tbuckley/cabot-search huggingface dataset:
CYP2A6 genetic polymorphism as a predictive marker for clinical outcomes in patients (pts) with metastastic gastric carcinoma (MGC) treated with S-1 plus docetaxel
Authors: S. R. Park, M. S. Park, Y. L. Park, N. K. Kim, J. S. Lee, H. K. Kim, H. S. Lim
Journal: Journal of Clinical Oncology (2007)

4633 CYP2A6 genetic polymorphism as a predictive marker for clinical outcomes in patients (pts) with metastastic gastric carcinoma (MGC) treated with S-1 plus docetaxel Background: Tegafur, a component of S-1, a novel oral fluoropyrimidine, is converted to 5-fluorouracil via CYP2A6. An allelic variant of CYP2A6, -48T&gt;G (CYP26A*9) encodes an enzyme with reduced activity. We investigated the association between the polymorphism of CYP2A6*9 and treatment outcomes in Korean pts with MGC who received S-1 plus docetaxel. Methods: From Oct 2005 to July 2006, 50 pts with MGC were enrolled for a phase II study of first line chemotherapy with S-1 and docetaxel. Treatment consisted of oral S-1 40 mg/m 2 bid on days 1–14, and i.v. docetaxel 35 mg/m 2 on days 1, 8, every 3 weeks. Genotypes were determined with single base extension method for CYP26A*9 from genomic DNA extracted from the peripheral blood samples. Results: The median age was 53 years (range, 23–70) with the median PS of 1 (range, 0–2). The frequency of wild type allele (w/w) was 34 (68%), heterozygous (*9/w), 12 (24%), and homozygous (*9/*9), 4 (8%). The response rate was 25.0% in homozygous pts, 50.0% in heterozygous and 76.5% in wild type (p=0.03, Fisher’s exact test). The median time to progression at a median follow-up of 9.8 months (mo) was shorter in homozygous pts (3.9 mo; 95% CI, 0.4–7.4) as compared to heterozygous and wild types (6.9 mo; 95% CI, 6.0–7.8) (p=0.11). Although the median overall survival did not reach in 4 homozygous pts, it was 13.5 mo (95% CI, 8.3–18.7) in heterozygous and wild type. The frequencies of grade (G) 3/4 toxicities were lower in homozygous pts than the others without statistical significance. Conclusions: The data suggest that CYP2A6*9 polymorphism might be a predictive marker for efficacy and toxicity of S-1 based chemotherapy in MGC pts. Further studies involving more pts are needed to confirm the results. (Supported by NCC Grant 0610520) [Table: see text] No significant financial relationships to disclose.
The Influence of Prednisolone (PRED) and Methotrexate (MTX) on the Cell and Connective Tissue Content of Subcutaneously Implanted Polyurethane Sponges in Rats
Authors: B. Vernon-Roberts, S. Hay, E. G. Cleary, O. W. Wiebkin, I. R. Garrett, P. M. Brooks, L. P. Bignold
Journal: Annals of the Rheumatic Diseases (1984)

Findings indicate that prednislone and methotrexate have profound effects on the cellular events of acute and chronic inflammation, and influence the synthesis or degradation of connective tissue macromolecules at certain stages of the inflammatory process.
Abstract 4340: Left Ventricular Dyssynchrony Measured by Speckle-Tracking Radial Strain Analysis Predicts Survival After Resynchronization Therapy
Authors: Rutger J Van Bommel, Victoria Delgado, Claudia Ypenburg, Sjoerd A Mollema, C. Jan Willem Borleffs, Ernst E van der Wall, Martin J Schalij, Jeroen J Bax
Journal: Circulation (2008)

Since the introduction of cardiac resynchronization therapy (CRT) in heart failure patients, many echocardiographic criteria, including left ventricular (LV) dyssynchrony, have been investigated in improving selection of suitable candidates. A novel method for the assessment of LV dyssynchrony is speckle-tracking radial strain analysis. Aim of this study was to investigate the impact of pre-implantation, speckle-tracking derived LV dyssynchrony on survival in patients treated with CRT A total of 537 consecutive patients undergoing CRT at our center were included. In all patients, speckle-tracking radial strain analysis was applied to standard LV short-axis images. Significant LV dyssynchrony was defined as a delay between the anteroseptal and posterior segments ≥130 ms. The primary endpoint was all-cause mortality Mean LV dyssynchrony in all 537 patients was 138±105 ms and 251 patients (47%) had predefined significant LV dyssynchrony ≥130 ms. For survival analysis, mean follow-up in the study population was 34±20 months. Within this period 145 patients (27%) died. Main cause of death remained heart failure (61% of all deaths). Multivariate Cox regression analysis with correction for age, gender, etiology, QRS duration, NYHA class, quality of life score, distance covered in the 6-minute walking test, LV volumes and LVEF, demonstrated a significant survival benefit for patients with significant LV dyssynchrony ≥130 ms (HR 0.63, 95% C.I. 0.43–0.92, p=0.017, Figure ). Presence of significant LV mechanical dyssynchrony, measured with speckle-tracking radial strain, is associated with improved survival probability after CRT
STUDIES IN HYPERTENSION; A PROPOSED CLASSIFICATION OF HYPERTENSION BASED UPON THE NITROGEN DISTRIBUTION OF THE SERUM PROTEINS
Authors: Henry A. Rafsky, Adolph Bernhard, George L. Rohdenburg
Journal: Annals of Internal Medicine (1936)

Article1 February 1936STUDIES IN HYPERTENSION; A PROPOSED CLASSIFICATION OF HYPERTENSION BASED UPON THE NITROGEN DISTRIBUTION OF THE SERUM PROTEINSHENRY A. RAFSKY, F.A.C.P., ADOLPH BERNHARD, GEORGE L. ROHDENBURGHENRY A. RAFSKY, F.A.C.P.Search for more papers by this author, ADOLPH BERNHARDSearch for more papers by this author, GEORGE L. ROHDENBURGSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-8-1091 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn a previous publication1we reported that experimental hypertension in rabbits produced by the injection of a mono-amino acid (aspartic acid) is associated with definite alterations in the nitrogen distribution of the serum proteins. These changes are an increase in the mono-amino nitrogen and a decrease in the basic amino nitrogen with a resultant change in the ratio between these two fractions (referred to as the M/B ratio). We have noted in further studies similar changes in the nitrogen distribution of the serum proteins in hypertension in man. Since these changes offer a basis for the classification of hypertension, the...References1. RAFSKYBERNHARDROHDENBURG HAAGL: Studies in hypertension. I. The production of experimental hypertension and a correlated effect upon the nitrogen distribution of the blood proteins, Am. Jr. Med. Sci., 1935, cxc, 187. CrossrefGoogle Scholar2. BERNHARDLEOPOLDDREKTER AJSIJ: Blood proteins of children; distribution of total nitrogen in whole blood, red blood cells and serum proteins from same specimen, Am. Jr. Dis. Child., 1934, xlvii, 1256-1260. BERNHARD, A., LEOPOLD, J. S., and DREKTER, I. J.: Blood proteins of children; distribution in same specimen of blood of hydrolyzable, amide, humin, basic amino and mono-amino nitrogen of whole blood, red cells and serum proteins, Am. Jr. Dis. Child., 1934, xlviii, 819-829. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: HENRY A. RAFSKY, F.A.C.P.; ADOLPH BERNHARD; GEORGE L. ROHDENBURGAffiliations: New York, N. Y.*Received for publication October 12, 1935.From the Achelis Laboratory of the Lenox Hill Hospital under a grant from the W. C. Durant Fund. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1936Volume 9, Issue 8 Page: 1091-1100 Keywords Hypertension Rabbits Research laboratories Serum proteins ePublished: 1 December 2008 Issue Published: 1 February 1936 PDF downloadLoading ...
Abstract 1287: TRPV4-Deficient Mice Exhibit Impaired Endothelium-Dependent Relaxation Induced by Acetylcholine <i>in Vitro and in Vivo</i>
Authors: David Zhang, Suelhem Mendoza, Aaron Bubolz, Makoto Suzuki, David Gutterman
Journal: Circulation (2007)

Agonist-induced Ca 2+ entry in endothelial cells is important for the synthesis and release of vasoactive factors, although mechanisms of Ca 2+ entry remain largely unknown. Emerging evidence suggests that the transient receptor potential vanilloid 4 (TRPV4) channel, a Ca 2+ -permeant TRP channel, is expressed in endothelial cells and may be involved in the regulation of vascular tone. Here we investigated the potential role of TRPV4 channels in acetylcholine-induced vasodilation in vitro and in vivo using the TRPV4 knockout (TRPV4 −/− ) mice model. Carotid arteries were isolated and preconstricted with the thromboxane A2 mimetic U46619. Concentration-dependent relaxations to acetylcholine (10 −9 –10 −5 M) were markedly reduced in carotids of TRPV4 −/− vs. wild-type (WT) mice (maximal relaxations of 31±12% vs 53±4%, respectively; n=4 mice). There was no significant change in the ED50 for Ach. In both WT and TRPV4 −/− , acetylcholine-induced relaxations were blocked and converted to constrictions by the NO synthase inhibitor L-NAME (maximal relaxations of −25±6% and −24±7%, respectively). There was no difference in papaverine-induced relaxations between WT and TRPV4 −/− mice (maximal relaxations of 93±3% vs. 90±3%, respectively). U46619 caused similar contractions in carotid arteries from those mice. We also compared in vivo vasodilator effects of acetylcholine by measuring changes in blood pressure in those animals. Intravenous administration of acetylcholine (15 ng/gm bolus) decreased blood pressure by 32±6 mmHg in WT mice (from 90±15 to 57±10 mmHg; n=6), whereas blood pressure was reduced by only 10 mmHg in TRPV4 −/− mice (from 67±6 to 56±4 mmHg; n=12). Acetylcholine caused similar reductions in heart rate in WT and TRPV4 −/− mice, with mean changes of 365±57 and 292±40 beats/min, respectively. We conclude that the endothelium-dependent vasodilator response to acetylcholine is reduced both in vitro and in vivo in TRPV4 −/− mice, and these findings may provide novel insight into the mechanisms of Ca 2+ entry evoked by chemical agonists in endothelial cells. The paradoxically lower baseline blood pressure in TRPV4 −/− mice requires further investigation.
332. Dual Gene Transfer and Transgenesis by Novel Lentiviral Vectors Carrying Synthetic Bi-Directional Promoters
Authors: Mario Amendola, Mary Anna Venneri, Elisa Vigna, Luigi Naldini
Journal: Molecular Therapy (2004)

Expression of more than one transgene within the same cell allows combining genetic correction with marking, selection, amplification, and conditional elimination of transduced cells. In addition, it is required when gene therapy depends on multiple or synergic genes. Unfortunately, reaching coordinate, high-level dual gene expression in the majority of transduced cells poses significant challenges to current gene transfer technologies. We showed that IRES-based bicistronic lentiviral vectors co-express two transgenes in only a fraction of transduced cells, and that transgene expression was significantly lower when IRES-dependent than when it was cap-dependent. Thus, selection of transduced cells was required to ensure coordinate expression of both transgenes in all target cells. To overcome these limitations, we developed a novel vector design in which a minimal core promoter was fused upstream and close to an efficient promoter, but in the opposite orientation. The resulting bi-directional promoter mediated coordinate transcription of two divergent mRNA's. We tested several constructs by changing the trailer core promoter and the driver enhancer/promoter, and found that the bi-directional design significantly enhanced transcription from the trailer core promoter, did not affect downstream expression from the driver promoter, and allowed stable co-expression of two genes from a single vector genome. Strikingly, this new type of vector enabled efficient dual gene transfer and expression in primary hematopoietic progenitors, both of human and mouse origin, tested as immature cells, and after transplantation and differentiation, and in primary T lymphocytes, transduced when proliferating and when non proliferating, after cytokine exposure. Importantly, the new vectors allowed proficient in vivo dual gene transfer and transgenesis. After perivitelline injection of bi-directional vector, we observed robust pan-cellular co-expression of two marker genes in all tissues analyzed of founder and progeny transgenic mice, including brain, liver, kidney, gut, spleen, heart and muscle. Intriguingly, a recent survey of the human genome indicated an abundance of divergently transcribed gene pairs, whose transcription start sites are separated by less than 1 kb. It is likely that many of the promoter elements found between these gene pairs can initiate transcription in both directions, and contain shared elements that regulate both genes. Thus, the synthetic bi-directional promoters that we developed may mimic a well-represented and evolutionary conserved feature of eukaryotic transcription, providing a structural basis for their robust performance. The new lentiviral vectors built around these bi-directional promoters will advance the reach of gene therapy and increase the power of gene-function and target validation studies.
For and against: Bone densitometry is not a good predictor of hip fracture For Against
Authors: T. J Wilkin, D. Devendra, J. Dequeker, F. P Luyten
Journal: BMJ (2001)

# Bone densitometry is not a good predictor of hip fracture {#article-title-2} Bone densitometry is widely used in osteoporosis clinics to identify people at increased risk of fracture. Terence Wilkin and Devasenan Devendra believe that evidence for the efficacy of bone densitometry is weak, but Jan Dequeker and Frank P Luyten argue that their interpretation of the evidence is too narrow and that screening high risk patients is cost effective # For {#article-title-3} The World Health Organization defines osteoporosis as a "progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture."1 The low bone mass used to define osteoporosis is arbitrarily fixed at 2.5 standard deviations or more below the mean bone density for premenopausal women. Assessment of bone density provides a precise figure to which doctors and patients feel able to relate with confidence. We believe this confidence is unjustified. By one definition, osteoporosis is an arbitrary point on a scale. By another, it is a pathological process of microarchitectural deterioration in which the unconstrained activity of bone osteoclasts accelerates bone resorption. The two definitions are fundamentally different. Accelerated bone resorprtion exists throughout postmenopausal life, whereas osteoporosis does not—and may never. Bone densitometry measures bone density, not bone turnover or bone stability. We have argued previously that bone turnover, rather than bone density, is the responsive element in treatments for preventing fractures.2 The pathology of osteoporosis is one of uncontrolled bone resorption and the treatment (whether hormone replacement therapy or bisphosphonates) antiresorptive. We present five evidence based reasons why the results of bone densitometry may not predict postmenopausal fracture of the hip in the way that many believe it to. The purpose of measuring bone density is to direct preventive treatments towards those who would most benefit. Drug treatment is principally antiresorptive and it clearly reduces … Correspondence to: J Dequeker
THE LEAVEN OF PSYCHOSOMATIC MEDICINE
Authors: Edward A. Strecker
Journal: Annals of Internal Medicine (1943)

Article1 May 1943THE LEAVEN OF PSYCHOSOMATIC MEDICINEEDWARD A. STRECKER, M.D., F.A.C.P.EDWARD A. STRECKER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-18-5-736 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe accomplishments of psychosomatic medicine are noteworthy; its objective is magnificent, but the name is unfortunate. Its comparatively recent usage makes it sound like the announcement of a marriage between body and mind, with the subdivisions and specialties of medicine and psychiatry in the bridal party. If the union of body and mind has just been consummated, then psychiatry for some time has sanctioned an illicit relationship. Long before the word psychosomatic was compounded, psychiatry had insistently taught that man was a total and indivisible unit and, therefore, in health and disease, every somatic process at once reverberated in all... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*Presented at the meeting of the American College of Physicians, St. Paul, Minnesota, April 20, 1942. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1943Volume 18, Issue 5Page: 736-740 ePublished: 1 December 2008 Issue Published: 1 May 1943 PDF downloadLoading ...
Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT
Authors: Helmut Baumgartner, Gerold Porenta, Yuk-Kong Lau, Michael Wutte, Ursula Klaar, Mohammad Mehrabi, Robert J Siegel, Johannes Czernin, Günther Laufer, Heinz Sochor, Heinrich Schelbert, Michael C Fishbein, Gerald Maurer
Journal: Journal of the American College of Cardiology (1998)
Abstract 12751: Impaired Elastin Function Promotes Acute Plaque Rupture, Cerebral Infarction and Sudden Death in ApoE-deficient Mice
Authors: Jozef L Van Herck, Guido R De Meyer, Wim Martinet, Greet Vanhoutte, Marleen Verhoye, Annemie Van Der Linden, Hidde Bult, Christiaan J Vrints, Arnold G Herman
Journal: Circulation (2010)

Background:  Arterial stiffness is an independent predictor of cardiovascular risk. The aim of this study was to investigate the effects of arterial stiffness on the progression of atherosclerosis.   Methods and results:  Mice with a mutation (C1039G +/− ) in the fibrillin-1 gene, leading to fragmentation of the elastic fibers and increased arterial stiffness, were cross-bred with ApoE −/−  mice. Subsequently, ApoE −/−  (n=8) and ApoE −/− C1039G +/−  mice (n=10) were fed a Western-type diet for 52 weeks. Arterial stiffening in ApoE −/− C1039G +/−  mice was associated with an increase in systolic blood pressure and pulse pressure. Moreover, atherosclerotic plaques in ApoE −/− C1039G +/−  mice showed a more unstable plaque phenotype, characterized by a decrease in collagen content and enlargement of the necrotic core. There were no premature deaths in the ApoE −/−  mice. However, fifty percent of the ApoE −/− C1039G +/−  mice died suddenly. Sudden death in ApoE −/− C1039G +/−  mice was associated with the presence of acute plaque rupture in the proximal ascending aorta. Furthermore, magnetic resonance imaging of the brain showed the presence of a high number of cerebral infarctions in the surviving ApoE −/− C1039G +/−  mice (median number of lesions = 3 [range 3 – 5] in ApoE −/− C1039G +/−  mice vs. 0 [range 0 – 3] in ApoE −/−  mice). The cerebral infarctions were characterized by the presence of foam cells and cholesterol clefts, indicating that these lesions were caused by cerebral embolization of plaque debris after rupture of atherosclerotic plaques in the aortic arch or a carotid artery.   Conclusions:  Our results indicate that arterial stiffness increases the risk of acute plaque rupture, cerebral infarction and sudden death. In addition, ApoE −/− C1039G +/−  mice represent a promising model of acute plaque rupture, enabling the investigation of novel plaque stabilizing therapies on clinical end points such as stroke and sudden death.
Comparative Clinical Outcomes of Paclitaxel- and Sirolimus-Eluting Stents
Authors: Charles A. Simonton, Bruce Brodie, Barrett Cheek, Fred Krainin, Chris Metzger, James Hermiller, Stanley Juk, Peter Duffy, Angela Humphrey, Marcy Nussbaum, Sherry Laurent
Journal: Journal of the American College of Cardiology (2007)
VENTRICULAR ANEURYSM A CAUSE OF PERSISTENT RS-T SEGMENT DISPLACEMENT
Authors: E EVANS
Journal: Annals of Internal Medicine (1951)

Case Reports1 April 1951VENTRICULAR ANEURYSM A CAUSE OF PERSISTENT RS-T SEGMENT DISPLACEMENTELWYN EVANS, M.D., F.A.C.P.ELWYN EVANS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-34-4-1048 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWilson et al.1 in their important paper, "The Precordial Electrocardiogram," described a case with persistent RS-T segment displacement and mentioned that in three cases of this sort, one seen by Langendorf, a ventricular aneurysm was present. On the basis of these observations, a tentative diagnosis of an aneurysm of the ventricle was made in a patient showing striking persistent RS-T segment displacement following typical acute posterior myocardial infarction. This diagnosis was later substantiated at autopsy.CASE REPORTA 50 year old white male was first seen in consultation on May 26, 1947, at which time he gave a history of...Bibliography1. WilsonJohnstonRosenbaumErlangerKossmannHechtCotrimMenezesScarsiBarker FNFDFFHCEHNRdRPS: The precordial electrocardiogram, Am. Heart J. 27: 19, 1944. CrossrefGoogle Scholar2. EvansBlack ETC: New chest lead terminology, to be published. Google Scholar3. Langendorf R: Personal communication. Google Scholar4. White PD: Personal communication. Google Scholar5. Nordenfelt O: The electrocardiogram in chronic aneurysm of the heart, Acta med. Scandinav. 102: 100, 1940. Google Scholar6. GoldbergerSchwartz ESP: Electrocardiographic patterns of ventricular aneurysm, Am. J. Med. 14: 243, 1948. CrossrefGoogle Scholar7. EliaserKonigsberg MJ: Electrocardiographic findings in cases of ventricular aneurysm, Arch. Int. Med. 64: 493, 1939. CrossrefGoogle Scholar8. Kohn MH: Aneurysm of the left ventricle, Am. J. M. Sc. 163: 839, 1922. Google Scholar9. ScherfBoyd DTJ: Cardiac aneurysm, M. Clin. North America 26: 919, 1942. CrossrefGoogle Scholar10. RosenbergMessinger BWJ: The electrocardiogram in ventricular aneurysm, Am. Heart J. 37: 267, 1949. CrossrefMedlineGoogle Scholar11. RosenbaumJohnstonAlzamora FFFDVV: Persistent displacement of the RS-T segment in a case of metastatic tumor of the heart, Am. Heart J. 27: 667-675, 1944. CrossrefGoogle Scholar12. Master AM: Roentgenoscopy as a diagnostic aid in coronary occlusion, Am. J. Roentgenol. 45: 350, 1941. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Orlando, Florida*Received for publication April 23, 1949. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCardiovascular SystemCARDIAC ANEURYSM WITH VENTRICULAR TACHYCARDIA: CASE REPORT AND BRIEF REVIEW OF THE LITERATURE*EDWARD WASSERMAN, M.D., JACOB YULES, M.D. 1 April 1951Volume 34, Issue 4Page: 1048-1055KeywordsAneurysmsAutopsyElectrocardiographyMyocardial infarction ePublished: 1 December 2008 Issue Published: 1 April 1951 PDF downloadLoading ...
beta-catenin hepatocellular adenomas (HCA) are rare but represents the most important subgroup of HCA associated with dysplasia, borderline lesion and hepatocellular carcinoma (HCC)
Authors: Christine Sempoux, Linda Ferrell, Young Nyun Park, Aileen Wee, Andrew D. Clouston, Emmanuelle Leteurtre, Valerie Paradis, Kimberley Evason, Brigitte Le Bail, Charles Balabaud, Paulette Bioulac-Sage
Journal: Hepatology (2012)