tbuckley/cabot-search huggingface dataset:
Abstract P2-09-02: BMN 673 is a PARP inhibitor in clinical development for the treatment of breast cancer patients with deleterious germline BRCA 1 and 2 mutations
Authors: LA Mina, RK Ramanathan, ZA Wainberg, LA Byers, R Chugh, JC Sachdev, D Matei, C Zhang, JW Henshaw, A Dorr, SB Kaye, JS de Bono
Journal: Cancer Research (2013)

Abstract Background: BMN 673 is the most potent and specific inhibitor of poly-ADP ribose polymerase (PARP) 1 and 2 in clinical development (IC50&amp;lt;1nM). In BRCA-related tumors, which are genetically dependent on PARP-mediated DNA repair by base excision repair, PARP inhibition induces synthetic lethality. Initial phase 1 results have been presented (de Bono et al JCO 31:5s, 2013 suppl; abstr 2580), showing good tolerability and anti-tumor activity with an MTD on a daily, oral dosing schedule of 1000 μ/day. Methods: In this 2-stage study, patients with solid tumors including BRCA-related cancers, were enrolled during dose-escalation followed by an expansion phase at the MTD in breast, ovarian, and pancreatic cancer patients with deleterious germline BRCA mutations and in small cell lung cancer and Ewing sarcoma patients to further characterize safety and efficacy. This abstract summarizes demographics and safety for all patients and efficacy for patients with BRCA-related cancers. Results: As of 17May2013, a total of 1 pancreatic, 18 breast (17F/1M), and 28 ovarian cancer pts with germline BRCA mutations were enrolled at doses from 100-1100 μg/day. All breast cancer patients were treated from 900-1100 μg/day. The median (range) age for all 70 patients is 51.5 (18-81), PS 0 (0-1) and # of prior therapies 4 (1-13), with 47 patients having deleterious BRCA mutations. An MTD of 1000 μg/day was established with thrombocytopenia being dose-limiting. Related adverse events occurring in &amp;gt; 10% of all 70 patients included fatigue, nausea, alopecia, anemia, thrombocytopenia and neutropenia. One patient has had related grade 4 thrombocytopenia. Grade 3 related AE's included fatigue in 1 patient (1%), anemia and thrombocytopenia in 9 each (13%) and neutropenia in 4 (6%). Dose reductions occurred in 11 pts due to myelosuppression. No patients discontinued for adverse events. Response in Germline BRCA PatientsBRCA Tumor TypeNDose Range (μ/day)ResponseBreast18900-11001CR/6PR/5SD≥12 weeksOvarian28100-11001CR/10PR/19GCIG/4SD≥24 weeksPancreas110001 SD ≥ 12weeksTwo of 2 BRCA breast responders had responded to prior platinum while 0 of 4 non-responders to prior platinum responded to BMN 673. Five of 12 breast cancer pts with no prior platinum have responded. Conclusions: BMN 673 is well tolerated with impressive anti-tumor activity in pts with deleterious germ line BRCA mutations. Myelosuppression and fatigue are the primary side effects associated with need for dose reduction. A phase 3 trial in metastatic breast cancer patients with deleterious germ line BRCA mutations is planned with single-agent, once-daily oral dosing of 1000 μg (1 mg) per day. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-02.
THE INHERITANCE OF DIABETES
Authors: PRISCILLA WHITE
Journal: JAMA (1934)

Is it possible to predict the onset of diabetes in a given individual at a given time? This question was uppermost in our minds, Dec. 17, 1931, for while we were treating a 5 year old girl for diabetic coma her solicitous similar twin sister waited nearby. Surely, we thought, if the theory of the inheritance of diabetes is correct here is an instance in which the prediction is possible. Our patient had just developed diabetes and the second twin should develop the disease and likely within a decade. April 10, 1934, the first child returned to the clinic with her twin sister. Three weeks previous to this the second twin had developed the symptoms of diabetes and her mother had found a red reduction with the Benedict test. At the clinic the diagnosis was confirmed, for the urine was found to contain 4.6 per cent of sugar and the
Popular diets yield only modest benefits, systematic review finds
Authors: Michael McCarthy
Journal: BMJ (2014)

Four of the most popular weight loss diets in North America yield similar but modest weight loss in the long term and their cardiovascular benefits are unclear, a systematic review of randomised controlled trials has found.

The review was published online on 11 November by the American Heart Association journal Circulation: Cardiovascular Quality and Outcomes .1 The senior author was Mark J Eisenberg, professor of medicine at the Jewish General Hospital affiliated with McGill University in Montreal, Quebec. The study was funded by the Canadian Institutes of Health Research.

In their review the researchers analysed trials that looked at the effectiveness of the Atkins, South Beach, and Zone diets and the Weight Watchers programme. These three book based diets all emphasise a low carbohydrate intake, and Weight Watchers is a behaviour modification programme organised around weekly group sessions where …
Physical training reduces circulating monocyte‐endothelial cell adhesive interaction markers in patients with chronic heart failure
Authors: S. Adamopoulos, J. Parissis, C. Kroupis, M. Georgiadis, D. Karatzas, G. Karavolias, K. Koniavitou, A.J.S. Coats, D.Th. Kremastinos
Journal: European Journal of Heart Failure (2000)
Screening and Assessing 11 <i>Mycobacterium Tuberculosis</i> Proteins as Potential Serodiagnostical Markers for Discriminating TB Patients from BCG Vaccinees
Authors: Guoqiang Zhang, Lingxia Zhang, Mingcheng Zhang, Linlin Pan, Fengyu Wang, Jun Huang, Guoli Li, Jun Yu, Songnian Hu
Journal: Genomics Proteomics & Bioinformatics (2009)

Abstract Purified protein derivative (PPD) skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tuberculosis infection and Bacille Calmette-Guerin (BCG) vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames (ORFs) based on the genome sequences of M. tuberculosis H37Rv and M. bovis BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coli. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay (ELISA) and involving a cohort composed of 58 TB patients (34 males and 24 females), 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD values for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination (P&amp;lt;0.01). They had at least 92% specificity in healthy controls and six seroantigens (Rv0251c, Rv1973, Rv2376c, Rv2537c, Rv2785c and Rv3873A) were never reported with seroantigenicities previously. Thus the approach combining comparative genomics, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.
Differential expression of guanosine triphosphate binding proteins in men at high and low risk for the future development of alcoholism.
Authors: G S Wand, C Waltman, C S Martin, M E McCaul, M A Levine, D Wolfgang
Journal: Journal of Clinical Investigation (1994)

We evaluated G-proteins that are components of adenylyl cyclase (AC) signal transduction in erythrocyte and lymphocyte membranes from 26 family history positive (FHP) non-alcoholic and 26 family history negative (FHN) nonalcoholic subjects. Subjects were classified as FHP if their father met criteria for alcohol dependence; as FHN, if there was no history of alcoholism in any first or second degree relatives. Immunoblot analysis indicated that levels of erythrocyte membrane Gs alpha from FHP subjects were greater than levels in FHN subjects (171 +/- 11 vs 100 +/- 6, P < 0.001). To confirm the results of the immunoblot analysis, Gs alpha was quantitated by cholera toxin-dependent [32P]ADP-ribosylation. Levels of erythrocyte [32P]ADP-ribose-Gs alpha from FHP subjects were greater than levels in FHN subjects (236 +/- 28 vs 100 +/- 14, P < 0.001). Gs alpha levels did not correlate with age or alcohol consumption. By contrast to differences in Gs alpha, immunoblot analysis showed similar levels of Gi(2)alpha and Gi(3)alpha in erythrocyte membranes of FHP and FHN subjects. Pertussis toxin-catalyzed [32P]ADP-ribosylation of Gi-like G-proteins confirmed the immunoblot observations. Lastly, compared to FHN subjects, FHP subjects had enhanced Gs alpha expression in lymphocyte membranes as well (138 +/- 11 vs 100 +/- 5.5; P < 0.02). In summary, compared to FHN nonalcoholic men, FHP nonalcoholic men had greater levels of the stimulatory G-protein, Gs alpha, in erythrocyte and lymphocyte membranes. Enhanced expression of Gs alpha may be a marker of increased risk for the future development of alcoholism.
Not all stoops are due to osteoporosis.
Authors: M R Ehrenstein, T Stoll, J C Edwards
Journal: Annals of the Rheumatic Diseases (1996)

Case report A 75 year old woman presented to her local hospital with diffuse low lumbar spine pain and a mild stoop.There was no radiation of pain to the lower limbs.A diagnosis of osteoporosis was made and the patient started to take etidronate (Didronel PMOT).At that time also, a plain lumbar spine radiograph was performed, but not bone densitometry.Three years later the patient presented to our unit with a six month history of an increasingly severe stoop involving the lumbar and thoracic spine despite continued use of etidronate.At the time of presentation, she was unable to rise from a 90 degree anterior inflexion of the spine and found it difficult to do any housework as her head was below the work surface (fig 1).However, the anterior curvature of the spine disappeared completely in the supine position.There was no relevant past medical or family history.The patient was a non-smoker.Apart from the abnormality of posture described above, the examination was normal-in particular, there was no significant weakness in the upper or lower limbs, and no other
Abstract LB-486: Overexpression of a mutated, constitutively active HIF2α promotes the carcinogenesis of TRACK mouse
Authors: Leiping Fu, Gang Wang, Maria M. Shevchuk, David M. Nanus, Lorraine J. Gudas
Journal: Cancer Research (2012)

Abstract Background: VHL disease patients have an increased risk of developing clear cell renal cell carcinomas (ccRCC). Increased expression of HIF1α and/or HIF2α has been proposed as a key step in ccRCC carcinogenesis. We recently reported a mouse model of VHL renal cancer, the TRACK model (Fu et al, Cancer research. 2011;71(21):6848-56.). In the TRACK model, proximal tubule (PT) cell overexpression of a triple mutant (P402A, P564A and N803A) HIF1α in the mouse mimics human VHL kidney disease. Methods: Here we report a mouse model expressing a triple mutant (P405A, P531A and N847A) HIF2α in PT cells. Mutant HIF2α was expressed in both WT and HIF1α-expressing C57BL/6 mice. Results: Transgenic (TG) mice expressing this HIF2α construct specifically in PT cells exhibit vacuolization consistent with glycogen accumulation and hydropic degeneration. The activation of HIF2α was confirmed by increased expression of HIF2α target genes, e.g. CA9. Neoplastic transformation was not observed in the kidneys of HIF2α TG+ mice. In HIF1α/HIF2α-expressing mice, disorganized PT cells mimicking in situ carcinoma was observed in 5 mo old mouse kidneys, which was seen only at 14 mo in mice expressing only mutant HIF1α. Conclusions: These data suggest HIF2α accelerates carcinogenesis in the mutant HIF1α TRACK model. These mouse models provide excellent models to study VHL renal disease and carcinogenesis, and provide an opportunity for chemoprevention studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-486. doi:1538-7445.AM2012-LB-486
Commission publishes damning report on first PFI hospital
Authors: D. Singh
Journal: BMJ (2003)

Britain's first hospital built with private finance “lacks leadership, direction and planning” according to a damning report published last week by the Commission for Health Improvement (CHI).

Nick Wood, the chief executive of the North Cumbria Acute Hospitals NHS Trust, resigned a few days before the report was published.

The trust was established in April 2001 after the merger between the West Cumberland Hospital in Whitehaven and Cumberland Infirmary in Carlisle. Cumberland Infirmary had been opened in April 2000 by Prime Minister …
Points from Letters: Induction of Labour and Perinatal Mortality
Authors: H. B. Borton
Journal: BMJ (1975)

Ketoprofen, one of the many propionic acid derivatives flooding the market, is the subject of another substantial promotional programme only 12 months after the first. . ..Pharmaceutical companies, it seems, are playing into the hands of "Bennery" witlh such blatant "burning" of profits.. The public can hardly be expected to support the call for more money for the N.H.S. when it seems the medical profession is doing little to discourage such wasteful practices....
Psychoanalytically Oriented Psychotherapy in Psychosomatic Disorders
Authors: George Spyros Philippopoulos
Journal: Psychotherapy and Psychosomatics (1959)

Research Articles| February 10 2010 Psychoanalytically Oriented Psychotherapy in Psychosomatic Disorders Subject Area: Psychiatry and Psychology George Spyros Philippopoulos George Spyros Philippopoulos Athens Search for other works by this author on: This Site PubMed Google Scholar Acta Psychotherapeutica et Psychosomatica (1959) 7 (1): 86–92. https://doi.org/10.1159/000285368 Article history Published Online: February 10 2010 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation George Spyros Philippopoulos; Psychoanalytically Oriented Psychotherapy in Psychosomatic Disorders. Acta Psychotherapeutica et Psychosomatica 1 January 1959; 7 (1): 86–92. https://doi.org/10.1159/000285368 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsActa Psychotherapeutica et Psychosomatica Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1959Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
Lower incidence of hepatocellular carcinoma in patients with transient virologic response to peginterferon and ribavirin combination therapy: Is it really the effect of the therapy?
Authors: Hidenori Toyoda, Takashi Kumada, Toshifumi Tada
Journal: Journal of Hepatology (2012)

[1] Ogawa E, Furusyo N, Kajiwara E, Takahashi K, Nomura H, Maruyama T, et al. Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma of patients with chronic hepatitis C: a prospective multicenter study. J Hepatol 2013;58:495–501. [2] Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000;132:517–524. [3] Akuta N, Suzuki F, Sezaki H, Suzuki Y, Hosaka T, Someya T, et al. Association of amino acid substitution pattern in core protein of hepatitis C virus genotype1b high viral load and non-virological response to interferonribavirin combination therapy. Intervirology 2005;48:372–380. [4] Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399–401. [5] Akuta N, Suzuki F, Seko Y, Kawamura Y, Sezaki H, Suzuki Y, et al. The complicated relationships of amino acid substitution in HCV core region and IL28B genotype influencing hepatocarcinogenesis. Hepatology 2012;56: 2134–2141. [6] Tillmann HL, Patel K, Muir AJ, Guy CD, Li JH, Lao XQ, et al. Beneficial IL28B genotype associated with lower frequency of hepatic steatosis in patients with chronic hepatitis C. J Hepatol 2011;55:1195–1200. [7] Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, et al. Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol 2010;53:439–443. [8] Pekow JR, Bhan AK, Zheng H, Chung RT. Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis. Cancer 2007;109:2490–2496. [9] Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, et al. Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy. J Med Virol 2011;83:1016–1022. [10] Toyoda H, Kumada T. Incidence of hepatocellular carcinoma and response to interferon therapy in HCV-infected patients: effect of factors associated with the therapeutic response and incidence of HCC. Liver Int 2012;32: 1029–1031.
Membrane transport influences the rate of accumulation of cytosine arabinoside in human leukemia cells.
Authors: J C White, J P Rathmell, R L Capizzi
Journal: Journal of Clinical Investigation (1987)

The role of membrane transport in the cellular accumulation of 1-beta-D-arabinofuranosylcytosine (ara-C) was studied in freshly isolated human acute leukemia cells. Patient cells had low rates for ara-C transport as compared with human and murine experimental cells and correspondingly low binding capacities for the nucleoside transport inhibitor, nitrobenzylmercaptopurine riboside (NBMPR). At 1 microM ara-C, the rate of net cellular accumulation was close to the membrane transport rate, and NBMPR inhibited transport and accumulation to the same extent. The rate of ara-C accumulation was half maximal at only 3-5 microM, a level much lower than that required for murine cells (67-85 microM). At concentrations below 1 microM the rate of ara-C accumulation was determined primarily by the transport rate, but at higher concentrations above 10 microM, phosphorylation capacity was the principal determinant of the net uptake rate. This difference in the role of transport at high and low ara-C concentrations may explain, in part, the efficacy of high-dose ara-C in patients refractory to standard dose protocols.
Common Enterobacterial Antigen in Human Chronic Pyelonephritis and Interstitial Nephritis
Authors: Melvin M. Schwartz, Ramzi S. Cotran
Journal: New England Journal of Medicine (1973)

An indirect immunofluorescent technic was used to search for common enterobacterial antigen in kidney specimens from patients with bacterial and "abacterial" pyelonephritis, chronic interstitial nephritis and nonspecific renal scars. Control studies showed adequate staining of enteric bacteria in smears and in tissues of animals with acute experimental Escherichia coli and proteus pyelonephritis. Bacterial antigen was unequivocally found in only one of nine kidneys with chronic pyelonephritis, and was uniformly absent in chronic interstitial nephritis and in nonspecific renal scars. Antigen was present in three of five kidneys with acute pyelonephritis caused by enteric organisms and in one of two with xanthogranulomatous pyelonephritis. These findings are in contrast with those of others showing common antigen in the majority (six out of seven) of kidneys with chronic "abacterial" pyelonephritis. Because of the relative insensitivity of the method the data do not exclude a role for bacteria but suggest continued search for other causes of interstitial renal diseases and better methods for their differential diagnosis. (N Engl J Med 289:830–835, 1973)
Lymphatic vessels as targets for intervention in the treatment of inflammatory airway diseases
Authors: J Quint
Journal: Thorax (2005)

▴ Baluk P, Tammela T, Ator E, et al . Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest2005;115:247–57 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This collaborative group investigated the factors triggering lymphangiogenesis in response to increased leakage in airway inflammation. They used mouse models with chronic respiratory tract infections with Mycoplasma pulmonis and models with adenoviral transduction of airway epithelium with VEGF family growth factors. In pathogen free mice, blood and lymphatic … [1]: {openurl}?query=rft.jtitle%253DJ%2BClin%2BInvest%26rft_id%253Dinfo%253Adoi%252F10.1172%252FJCI200522037%26rft_id%253Dinfo%253Apmid%252F15668734%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1172/JCI200522037&link_type=DOI [3]: /lookup/external-ref?access_num=15668734&link_type=MED&atom=%2Fthoraxjnl%2F60%2F6%2F487.atom [4]: /lookup/external-ref?access_num=000226867300010&link_type=ISI
Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthma
Authors: Koichiro Asano, Craig M. Lilly, Walter J. O'Donnell, Elliot Israel, Andrew Fischer, Bernard J. Ransil, Jeffrey M. Drazen
Journal: Journal of Allergy and Clinical Immunology (1995)