tbuckley/cabot-search huggingface dataset:
Patient privacy rule goes into effect
Authors: Charles Marwick
Journal: BMJ (2003)

This article originally appeared in BMJ USA 

Washington—As the final rule aimed at protecting the privacy of patients' medical records goes into effect, it is giving rise to just as much controversy as it generated when it was being drafted. The criticisms come, not just from health insurers, hospitals, and the health care industry (who say it will impose unacceptable costs), but also from significant segments of the medical profession, such as the American Medical Association (AMA) and the American Psychiatric Association (APA). At the same time, among the professional medical groups at least, there is agreement that it is better than nothing. The AMA has long supported patient records protection, but points out that the final rule does not fully achieve that goal.

The rule was issued by the Department of Health and Human Services (HHS) at the end of December. It lays out standards for protecting personal health records of all types—electronic, paper and even oral communications. “This is what American patients and their providers want and need,” said Dr Donna Shalala, the previous HHS Secretary, speaking at a press conference. She hailed the rule as a landmark in achieving privacy of medical records. …
The role of the frizzled-8 receptor in COPD with chronic mucus hypersecretion
Authors: Anita Spanjer, Mark Menzen, Akkelies Dijkstra, Corry-Anke Brandsma, Dirkje Postma, Wim Timens, Herman Meurs, Irene Heijink, Reinoud Gosens
Journal: European Respiratory Journal (2013)

RATIONALE

Chronic mucus hypersecretion (CMH) is a phenotype of chronic obstructive pulmonary disease (COPD) and is associated with accelerated lung function decline and increased mortality. Upon damage, the airway epithelium can release interleukin (IL)-1β and epidermal growth factor (EGF). These factors can influence fibroblasts directly beneath the epithelium, resulting in the production of cytokines which can initiate mucus hypersecretion. We have previously shown increased expression of the Frizzled-8 receptor (FZD8) in fibroblasts of COPD patients. Here we investigated a possible link between FZD8 and CMH in COPD.

METHODS

Human airway and parenchymal lung fibroblasts were stimulated with IL-1β or EGF. Specific siRNA was used to knock down FZD8. Gene expression and cytokine secretion were measured using qPCR, Luminex® and ELISA. Genetic association studies for the FZD8 gene and CMH were performed in the NELSON cohort.

RESULTS

IL-1β and EGF increased FZD8 gene expression more in fibroblasts from COPD GOLD stage IV patients with CMH than in those without CMH and healthy controls. This effect was specific for FZD8, and not seen for other WNT pathway genes. In addition, a genetic association was found between SNP rs663700 in the FZD8 gene and CMH (p<0.01), further supporting a role for FZD8 in CMH in COPD. Interestingly, FZD8 siRNA reduced IL-1β-induced granulocyte macrophage colony-stimulating factor (GM-CSF) and G-CSF secretion as well as IL-1β- and EGF-induced IL-8 gene expression and cytokine secretion.

CONCLUSION

These findings imply a pro-inflammatory role for FZD8 in lung fibroblasts of COPD patients with chronic mucus hypersecretion.

Funded by the Netherlands Lung Foundation (NLF grant 3.2.10.042).
Agitation and Delirium at the End of Life
Authors: William Breitbart, Yesne Alici
Journal: JAMA (2008)

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TMPRSS2-ERGfusion transcript has diagnostic and prognostic potential in prostate cancer patients
Authors: Gyorgy Petrovics, Syed Shaheduzzaman, Bungo Furusato, Albert Dobi, Lakshmi Ravindranath, Christopher Cook, Yongmei Chen, Vasantha Srikantan, Jennifer Cullen, Isabell A. Sesterhenn, David G. McLeod, Shiv Srivastava
Journal: Clinical Cancer Research (2006)

A39   Introduction:  ERG  has been reported to be the most frequently overexpressed proto-oncogene in prostate cancer (CaP) (Petrovics  et al , Oncogene, 2006) due to recurrent gene fusion (Tomlins  et al , Science, 2006). To further determine diagnostic and prognostic potentials of  ERG  in CaP,  TMPRSS2-ERG  fusion and expression was analyzed in CaP patients for correlation with clinico-pathological features.Methods: Matched benign and malignant epithelial cells were obtained by laser capture micro-dissection (LCM) of radical prostatectomy (RP) specimens. RNA specimens from these cells were used for quantitative expression analyses (TaqMan RT-PCR) of  ERG  and  TMPRSS2 - ERG  fusion transcripts. Patients with predominantly well differentiated (WD, N=18) and poorly differentiated (PD, N=17) tumor foci were pre-selected for analysis from a pool of over 300 CaP patients undergoing RP. Correlation with clinico-pathologic features of CaP patients was evaluated using SAS version 9.1.Results: The expression of  TMPRSS2-ERG  fusions, and of  ERG1 , was determined by QRT-PCR (normalized to  GAPDH ) in matched microdissected tumor and benign epithelial cells from frozen RP specimens of 112 CaP patients (224 specimens). Overall 65 (58%) of CaP patients had detectable expression of  TMPRSS2-ERG  fusion A transcripts in CaP cells, but not in benign prostate epithelium. However, 15 (83%) of patients with predominantly WD tumor had detectable  TMPRSS2-ERG  fusion A transcript in contrast to 7 (41%) of patients with substantial amount of PD tumor cells. In line with our previous observations based on  ERG1  expression levels, patients with pT3-4 CaP (locally invasive tumor growing outside the capsule) had significantly lower expression of  TMPRSS2-ERG  fusion A transcript as compared to patients with pT2 stage disease (organ confined).Conclusions: Our study underscores both diagnostic and prognostic features of  ERG  and  TMPRSS2-ERG  gene fusion expression in CaP, and confirms that  ERG  fusion A is the predominant gene fusion in CaP cells. Decreased expression of  TMPRSS2-ERG  fusion transcript significantly associated with poor tumor differentiation status and with more advanced pathological stage of CaP.
Abstract 17381: Hyponatremia as a Predictor for Adverse Events in Patients With Heart Failure Receiving Cardiac Resynchroniation Therapy
Authors: Ajay K Sharma, Jagdesh Kandala, Eszter M Vegh, Mary Orencole, Alexandra Miller, Kimberly A Parks, E. Kevin Heist, Jagmeet P Singh
Journal: Circulation (2013)

INTRODUCTION:  Hyponatremia portends a poor prognosis in patients with heart failure. The aim of this study was to evaluate prognostic implication of hyponatremia on adverse events in heart failure patients receiving cardiac resynchronization therapy (CRT). Additionally, the impact of improvement of hyponatremia after CRT implant is evaluated.   METHODS:  In this retrospective analysis, we included patients in whom a CRT device was implanted between April 2004 and April 2011 at our institution and had baseline sodium within 72 hours of implant. The patients were followed up for 3 years post-implant for blood chemistry and subsequent adverse clinical events, i.e. hospitalization for heart failure, left ventricular assist device or heart transplant and cardiac death. Hyponatremia was defined as a serum sodium level    RESULTS:  In all 319 patients were included (age 69± 12 years, females 20%). 149 adverse events were noted in this period. In a multivariate model, hyponatremia [HR 1.52, 95%CI (1.06-2.17), p=0.021], Creatinine greater than 2 mg/dl [HR 1.75, 95%CI (1.2-2.5) p=0.004] and need for diuretics [HR 2.14, 95%CI (1.05-4.38), p=0.036] were associated with occurrence of adverse events. 62% of patients with hyponatremia at baseline had adverse events as compared to 42% of those with normal sodium concentration (p=0.002). Kaplan Meier curve showed that hyponatremic patients fared worse (Figure A). Also, patients in whom hyponatremia resolved after CRT implantation had less frequent adverse events as compared to patients who had normal pre-CRT sodium but developed hyponatremia later (Figure B).   CONCLUSIONS:  Baseline hyponatremia is associated with a worse prognosis after CRT implantation. Post-CRT improvement of hyponatremia is associated with improved clinical outcomes.
Abstract 1685: HER2 upregulation induced by gemcitabine treatment augments antitumor effect of trastuzumab emtansine against pancreatic cancer
Authors: Shin Kan, Shigeo Koido, Masato Okamoto, Kazumi Hayashi, Masaki Ito, Yuko Kamata, Hideo Komita, Eijiro Nagasaki, Sadamu Homma
Journal: Cancer Research (2014)

Abstract [Background] Although human pancreatic cancer (PC) frequently expresses human epidermal growth factor receptor type 2 (HER2), Trastuzumab has not provided sufficient therapeutic effect on PC probably due to low HER2 expression level. Recently we discovered HER2 expression of human PC cell lines was enhanced by gemcitabine (GEM) treatment. Furthermore, Trastuzumab Emtansine (T-DM1), Trastuzumab conjugated with a cytotoxic agent, showed promising results in breast cancer therapy. We investigated the possibility of new molecular targeting therapy against PC by combined treatment with GEM and T-DM1. [Materials and Methods] HER2 expression was analyzed by quantitative Real Time-PCR, western blotting and flowcytometry. The cell proliferation was examined by spectrophotometry using the counting reagents. T-DM1 was provided by Genentech Inc. T-DM1 bindinig to HER2 on PC cell surface was analyzed by flowcytometry. [Results] GEM treatment enhanced HER2 expression at around two fold in three out of five human PC cell lines. GEM was the most potent agent to enhance HER2 expression of PC cells among the standard chemotherapeutic agents for PC treatment. T-DM1 binding to HER2 on GEM-treated MiaPaca-2 cells was increased in accordance with the up-regulation of HER2 expression. Combined treatment with GEM and T-DM1 synergistically inhibited the cell growth of MiaPaca-2, and this cytotoxic effect was inhibited by adding to Trastuzumab which did not show direct cytotoxic activity to PC cells. [Conclusions] GEM treatment enhances HER2 expression of PC cells which promotes T-DM1 binding to HER2 on PC cells. Combined treatment with GEM and T-DM1 might become a promising modality against HER2 positive PC. Citation Format: Shin Kan, Shigeo Koido, Masato Okamoto, Kazumi Hayashi, Masaki Ito, Yuko Kamata, Hideo Komita, Eijiro Nagasaki, Sadamu Homma. HER2 upregulation induced by gemcitabine treatment augments antitumor effect of trastuzumab emtansine against pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1685. doi:10.1158/1538-7445.AM2014-1685
Abstract 5547: A genetic variant near <i>KLK3</i> gene is associated with aggressive prostate cancer and can stratify Gleason score 7 patients
Authors: Jian Gu, Yonggang He, Sara S. Strom, Christopher J. Logothetis, Jeri Kim, Xifeng Wu
Journal: Cancer Research (2014)

Abstract Purpose: Gleason score (GS) 7 prostate cancer is a heterogeneous disease with significant differences in aggressiveness and prognosis. We sought to identify genetic biomarkers that may predict the aggressiveness of GS 7 diseases. Experimental Design: We genotyped 72 prostate cancer susceptibility single nucleotide polymorphisms (SNPs) identified in genome-wide association studies in 1827 white men with histologically confirmed prostate adenocarcinoma. SNPs associated with disease aggressiveness were identified by comparing high-aggressive (GS ≥8) and low-aggressive (GS ≤6) cases. The significant SNPs were then tested to see whether they could further stratify GS 7 prostate cancer. Results: Three SNPs_rs2735839, rs10486567, and rs103294_were associated with biopsy-proven high-aggressive (GS ≥8) prostate cancer (P &amp;lt; 0.05). Rs2735839 and rs10486567 were also associated with high D'Amico risk groups. Furthermore, the frequency of the variant allele (A) at rs2735839 was significantly higher in patients with biopsy-proven GS 4+3 disease than in those with GS 3+4 disease (P = 0.003). In multivariate logistic regression analysis, patients carrying the A allele at rs2735839 exhibited a 1.85-fold (95% 1.31-2.61) increased risk of being GS 4+3 compared to those with GS 3+4. Rs2735839 is located 600 base pair downstream of KLK3 gene (encoding PSA) on 19q13.33 and has been shown to modulate PSA level, providing strong biological plausibility for its association with prostate cancer aggressiveness. Conclusions: We showed the association of the rs2735839 with high-aggressive prostate cancer (GS ≥8). Moreover, we reported for the first time that rs2735839 can stratify GS 7 patients, which would be clinically important for more accurately assessing the clinical behavior of the intermediate-grade prostate cancer and for tailoring personalized treatment and post-treatment management. Citation Format: Jian Gu, Yonggang He, Sara S. Strom, Christopher J. Logothetis, Jeri Kim, Xifeng Wu. A genetic variant near KLK3 gene is associated with aggressive prostate cancer and can stratify Gleason score 7 patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5547. doi:10.1158/1538-7445.AM2014-5547
Misinformation on Plant Proteins
Authors: John McDougall
Journal: Circulation (2002)

of mine 1 in which I corrected a statement made by the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. 2 This report states, "Although plant proteins form a large part of the human diet, most are deficient in 1 or more essential amino acids and are therefore regarded as incomplete proteins."This statement is not correct, as I have clearly shown in my letter.Accompanying my letter was a response from Barbara Howard, PhD, 3 who, I assume, represents the Nutrition Committee.Her letter was confusing and undocumented by a single scientific citation.However, rather than admit the Committee's report was in error, she reaffirmed their previous position by writing ". ..we did carefully state that 'most' are deficient in one or more essential amino acids.
Abstract 19539: Obstructive Sleep Apnea Screening Resulting in Improved CVD Risk Score
Authors: Mary Ann McLaughlin, Rupa L Iyengar, Heather N Beebe, Bianca Jamar, Mark Woodward, Laura Crowley, Cynara Maceda
Journal: Circulation (2014)

Introduction: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder with a prevalence of 15 - 20% in the general population. OSA is related to numerous disorders and increases risk of cardiovascular disease (CVD) and CV events including myocardial infarction and cerebrovascular accidents. Behavioral modification is a quintessential component of treatment for OSA. Hypothesis: We sought to evaluate and quantify the impact of Law Enforcement Cardiac Screening (LECS) program on change in OSA risk. Methods: Patients seen in World Trade Center (WTC) LECS from 2008 - 2010 were reevaluated in WTC CHEST from 2012 - 2014. We analyzed 959 patients’ anthropometric measurements and CV risk factors against status of high risk for OSA (OSA+) defined as never met, only met criteria in LECS, only met criteria in CHEST and met criteria in both LECS and CHEST. OSA+ was defined as 2 or more positive categories on the Berlin Questionnaire (BQ). Independent t-test, ANOVA, and multivariate regression analyses were used to assess the impact of WTC LECS on OSA+ as it relates to body mass index (BMI), waist circumference, and high sensitivity CRP (hsCRP) Results: We found that those who only met high risk for OSA criteria in 2008 - 2010 (LECS only) had a significant decrease in BMI when reevaluated in 2012 - 2014 (CHEST) (41.5 kg/m2 vs. 38.4 kg/m2 respectively; p &lt; 0.001). Patients only diagnosed in 2008 - 2010 had a significant decrease in hsCRP compared to those diagnosed in 2012 - 2014 (-1.44 vs -0.37 respectively, p = 0.040). Conclusions: Using the BQ as screening tool for OSA in a large population of asymptomatic middle aged participants allowed identification approximately 40% of the initial screening population to be at OSA+. Identifying these participants allowed us to counsel and advise patients of pertinent behavioral modifications known to improve risks for OSA. These efforts resulted in significant reduction in anthropometric measurements and improved CVD 10 year risk.
Malignant Gliomas in Adulthood
Authors: Michael Ivan, Matthew Tate, Jennifer L. Clarke
Journal: Neuro-Oncology (2012)

Malignant gliomas are the most common type of primary malignant brain tumor, and glioblastoma is the most common malignant glioma. Standard initial therapy for glioblastoma includes aggressive surgical resection followed by a combination of focal radiation and chemotherapy with temozolomide; the role for chemotherapy in initial treatment of other malignant gliomas is less clear. Prognosis is poor, and recurrence of any malignant glioma is almost universal. This chapter provides an overview of malignant gliomas, their treatment, and ongoing research looking for more effective treatments.
Abstract 17683: Continuous Positive Airway Pressure Therapy Decreases Plasma Glucose Levels after the Glucose Load Even in Non-Diabetic Patients with Obstructive Sleep Apnea
Authors: Toru Watanabe, Akira Tamura, Yoshiyuki Kawano, Chikara Yoshimura, Shinichi Ando, Junichi Kadota
Journal: Circulation (2010)

Background: Much attention has been recently paid to the association between obstructive sleep apnea (OSA) and impaired glucose metabolism. However, little information is available on the effects of continuous positive airway pressure (CPAP), an established therapy for OSA, on plasma glucose levels in an oral glucose tolerance test (OGTT) in patients with OSA. Methods: A total of 43 non-diabetic patients who underwent full polysomnography and who were diagnosed as having OSA with an apnea-hypopnea index (AHI) ≥20 were enrolled in this study. The patients underwent 75-g OGTTs at baseline and after 6 months. The patients were divided into the following 2 groups: 29 patients (CPAP group) who continued CPAP therapy for 6 months and 14 patients (non-CPAP group) in whom CPAP therapy could not be initiated because of intolerance of the therapy. Results: The fasting glucose level increased significantly in the non-CPAP group, whereas it did not change significantly in the CPAP group. The plasma glucose level at 2...
448. Armed Oncolytic Adenovirus with an Antiangiogenic Gene, sflt-1: A Novel Effective Antitumor Approach
Authors: Zilai Zhang, Jinhui Wang, Weiguo Zou, Binghua Li, Zifei Pei, Jinfa Gu, Cheng Qian, Xinyuan Liu
Journal: Molecular Therapy (2004)

Top of pageAbstract
Armed oncolytic adenoviruses represent an appealing tumor treatment. In this paper, considing that angiogenesis play an important role in tumor growth, the antiangiogenic gene, sflt-1(1-3) (the first three extracellular domain of hVEGF receptor) was inserted into ZD55 (an E1B55-kD deleted oncolytic adenovirus previously constructed in our lab) to form ZD55-sflt-1. ZD55-sflt-1 could specifically induce cytopathic effect in tumor cells in vitro. The expression of sFLT-1 from ZD55-sflt-1 was much higher than that of replication–deficient Ad-sflt-1, which contributed to its stronger inhibitory effect of VEGF-induced HUVEC proliferation (35.4386% of control). Furthermore, a marked reduction of tumor growth was observed in ZD55-sflt-1-treated nude mice with subcutaneous human SW620 colon tumor. Its efficacy directly corrected with a decrease in microvessel density and an increase in apoptosis of tumor cells. A much more efficient antitumoral effect was obtained when ZD55-sflt-1 was combined with ZD55-trail (another oncolytic adenovirus engineered to express the tumor necrosis factor-related apoptosis-inducing ligand), which resulted in 57.14% complete tumor regression and 71.43% prolonged survival of mice. These results indicate that ZD55-sflt-1, which combines the advantages of oncolytic adenovirus and the antiangiogenic gene system, can result in a striking improvement in treatment efficacy, and is suitable for synergistic therapy with other agents.
Cytoskeletal regulation of the platelet glycoprotein Ib/V/IX–von Willebrand factor interaction
Authors: Nayna Mistry, Susan L. Cranmer, Yuping Yuan, Pierre Mangin, Sacha M. Dopheide, Ian Harper, Simon Giuliano, Dave E. Dunstan, Francois Lanza, Hatem H. Salem, Shaun P. Jackson
Journal: Blood (2000)
Abstract 11329: The Plasma Membrane Calcium ATPase Regulates Calcium Homeostasis, Function and Negative Signalling Events in Platelets
Authors: Antonia Solomon, Sarah Jones, David Sanz-Rosa, Lisa-Marie Holbrook, Christopher Moore, Ludwig Neyses, Michael Emerson
Journal: Circulation (2010)

Plasma membrane calcium ATPases (PMCAs) extrude calcium from a variety of cell types and have recently been shown to regulate signalling events and function in the cardiovascular system. PMCAs are ...
Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial
Authors: A M Grant, A Avenell, M K Campbell, A M McDonald, G S MacLennan, G C McPherson, F H Anderson, C Cooper, R M Francis, C Donaldson, W J Gillespie, C M Robinson, D J Torgerson, W A Wallace
Journal: The Lancet (2005)