tbuckley/cabot-search huggingface dataset:
Abstract 1344: Biphasic Effect of Electrotonic Fibroblast-Myocyte Coupling on 2D Wave Conduction Velocity and Reentry
Authors: Sharon Zlochiver, Viviana Munoz, Eva M Oxford, Karen L Vikstrom, Omer Berenfeld, Jose Jalife
Journal: Circulation (2007)

Fibroblast proliferation is common to various cardiac diseases. Differentiation of fibroblasts into myofibroblasts may result in myocyte-fibroblast electrical coupling via gap junctions. We hypothesized that fibroblast proliferation and varying heterocellular coupling significantly alter 2-dimensional cardiac wave propagation and reentry dynamics. Methods : Monolayers of co-cultured fibroblasts and myocytes from neonatal rat ventricles were optically mapped. The junctional coupling was reduced using Cx43 RNA silencer in the fibroblasts. Simulations were used to quantify the effects of heterocellular coupling variation. Conduction velocity (CV) was measured when pacing at 2 Hz. Results : Experiments and simulations show linear CV and reentry frequency reduction with increased number of wavebreaks as fibroblast/myocyte mixed area ratio increases. However, simulations show that the effect of fibroblast-myocyte coupling on CV and reentry frequency is biphasic: as coupling increases reentry frequency and CV initially decrease and then increase. Panel A shows that for a 1/4 fibroblasts/myocytes mixture the minimum CV is at ~10% of the myocytes coupling. In both experiments and simulations, low heterocellular coupling can result in similar CV and frequency of rotation (p&lt;0.05), but more fragmented wavefronts as compared with high coupling (panel B). Conclusion: Fibroblasts may have a dual role as current “sinks” and “transmitters”, depending on the level of heterocellular coupling. This study provides novel insight into the mechanisms whereby electrical interactions between myocytes and fibroblasts modify wave propagation and the propensity to arrhythmias.
Regulation of corticosteroid binding globulin (CBG) in the inflammatory context of cystic fibrosis
Authors: Jessica Taytard, Carine Rebeyrol, Dominique Debray, Annick Clement, Nicolas Chignard, Philippe Le Rouzic
Journal: European Respiratory Journal (2011)

Background:  Cystic Fibrosis (CF) is characterised by chronic lung inflammation. In CF, glucocorticoids (GC) are a widely used therapeutic tool. However, their efficiency, and the benefit/risk ratio are still discussed. In plasma, 90% of GC is bound to the chaperone protein CBG which regulates its bio-disponibility. CBG is mainly produced by the liver. Recent works enlightened the fact that, more than a simple carrier protein, CBG could also address GC specifically to the inflammation site, thereby modulating the response to GC in an inflammatory context.   Objectives:  Study the expression and regulation of CBG in the liver and assess its pulmonary expression in the inflammatory context of CF.   Methods:  Hepatic levels of CBG:   Biopsies from healthy donors, cirrhotic CF and non CF patients: measure of the transcripts levels of CBG and interleukin-6.  Hepatocarcinoma derived cell-lines Hep3B and HepG2: regulation of CBG expression.   Lung levels of CBG:   Lung biopsies; expression of CBG  Bronchial epithelial cell lines; regulation of CBG expression   Results:  We show an increase in CBG expression:  in the liver and lung of CF patients.  in the hepatic and lung cell lines in an inflammatory context.  GC has no effects on CBG expression in hepatic cell lines, but increases CBG levels in the lung cell lines.   Discussion:  We show stimulation of the expression of CBG in the inflammatory context of CF. Comparative results from hepatic and lung cell lines enlight a different regulation of CBG expression. Overall, increase in CBG expression in CF could mean initially a decrease in GC bio-disponibility but, ultimately, an enhanced corticosteroid half life and possible prolonged effects.
Financial Benefits of Laparoscopic Colectomy
Authors: Aruna Munasinghe, Mauro Laudicella, Omar Faiz
Journal: JAMA Surgery (2015)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
Abstract 1164: Mast Cells Contribute to Pathogenesis in the Progression of Abdominal Aortic Aneuyrsm
Authors: Toshihiro Tsuruda, Johji Kato, Kinta Hatakeyama, Kunihide Nakamura, Takuroh Imamura, Toshio Onitsuka, Yujiro Asada, Kazuo Kitamura
Journal: Circulation (2007)

Abdominal aortic aneurysm (AAA) is histologically characterized by medial degeneration and various degrees of chronic adventitial inflammation, while the mechanisms for progression of aneurysm are poorly understood. In the present study, we carried out histological study of AAA tissues of patients (75±1 years, Mean±SEM), and interventional animal and cell culture experiments to investigate the role of mast cells in the pathogenesis of AAA. The number of mast cells determined by positive staining for tryptase, a major neutral protease of human mast cell secretory granules, was found to increase in the outer media or adventitia of human AAA, compared to those in the control aorta (2.1±1.1/mm 2 (n=57) vs. 0.6±0.4/mm 2 (n=22), p&lt;0.01), showing a positive correlation (r=0.442, p&lt;0.01) between the cell number and the AAA diameter. Western blot demonstrated that the protein expressions of tryptase, stem cell factor (a ligand for c-kit) and the phosphorylation of c-kit were significantly (p&lt;0.01) increased in the AAA tissues, compared with the control aorta. In the animal experiments, diameter of abdominal aorta of the control (+/+) rats was increased up to 55% at 14 days following peri-aortic application of 0.4 mol/L calcium chloride, but only a 13% increase in the mast cell-deficient mutant Ws/Ws rats. The AAA formation was accompanied by accumulation of mast cells, T-lymphocytes, interferon-γ positive cells and by activated matrix metalloproteinases (MMP)-2 and -9, reduced elastin levels and augmented angiogenesis in the aortic tissue, but these changes were much less in the Ws/Ws rats than in the control (+/+) rats. The pharmacological intervention with the mast cell stabilizer tranilast (400 mg/kg/day) for 14 days significantly (p&lt;0.01) attenuated the AAA development in the control (+/+) rats. Co-culturing the mast cell line HMC-1 with the monocyte/macrophage cell line U937 significantly (p&lt;0.01) augmented MMP-9 activity. Furthermore, 100 and 300 μmol/L of tranilast significantly (p&lt;0.01) decreased MMP-9 activity in those cells. Collectively, these data suggest that mast cells may play important roles in the progression of AAA.
The influence of metabolic syndrome in mortality rate of COPD patients: A five years follow up study
Authors: Karime Schelini, Suzana Tanni, Amanda Zamuner, Liana Coelho, Simone Vale, Renata Ferrari, Laura Caram, Ilda Godoy, Sergio Paiva, Irma Godoy
Journal: European Respiratory Journal (2012)

Background: Patients with chronic obstructive pulmonary disease (COPD) or metabolic syndrome (MS) present systemic inflammation and the association between diseases can increase risk of cardiovascular events. However, the influence of MS in survival of COPD patients is still unclear. Methods: We followed 115 COPD patients (age:64.5 ± 1.21years, FEV1:58.7 ± 2.75%) during five years and causes of death were noted. At baseline, patients' clinical history and physical examination were assessed, and anthropometric (weight, height, body mass index and waist circumference), spirometry, 6-minute walking distance (6MWD), dyspnea perception by the modified medical research council (MMRC), serum lipid profile and triglycerides measurements were performed. The diagnosis of MS was established by harmonization MS criteria. The Cox proportional hazard analysis was used to evaluate the influence of MS in the survival time, adjusted for potential confounders (age, gender and BODE index). Results: MS was present in 35.6% of patients and hypertension (47.8%) was the MS component more prevalent. More than 80% of the patients presented at least one diagnostic component of MS. During the period of study, 17.0% died. We did not observe statistical difference in mortality between groups with and without MS (HR:1.30, 95%CI: 0.32-5.20). Conclusion: Patients with COPD have intermediate prevalence of MS; however, no association between MS and mortality was found in these patients.
Abstract 879: New serum biomarkers for prostate cancer diagnosis
Authors: Kailash C. Chadha, Austin Miller, Bindukumar B. Nair, Stanley A. Schwartz, Donald L. Trump, Willie Underwood
Journal: Cancer Research (2014)

Abstract Prostate-specific antigen (PSA) is currently used as a biomarker for the early diagnosis and management of prostate cancer (CaP). However, PSA generally lacks the sensitivity and specificity desired of an effective diagnostic biomarker. The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign vs. malignant prostate disease and/or localized CaP vs. metastatic CaP. Concurrent measurements of circulating IL-8, TNF-alpha (TNF-α) and sTNFR1 were obtained from four groups of men: (1) controls (2) men with elevated PSA with a negative prostate biopsy (eIPSA_negBx) (3) men with clinically localized CaP and (4) men with castration resistant CaP (CRPC). TNF-α (AUC=0.93) and sTNFR1 (AUC=0.97) were strong predictors of elPSA_negBx vs CaP). The best predictor of elPSA_negBx vs prostate cancer was sTNFR1 and IL8 combined (AUC=0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC=0.992) and PSA (AUC=0.963) levels. Conclusions: The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in larger cohort consisting of Caucasians and African Americans is warranted. Citation Format: Kailash C. Chadha, Austin Miller, Bindukumar B. Nair, Stanley A. Schwartz, Donald L. Trump, Willie Underwood. New serum biomarkers for prostate cancer diagnosis. [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 879. doi:10.1158/1538-7445.AM2014-879
Long-term vs Short-term Therapy With Vitamin K Antagonists for Symptomatic Venous Thromboembolism
Authors: Saskia Middeldorp, Barbara A. Hutten
Journal: JAMA (2015)

Is long-term (≥3 months) vs short-term therapy with vitamin K antagonists (VKAs) associated with differences in the incidence of recurrent venous thromboembolism (VTE), major bleeding, and mortality in patients with symptomatic VTE?Long-term treatment with VKAs is associated with a reduced risk for recurrent VTE and an increased risk for major bleeding compared with short-term treatment in patients with VTE, but is not associated with differences in mortality.
Osteomyelitis due to Salmonella enterica subsp. arizonae: the price of exotic pets
Authors: S. Kolker, T. Itsekzon, A.M. Yinnon, T. Lachish
Journal: Clinical Microbiology and Infection (2011)

We describe a 31-year-old immunocompromised patient who developed sepsis and osteomyelitis due to Salmonella enterica subsp. arizonae secondary to exposure to iguana and snakes kept as pets at her home, and review all 23 previously published cases of bone and joint infections due to this organism, for a total of nine children and 15 adults. Eleven of the adults were female (73%), compared with three (33%) of the children (p <0.01). Significant underlying illnesses were present in all 15 adults and in five children (55%, p <0.05); 10 (77%) of the adults were immunosuppressed, compared with one child only (17%) (p <0.05). In ten of the adults the knee was infected (67%), compared with one child only (11%, p <0.01). Antibiotic therapy was prolonged in both adults and children, and in most cases consisted of 4-6 weeks of parenteral treatment. Complete cure and survival was attained in 11 of 15 adults (73%) and all nine children (NS). Optimal antibiotic treatment probably consists of ceftriaxone or a fluoroquinolone, if the organism is susceptible.
Low dose varenicline. Efficacy, side effects and treatment completion
Authors: Natalia Fouz Rosón, Ana Paulina Gómez-Bastero Fernández, Andrés Humberto Vega Arias, Virginia Almadana Pacheco, Soledad Montserrat García, Teodoro Montemayor Rubio
Journal: European Respiratory Journal (2014)

Introduction: 

Varenicline is one of the drugs used to help quit smoking. The approved dose is 1 mg twice daily during 12 weeks. However, treatment completion is usually poor, because of the price or the side effects.

Our aim with this study was to compare a standar course of 1 mg twice daily during 8 weeks (already validated at our Unit) versus 0'5 mg twice daily during 8 weeks.

Material and methods: 

randomised clinical trial, with 2 groups, at a daily clinical practice of a Stop-Smoking Unit.

The program lasts 3 months. It begins with a doctor's visit who prescribes the treatment and the follow-up consists of cognitive-conductual support from the specialised psychologist.

Results: 

-Abstinence rate after 3 months was 53'9% with regimen A and 56'8% with regimen B, without significative statistical differences. Abstinence was verified with the determination of exhaled carbon monoxide.

-90'6% (n=202) of the patients who successfully quitted smoking had completed the treatment during 2 months.

-17% of patients who took the treatment had some side effects, most of them mild or moderate. The side effects described were: gastrointestinal discomfort, mostly nausea (9'9%), sleep problems / nightmares (4'9%) and headaches (2'1%). There is a wider tendency to present side effects with the regimen A of 1 mg (21%) versus the 13'1% with regimen B of 0'5 mg, however, there are no significative statistical differences, with p=0'171.

Conclusions: 

-Both regimens are equally effective for quitting smoking, achieving in both groups a similar abstinence rate.

-Short programmes and medication completion are determinant in results.
Acceptability of Binaural Hearing Aids: A Cross-Over Study
Authors: S D G Stephens, D E Callaghan, S Hogan, R Meredith, A Rayment, A Davis
Journal: Journal of the Royal Society of Medicine (1991)

Using screening questionnaires we were able to detect individuals aged 50–65 years with hearing disability in a general practice population. Those who had better ear hearing levels of 30 dB or worse were invited to take place in a cross-over study comparing the acceptability of a monaural or binaural hearing-aid fitting. Fifty-five per cent ultimately opted for a binaural fitting and had greater hearing disability and worse mean hearing levels than those who opted for a monaural fitting. They made their choice for acoustical reasons, particularly on the basis of improved localization ability.
Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy.
Authors: R J Gralla, R M Navari, P J Hesketh, W Popovic, J Strupp, J Noy, L Einhorn, D Ettinger, W Bushnell, C Friedman
Journal: Journal of Clinical Oncology (1998)

PURPOSE To compare the antiemetic efficacy of a single dose of an oral antiemetic (granisetron 2 mg) with a single dose of an intravenous (i.v.) antiemetic (ondansetron 32 mg) given before cisplatin-based chemotherapy. PATIENTS AND METHODS This was a multicenter, randomized, double-blind, parallel-group study. Patients (N = 1,054) scheduled to receive cisplatin (&gt; or = 60 mg/m2)-based chemotherapy were randomized to receive either 2 mg of oral granisetron tablets 1 hour before chemotherapy (n = 534) or i.v. ondansetron (32 mg) 30 minutes before chemotherapy (n = 520). The primary efficacy end point was total control (no emesis, no nausea, and no use of antiemetic rescue medication) over the initial 24 hours after the start of chemotherapy. Dexamethasone or methylprednisolone were permitted, but not required, as concomitant prophylactic antiemetics. RESULTS Total control was equivalent 24 hours after cisplatin chemotherapy for single-dose oral granisetron (54.7%) and i.v. ondansetron (58.3%) (95% confidence interval [CI], -9.6 to 2.4). Similar proportions of patients remained nausea-free in the granisetron group (55.4%) and the ondansetron group (59%) (95% CI, -9.6 to 2.4). The rate of complete control of emesis was 61.2% in the granisetron group and 67.1% in the ondansetron group (95% CI, -11.7 to -0.1). Both treatment regimens were well tolerated, with similar patterns of adverse reactions, generally of a mild degree. The most common side effects included constipation (14%), headache (15%), and diarrhea (10%). CONCLUSION Oral granisetron, administered as a single 2-mg dose, provided equivalent total antiemetic control when compared with i.v. ondansetron (32 mg) in patients who received highly emetogenic, cisplatin-based chemotherapy.
Internalization of Rituximab and the Efficiency of B Cell Depletion in Rheumatoid Arthritis and Systemic Lupus Erythematosus
Authors: Venkat Reddy, Geraldine Cambridge, David A. Isenberg, Martin J. Glennie, Mark S. Cragg, Maria Leandro
Journal: Arthritis & Rheumatology (2015)

Objective Rituximab, a type I anti‐CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. Methods We used an in vitro whole blood B cell–depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence–quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t ‐test or Mann‐Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. Results We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2‐fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell–depletion assays. The lowest levels of internalization were seen in IgD– B cells, including postswitched (IgD–CD27+) memory cells. Internalization of type I anti‐CD20 mAb was also partially inhibited by anti‐IgM stimulation. Conclusion Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower‐internalizing type II mAb should be considered as alternative B cell–depleting agents for the treatment of RA and SLE.
Phase I study of BMS-247550 (ixabepilone) given every 3 weeks in Japanese patients with refractory solid tumors
Authors: T. Shimizu, N. Yamamoto, Y. Fujisaka, Y. Yamada, T. Sakamoto, K. Takayama, M. Hirose, T. Tamura, T. Tokudome, J. Klimovsky
Journal: Journal of Clinical Oncology (2005)

2050 Background: The epothilones are a new class of non-taxane tubulin- polymerizing agents obtained by fermentation of the myxobacterium Sorangium cellulosum. ixabepilone, a semi-synthetic analog of the natural product of epothilone B, is active against taxane-resistant tumors. Primary objective of this study was to establish the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and a recommended dose given every 3 weeks. Secondary objectives were to evaluate safety, pharmacokinetics (PK), and antitumor activity. Methods: Ixabepilone was administered intravenously as 3-hr infusion every three weeks to patients with solid tumors previously treated with up to 4 prior chemotherapy regimens. The starting dose was 15 mg/m2, and the dose was escalated to 30, 40 and 50 mg/m2. Cohorts of at least three patients were treated at each dose level. Blood samples for PK were collected for 72 h post-dose during cycle 1(t: 0, 1:30, 3:00, 3:30, 4:00, 5:00, 6:00, 8:00, 24:00, 48:00, 72:00). Results: Thirteen patients (M/F: 11/2) have been enrolled to date with a median age of 55 (range 40–72). Tumor types included: non-small cell lung cancer (NSCLC) (8), cholangiocarcinoma(1), colon cancer(1), ovarian cancer(1), mesothelioma(1), liposarcoma(1). No DLTs were observed in patients at the dose of 15 or 30 mg/m2. One of 6 patients at the dose of 40mg/m2 developed DLT (G4 neutropenia for 5 or more consecutive days). Non-hematologic toxicities were mild to moderate, except for G3 nausea, vomiting and dehydration (N=1) at the dose of 40 mg/m2. Six patients developed asymptomatic superficial phlebitis during infusion of ixabepilone. The area under the plasma concentration versus time curve (AUC) increased with the dose of ixabepilone, suggesting linear pharmacokinetics within these dose ranges. Twelve patients were evaluable for response. There were no objective tumor responses. Eight patients (67%) had stable disease with tumor shrinkage of 12.4 - 25.6%. Five NSCLC patients (42%) received 4 or more cycles, and 3 patients of them (25%) had 6 or more cycles and have stable disease. Conclusions: BMS-247550 is tolerable at the dose of 40 mg/m2, and the phase II evaluations are encouraging, especially in patients with NSCLC. No significant financial relationships to disclose.