tbuckley/cabot-search huggingface dataset:
Abstract 4854: Acute Systemic Inflammation Increases Central Blood Pressure and Pulse Wave Velocity in Healthy Subjects
Authors: Sae Young Jae, Kevin Heffernan, Jeffrey Woods, Victoria Vieira, Stephen Martin, Brandt Pence, Bo Fernhall
Journal: Circulation (2009)

Objective. Acute systemic inflammation or infection transiently increases risk of cardiovascular events, but the underlying mechanisms are not fully understood. Although observational studies suggest that inflammation is associated with arterial stiffness and blood pressure, the causal relationship of this is not clear. We tested the hypothesis that induced acute inflammation causes an increase in blood pressure and arterial stiffness. Methods. Using a randomized double blind sham placebo-controlled cross over design, nineteen healthy subjects (male 10, female 9; age 24±4 yrs) were injected with an influenza vaccine (0.5m/L) as a model to generate systemic inflammation, and a sham vaccine (normal saline). C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-a) were measured as a markers of inflammation. Central aortic blood pressure was measured by radial artery tonometry and a generalized transfer function. Carotid-radial pulse wave velocity (PWV) was measured using applanation tonometry. These variables were measured at baseline 24 hours and 48 hours after each vaccination. Results. The influenza vaccination caused a significant increase in CRP (1.42±0.6 at baseline, 2.81±1.0 after 24 hours, 5.0±1.3mg/L after 48 hours, p&lt;0.05) and IL-6 (1.12±0.3, 2.56±0.4, 2.26±0.6, p&lt;0.05) but not TNF-a compared with sham placebo. Brachial artery systolic blood pressure was not significantly increased after an influenza vaccination (115.9±9.9, 118.8±10.9, 118.3±10.2mmHg, NS). However, central systolic blood pressure (98.0±7.4, 104.5±10.8, 100.7±8.4mmHg, p&lt;0.05) and PWV (7.8±0.9, 8.6±1.5, 8.7±1.3m/s, p&lt;0.05) were significantly increased after an influenza vaccination but not sham vaccination. Conclusions. These findings show that an acute inflammation caused a temporary increase in central blood pressure and arterial stiffness. This offers insight regarding the noted increased risk of cardiovascular events associated with acute systemic inflammation. This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota &amp; Wisconsin).
Abstract 2468: Chronic Treatment Of Hypertensive Patients With The At1 Receptor Blocker Losartan Results In Sufficient Serum Levels Of The Metabolite Exp3179 Exhibiting Pparγ-stimulating Properties
Authors: Kai Kappert, Oleg Tsuprykov, Jan Kaufmann, Ingo Ott, Matthias Goebel, Ilse Nirmala Bähr, Paul-Laszlo Häβle, Ronald Gust, Eckart Fleck, Thomas Unger, Philipp Stawowy, Ulrich Kintscher
Journal: Circulation (2008)

The losartan metabolite EXP3174 exhibits angiotensin II receptor 1 (AT1R)-blocking properties, whereas the metabolite EXP3179 potently induces the activity of the insulin-sensititzing peroxisome proliferator-activated receptor γ (PPARγ) as a partial agonist in vitro.. We investigated, whether hypertensive patients chronically treated with losartan exhibit sufficient plasma levels of EXP3179 to activate PPARγ in monocytes derived from losartan-treated patients. Hypertensive patients (n=9) treated with losartan (100mg/daily during at least the past two months), and control patients (n=7) with no chronic AT1R-blocking therapy were included. Blood was taken from all individuals and serum was prepared. Monocytes were extracted by negative isolation using a Dynal Monocyte Kit, followed by RNA-isolation and measurement of PPARγ target gene expression (CD36, ABC transporter G1 (ABCG1)) by quantitative real-time RT-PCR. Losartan-treated patients received 100mg orally, and serum was prepared 2, 4, and 6h after drug ingestion for HPLC-based determination of losartan and losartan metabolites (EXP3174/ EXP3179) in serum. Serum levels were standardized to measurements of purified compounds. Chronic treatment with losartan resulted in basal levels (24h after drug intake) of losartan, EXP3174 and EXP3179 of 382,5ng/ml, 97,0ng/ml and 164,2ng/ml, respectively. Levels of both, EXP3174 and EXP3179 were time-dependently enhanced in serum with a maximum 2h after drug intake (2619,6ng/ml, 980,9ng/ml, respectively). In order to evaluate the possible agonistic property of chronic EXP3179 serum levels on PPARγ, we determined the transcript levels of CD36 and ABCG1 as known PPARγ target genes. Gene expression was significantly upregulated in patients chronically treated with losartan by 5.26±1.55- and 188.54±56.92-fold for CD36 and ABCG1 (p=0.039, p=0.023 vs. control patients, respectively). This is the first clinical description of monocytic PPARγ-target gene regulation by chronic treatment with losartan, which likely is mediated by its metabolite EXP3179. Our data show that sufficient serum levels of EXP3179 are present under losartan treatment. PPARγ activation by AT1R-blockers may translate into synergistic beneficial actions in monocytes.
Abstract 114: Effect of Sodium Bicarbonate on Advanced Cardiac Life Support
Authors: Jungyoup Lee
Journal: Circulation (2014)

Introduction: Current guidelines do not support routine administration of sodium bicarbonate during cardiopulmonary resuscitation (CPR). Previous studies did not recommend bicarbonate unless there is severe metabolic acidosis or hyperkalemia. We hypothesized that the sodium bicarbonate, regardless of its effect on long-term outcomes, may improve the chance of achieving return-of-spontaneous circulation (ROSC). Methods: We used out of cardiac arrest registry in our hospital and analyzed retrospectively. The primary endpoint was to assess the association between 1) the timing first administration as well as 2) the total amount of sodium bicarbonate administered until ROSC and the chance of achieving ROSC. The secondary endpoint was to assess whether there is significant decrease in early survival if sodium bicarbonate was administered during CPR. We built multivariable logistic regression model by the use of the amount of sodium bicarbonate, age, initial base deficit, serum potassium level and usual Utstein template factors with their p-value &lt; 0.1 in univariable analysis. Results: Total 697 patients were enrolled. The amount of sodium bicarbonate administered until ROSC (or CPR termination if there is no ROSC) was significantly associated with the chance of ROSC (Odds ratio [OR], 1.10; 95% confidence interval [CI], 1.01-1.19; p=0.028). The association was still valid after additional adjustment with factors with their p-value &lt; 0.1 in univariable conditional logistic regression analysis. (OR, 1.14; 95% CI, 1.01-1.29; p=0.031) The time to first administration of sodium bicarbonate did not show significant univariable association (OR, 0.99; 95% CI, 0.99-1.00; p=0.193). Kaplan-Meyer survival curves showed significantly increased death rate in patients administered with sodium bicarbonate (log-rank test, p=0.002) Conclusion: Administration of higher dose of sodium bicarbonate during CPR was associated with increased chance of achieving ROSC. However, such benefit was negated soon after by higher early mortality rate in the group where sodium bicarbonate was administered.
Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93
Authors: Marco Colleoni, Shari Gelber, Edda Simoncini, Olivia Pagani, Richard D Gelber, Karen N Price, Monica Castiglione-Gertsch, Alan S Coates, Aron Goldhirsch
Journal: Annals of Oncology (2007)
Abstract 11936: The Value of Pulse Wave Timing Properties in the Detection of Circulatory Shock
Authors: Marc J van Houwelingen, Daphne Merkus, Dirk J Duncker
Journal: Circulation (2011)

The value of pulse wave timing properties in detection of circulatory shock has recently been shown using the relative ventilatory variation in the pre-ejection period (ΔPEP). Here we aimed to improve the use of pulse wave timing properties in shock by testing the hypothesis that the relative ventilatory variation in the isovolumic contraction period determined by arterial pulse wave analysis (ΔAIC) is a more reliable indicator of blood loss than ΔPEP, as ΔPEP is influenced by pulse wave travel time and ventricular electro-mechanical delay. For this purpose, we studied the responses of ΔAIC and ΔPEP to a graded hemorrhage protocol, and compared these to the response of stroke volume (SV) and the clinically used pulse pressure variation (ΔPP). ΔAIC and ΔPEP were determined from both the aortic and the carotid pulse wave (subscript indices  Ao  and  Ca  respectively). A graded hemorrhage protocol (blood withdrawal up to 20ml/kg) was performed in 7 anesthetized swine. Both ΔPEP Ao  and ΔAIC Ao  correlated well with SV (r=-0.51, p Ca  and ΔAIC Ca  correlated well with SV (r=-0.49, p=0.01 and r=-0.63, p Ao  following hemorrhage, indicated by the lower magnitude of ΔPEP Ao  as compared to that of ΔAIC Ao  (see figure). As expected, pulse travel time decreased ΔPEP, indicated by a significantly lower ΔPEP Ca  as compared to ΔPEP Ao  (p Ao  was not significantly different from ΔAIC Ca . These results support the value of pulse wave timing properties in the detection of shock, and show the superiority of ΔAIC over ΔPEP as an indicator of a decreased circulating blood volume since it is independent of the measurement site.
New Trends in Basic Lymphology.
Authors: J. A. Sharp
Journal: Annals of Internal Medicine (1968)

This pamphlet gives the text of a lecture delivered by Professor Bargmann on the occasion of the conferment on him of the Schleiden medal in Halle in 1966.It is, as one would expect, a masterly, wide-ranging, but yet concise review of a complex subject and constitutes an up-to-date assessment, in a form which may be readily appreciated by non-specialists, of structural and functional correlations in this intriguing junctional zone between the nervous and endocrine systems.
"Just right" perceptions associated with compulsive behavior in Tourette's syndrome
Authors: J F Leckman, D E Walker, W K Goodman, D L Pauls, D J Cohen
Journal: American Journal of Psychiatry (1994)

Tourette's syndrome is a chronic disorder of childhood onset that is characterized by motor and phonic tics and a broad range of associated behavior including obsessive-compulsive symptoms. Less well appreciated are the sensory and other perceptually tinged mental phenomena associated with both tic and compulsive behavior. This cross-sectional study evaluated the "just-right" phenomena commonly associated with compulsive behavior in subjects with tic disorders.A total of 134 subjects with tic disorders, aged 9 to 71 years, completed a questionnaire concerning their current and past tic symptoms. Subjects were also asked to describe their "just right" perceptions. The Yale-Brown Obsessive Compulsive Scale was used to assess severity of current obsessive-compulsive symptoms.Eight-one percent of the subjects with both Tourette's syndrome and obsessive-compulsive disorder (N = 31) and 56% of the subjects with Tourette's syndrome and obsessive-compulsive symptoms (N = 61) reported being aware of a need to perform compulsions until they were "just right." This awareness most commonly referred to visual or tactile (as opposed to auditory) features of the compulsive act or its consequences. Three-quarters of the subjects with these perceptions reported that they usually were aware of them immediately before or concurrently with the initiation of compulsions.While epidemiological studies of tic disorders and obsessive-compulsive disorder have yet to incorporate questions concerning "just right" perceptions, these results suggest that such perceptions may be commonplace in adolescent and adult subjects with both obsessive-compulsive disorder and tic disorders. They also implicate brain regions involved in the processing of sensorimotor information in the pathobiology of tic disorders.
Bortezomib enhances radiosensitization in human oral squamous carcinoma cells via suppressing the irradiation-induced expression of antiapoptotic proteins
Authors: Katsumi Motegi, Masayuki Azuma, Tetsuya Tamatani, Natsumi Takamaru, Mitsunobu Sato
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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[Background] The nuclear factor κB (NF-κB) plays an important role in the development and progression of cancers. We had already reported that NF-κB activity in head and neck carcinoma cells was significantly higher than that in normal oral epithelial cells due to the enhanced phosphorylation and degradation of IκBα protein, and that inhibition of NF-κB activity by introducing a super-repressor form of IκBα cDNA into oral cancer (B88) cells led to a drastic decrease in tumorigenicity in nude mice and an acquisition of enhanced radiosensitization. [Purpose] In this study, we examined a possibility that bortezomib (VELCADE®, Millennium Pharmaceutical, Inc.) enhances radiosensitivity in B88 cells. [Methods and Results] B88 cells were subcutaneously inoculated into the backs of nude mice. When the tumor reached 0.5 cm in diameter, tumor-bearing nude mice received either the intravenous administration of bortezomib (0.1 mg/kg/day, three times a week for 4 weeks) or irradiation (IR) (1.5 Gy/day, three times a week for 4 weeks) alone, or combination of bortezomib with IR. Suppression of tumor growth was significantly augmented by the combined treatment with IR and bortezomib as compared to IR or bortezomib alone. To investigate the mechanism involved in the enhancement of radiosensitization by bortezomib, expression of NF-κB-regulated antiapoptotic proteins, including cellular inhibitor of apoptosis protein (cIAP)-1, cIAP-2, XIAP, Bcl-2, Bcl-x and FLICE inhibitory protein (FLIP), was examined. When B88 cells reached subconfluence in culture, they were exposed to IR (7.5 Gy) with or without bortezomib (5 nM). Forty-eight hours later, total RNA was extracted and examined the expression of anti-apoptotic proteins by quantitative real-time RT-PCR. Although IR alone enhanced the expression of both cIAP-1 and cIAP-2 mRNAs in B88 cells, treatment of cells with bortezomib and IR caused the suppression of these mRNA expression. However, mRNA expression levels of the remaining antiapoptotic proteins was found not to be significantly affected by treatment with bortezomib and IR. Next we examined the cleavage of PARP protein to determine whether treatment with bortezomib and IR enhances the apoptotic cell death in B88 cells. This analysis showed that the treatment with the combination of bortezomib and IR led to the enhanced cleavage of PARP protein with a molecular weight of 29 kDa, indicating the augmentation of apoptotic cell death in B88 cells. [Conclusion] These findings indicate that bortezomib enhances the apoptosis in oral cancer cells by inhibiting the irradiation-induced production of antiapoptotic proteins through the inhibition of NF-κB activation.
Preclinical chemotherapy with the VEGFR-2 and PDGFR inhibitor, BAY 57-9352, in combination with Capecitabine and Paclitaxel
Authors: Yong S. Chang, Christian Cortes, Barbara Polony, Cheryl Brink, James J. Elting
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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BAY 57-9352 is an orally active, small molecule inhibitor of VEGFR-2 and PDGFR-b tyrosine kinases, which is currently in Phase I clinical trials. BAY 57-9352 blocks tumor growth through the inhibition of these key regulators of tumor angiogenesis. It exhibits a broad-spectrum of activity as a single agent in multiple human tumor xenograft models representing breast, colon, prostate and lung cancer. The clinical development of BAY 57-9352 is anticipated to include combination chemotherapy with the current standards of care for a variety of histological types of cancer. In the current studies, we have examined the anti-tumor activity and tolerability of BAY 57-9352 when co-administered with either capecitabine (Xeloda® ) or paclitaxel (Taxol® ). The anti-tumor efficacy and tolerability of BAY 57-9352 in combination with capecitabine or paclitaxel were examined using subcutaneous Colo-205 human colorectal cancer or H460 human non-small cell lung cancer xenograft models, respectively, implanted in female athymic (NCr- nu/nu ) mice. In two studies combining BAY 57-9352 with capecitabine, both agents were administered p.o. for 9 or 10 days. When combined with paclitaxel, BAY 57-9352 was administered p.o. for 9 days and paclitaxel was administered concurrently (i.v.) for the first 5 days. Efficacy was assessed as the days delay in tumor growth to reach a specified size (TGD). BAY 57-9352 (60 mg/kg, p.o.) and capecitabine (500 mg/kg, p.o.) demonstrated significant anti-tumor activity following once daily administration as single agents in the Colo-205 model with an average TGD of 16 and 30 days, respectively. Combination of these agents showed an average TGD of 40 days with no toxicity. Combination of BAY 57-9352 with paclitaxel required reduction of BAY 57-9352 from 60 mg/kg to 40 mg/kg to achieve acceptable tolerability. In the H460 model, BAY 57-9352 (40 mg/kg, p.o.) and paclitaxel (15 mg/kg, i.v.) exhibited anti-tumor activity as single agents with a TGD of 6 days and 10 days, respectively. When combined, these agents produced a TGD of 14 days and demonstrated acceptable toxicity. In all studies, the combination of BAY 57-9352 with capecitabine or paclitaxel was at least as effective as the individual agents administered alone. The results of these studies support the combination of BAY 57-9352 with either capecitabine or paclitaxel in clinical studies with these agents.
Central funding and a central resource providing information are needed
Authors: I. Barker
Journal: BMJ (1996)

EDITOR,—R H Davies is to be praised for the sensitive approach taken in striving to obtain the most appropriate care for a ventilated patient.1 Undoubtedly those readers who have been in a similar situation will have been reminded of their own experiences and the seemingly endless round of meetings that took place.

In 1993 I undertook a postal survey of members of the Paediatric Intensive Care Society asking about children ventilated at home in Britain. I hoped, forlornly, to organise a …
Fortnightly Review: New methods of making blocked coronary arteries patent again
Authors: L Corr
Journal: BMJ (1994)

The use of percutaneous transluminal coronary angioplasty is limited by procedural complications and the serious drawback of restenosis, but some new techniques have been developed in an attempt to lower the complication rate for difficult lesions and reduce the rate of restenosis. These include devices to physically remove atheromatous plaque, such as the Simpson Coronary AtheroCath and the transluminal extraction catheter, as well as devices to ablate the plaque in situ, including the Rotablator and the excimer laser catheter. Although each device may have advantages in certain types of lesion, few data on their use have been reported in properly controlled randomised trials. The data available so far do not suggest that these devices will be safer than balloon angioplasty or that they will reduce restenosis. However, using metallic stents to support coronary arteries after balloon angioplasty seems to reduce acute complications and to lower the rate of restenosis, and the use of stents is likely to increase.
Intracellular stability of TiO2-DNA nanocomposites in breast and prostate cancer cells
Authors: Kenneth Thurn, Tatjana Paunesku, Eric Brown, Aiguo Wu, Benjamin Haley, Barry Lai, Stefan Vogt, Jorg Maser, Gayle Woloschak
Journal: Cancer Research (2007)

1408   We have created an inducible titanium dioxide (TiO2)-DNA nanocomposite that is capable of sequence specific scission of nucleic acids, which we will attempt to use to target mutated oncogenes in malignant cells. TiO2-DNA nanocomposites consist of a 4.5 nm TiO2 nanoparticle covalently bound to a single stranded DNA using dopamine as a conductive linker. The nucleic acid maintains its ability to hybridize to complementary sequences[1]. Excitation of the nanoparticle with energies above 3.2 eV (white light, radiation) results in a charge separation in the nanoparticle. This causes electropositive holes to migrate through dopamine into the pi stack of the bound DNA resulting in cleavage of the nucleic acid [1]. By optimizing cleavage of the interstrand (target strand), we hope to be able to induce sequence specific scission of genomic DNA in living cells. Therefore we hypothesize that by targeting mutated genomic sequences specifically in malignant cells, it will be possible to knock out the oncogenes to which they have become “addicted.”  The present experiments were aimed at characterizing the precise subcellular distribution and integrity of TiO2-DNA nanocomposites in prostate carcinoma PC3M and breast carcinoma MCF-7 cells. We have shown previously that localization of the nanocomposite depends on the presence of available complementary cellular DNA. Cells were transfected with nanocomposites whose DNA component was fluorescently labeled with tetramethylrhodamine(TAMRA) and was complementary to genomic DNA encoding 18S rRNA (ttccttggatgtggt) (where 200-300 copies are present in the nucleolus[2]). By visualizing the exact same cells by X-Ray induced X-Ray Fluorescence (XRF, performed at the 2-ID-D beamline at the Advanced Photon Source at Argonne National Laboratory) and fluorescent confocal microscopy, we are able to determine the intracellular stability of the nanocomposite. Since the titanium (nanoparticle) and TAMRA (DNA) distribution was virtually identical, it suggests that the nanocomposite is intact within living cells at 24 and 72 hours. Other experiments show for the first time that by coating the nanoparticle surface with Alizarin Red S, we are able to track the nanoparticle component directly with fluorescent confocal microscopy and flow cytometry. This has been verified with XRF. Therefore we conclude that (1) it is possible to independently track the DNA and TiO2 component within malignant cells using fluorescent confocal microscopy, and flow cytometry, (2) a significant amount of the nanocomposite remains intact in living cells for up to 72 hours. These results will allow future experiments to determine the precise mechanism by which the nanocomposites are internalized in order to optimize and characterize subcellular localization for oncogene targeting.  [1] T. Paunesku,  et. al.  Nat. Mat., 2 :343,2002.  [2] W. Makalowski, Acta Bioch. Pol., 48 (3):587,2001.
P0796 : New direct acting antivirals for hepatitis C treatment: first results in a real-life setting in France
Authors: A. Pariente, A.-J. Rémy, J.-P. Arpurt, I. Rosa-Hézode, C. Renou, R. Arotcarena, G. Macaigne, H. Lison, F. Bourhis, X. Causse, A. Pauwels, S. de Montigny-Lenhardt, V. Jouannaud, H. Labadie, E. Maringe, J.-H. Salloum, E. Gagea, H. Hagège, B. Lesgourgues
Journal: Journal of Hepatology (2015)
Acupuncture for treatment of chronic neck pain
Authors: A. Vickers, D. Irnich, M. Krauss
Journal: BMJ (2001)

Medical Council is flawed as he assumes that Worcestershire Health Authority has power in managing its responsibility for a successful public health immunisation campaign. 1It is precisely because the authority is impotent as a public statutory public body that it asked the GMC to intervene.The continuing debate about measles, mumps, and rubella vaccine dents the confidence of many public and professional people, not least because of the assumption that there is no smoke without fire.Majeed's third reference indicates his anxiety despite his initial position statement on the safety of the vaccine.Patients and the media take heed of these different emphases.Maintaining a high level of vaccination cover against diseases that are seen rarely or not at all poses serious difficulties.Majeed's role as an educationalist-a position of power and responsibility-could provide a forum where these difficulties are debated.The role of medical journals and the media should not be ignored in that debate.Their keenness for headlines containing bad news, however misguided or ill informed, while