tbuckley/cabot-search huggingface dataset:
Abstract 2869: Mitral Valve Repair using Autologous Pericardium Annuloplasty: Eighteen-Years Experience in 490 Patients
Authors: Loris Salvador, Giuseppe Minniti, Elena Cavarretta, Salvatore Mirone, Wadih Tamari, Francesco Rocco, Valeria Salandin, Thanos Athanasiou, Emanuele Di Angelantonio, Carlo Valfrè
Journal: Circulation (2008)

Autologous Pericardium Annuloplasty (APA) is an alternative option to prosthetic ring, avoiding foreign material implantation and preserving the physiological motion of mitral annulus but contrasting data on durability are reported. We sought to evaluate the very long term results of mitral valve repair (MVR), for mitral regurgitation (MR), with posterior annuloplasty performed with glutaraldehyde-treated autologous pericardium. Between July 1988 and Dec 2006, 490 consecutive patients underwent MVR with posterior APA, in addition to other repair procedures. Mean age was 54.3±11.3 (range 15–77y) and 360 (74.1%) men. Valve disease was purely degenerative in 434 (89.3%) patients, endocarditis was present in 44 (9.1%). Anterior, posterior and bileaflet leaflet prolapse were present in 32 (6.6%), 241 (49.6%) and 213 (43.8%) respectively. Gore-Tex® neo-chordae were implanted in all patients. Posterior leaflet quadrangular resection was performed in 283 patients (58.2%). Echocardiographic Doppler studies were obtained annually and clinical follow-up was 100% complete at a mean of 7.1±4.4 years (range 1–18y). In-hospital mortality was 1% (5 deaths), overall and cardiac late mortality 7.6% and 3.9% (37 and 19 deaths). Kaplan-Meier curves for mortality and freedom from reoperation at 15 years were 83% (95% CI 71–90) and 93% (95% CI 88–96) (20 patients). At 15 years freedom from recurrent MR and endocarditis were 86% (95% CI 77–91) (28 patients) and 97% (95% CI 92–99) (6 events), respectively. Dehiscence or calcification of APA were never reported. At reoperation, annular pericardium appeared covered by a smooth layer of tissue, without signs of degeneration. None of the patients experienced hemolysis. MVR with posterior autologous pericardial annuloplasty is feasible, safe and cost effective, providing long-term durability. APA is intended to preserve the anatomical and physiological characteristics of the mitral annulus, avoiding prosthetic material, especially in young patients or endocarditis etiology. In contrast to data presented in literature, in our series, APA showed a high survival and low rates of valve-related complications at very long-term follow-up, with a high freedom from recurrent MR.
In non-ICU suspected CAP, β-lactam was noninferior to β-lactam–macrolide or fluoroquinolone for 90-d mortality
Authors: Thomas Fekete
Journal: Annals of Internal Medicine (2015)

Source Citation Postma DF, van Werkhoven CH, van Elden LJ, et al; CAP-START Study Group. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372:1312-23. 25830421
Ethnic peculiarities of chlamydiosis in bronchial asthma
Authors: Svetlana Smirnova, Alevtina Sharavii
Journal: European Respiratory Journal (2012)

Aim: To study ethnic peculiarities of chlamydiosis prevalence in bronchial asthma (BA) patients of Krasnoyarsk and Kyzyl.  Materials and Methods. We have examined 239 subjects (from 17 to 78 years): the Europoids (n=159), the Mongoloids (n=80). Among them: BA (n=187), control (n=52). We have determined Chlamydophila pneumoniae et psittaci (C.pneumoniae et psittaci), Chlamydia trachomatis (C.trachomatis) by direct immune fluorescence technique (DIF) for smears of oropharynx, their antibodies from blood serum by immune enzyme analysis (IEA).  Results. The frequency of C.pneumoniae et psittaci in BA: in the Europoids by DIF – 14.5%, IEA IgM – 3.9%, IgG – 41.9%; in the Mongoloids – 25.9%, 10.3%, 17.2%, correspondingly. In control groups C.pneumoniae et psittaci had been revealed in the Europoids by DIF – 6.7%, IEA IgM – 0.0%, IgG – 23.3%; in the Mongoloids – 27.3%, 4.5%, 18.2%, correspondingly.  The frequency of C.trachomatis in BA: in the Europoids by DIF – 10.8%, IEA IgA – 3.9%, IgM – 3.1%, IgG – 25.6%; in the Mongoloids – 19.0%, 3.4%, 1.7%, 19.0%, correspondingly. In control groups C.trachomatis in the Europoids by DIF –30.0%, IEA IgA – 0.0%, IgM – 0.0%, IgG – 6.7%; in the Mongoloids – 13.6%, 0.0%, 9.1%, 40.9%, correspondingly.  Conclusion. Were found ethnic peculiarities: in the Mongoloids more frequent than in the Europoids – IgM to C.pneumoniae in BA; IgM to C.pneumoniae, IgM to C.trachomatis in control groups.
Visual field required for safe driving wrongly defined
Authors: A. R Elkington
Journal: BMJ (1995)

Driving, glaucoma, and the law Regular checks on medical fitness to drive needed EDITOR,-Potamitis and colleagues draw attention to widespread ignorance about regulations con- cerning visual fields for driving.'Because drivers are required to pass a visual acuity test as part of their driving test, however, most are aware of visual acuity as a component of visual function and of its relevance to driving.This does not necessarily imply greater compliance with the regulation concerning visual acuity than with those concerning visual fields.We recorded visual acuity (with glasses if wom) in consecutive patients attending the accident and emergency service at Manchester Royal Eye Hospital.Over one month 1426 patients were tested, of whom 177 had a visual acuity insufficient for legal driving.Most of these patients did not drive, but 42 still drove a car.Of these 42, 21 were "borderline" failures (6/12 in the better eye) but the remaining 21 would definitely have failed a standard numberplate reading test.All these patients had evidence of chronic visual loss, which was correctable by refraction in only some cases.Clearly, patients with acute eye problems may have acute visual deterioration.Such deterioration, however, is almost invariably unilateral.For driving a car, acceptable vision is only required in one eye.There was no evidence to suggest that these data were invalidated by acute, temporary visual loss in these patients.Potamitis and colleagues rightly recommend that greater information should be made available to drivers, both from the Driver and Vehicle Licensing Agency and from ophthalmologists.The key role of optometrists should also be made clear.The authors comment that patients need more information and imply that this will in itself improve driving safety by resulting in voluntary withdrawal on the part of unfit drivers, but this is merely an assumption.Do we not need regular checks on medical aspects of fitness to drive, even for people under retirement age?
The Effectiveness of Combinations of Antileukemic Agents in Inducing and Maintaining Remission in Children with Acute Leukemia
Authors: EMIL FREI, MYRON KARON, ROBERT H. LEVIN, EMIL J. FREIREICH, ROBERT J. TAYLOR, JULIET HANANIAN, OLEG SELAWRY, JAMES F. HOLLAND, BARTH HOOGSTRATEN, IRVING J. WOLMAN, ESSHAGH ABIR, ARTHUR SAWITSKY, STANLEY LEE, STEPHAN D. MILLS, E. OMER BURGERT, CHARLES L. SPURR, RICHARD B. PATTERSON, FRANKLIN G. EBAUGH, G. WATSON JAMES, JOHN H. MOON
Journal: Blood (1965)
T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion injury in patients
Authors: Stephen E. Boag, Rajiv Das, Evgeniya V. Shmeleva, Alan Bagnall, Mohaned Egred, Nicholas Howard, Karim Bennaceur, Azfar Zaman, Bernard Keavney, Ioakim Spyridopoulos
Journal: Journal of Clinical Investigation (2015)

Lymphocytes contribute to ischemia/reperfusion (I/R) injury in several organ systems, but their relevance in ST elevation myocardial infarction (STEMI) is unknown. Our goal was to characterize lymphocyte dynamics in individuals after primary percutaneous coronary intervention (PPCI), assess the prognostic relevance of these cells, and explore mechanisms of lymphocyte-associated injury.Lymphocyte counts were retrospectively analyzed in 1,377 STEMI patients, and the prognostic relevance of post-PPCI lymphopenia was assessed by Cox proportional hazards regression. Blood from 59 prospectively recruited STEMI patients undergoing PPCI was sampled, and leukocyte subpopulations were quantified. Microvascular obstruction (MVO), a component of I/R injury, was assessed using MRI.In the retrospective cohort, lymphopenia was associated with a lower rate of survival at 3 years (82.8% vs. 96.3%, lowest vs. highest tertile; hazard ratio 2.42). In the prospective cohort, lymphocyte counts fell 90 minutes after reperfusion, primarily due to loss of T cells. CD8+ T cells decreased more than CD4+ T cells, and effector subsets exhibited the largest decline. The early decrease in effector T cell levels was greater in individuals that developed substantial MVO. The drop in T cell subsets correlated with expression of the fractalkine receptor CX3CR1 (r2 = 0.99, P = 0.006). Serum fractalkine concentration peaked at 90 minutes after reperfusion, coinciding with the T cell count nadir.Lymphopenia following PPCI is associated with poor prognosis. Our data suggest that fractalkine contributes to lymphocyte shifts, which may influence development of MVO through the action of effector T cells.Not applicable.British Heart Foundation (FS/12/31/29533) and National Institute of Health Research (NIHR) Newcastle Biomedical Research Centre.
Saponin Polyphyllin D induced apoptosis in human hepatocellular carcinoma and multidrug resistant liver cancer cells
Authors: Rose C. Y. Ong, Jenny Y. N. Cheung, Henry N. C. Wong, Thomas C. W. Mak, S. K. Kong, Biao Yu, K. P. Fung
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2979 

Saponins are the active components of many medicinal herbs such as Panax ginseng. Polyphyllin D ([Figure 1][1]) is a steroidal saponin present in the plant Paris Pollyphylla which has been used in China to treat cancer for many years. As the isolation and purification of saponins from plants had been very difficult, Polyphyllin D was chemically synthesized and purified. By using this synthesized Polyphyllin D, its apoptotic effects in a human hepatocellular carcinoma cell line HepG2 and its doxorubicin resistant derivative RHepG2 cells (with an over-expression of P-glycoprotein) were investigated. As compared to the commonly used anticancer drug doxorubicin (DOX), the IC50 of Polyphyllin D and that of DOX were more or less the same in HepG2 cells after 24 hours treatment (∼6μM). However, the IC50 of Polyphyllin D in RHepG2 cells was 5μM, and that of DOX was higher than 250μM. Hallmarks of apoptosis, including externalization of phosphatidylserine, DNA ladder and chromatin condensation were observed in both cell lines after 24 hours treatment with 5μM Polyphyllin D. Further studies showed that Polyphyllin D induced apoptosis through mitochondrial dysfunction, as evidenced by mitochondrial depolarization and release of cytochrome c , a key protein in mitochondria mediated apoptosis. To demonstrate its direct effects on mitochondria, mitochondria from HepG2 and RHepG2 cells were isolated and treated with Polyphyllin D. Mitochondrial depolarization and cytochrome c release from the isolated mitochondria were again observed. Thus, Polyphyllin D acts directly on mitochondria to cause apoptosis. Furthermore, in a 12 day-treatment of RHepG2 cells with 1.2μM Polyphyllin D, 27% of cells accumulated more DOX when compared to that of an untreated group. Preliminary assay by Western blot showed that P-glycoprotein expression was down-regulated too. Conclusively, Polyphyllin D is a potent anticancer agent or mitochondrial toxin against “normal” and drug-resistant cancer cells which acts on the mitochondria to trigger apoptosis in HepG2 and RHepG2 cells. More work is needed to confirm its effects in P-glycoprotein expression and the corresponding action mechanism. This work is supported by the Shanghai-Hong Kong Anson Research Foundation. [Figure 1][1]. The structure of Polyphyllin D.



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 [2]: pending:yes
Abstract 2824: Evaluation of Ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention
Authors: Arvind Thakkar, Sushma Chenreddy, Jeffrey Wang, Sunil Prabhu
Journal: Cancer Research (2015)

Abstract The objective of the present study was to establish the individual and combined chemopreventive potential of a widely used non-steroidal anti-inflammatory drug, ibuprofen (IBU), encapsulated in solid lipid nanoparticles (SLNs) for the chemoprevention of pancreatic cancer. The synergistic effect of combination of IBU with sulforaphane (SFN) was also evaluated. Cell viability studies were conducted followed by colony formation and NF-κB DNA binding assays. The IC50 concentration of free IBU in human pancreatic cancer cells Panc-1 and MIA PaCa-2 were 1.25mM and 1.26 mM, respectively. SLN optimization study of IBU revealed stearic acid (1:2 drug to lipid ratio) formulated with Poloxamer 188 to be the most efficacious in cell viability study. Upon encapsulation in SLNs, IC50 concentration of IBU-SLN was 113.8 μM and 122.6 μM for Panc-1 and MIA PACa-2 cells respectively, reflecting a 10-fold reduction compared to free IBU. Combinations of low doses of free IBU (250 μM) and SFN (5 μM) reduced cell viability by ∼55% (P&amp;lt;0.01), whereas a lower dose of encapsulated IBU-SLN (62.5 μM) and free SFN (5 μM) reduced cell viability by ∼80% (P&amp;lt;0.001) for both Panc-1 and MIA PaCa-2 cells. These results reflect 4-fold reduction in IBU-SLN dose in combination compared to free IBU. Moreover, IBU-SLN and free SFN combination reduced number of colonies by ∼50% (P&amp;lt;0.01). Further, IBU-SLN and SFN combinations showed down-regulation of DNA binding activity of the p50 subunit of NF-κB. In conclusion, these preliminary results demonstrate the potential of IBU as a chemopreventive agent against pancreatic cancer. Furthermore, when encapsulated in nanotechnology-based SLN delivery systems and delivered in combination with SFN provide evidence of a promising approach for pancreatic cancer prevention and therapy. Citation Format: Arvind Thakkar, Sushma Chenreddy, Jeffrey Wang, Sunil Prabhu. Evaluation of Ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2824. doi:10.1158/1538-7445.AM2015-2824
Abstract 1840: Contribution of miR-205 in gefitinib-resistant lung cancer cell lines
Authors: Toshihiro Suzuki, Ikuko Nagasawa, Toshimitsu Yamaoka, Tohru Ohmori, Kazuto Nishio, Kiyotaka Koyama, Yuki Ogasawara
Journal: Cancer Research (2014)

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib is effective therapies for patients with advanced non-small cell lung cancer (NSCLC). Treatment with gefitinib frequently induces drug resistance in NSCLC. Two mechanisms of acquired resistance have been validated in patients. Secondly mutations in EGFR itself, EGFR T790M and amplification of the MET oncogene are observed in resistance case. However, it remains unclear how MET over expression contributes to TKI resistant NSCLC. Recently, micro RNA (miRNA) expression is noted and analyzed because the concern of these molecules in cancer pathogenesis and drug resistance has been elucidated. Circulating tumor cell (CTC) and miRNA are focused as sensitive and non-invasive biomarkers for cancer diagnosis. In this study, we aimed at the miRNA in the gefitinib-resistant cell lines, and evaluated the miRNAs being associated with resistance of gefitinib. We established gefitinib resistant cell lines, in which MET is amplified, PC-9/MET and PC-9/MET-1K by a stepwise escalation of gefitinib concentrations in vitro. Microarray and real time PCR analysis indicated that miR-205 is significantly elevated in both resistant cell lines, and ErbB3 was a significant target. We examine further to reveal that relation between miR-205 and EGFR family, such as ErbB2 and ErbB3. Our results suggest that miR-205 may function as a gefitinib resistance in NSCLC. Citation Format: Toshihiro Suzuki, Ikuko Nagasawa, Toshimitsu Yamaoka, Tohru Ohmori, Kazuto Nishio, Kiyotaka Koyama, Yuki Ogasawara. Contribution of miR-205 in gefitinib-resistant lung cancer cell lines. [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 1840. doi:10.1158/1538-7445.AM2014-1840
Abstract P6-09-08: Can proton therapy for localized mediastinal Hodgkin's lymphoma reduce second breast cancer incidence?
Authors: Samy R Horn, Victor Pernin, Nathalie Fournier-Bidoz, Youlia Kirova
Journal: Cancer Research (2015)

Abstract Introduction Secondary breast cancer (SBC) is a recognized late complication of radiation therapy, after treatment for Hodgkin lymphoma (HL), with reported relative risks as high as 50 with older techniques (Mantle Field). Within the past, it has been estimated that reduction in dose and volume will reduce the incidence of late complications such as secondary neoplasms and cardiovascular disease. We evaluate the impact of mediastinal proton therapy on potential limitation of SBC risk. Material &amp; methods For 14 young female patients with early-stage, mediastinal HL, treated with chemotherapy and involved-field raditation therapy (IFRT), we simulated similar treatment plans with conformal radiotherapy (CRT), helical tomotherapy (HT) and proton therapy at the dose of 30 Gy. We report the respective doses to the breasts. Treatment plans were not specifically designed for breast sparing. Results Proton therapy significantly lowered the dose to the breasts, with mean doses of 2,76/1,53 Gy to the left and right breast respectively with proton therapy (vs. 4,95/3,88 Gy with HT and vs. 5,56/3,58 Gy with CRT). Proton therapy best limited lower doses (V4Gy and V10Gy) compared to CRT, while HT could limit the higher doses (V20Gy) at the expense of larger volume irradiated at low doses (V4Gy). Conclusion Relative reduction in mean doses to the left and right breasts was of 50 and 57% respectively with proton therapy compared to CRT. Relation between radiation dose and SBC seems to be linear, and reduction in SBC should be in such proportion with proton therapy. Proton therapy seems highly interesting for breast sparing after curative treatment for HL, but these results need to be confirmed by individualized risk estimations and prospective trials. Citation Format: Samy R Horn, Victor Pernin, Nathalie Fournier-Bidoz, Youlia Kirova. Can proton therapy for localized mediastinal Hodgkin's lymphoma reduce second breast cancer incidence? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-09-08.
Abstract 5858: Role of Oxygen Tension and Oxidative Stress in Human Saphenous Vein Remodeling
Authors: Binata Joddar, Rashmeet K Reen, Michael Firstenberg, Keith J Gooch
Journal: Circulation (2008)

Vessels cultured ex vivo maintain viability and vasoactivity for weeks and can remodel in response to mechanical cues. When cultured in the presence of 5% CO2/balance air veins develop neointimal hyperplasia (IH) while arteries do not suggesting that exposure to significant increases in pO2 levels might stimulate IH. Neointimal hyperplasia (IH) is a known mechanism by which saphenous veins have a decreased patency compared to arterial conduits when used for coronary artery bypass. We sought to explore the role of oxygen tension and oxidative stress in IH. Test the hypothesis that exposure of human saphenous veins (HSV) to arterial pO2 stimulates IH via ROS-mediated pathways. Almost 40 HSV remnants acquired following CABG were cultured ex vivo with arterial (~95mmHg) pO2 or venous (~40mmHg) pO2 for 14 days. All differences reported have a p&lt;0.05 via Student’s t-test. Results: HSV cultured at arterial pO2 exhibited significant IH as evidenced by disruption of the IEL, invasion of cells from the media, and a 2.8-fold greater intimal area than fresh HSV, a 5.8-fold increase in cell proliferation compared to fresh HSV, increased ROS levels and oxidative stress as evidenced by 4-fold increase in 4-HNE level (a marker of oxidative stress), increased DHE staining (indicative of superoxide generation), and a progressive increase in total ROS levels with time as assessed by DCF fluorescence, and a 3-fold increase in phosphorylated p38-MAPK, which is implicated in SMC proliferation. In stark contrast vessels culture at arterial pO2, HSV cultured with venous pO2 did not develop increased IH and were indistinguishable from fresh vessels with respect to proliferation, markers of oxidative stress, and MAPK expression levels. Supplementing culture medium with antioxidants including Tiron or NAC blocked the pO2-induced changes. These data indicate that exposure to arterial pO2 increases cellular proliferation and stimulates IH, potentially via oxidative stress or ROS signaling and also suggest that exposure to elevated arterial pO2 might stimulate pathological remodeling of veins grafted into the arterial circulation. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania &amp; West Virginia).
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach
Authors: Marianna Cerasuolo, Debora Paris, Fabio A. Iannotti, Dominique Melck, Roberta Verde, Enrico Mazzarella, Andrea Motta, Alessia Ligresti
Journal: Cancer Research (2015)

Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignantneuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence.