic bone surveys (MBSs).Both baseline MBS and MRI were available in 611 of 668 myeloma patients who were treated uniformly with a tandem autologous transplantation-based protocol and were evaluated to determine their respective merits for disease staging, response assessment, and outcome prediction.MRI detected focal lesions (FLs) in 74% and MBS in 56% of imaged anatomic sites; 52% of 267 patients with normal MBS results and 20% of 160 with normal MRI results had FL on MRI and MBS, respectively. MRI- but not MBS-defined FL independently affected survival. Cytogenetic abnormalities (CAs) and more than seven FLs on MRI (MRI-FLs) distinguished three risk groups: 5-year survival was 76% in the absence of both more than seven MRI-FLs and CA (n = 276), 61% in the presence of one MRI-FL (n = 262), and 37% in the presence of both unfavorable parameters (n = 67). MRI-FL correlated with low albumin and elevated levels of C-reactive protein, lactate dehydrogenase, and creatinine, but did not correlate with age, beta-2-microglobulin, and CA. Resolution of MRI-FL, occurring in 60% of cases and not seen with MBS-defined FL, conferred superior survival.MRI is a more powerful tool for detection of FLs than is MBS. MRI-FL number had independent prognostic implications; additionally, MRI-FL resolution identified a subgroup with superior survival. We therefore recommend that, in addition to MBS, MRI be used routinely for staging, prognosis, and response assessment in myeloma.
Diagnostic and therapeutic problems in two patients with antiphospholipid antibodies, heart valve lesions, and transient ischaemic attacks.
Authors: R A Asherson, D G Gibson, D W Evans, E Baguley, G R Hughes
Journal: Annals of the Rheumatic Diseases (1988)

Two young women (aged 32 and 25 years) with systemic lupus erythematosus and heart valve lesions in association with antiphospholipid antibodies are presented. In addition to the presence of the 'lupus anticoagulant' and false positive Venereal Disease Research Laboratory (VDRL) tests, both patients had high levels of IgG anticardiolipin antibodies. The first patient additionally had contraceptive induced chorea, chorea gravidarum, seven miscarriages, livedo reticularis, pulmonary embolism, and thrombocytopenia and developed culture negative endocarditis as well as hypertension. The second patient, who had presented with hypertension, developed aortic and mitral regurgitation, suspected myocarditis, manifested transient ischaemic attacks, and responded well to anticoagulation and steroid treatment.
Topical steroid treatment of allergic rhinitis decreases nasal fluid TH2 cytokines, eosinophils, eosinophil cationic protein, and IgE but has no significant effect on IFN-γ, IL-1β, TNF-α, or neutrophils
Authors: Mikael Benson, Inga-Lisa Strannegård, Örjan Strannegård, Göran Wennergren
Journal: Journal of Allergy and Clinical Immunology (2000)
Special delivery of insulin to the liver
Authors: Ralph A. Defronzo
Journal: Hepatology (1986)

Insulin encapsulated in lipid vesicles and targeted to hepatocytes by means of a digalactosy diglyceride moiety [(designated vesicle encapsulated insulin (VEI)] was administered intrave nously to conscious catheterized diabetic dogs to determine the effects on hepatic and extrahepatic glucose utilization. Our results indicate that VE administered intravenously to diabetic dogs ove a dose range of 0.5 to 2.0 mU · kg −1 ·min −1 reduce hepatic glucose output or induces hepatic glucos uptake without causing any significant alteratios in the rate of extrahepatic glucose utilization. Steady-state comparisons of 1.0 mU·kg −1 ·min −1 VEI with intraportal and peripherally administered insulin revealed that VEI and intraportal insulin result in significantly less extrahepatic glucose utilization than does an equivalent dose of peripherally administered insulin (6.36 ± 1.21 and 5.08 ± 0.97 vs. 8.82 ± 1.61 mg.kg −1 .min −1 ; P &lt; 0.03). Through the use of VEI, we were able to significantly alter the deposition of intravenously administered glucose from 11% hepatic and 89% extrahepatic noted with peripheral insulin to 35% hepatic and 65% extrahepatic with VEI (P &lt; 0.03). Thus, by encapsulating insulin into a lipid carrier specifically targeted to the liver, selective hepatic insulinization can be achieved. As a result of this approach, one can alter the distribution of a glucose load to favor hepatic deposition.
Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension
Authors: Abraham R. Tzafriri, John H. Keating, Peter M. Markham, Anna-Maria Spognardi, James R. L. Stanley, Gee Wong, Brett G. Zani, Debby Highsmith, Patrick O’Fallon, Kristine Fuimaono, Felix Mahfoud, Elazer R. Edelman
Journal: Science Translational Medicine (2015)

Local tissue anatomy determines the success of renal nerve ablation and explains its variable effects on blood pressure.
2-Deoxy-<scp>d</scp>-Glucose Combined with Cisplatin Enhances Cytotoxicity via Metabolic Oxidative Stress in Human Head and Neck Cancer Cells
Authors: Andrean L. Simons, Iman M. Ahmad, David M. Mattson, Kenneth J. Dornfeld, Douglas R. Spitz
Journal: Cancer Research (2007)

Abstract Glucose deprivation has been hypothesized to cause cytotoxicity by inducing metabolic oxidative stress in human cancer cells. The current work tests the hypothesis that 2-deoxy-d-glucose (2DG) combined with cisplatin [cis-diamminedichloroplatinum(II)] can enhance cytotoxicity in human head and neck cancer cells (FaDu) by mechanisms involving oxidative stress. Exposure of FaDu cells to the combination of 2DG and cisplatin resulted in a significant decrease in cell survival when compared with 2DG or cisplatin alone. Treatment with 2DG and cisplatin also caused perturbations in parameters indicative of oxidative stress, including decreased intracellular total glutathione and increased percentage of glutathione disulfide. Simultaneous treatment with the thiol antioxidant N-acetylcysteine (NAC) inhibited parameters indicative of oxidative stress, as well as protected FaDu cells from the cytotoxic effects of cisplatin alone and the combination of 2DG and cisplatin. In addition, polyethylene glycol–conjugated antioxidant enzymes (PEG-superoxide dismutase and PEG-catalase) also protected FaDu cells from 2DG toxicity. An inhibitor of glutathione synthesis, l-buthionine-[S,R]-sulfoximine (BSO), sensitized FaDu cells to the cytotoxic effects of 2DG and cisplatin, and these effects were inhibited by NAC. Furthermore, the combination of 2DG, cisplatin, and BSO significantly increased the percentage of glutathione disulfide, which was also inhibited by NAC. These results support the hypothesis that exposure of human head and neck cancer cells to 2DG combined with cisplatin enhances cytotoxicity via metabolic oxidative stress. These findings provide a strong biochemical rationale for evaluating inhibitors of glucose and hydroperoxide metabolism in combination with cisplatin for the treatment of head and neck cancer. [Cancer Res 2007;67(7):3364–70]
Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection
Authors: Daisuke Tokuhara, Beatriz Álvarez, Mio Mejima, Tomoko Hiroiwa, Yuko Takahashi, Shiho Kurokawa, Masaharu Kuroda, Masaaki Oyama, Hiroko Kozuka-Hata, Tomonori Nochi, Hiroshi Sagara, Farah Aladin, Harold Marcotte, Leon G.J. Frenken, Miren Iturriza-Gómara, Hiroshi Kiyono, Lennart Hammarström, Yoshikazu Yuki
Journal: Journal of Clinical Investigation (2013)

Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.
Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives
Authors: Maria Vittoria Dieci, Monica Arnedos, Fabrice Andre, Jean Charles Soria
Journal: Cancer Discovery (2013)

Abstract The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifications, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, class-specific toxicity profiles and correctly designing clinical trials to address these different issues. Significance: FGF/FGFR pathway deregulations are increasingly recognized across different human cancers. Understanding the mechanisms at the basis of these alterations and their multiple roles in cancer promotion and drug resistance is a fundamental step for further implementation of targeted therapies and research strategies. Cancer Discov; 3(3); 264–79. ©2012 AACR.
Patient Characteristics and Differences in Hospital Readmission Rates
Authors: Michael L. Barnett, John Hsu, J. Michael McWilliams
Journal: JAMA Internal Medicine (2015)

Medicare penalizes hospitals with higher than expected readmission rates by up to 3% of annual inpatient payments. Expected rates are adjusted only for patients' age, sex, discharge diagnosis, and recent diagnoses.To assess the extent to which a comprehensive set of patient characteristics accounts for differences in hospital readmission rates.Using survey data from the nationally representative Health and Retirement Study (HRS) and linked Medicare claims for HRS participants enrolled in Medicare who were hospitalized from 2009 to 2012 (n = 8067 admissions), we assessed 29 patient characteristics from survey data and claims as potential predictors of 30-day readmission when added to standard Medicare adjustments of hospital readmission rates. We then compared the distribution of these characteristics between participants admitted to hospitals with higher vs lower hospital-wide readmission rates reported by Medicare. Finally, we estimated differences in the probability of readmission between these groups of participants before vs after adjusting for the additional patient characteristics.All-cause readmission within 30 days of discharge.Of the additional 29 patient characteristics assessed, 22 significantly predicted readmission beyond standard adjustments, and 17 of these were distributed differently between hospitals in the highest vs lowest quintiles of publicly reported hospital-wide readmission rates (P ≤ .04 for all comparisons). Almost all of these differences (16 of 17) indicated that participants admitted to hospitals in the highest quintile of readmission rates were more likely to have characteristics that were associated with a higher probability of readmission. The difference in the probability of readmission between participants admitted to hospitals in the highest vs lowest quintile of hospital-wide readmission rates was reduced by 48% from 4.41 percentage points with standard adjustments used by Medicare to 2.29 percentage points after adjustment for all patient characteristics assessed (reduction in difference: -2.12; 95% CI, -3.33 to -0.67; P = .003).Patient characteristics not included in Medicare's current risk-adjustment methods explained much of the difference in readmission risk between patients admitted to hospitals with higher vs lower readmission rates. Hospitals with high readmission rates may be penalized to a large extent based on the patients they serve.