tbuckley/cabot-search huggingface dataset:
Rectal mucosal ornithine decarboxylase activity in familial adenomatous polyposis after ileorectal anastomosis.
Authors: S E Patchett, E M Alstead, L Trzeciak, T Wocial, R K Phillips, M J Farthing
Journal: Gut (1994)

Resection of the colon in patients with familial adenomatous polyposis frequently results in the regression of polyps in the remaining rectum, suggesting a reduction of cellular proliferation. These patients remain at risk of developing rectal cancer but whether this risk increases with time is uncertain. Since ornithine decarboxylase activity is associated with cellular proliferation, mucosal ornithine decarboxylase was measured in rectal biopsy specimens from patients with familial adenomatous polyposis after ileorectal anastomosis (n = 36) and from normal controls (n = 30). The relationship between ornithine decarboxylase activity, age, and time from surgery was also examined. Median ornithine decarboxylase activity in familial adenomatous polyposis patients after ileorectal anastomosis (186, interquartile range (IQR) 107-534 pmol/mg protein/h) was not different from that in control subjects (227, IQR 123-374, p = 0.6). When patients were divided into three equal groups according to age, however, younger patients (&lt; 25 years) had significantly higher activity than both older age groups (p &lt; 0.02). Similarly, when patients were stratified according to the time elapsed since surgery, those who had had surgery less than six years previously had a significantly higher ornithine decarboxylase activity than those in whom a longer time interval had elapsed since surgery (p = 0.02). These results indicate that after colon resection, ornithine decarboxylase activity in patients with familial adenomatous polyposis is similar to that in normal controls but seems to fall over time. This may explain the regression of rectal polyps after colonic resection in this disorder.
Effect of whole-body CT during trauma resuscitation on survival: a retrospective, multicentre study
Authors: Stefan Huber-Wagner, Rolf Lefering, Lars-Mikael Qvick, Markus Körner, Michael V Kay, Klaus-Jürgen Pfeifer, Maximilian Reiser, Wolf Mutschler, Karl-Georg Kanz
Journal: The Lancet (2009)
A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences
Authors: Thomas J. Hoffmann, Stephen K. Van Den Eeden, Lori C. Sakoda, Eric Jorgenson, Laurel A. Habel, Rebecca E. Graff, Michael N. Passarelli, Clinton L. Cario, Nima C. Emami, Chun R. Chao, Nirupa R. Ghai, Jun Shan, Dilrini K. Ranatunga, Charles P. Quesenberry, David Aaronson, Joseph Presti, Zhaoming Wang, Sonja I. Berndt, Stephen J. Chanock, Shannon K. McDonnell, Amy J. French, Daniel J. Schaid, Stephen N. Thibodeau, Qiyuan Li, Matthew L. Freedman, Kathryn L. Penney, Lorelei A. Mucci, Christopher A. Haiman, Brian E. Henderson, Daniela Seminara, Mark N. Kvale, Pui-Yan Kwok, Catherine Schaefer, Neil Risch, John S. Witte
Journal: Cancer Discovery (2015)

A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated in PEGASUS (N = 7,539) and the Multiethnic Cohort (N = 4,679) with an overall P = 1.0 × 10(-19) (OR, 1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (P = 1.3 × 10(-23)) and SLC22A3 (P = 3.2 × 10(-52)). At the known 19q13.33 locus, rs2659124 (P = 1.3 × 10(-13); OR, 1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (P < 1.0 × 10(-8)). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained approximately 7.6% of disease heritability. The entire GWAS array explained approximately 33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (P = 0.004).
Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer
Authors: Jack Cuzick, Mitch Dowsett, Silvia Pineda, Christopher Wale, Janine Salter, Emma Quinn, Lila Zabaglo, Elizabeth Mallon, Andrew R. Green, Ian O. Ellis, Anthony Howell, Aman U. Buzdar, John F. Forbes
Journal: Journal of Clinical Oncology (2011)

Purpose We recently reported that the mRNA-based, 21-gene Genomic Health recurrence score (GHI-RS) provided additional prognostic information regarding distant recurrence beyond that obtained from classical clinicopathologic factors (age, nodal status, tumor size, grade, endocrine treatment) in women with early breast cancer, confirming earlier reports. The aim of this article is to determine how much of this information is contained in standard immunohistochemical (IHC) markers. Patients and Methods The primary cohort comprised 1,125 estrogen receptor–positive (ER-positive) patients from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial who did not receive adjuvant chemotherapy, had the GHI-RS computed, and had adequate tissue for the four IHC measurements: ER, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Distant recurrence was the primary end point, and proportional hazards models were used with sample splitting to control for overfitting. A prognostic model that used classical variables and the four IHC markers (IHC4 score) was created and assessed in a separate cohort of 786 patients. Results All four IHC markers provided independent prognostic information in the presence of classical variables. In sample-splitting analyses, the information in the IHC4 score was found to be similar to that in the GHI-RS, and little additional prognostic value was seen in the combined use of both scores. The prognostic value of the IHC4 score was further validated in the second separate cohort. Conclusion This study suggests that the amount of prognostic information contained in four widely performed IHC assays is similar to that in the GHI-RS. Additional studies are needed to determine the general applicability of the IHC4 score.
Antioxidant Vitamin C Improves Endothelial Function in Obstructive Sleep Apnea
Authors: Mathias Grebe, Hans Joachim Eisele, Norbert Weissmann, Christian Schaefer, Harald Tillmanns, Werner Seeger, Richard Schulz
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Obstructive sleep apnea (OSA) is associated with oxidative stress, endothelial dysfunction, and increased cardiovascular morbidity and mortality.We tested the hypothesis that endothelial dysfunction in patients with OSA is linked to oxidative stress.In the present study, we measured flow-mediated dilation (FMD) of the brachial artery by ultrasound in 10 otherwise healthy, untreated patients with OSA and 10 age-and sex-matched control subjects without sleep-disordered breathing before and after intravenous injection of the antioxidant vitamin C. The investigator performing the FMD measurements was blinded to the status of the patients.When compared with control subjects, baseline FMD was significantly reduced in the patients with OSA. After intravenous injection of 0.5 g vitamin C, vasoreactivity remained unchanged in the control subjects. In the patients with OSA, ascorbate led to an increase in FMD to a level comparable to that observed in the control group.The reduced endothelial-dependent vasodilation in untreated patients with OSA acutely improves by the free radical scavenger vitamin C. These results are in favor of oxidative stress being responsible for the endothelial dysfunction in OSA. Antioxidant strategies should be explored for the treatment of OSA-related cardiovascular disease.
Human Epidermal Growth Factor Receptor 2 Overexpression As a Prognostic Factor in a Large Tissue Microarray Series of Node-Negative Breast Cancers
Authors: Stephen Chia, Brian Norris, Caroline Speers, Maggie Cheang, Blake Gilks, Allen M. Gown, David Huntsman, Ivo A. Olivotto, Torsten O. Nielsen, Karen Gelmon
Journal: Journal of Clinical Oncology (2008)

Purpose Human epidermal growth factor receptor 2 gene (HER2) is associated with a poorer outcome in node-positive breast cancer, but the results are conflicting in node-negative disease. This study assessed the prognostic impact of HER2 overexpression/amplification in a large series of node-negative breast cancers. Patients and Methods A tissue microarray (TMA) series was constructed consisting of 4,444 invasive breast cancers diagnosed in British Columbia from 1986 to 1992. Within this series, 2,026 patients were node negative, of whom 70% did not receive adjuvant systemic therapy. The TMA series was assessed for estrogen receptor (ER) and HER2. Logistic regression modeling was used to estimate odds ratios at the 10-year follow-up. Results HER2 was positive in 10.2% of the node-negative cohort. In this cohort, an inferior outcome was seen in patients with HER2-positive tumors compared with HER2-negative tumors for 10-year relapse-free survival (RFS; 65.9% v 75.5%, respectively; P = .01), distant RFS (71.2% v 81.8%, respectively; P = .004), and breast cancer–specific survival (BCSS; 75.5% v 86.3%, respectively; P = .001). A trend for a worse overall survival was also seen (P = .06). HER2 was an independent poor prognostic factor for RFS and BCSS at 10 years, with odds ratios of 1.71 (P = .01) and 2.03 (P = .003), respectively. The number of HER2-positive tumors that were ≤ 1 cm was small, but there was a trend for a worse outcome in T1b tumors. Conclusion HER2 overexpression/amplification is correlated with a poorer outcome in node-negative breast cancer. Larger studies are needed to more clearly define the prognostic impact of HER2 in tumors ≤ 1 cm, particularly within the separate hormone receptor subgroups.
Outcome of COPD patients with mild daytime hypoxaemia with or without sleep-related oxygen desaturation
Authors: A. Chaouat, E. Weitzenblum, R. Kessler, R. Schott, C. Charpentier, P. Levi-Valensi, J. Zielinski, L. Delaunois, R. Cornudella, J. Moutinho dos Santos
Journal: European Respiratory Journal (2001)

The aim of the present study was to compare the evolution of pulmonary haemodynamics and of arterial blood gases in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate hypoxaemia, with or without sleep-related oxygen desaturation. COPD patients with daytime arterial oxygen partial pressure in the range 56–69 mmHg were included prospectively. Sleep-related oxygen desaturation was defined as spending ≥30% of the nocturnal recording time with arterial oxygen saturation &lt;90%. From the 64 patients included, 35 were desaturators (group 1) and 29 were nondesaturators (group 2). At baseline ( t 0 ), patients with sleep-related desaturation had a significantly higher daytime (mean±sd) arterial carbon dioxide partial pressure ( P a,CO 2 ) (44.9±4.9 mmHg versus 41.0±4.1 mmHg, p=0.001) whereas mean pulmonary artery pressure (mPAP) was similar in the two groups. After 2 yrs ( t 2 ) of follow-up, 22 desaturators and 14 nondesaturators could be re-evaluated, including pulmonary haemodynamic measurements. None of the nondesaturator patients became desaturators at t 2 . The difference between the two groups in terms of daytime P a,CO 2 was still present at t 2 . The mean changes in mPAP from t 0 to t 2 were similar between the two groups, as were the rates of death or requirement for long-term oxygen therapy (American Thoracic Society criteria) during follow-up of up to 6 yrs. The presence of sleep-related oxygen desaturation is not a transitional state before the worsening of daytime arterial blood gases, but is a characteristic of some chronic obstructive pulmonary disease patients who have a higher daytime arterial carbon dioxide partial pressure. Such isolated nocturnal hypoxaemia or sleep-related worsening of moderate daytime hypoxaemia does not appear to favour the development of pulmonary hypertension, nor to lead to worsening of daytime blood gases.
ZINC AND THE RISK FOR INFECTIOUS DISEASE
Authors: Christa Fischer Walker, Robert E. Black
Journal: Annual Review of Nutrition (2004)

Zinc is an essential micronutrient for human growth, development, and immune function. Zinc deficiency impairs overall immune function and resistance to infection. Mild to moderate zinc deficiency can be best detected through a positive response to supplementation trials. Zinc supplementation has been shown to have a positive effect on the incidence of diarrhea (18% reduction, 95% CI: 7-28%) and pneumonia (41% reduction, 95% CI: 17-59%), and might lead to a decrease in the incidence of malaria. Zinc has also proven to decrease the duration of diarrhea by 15% (95% CI: 5-24%). Maternal zinc supplementation may lead to a decrease in infant infections. Studies assessing the role of zinc supplementation among persons with HIV, tuberculosis, and the common cold have not been conclusive. Two studies have shown zinc supplementation to decrease child mortality by more than 50%. Zinc clearly has an important role in infant and childhood infectious diseases; programs to increase the intake of zinc among deficient populations are needed.
Thrombomodulin mutant mice with a strongly reduced capacity to generate activated protein C have an unaltered pulmonary immune response to respiratory pathogens and lipopolysaccharide
Authors: Anita W. Rijneveld, Sebastiaan Weijer, Sandrine Florquin, Charles T. Esmon, Joost C. M. Meijers, Peter Speelman, Pieter H. Reitsma, Hugo Ten Cate, Tom van der Poll
Journal: Blood (2003)
Troponin T and β-myosin mutations have distinct cardiac functional effects in hypertrophic cardiomyopathy patients without hypertrophy
Authors: Miriam Revera, Lize van der Merwe, Marshall Heradien, Althea Goosen, Valerie A. Corfield, Paul A. Brink, Johanna C. Moolman-Smook
Journal: Cardiovascular Research (2007)

The validity of genotype:phenotype correlation studies in human hypertrophic cardiomyopathy (HCM) has recently been questioned, yet animal models and in vitro studies suggest distinct effects for different mutations. The aims of this study were to investigate whether distinct HCM-mutations have different consequences for cardiac structure and function in the absence of the confounding effects of hypertrophy. Individuals aged 20–65 belonging to 21 R92WTNNT2, R403WMYH7, or A797TMYH7 mutation-bearing families were investigated with 2D, M-mode, and Doppler echocardiography. Cardiac structural and functional parameters were compared between prehypertrophic mutation-carriers and their non-carrier family members, with concomitant adjustment for appropriate covariates. Findings were evaluated against existing animal and in vitro functional data. The distinct functional effect of the R92WTNNT mutation was a relative increase in systolic functional parameters, that of the A797TMYH7 mutation was reduced diastolic function, while the R403WMYH7 mutation reduced both systolic and diastolic function. The observed early effects of the R92WTNNT2 mutation mechanistically fit with prolonged force-transients precipitated by increased Ca2+ sensitivity of the thin filament, and that of the MYH7 mutations with local ATP depletion. Evaluation of the impact of the mutations on cardiac structure and function in prehypertrophic mutation-carriers, relative to the baseline norm provided by their non-carrier family members, best recapitulated existing animal and in vitro functional data, while inclusion of mutation-carriers with hypertrophy obscured such findings. The results prompt speculation that timely treatment aimed at ameliorating Ca2+ sensitivity for R92WTNNT2-carriers, and energy depletion for MYH7 mutation-carriers, may offer a plausible approach for preventing progression from a preclinical into a decompensated state.
Significance of Morphological Abnormalities Detected by MRI in Patients Undergoing Successful Ablation of Right Ventricular Outflow Tract Tachycardia
Authors: Sebastian Globits, Gerhard Kreiner, Herbert Frank, Gottfried Heinz, Ursula Klaar, Bernhard Frey, Heinz Gössinger
Journal: Circulation (1997)

Background MRI can demonstrate subtle morphological changes of the right ventricle in patients with idiopathic right ventricular outflow tract tachycardia (RVOT). The present study examines the incidence and significance of right ventricular (RV) abnormalities detected by MRI with respect to the site of successful radiofrequency catheter ablation of the clinical tachycardia. Methods and Results The study population comprised 20 patients (mean age, 40±12 years) undergoing elimination of recurrent RVOT by radiofrequency catheter ablation. MRI studies were performed before ablation to assess RV volumes and function, as well as structural abnormalities of the RV myocardium. Ten healthy age- and sex-matched subjects served as control subjects. The successful ablation sites, as documented by radiographs of the catheter position, were compared with MRI findings. Patients with RVOT showed no difference in respect to RV volumes and ejection fractions compared with control subjects. Whereas RV abnormalities were limited to prominent fatty deposits of the right atrioventricular groove extending into the inlet portion of the RV wall in 2 of 10 control subjects, MRI studies demonstrated morphological changes of the RV free wall in 13 (65%) of 20 patients with RVOT, including presence of fatty tissue (n=5), wall thinning (n=9), and dyskinetic wall segments (n=4). Eight of these patients had additional fat deposits, thinning, or a saccular aneurysm in the RV outflow tract, corresponding with the ablation site in 6 patients. Conclusions In RVOT, structural abnormalities of the right ventricle can be detected in a substantial number of patients despite normal RV volumes and global function. MRI abnormalities within the RV outflow tract are significantly associated with the origin of tachycardia.
Generation and characterisation of monoclonal antibodies from single RA synovial B cells
Authors: Khaled Amara, Eric Meffre, Lena Israelsson, Monika Hansson, Omri Snir, Johanna Steen, Fiona Murray, Hedda Wardemann, Lars Klareskog, Vivianne Malmström
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Anticitrulline protein antibodies (ACPA) are a hallmark of HLA-associated rheumatoid arthritis (RA), but it is still not established whether these antibodies represent a cause or a consequence of arthritis. It is however clear that such antibodies can enhance murine arthritis, but a corresponding effect in patients is difficult to prove. In this study the authors aimed to assess the specificity and the immunoglobulin gene characteristics of B cells derived from RA synovial fluid of RA by using a method that allows in vitro production of monoclonal antibodies derived from single human memory B cells. <h3>Materials and methods</h3> The authors have cloned and expressed antibodies from single flow cytometry purified CD19+IgG+ B cells from synovial fluid of two ACPA+ and two ACPA- RA patients and tested, by ELISA, the generated recombinant monoclonal antibodies for reactivity to different known citrullinated antigens. <h3>Results</h3> On the molecular level, striking differences were found between ACPA+ and ACPA− patients taking into consideration the mutational pattern of the Ig genes. Indeed, based on DNA sequences, the authors could demonstrate that B cells from ACPA+ patients did not have more total mutations than ACPA− patients but when focusing on the CDR1, two and three regions of the Ig variable region, the ACPA+ clones displayed more replacement mutations than did the ACPA− clones. Regarding the specificity of the generated monoclonal antibodies, the authors have analysed clones from one ACPA+ and one ACPA negative patient. Our results so far show that 10 out of 23 antibodies generated from an ACPA+ RA patient, proved to bind, to variable degrees, to cyclic citrullinated peptide and different citrullinated antigens including citrullinated a-enolase, fibrinogen, vimentin and type II collagen. In contrast, no ACPA positive clones were identified amongst the antibodies derived from the ACPA− RA patient. <h3>Conclusions</h3> Our data suggest that citrulline-reactive B cells are common in synovial fluid and the Ig molecules bear clear signs of antigen-driven maturation.
International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation
Authors: Antonio Palumbo, S. Vincent Rajkumar, Jesus F. San Miguel, Alessandra Larocca, Ruben Niesvizky, Gareth Morgan, Ola Landgren, Roman Hajek, Hermann Einsele, Kenneth C. Anderson, Meletios A. Dimopoulos, Paul G. Richardson, Michele Cavo, Andrew Spencer, A. Keith Stewart, Kazuyuki Shimizu, Sagar Lonial, Pieter Sonneveld, Brian G.M. Durie, Philippe Moreau, Robert Z. Orlowski
Journal: Journal of Clinical Oncology (2014)

To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation.A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized.Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care.These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice.
Isolated Cardiac Involvement of B-Cell Acute Lymphoblastic Leukemia Mimicking Acute Myocardial Infarction With Persistent Broad ST-Segment Elevation
Authors: Yuki Kakefuda, Akira Sato, Tomoya Hoshi, Tomoko Ishizu, Hiroshi Tada, Kaishi Satomi, Yukio Morishita, Yasushi Okoshi, Chiho Tokunaga, Yuzuru Sakakibara, Kazutaka Aonuma
Journal: Circulation (2012)