tbuckley/cabot-search huggingface dataset:
Abstract 162: Cardiac Overexpression of Senescence Marker Protein 30 Inhibits Angiotensin II-Induced Cardiac Hypertrophy and Remodeling
Authors: Tomofumi Misaka, Satoshi Suzuki, Makiko Miyata, Atsushi Kobayashi, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation Research (2012)

Backgrounds: Senescence marker protein 30 (SMP30) was originally identified as an important aging marker protein, and assumed to behave as an anti-aging factor. Previously, we demonstrated that deficiency of SMP30 exacerbates angiotensin II (Ang II)-induced reactive oxygen species (ROS) and cardiac adverse remodeling, suggesting that SMP30 may have a protective role in the heart. Thus, this study aimed to test the hypothesis that up-regulation of SMP30 inhibits cardiac hypertrophy and remodeling in response to Ang II. Methods: We generated transgenic (SMP30-TG) mice with cardiac-specific overexpression of SMP30 gene using α-myosin heavy chain promoter. SMP30-TG mice and wild type littermate (WT) were subjected to continuous Ang II infusion (800 ng/kg/min). Results: After 2 weeks, heart weight was significantly lower in SMP30-TG mice than in WT mice (P&lt;0.01). Echocardiography revealed that calculated left ventricular mass and E/e’ were lower in SMP30-TG mice than in WT mice (P&lt;0.01 and P&lt;0.05, respectively), suggesting that diastolic function was preserved in SMP30-TG mice. Histological analysis showed that the degree of cardiac fibrosis was significantly decreased in SMP30-TG mice than in WT mice (P&lt;0.05). Dihydroethidium staining demonstrated that generation of ROS was reduced in SMP30-TG mice compared with WT mice (P&lt;0.05). Furthermore, the numbers of senescence-associated β-galactosidase-positive cardiomyocytes were decreased in SMP30-TG mice compared to WT mice (P&lt;0.05). In addition, p21 mRNA level was significantly suppressed in SMP30-TG mice compared to WT mice (P&lt;0.01). Conclusions: This study demonstrated cardiac-specific overexpression of SMP30 inhibits Ang II-induced cardiac hypertrophy and remodeling. These findings suggested that SMP30 has a cardio-protective role with anti-oxidative and anti-aging effects. Up-regulation of SMP30 might be a new strategy to approach senescent cardiac diseases and attenuate the development of heart failure particularly with hypertension.
Phase 1 study of the PARP inhibitor E7449 as a single agent in patients with advanced solid tumors or B-cell lymphoma.
Authors: Ruth Plummer, Divyanshu Dua, Nicola Cresti, Aneta Suder, Yvette Drew, Vasanthi Prathapan, Peter Stephens, Jared K Thornton, Begoña de las Heras, Barbara Ink, Lucy Lee, Mark Matijevic, Shannon McGrath, Debashis Sarker
Journal: Journal of Clinical Oncology (2014)

e19531^ Background: E7449 is an orally bioavailable, likely brain penetrable, potent small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) 1 and PARP 2 with an IC50 of 1.0 and 1.2 nmol/L respectively. E7449 is a poor P-gp substrate. Preclinically, E7449 potentiates the antitumor activity of chemotherapy and radiotherapy and has activity as a single-agent in BRCA-deficient and other tumors. A Phase 1 study of E7449 as a single agent is underway to determine the MTD, safety, PK, PD, preliminary activity and perform exploratory biomarker analysis. Methods: Patients (pts) with advanced solid tumors or B-cell lymphoma, ECOG PS 0-1, > 18 years (yrs) and adequate organ function are eligible. E7449 is administered orally, once daily (QD), continuously. Blood samples for PK, PD and biomarkers are collected at multiple time points. Results: 25 pts (median age: 66 yrs; M/F: 14/ 11) have been treated at 6 dose levels: 50, 100, 200, 400, 800 and 600 mg QD. Tumor types included: pancreatic (n=5), lung (n=4), ovarian (n=4), mesothelioma (n=3), breast (n=2) and others (n=7). Four DLTs have been observed at 800 mg: Gr3 fatigue (n=1) and Gr2 fatigue requiring more than 7days dose interruption (n=3). The MTD is expected to be 600 mg QD. Frequently occurring related adverse events (AEs) (any grade) are fatigue: 48% (Gr3: 12%), photosensitive rash (48%), diarrhea and nausea: 32% each, chromaturia: 28%, depression: 20%, and decreased appetite: 20% (Gr3: 4%). No significant hematological toxicity and no Gr4 related or fatal AEs have been reported. One partial response in a high grade serous ovarian cancer pt (BRCA unknown) and 5 stable diseases for >23 weeks have been observed, including one in a pancreatic cancer pt with BRCA2 variant of uncertain significance. E7449 PK exhibits rapid absorption, tmax ~1.5 hrs and elimination t1/2 ~ 9 hrs, with dose proportional exposures. Sustained PARP inhibition (PARPi) of ~90% is observed in PMBCs at 600 mg QD. Predictive biomarker analysis is ongoing. Conclusions: In this study, E7449 was generally well tolerated at the potential MTD of 600 mg QD, with preliminary evidence of antitumor activity and sustained PARPi in PMBCs. Further evaluation will continue in Phase 1b/2 combination studies. Clinical trial information: NCT01618136.
Corneal Topography of Phase III Excimer Laser Photorefractive Keratectomy
Authors: Barbara H. Schwartz-Goldstein, Peter S. Hersh, Marc Michelson, John Owen, Michael Gordon, John R. Wright, R. Doyle Stulting, Keith Thompson, George O. Waring, Stephen Brint, Roger Steinert, Carmen Puliafito, Michael Raizman, Daniel Durrie, Timothy Cavanaugh, John Hunkeler, Jay Pepose, J. Harley Galusha, Daniel H. Gold, Bernard A. Milstein, Daniel Durrie, Timothy Cavanaugh, John Hunkeler, Marc Michelson, John Owen, Michael Gordon, Roger Steinert, Carmen Puliafito, Michael Raizman, Jay Pepose
Journal: Ophthalmology (1995)
Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial
Authors: Annikki de Niet, Louis Jansen, Femke Stelma, Sophie B Willemse, Sjoerd D Kuiken, Sebastiaan Weijer, Carin M J van Nieuwkerk, Hans L Zaaijer, Richard Molenkamp, R Bart Takkenberg, Maarten Koot, Joanne Verheij, Ulrich Beuers, Hendrik W Reesink
Journal: The Lancet. Gastroenterology & hepatology (2017)
PWE-104 Prevalance and significance of sessile serrated lesions from a large prospective UK series in the setting of bowel cancer screening programme: Abstract PWE-104 Table 1
Authors: S Tholoor, P Basford, P Bhandari
Journal: Gut (2012)

<h3>Introduction</h3> Screening colonoscopy has not had a big impact in reducing right sided cancer mortality and it is believed that this could partly be due to sessile serrated lesions (SSLs) which are thought to be the precursors of microsatellite adenocarcinomas. In the UK, people from the age of 60 to 75 with positive faecal occult blood undergo screening colonoscopy. We aim to evaluate the prevalence and significance of SSLs in our screening population. <h3>Methods</h3> All colonoscopies performed between 2007 and 2011 were prospectively recorded on a screening database along with the histology. Pathology was reported as per standards laid out by the National screening programme by accredited Pathologists. <h3>Results</h3> We analysed 1948 polyps from a total of 1576 patients. 28/1948 polyps in 25/1576 patients were found to have sessile serrated lesions. This amounted to 1.4% of the total polyps found. Out of 25 patients, 13 patients were men. The prevalence of sessile serrated lesions in all patients with polyps was 1.7% 17/28 lesions. (60%) of the lesions were smaller than 10 mm. 17/28 (60%) were in the right colon. 14/28 (50%) had no dysplasia. 14/28 (50%) had low grade dysplasia. None had high grade dysplasia or cancer. No interval cancer was found in a mean follow-up of 12 months. All 25 patients with sessile serrated lesions were also found to have conventional adenomas. 1–2 adenomas were found in 6/25 patients, 3–4 adenomas in 6/25 patients and 13/25 patients had at least 5 adenomas. Prevalance of dysplasia: SSLs with dysplasia: 14/28 (50%) –Low grade dysplasia: 14/14, High grade dysplasia/cancer: 0/14 SSLs with NO dysplasia: 14/28 (50%). <h3>Conclusion</h3> (1) Our study shows a low prevalence of 1.7% of sessile serrated lesions accounting to &lt;1.5% of the total number of polyps found in the setting of bowel cancer screening programme. (2) We did not find any high grade dysplasia or cancer in these patients. No interval cancer or synchronous cancers were found. (3) All patients with SSLs had conventional adenomas and the presence of SSLs had no effect on their surveillance plans. (4) Our study does not show any clinical impact of the sessile serrated lesions on patient outcomes. This questions the clinical relevance of SSLs. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Lash RH</b>, Genta RM, Schuler CM. Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients. <i>J Clin Pathol</i> 2010;<b>63</b>:681–6. 2. <b>Freeman HJ</b>. Heterogeneity of colorectal adenomas, the serrated adenoma, and implications for screening and surveillance. <i>World J Gastroenterol</i> 2008;<b>14</b>:3461–3.
Sexually Transmitted Diseases: Diagnosis and Treatment
Journal: JAMA (1987)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Increased Frequency Of Dual Positive Th2/Th17 Cells In Bronchoalveolar Lavage Characterizes a Population Of Severe Asthmatic Patients
Authors: Rafeul Alam, Chaoyu Irvin, James Good, Donald Rollins, Christina Christianson, Iram Zafar, Magdalena Gorska, Richard J. Martin
Journal: Journal of Allergy and Clinical Immunology (2014)
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Oswald T. Avery, Walther F. Goebel, Frank H. Babers
Journal: The Journal of Experimental Medicine (1932)

The chemical and immunological properties of the p-aminophenol alpha- and beta-glucosides of glucose are described and correlated. The results are discussed with reference to their possible bearing on the chemo-immunological nature of the specific polysaccharides of bacterial origin.
The Protective Effects of Estrogen on the Cardiovascular System
Authors: Michael E. Mendelsohn, Richard H. Karas
Journal: New England Journal of Medicine (1999)

The incidence of cardiovascular disease differs significantly between men and women, in part because of differences in risk factors and hormones.1 The incidence of atherosclerotic diseases is low in premenopausal women, rises in postmenopausal women, and is reduced to premenopausal levels in postmenopausal women who receive estrogen therapy.13 Until recently, the atheroprotective effects of estrogen were attributed principally to the hormone's effects on serum lipid concentrations. However, estrogen-induced alterations in serum lipids account for only approximately one third of the observed clinical benefits of estrogen.35 Reviews of the data suggest that the direct actions of estrogen on blood . . .
A phase III trial of <i>nab</i>-paclitaxel versus dacarbazine in chemotherapy-naive patients (pts) with metastatic melanoma: Analysis of peripheral neuropathy.
Authors: Michele Del Vecchio, Evan Hersh, Michael Paul Brown, Arthur Clements, Carmen Loquai, Pier Francesco Ferrucci, Caroline Robert, Mingyu Li, Ilena Elias, Markus F. Renschler, Axel Hauschild
Journal: Journal of Clinical Oncology (2013)

e20025 Background: Peripheral neuropathy (PN) is a common side effect associated with taxane treatment. In a phase III trial, nab-paclitaxel vs dacarbazine demonstrated a significant improvement in progression-free survival (4.8 vs 2.5 months; P = 0.044) and at the interim survival analysis, a trend toward prolonged overall survival (12.8 vs 10.7 months; P = 0.094) for the treatment of chemotherapy-naive patients with metastatic melanoma. Here we report on the PN profile of nab-paclitaxel in this phase III trial. Methods: Pts (median age, 63 years) with chemotherapy-naive stage IV melanoma (M1c stage, 65%; elevated LDH, 28%) and an ECOG performance status 0-1 were randomized to nab-paclitaxel 150 mg/m 2 on days 1, 8, and 15 of a 28-day cycle (n = 264) or dacarbazine 1000 mg/m 2 on day 1 of each 21-day cycle (n = 265). PN events were defined based on the Standardized MedDRA Query (V 12.1, broad scope). Results: As expected, a higher proportion of pts receiving nab-paclitaxel vs dacarbazine had ≥ 1 treatment-related PN event (68% vs 8%; P &lt; 0.001). Treatment-related grade ≥ 3 PN was more frequent with nab-paclitaxel vs dacarbazine (25% vs 0%; P &lt; 0.001); 2 grade 4 events were reported in the nab-paclitaxel arm. Treatment-related grade ≥ 3 PN was 15% in pts who received up to the median of 3 cycles of nab-paclitaxel. PN led to dose reduction in 13% or discontinuation in 15% of nab-paclitaxel–treated pts. The median time to onset of grade ≥ 3 PN was 101 days (95% CI, 85 - 113). Most early-onset PN events, occurring within the first 3 cycles, were grade 1. Grade ≥ 2 PN events peaked by cycle 4 and subsided by cycle 9. Forty-one of the 64 (64%) pts with a grade ≥ 3 PN event had an improvement of ≥ 1 grade, with a median time to improvement of 28 days (95% CI, 17 - 64), and 33 of 64 (52%) pts had improved to grade 1 or better by a median of 67 days from onset (95% CI, 22- upper limit not estimable); 30 of 64 (47%) pts resumed treatment with nab-paclitaxel. Conclusions: In this phase III trial, grade ≥ 3 PN was the main treatment-related toxicity with nab-paclitaxel as observed in other studies. However, PN was rapidly reversible; a majority of pts had improvement of PN symptoms within 1 month and resumed treatment. Clinical trial information: NCT00864253.
Intubation During In-Hospital Cardiac Arrest—Reply
Authors: Lars W. Andersen, Michael W. Donnino
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Musician’s Focal Dystonia
Authors: Joanna White
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Appraising food insecurity
Authors: Géraldine Coppin
Journal: Behavioral and Brain Sciences (2017)

Abstract This commentary focuses on the mechanisms underlying the appraisal of food insecurity. I first describe what appraisal is and why it plays a major role in explaining how different individuals consider food supply as more or less secure. I then describe the potential reciprocal links between appraisal and obesity, based on the well-documented evidence that obesity can cause cognitive deficits.
PTU-077 Association between crohn’s disease activity and therapeutic drug monitoring of thiopurines and infliximab comparing free and total antidrug antibody measurement: Abstract PTU-077 Table 1
Authors: BD Warner, MG Ward, EL Johnston, PM Irving
Journal: Gut (2015)

<h3>Introduction</h3> Therapeutic drug monitoring (TDM) of infliximab (IFX) is useful in patients with Crohn’s disease (CD). Therapeutic cut-offs to predict active disease and the influence of thiopurines on drug levels (DL) according to 6-thioguanine nucleotide (TGN) are not defined. There is limited data on the utility of free anti-drug antibodies (ADAb) against total ADAb. We assessed the utility of TDM of IFX in CD using a commercially available ELISA and investigated the influence of TGNs on DL and free/total ADAb. <h3>Method</h3> Prospective evaluation of trough DL and ADAb using Lisa-Tracker, ((LT), Theradiag, France) and Immundiagnostik ELISA, ((IM), Germany) in 79 CD patients (male = 40) between January and May 2014. Only free ADAb is detected with LT assay, whereas IM assay measures total ADAb (semiquantitative). Total ADAb results were calculated using the cut off control. Results of TDM were assessed with respect to faecal calprotectin (FC), C-reactive protein (CRP) and clinical activity (Harvey Bradshaw Index, (HBI) &lt;5 remission). The relationship between TGN and DL/ADAb was also assessed. LT kits were provided by Theradiag. <h3>Results</h3> Higher DL were observed amongst patients in remission (HBI &lt;5 DL 4.7 vs 1.7 μg/mL (p = 0.01), CRP &lt;5 mg/L DL 5 vs 2.5 μg/mL (p = 0.007), FC &lt;250 μg/g DL 5.6 vs 2.9 μg/mL (p = 0.001), FC &lt;59 μg/g DL 5.8 vs 3.3 μg/mL (p = &lt;0.001)). ROC curve analysis including thresholds to detect active disease are shown in Table 1. ADAb were detected in 3 (4%) patients using LT vs 19 (24%) using IM assay. All patients with ADAb with LT had undetectable DL and had active disease on FC59. Total ADAb with IM assay did not correlate with outcomes. Concomitant immunomodulation use was associated with absence of ADAb using IM assay (p = 0.03), however a therapeutic TGN (&gt;245 pmol/8 × 10<sup>8</sup>) was not associated with ADAb (p = 0.5). TGN quartile analysis did not identify a value associated with DL (p &gt; 0.5), nor was a therapeutic TGN associated with higher DL (p = 0.7). <h3>Conclusion</h3> IFX DL were inversely related to disease activity. A cut-off of 3.0–5.7 μg/mL was associated with active disease depending on the definition used. The presence of free ADAb was associated with active inflammation, whereas the presence of total ADAb was not. There was no relationship between TGN and DL or ADAb, although most patients were adequately dosed. This study highlights the limitations and utility of TDM in IBD. <h3>Disclosure of interest</h3> B. Warner: None Declared, M. Ward: None Declared, E. Johnston: None Declared, P. Irving Speaker Bureau of: AbbVie, MSD, Takeda, Warner Chilcott, Shire, Ferring and Tillotts Pharma.
Sleeve lobectomy an affidable lung sparing procedure
Authors: G. Cavallesco, P. Maniscalco, F. Quarantotto, F. Acerbis, M. Santini, C. Brombin, L. Valieri, G. Azzena
Journal: Journal of Clinical Oncology (2006)

17159 Background: Sleeve Lobectomy (Sl) is generally considered a surgical alternative of choice to Pneumonectomy (Pn) for the treatment of central NSCLC. The aim of this study is to value if the Sl could be really a Lung saving procedure that warrants right survivals, according to stage of disease, with acceptable perioperative risks. Methods: In 165 patients (67 Sl and 98 Pn) operated from 1995 to 2003 for NSCLC of main bronchus we have analyzed the hospital stay, morbidity and mortality within 30 days, long term survival. In 39 Sl and 46 Pn we compared spyrometric volume’s changes at a distance of 6–24 months from operation. Sl was performed where it was technically possible. Long term survivals had been separated and comparated according to pathologic stadium (TNM 1997) and lymphonodal involvement: all these data were estimated by Kaplan-Meier method and log rank test. All statistical data underwent SPSS elaboration and significant assumption for p &lt; 0.05. Results: In our population of study we didn’t check any statistically significant’s differences comparing age, sex or preoperative Fev1. Complications occurred in 28% of cases where Sl was performed and in 36.7% after Pn with a mortality rate of 2.9% vs 5.1%. Average hospital staying was longer in patients underwent to Pneumonectomy. Long term survival (5 years) in Sl group is 36% and 24% in Pn group with a statistically significant difference P = 0.016, but this difference is not evident from the comparison between the two group’s survivals based on pathological stadium or lymphonodal involvement. Spyrometric values showed a global Fev1 reduction of 245 ml (−10%) after Sl procedure and 884ml (36.3%) after Pn with a significant difference of p = 0.0042. Conclusions: In this study Sl got similar survival results if not better, with those obtained after Pn. Moreover, Sl showed to be a lung sparing procedure with an acceptable operative risk. These data confirmed that SL is the gold standard surgical procedure in the treatment of central tumors where if technically possible. [Table: see text] No significant financial relationships to disclose.
GP leader urges politicians to end “callous disregard” for NHS
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Politicians must end their “callous disregard” for the NHS and commit extra funding to save general practice from the verge of collapse, the head of the BMA’s GP committee has urged.

In his keynote speech at the annual UK conference of local medical committees held in Edinburgh on 18 May, Chaand Nagpaul accused politicians of turning a blind eye to the huge pressures affecting the whole health and social care system, calling for a long term funding solution to protect the NHS and general practice.

He reserved particular scorn for the “false promises” about extra NHS funding made by politicians who spearheaded the …