tbuckley/cabot-search huggingface dataset:
Abstract 102: The Detrimental Role Of iPLA2β In Ischemia/reperfusion Injury
Authors: Hitomi Matsuga, Osamu Yamaguchi, Yoshihide Tsujimoto, Kinya Otsu
Journal: Circulation Research (2013)

Background: Ca 2+ -independent phospholipase A2 (iPLA2) is crucial for a caspase-independent non-apoptotic cell death signaling pathway and involved in nuclear shrinkage induced by hypoxia. PLA2 family hydrolyzes the sn-2 ester bond in phospholipids to release free fatty acids and lysophospholipids. PLA2 inhibitors are known to prevent ischemic-reperfusion (I/R) injury. Here, we attempted to clarify the role of iPLA2β in myocardial I/R injury using cardiac-specific iPLA2β-deficient mice. Methods: Pla2g6 gene-targeting vector was constructed using mouse BAC genomic library. The ES clones with targeted homologous recombination were injected into blastocyst mouse embryos. Floxed iPLA2β mice were crossed with transgenic mice expressing Cre recombinase under the control of the α-myosin heavy chain ( αMHC ) promoter to generate cardiac-specific iPLA2β-deficient mice ( pla2g6 flox/flox αMHC-Cre + : CKO). We used pla2g6 flox/flox αMHC-Cre - littermates as controls (CTRL). We performed transthoracic M-mode echocardiographic analysis to examine the cardiac function of CKO and CTRL. Next, we subjected CKO and CTRL to I/R injury by using Langendorff-perfused mouse heart model. The heart was subjected to 30 minutes of global ischemia followed by 30 minutes of reperfusion. After the reperfusion, infarct area was determined with 1% triphenyltetrazolium chloride, and apoptotic cell death was detected by in situ TUNEL assay on heart sections. We exposed isolated adult cardiomyocytes from CKO and CTRL to various stimuli, such as Ca 2+ ionophore, H 2 O 2 and staurosporine, to examine the involvement of necrosis and apoptosis. Results: CKO and CTRL mice were born at the expected Mendelian ratio. There were no differences in cardiac function between CKO and CTRL. The functional recovery during reperfusion was significantly greater in CKO than in CTRL. CKO exhibited a significant decrease in the size of myocardial infarct. There were no significant differences in necrotic cell death induced by necrotic stimuli in vitro, while apoptotic cell death tended to decrease in CKO heart. Conclusions: These results suggest that iPLA2β exacerbates apoptotic cell death in I/R.
Is Terminal Ileal Intubation Necessary During Colonoscopy? – A Retrospective Analysis
Authors: E Nzewi, D McDowell, J Deasy
Journal: Endoscopy (2006)

Aims: Terminal ileal intubation is not routinely performed by surgeons because of difficulties with technique, time and a low diagnostic yield. The aim of this study is to assess the role of terminal ileal intubation during colonoscopy and its impact on patient management.
Angiotensin II infusion into ApoE-/- mice: a model for aortic dissection rather than abdominal aortic aneurysm?
Authors: Bram Trachet, Lydia Aslanidou, Alessandra Piersigilli, Rodrigo A. Fraga-Silva, Jessica Sordet-Dessimoz, Pablo Villanueva-Perez, Marco F.M. Stampanoni, Nikolaos Stergiopulos, Patrick Segers
Journal: Cardiovascular Research (2017)

Angiotensin II-infused ApoE-/- mice are a popular mouse model for preclinical aneurysm research. Here, we provide insight in the often-reported but seldom-explained variability in shape of dissecting aneurysms in these mice.N = 45 excised aortas were scanned ex vivo with phase-contrast X-ray tomographic microscopy. Micro-ruptures were detected near the ostium of celiac and mesenteric arteries in 8/11 mice that were sacrificed after 3 days of angiotensin II-infusion. At later time points (after 10, 18, and 28 days) the variability in shape of thoraco-abdominal lesions (occurring in 31/34 mice) was classified into 7 different categories based on the presence or absence of a medial tear (31/31), an intramural hematoma (23/31) or a false channel (11/23). Medial tears were detected both in the thoracic and the abdominal aorta and were most prevalent at the left and ventral aspects of celiac and mesenteric arteries. The axial length of the hematoma strongly correlated to the total number of ruptured branch ostia (r2 = 0.78) and in 22/23 mice with a hematoma the ostium of the left suprarenal artery had ruptured. Supraceliac diameters at baseline were significantly lower for mice that did not develop an intramural hematoma, and the formation of a false channel within that intramural hematoma depended on the location, rather than the length, of the medial tear.Based on our observations we propose an elaborate hypothesis that explains how aortic side branches (i) affect the initiation and propagation of medial tears and the subsequent adventitial dissection and (ii) affect the variability in shape of dissecting aneurysms. This hypothesis was partially validated through the live visualization of a dissecting aneurysm that formed during micro-CT imaging, and led us to the conclusion that angiotensin II-infused mice are more clinically relevant for the study of aortic dissections than for the study of abdominal aortic aneurysms.
Correlation among the biomarkers for oral anti-cancer agents in lung adenocarcinoma.
Authors: Nariyasu Nakashima, Shinya Ishikawa, Dage Liu, Yoshimasa Tokunaga, Yoshuke Kita, Kazuhito Nii, Natsumi Matsuura, Jun Nakano, Shintaro Tarumi, Masaya Okuda, Tetsuhiko Go, Xia Zhang, Yoshiyuki Kakehi, Hiroyasu Yokomise
Journal: Journal of Clinical Oncology (2016)

e20015 Background: Oral administration is an easy and convenient way outpatient administration. It is also considered to be superior in terms of medical economics. In recent years, the development of individualized treatment in non-small cell lung cancer is remarkable, also the usefulness of biomarkers has been well proven. Among the biomarkers of oral anti-cancer agents, thymindylate synthase (TS) expression is related to 5-FU-based anti-tumor agent, and EGFR to TKI-based anti-tumor agent, in addition to the effectiveness of the c-Met-overexpressing in lung cancer has been evolved and phase III clinical trial of oral c-Met inhibitors have been reported. In oral therapeutic agents in lung adenocarcinoma, TS expression, EGFR mutation and c-Met expression was examined and its clinical significance will be applied to the future individualized therapy. Methods: For the tumors from 71 patients with lung adenocarcinoma who underwent surgery in our department, the intratumoral expression of TS and c-Met were evaluated with immunohistochemical staining. The status of EGFR mutations was examined by direct sequence method using extracted DNA from tumors. Results: (1) In the group observed the effect of corresponding therapeutic agent, TS negative was 40 cases (56.3%), EGFR mutant 23 was cases (32.3%), c-Met strongly positive was 17 cases (23.9%). (2) TS, c-Met expression, EGFR mutations, were proved to be the independent predictor for correspounding anti-cancer drug, and there were no significant correlation among these three biomarkers was abserved. (3) TS-negative or EGFR mutant-type was 49/71 (69.0%). Also in the TS-positive and EGFR wild-type, c-Met strongly positive example 5 cases (5/22 cases, 22.7%) was observed. It was considered to be the target of administration, if c-Met inhibitors is commercialized in the future. (4) The possible cases of individualized chemotherapy with oral therapeutic agents was 54/71 cases (76.1%). Conclusions: Three biomarkers in lung adenocarcinoma (TS, EGFR, c-Met) is respectively independent, the possibility of individualized treatment with oral agents based on biomarker analysis has been suggested.
Pill Reminders Don’t Improve Adherence
Authors: Anita Slomski
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
Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial
Authors: Toshiaki Ohkuma, Min Jun, Mark Woodward, Sophia Zoungas, Mark E. Cooper, Diederick E. Grobbee, Pavel Hamet, Giuseppe Mancia, Bryan Williams, Paul Welsh, Naveed Sattar, Jonathan E. Shaw, Kazem Rahimi, John Chalmers
Journal: Diabetes Care (2017)

OBJECTIVE This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTS A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37, 3.96) for NT-proBNP, 1.50 (1.27, 1.77) for hs-cTnT, 1.48 (1.27, 1.72) for IL-6, and 1.32 (1.12, 1.55) for hs-CRP. The addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk-predictive performance (C statistic 0.8162 to 0.8800; continuous net reclassification improvement [NRI] 73.1%; categorical NRI [&amp;lt;5%, 5–10%, &amp;gt;10% 5-year risk] 24.2%). In contrast, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. CONCLUSIONS Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.
Delayed‐type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T‐cell reactivity study
Authors: C.‐y. Lin, C.‐W. Wang, C.‐Y. R. Hui, Y.‐C. Chang, C.‐H. Yang, C.‐Y. Cheng, W.‐W. Chen, W.‐M. Ke, W.‐H. Chung
Journal: Allergy (2017)

Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients.We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities.There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay.PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.
Erratum: Sleepiness, Quality of Life, and Sleep Maintenance in REM versus NREM Sleep-Disordered Breathing
Authors: Hassan A. Chami, Carol M. Baldwin, Angela Silverman, Ying Zhang, David M. Rapoport, Naresh Punjabi, Daniel J. Gottlieb
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Five of the deaths occurred in the placebo group, but only one in the vitamin C group.In a study using a combination of vitamins C and E, Nathens and coworkers (5) found no effect on the incidence of nosocomial pneumonia in critically ill surgical patients, but days of mechanical ventilation (20.9; 20.6 to 21.2) were significantly reduced in the antioxidant group.Although this study is not specific to vitamin C, it suggests that antioxidants may affect pulmonary morbidity.More research on vitamin C and other antioxidants seems to be warranted.
Targeting nucleolin for better survival in diffuse large B-cell lymphoma
Authors: N Jain, H Zhu, T Khashab, Q Ye, B George, R Mathur, R K Singh, Z Berkova, J F Wise, F K Braun, X Wang, K Patel, Z Y Xu-Monette, J Courty, K H Young, L Sehgal, F Samaniego
Journal: Leukemia (2017)
Film forming systems for topical and transdermal drug delivery
Authors: Kashmira Kathe, Harsha Kathpalia
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system's ability to adhere to skin during the therapy so as to promote drug penetration through the skin barrier. Conventional formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient compliance. For the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient acceptance. In the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions) along with their evaluation parameters have also been reviewed.
Trabectedin and radiotherapy in soft-tissue sarcoma (TRASTS) study: An international, prospective, phase I/II trial—A collaborative Spanish (GEIS), Italian (ISG), and French (FSG) groups study.
Authors: Alessandro Gronchi, Nadia Hindi, Josefina Cruz, Jean-Yves Blay, Roberta Sanfilippo, Carlo Morosi, Jesus Romero, Javier Peinado, Antonio Lopez-Pousa, Rosa Maria Alvarez Alvarez, Antoine Italiano, Jose Luis Perez, Claudia Sangalli, Marie Pierre Sunyach, Cleofe Romagosa, Dominique Ranchère-Vince, Paola Collini, Javier Martin Broto
Journal: Journal of Clinical Oncology (2017)

11061 Background: Myxoid liposarcoma/round cell liposarcoma (ML) exhibits especial sensitivity to trabectedin (T). In prospective series, long-lasting T treatment showed responses in 44% of patients (pts) with ML. ML is also sensitive to radiation therapy (RT) and preclinical data suggested radiosensitizing properties of T. Preoperative short-course of T with concurrent low-dose RT was conducted in a multicenter, European, phase I/II trial. We present here data from the phase I part in pts with centralized diagnosis of locally advanced, resectable ML. Methods: Pts received 3 cycles (C) of T in combination with RT (45 Gy) in 25 fractions (1.8Gy/fraction). The phase I had the classic 3+3 design. Dose Levels for T were: -1 (1.1 mg/m 2 ), 1 (1.3 mg/m 2 ) and 2 (1.5 mg/m 2 ). Dose-limiting toxicity (DLT) were defined as grade ≥3 events excluding G3/4 neutropenia lasting &lt; 5 days and G3-4 nausea/vomiting due to inadequate prophylaxis. RECIST responses were evaluated preoperatively at week 10. Surgical specimens were processed for histologic changes and residual tumor. Results: From February 2015 to May 2016,14 pts (M/F 7/7) with median age 36y (24-71) and median tumor size 12.5 cm were enrolled. 7 pts received T at dose Level 1 and 7 pts at Level 2. One DLT (G3 transaminitis) occurred at Level 1 and another (sepsis due to catheter infection) at Level 2. Overall, grade G 3/4 AEs were: ALT elevation (n = 6, 43%), and GGT elevation, neutropenia, anemia, epithelitis and sepsis (n = 1, 7% each). There were no deaths. One pt developed metastasis after C3 and did not undergo surgery; another one had a sepsis after C1 and received definitive RT. All pts completed RT. 13 pts were evaluable for response: 5 achieved PR (38%), 7 SD (53%), 1 distant PD (8%). 12 pts underwent surgery (7 R0/5 R1). Median viable residual tumor was 5% (0-60) with 9/12 pts (75%) with ≤ 10% viable remaining tumor, 3/12 (25%) complete responses. Conclusions: T in combination with RT was feasible and well tolerated in the preoperative setting. T dose of 1.5 mg/m 2 is the recommended phase II dose. A high proportion of patients achieved a good pathological response, with 3/12 (25%) complete responses. Clinical trial information: 2014-001549-26.
Management of incidental pulmonary embolism
Authors: Frederikus A. Klok, Menno V. Huisman
Journal: European Respiratory Journal (2017)

Incidental pulmonary embolism (PE) is a frequent finding on routine computed tomography (CT) scans of the chest, occurring in 1.1% of coronary CT scans and 3.6% of oncological CT scans. Despite this high frequency, optimal management of incidental PE has not been addressed in clinical trials and remains the subject of debate. Although these CT scans have not been performed with a dedicated PE protocol and have suboptimal contrast enhancement, diagnosis of incidental PE has been shown to be accurate up to the segmental and subsegmental arteries. The embolic load in incidental PE is lower than that in symptomatic PE. Even so, observational studies suggest that the natural course of incidental PE is similar to that of symptomatic PE with regard to the risk of recurrent venous thrombotic disease and mortality. Interestingly, the increased use of more advanced CT technology has coincided with an increase in the rate of incidental subsegmental PE, as is the case for symptomatic subsegmental PE. Although clinical trials are lacking, and observational data are limited to cancer-associated incidental PE, the consensus is that the management of incidental PE is identical to that of symptomatic PE, including the choice of optimal drug class, outpatient treatment and total duration of treatment.
Correlation between the prognostic value of tumor-infiltrating lymphocytes (TILS) and sidedness in colorectal cancer (CC) patients (pts)
Authors: Cristina Granetto, Vincenzo Ricci, Elena Fea, Daniela Vivenza, Cristiana Lo Nigro, Mirella Fortunato, Alberto Comino, Marco Merlano
Journal: Annals of Oncology (2017)
Humoral Immunity in Arsenic-Exposed Children in Rural Bangladesh: Total Immunoglobulins and Vaccine-Specific Antibodies
Authors: Rubhana Raqib, Sultan Ahmed, Khalid Bin Ahsan, Maria Kippler, Evana Akhtar, Anjan Kumar Roy, Ying Lu, Shams El Arifeen, Yukiko Wagatsuma, Marie Vahter
Journal: Environmental Health Perspectives (2017)

Background: Early-life arsenic exposure has been associated with reduced cell-mediated immunity, but little is known about its effects on humoral immunity. Objective: We evaluated whether prenatal and childhood arsenic exposure was associated with humoral immune function in school-aged children. Methods: Children born in a prospective mother–child cohort in rural Bangladesh were immunized with measles, mumps, and rubella (MMR) vaccines at 9 years of age (n=525). Arsenic exposure was assessed in urine (U-As), from mothers during pregnancy and their children at 4.5 and 9 years of age. Total IgG (tIgG), tIgE, tIgA, and MMR-specific IgG concentrations were measured in plasma using immunoassays. Results: Arsenic exposure was positively associated with child tIgG and tIgE, but not tIgA. The association with tIgG was mainly apparent in boys (p for interaction=0.055), in whom each doubling of maternal U-As was related to an increase in tIgG by 28mg/dL. The associations of U-As at 9 years with tIgG and tIgE were evident in underweight children (p for interaction &lt;0.032). Childhood arsenic exposure tended to impair mumps-specific vaccine response, although the evaluation was complicated by high preimmunization titers. Postimmunization mumps–specific IgG titers tended to decrease with increasing U-As at 4.5 and 9 years of age [regression coefficient (β)=−0.16; 95% confidence interval (CI): −0.33, 0.01; p=0.064 and β=−0.12; 95% CI: −0.27, −0.029; p=0.113, respectively) in 25% children with the lowest preexisting mumps-specific IgG titers. Conclusions: Arsenic exposure increased tIgG and tIgE in plasma, and tended to decrease mumps-specific IgG in children at 9 years of age. https://doi.org/10.1289/EHP318