tbuckley/cabot-search huggingface dataset:
Enrolling Older Persons in Cancer Trials: The Effect of Sociodemographic, Protocol, and Recruitment Center Characteristics
Authors: Cary P. Gross, Jeph Herrin, Natalie Wong, Harlan M. Krumholz
Journal: Journal of Clinical Oncology (2005)

Purpose To determine the effect of patient, protocol, geographic, and institutional factors on enrollment of older persons onto cancer trials. Methods We conducted a cross-sectional analysis of patients enrolled onto National Cancer Institute–sponsored lung, breast, colorectal, and prostate cancer trials during 1996 to 2002. We used a cross-classified logistic multilevel model to examine the associations between patient, hospital, county, and protocol characteristics, and the likelihood of participants being elderly (≥ 65 years old). Results The final study sample consisted of 36,167 patients enrolled onto 33 trials. After accounting for cancer type, only 6% of the variation in elderly enrollment onto cancer trials was at the protocol level. In contrast, more than 55% of the variation in elderly enrollment was attributable to patient level variation. In multivariate analysis, nonwhite patients were significantly less likely to be elderly than whites (odds ratio [OR] for blacks, 0.51; 95% CI, 0.44 to 0.58; and OR for Hispanics, 0.49; 95% CI, 0.40 to 0.59 v whites). Participants living less than 7 miles from their recruitment center were significantly more likely to be elderly (OR, 1.31; 95% CI, 1.24 to 1.38). Among the 910 recruitment centers, the median adjusted proportion of patients who were elderly was 24.9% (interquartile range, 24.0% to 26.9%). There were a significantly higher number of outlier centers (≤ 20.8% or ≥ 29.3% elderly) than would be expected by a normal distribution (68 observed v six expected; P &lt; .0001). Conclusion Race and proximity to trial enrollment centers were significantly related to age of trial participants after adjusting for protocol factors. Additional work should explore why some recruitment centers were outliers regarding enrollment of older persons.
Timing of Replication Is a Determinant of Neutral Substitution Rates but Does Not Explain Slow Y Chromosome Evolution in Rodents
Authors: C. J. Pink, L. D. Hurst
Journal: Molecular Biology and Evolution (2009)

Mutation rates, assayed as substitution rates of putatively neutral sites, are highly variable around mammalian genomes: There is heterogeneity between genes, between autosomes, and between X, Y, and autosomes. The differences between X, Y, and autosomes are typically assumed to reflect the greater number of cell divisions in the male germ-line. Such an effect can neither account for within-autosome differences nor does it predict the differences between X, Y, and autosome observed in rodents. It has recently been proposed that in primates, the time during S-phase when a gene is replicated is an important determinant of neutral rates of evolution. Here we ask 1) whether we can replicate this result in rodents, 2) whether different autosomes replicate on average at different times, and 3) whether this might explain differences in their substitution rates. Finally we ask 4) whether X, Y, and autosome replicate at different times and 5) whether any difference might explain why the number of replication events alone cannot explain their substitution rates. We find that, as in primates, autosomal intronic rates of evolution increase significantly during S-phase. Different autosomes do have different average replication times, and together with rearrangement, this is a significant predictor of between-autosome differences in substitution rate. Although we find that autosomal, X-, and Y-linked genes replicate at different times, it is paradoxical that the Y-linked genes replicate latest, and replicate more often, but are not especially fast evolving. These results support the hypothesis that replication timing is an important source of substitution rate heterogeneity.
SCN5A and sinoatrial node pacemaker function
Authors: M LEI, H ZHANG, A GRACE, C HUANG
Journal: Cardiovascular Research (2007)

The SCN5A gene encodes specific voltage-dependent Na+ channels abundant in cardiac muscle that open and close at specific stages of cardiac activity in response to voltage change, thereby controlling the magnitude and timecourse of voltage-dependent Na+ currents (iNa) in cardiac muscle cells. Although iNa has been recorded from sinoatrial (SA) node pacemaker cells, its precise role in SA node pacemaker function remains uncertain. This review summarizes recent findings bearing upon: (i) Sinus node dysfunction resulting from genetic mutations in SCN5A; (ii) Sinus node function in the murine cardiac model with targeted disruptions of the SCN5A gene; (iii) Experimental and computational evaluations of the functional roles of iNa in SA node pacemaker function. Taken together, these new observations suggest strong correlations between SCN5A-encoded Na+ channel and SA node pacemaker function.
Diagnosing Tuberculosis in Patients with HIV
Authors: David C. Perlman, Chi Chiu Leung, Wing Wai Yew
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

This editorial focuses on HIV patients and the diagnosis of tuberculosis (TB) specifically in developing areas in Africa. It states that necessary investment must be made in the cultures or the newer genotypic/phenotypic methods that are essential for the appropriate diagnosis and management of patients with TB.
Results of compartment decompression in chronic forearm compartment syndrome: six case presentations
Authors: H Zandi, S Bell
Journal: British Journal of Sports Medicine (2005)

Background: There are few reports concerning chronic compartment syndrome producing symptoms in the forearm, although in the lower limb this is a well recognised condition. The objective was to demonstrate that chronic compartment syndrome is a cause of exercise induced forearm pain and transient upper limb dysfunction and that forearm compartment decompression can reliably relieve the associated symptoms. Methods: Six patients with a flexor compartment chronic compartment syndrome, documented by pressure studies, had forearm compartment decompression. Results: All patients had good relief of their exercise associated forearm pain following the decompression. Widening of the incisional scar was frequently reported. Conclusion: Forearm compartment decompression is effective in relieving the symptoms related to chronic forearm compartment syndrome.
IgA proteases of two distinct specificities are released by Neisseria meningitidis.
Authors: M H Mulks, A G Plaut, H A Feldman, B Frangione
Journal: The Journal of Experimental Medicine (1980)

Strains of Neisseria meningitidis produce two distinct extracellular IgA proteases that cleave the human IgA1 heavy chain at different points within the hinge region. Type 1 protease cleaves the prolyl-seryl peptide bond at position 237-238; type type 2 protease cleaves the prolyl-threonyl bond two residues amino terminal to that bond attacked by type 1 enzyme. Each meningococcal isolate elaborates only one of these two enzymes, and the type of protease produced correlates with certain serogroups: group A yielding only type 1, and groups X and Y only type 2 enzyme. In addition, analysis of amino acid sequences of human alpha-chain proteins reveals that the repeating octapeptide characteristic of the IgA1 hinge region is actually triplicated.
Are Organic Foods Safer or Healthier Than Conventional Alternatives?
Authors: Crystal Smith-Spangler, Margaret L. Brandeau, Grace E. Hunter, J. Clay Bavinger, Maren Pearson, Paul J. Eschbach, Vandana Sundaram, Hau Liu, Patricia Schirmer, Christopher Stave, Ingram Olkin, Dena M. Bravata
Journal: Annals of Internal Medicine (2012)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Background: The health benefits of organic foods are unclear. Purpose: To review evidence comparing the health effects of organic and conventional foods. Data Sources: MEDLINE (January 1966 to May 2011), EMBASE, CAB Direct, Agricola, TOXNET, Cochrane Library (January 1966 to May 2009), and bibliographies of retrieved articles. Study Selection: English-language reports of comparisons of organically and conventionally grown food or of populations consuming these foods. Data Extraction: 2 independent investigators extracted data on methods, health outcomes, and nutrient and contaminant levels. Data Synthesis: 17 studies in humans and 223 studies of nutrient and contaminant levels in foods met inclusion criteria. Only 3 of the human studies examined clinical outcomes, finding no significant differences between populations by food type for allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. Two studies reported significantly lower urinary pesticide levels among children consuming organic versus conventional diets, but studies of biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful differences. All estimates of differences in nutrient and contaminant levels in foods were highly heterogeneous except for the estimate for phosphorus; phosphorus levels were significantly higher than in conventional produce, although this difference is not clinically significant. The risk for contamination with detectable pesticide residues was lower among organic than conventional produce (risk difference, 30% [CI, −37% to −23%]), but differences in risk for exceeding maximum allowed limits were small. Escherichia coli contamination risk did not differ between organic and conventional produce. Bacterial contamination of retail chicken and pork was common but unrelated to farming method. However, the risk for isolating bacteria resistant to 3 or more antibiotics was higher in conventional than in organic chicken and pork (risk difference, 33% [CI, 21% to 45%]). Limitation: Studies were heterogeneous and limited in number, and publication bias may be present. Conclusion: The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria. Primary Funding Source: None.
Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema
Authors: K Takeyabu, T Betsuyaku, M Nishimura, A Yoshioka, M Tanino, K Miyamoto, Y Kawakami
Journal: European Respiratory Journal (1998)

This study examined the role of cysteine proteinases and their inhibitor in the development of emphysema in comparison with neutrophil elastase (NE) complexed with alpha1-protease inhibitor (NE-alpha1-PI), which was previously demonstrated to be increased in bronchoalveolar lavage (BAL) fluid from subjects with subclinical emphysema. Eight nonsmokers and 31 current smokers with (n=17) and without (n=14) emphysema, as evidenced by lung computed tomographic scans, were studied. The concentrations of immunologically detected cathepsin L and cystatin C, but not cathepsin B, were significantly increased in BAL fluid from the smokers with emphysema compared with those without emphysema, although the activity of cathepsin L, measured using a synthetic substrate and cathepsin L, released from cultured alveolar macrophages at 24 h, did not show any significant difference between the two groups. When comparison was made only for the subjects aged &lt;60 yrs, the difference between the two groups disappeared for cathepsin L, but remained for NE-alpha1-PI. There was no significant correlation between the level of cathepsin L and that of NE-alpha1-PI in BAL fluid from the subjects with emphysema. In conclusion, increased levels of cathepsin L and cystatin C were demonstrated in bronchoalveolar lavage fluid from subjects with subclinical emphysema. However, the roles of cathepsin L and neutrophil elastase in the development of emphysema may vary between subjects and between the young and the old.
ChIPOTle: a user-friendly tool for the analysis of ChIP-chip data.
Authors: Michael J Buck, Andrew B Nobel, Jason D Lieb
Journal: Genome biology (2005)

ChIPOTle (Chromatin ImmunoPrecipitation On Tiled arrays) takes advantage of two unique properties of ChIP-chip data: the single-tailed nature of the data, caused by specific enrichment but not specific depletion of genomic fragments; and the predictable enrichment of DNA fragments adjacent to sites of direct protein-DNA interaction. Implemented as a Microsoft Excel macro written in Visual Basic, ChIPOTle uses a sliding window approach that yields improvements in the identification of bona fide sites of protein-DNA interaction.
Improved Evidence Will Support Sound Decision Making but Will Not Solve the Problem of Cost Containment in Oncology
Authors: Jan Schildmann, Daniel Strech, Eva Winkler
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: In his recent contribution, Caplan 1 suggested four shifts in thinking about the ethics of health care to strengthen the role of evidence in current debates on cost containment. We agree with the statement of Caplan that “evidence is not determinative about what we ought to do.” However, we argue that it is already possible to determine more clearly the kind of evidence that is needed for decision making than was done in the article. Moreover, it seems crucial to clarify the limits of evidence with regards to setting the limits of public health care funding fairly. Caplan 1 envisaged the decision making between patients and physicians as a process in which oncologists provide guidance for prudent choices, especially regarding tough choices in end-stage cancer care. We sympathize with such an approach to deliberative or shared decision making. However, current clinical research does not often provide the evidence needed for discussions about benefits and burdens of “another round of chemotherapy.” 1 Although clinical researchers published rich data regarding the improvement of progression-free survival that did not often translate in the same way to a longer overall survival, 2 there is a scarcity of data on the burdens of such treatment and its effect on the quality of life, especially with respect to the last phase of life. Such patient-orientated research is a prerequisite for “offering an opinion informed by evidence” in situations in which a significant number of patients with advanced cancer understandably enough ask for anything available at the end of their disease trajectory. 3 The need for the right data indicates that value judgments become relevant long before the interpretation of evidence, as seemed to be suggested by Caplan. 1 Examples for normative relevant decisions when data are generated and published are the well-known practices of selective reporting of favorable results and decisions about the study design (ie, noninferior studies, exclusion criteria, and study duration) and the choice of patient-relevant end points or the early stoppage of trials. Value judgments also come into play when systematic reviews are generated that need to synthesize study findings and often play a crucial role in coverage decisions (eg, in the purposes of the Patient
Expressions of Nuclear Factor κB, Inducible Nitric Oxide Synthase, and Vascular Endothelial Growth Factor in Adenoid Cystic Carcinoma of Salivary Glands: Correlations with the Angiogenesis and Clinical Outcome
Authors: Jiali Zhang, Bin Peng, Xinming Chen
Journal: Clinical Cancer Research (2005)

Abstract Objective: To evaluate the expressions of nuclear factor κB (NF-κB p65), inducible nitric oxide synthase enzyme (iNOS), and vascular endothelial growth factor (VEGF) in relation to angiogenesis (microvessel density, MVD) and clinical outcomes in adenoid cystic carcinoma (ACC) of salivary glands. Methods: Immunohistochemical staining was used to quantify the protein expression levels of NF-κB p65, iNOS, and VEGF in 80 surgically resected ACCs and 20 normal salivary tissues. In all cases of ACCs, MVD was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. Results: The nuclear localization of NF-κB p65 was only detected in ACC cells. Both iNOS and VEGF staining activities in ACCs were more significant than those in normal gland tissues (P &amp;lt; 0.01). MVD had significant correlations with NF-κB p65, iNOS, and VEGF expressions (P &amp;lt; 0.01). In three histologic types of ACCs, the NF-κB, iNOS, VEGF expressions, and MVD were significantly higher in solid type than in cribriform and tubular types (P &amp;lt; 0.01). The NF-κB, iNOS, VEGF expressions, and MVD were significantly correlated with clinical stage, tumor size, vascular invasion, recurrence, and metastasis (P &amp;lt; 0.05). Multivariate analysis showed NF-κB, iNOS and VEGF expression, MVD, solid histotype, and perineural invasion had an independent prognostic effect on overall survival. Conclusion: The expressions of NF-κB p65, iNOS, and VEGF were related with MVD. Clinical outcomes raised the possibility that the overexpression of these cytokines might contribute to tumor angiogenesis and have prognostic value in ACCs.
Granulocyte-Macrophage Colony–Stimulating Factor and Lung Immunity in Pulmonary Alveolar Proteinosis
Authors: Ryushi Tazawa, Emi Hamano, Toru Arai, Hiromitsu Ohta, Osamu Ishimoto, Kanji Uchida, Masato Watanabe, Junichi Saito, Miki Takeshita, Yasuhiko Hirabayashi, Ikuo Ishige, Yoshinobu Eishi, Koichi Hagiwara, Masahito Ebina, Yoshikazu Inoue, Koh Nakata, Toshihiro Nukiwa
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The anti–granulocyte-macrophage colony–stimulating factor (GM-CSF) autoantibody is inferred to cause idiopathic pulmonary alveolar proteinosis (iPAP): the antibody neutralizes GM-CSF and thereby impairs differentiation of alveolar macrophages. Administration of GM-CSF improves respiratory function of patients with iPAP, as confirmed in this study using aerosolized GM-CSF. To elucidate its mechanism, we characterized bronchoalveolar lavage fluid and alveolar macrophages obtained from three patients with iPAP who were treated successfully with aerosolized GM-CSF. Cell number, expressions of surface mannose receptor and the transcription factor PU.1, and phagocytic ability of alveolar macrophages were all restored to control levels. With treatment, the neutralizing capacity of GM-CSF activity was reduced markedly, concomitant with the decreasing autoantibody levels. Interestingly, the amount of GM-CSF autoantibody complex also decreased. In one case in which the complex was analyzed, the majority of GM-CSF binding the complex was endogenous protein, suggesting that the complex is removed immediately from the lung after treatment. Our study shows that GM-CSF administration engenders a decrease in the neutralizing capacity against the protein in the lungs. Thereby, it facilitates restoration of the normal function of alveolar macrophages.
Get With the Guidelines–Stroke Is Associated With Sustained Improvement in Care for Patients Hospitalized With Acute Stroke or Transient Ischemic Attack
Authors: Lee H. Schwamm, Gregg C. Fonarow, Mathew J. Reeves, Wenqin Pan, Michael R. Frankel, Eric E. Smith, Gray Ellrodt, Christopher P. Cannon, Li Liang, Eric Peterson, Kenneth A. LaBresh
Journal: Circulation (2008)

Adherence to evidence-based guidelines for treatment of stroke or transient ischemic attack is suboptimal. We sought to establish whether participation in Get With the Guidelines-Stroke was associated with improvements in adherence.This prospective, nonrandomized, national quality improvement program measured adherence to guideline recommendations in 322 847 hospitalized patients discharged with a diagnosis of ischemic stroke or transient ischemic attack. A volunteer sample of 790 US academic and community hospitals participated from 2003 through 2007. The main outcome measures were change in adherence over time to 7 prespecified performance measures and a composite measure (total number of interventions provided in eligible patients divided by total number of care opportunities among eligible patients). Generalized estimating equations were used to identify factors associated with improvement. Participation in Get With the Guidelines-Stroke was associated with improvements in the 7 individual and 1 composite measures from baseline to the fifth year: intravenous thrombolytics (42.09% versus 72.84%), early antithrombotics (91.46% versus 97.04%), deep vein thrombosis prophylaxis (73.79% versus 89.54%), discharge antithrombotics (95.68% versus 98.88%), anticoagulation for atrial fibrillation (95.03% versus 98.39%), lipid treatment for low-density lipoprotein >100 mg/dL (73.63% versus 88.29%), smoking cessation (65.21% versus 93.61%), and composite (83.52% versus 93.97%) (P<0.0001 for all comparisons). Multivariate analysis showed that time in Get With the Guidelines-Stroke was associated with a 1.18-fold yearly increase in the odds of fulfilling care opportunities that was independent of secular trends.Get With the Guidelines-Stroke participation was associated with increased adherence to all stroke performance measures. Markedly improved stroke care was seen in all hospitals regardless of size, geography, and teaching status.
Clinical impact of whole-body FDG-PET for evaluation of response and therapeutic decision-making of primary lymphoma of bone
Authors: Y.H. Park, S. Kim, S.-J. Choi, B.-Y. Ryoo, S.H. Yang, G.J. Cheon, C.-W. Choi, S.M. Lim, J.Y. Yoo, S.-S. Lee
Journal: Annals of Oncology (2005)
Impaired Reflex Vasoconstriction in Chronically Hypoxemic Patients
Authors: Donald D. Heistad, Francois M. Abboud, Allyn L. Mark, Phillip G. Schmid
Journal: Journal of Clinical Investigation (1972)

Acute hypoxia impairs vasoconstrictor responses in normal men. The present study was done to determine whether reflex vasoconstriction is impaired in chronically hypoxemic patients and whether correction of hypoxemia in these patients improves their cardiovascular reflexes. In eight chronically hypoxemic patients, arterial P(O2) was increased from an average of 45 mm Hg while breathing room air to 161 mm Hg while breathing 40-100% oxygen, with minimal changes in arterial P(CO2) or pH. Correction of hypoxemia did not cause changes in resting arterial pressure or in forearm vascular resistance, but it caused a small increase in resting heart rate. Reflex responses to lower body negative pressure, which causes pooling of blood in the lower part of the body, were observed. When the patients were hypoxemic, lower body negative pressure caused a fall in arterial pressure, slight constriction of forearm vessels, and a small increase in heart rate. When hypoxemia was corrected, the same intervention caused marked vasoconstriction and a greater increase in heart rate, and there was no decrease in arterial pressure. The results indicate that reflex vasoconstrictor responses are depressed in chronic hypoxemia, indicating that adaptive mechanisms which occur in chronic hypoxemia do not include preservation of sympathetic reflexes.
The action of a urea—lactic acid ointment in ichthyosis.
Authors: CICELY BLAIR
Journal: British Journal of Dermatology (1976)

The effect of urea—lactic acid ointment on the scales of ichthyotic skin was assessed using the ‘cell swelling’ technique of Christophers & Kligman. The thickness of the horny layer and of the scales was reduced both by the ointment and by the base. The formation of scales was shown to differ from that in psoriasis where the scale forms at the apex of a rete peg and is symmetrical whereas in ichthyosis the separation of the scale may be at an entirely different depth at one margin. There is an increase in the number of ‘T’ cells in X‐linked recessive ichthyosis.