tbuckley/cabot-search huggingface dataset:
Abstract 15632: The Implications of the Recent American College of Cardiology/American Heart Association Guidelines for the Treatment of Blood Cholesterol on a Rural Community: The Heart of New Ulm Project
Authors: Michael D Miedema, Abbey C Sidebottom, Arthur Sillah, Gretchen Benson, Jackie Boucher, Tom Knicklebine, Jeffrey J VanWormer
Journal: Circulation (2014)

Introduction: The impact of the new American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines on the volume of statin-eligible patients requires further analysis, particularly in rural communities who are rarely included in traditional large observational cohorts. Methods: We performed a cross-sectional analysis using data from the Heart of New Ulm Project, a population-based program aimed at reducing modifiable cardiovascular disease (CVD) risk factors in rural New Ulm, MN. According to 2010 census data, there were 7,855 adults aged 40-79 years in the target population at that time. The community is served by one health and electronic health records (EHR) system. EHR-based demographics, diagnoses, and medications were analyzed in residents aged 40-79 years in 2012-2013. The prevalence of indications for statin therapy and of use of statins and other lipid-lowering medications were analyzed according to the ACC/AHA guidelines. Results: There were 6,357 residents with a visit during the study period, of which 4,281 had adequate data and were included in the analysis (mean age 59.4 [10.2] years, 52.7% female). In our study sample, 2,529 (59%) met one of the 4 major indications for statin therapy (Table). Of those with an indication, 65% were on a statin, 11% were on a high-intensity statin, and 5% on other lipid-lowering agents. An age stratified analysis demonstrated that 86% of individuals 60-79 years old (n=2,036) are now statin-eligible compared to 35% of individuals 40-59 years old (n=2,245). Conclusion: Using contemporary EHR data from a rural Midwest community, approximately 3 in 5 middle-age residents qualify for statin therapy according to the new guidelines, but only two-thirds of those individuals were taking a statin. Full compliance with the new guidelines will require a significant increase in statin utilization, including more frequent use of high-intensity statins.
Identification of α<sub>2</sub>‐Macroglobulin as a Master Inhibitor of Cartilage‐Degrading Factors That Attenuates the Progression of Posttraumatic Osteoarthritis
Authors: Shaowei Wang, Xiaochun Wei, Jingming Zhou, Jing Zhang, Kai Li, Qian Chen, Richard Terek, Braden C. Fleming, Mary B. Goldring, Michael G. Ehrlich, Ge Zhang, Lei Wei
Journal: Arthritis & Rheumatology (2014)

To determine if supplemental intraarticular α2-macroglobulin (α2 M) has a chondroprotective effect in a rat model of osteoarthritis (OA).Using Western blotting, mass spectrometry, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry, α2 M was identified as a potential therapeutic agent through a comparison of α2 M concentrations in serum, synovial fluid (SF), and cartilage from normal subjects and patients with OA. In cultured chondrocytes, the effects of α2 M on interleukin-1 (IL-1)-induced cartilage catabolic enzymes were evaluated by Luminex assay and ELISA. In vivo effects on cartilage degeneration and matrix metalloproteinase 13 (MMP-13) concentration were evaluated in male rats (n = 120) randomized to 1 of 4 treatments: 1) anterior cruciate ligament transection (ACLT) and saline injections, 2) ACLT and 1 IU/kg injections of α2 M, 3) ACLT and 2 IU/kg injections of α2 M, or 4) sham operation and saline injections. Rats were administered intraarticular injections for 6 weeks. The concentration of MMP-13 in SF lavage fluid was measured using ELISA. OA-related gene expression was quantified by real-time quantitative polymerase chain reaction. The extent of OA progression was graded by histologic examination.In both normal subjects and OA patients, α2 M levels were lower in SF as compared to serum, and in OA patients, MMP-13 levels were higher in SF than in serum. In vitro, α2 M inhibited the induction of MMP-13 by IL-1 in a dose-dependent manner in human chondrocytes. In the rat model of ACLT OA, supplemental intraarticular injection of α2 M reduced the concentration of MMP-13 in SF, had a favorable effect on OA-related gene expression, and attenuated OA progression.The plasma protease inhibitor α2 M is not present in sufficient concentrations to inactivate the high concentrations of catabolic factors found in OA SF. Our findings suggest that supplemental intraarticular α2 M provides chondral protection in posttraumatic OA.
Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis
Authors: Crandall E. Peeler, Lindsey B. De Lott, Lina Nagia, Joao Lemos, Eric R. Eggenberger, Wayne T. Cornblath
Journal: JAMA Neurology (2015)

<h3>Importance</h3> The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. <h3>Objectives</h3> To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. <h3>Design, Setting, and Participants</h3> A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. <h3>Main Outcomes and Measures</h3> Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. <h3>Results</h3> Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04;<i>P</i> = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26;<i>P</i> = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68;<i>P</i> = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L;<i>P</i> = .002). <h3>Conclusions and Relevance</h3> We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease.
Abstract 278: The Association of Gender and Age with the Quality of Layperson CPR Performance
Authors: Marion Leary, David Buckler, Amit Agarwal, Benjamin S Abella, Audrey L Blewer
Journal: Circulation (2014)

Background: Clinical investigations have suggested that gender is associated with the quality of CPR, particularly chest compression (CC) depth, when performed by healthcare providers. Other studies have shown that performing CC depth &gt;50 mm may be difficult in clinical practice, and may depend on provider characteristics that impact strength. Few studies have examined the association of gender and age with layperson CPR. Objective: We sought to determine the association of gender and age on the quality of CPR performed by laypersons during simulated CPR performance. We hypothesize that female gender and increasing age may be associated with shallower CC depth. Methods: In a secondary analysis of a multicenter trial of CPR training for cardiac patient caregivers, CPR skills were assessed 6 months after training. We analyzed the association of subject age and gender with CC rate, depth and no-flow time. CPR metrics were captured using a CPR skill-recorder manikin. Each variable was analyzed independently, then via a multivariable regression model to adjust for confounders such as BMI. Results: Between 7/2012-4/2014, 401 laypersons completed a CPR assessment. Mean age was 51.5±14.0 years, 74% were female, and 50% had a high school diploma/GED. Overall, mean CC depth was 43.8±14.2 mm, mean rate was 87.9±14.2 per min, and mean no-flow time per min was 7.5±11.0 sec. Male subjects performed deeper CC than female subjects (48.2±1.2 v. 42.2±0.7, p&lt;0.01). As age increased, both male and female CC depth decreased significantly (see Table 1a and 1b). When analyzed independently, and controlling for other variables, BMI was not associated with CC depth. Additionally, there was no association between gender or age with CC rate or no-flow time while controlling for other variables. Conclusions: We found that female gender is associated with shallower CC depth and this difference was not confounded by BMI. Additionally, as lay providers increased in age, their CC depth decreased.
Infliximab for the treatment of psoriasis in the U.K.: 9 years’ experience of infusion reactions at a single centre
Authors: J.S. Wee, G. Petrof, K. Jackson, J.N.W.N. Barker, C.H. Smith
Journal: British Journal of Dermatology (2012)

Infliximab is an antitumour necrosis factor-α chimeric monoclonal antibody that is an established treatment for severe chronic plaque psoriasis. The recommended administration of a 2-h infusion followed by 2 h of monitoring is practised due to the potential occurrence of infusion reactions. However, accelerated infusions and shortened monitoring periods are used in patients with rheumatological disorders and inflammatory bowel disease without an increase in adverse events.To review the standard infliximab infusion protocol, the incidence of acute infusion reactions, the use of concomitant methotrexate and the clinical relevance of the 2-h postinfusion monitoring period.A retrospective case note and pharmacy database review of all infliximab infusions administered to patients with psoriasis at a tertiary dermatology centre was carried out.Fifty-nine consecutive patients received a total of 858 infliximab infusions (range 1-43 infusions per patient) between January 2001 and June 2010. The incidence of infusion reactions was 1.5%, affecting 16.9% of patients and occurring between the first and eleventh infusions. Mild, moderate and severe acute reactions occurred in 0.6% (n=5), 0.3% (n=3) and 0.3% (n=3) of infliximab infusions, respectively. Thirty-three patients (56%) received concomitant systemic treatments during part of or throughout the infliximab treatment, including 24 (41%) on methotrexate (5-20 mg weekly). The prevalence of infusion reactions in patients receiving infliximab alone was 27% compared with 4% in those receiving concomitant methotrexate (P=0.05). All infusion reactions were managed as per our trust protocol with only one infusion reaction occurring in the postinfusion period (10 min after infusion completion).The risk of infusion reactions in our cohort of patients was low, with the majority occurring early in the treatment cycle. Concomitant methotrexate may reduce this risk. A shortened postinfusion monitoring period can be safely considered.
Sexually Transmitted Diseases Among Users of Erectile Dysfunction Drugs: Analysis of Claims Data
Authors: Anupam B. Jena
Journal: Annals of Internal Medicine (2010)

Background: Pharmacologic treatments for erectile dysfunction (ED) have gained popularity among middle-aged and older men. Increased sexual activity among those who use these drugs raises concerns about sexually transmitted diseases (STDs). Objective: To examine the rates of STDs in men who use and do not use ED drugs. Design: Retrospective cohort study. Setting: Database of claims from 1997 to 2006 for 1 410 806 men older than age 40 years with private, employer-based insurance from 44 large companies. Patients: 33 968 men with at least 1 filled prescription for an ED drug and 1 376 838 patients with no prescription. Measurements: STD prevalence among users and nonusers of ED drugs. Results: Users of ED drugs had higher rates of STDs than nonusers the year before initiating ED drug therapy (214 vs. 106 annually per 100 000 persons; P = 0.003) and the year after (105 vs. 65; P = 0.004). After adjustment for age and other comorbid conditions, users of ED drugs had an odds ratio (OR) for an STD of 2.80 (95% CI, 2.10 to 3.75) in the year before initiating drug therapy; the OR was 2.65 (CI, 1.84 to 3.81) in the year after. These differences were largely due to infections with HIV. The OR for HIV infection was 3.32 (CI, 2.38 to 4.36) in the year before and 3.19 (CI, 2.11 to 4.83) in the year after an ED drug prescription was filled. Significant changes in STD rates from the year before to the year after the first ED drug prescription was filled were not documented (adjusted OR for STD for users before vs. after the first ED drug prescription was filled, 0.96 [CI, 0.87 to 1.06]). Limitation: Selection bias precludes conclusions about whether use of ED treatments directly leads to increases in STDs. Conclusion: Men who use ED drugs have higher rates of STDs, particularly HIV infection, both in the year before and after use of these drugs. The observed association between ED drug use and STDs may have more to do with the types of patients using ED drugs rather than a direct effect of ED drug availability on STD rates. Counseling about safe sexual practices and screening for STDs should accompany the prescription of ED drugs. Primary Funding Source: RAND Roybal Center, National Institutes of Health, and Agency for Healthcare Research and Quality.
Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial
Authors: Helena M Earl, Louise Hiller, Janet A Dunn, Clare Blenkinsop, Louise Grybowicz, Anne-Laure Vallier, Jean Abraham, Jeremy Thomas, Elena Provenzano, Luke Hughes-Davies, Ioannis Gounaris, Karen McAdam, Stephen Chan, Rizvana Ahmad, Tamas Hickish, Stephen Houston, Daniel Rea, John Bartlett, Carlos Caldas, David A Cameron, Larry Hayward
Journal: The Lancet Oncology (2015)

The ARTemis trial was developed to assess the efficacy and safety of adding bevacizumab to standard neoadjuvant chemotherapy in HER2-negative early breast cancer.
Clinical and microbiologic characteristics of adult patients with recurrent bacteraemia caused by extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae
Authors: C.-H. Lee, L.-H. Su, F.-J. Chen, Y.-F. Tang, C.-C. Chien, J.-W. Liu
Journal: Clinical Microbiology and Infection (2015)

The characteristics of patients with recurrent bacteraemia caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae (EK) are rarely described. Flomoxef belongs to the cephamycins group and demonstrates in vitro activity against ESBL-producing organisms. Whether flomoxef may be used for the treatment of such infections remains controversial. This retrospective case-control study enrolled adult patients who had bacteraemia caused by ESBL-EK during 2005-2011. Case patients were those who had more than one episode of ESBL-EK bacteraemia. Controls were those who were matched for age and interval time of blood sampling and had only one episode of ESBL-EK bacteraemia with subsequent bacteraemia episodes caused by other non-ESBL-EK bacteria. Pulsed-field gel electrophoresis and microbiologic profiles of the initial and subsequent ESBL-EK isolates were analysed. During the study period, 424 patients were found to have at least one positive blood culture after the first ESBL-EK bacteraemia episode, and 67 (15.8%) had a second episode of ESBL-EK bacteraemia. Bacteraemia resulting from vascular catheter-related infection (odds ratio, 3.24; 95% confidence interval, 1.31-8.05), and definitive therapy with flomoxef (odds ratio, 2.99; 95% confidence interval, 1.10-8.15) were both independent risk factors for the recurrence. Among the 56 patients with available ESBL-EK isolates for analysis, 38 (67.8%) were infected by genetically similar strains. In three of these 38 recurrent ESBL-EK bacteraemia cases caused by an identical strain, the minimum inhibitory concentrations of carbapenem for the subsequent K. pneumoniae isolates were fourfold or higher than the initial isolates. Recurrent bacteraemia was not uncommon in our patients with ESBL-EK bacteraemia, and most of the episodes were caused by identical strains.
Evaluation of isothiocyanates as potent inducers of carcinogen-detoxifying enzymes in the urinary bladder: critical nature of in vivo bioassay.
Authors: Rex Munday, Yuesheng Zhang, Jed W. Fahey, Hillary E. Jobson, Christine M. Munday, Jun Li, Katherine K. Stephenson
Journal: Cancer Research (2006)

5590   Deficiency of carcinogen-detoxifying phase 2 enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), increases bladder cancer risk in humans. We report that several isothiocyanates (ITCs) that have not been previously examined, 1-methylbutyl ITC in particular, potently and preferentially induce both GST and NQO1 in the rat bladder. Comparison of 25 ITCs that are closely related in chemical structures showed that a 3–5-carbon aliphatic side chain with a methyl group attached to the alpha carbon was crucial for maximal inducer activity in the bladder. Surprisingly, cell-based bioassays failed to predict the phase 2 enzyme-inducing activity of the ITCs in the bladder. Furthermore, while ITCs are principally metabolized  in vivo  to dithiocarbamates (DTCs), which are believed to serve as the carriers of ITCs and are rapidly eliminated and concentrated in the urine, the total urinary levels of ITC plus DTC did not correlate with the degree of GST and NQO1 induction by the ITCs in the bladder of rats. Thus, several underappreciated ITCs are exceedingly potent inducers of GST and NQO1 in the rat bladder, but were predicted neither by  in vitro  bioassays of phase 2 enzyme induction, nor by their appearance or concentration in urine  in vivo . Supported by Waikato Medical Research Foundation (New Zealand) and National Cancer Institute Grants CA80962 and CA100623 (USA).
SYMPATHICOBLASTOMA: REPORT OF A CASE IN AN ADULT, WITH A DISCUSSION OF THE PATHOGENESIS OF CEREBRAL METASTASES
Authors: J A DI FIORE
Journal: Annals of Internal Medicine (1956)

Case Reports1 December 1956SYMPATHICOBLASTOMA: REPORT OF A CASE IN AN ADULT, WITH A DISCUSSION OF THE PATHOGENESIS OF CEREBRAL METASTASESJOHN A. DI FIORE, M.D.JOHN A. DI FIORE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-45-6-1229 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSympathicoblastoma is a highly malignant tumor arising from sympathetic nerve tissues; relatively rare, it is yet one of the most frequently observed abdominal tumors in children under the age of four years.1 Its occurrence in an adult is indeed a rarity, and it is for this reason that the following case is presented. In addition, the primary site finally disclosed at autopsy proved to be most interesting.Sympathicoblastomas are known to arise most frequently from the adrenal medulla; however, they may take origin from other sympathetic tissues, such as in the paraganglionic tissue adjacent to the adrenals, in the retroperitoneal...Bibliography1. Ariel IM: Neuroblastoma (sympathicoblastoma), J. Neuropath. and Exper. Neurol. 11: 235, 1952. Google Scholar2. Globus JH: Metastatic brain tumors with bronchogenic carcinoma as a primary source, J. Mt. Sinai Hosp. 10: 533, 1944. Google Scholar3. Baker AB: Metastatic tumors of the nervous system, Arch. Path. 34: 495, 1942. Google Scholar4. Batson OV: The function of the vertebral veins and their role in the spread of metastases, Ann. Surg. 112: 138, 1940. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication July 22, 1955.From The Medical Division, St. Vincent's Hospital, New York, N. Y.Requests for reprints should be addressed to John A. Di Fiore, M.D., 11 Fifth Ave., New York 3, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1956Volume 45, Issue 6Page: 1229-1234KeywordsAutopsyChildrenLesionsMalignant tumorsNervesPancreasPathogenesis ePublished: 1 December 2008 Issue Published: 1 December 1956 PDF downloadLoading ...
Avrupa Üroloji Derneği Nörojenik Alt Üriner Sistem Disfonksiyonu Kılavuzu
Authors: Manfred Stöhrer a, Bertil Blok, David Castro-Diaz, Emanuel Chartier-Kastler, Giulio Del Popolo, Guus Kramer, Jürgen Pannek, Piotr Radziszewski, Jean-JacquesWyndaele
Journal: European Urology (2009)
Carboxyl Terminus of Hsp70‐Interacting Protein Regulation of Osteoclast Formation in Mice Through Promotion of Tumor Necrosis Factor Receptor–Associated Factor 6 Protein Degradation
Authors: Shan Li, Bing Shu, Yanquan Zhang, Jia Li, Junwei Guo, Yinyin Wang, Fangli Ren, Guozhi Xiao, Zhijie Chang, Di Chen
Journal: Arthritis & Rheumatology (2014)

Carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) is an E3 ligase that regulates the stability of several proteins involved in tumor growth and metastasis. However, the role of CHIP in bone growth and bone remodeling in vivo has not been reported. This study was undertaken to investigate the role and mechanism of CHIP in regulation of bone mass and bone remodeling.The bone phenotype of Chip(-/-) mice was assessed by histologic, histomorphometric, and micro-computed tomographic analyses. The mechanism by which CHIP regulates the degradation of tumor necrosis factor receptor-associated factor 6 (TRAF6) and the inhibition of NF-κB signaling was examined by immunoprecipitation, Western blot, and luciferase reporter assays.Deletion of the Chip gene led to an osteopenic phenotype and increased osteoclast formation. TRAF6, an adaptor protein that is a key regulator of NF-κB signaling and is critical for RANKL-induced osteoclastogenesis, was up-regulated in osteoclasts from Chip(-/-) mice. CHIP interacted with TRAF6 to promote TRAF6 ubiquitination and proteasome degradation. Further, CHIP inhibited p65 nuclear translocation, leading to the repression of TRAF6-mediated NF-κB transcription.CHIP inhibits NF-κB signaling by promoting TRAF6 degradation and plays an important role in osteoclastogenesis and bone remodeling. These findings suggest that CHIP may be a novel therapeutic target in bone loss-associated disorders.