tbuckley/cabot-search huggingface dataset:
Premature Atrial Contractions in the General Population
Authors: David Conen, Martin Adam, Frederic Roche, Jean-Claude Barthelemy, Denise Felber Dietrich, Medea Imboden, Nino Künzli, Arnold von Eckardstein, Stephan Regenass, Thorsten Hornemann, Thierry Rochat, Jean-Michel Gaspoz, Nicole Probst-Hensch, David Carballo
Journal: Circulation (2012)

Background— Premature atrial contractions (PACs) are independent predictors of atrial fibrillation, stroke, and death. However, little is known about PAC frequency in the general population and its association with other cardiovascular risk factors. Methods and Results— We performed a cross-sectional analysis among participants of the population-based Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). 24-hour Holter electrocardiograms to assess PAC prevalence and frequency were performed in a random sample of 1742 participants aged ≥50 years. The median (interquartile range) number of PACs per hour was 0.8 (0.4–1.8), 1.1 (0.5–2.4), 1.4 (0.7–4.6), 2.3 (0.8–6.9), and 2.6 (1.2–6.5) among participants aged 50 to 55, 55 to 60, 60 to 65, 65 to 70, and ≥70 years, respectively ( P &lt;0.0001). Only 18 (1.0%) participants did not have at least 1 PAC during Holter monitoring. In multivariable negative binomial regression models, PAC frequency was significantly associated with age (risk ratio [RR] per SD 1.80; P &lt;0.0001), height (RR per SD 1.52; P &lt;0.0001), prevalent cardiovascular disease (RR 2.40; P &lt;0.0001), log-transformed N-terminal pro B-type natriuretic peptides (RR per SD 1.27; P &lt;0.0001), physical activity ≥2 hours per day (RR 0.69; P =0.002), and high-density lipoprotein cholesterol (RR per SD 0.80; P =0.0002). Hypertension and body mass index were not significantly related to PAC frequency. Conclusions— To our knowledge, this is the first study to assess risk factors for PAC frequency in the general population aged ≥50 years. PACs are common, and their frequency is independently associated with age, height, history of cardiovascular disease, natriuretic peptide levels, physical activity, and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships need to be addressed in future studies.
Abstract 2895: Small cell lung cancer cells express the late stage gBK tumor antigen: a possible immunotarget for the terminal disease
Authors: Neil T. Hoa, Lisheng Ge, Rajeev B. Tajhya, Christine Beeton, Andrew N. Cornforth, Amir Abolhoda, Nils Lambrecht, Maria Dacosta-Iyer, Yi Ouyang, Michelle J. Hickey, Kate L. Erickson, Carol A. Kruse, Martin R. Jadus
Journal: Cancer Research (2014)

Abstract Big Potassium (BK) ion channels have several splice variants. One splice variant initially described within human glioma cells is called the glioma BK channel (gBK). This isoform consists of 33 amino acids inserted into the intracellular region of the BK ion channel. Using a gBK-specific antibody, we detected gBK within 3 human small cell lung cancer (SCLC) lines. Patch clamping revealed that functional membrane channels were found on the SCLC cells. Prolonged exposure to BK channel activators caused the SCLC cells to swell within 20 minutes and resulted in their cytotoxicity within 5 hours. Transfection of BK-negative HEK cells with gBK produced functional gBK channels. Quantitative RT-PCR analysis using primers specific for gBK, but not with a lung-specific marker, Sox11, confirmed that advanced, late-stage human SCLC tissues strongly expressed gBK mRNA. Normal human lung tissue and early, lower stage SCLC resected tissues very weakly expressed this transcript. Immunofluorescence using the gBK antibodies confirmed that SCLC cells taken at the time of autopsy intensely displayed this protein. gBK may represent a late-stage marker for SCLC. HLA-A*0201 restricted human CTL were generated in vitro by one-way mixed lymphocyte reactions or mixed lymphocyte dendritic cell reactions, the latter using gBK peptide pulsed dendritic cells. The exposure of SCLC cells to interferon-γ (IFN-γ) increased the expression of HLA; these treated cells were killed by the CTL better than non-IFN-γ treated cells even though the IFN-γ treated SCLC cells displayed diminished gBK protein expression. Prolonged incubation with recombinant IFN-γ slowed the in vitro growth and migration of the SCLC cells, suggesting it might inhibit tumor growth in vivo. Immunotherapy targeting gBK might possibly impede advancement to terminal state of SCLC. Citation Format: Neil T. Hoa, Lisheng Ge, Rajeev B. Tajhya, Christine Beeton, Andrew N. Cornforth, Amir Abolhoda, Nils Lambrecht, Maria Dacosta-Iyer, Yi Ouyang, Michelle J. Hickey, Kate L. Erickson, Carol A. Kruse, Martin R. Jadus. Small cell lung cancer cells express the late stage gBK tumor antigen: a possible immunotarget for the terminal disease. [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 2895. doi:10.1158/1538-7445.AM2014-2895
Performance enhancing substances in sport and exercise
Authors: C Jarvis
Journal: British Journal of Sports Medicine (2005)

Edited by Michael S Bahrke, Charles E Yesalis. Published by Human Kinetics, 2002, £43.00 (hardcover), pp 384. ISBN 0736036792

This is a worthwhile addition to the library of all who work in sport and exercise medicine whether as physician, physiotherapist, or sports scientist. It extends to over 350 pages, is straightforward to read, well arranged, and with a useful index.

The initial chapter on the history of performance enhancing substances (PES) contains considerable information on early attempts at performance enhancement within sport, with much that was new to the reviewer. It even manages a brief reference to the current Governor of California under the subject of body building and anabolic agents!

The first 300 pages consider ergogenic agents in specific groups—identifying the mode of action, likely performance gains, relevant clinical studies, potential problems resulting from use, and ending with a brief overall conclusion. The statements made are …
The Role of Culture in Health Communication
Authors: Matthew W. Kreuter, Stephanie M. McClure
Journal: Annual Review of Public Health (2004)

This paper examines the role of culture as a factor in enhancing the effectiveness of health communication. We describe culture and how it may be applied in audience segmentation and introduce a model of health communication planning--McGuire's communication/persuasion model--as a framework for considering the ways in which culture may influence health communication effectiveness. For three components of the model (source, message, and channel factors), the paper reviews how each affects communication and persuasion, and how each may be affected by culture. We conclude with recommendations for future research on culture and health communication.
Follicular Lymphoma Revisited
Authors: Saul A. Rosenberg
Journal: Journal of Clinical Oncology (2008)

The last quarter century has seen significant advances in the management and understanding of many human malignancies. This is especially true for the malignant lymphomas. The invitation to reflect on a report from Stanford, published 25 years ago, and the changes that have occurred since then, is a rare opportunity to look at what we have learned about the follicular non-Hodgkin’s lymphomas, generally, and their histologic and clinical transformation, specifically. It is useful to divide the Editorial into three parts: diagnostic advances, management advances, and transformation, of both the follicular lymphomas, but, also of the physicians who care for them.
Adenovirus Vector-Mediated<b><i>in Vivo</i></b>Gene Transfer of OX40 Ligand to Tumor Cells Enhances Antitumor Immunity of Tumor-Bearing Hosts
Authors: Sita Andarini, Toshiaki Kikuchi, Mio Nukiwa, Prasenohadi Pradono, Takuji Suzuki, Shinya Ohkouchi, Akira Inoue, Makoto Maemondo, Naoto Ishii, Yasuo Saijo, Kazuo Sugamura, Toshihiro Nukiwa
Journal: Cancer Research (2004)

OX40 ligand (OX40L), the ligand for OX40 on activated CD4+ T cells, has adjuvant properties for establishing effective T-cell immunity, a potent effector arm of the immune system against cancer. The hypothesis of this study is that in vivo genetic engineering of tumor cells to express OX40L will stimulate tumor-specific T cells by the OX40L-OX40 engagement, leading to an induction of systemic antitumor immunity. To investigate this hypothesis, s.c. established tumors of three different mouse cancer cells (B16 melanoma, H-2b; Lewis lung carcinoma, H-2b; and Colon-26 colon adenocarcinoma, H-2d) were treated with intratumoral injection of a recombinant adenovirus vector expressing mouse OX40L (AdOX40L). In all tumor models tested, treatment of tumor-bearing mice with AdOX40L induced a significant suppression of tumor growth along with survival advantages in the treated mice. The in vivo AdOX40L modification of tumors evoked tumor-specific cytotoxic T lymphocytes in the treated host correlated with in vivo priming of T helper 1 immune responses in a tumor-specific manner. Consistent with the finding, the antitumor effect provided by intratumoral injection of AdOX40L was completely abrogated in a CD4+ T cell-deficient or CD8+ T cell-deficient condition. In addition, ex vivo AdOX40L-transduced B16 cells also elicited B16-specific cytotoxic T lymphocyte responses, and significantly suppressed the B16 tumor growth in the immunization-challenge experiment. All of these results support the concept that genetic modification of tumor cells with a recombinant OX40L adenovirus vector may be of benefit in cancer immunotherapy protocols.
Epigenetic Regulation of MicroRNAs Controlling CLDN14 Expression as a Mechanism for Renal Calcium Handling
Authors: Yongfeng Gong, Nina Himmerkus, Allein Plain, Markus Bleich, Jianghui Hou
Journal: Journal of the American Society of Nephrology (2014)

The kidney has a major role in extracellular calcium homeostasis. Multiple genetic linkage and association studies identified three tight junction genes from the kidney--claudin-14, -16, and -19--as critical for calcium imbalance diseases. Despite the compelling biologic evidence that the claudin-14/16/19 proteins form a regulated paracellular pathway for calcium reabsorption, approaches to regulate this transport pathway are largely unavailable, hindering the development of therapies to correct calcium transport abnormalities. Here, we report that treatment with histone deacetylase (HDAC) inhibitors downregulates renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice. Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress the expression of claudin-14, the negative regulator of the paracellular pathway. With renal clearance and tubule perfusion techniques, we showed that HDAC inhibitors transiently increase the paracellular cation conductance in the thick ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH) repressed the transcription of miR-9 and miR-374 genes, and treatment with an HDAC inhibitor rescued the phenotypes of cell and animal models of ADH. Furthermore, systemic treatment of mice with antagomiRs against these miRs relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together, our findings provide proof of concept for a novel therapeutic principle on the basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases.
Antitumor Effects of Doxorubicin Followed by Zoledronic Acid in a Mouse Model of Breast Cancer
Authors: P. D. Ottewell, H. Monkkonen, M. Jones, D. V. Lefley, R. E. Coleman, I. Holen
Journal: JNCI Journal of the National Cancer Institute (2008)

The potent antiresorptive drug zoledronic acid (Zol) enhances the antitumor effects of chemotherapy agents in vitro. We investigated the effects of clinically achievable doses of doxorubicin (Dox) and Zol, given alone, in sequence, and in combination, on the growth of established breast tumors in vivo. Female MF1 nude mice were inoculated subcutaneously with 5 × 10 5 human breast cancer MDA-MB-436 cells that stably expressed green fluorescent protein (ie, MDA-G8 cells). Beginning on day 7 after tumor cell injection, the mice were injected weekly for 6 weeks with saline, Dox (2 mg/kg body weight via intravenous injection), Zol (100 μg/kg body weight via intraperitoneal injection), Dox plus Zol, Zol followed 24 hours later by Dox, or Dox followed 24 hours later by Zol (n = 8–9 mice per group). The effects of treatment on tumor growth were determined by measuring tumor volume; on tumor cell apoptosis and proliferation by immunohistochemistry using antibodies for caspase-3 and Ki-67, respectively; and on bone by microcomputed tomography and bone histomorphometry. All P values are two-sided. Treatment with Dox or Zol alone or Zol followed 24 hours later by Dox did not statistically significantly decrease final tumor volume compared with saline. Mice treated with Dox plus Zol had statistically significantly smaller final tumor volumes than those treated with Dox alone (mean = 122 mm 3 vs 328 mm 3 , difference = 206 mm 3 , 95% confidence interval [CI] = 78 to 335 mm 3 , P < .001), with Zol alone (122 mm 3 vs 447 mm 3 , difference = 325 mm 3 , 95% CI = 197 to 454 mm 3 , P < .001), or with Zol followed 24 hours later by Dox (122 mm 3 vs 418 mm 3 , difference = 296 mm 3 , 95% CI = 168 to 426 mm 3 , P < .001). Treatment with Dox followed 24 hours later by Zol almost completely abolished tumor growth. Tumors from mice that were treated with Dox followed by Zol had more caspase-3–positive cells than tumors from mice treated with saline (mean number of caspase-3–positive cells per square millimeter: 605.0 vs 82.19, difference = 522.8, 95% CI = 488.2 to 557.4, P < .001), with Zol alone (605.0 vs 98.44, difference = 506.6, 95% CI = 472.0 to 541.2, P < .001), or with Zol followed by Dox (605.0 vs 103.1, difference = 501.9, 95% CI = 467.3 to 536.5, P < .001). The treatment-induced increase in the number of caspase-3–positive cells was mirrored by a decrease in the number of tumor cells positive for the proliferation marker Ki-67. No evidence of bone disease was detected in any of the treatment groups following microcomputed tomography and histological analysis of bone. Sequential treatment with Dox followed by Zol elicited substantial antitumor effects in subcutaneous breast tumors in vivo, in the absence of bone disease.
Management of parapneumonic effusion - Does the size of the chest drain matter?
Authors: Shashank Sharma, James Kuah, Ahmed Liju
Journal: European Respiratory Journal (2014)

Background: There is no clear evidence for optimal drain size in the management of parapneumonic effusions. There is some evidence that lesser the “Drainage time” better the outcome. Fluid flow is affected by the radius of the tube and fluid viscosity. We compared the time required to drain parapneumonic effusion (“Drainage time”), with small-bore (12F) Vs conventional large-bore (20-24F) chest drain.To our knowledge, this is first such study to compare the“Drainage time”. Methods: Data from 54 patients with parapneumonic effusions who had chest drains inserted were collected retrospectively and analysed in a tertiary UK hospital. Results: The “Drainage time”, was significantly lesser (p=0.01) with large bore chest drains (n=3.87 days) as compared to the small-bore catheter (n=5.3 days). Analysis also showed that large-bore cohort had more complex parapneumonic effusion than the small-bore cohort with higher LDH levels (9043 Vs1968 IU/L) and lower glucose levels (3.37 Vs 5.13 mmol/L). Small Vs large bore mortality was 3/36 Vs 0/18 (p=0.54); surgical referral rate was 4/36 Vs 3/18 (p=0.68). Conclusion: “Drainage time” with the large bore chest drain was significantly lesser than the small bore chest drain despite having patients with more complex parapneumonic effusion.

View this table:

Summary of the patient characteristics and outcomes between the two different size chest drains
<i>In vitro</i> and <i>In vivo</i> Radiosensitization Induced by the DNA Methylating Agent Temozolomide
Authors: Whoon Jong Kil, David Cerna, William E. Burgan, Katie Beam, Donna Carter, Patricia S. Steeg, Philip J. Tofilon, Kevin Camphausen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Temozolomide, a DNA methylating agent, is currently undergoing clinical evaluation for cancer therapy. Because temozolomide has been shown to increase survival rates of patients with malignant gliomas when given combined with radiation, and there is conflicting preclinical data concerning the radiosensitizing effects of temozolomide, we further investigated the possible temozolomide-induced enhancement of radiosensitivity. Experimental Design: The effects of temozolomide on the in vitro radiosensitivity of U251 (a human glioma) and MDA-MB231BR (a brain-seeking variant of a human breast tumor) cell lines was evaluated using clonogenic assay. DNA damage and repair were evaluated using phosphorylated histone H2AX (γH2AX), and mitotic catastrophe was measured using nuclear fragmentation. Growth delay was used to evaluate the effects of temozolomide on in vivo (U251) tumor radiosensitivity. Results: Exposure of each cell line to temozolomide for 1 h before irradiation resulted in an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1 ranging from 1.30 to 1.32. Temozolomide had no effect on radiation-induced apoptosis or on the activation of the G2 cell cycle checkpoint. As a measure of DNA double strand breaks, γH2AX foci were determined as a function of time after the temozolomide + irradiation combination. The number of γH2AX foci per cell was significantly greater at 24 h after the combined modality compared with the individual treatments. Mitotic catastrophe, measured at 72 h, was also significantly increased in cells receiving the temozolomide + irradiation combination compared with the single treatments. In vivo studies revealed that temozolomide administration to mice bearing U251 tumor xenografts resulted in a greater than additive increase in radiation-induced tumor growth delay with a dose enhancement factor of 2.8. Conclusions: These results indicate that temozolomide can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an inhibition of DNA repair leading to an increase in mitotic catastrophe.
Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro
Authors: H J Pennings, K Kramer, A Bast, W A Buurman, E F Wouters
Journal: European Respiratory Journal (1998)

Recent studies have implicated a role for tumour necrosis factor-alpha (TNFalpha) in the development of the asthmatic reaction. In this study, we examined the influence of TNFalpha on isotonic contraction of tracheal smooth muscle of the guinea-pig in vitro in response to methacholine. Tracheal rings were incubated with recombinant human (rh)TNFalpha (3x10(-11) M) for 30 min, and concentration-response curves to methacholine before and after incubation with rhTNFalpha were compared with the control. The present study demonstrates that rhTNFalpha increases maximal isotonic contraction of tracheal smooth muscle to methacholine (mean+/-SEM 169.6+/-43%, p<0.005). This effect was observed only after a 30 min delay between incubation and methacholine challenge testing. Experiments with 10(-13) - 10(-10) M rhTNF-alpha yielded similar results at all concentrations used. The effects of rhTNFalpha (10(-11) M) on tracheal hyperreactivity could be completely inhibited by coincubation with dimeric rTNF-receptor-p80 construct (10(-10) M) (p<0.01). In order to analyse secondary mediator release, experiments using coincubation with indomethacin (10(-5) M) and WEB 2086 (10(-6) M), a specific platelet activating factor (PAF) antagonist, demonstrated that the effect of rhTNFalpha on tracheal rings was mediated by PAF, since WEB 2086 completely inhibited rhTNFalpha-induced hyperreactivity (p<0.05). In conclusion, this study demonstrates that recombinant human tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle in vitro, which was shown to be mediated by platelet activating factor. Our study emphasizes the role of tumour necrosis factor-alpha in the pathophysiology of bronchial hyperresponsiveness.
Carbapenemase producing Klebsiella pneumoniae (KPC+) colonization/infection in a respiratory intensive care unit: Prevalence, length of stay(LOS) and mortality
Authors: Lara Pisani, Luca Fasano, Anna Koutelou, Simone Ambretti, Viviana Ribuffo, Filippo Natali, Sara Tedeschi, Fabio Tumietto, Stefano Nava
Journal: European Respiratory Journal (2014)

BACKGROUND. Infections by multidrug resistant (MDR) Enterobacteriaceae in patients admitted in Intensive Care Units (ICU) are rapidly increasing and have become a worrisome problem both in terms of resources allocation and in terms of patient outcome. The prognosis of KPC+ infection is poor lacking an effective treatment. There are no specific data about the prevalence of KPC+ in a Respiratory ICU (RICU) and about lower respiratory tract infection (LRTI) outcome.  AIM of this study is to assess prevalence,LOS and mortality in RICU of patients colonized/infected by KPC+.  METHOD. The study was performed in a RICU of a large teaching hospital over a period of 30 months. KPC+ presence was assessed by rectal swab at admission and then every seventh day and for LRTI by BAL.  RESULTS. Among 547 patients admitted in our 7-bed RICU; mortality was 25% (138/547) and the average LOS was 10.8+ 8.2days.  7.7% of the patients (42/547) were colonized/infected by KPC+. 10 of these 42 subjects (24%) died in the RICU. The average LOS in RICU in this group was 24.8+ 12.3days (Pl0.05 vs the overall LOS). 15/42 patients had a positive BAL and LRTI; mortality in this group was 27% (4/27).  CONCLUSIONS. KPC+ colonization/infection significantly prolongs RICU LOS but does not affect mortality vs the overall population. Although based on a relatively small number of cases, this observational analysis indicates that KPC+ colonization/infection is a significant burden also in a RICU, despite it does not seem to increase the mortality rate vs non-positive patients.