tbuckley/cabot-search huggingface dataset:
Smoldering (Asymptomatic) Multiple Myeloma: Current Diagnostic Criteria, New Predictors of Outcome, and Follow-Up Recommendations
Authors: Joan Bladé, Meletios Dimopoulos, Laura Rosiñol, S. Vincent Rajkumar, Robert A. Kyle
Journal: Journal of Clinical Oncology (2009)

To provide an overview on smoldering (asymptomatic) multiple myeloma (SMM) including current diagnostic criteria, predictors of progression, pattern of progression, and outcome.A comprehensive review of the literature on risk factors for progression, treatment attempts to delay progression and outcome in patients with SMM.The risk factors for progression of SMM include: plasma cell mass including M-protein size and percentage of bone marrow clonal plasma cells (BMPC), abnormal free light chain ratio, proportion of phenotypically abnormal BMPC, immunoparesis, evolution pattern (evolving v nonevolving), and pattern of magnetic resonance imaging abnormalities. Most patients with SMM progress with anemia and/or skeletal involvement. Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome. Patients should not be treated until progressive disease with end-organ damage occurs. Increasing anemia is the most reliable indicator of progression.These recently recognized predictors of outcome may be helpful for better disease monitoring and for investigation of new treatment approaches. Thus, recommendations for follow-up every to 3 to 6 months depending on the risk of progression are suggested, and clinical trials with new noncytotoxic biologically derived agents to delay progression, particularly in high-risk patients, are ongoing.
Assessment of dietary exposure to some persistent organic pollutants in the Republic of Karakalpakstan of Uzbekistan.
Authors: Nigina Muntean, Marco Jermini, Ian Small, Dennis Falzon, Peter Fürst, Giacomo Migliorati, Giampiero Scortichini, Anna Francesca Forti, Elke Anklam, Christoph von Holst, Bakhtier Niyazmatov, Shakub Bahkridinov, Roger Aertgeerts, Roberto Bertollini, Cristina Tirado, Anthony Kolb
Journal: Environmental Health Perspectives (2003)

A 1999 study heightened long-standing concerns over persistent organic pollutant contamination in the Aral Sea area, detecting elevated levels in breast milk and cord blood of women in Karakalpakstan (western Uzbekistan). These findings prompted a collaborative research study aimed at linking such human findings with evidence of food chain contamination in the area. An international team carried out analyses of organochlorine and organophosphate pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) on samples of 12 foods commonly produced and consumed in Karakalpakstan. Analysis consistently detected long-lasting organochlorine pesticides and their metabolites in all foods of animal origin and in some vegetables such as onions and carrots--two low-cost components of many traditional dishes. Levels of PCBs were relatively low in all samples except fish. Analyses revealed high levels of PCDDs and PCDFs (together often termed "dioxins") in sheep fat, dairy cream, eggs, and edible cottonseed oil, among other foodstuffs. These findings indicate that food traditionally grown, sold, and consumed in Karakalpakstan is a major route of human exposure to several persistent toxic contaminants, including the most toxic of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Intake estimations demonstrate that consumption of even small amounts of locally grown food may expose consumers to dioxin levels that considerably exceed the monthly tolerable dioxin intake levels set by the World Health Organization. Data presented in this study allow a first assessment of the risk associated with the consumption of certain food products in Karakalpakstan and highlight a critical public health situation.
Donor conversion rates depend on the assessment tools used in the evaluation of potential organ donors
Authors: Yorick J. de Groot, Eelco F. M. Wijdicks, Mathieu van der Jagt, Jan Bakker, Hester F. Lingsma, Jan N. M. IJzermans, Erwin J. O. Kompanje
Journal: Intensive Care Medicine (2011)

It is desirable to identify a potential organ donor (POD) as early as possible to achieve a donor conversion rate (DCR) as high as possible which is defined as the actual number of organ donors divided by the number of patients who are regarded as a potential organ donor. The DCR is calculated with different assessment tools to identify a POD. Obviously, with different assessment tools, one may calculate different DCRs, which make comparison difficult. Our aim was to determine which assessment tool can be used for a realistic estimation of a POD pool and how they compare to each other with regard to DCR.Retrospective chart review of patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage. We applied three different assessment tools on this cohort of patients.We identified a cohort of 564 patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage of whom 179/564 (31.7%) died. After applying the three different assessment tools the number of patients, before exclusion of medical reasons or age, was 76 for the IBD-FOUR definition, 104 patients for the IBD-GCS definition and 107 patients based on the OPTN definition of imminent neurological death. We noted the highest DCR (36.5%) in the IBD-FOUR definition.The definition of imminent brain death based on the FOUR-score is the most practical tool to identify patients with a realistic chance to become brain dead and therefore to identify the patients most likely to become POD.
Decreased angiogenesis and arthritic disease in rabbits treated with an αvβ3 antagonist
Authors: Chris M. Storgard, Dwayne G. Stupack, Alfred Jonczyk, Simon L. Goodman, Robert I. Fox, David A. Cheresh
Journal: Journal of Clinical Investigation (1999)

Rheumatoid arthritis (RA) is an inflammatory disease associated with intense angiogenesis and vascular expression of integrin αvβ3. Intra-articular administration of a cyclic peptide antagonist of integrin αvβ3 to rabbits with antigen-induced arthritis early in disease resulted in inhibition of synovial angiogenesis and reduced synovial cell infiltrate, pannus formation, and cartilage erosions. These effects were not associated with lymphopenia or impairment of leukocyte function. Furthermore, when administered in chronic, preexisting disease, the αvβ3 antagonist effectively diminished arthritis severity and was associated with a quantitative increase in apoptosis of the angiogenic blood vessels. Therefore, angiogenesis appears to be a central factor in the initiation and persistence of arthritic disease, and antagonists of integrin αvβ3 may represent a novel therapeutic strategy for RA.
Host-Pathogen Interactions in Emerging and Re-emerging Infectious Diseases: A Genomic Perspective of Tuberculosis, Malaria, Human Immunodeficiency Virus Infection, Hepatitis B, and Cholera
Authors: Janet M. McNicholl, Marie V. Downer, Venkatachalam Udhayakumar, Chester A. Alper, David L. Swerdlow
Journal: Annual Review of Public Health (2000)

▪ Abstract On exposure to a pathogen, a host may resist infection, become subclinically infected, or progress through several stages from mild to severe infection. Chronic sequelae may or may not occur. Host factors, particularly host genes, influence many of these stages. We have used a model of the continuum of pathogenesis of infectious diseases to consider the effect of host genes on five pathogens of significant public health burden: Mycobacterium tuberculosis, Plasmodium species, human immunodeficiency virus, hepatitis B virus, and Vibrio cholerae. The relationships between these infections and polymorphisms in human leukocyte antigen, cytokines, other immune response, or pathogen receptor genes are reviewed. We discuss gene-gene interactions and their effects in complex settings, such as coinfections with several pathogens. Priorities for prevention and control of these pathogens include vaccines and antimicrobial drugs. Research on how host genes can influence vaccine responses and the efficacy of drugs or other interventions, as well as further research into the relationship of host genes to infectious disease outcomes, may lead to new strategies for prevention and control.
Fenoldopam Mesylate for the Prevention of Contrast-Induced Nephropathy
Authors: Gregg W. Stone, Peter A. McCullough, James A. Tumlin, Norman E. Lepor, Hooman Madyoon, Patrick Murray, Andrew Wang, A. Alan Chu, Gary L. Schaer, Melissa Stevens, Robert L. Wilensky, William W. O'Neill
Journal: JAMA (2003)

<h3>Context</h3> The development of contrast-induced nephropathy in patients undergoing invasive cardiac procedures is associated with a marked increase in cardiovascular morbidity and mortality. Fenoldopam mesylate, a specific agonist of the dopamine-1 receptor, preserves renal blood flow after iodinated contrast administration and has shown promise in ameliorating contrast nephropathy in previous observational and small randomized trials. <h3>Objective</h3> To examine the efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive cardiovascular procedures. <h3>Design</h3> Prospective, placebo-controlled, double-blind, multicenter randomized trial with serial serum creatinine levels measured at a central biochemistry laboratory (at baseline and 1, 24, 48, and 72 to 96 hours after study drug administration) and 30-day clinical follow-up. <h3>Patients and Setting</h3> Between March 2001 and July 2002, 315 patients with creatinine clearance less than 60 mL/min (1.00 mL/s) at 28 centers in the United States were randomized to receive fenoldopam mesylate (n = 157) or placebo (n = 158). <h3>Interventions</h3> Patients were hydrated and randomized to receive intravenous fenoldopam (0.05 µg/kg/min titrated to 0.10 µg/kg/min) vs matching placebo, starting 1 hour prior to angiography and continuing for 12 hours. <h3>Main Outcome Measure</h3> Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine level within 96 hours postprocedure. <h3>Results</h3> Mean (SD) patient age was 70 (11) years, and 49% had diabetes mellitus. Mean (SD) baseline creatinine clearance was 29.0 (10.0) mL/min (0.48 [0.16] mL/s) (range, 7.5-56.8 mL/min [0.12-0.94 mL/s]), and 157 (108) mL of contrast was administered during the procedures. The primary end point of contrast-induced nephropathy occurred in 33.6% of patients assigned to receive fenoldopam vs 30.1% assigned to receive placebo (relative risk, 1.11; 95% confidence interval, 0.79-1.57;<i>P</i>= .61). There were no significant differences in the 30-day rates of death (2.0% vs 3.8%,<i>P</i>= .50), dialysis (2.6% vs 1.9%,<i>P</i>= .72), or rehospitalization (17.6% vs 19.9%,<i>P</i>= .66) in fenoldopam vs placebo randomized patients, respectively. <h3>Conclusion</h3> The selective dopamine-1 agonist fenoldopam mesylate does not prevent further renal function deterioration after contrast administration in patients with chronic renal insufficiency.
Short- and long-term response to corticosteroid therapy in chronic beryllium disease
Authors: S. Marchand-Adam, A. El Khatib, F. Guillon, M. W. Brauner, C. Lamberto, V. Lepage, J-M. Naccache, D. Valeyre
Journal: European Respiratory Journal (2008)

Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy. Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4-12 months), at relapse and at the final visit. Beryllium exposure, Glu(69) (HLA-DPB1 genes coding for glutamate at position beta69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed. The CBD patients were observed for a median (range) of 69 (20-180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients. Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.
Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial
Authors: Andrew IR Maas, Gordon Murray, Herbert Henney, Nadim Kassem, Valerie Legrand, Miriam Mangelus, Jan-Paul Muizelaar, Nino Stocchetti, Nachshon Knoller
Journal: The Lancet Neurology (2005)
Endothelial modulation of the ouabain-induced contraction in human placental vessels.
Authors: C F Sánchez-Ferrer, M S Fernández-Alfonso, A Ponte, M A Casado, R González, L Rodríguez-Mañas, A Pareja, J Marín
Journal: Circulation Research (1992)

Ouabain (1 x 10(-7)-3 x 10(-5) M) elicited concentration-dependent vasoconstriction in human placental arteries and veins. These responses, but not those produced by 10(-6) M 5-hydroxytryptamine, were increased after the removal of vascular endothelium. In placental arteries, the respective blockade of cyclooxygenase or lipoxygenase with indomethacin of 5,8,11,15-eicosatetraynoic acid as well as the inactivation of nitric oxide with phenidone or oxyhemoglobin and the inhibition of nitric oxide synthesis with NG-monomethyl L-arginine (all at 10(-5) M) did not mimic the effects of endothelial denudation on ouabain-evoked contractions. Bioassay experiments suggested that the above-mentioned endothelial effects are mediated by diffusible factors. 86Rb+ uptake, a method to measure sodium pump activity, was significantly reduced by the removal of endothelium. These results suggest the existence of an inhibitory modulation by the endothelium of the contractions induced by ouabain, likely mediated by a diffusible factor(s) released from these cells. The nature of this substance is unknown but is not related to prostaglandins or leukotrienes, and neither is it a nitric oxide-related compound. Its mechanism of action could be stimulating the activity of vascular sodium pump and/or antagonizing its inhibition by ouabain.
What Is the Value of the Routine Use of Patient-Reported Outcome Measures Toward Improvement of Patient Outcomes, Processes of Care, and Health Service Outcomes in Cancer Care? A Systematic Review of Controlled Trials
Authors: Grigorios Kotronoulas, Nora Kearney, Roma Maguire, Alison Harrow, David Di Domenico, Suzanne Croy, Stephen MacGillivray
Journal: Journal of Clinical Oncology (2014)

The systematic use of patient-reported outcome measures (PROMs) has been advocated as an effective way to standardize cancer practice. Yet, the question of whether PROMs can lead to actual improvements in the quality of patient care remains under debate. This review examined whether inclusion of PROM in routine clinical practice is associated with improvements in patient outcomes, processes of care, and health service outcomes during active anticancer treatment.A systematic review of five electronic databases (Medline, EMBASE, CINAHL [Cumulative Index to Nursing and Allied Health Literature], PsycINFO, and Psychology and Behavioral Sciences Collection [PBSC]) was conducted from database inception to May 2012 to locate randomized and nonrandomized controlled trials of patients receiving active anticancer treatment or supportive care irrespective of type of cancer.Based on prespecified eligibility criteria, we included 26 articles that reported on 24 unique controlled trials. Wide variability in the design and use of interventions delivered, outcomes evaluated, and cancer- and modality-specific context was apparent. Health service outcomes were only scarcely included as end points. Overall, the number of statistically significant findings were limited and PROMs' intervention effect sizes were predominantly small-to-moderate.The routine use of PROMs increases the frequency of discussion of patient outcomes during consultations. In some studies, PROMs are associated with improved symptom control, increased supportive care measures, and patient satisfaction. Additional effort is required to ensure patient adherence, as well as additional support to clinicians who will respond to patient concerns and issues, with clear system guidelines in place to guide their responses. More research is required to support PROM cost-benefit in terms of patient safety, clinician burden, and health services usage.
Southwest Oncology Group S0008: A Phase III Trial of High-Dose Interferon Alfa-2b Versus Cisplatin, Vinblastine, and Dacarbazine, Plus Interleukin-2 and Interferon in Patients With High-Risk Melanoma—An Intergroup Study of Cancer and Leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group
Authors: Lawrence E. Flaherty, Megan Othus, Michael B. Atkins, Ralph J. Tuthill, John A. Thompson, John T. Vetto, Frank G. Haluska, Alberto S. Pappo, Jeffrey A. Sosman, Bruce G. Redman, James Moon, Antoni Ribas, John M. Kirkwood, Vernon K. Sondak
Journal: Journal of Clinical Oncology (2014)

High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective.S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS).In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms.Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.
Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles.
Authors: A Moretta, M Vitale, S Sivori, C Bottino, L Morelli, R Augugliaro, M Barbaresi, D Pende, E Ciccone, M Lopez-Botet, L Moretta
Journal: The Journal of Experimental Medicine (1994)

GL183 or EB6 (p58) molecules have been shown to function as receptors for different HLA-C alleles and to deliver an inhibitory signal to natural killer (NK) cells, thus preventing lysis of target cells. In this study, we analyzed a subset of NK cells characterized by a p58-negative surface phenotype. We show that p58-negative clones, although specific for class I molecules do not recognize HLA-C alleles. In addition, by the use of appropriate target cells transfected with different HLA-class I alleles we identified HLA-B7 as the protective element recognized by a fraction of p58-negative clones. In an attempt to identify the receptor molecules expressed by HLA-B7-specific clones, monoclonal antibodies (mAbs) were selected after mice immunization with such clones. Two of these mAbs, termed XA-88 and XA-185, and their F(ab')2 fragments, were found to reconstitute lysis of B7+ target cells by B7-specific NK clones. Both mAbs were shown to be directed against the recently clustered Kp43 molecule (CD94). Thus, mAb-mediated masking of Kp43 molecules interferes with recognition of HLA-B7 and results in target cell lysis. Moreover, in a redirected killing assay, the cross-linking of Kp43 molecules mediated by the XA185 mAb strongly inhibited the cytolytic activity of HLA-B7-specific NK clones, thus mimicking the functional effect of B7 molecules. Taken together, these data strongly suggest that Kp43 molecules function as receptors for HLA-B7 and that this receptor/ligand interaction results in inhibition of the NK-mediated cytolytic activity. Indirect immunofluorescence and FACS analysis of a large number of random NK clones showed that Kp43 molecules (a) were brightly expressed on a subset of p58-negative clones, corresponding to those specific for HLA-B7; (b) displayed a medium/low fluorescence in the p58-negative clones that are not B7-specific as well as in most p58+ NK clones; and (c) were brightly expressed as in the p58+ clone ET34 (GL183-/EB6+, Cw4-specific). Functional analysis revealed that Kp43 functioned as an inhibitory receptor only in NK clones displaying bright fluorescence. These studies also indicate that some NK clones (e.g., the ET34) can coexpress two distinct receptors (p58 and Kp43) for different class I alleles (Cw4 and B7). Finally, we show that Kp43 molecules function as receptors only for some HLA-B alleles and that still undefined receptor(s) must exist for other HLA-B alleles including B27.
The First AACR Special Conference on Stem Cells, Development, and Cancer: Some of These Cells Are Not Like the Others
Authors: David G. Kent, Jennifer C. Lin, Geraldine Aubert
Journal: Cancer Research (2011)

The American Association for Cancer Research (AACR) held an exciting conference on Stem Cells, Development, and Cancer in Vancouver, British Columbia, Canada (March 3-6, 2011). The meeting was cochaired by Geoffrey Wahl, Connie Eaves, and Hans Clevers and was attended by 250 international researchers, 40% of whom were young investigators. Three key themes emerged: (i) heterogeneity in stem cells and cancer, (ii) solid tissue cancer stem cells, and (iii) lessons from development. The interdisciplinary foundation of this meeting was central to its success and appeal, underscoring the value of juxtaposing and interrelating work from the three topics addressed.