tbuckley/cabot-search huggingface dataset:
Abstract 737: Multispectral Optoacoustic Tomography (MSOT) imaging and quantification of apoptosis in vivo.
Authors: Wouter H. Driessen, Neal C. Burton, Thomas Sardella, Stefan Morscher, Daniel Razansky, Vasilis Ntziachristos
Journal: Cancer Research (2013)

Abstract Apoptosis is an important mechanism in cellular homeostasis and imbalances in the apoptotic process are associated with various disease states. An important example is the acquired ability of cancer cells to resist their own programmed cell death and therefore it is the aim of many tumor therapies to either reestablish pro-apoptotic signaling pathways or induce apoptosis through activation of existing mechanisms within the cell. Therefore, visualizing and quantifying the apoptotic process in vivo has great value in monitoring therapy response, diagnosis and staging disease. By being able to detect subtle changes in perfusion and tissue oxygenation, the small animal Multispectral Optoacoustic Tomography (MSOT) scanner offers unprecedented performance in cross-sectional imaging of tumor heterogeneity as well as a powerful capacity to simultaneously image molecular processes such as apoptosis by utilizing novel molecular probes. In this study, apoptotic regions within a mouse mammary tumor where visualized using a dye-conjugated caspase probe and compared to the hypoxia status of each tumor region. The temporal resolution of the MSOT small animal scanner (generation of multispectral cross-sectional data in less than 1 second) allows for the dynamic imaging of targeted and control probe simultaneously. To illustrate this point apoptosis probe was co-injected with a control dye with similar physical and chemical properties, but a different absorbance maximum after which the tumor region was imaged over 1 hour with multi-spectral image acquisition. Next, mice were imaged by MSOT immediately before and 24 hours post treatment with the chemotherapeutic Doxorubicin and the induction of apoptosis was visualized and quantified. Doxorubicin treatment led to a significant increase in signal resulting from the DyLight 747-conjugated apoptosis probe. In summary, MSOT can be used to determine the extent of apoptosis in tumors in vivo and thus has great value in monitoring therapy response, diagnosis and staging disease. Citation Format: Wouter H. Driessen, Neal C. Burton, Thomas Sardella, Stefan Morscher, Daniel Razansky, Vasilis Ntziachristos. Multispectral Optoacoustic Tomography (MSOT) imaging and quantification of apoptosis in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 737. doi:10.1158/1538-7445.AM2013-737
Amiodarone in the treatment of chronic atrial fibrillation: results of a randomised, controlled study
Authors: N.E. Igoumenidis, G.E. Kochiadakis, M.E. Marketou, M.C. Solomou, F.M. Zambetakis, E.G. Zuridakis, P.E. Vardas
Journal: Journal of the American College of Cardiology (1998)
Patient education to encourage graded exercise in chronic fatigue syndrome
Authors: A. Chaudhuri
Journal: BMJ (2001)

Medicine information leaflets fail concordance testEditor-Two initiatives about the use of medicines reflect the growing movement towards involving patients in their health care.The first is concordance, which promotes a model of prescribing based on negotiated agreements that respect the patient's perspective. 1 The second is a European directive requiring mandatory patient leaflets with all medicines. 2Manufacturers must produce these comprehensive leaflets, including all datasheet information, in a form understandable to patients.Unfortunately, concordance and such mandatory leaflets seem to be mutually incompatible.Concordance requires that patients be fully informed about their medicines in the widest sense.Perversely, the mandatory leaflets are in most senses narrow and undermine concordance.Firstly, patients only receive the information when they open their medicines.Any information throwing doubt on the appropriateness of the drug therefore comes too late.Secondly, patients need to know the various options for treatment.Currently leaflets include only information about the drug in question.Thirdly, patients need balanced information, but the leaflets present mainly negative information, such as side effects.Other problems exist.Recent research found that nearly a fifth of patients failed to notice the package leaflet.Of those who recalled receiving a leaflet, only two fifths read some of it and two tenths all of it. 3Unlike computer generated pharmacy leaflets (which are used in the United States and Australasia), the leaflets cannot be individualised. 3 Computer generation allows pharmacists to use leaflets as aides mémoire and go through them with patients.The electronic form also gives options for providing access to partially sighted people. 4 Surgery computers are already able to print condition-specific leaflets at doctors' desks. 5 They could be adapted as decision making aids for patients and hence facilitate concordance.The doctor makes a diagnosis and supplies a leaflet, which includes all treatment options.Having read and digested this information, the patient returns to make a decision jointly with the prescriber.This may reduce misunderstandings but might increase the number of consultations.But common conditions such as hypertension already necessitate multiple consultations before long term treatment options are decided.The introduction of comprehensive medicine leaflets is an important development in the provision of information, but the opportunity has been lost to support concordance in medicine taking, which is now endorsed by the NHS Plan.The inadequacies of such leaflets mean that they may become a legal backstop, with patients accessing more relevant, individualised, and wideranging information generated electronically.European law needs amending to reflect this.
Prospective, randomized comparison of conventional and high dose loading regimens of amiodarone in the treatment of ventricular tachycardia
Authors: Steven J. Kalbfleisch, Brian Williamson, K.Ching Man, Vicken Vorperian, John D. Hummel, Carol Hasse, S.Adam Strickberger, Hugh Calkins, Jonathan J. Langberg, Fred Morady
Journal: Journal of the American College of Cardiology (1993)
Abstract OT1-4-02: Phase I study of the combination of BKM120 and olaparib for the treatment of high grade serous ovarian cancer (HGSC) and triple negative breast cancer (TNBC)
Authors: UA Matulonis, G Wulf, L Cantley, G Mills, B Lasonde, T Atkinson, C Whalen, SJ Isakoff, S Westin, K Bell-McGuinn, E Winer
Journal: Cancer Research (2013)

Abstract Background: In vivo synergy of the PI3-kinase inhibitor BKM120 with the PARP inhibitor olaparib has been observed using a mouse model of BRCA1-related breast cancer and sporadic TNBC (Juvekar et al and Ibrahim et al, Cancer Discovery 2012). In addition, olaparib has single agent activity in both HGSC and BRCA-associated breast cancer. The PI3kinase pathway is activated in both TNBC and HGSC (www.cancergenome.nih.gov). These preclinical and clinical data have served as the rationale for this phase I, multi-center study (NCT01623349) combining the oral PARP inhibitor olaparib with the oral PI3-kinase inhibitor BKM120 in patients with recurrent HGSC or recurrent TNBC. This study is being conducted through the Stand Up to Cancer (SU2C)'s Targeting PI3-kinase in Women's Cancers Dream Team. Study Design: This study has a 3 + 3 design, escalating if 0/3 or 1/6 participants have a dose limiting toxicity (DLT) during the first cycle of therapy (first 28 days). The study objectives are to determine the recommended phase II dose (RP2D) of daily continuous oral olaparib (using the tablet formulation) and BKM120, assess toxicities, safety, and preliminary activity of this combination, and determine pharmacokinetic profiles of both agents. In addition, there are several translational endpoints including elucidation of downstream signaling effects of the PI3-kinase pathway, examination of BRCA1 immunostaining, and assessment of BRCA1 promoter hypermethylation and somatic mutations in BRCA1 and BRCA2 using archived formalin fixed paraffin embedded (FFPE) tissue. Serial IL-8 and circulating DNA levels are also being monitored as well. Eligibility includes a diagnosis of recurrent TNBC or HGSC, PS 0 or 1, measurable or evaluable cancer, and normal lab values and organ function. Prior PARP inhibitor exposure is allowed. In addition, breast cancer or ovarian cancer patients with any histologic subtype are eligible if they have a known germline BRCA1 or BRCA2 mutation. At the RP2D, 10 pts each with a diagnosis of TNBC or HGSC will be enrolled to further determine safety and efficacy profiles in addition to more thoroughly studying translational endpoints. As of June 7, 2013, 16 patients have been enrolled into this study with a planned accrual of approximately 50 patients which may change based on number of dose levels tested during dose escalation. In addition, an amendment is pending that will add a second cohort studying the combination of olaparib and BYL719 based on robust pre-clinical activity observed in murine models which will increase our total accrual. Once this new cohort is open, both arms will enroll simultaneously. For further information, contact Ursula Matulonis at: umatulonis@partners.org. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-4-02.
THE ORAL MANIFESTATIONS OF VITAMIN DEFICIENCIES
Authors: LOUIS A. ROSENBLUM
Journal: JAMA (1941)

As the main system for the ingestion and absorption of foodstuffs, the gastrointestinal tract occupies a prominent position in the causation of vitamin deficiencies. Thus it has been pointed out that "any pathologic condition which interferes with normal food intake, normal digestion, normal absorption of the products of digestion, and normal utilization of these products by the liver, may produce secondary or conditioned avitaminosis."<sup>1</sup>In addition, the gastrointestinal tract is one of the first systems to present objective clinical signs when deficiencies of certain vitamins occur. An examination of the diets usually prescribed for patients with peptic ulcer, colitis and disease of the gallbladder shows that they often consist mainly of refined carbohydrate and are apt to be deficient in one or more of the vitamins. Patients with idiosyncrasies regarding food expressed in the diet they select will more often than not favor refined foods low in vitamins. On the
429 ADRENAL INSUFFICIENCY IN PATIENTS WITH CIRRHOSIS AND VARICEAL BLEEDING
Authors: C. Triantos, M. Marzigie, G. Fede, M. Michalaki, D. Giannakopoulou, K. Zisimopoulos, K. Thomopoulos, M. Makri, V. Kyriazopoulou, E. Jelastopulu, V. Nikolopoulou, J. O'Beirne, A.K. Burroughs
Journal: Journal of Hepatology (2010)
Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill.
Authors: M J Griffith, L Breitkreutz, H Trapp, E Briet, C M Noyes, R L Lundblad, H R Roberts
Journal: Journal of Clinical Investigation (1985)

Two structurally different forms of activated human Factor IX (Factor IXa alpha and IXa beta) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IX Chapel Hill, an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXa alpha are structurally very similar, the clotting activity of activated Factor IX Chapel Hill is much lower (approximately fivefold) than that of normal Factor IXa beta. In the present study we have prepared activated Factor IX by incubating human Factor IX with calcium and Russell's viper venom covalently bound to agarose. Fractionation of the activated Factor IX by high-performance liquid chromatography demonstrated the presence of both Factors IXa alpha and IXa beta. On the basis of active site concentration, determined by titration with antithrombin III, the clotting activities of activated Factor IX Chapel Hill and IXa alpha were similar, but both activities were less than 20% of the clotting activity of Factor IXa beta. Activated Factor IX activity was also measured in the absence of calcium, phospholipid, and Factor VIII, by determination of the rate of Factor X activation in the presence of polylysine. In the presence of polylysine, the rates of Factor X activation by activated Factor IX Chapel Hill, Factor IXa alpha, and Factor IXa beta were essentially identical. We conclude that the clotting activity of activated Factor IX Chapel Hill is reduced when compared with that of Factor IXa beta but essentially normal when compared with that of Factor IXa alpha.
Time course of bronchodilating effect of inhaled formoterol, a potent and long acting sympathomimetic.
Authors: E Y Derom, R A Pauwels
Journal: Thorax (1992)

BACKGROUND: Most of the currently available inhaled beta 2 agonists are short acting bronchodilators. The aim of this study was to compare the rate of onset and duration of the bronchodilating activity of formoterol and salbutamol. METHODS: Fourteen patients with reversible airways obstruction received placebo, 200 micrograms salbutamol, and 12, 24, and 48 micrograms formoterol from a metered dose inhaler, according to a double blind, randomised crossover design. Forced expiratory volume in one second (FEV1) and specific airways conductance (sGaw) were measured over 12 hours. RESULTS: Salbutamol and all doses of formoterol caused a significant and substantial increase in sGaw one minute after inhalation. The mean maximum increase in FEV1 was 58% (8%) after 200 micrograms salbutamol compared with 63% (11%), 62% (10%), and 74% (10%) after 12, 24, and 48 micrograms formoterol, respectively. The mean maximum increase in FEV1 occurred 57 (12) minutes after administration of salbutamol compared with 137 (16), 141 (21), and 161 (33) minutes after 12, 24, and 48 micrograms formoterol respectively. The bronchodilating effect of salbutamol did not differ from placebo after six hours. In contrast, the mean increase in FEV1 12 hours after 12 micrograms formoterol (26% (8%) of baseline) significantly exceeded the change after placebo. Tremor was recorded in four patients after 48 micrograms formoterol. CONCLUSION: Formoterol is a potent, fast acting bronchodilator with a long duration of action.
Identification of proteins from a human liver cDNA library that bind to wild-type human p53
Authors: H YUWEN
Journal: Hepatology (1995)

We have recently reported that attenuated phosphorylation of heat shock protein (HSP) 27 correlates with tumor progression in patients with hepatocellular carcinoma (HCC). In the present study, we investigated what kind of kinase regulates phosphorylation of HSP27 in human HCC-derived HuH7 cells. 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleoyl-2-acetylglycerol, direct activators of protein kinase C (PKC), markedly strengthened the phosphorylation of HSP27. Bisindorylmaleimide I, an inhibitor of PKC, suppressed the TPA-induced levels of HSP27 phosphorylation in addition to its basal levels. Knock down of PKCδ suppressed HSP27 phosphorylation, as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. SB203580, an inhibitor of p38 MAPK, suppressed the TPA-induced HSP27 phosphorylation. Our results strongly suggest that activation of PKCδ regulates the phosphorylation of HSP27 via p38 MAPK in human HCC.
THE BILIARY FACTOR IN LIVER LESIONS
Authors: Peyton Rous, Louise D. Larimore
Journal: The Journal of Experimental Medicine (1920)

There are excellent reasons for employing the rabbit in an experimental analysis of the biliary factor in liver lesions; and it is possible to obtain in this animal results uncomplicated by infection or by intercurrent cirrhosis. Ligation of the common duct of the rabbit results in a mixed lesion from injury throughout the entire length of the bile channels. By obstructing single ducts and altering the portal stream we have produced cirrhoses of pure monolobular and diffusely intralobular types. The character of the connective tissue changes is determined by the path of escape of bile from the collecting system, which in turn is largely conditional upon the secretory activity, while this again is dependent upon blood flow. The portal flow is largely diverted from regions of local stasis through encroachment on the stream bed by the dilated ducts. There is a large margin of safety in bile elimination by the normal hepatic tissue. Less than a quarter of the liver of the rabbit, and this deprived of its entire portal stream, will suffice to keep the organism free from clinical jaundice and healthy when the remainder of the liver, which receives all of the portal blood, has its ducts ligated. The vicarious elimination thus illustrated is of great importance for regions of local stasis by keeping the blood relatively free from bile, thus preventing resecretion into such regions and facilitating exchange from them into the body fluids. Our experimental monolobular and intralobular cirrhoses are the result of the limitation of biliary lesions to special levels of the duct system. Their resemblance to the different forms of "biliary" cirrhosis associated with Hanot's name is close, and the diverse liver lesions of Hanot's disease are readily explained on the assumption that the stasis, with or without infection, which is indubitably here present, has its situation at different levels in different cases. There are reasons for the view that bile stasis per se may sometimes be a prime cause of the malady. Certainly such stasis must be thought of as acting to complicate many chronic liver lesions. In a later paper experiments on the dog will be described essentially similar in result to those on the rabbit as here set forth.
A Dangerous Fad
Authors: William M. Daly
Journal: JAMA (1974)

To the Editor.—  I would like to plead for the abandonment of a growing, all too common practice of so-called background music in operating rooms. Any operating room worker who is actually hearing the music is not concentrating on his job.  The alert anesthesiologist depends a great deal on his ears to aid him in safe conduct. He cannot give his full attention to such vital sounds such as those arising from cardiac monitors, blood pressure determinations, pulse meters, presences or absences of normal or abnormal respiratory noises, proper cycling of ventilators, gas leaks, and others, and also sing along with Mitch.  Operating rooms should be as quiet as possible except for the essential sounds of communication between personnel directly concerned with the patient's care. The patient is deserving of all the staff's continuous complete attention and not just between musical scores. When a surgeon hums or whistles during an
Acute lymphoblastic leukemia: End‐result analysis of treatment and prognostic factors in Indian patients
Authors: S. H. Advani, D. N. Rao, R. Gopal, C. N. Nair, M. Battacharya
Journal: American Journal of Hematology (1983)

Abstract Acute Lymphatic Leukemia (ALL) patients seen during the period 1974–1978 at the Tata Memorial Hospital, Bombay, are analyzed retrospectively to evaluate the clinical features at presentation, results of sequential therapy, and prognostic factors. A total of 301 patients were registered during the study period. There were 153 evaluable patients. Of these 73 patients received induction therapy with vincristine and prednisolone (VP) followed by cranial prophylaxis (cranial radiotherapy, 2,400 rads, and 10 weekly intrathecal injections of methotrexate 7.5 mg/m 2 ) and continuous oral maintenance with daily 6‐mecrapatopurine and weekly methrotrexte (group A). Another 39 patients (group B) received pulse therapy with vincristine and prednisolone during maintenance therapy. Finally 41 patients (group C) received L‐asparaginase during induction and pulse therapy in addition to drugs as in group A. Of the 153 patients, 88 (58%) achieved complete response after induction treatment. Induction remission was 53% with vincristine and prednisolone (group A and group B), whereas it was 70% in group C. The difference in complete response rate in group C was statistically significant (P&lt;0.05). The 3‐year survival in our series was 22%, with median survival of 11 months. Group C patients receiving L‐asparaginase along with vincristine and prednisolone showed 41% 3‐year survival compared to 16% for group B. The 3‐year survival in group A patients was only 7%, probably owing to lack of pulse therapy during maintenance treatment. The prognostic factors such as age, sex, WBC count, and mediastinal node were compared for induction remission and total survival. Possible factors relating to poor results in our series as compared to developed countries are discussed.
Success and Crisis in National Health Systems: A Comparative Approach
Authors: William J. Bicknell
Journal: JAMA (1990)

This book provides a stimulating and provocative examination of common problems facing the health systems in all developed countries. The fundamental question it seeks to illuminate is What can we learn from the experience of the others? Professor Field and his colleagues set themselves a difficult but useful task and have done it well. The reader is rewarded with a well-orchestrated tour of diverse health systems that usefully illuminate different approaches to common issues of aging, access, technology, specialization, medical education, rising consumer expectations, growing costs, and limited resources. The serious student of public policy in health is provided with an accessible and focused approach to strikingly different health care systems. The result of comparing national health systems could easily be a descriptive and analytic tome that is unreadable. This insightful and reasonably short work neatly avoids this without running aground on the shoals of superficiality. Field contributes greatly with
Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis
Authors: M V Apte, P S Haber, S J Darby, S C Rodgers, G W McCaughan, M A Korsten, R C Pirola, J S Wilson
Journal: Gut (1999)

The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells play a major role in fibrogenesis by synthesising increased amounts of collagen and other extracellular matrix (ECM) proteins when activated by profibrogenic mediators such as cytokines and oxidant stress.To determine whether cultured rat pancreatic stellate cells produce collagen and other ECM proteins, and exhibit signs of activation when exposed to the cytokines platelet derived growth factor (PDGF) or transforming growth factor beta (TGF-beta).Cultured pancreatic stellate cells were immunostained for the ECM proteins procollagen III, collagen I, laminin, and fibronectin using specific polyclonal antibodies. For cytokine studies, triplicate wells of cells were incubated with increasing concentrations of PDGF or TGF-beta.Cultured pancreatic stellate cells stained strongly positive for all ECM proteins tested. Incubation of cells with 1, 5, and 10 ng/ml PDGF led to a significant dose related increase in cell counts as well as in the incorporation of 3H-thymidine into DNA. Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-beta showed a dose dependent increase in alpha smooth muscle actin expression and increased collagen synthesis. In addition, TGF-beta increased the expression of PDGF receptors on stellate cells.Pancreatic stellate cells produce collagen and other extracellular matrix proteins, and respond to the cytokines PDGF and TGF-beta by increased proliferation and increased collagen synthesis. These results suggest an important role for stellate cells in pancreatic fibrogenesis.