tbuckley/cabot-search huggingface dataset:
Effect of Nosocomial Bloodstream Infection on the Outcome of Critically Ill Patients with Acute Renal Failure Treated with Renal Replacement Therapy
Authors: Eric A J Hoste, Stijn I Blot, Norbert H Lameire, Raymond C Vanholder, Dirk De Bacquer, Francis A Colardyn
Journal: Journal of the American Society of Nephrology (2004)

Critically ill patients with acute renal failure (ARF) treated with renal replacement therapy (RRT) have a high mortality. The authors evaluated a cohort of 704 consecutive intensive care unit (ICU) patients with ARF treated with RRT to determine whether there was an increased incidence of nosocomial bloodstream infection and whether this resulted in a worse outcome. The incidence of nosocomial bloodstream infection was 8.8%, higher than that reported in other series of general ICU patients and also higher than the 3.5% incidence of bloodstream infection in non-ARF patients in the same unit (P < 0.001). There were more bloodstream infections caused by Gram-positive species compared with Gram-negative species or fungi. The distribution over the species was comparable to that reported by others for a general ICU population. The outcome was evaluated with matched cohort analysis. With this technique, patients with bloodstream infection (exposed) were closely matched with patients without bloodstream infection (non-exposed) in a 1:2 ratio. Matching was based on the APACHE II system and length of stay before bloodstream infection (exposure time). Length of stay and mortality were equal in exposed and non-exposed patients. There was also no difference in hospital costs. It can be concluded that critically ill patients with ARF treated with RRT were more susceptible to nosocomial bloodstream infection. Nevertheless, the outcome was not influenced by the presence of bloodstream infection. The high mortality observed in ARF patients could therefore not be attributed to the higher incidence of bloodstream infection.
Improving Diabetes Care in Practice
Authors: Kevin A. Peterson, David M. Radosevich, Patrick J. O'Connor, John A. Nyman, Ronald J. Prineas, Steven A. Smith, Thomas J. Arneson, Victor A. Corbett, Joyce C. Weinhandl, Carol J. Lange, Peter J. Hannan
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to determine whether implementation of a multicomponent organizational intervention can produce significant change in diabetes care and outcomes in community primary care practices. RESEARCH DESIGN AND METHODS—This was a group-randomized, controlled clinical trial evaluating the practical effectiveness of a multicomponent intervention (TRANSLATE) in 24 practices. The intervention included implementation of an electronic diabetes registry, visit reminders, and patient-specific physician alerts. A site coordinator facilitated previsit planning and a monthly review of performance with a local physician champion. The principle outcomes were the percentage of patients achieving target values for the composite of systolic blood pressure (SBP) &amp;lt;130 mmHg, LDL cholesterol &amp;lt;100 mg/dl, and A1C &amp;lt;7.0% at baseline and 12 months. Six process measures were also followed. RESULTS—Over 24 months, 69,965 visits from 8,405 adult patients with type 2 diabetes were recorded from 238 health care providers in 24 practices from 17 health systems. Diabetes process measures increased significantly more in intervention than in control practices, giving net increases as follows: foot examinations 35.0% (P &amp;lt; 0.0.001); annual eye examinations 25.9% (P &amp;lt; 0.001); renal testing 28.5% (P &amp;lt; 0.001); A1C testing 8.1%(P &amp;lt; 0.001); blood pressure monitoring 3.5% (P = 0.05); and LDL testing 8.6% (P &amp;lt; 0.001). Mean A1C adjusted for age, sex, and comorbidity decreased significantly in intervention practices (P &amp;lt; 0.02). At 12 months, intervention practices had significantly greater improvement in achieving recommended clinical values for SBP, A1C, and LDL than control clinics (P = 0.002). CONCLUSIONS—Introduction of a multicomponent organizational intervention in the primary care setting significantly increases the percentage of type 2 diabetic patients achieving recommended clinical outcomes.
Marked Discordance Between Dynamic and Passive Diastolic Pressure-Volume Relations in Idiopathic Hypertrophic Cardiomyopathy
Authors: Peter H. Pak, W. Lowell Maughan, Kenneth L. Baughman, David A. Kass
Journal: Circulation (1996)

Background Dynamic diastolic pressure-volume curves measured during filling (PVR fill ) in patients with idiopathic hypertrophic cardiomyopathy (HCM) are often considerably shallower than would be anticipated if one assumed high chamber stiffness. We hypothesized that these curves deviate markedly from the passive end-diastolic pressure-volume relation (EDPVR) and explored the mechanisms for such a discordance. Methods and Results We used invasive pressure-volume analysis and conductance catheter methodology to study 42 patients. Nine had HCM, and the remaining patients comprised three comparison groups: 11 with normal left ventricular (LV) function, 13 with LV hypertrophy secondary to chronic hypertension (LVH-HTN), and 9 with idiopathic dilated cardiomyopathy (DCM). EDPVRs were recorded during balloon catheter obstruction of inferior vena cava inflow. In normal subjects, LVH-HTN patients, and DCM patients, PVR fill curves deviated only slightly from the passive EDPVR. In striking contrast, HCM patients displayed a flat PVR fill that was very different from the steep EDPVR. On reduction of preload, PVR fill relations in HCM shifted downward in parallel, with a net pressure decline at the same chamber volume of −10±4 mm Hg. This staircaselike shift was much less in the other patient groups (−2±2 mm Hg; P &lt;.001). The unusual behavior in HCM could not be attributed directly to increased viscosity, enhanced pericardial constraint, or preload dependence of isovolumic relaxation. Regional heterogeneity of relaxation may play a role; however, we speculate that the major mechanism relates to the unique fiber and chamber architecture seen with HCM and possibly to enhanced ventricular interaction. Conclusions Elevated LV filling pressures in HCM are not due simply to a stiff cavity but also reflect a major influence of offset pressures that vary with chamber loading. The large disparity between flat pressure-volume relations during filling and steep end-diastolic relations appears unique to HCM. This indicates that caution should be used in the interpretation of stiffness results derived from steady-state data and suggests that therapies that alter cavity geometry and/or reduce interaction may markedly influence LV diastolic pressures in HCM.
Partial CD4 Depletion Reduces Regulatory T Cells Induced by Multiple Vaccinations and Restores Therapeutic Efficacy
Authors: Michael G. LaCelle, Shawn M. Jensen, Bernard A. Fox
Journal: Clinical Cancer Research (2009)

Abstract Purpose: A single vaccination of intact or reconstituted-lymphopenic mice (RLM) with a granulocyte macrophage colony-stimulating factorsecreting B16BL6-D5 melanoma cell line induces protective antitumor immunity and T cells that mediate the regression of established melanoma in adoptive immunotherapy studies. We wanted to study if multiple vaccinations during immune reconstitution of the lymphopenic host would maintain a potent antitumor immune response. Experimental Design: RLM were vaccinated multiple times over a 40-day period. Spleens were isolated from these mice, activated in vitro, and adoptively transferred into mice bearing 3-day experimental pulmonary metastases. Results: Multiple vaccinations, rather than boosting the immune response, significantly reduced therapeutic efficacy of adoptive immunotherapy and were associated with an increased frequency and absolute number of CD3+CD4+Foxp3+ T regulatory (Treg) cells. Anti-CD4 administration reduced the absolute number of Treg cells 9-fold. Effector T-cells generated from anti-CD4treated mice were significantly (P &amp;lt; 0.0001) more therapeutic in adoptive transfer studies than T cells from multiply vaccinated animals with a full complement of CD4+ cells. Conclusion: These results suggest that CD4+ Treg cells limit the efficacy of multiple vaccinations and that timed partial depletion of CD4+ T cells may reduce suppression and tip-the-balance in favor of therapeutic antitumor immunity. The recent failure of large phase III cancer vaccine clinical trials, wherein patients received multiple vaccines, underscores the potential clinical relevance of these findings. (Clin Cancer Res 2009;15(22):688190)
Preventive versus “on-demand” nutritional support during antiviral treatment for hepatitis C: A randomized controlled trial
Authors: Ellen J. Huisman, Bart van Hoek, Hanneke van Soest, Karin M. van Nieuwkerk, Joop E. Arends, Peter D. Siersema, Karel J. van Erpecum
Journal: Journal of Hepatology (2012)
Hox Genes and Regionalization of the Nervous System
Authors: R Keynes, R Krumlauf
Journal: Annual Review of Neuroscience (1994)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Routine Iron Supplementation During Pregnancy
Authors: Harold C. Sox, Donald M. Berwick, Alfred O. Berg, Paul S. Frame, Dennis G. Fryback, David A. Grimes, Robert S. Lawrence, Robert B. Wallace, A. Eugene Washington, Modena E. H. Wilson, Steven H. Woolf
Journal: JAMA (1993)

MINERAL and vitamin supplements are prescribed routinely to pregnant women in the United States as a normal part of prenatal care. These supplements are usually prescribed as preparations that include 25 to 65 mg of elemental iron, along with other minerals (eg, calcium, zinc, magnesium, and copper) and vitamins. Few studies have examined the clinical effectiveness of prenatal vitamin preparations as a group. In this report, the US Preventive Services Task Force examines the efficacy and effectiveness of iron in improving outcomes for the mother, fetus, and developing child. Iron is prescribed routinely, even without laboratory evidence of anemia or iron deficiency, because both conditions are thought to be common during pregnancy; potentially harmful to the mother, fetus, and newborn; and preventable through iron supplementation. The purpose of this review is to evaluate these assumptions, based on current scientific evidence from published clinical research. Recommendations based on this evidence are
Peroxisome Proliferator-Activated Receptor α Gene Variants Influence Progression of Coronary Atherosclerosis and Risk of Coronary Artery Disease
Authors: David M. Flavell, Yalda Jamshidi, Emma Hawe, Inés Pineda Torra, Marja-Riitta Taskinen, M. Heikki Frick, Markku S. Nieminen, Y. Antero Kesäniemi, Amos Pasternack, Bart Staels, George Miller, Steve E. Humphries, Philippa J. Talmud, Mikko Syvänne
Journal: Circulation (2002)

Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD). We investigated the association between the leucine 162 to valine (L162V) polymorphism and a G to C transversion in intron 7 of the PPARalpha gene and progression of atherosclerosis in the Lopid Coronary Angiography Trial (LOCAT), a trial examining the effect of gemfibrozil treatment on progression of atherosclerosis after bypass surgery and on risk of IHD in the second Northwick Park Heart Study (NPHS2), a prospective study of healthy middle-aged men in the United Kingdom. There was no association with plasma lipid concentrations in either study. Both polymorphisms influenced progression of atherosclerosis and risk of IHD. V162 allele carriers had less progression of diffuse atherosclerosis than did L162 allele homozygotes with a similar trend for focal atherosclerosis. Intron 7 C allele carriers had greater progression of atherosclerosis than did G allele homozygotes. The V162 allele attenuated the proatherosclerotic effect of the intron 7 C allele. Homozygotes for the intron 7 C allele had increased risk of IHD, an effect modulated by the L162V polymorphism The PPARalpha gene affects progression of atherosclerosis and risk of IHD. Absence of association with plasma lipid concentrations suggests that PPARalpha affects atherosclerotic progression directly in the vessel wall.
Strategies to recruit hard-to-reach smokers into Exercise Assisted Reduction then Stop (EARS): a pragmatic pilot randomised trial
Authors: Tom P Thompson, Paul Aveyard, Richard Ayres, Rod Taylor, Fiona Warren, John Campbell, Richard Byng, Michael Ussher, Susuan Michie, Robert West, Colin Green, Colin Greaves, Adrian H Taylor
Journal: The Lancet (2012)
Down-regulation of PU.1 by Methylation of Distal Regulatory Elements and the Promoter Is Required for Myeloma Cell Growth
Authors: Hiro Tatetsu, Shikiko Ueno, Hiroyuki Hata, Yasuhiro Yamada, Motohiro Takeya, Hiroaki Mitsuya, Daniel G. Tenen, Yutaka Okuno
Journal: Cancer Research (2007)

The transcription factor PU.1 is essential for myeloid and B-cell development. Down-regulation of PU.1 by disruption of its 14-kb 5' upstream regulatory element induced acute myeloid leukemia, T-cell lymphoma, and chronic lymphocytic leukemia-like disease in murine models. In the present study, we found that PU.1 was down-regulated in the majority of human myeloma cell lines and a subset of freshly isolated myeloma cells, in contrast to relatively high expression of PU.1 in normal plasma cells. Patients in this low PU.1 expression subset may have a poor prognosis. In human myeloma cell lines, the 17-kb 5' upstream enhancer and the promoter region of the PU.1 gene were highly methylated, and this is consistent with disappearance of DNase I-hypersensitive sites in these regions. To elucidate the significance of down-regulation of PU.1, we generated stable myeloma cell lines with an inducible PU.1 expression system. Exogenous expression of PU.1 in PU.1 null myeloma cell lines, U266 and KMS12PE, induced complete growth arrest and cell death. Up-regulation of PU.1 by 5-aza-2'-deoxycytidine also induced growth arrest of KMS12PE and KHM11 myeloma cells. These data suggest that down-regulation of PU.1 is an essential step for the survival of a subset of myeloma cells and that up-regulation of PU.1 by demethylation agents or other types of agents may represent a new therapeutic strategy for treatment of multiple myeloma patients.
Biologically Variable or Naturally Noisy Mechanical Ventilation Recruits Atelectatic Lung
Authors: W.ALAN C. MUTCH, STEFAN HARMS, M. RUTH GRAHAM, STEPHEN E. KOWALSKI, LINDA G. GIRLING, GERALD R. LEFEVRE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Biologically variable mechanical ventilation (V˙bv)—using a computer-controller to mimic the normal variability in spontaneous breathing—improves gas exchange in a model of severe lung injury (Lefevre, G. R., S. E. Kowalski, L. G. Girling, D. B. Thiessen, W. A. C. Mutch. Am. J. Respir. Crit. Care Med. 1996;154:1567–1572). Improved oxygenation with V˙bv, in the face of alveolar collapse, is thought to be due to net volume recruitment secondary to the variability or increased noise in the peak inspiratory airway pressures (Ppaw). Biologically variable noise can be modeled as an inverse power law frequency distribution (y ∝ 1/fa) (West, B. J., M. Shlesinger. Am. Sci. 1990;78:40–45). In a porcine model of atelectasis—right lung collapse with one-lung ventilation—we studied if V˙bv (n = 7) better reinflates the collapsed lung compared with conventional monotonously regular control mode ventilation (V˙c; n = 7) over a 5-h period. We also investigated the influence of sigh breaths with V˙c (V˙s; n = 8) with this model. Reinflation of the collapsed lung was significantly enhanced with V˙bv—greater PaO2 (502 ± 40 mm Hg with V˙bv versus 381 ± 40 mm Hg with V˙c at 5 h; and 309 ± 79 mm Hg with V˙s; mean ± SD), lower PaCO2 (35 ± 4 mm Hg versus 48 ± 8 mm Hg and 50 ± 8 mm Hg), lower shunt fraction (9.7 ± 2.7% versus 14.6 ± 2.0% and 22.9 ± 6.0%), and higher respiratory system compliance (Crs) (1.15 ± 0.15 ml/cm H2O/kg versus 0.79 ± 0.19 ml/cm H2O/kg and 0.77 ± 0.13 ml/cm H2O/kg)—at lower mean Ppaw (15.7 ± 1.4 cm H2O versus 18.8 ± 2.3 cm H2O and 18.9 ± 2.8 cm H2O). V˙bv resulted in an 11% increase in measured tidal volume (Vt m) over that seen with V˙c by 5 h (14.7 ± 1.2 ml/kg versus 13.2 ml/kg). The respiratory rate variability programmed for V˙bv demonstrated an inverse power law frequency distribution ( y ∝ 1/fa) with a = 1.6 ± 0.3. These findings provide strong support for the theoretical model of noisy end-inspiratory pressure better recruiting atelectatic lung. Our results suggest that using natural biologically variable noise has enhanced the performance of a mechanical ventilator in control mode.
B Cell Receptor–independent Stimuli Trigger Immunoglobulin (Ig) Class Switch Recombination and Production of IgG Autoantibodies by Anergic Self-Reactive B Cells
Authors: Tri Giang Phan, Michelle Amesbury, Sandra Gardam, Jeffrey Crosbie, Jhagvaral Hasbold, Philip D. Hodgkin, Antony Basten, Robert Brink
Journal: The Journal of Experimental Medicine (2003)

In both humans and animals, immunoglobulin (Ig)G autoantibodies are less frequent but more pathogenic than IgM autoantibodies, suggesting that controls over Ig isotype switching are required to reinforce B cell self-tolerance. We have used gene targeting to produce mice in which hen egg lysozyme (HEL)-specific B cells can switch to all Ig isotypes (SWHEL mice). When crossed with soluble HEL transgenic (Tg) mice, self-reactive SWHEL B cells became anergic. However, in contrast to anergic B cells from the original nonswitching anti-HEL × soluble HEL double Tg model, self-reactive SWHEL B cells also displayed an immature phenotype, reduced lifespan, and exclusion from the splenic follicle. These differences were not related to their ability to Ig class switch, but instead to competition with non-HEL–binding B cells generated by VH gene replacement in SWHEL mice. When activated in vitro with B cell receptor (BCR)-independent stimuli such as anti-CD40 monoclonal antibody plus interleukin 4 or lipopolysaccharide (LPS), anergic SWHEL double Tg B cells proliferated and produced IgG anti-HEL antibodies as efficiently as naive HEL-binding B cells from SWHEL Ig Tg mice. These results demonstrate that no intrinsic constraints to isotype switching exist in anergic self-reactive B cells. Instead, production of IgG autoantibodies is prevented by separate controls that reduce the likelihood of anergic B cells encountering BCR-independent stimuli. That bacteria-derived LPS could circumvent these controls may explain the well-known association between autoantibody-mediated diseases and episodes of systemic infection.
Upregulation of Reg 1α and GW112 in the epithelium of inflamed colonic mucosa
Authors: S Shinozaki, T Nakamura, M Iimura, Y Kato, B Iizuka, M Kobayashi, N Hayashi
Journal: Gut (2001)

BACKGROUND AND AIMS Colonic epithelium is involved in the regulation of intestinal function and mucosal immune responses, and its function is altered in inflammatory bowel disease (IBD). However, a comprehensive analysis of the genetic alterations in inflamed colonic epithelium is not available at present. The aim of our study was to detect genes that are preferentially expressed in inflamed colonic epithelia and clarify the biochemical responses of epithelial cells in inflamed colonic mucosa. METHODS cDNA representation difference analysis was used to identify candidate genes selectively expressed in inflamed colonic epithelia. Selective expression of these genes in the epithelium of inflamed colonic mucosa, including IBD and non-IBD tissues, was examined by real time polymerase chain reaction and in situ hybridisation. The effect of cell confluence and inflammatory mediators on Reg 1α gene expression was examined using a colon cancer cell line (HT29). RESULTS We identified seven candidate genes that were presumed to be upregulated in the inflamed colonic epithelium. Of these, Reg 1α and GW112 were the dominant species and expression of these genes was confined to the crypt epithelium. In vitro studies using a colonic epithelial cell line suggested that cell confluence regulates Reg 1α gene expression. CONCLUSIONS Selective expression of Reg 1α and GW112 genes in the crypt epithelium of inflamed colonic mucosa suggests the important regulatory functions of these genes.
Lymph Node Dissection: Is It Diagnostic or Therapeutic?
Authors: Elin R. Sigurdson
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.11.944 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12637458 Lymph Node Dissection: Is It Diagnostic or Therapeutic? Elin R. SigurdsonxElin R. SigurdsonSearch for articles by this author Show More Fox Chase Cancer Center, Philadelphia, PA https://doi.org/10.1200/JCO.2003.11.944 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Exploring the cost–utility of stratified primary care management for low back pain compared with current best practice within risk-defined subgroups
Authors: David G T Whitehurst, Stirling Bryan, Martyn Lewis, Jonathan Hill, Elaine M Hay
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Stratified management for low back pain according to patients' prognosis and matched care pathways has been shown to be an effective treatment approach in primary care. The aim of this within-trial study was to determine the economic implications of providing such an intervention, compared with non-stratified current best practice, within specific risk-defined subgroups (low-risk, medium-risk and high-risk). Methods Within a cost–utility framework, the base-case analysis estimated the incremental healthcare cost per additional quality-adjusted life year (QALY), using the EQ-5D to generate QALYs, for each risk-defined subgroup. Uncertainty was explored with cost–utility planes and acceptability curves. Sensitivity analyses were performed to consider alternative costing methodologies, including the assessment of societal loss relating to work absence and the incorporation of generic (ie, non-back pain) healthcare utilisation. Results The stratified management approach was a cost-effective treatment strategy compared with current best practice within each risk-defined subgroup, exhibiting dominance (greater benefit and lower costs) for medium-risk patients and acceptable incremental cost to utility ratios for low-risk and high-risk patients. The likelihood that stratified care provides a cost-effective use of resources exceeds 90% at willingness-to-pay thresholds of £4000 (≈ 4500; $6500) per additional QALY for the medium-risk and high-risk groups. Patients receiving stratified care also reported fewer back pain-related days off work in all three subgroups. Conclusions Compared with current best practice, stratified primary care management for low back pain provides a highly cost-effective use of resources across all risk-defined subgroups.