tbuckley/cabot-search huggingface dataset:
Discordance of Low-Density Lipoprotein (LDL) Cholesterol With Alternative LDL-Related Measures and Future Coronary Events
Authors: Samia Mora, Julie E. Buring, Paul M Ridker
Journal: Circulation (2013)

Background— Low-density lipoprotein cholesterol (LDL-C) is the traditional measure of risk attributable to LDL. Non–high-density lipoprotein cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) are alternative measures of LDL-related risk. However, the clinical utility of these measures may only become apparent among individuals for whom levels are inconsistent (discordant) with LDL-C. Methods and Results— LDL-C was measured directly, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy among 27 533 healthy women (median follow-up 17.2 years; 1070 incident coronary events). Participants were grouped by median LDL-C (121 mg/dL) and each of NHDL-C, apoB, and LDL-P. Discordance was defined as LDL-C greater than or equal to the median and the alternative measure less than the median, or vice versa. Despite high LDL-C correlations with NHDL-C, apoB, and LDL-P ( r =0.910, 0.785, and 0.692; all P &lt;0.0001), prevalence of LDL-C discordance as defined by median cut points was 11.6%, 18.9%, and 24.3% for NHDL-C, apoB, and LDL-P, respectively. Among women with LDL-C less than the median, coronary risk was underestimated for women with discordant (greater than or equal to the median) NHDL-C (age-adjusted hazard ratio, 2.92; 95% confidence interval, 2.33–3.67), apoB (2.48, 2.01–3.07), or LDL-P (2.32, 1.88–2.85) compared with women with concordant levels. Conversely, among women with LDL-C greater than or equal to the median, risk was overestimated for women with discordant (less than the median) NHDL-C (0.40, 0.29–0.57), apoB (0.34, 0.26–0.46), or LDL-P (0.42, 0.33–0.53). After multivariable adjustment for potentially mediating factors, including HDL cholesterol and triglycerides, coronary risk remained underestimated or overestimated by ≈20% to 50% for women with discordant levels. Conclusions— For women with discordant LDL-related measures, coronary risk may be underestimated or overestimated when LDL-C alone is used. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000479.
Medical fallibility – cultural recognition and representation
Authors: Brian Hurwitz, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2009)

Medicalerrorswerepreviouslyseen as residual phenomena, unfortunate events onthe margins of healthcare. Today they are under-stood to be integral to the medical endeavour.Here, we identify the cultural and intellectualantecedentsofscientificandsafetyinterestinaber-rantly provided healthcare. Investigators beganformally to enquire into human error just over acentury ago. Freud’s
Pathophysiology of human ventilatory control
Authors: Jerome A. Dempsey, Curtis A. Smith
Journal: European Respiratory Journal (2014)

We review the substantial recent progress made in understanding the underlying mechanisms controlling breathing and the applicability of these findings to selected human diseases. Emphasis is placed on the sites of central respiratory rhythm and pattern generation as well as newly described functions of the carotid chemoreceptors, the integrative nature of the central chemoreceptors, and the interaction between peripheral and central chemoreception. Recent findings that support critical contributions from cortical central command and muscle afferent feedback to exercise hyperpnoea are also reviewed. These basic principles, and the evidence supporting chemoreceptor and ventilatory control system plasticity during and following constant and intermittent hypoxaemia and stagnant hypoxia, are applied to: 1) the pathogenesis, consequences and treatment of obstructive sleep apnoea; and 2) exercise hyperpnoea and its control and limitations with ageing, chronic obstructive pulmonary disease and congestive heart failure.
Inspiratory vocal cord dysfunction, a new approach in treatment
Authors: G.j Archer, J.l Hoyle, A McCluskey, J Macdonald
Journal: European Respiratory Journal (2000)

Vocal cord dysfunction is a well recognized respiratory condition in which adduction of the vocal cords during either inspiration or expiration, or both, causes functional airways obstruction. Diagnosis is usually made by laryngofibreoscopy, however treatment of this condition has generally been unsatisfactory, requiring a multi-disciplinary approach consisting of speech therapy, psychological counselling, sedatives and anaesthetic agents. Here we use an innovative approach which requires relatively inexpensive and simple anaesthetic equipment in order to manipulate airways resistance and thus reduce any vocal cord dysfunction as it occurs. The patient involved found instant relief when using this simple device which is easy to use and is portable.
Langerhan's cell histiocytosis complicating small bowel Crohn's disease.
Authors: C Lee-Elliott, J Alexander, A Gould, R Talbot, J A Snook
Journal: Gut (1996)

Langerhan9s cell histiocytosis is a rare infiltrative disorder of unknown aetiology. A variety of tissues may be affected, but clinically evident intestinal involvement is unusual. An adult patient is described with Crohn9s disease of the terminal ileum who subsequently developed Langerhan9s cell histiocytosis with extensive infiltration of the small bowel.
Safe and Successful Treatment With Erlotinib After Gefitinib-Induced Hepatotoxicity: Difference in Metabolism As a Possible Mechanism
Authors: Takashi Kijima, Tomohito Shimizu, Shinpei Nonen, Mitsugi Furukawa, Yasushi Otani, Toshiyuki Minami, Ryo Takahashi, Haruhiko Hirata, Izumi Nagatomo, Yoshito Takeda, Hiroshi Kida, Sho Goya, Yasushi Fujio, Junichi Azuma, Isao Tachibana, Ichiro Kawase
Journal: Journal of Clinical Oncology (2011)
Asthma severity and susceptibility to air pollution
Authors: TJ Hiltermann, J Stolk, SC van der Zee, B Brunekreef, CR de Bruijne, PH Fischer, CB Ameling, PJ Sterk, PS Hiemstra, L van Bree
Journal: European Respiratory Journal (1998)

Exacerbations of asthma have been associated with exposure to ozone or particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10). We postulated in this study that the association of summertime air pollution (i.e. ozone and PM10) with acute respiratory symptoms, medication use and peak expiratory flow differs among patients grouped according to asthma severity. During the summer of 1995, effects of ambient air pollution on these parameters were studied in a panel of 60 nonsmoking patients with intermittent to severe persistent asthma. These patients were recruited from our Pulmonary Out-patient Clinic. Subgroup analysis was performed on the degree of hyperresponsiveness and lung steroid use before the start of the study, as indictors for the severity of asthma. Associations of the parameters studied with ozone, PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and black smoke were evaluated using time series analysis. Several episodes with increased summertime air pollution occurred during the 96 day study period. Eight hour average ozone concentrations exceeded the World Health Organization (WHO) Air Quality Guidelines (120 microg x m(-3)) on 16 occasions. Daily mean levels of PM10 were moderately elevated (range 16-98 microg x m(-3)). Levels of the other measured pollutants were low. There was a consistent, positive association of the prevalence of shortness of breath (maximal relative risk (RRmax) 1.18) with ozone, PM10, black smoke and NO2. In addition, bronchodilator use was associated with both ozone and PM10 levels (RRmax 1.16). Stratification by airway hyperresponsiveness and steroid use did not affect the magnitude of the observed associations. No associations with peak expiratory flow measurements were found. We conclude that the severity of asthma is not an indicator for the sensitivity to air pollution.
Blast-Related Traumatic Brain Injury in U.S. Military Personnel
Authors: Brian P Walcott, Kristopher T Kahle
Journal: New England Journal of Medicine (2011)

To the Editor: Mac Donald et al. (June 2 issue)(1) executed a unique and logistically difficult study in which they used quantitative diffusion tensor imaging (DTI) metrics to evaluate blast-injured military personnel with and without a clinical diagnosis of mild traumatic brain injury (mTBI).(2)-(4) Although nominally identical magnetic resonance imaging (MRI) scanners were used at the two locations, the measurements of relative anisotropy in the cingulum bundles obtained in Landstuhl, Germany, for the two cohorts (about 0.39 for the control group and about 0.37 for the TBI group [Figure 4A of the article]) differed from those noted on the . . . Language: en
Successful Treatment of an Adynamic Bone Disorder with Bone Morphogenetic Protein-7 in a Renal Ablation Model
Authors: Richard J. Lund, Matthew R. Davies, Alex J. Brown, Keith A. Hruska
Journal: Journal of the American Society of Nephrology (2004)

An adynamic bone disorder (ABD) is an important complication of chronic kidney disease (CKD) of unknown etiology for which there is no adequate treatment. Reported is an animal model of ablative CKD complicated by an ABD characterized by the absence of secondary hyperparathyroidism and its successful treatment with a skeletal anabolic factor, bone morphogenetic protein-7 (BMP-7). Adult mice were subjected to electrocautery of the right kidney followed by left nephrectomy. Animals were randomized into groups fed normal chow or fed low-phosphate chow supplemented with calcitriol to maintain normophosphatemia in CKD. All groups were maintained on the regimens for 12 wk. Hyperphosphatemia, secondary hyperparathyroidism, and a mild osteodystrophy developed in the CKD/chow-fed group, as expected. When dietary phosphorus was restricted and calcitriol was administered in the CKD low-phosphate/calcitriol group (ABD), Ca, PO(4), and parathyroid hormone levels were maintained normal. A significant ABD developed in the ABD group characterized by significant depressions in osteoblast number, perimeters, bone formation rates, and mineral apposition rates when compared with the sham-operated, chow-fed group. The abnormal skeletal histomorphometry was reversed by BMP-7 therapy to normal values and significantly improved from the ABD group (P < 0.05). The sham-operated low-phosphate/calcitriol-fed control group and the CKD low-phosphate/calcitriol/BMP-7 groups had reduced phosphate levels compared with the other groups (P < 0.05). ABD produced in mice with CKD in the absence of hyperparathyroidism was successfully reversed with a bone anabolic, BMP-7, associated with a reduction in plasma phosphorus.
Functional Variants in the Lymphotoxin-α Gene Predict Cardiovascular Disease in Dialysis Patients
Authors: Yongmei Liu, Yvette Berthier-Schaad, Laura Plantinga, Nancy E. Fink, Russell P. Tracy, Wen Hong Kao, Michael J. Klag, Michael W. Smith, Josef Coresh
Journal: Journal of the American Society of Nephrology (2006)

TNF-beta that is encoded by lymphotoxin-alpha gene (LTA) regulates adhesion molecules and IL-6. Previously, a genome-wide case-control study showed that LTA gene variants predisposed to cardiovascular disease (CVD). In a prospective study of 775 dialysis patients, LTA and IL-6 gene variants were tested as independent predictors of CVD risk. Four polymorphisms in the LTA gene and one in the IL-6 gene were genotyped. CVD events were ascertained from medical records. During a mean follow-up of 2.6 yr, 294 first-incident CVD events occurred. The LTA 26Asn variant predicted higher adjusted CVD risk (hazard ratio HR 1.33 for each additional copy of Asn allele; 95% confidence interval 1.14 to 1.55; P = 0.0003). Two other nonsynonymous polymorphisms in the LTA, 13Agr and 51Pro, were associated with lower inflammatory activity and CVD risk. LTA haplotypes (based on all four single-nucleotide polymorphisms) were associated with inflammatory markers and predicted CVD risk (P = 0.005) after adjustment. These LTA genotype associations were independent of the IL-6 -174G/C genotype association that was reported recently. LTA and IL-6 gene variants independently predicted risk for CVD among dialysis patients, suggesting that susceptibility in multiple inflammatory pathways contribute to the development of CVD.
Density of adrenoceptors in rat heart and lymphocytes 48 hours and 7 days after acute myocardial infarction
Authors: W VLEEMING, P A VAN DER WOUW, J D TE BIESEBEEK, H H VAN ROOIJ, J WEMER, A J PORSIUS
Journal: Cardiovascular Research (1989)

Journal Article Density of β adrenoceptors in rat heart and lymphocytes 48 hours and 7 days after acute myocardial infarction Get access W VLEEMING, W VLEEMING From the Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands Address for correspondence and reprints: W Vleeming Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, Croesestraat 79, 3522 AD Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar P A VAN DER WOUW, P A VAN DER WOUW From the Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar J D TE BIESEBEEK, J D TE BIESEBEEK From the Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar H H VAN ROOIJ, H H VAN ROOIJ From the Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar J WEMER, J WEMER From the Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar A J PORSIUS A J PORSIUS From the Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 10, October 1989, Pages 869, https://doi.org/10.1093/cvr/23.10.869 Published: 01 October 1989 Article history Accepted: 27 April 1989 Published: 01 October 1989
Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease
Authors: Meritxell Gironella, Juan Lucio Iovanna, Miquel Sans, Félix Gil, Mireia Peñalva, Daniel Closa, Rosa Miquel, Josep Maria Piqué, Julián Panés
Journal: Gut (2005)

Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation.Serum PAP levels were determined in healthy controls (n = 29), inflammatory controls (n = 14), and IBD patients (n = 171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor kappaB (NFkappaB) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo.Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn's disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-alpha induced NFkappaB activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression.PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NFkappaB activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.
The Cytoplasmic Deacetylase HDAC6 Is Required for Efficient Oncogenic Tumorigenesis
Authors: Yi-Shan Lee, Kian-Huat Lim, Xing Guo, Yoshiharu Kawaguchi, Yasheng Gao, Tomasa Barrientos, Peter Ordentlich, Xiao-Fan Wang, Christopher M. Counter, Tso-Pang Yao
Journal: Cancer Research (2008)

Abstract Histone deacetylase inhibitors (HDACI) are promising antitumor agents. Although transcriptional deregulation is thought to be the main mechanism underlying their therapeutic effects, the exact mechanism and targets by which HDACIs achieve their antitumor effects remain poorly understood. It is not known whether any of the HDAC members support robust tumor growth. In this report, we show that HDAC6, a cytoplasmic-localized and cytoskeleton-associated deacetylase, is required for efficient oncogenic transformation and tumor formation. We found that HDAC6 expression is induced upon oncogenic Ras transformation. Fibroblasts deficient in HDAC6 are more resistant to both oncogenic Ras and ErbB2-dependent transformation, indicating a critical role for HDAC6 in oncogene-induced transformation. Supporting this hypothesis, inactivation of HDAC6 in several cancer cell lines reduces anchorage-independent growth and the ability to form tumors in mice. The loss of anchorage-independent growth is associated with increased anoikis and defects in AKT and extracellular signal-regulated kinase activation upon loss of adhesion. Lastly, HDAC6-null mice are more resistant to chemical carcinogen-induced skin tumors. Our results provide the first experimental evidence that a specific HDAC member is required for efficient oncogenic transformation and indicate that HDAC6 is an important component underlying the antitumor effects of HDACIs. [Cancer Res 2008;68(18):7561–9]
Clinical applications of preimplantation genetic testing
Authors: P. R. Brezina, W. H. Kutteh
Journal: BMJ (2015)

Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most.
Diagnosis of<i>Clostridium difficile</i>Infection
Authors: Erik R. Dubberke, Carey-Ann D. Burnham
Journal: JAMA Internal Medicine (2015)

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Possible Prediction of Chemoradiosensitivity of Esophageal Cancer by Serum Protein Profiling
Authors: Yasuharu Hayashida, Kazufumi Honda, Yoshiaki Osaka, Tomohiko Hara, Tomoko Umaki, Akihiko Tsuchida, Tatsuya Aoki, Setsuo Hirohashi, Tesshi Yamada
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Establishment of a reliable method of predicting the efficacy of chemotherapy and radiotherapy is necessary to provide the most suitable treatment for each cancer patient. We investigated whether proteomic profiles of serum samples obtained from untreated patients were capable of being used to predict the efficacy of combined preoperative chemoradiotherapy against esophageal cancer. Experimental Design: Proteomic spectra were obtained from a training set of 27 serum samples (15 pathologically diagnosed responders to preoperative chemoradiotherapy and 12 nonresponders) by surface-enhanced laser desorption and ionization coupled with hybrid quadrupole time-of-flight mass spectrometry. A proteomic pattern prediction model was constructed from the training set by machine learning algorithms, and it was then tested with an independent validation set consisting of serum samples from 15 esophageal cancer patients in a blinded manner. Results: We selected a set of four mass peaks, at 7,420, 9,112, 17,123, and 12,867 m/z, from a total of 859 protein peaks, as perfectly distinguishing responders from nonresponders in the training set with a support vector machine algorithm. This set of peaks (i.e., the classifier) correctly diagnosed chemoradiosensitivity in 93.3% (14 of 15) of the cases in the validation set. Conclusions: Recent mass spectrometric approaches have revealed that serum contains a large volume of information that reflects the microenvironment of diseased organs. Although a multi-institutional large-scale study will be necessary to confirm each component of the classifier, there is a subtle but definite difference in serum proteomic profile between responders and nonresponders to chemoradiotherapy.
Agreement Between Artificial Neural Networks and Experienced Electrocardiographer on Electrocardiographic Diagnosis of Healed Myocardial Infarction11This study was supported by grants from the Swedish Medical Research Council (B95-14X-09893-04B), Stockholm; Swedish National Board for Industrial and Technical Development, Stockholm; the Faculty of Medicine at Lund University, Lund, Sweden; the Göran Gustafsson Foundation for Research in National Science and Medicine, Stockholm; and the Swedish …
Authors: BO HEDÉN, MATTIAS OHLSSON, RALF RITTNER, OLLE PAHLM, WESLEY K. HAISTY, CARSTEN PETERSON, LARS EDENBRANDT
Journal: Journal of the American College of Cardiology (1996)