tbuckley/cabot-search huggingface dataset:
Morbidity and Mortality from Medical Errors: An Increasingly Serious Public Health Problem
Authors: David P. Phillips, Charlene C. Bredder
Journal: Annual Review of Public Health (2002)

▪ Abstract From 1983 to 1998, U.S. fatalities from acknowledged prescription errors increased by 243%, from 2,876 to 9,856. This percentage increase was greater than for almost any other cause of death, and far outpaced the increase in the number of prescriptions. Many nonfatal prescription errors also occur, but estimates of the frequency of these errors vary widely, because various definitions, geographic settings, and institutions have been used. Efforts to reduce fatal and nonfatal prescription errors have encountered perceptual, legal, medical, and cultural barriers. It may be possible to reduce prescription errors by instituting a central agency responsible for collecting, analyzing, and reporting harmful or potentially harmful drug events, and for issuing recommendations and directives.
Increased Circulating Nitrogen Oxides After Human Tumor Immunotherapy: Correlation With Toxic Hemodynamic Changes
Authors: J. B. Ochoa, B. Curti, A. B. Peitzman, R. L. Simmons, T. R. Billiar, R. Hoffman, R. Rault, D. L. Longo, W. J. Urba, A. C. Ochoa
Journal: JNCI Journal of the National Cancer Institute (1992)

Toxicity to interleukin-2 (IL-2) tumor immunotherapy is manifested principally by the vascular leak syndrome, hypotension, and a hyperdynamic response with low systemic vascular resistance. Nitric oxide (.N = O), a recently discovered biological mediator of vascular smooth muscle relaxation, is produced in increased amounts by numerous cell types exposed to a number of inflammatory cytokines.Our purpose was to determine if there is an increased production of .N = O in patients receiving IL-2 tumor immunotherapy, and, if so, whether increases in .N = O production correlate with hemodynamic instability.Twelve patients undergoing immunotherapy trials with IL-2 and anti-CD3 monoclonal antibody-activated lymphocytes (T-AK cells) were studied. Plasma levels of nitrate (NO3-), the stable end metabolic product of .N = O synthesis, were measured before and at the end of IL-2 treatment cycles.We observed a ninefold increase in plasma levels of NO3- in patients after 7 days of treatment (P less than .0001). A significant decrease in both systolic and diastolic blood pressures was observed in all patients (P less than .001).We propose that mediated induction of .N = O synthase enzyme leads to progressive increases in .N = O production which, in turn, produces clinically significant hypotension.Since .N = O synthesis can be competitively inhibited by L-arginine analogues, a possible pharmacologic modulation of .N = O production could potentially contribute to better management of toxic side effects seen in IL-2 cancer therapies.
Uncontrolled Inflammation Induced by AEG-1 Promotes Gastric Cancer and Poor Prognosis
Authors: Guanghua Li, Zhao Wang, Jinning Ye, Xinhua Zhang, Hui Wu, Jianjun Peng, Wu Song, Chuangqi Chen, Shirong Cai, Yulong He, Jianbo Xu
Journal: Cancer Research (2014)

Gastric cancer is one of the most common causes of cancer-related death worldwide. Helicobacter pylori infection plays an important role in the development and progression of gastric cancer. The expression of astrocyte-elevated gene-1 (AEG-1) is increased in gastric cancer tissues, thereby contributing to the inflammatory response. We investigated whether and how AEG-1 regulated proinflammatory signaling in gastric cancer cells. We used human gastric cancer cell lines and athymic nude mice to investigate the role of AEG-1 in the regulation of the TLR4/nuclear factor-κB (NF-κB) signaling pathway and cancer invasion and compared the expression of AEG-1 and related proteins in 93 patients with gastric cancer by immunohistochemistry. In human gastric cancer cells, both AEG-1 and TLR4 could be induced by lipopolysaccharide (LPS) stimulation. AEG-1 was upregulated via LPS-TLR4 signaling and in turn promoted nuclear translocation of the NF-κB p65 subunit. At the same time, AEG-1 overexpression decreased the levels of suppressor of cytokine signaling (SOCS) protein SOCS-1, a negative regulator of the TLR4 pathway. Furthermore, nude mice engrafted with AEG-1/TLR4-expressing cells demonstrated larger tumor volumes than control animals. In patients with gastric cancer, the expression of AEG-1 correlated with that of TLR4, SOCS-1, and NF-κB and was higher in tumors compared with noncancerous adjacent tissues. Overall survival in patients with gastric cancer with simultaneous expression of AEG-1 and TLR4 was poor. Our results demonstrate that AEG-1 can promote gastric cancer progression by a positive feedback TLR4/NF-κB signaling-related mechanism, thus providing new mechanistic explanation for the role of inflammation in cancer progression.
Colorectal Cancer Epigenetics: Complex Simplicity
Authors: Manon van Engeland, Sarah Derks, Kim M. Smits, Gerrit A. Meijer, James G. Herman
Journal: Journal of Clinical Oncology (2011)

Colorectal cancer (CRC) has predominantly been considered a genetic disease, characterized by sequential accumulation of genetic alterations. Growing evidence indicates that epigenetic alterations add an additional layer of complexity to the pathogenesis of CRC, and characterize a subgroup of colorectal cancers with a distinct etiology and prognosis. Epigenetic dysregulation in colorectal cancer is organized at multiple levels, involving DNA methylation, histone modifications, nucleosomal occupancy and remodeling, chromatin looping, and noncoding RNAs. Interactions between these processes and complex associations with genetic alterations have recently been unraveled. It appears that CRC epigenetics will be the paradigm for multistep carcinogenesis, as CRC genetics has been for the past three decades. This review integrates recent data on epigenetic regulation of gene expression in CRC and describes how the understanding of these processes will alter the management of CRC.
Hospital mortality is associated with ICU admission time
Authors: Hans A. J. M. Kuijsten, Sylvia Brinkman, Iwan A. Meynaar, Peter E. Spronk, Johan I. van der Spoel, Rob J. Bosman, Nicolette F. de Keizer, Ameen Abu-Hanna, Dylan W. de Lange
Journal: Intensive Care Medicine (2010)

Previous studies have shown that patients admitted to the intensive care unit (ICU) after "office hours" are more likely to die. However these results have been challenged by numerous other studies. We therefore analysed this possible relationship between ICU admission time and in-hospital mortality in The Netherlands.This article relates time of ICU admission to hospital mortality for all patients who were included in the Dutch national ICU registry (National Intensive Care Evaluation, NICE) from 2002 to 2008. We defined office hours as 08:00-22:00 hours during weekdays and 09:00-18:00 hours during weekend days. The weekend was defined as from Saturday 00:00 hours until Sunday 24:00 hours. We corrected hospital mortality for illness severity at admission using Acute Physiology and Chronic Health Evaluation II (APACHE II) score, reason for admission, admission type, age and gender.A total of 149,894 patients were included in this analysis. The relative risk (RR) for mortality outside office hours was 1.059 (1.031-1.088). Mortality varied with time but was consistently higher than expected during "off hours" and lower during office hours. There was no significant difference in mortality between different weekdays of Monday to Thursday, but mortality increased slightly on Friday (RR 1.046; 1.001-1.092). During the weekend the RR was 1.103 (1.071-1.136) in comparison with the rest of the week.Hospital mortality in The Netherlands appears to be increased outside office hours and during the weekends, even when corrected for illness severity at admission. However, incomplete adjustment for certain confounders might still play an important role. Further research is needed to fully explain this difference.
TB in Migrant Farmworkers
Authors: J. Randall Richard
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The Office of Migrant Health, Department of Health and Human Services, estimates there to be more than 4 million migrant and seasonal farmworkers in the United States. Among other health problems, these workers suffer a significantly higher rate of tuberculosis (TB) infection compared with the general population. This also includes a high rate of asymptomatic TB, found to be 33% in Hispanic migrant workers in one typical study.<sup>1</sup>With a lifetime risk of 10% for developing active TB, it is understandable that this high-risk population constitutes one of the top priorities of the Advisory Council for Elimination of Tuberculosis, Department of Health and Human Services. In attempting to comply with Centers for Disease Control and Prevention recommendations for TB screening,<sup>2</sup>our mobile migrant worker clinic in north central Ohio offered Mantoux tuberculin skin testing to farmworkers and their families from June through September 1993. Approximately
Genetic Ancestry and Risk of Breast Cancer among U.S. Latinas
Authors: Laura Fejerman, Esther M. John, Scott Huntsman, Kenny Beckman, Shweta Choudhry, Eliseo Perez-Stable, Esteban González Burchard, Elad Ziv
Journal: Cancer Research (2008)

Abstract U.S. Latinas have a lower incidence of breast cancer compared with non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their genetic ancestry from Europeans and Indigenous Americans. We used genetic markers to estimate the ancestry of Latina breast cancer cases and controls and assessed the association with genetic ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 ancestry informative markers in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco Bay area and estimated genetic ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (95% CI) for ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European ancestry was associated with increased breast cancer risk. The OR for a 25% increase in European ancestry was 1.79 (95% CI, 1.28–2.79; P &amp;lt; 0.001). When known risk factors and place of birth were adjusted for, the association with European ancestry was attenuated but remained statistically significant (OR, 1.39; 95% CI, 1.06–2.11; P = 0.013). Further work is needed to determine if the association is due to genetic differences between populations or possibly due to environmental factors not measured. [Cancer Res 2008;68(23):9723–8]
Right ventricular diastolic function in chronic obstructive lung disease
Authors: S Marangoni, S Scalvini, M Schena, M Vitacca, A Quadri, G Levi
Journal: European Respiratory Journal (1992)

Early detection of diastolic dysfunction in chronic obstructive lung disease (COLD) patients could have great prognostic value. Echocardiography has been shown to be a useful technique in studying left ventricular diastolic function. A noninvasive method of studying right ventricular diastolic function has not yet been reported. Pulsed Doppler echocardiography was used to assess right ventricular diastolic function in three groups of subjects: Group I: 35 COLD patients with pulmonary hypertension; Group II: 32 COLD patients without pulmonary hypertension; and Group III: 18 control subjects. Ratios between peak atrial filling velocity (A) and peak early filling velocity (E) (A/E), deceleration half times of the right ventricular rapid filling wave (DHT), and the interval between pulmonary valve closure and tricuspid valve opening (isovolumic relaxation times) (Pc-To) were significantly different in Group I in comparison to Groups II and III. Sensitivity of A/E ratio and Pc-To were 82 and 77%, respectively, and specificity 90 and 72%, respectively; positive predictive values were 90 and 75%, respectively, and negative predictive value 82 and 74% respectively. The multiple correlation coefficient between A/E, acceleration time (ACT), DHT, Pc-To and mean pulmonary artery pressure was 0.75 for Groups I and II together. In conclusion 2D echo-Doppler proved to be useful in evaluating right ventricular diastolic function in all hypertensive COLD patients, revealing a high correlation between diastolic parameters and mean pulmonary artery pressure in both normotensive and hypertensive COLD patients.
Characterization of the Long-Wavelength Opsin from Mecoptera and Siphonaptera: Does a Flea See?
Authors: Sean D. Taylor, Katharina Dittmar de la Cruz, Megan L. Porter, Michael F. Whiting
Journal: Molecular Biology and Evolution (2005)

Mecoptera and Siphonaptera represent two insect orders that have largely been overlooked in the study of insect vision. Recent phylogenetic evidence demonstrates that Mecoptera (scorpionflies) is paraphyletic, with the order Siphonaptera (fleas) nesting as sister to the family Boreidae (snow fleas), showing an evolutionary trend towards reduction in gross eye morphology within fleas. We provide the first molecular characterization of long-wavelength opsins from these three lineages (opsin gene from fleas [FL-Opsin], the Boreidae [B-Opsin], and a mecopteran family [M-Opsin]) and assess the effects of loss of visual acuity on the structure and function of the opsin gene. Phylogenetic analysis implies a physiological sensitivity in the red-green spectrum for these opsins. Analysis of intron splice sites reveals a high degree of similarity between FL-Opsin and B-Opsin as well as conserved splice sites across insect blue-green and long-wavelength opsins. Calculated rates of evolution and tests for destabilizing selection indicate that FL-Opsin, B-Opsin, and M-Opsin are evolving at similar rates with no radical selective pressures, implying conservative evolution and functional constraint across all three lineages.
Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial
Authors: John C Mathers, Mohammad Movahedi, Finlay Macrae, Jukka-Pekka Mecklin, Gabriela Moeslein, Sylviane Olschwang, Diana Eccles, Gareth Evans, Eamonn R Maher, Lucio Bertario, Marie-Luise Bisgaard, Malcolm Dunlop, Judy WC Ho, Shirley Hodgson, Annika Lindblom, Jan Lubinski, Patrick J Morrison, Victoria Murday, Raj Ramesar, Lucy Side, Rodney J Scott, Huw JW Thomas, Hans Vasen, Anne-Marie Gerdes, Gail Barker, Gillian Crawford, Faye Elliott, Kirsi Pylvanainen, Juul Wijnen, Riccardo Fodde, Henry Lynch, D Timothy Bishop, John Burn
Journal: The Lancet Oncology (2012)
Peroxisome proliferator-activated receptors in cutaneous biology
Authors: S. Kuenzli, J-H. Saurat
Journal: British Journal of Dermatology (2003)

Summary Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of target genes involved in many cellular functions including cell proliferation, differentiation and immune/inflammation response. The PPAR subfamily consists of three isotypes: PPARα, PPARβ/δ and PPARγ, which have all been identified in keratinocytes. PPARβ/δ is the predominant subtype in human keratinocytes, whereas PPARα and PPARγ are expressed at much lower levels and increase significantly upon keratinocyte differentiation. PPARβ/δ is not linked to differentiation, but is significantly upregulated upon various conditions that result in keratinocyte proliferation, and during skin wound healing. In vitro and in vivo evidence suggests that PPARs appear to play an important role in skin barrier permeability, inhibiting epidermal cell growth, promoting epidermal terminal differentiation and regulating skin inflammatory response by diverse mechanisms. These proprieties are pointing in the direction of PPARs being key regulators of skin conditions characterized by hyperproliferation, inflammatory infiltrates and aberrant differentiation such as psoriasis, but may also have clinical implications in inflammatory skin disease (e.g. atopic dermatitis), proliferative skin disease, wound healing, acne and protease inhibitor associated lipodystrophia.
Comparison of a Homogeneous Assay With a Precipitation Method for the Measurement of HDL Cholesterol in Diabetic Patients
Authors: Tonny Jensen, Quan Truong, Merete Frandsen, Bo Dinesen, Steen Stender
Journal: Diabetes Care (2002)

OBJECTIVE—To compare direct-measured HDL cholesterol with HDL cholesterol measured by a precipitation method. RESEARCH DESIGN AND METHODS—We compared a homogeneous assay for direct HDL cholesterol analysis with the phosphotungstic acid magnesium chloride precipitation method in 55 type 1 diabetic patients, 70 type 2 diabetic patients, and 82 nondiabetic normal control subjects with plasma triglyceride levels &amp;lt;4.6 mmol/l. The cholesterol content of HDL determined by the direct assay was overall 0.1 mmol/l higher in all three groups than HDL cholesterol measured after precipitation, but the two methods were closely correlated (r2 = 0.98, P &amp;lt; 0.001). RESULTS—HbA1c, blood glucose, serum albumin, serum bilirubin, or triglyceride did not influence the differences of the two HDL cholesterol measurements. Because we have previously shown HDL cholesterol isolated by phosphotungstic acid precipitation to be lower than that by ultracentrifugation, the positive bias found in this study was expected. It seems that the direct HDL cholesterol assay reacts with apolipoprotein (apo) B-containing lipoproteins in the fraction with a density of &amp;gt;1.063; these apo B-containing lipoproteins are suggested to be coprecipitated with the phosphotungstic acid method. We also measured LDL cholesterol directly by a LDL cholesterol plus method and found no significant differences between this method and LDL cholesterol calculated from Friedewald’s formula. CONCLUSIONS—Direct homogeneous assay for HDL cholesterol determination in diabetic patients seems not to exhibit a negative bias, in contrast to the precipitation method, when compared with the ultracentrifugation method. In addition, the direct assay saves time and is not influenced by type of diabetes or degree of metabolic control.
Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity
Authors: L Carmona
Journal: Annals of the Rheumatic Diseases (2003)

To characterise RA in a sample of Spanish patients by estimating mean clinical activity, functional ability, and radiological damage, and current and cumulative prevalence of extra-articular manifestations.Cross sectional analysis of a cohort of patients with RA randomly selected from the clinical databases of 34 centres. Standard definitions and measurements were used, and radiographs read centrally. Estimates and confidence intervals were adjusted to sampling.Data were available for 788 patients. Extra-articular RA was present in 285 (36.2%) patients. Cumulative prevalence and 95% confidence intervals of extra-articular manifestations were estimated: nodules 24.5% (21.5 to 27.5), Sjögren's syndrome 17.0% (14.4 to 19.6), atlantoaxial subluxation 12.1% (9.8 to 14.4), carpal tunnel syndrome 10.7% (7.8 to 13.6), interstitial lung disease 3.7% (2.4 to 5.0), serositis 2.5% (1.4 to 3.5), eye disease 2.5% (1.1 to 3.9), vasculitis 1.3% (0.5 to 2.1), amyloidosis 0.6% (0.1 to 1.2), and Felty's syndrome 0.3% (<0.6). Mean (SD) activity/progression indexes were: DAS28-3 3.4 (1.2), HAQ 1.6 (0.4), Larsen score 54.7 (26.4). Less than 5% of the patients were in remission. 205 (72%) patients were receiving disease modifying antirheumatic drugs (DMARDs).Spanish patients with RA ever seen by a rheumatologist have, on average, a moderate degree of activity, despite widespread use of DMARDs. Measures of the degree of progression do not show a benign disease. The proportion of extra-articular manifestations in Spanish patients with RA is similar to that found in other Mediterranean populations, and lower than that reported in Anglo Saxon countries.
Continuous versus intermittent inhaled corticosteroid (budesonide) for mild persistent asthma in children—not too much, not too little: Figure 1
Authors: Markku Turpeinen, Anna S Pelkonen, Olof Selroos, Kurt Nikander, Tari Haahtela
Journal: Thorax (2011)

The clinical efficacy of inhaled corticosteroids (ICSs) in asthma has been demonstrated in long-term intervention studies,1 2 and ICSs are recommended first-line treatment of persistent asthma, even in children.3 The long-term benefits of early intervention with ICS have been well documented in adults with asthma.4 In children, early intervention with ICS has not altered the natural history of the disease.1 We have recently finalised a series of studies related to the Helsinki Early Intervention Childhood Asthma Programme.5 The programme highlights the benefits and safety aspects of intermittent treatment with an ICS, budesonide, in comparison with continuous daily ICS and non-steroidal maintenance treatment. In this study, we summarise our experiences.

In the 18-month intervention, we compared two budesonide regimens with a control group treated with a fixed dose of disodium cromoglycate (DSCG). The study evaluated the antiasthmatic efficacy and systemic effects of daily versus as-needed intermittent budesonide in prepubertal children with mild persistent asthma. The efficacy variables were morning peak expiratory flow, FEV1, the number of asthma exacerbations and asthma-free days. The indicators of systemic effect were standing-height velocity, bone mineral density (BMD), skin thickness, intraocular pressure and the occurrence of lens opacities.

Children aged 5–10 years (n=176) with newly detected asthma were randomised into three treatment groups: (1) continuous budesonide (400 μg twice daily for 1 month, 200 μg twice daily for months 2–6 and 100 μg twice daily for months 7–18), (2) budesonide, identical treatment to group 1 during months 1–6, then placebo as regular treatment and budesonide intermittently for exacerbations during months 7–18 and (3) DSCG 10 mg three times daily for months 1–18. Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks. If an oral or parenteral corticosteroid was needed, the child was withdrawn …
Iron supplementation may attenuate the effects of hypoxia on pulmonary vasculature
Authors: S. Dyer
Journal: Thorax (2010)

Hypoxia causes pulmonary hypertension in disease and at altitude. Evidence suggests that hypoxia-inducible factor (HIF) regulates the response to hypoxia across organ systems responsible for oxygen delivery to cells, including erythropoiesis, pulmonary and cardiovascular function. HIF is iron-dependent, requiring Fe(II) as a cofactor.

In two studies, the effect of iron infusion and depletion on pulmonary artery pressure (PASP) was investigated …