tbuckley/cabot-search huggingface dataset:
Treatment resistance in schizophrenia
Authors: E. C Johnstone, R. Sandler
Journal: BMJ (1996)

patients requiring active management.6If this information helped to identify those with inherited hyperlipidaemias it would be useful.However, the incidence of familial hypercholesterolaemia is about 1 in 500,7 and only half of these people have a family history of coronary heart disease.8From these figures, not more than one case of familial hypercholesterolaemia would be found in 1000 screened adults, with 170 patients requiring a blood test.8One further case of familial hypercholesterolaemia would go undetected, as would 50-65% of patients with serum cholesterol concentrations greater than 8 mmo0l/.6Too important to be bargained away But perhaps the most worrying aspect of the new proposals is the abolition ofthe requirement to stratify the data recorded by age and sex.Without stratification, the data will be uninterpretable and of no value in planning effective health promotion.With most general practices now being com- puterised, it is simple to produce data stratified by age and sex.This requirement to stratify should be reintroduced, at least in computerised practices.Health promotion is too important to be used by the Department of Health as a bargaining counter to appease general practitioners who are increasingly disillusioned by an onerous scheme unsupported by science.The whole scheme should be comprehensively reviewed.If financial incentives for health promotion are to be retained, they should be linked to evidence based interventions focused on people at higher risk.A series ofhurried decisions has failed to provide a policy for health promotion in primary care that could add length and quality to many lives.An opportunity for a broader review leading to an effective strategy integrating the many agencies involved in disease prevention has been missed.
Elevated Endothelin-1 Levels Impair Nitric Oxide Homeostasis Through a PKC-Dependent Pathway
Authors: Danny Ramzy, Vivek Rao, Laura C. Tumiati, Ning Xu, Rohit Sheshgiri, Santiago Miriuka, Diego H. Delgado, Heather J. Ross
Journal: Circulation (2006)

Background— Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone and pathological states such as ischemia/reperfusion (I/R) injury, coronary vasospasm, and cardiac allograft vasculopathy. We assessed the effects of elevated ET-1 levels as seen after I/R to determine if ET-1 modulates nitric oxide (NO) production via the translocation of specific protein kinase C (PKC) isoforms. Methods and Results— Human saphenous vein endothelial cells (HSVECs) (n=8) were incubated with ET-1 or phosphate-buffered saline (PBS) for 24 hours. NO production was determined in the supernatant by measuring nitrate/nitrite levels. Protein expression of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), caveolin-1 and PKC were determined. Lastly, PKC translocation and activity were assessed after exposure to the drug of interest. HSVECs exposed to ET-1 displayed decreased NO production. PKC inhibition reduced NO production, whereas PKC activation increased production. NO production was maintained when HSVECs exposed to ET-1 were treated with the PKC agonist, PMA. eNOS protein expression was reduced after ET-1 treatment. PKC inhibition also downregulated eNOS protein expression, whereas PMA upregulated expression. ET-1 exposure led to a significant increase in PKCδ and PKCα translocation compared with control, whereas translocation of PKCλ was inhibited. ET-1 exposure significantly reduced overall PKC activity compared with control. Conclusions— Our study demonstrates that high levels of ET-1 impair endothelial NO production via an isoform-specific PKC-mediated inhibition of eNOS expression. ET-1 antagonism with bosentan stimulates translocation of PKCλ and leads to increased PKC activity and NO production. ET-1 antagonism may provide a novel therapeutic strategy to improve vascular homeostasis.
Not a Linebacker-Reply
Authors: M. Therese Southgate
Journal: JAMA (1982)

<h3>In Reply.—</h3> The incongruity of the "linebacker's" number did not entirely escape Ms Meyer's discerning eye. Dr Poletti is probably correct in noting that the "linebacker" is really a tackle. The most interesting comment, however, comes from the artist himself. Just weeks before Joseph Hirsch died on Sept 21, 1981, he happened to see<i>Linebacker</i>at the Kennedy Galleries, New York, paused in front of it, and after examining it noted that the painting was really not a linebacker at all. How the painting came to be titled<i>Linebacker</i>is not known.
Intestinal permeability in patients with yersinia triggered reactive arthritis.
Authors: R Lahesmaa-Rantala, K E Magnusson, K Granfors, R Leino, T Sundqvist, A Toivanen
Journal: Annals of the Rheumatic Diseases (1991)

The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease.
ON THE RELATIVE MERITS OF THE DIFFERENT METHODS OF TREATING FRACTURES OF THE LIMBS
Authors: J. S. Gamgee
Journal: BMJ (1854)

Pux2uAPS there is no subject more interesting to the practical surgeon than this of fracture of the limbs.....This is one of those subjects which has fallen into almost inextricable confusion; none, I believe, requires more to be historically explained.It is, I fear, but too certain,
False-negative qualitative cardiac troponin T in a 79-year-old man with myocardial infarction
Authors: M. Mahalingam
Journal: JAMA (1997)

To the Editor.  —Cardiac troponin T (cTnT) thought to be a more specific indicator of myocardial cell necrosis than serum creatine kinase—MB (CK-MB). 1-3 The CardiacT assay is the Food and Drug Administration—approved point-of-care device increasingly used in the detection of cTnT. To our knowledge, this is the first report of a case in which the CardiacT assay failed to detect myocardial infarction (MI) in contradiction to other biochemical markers.  A 79-year-old man, with a history of non-Q wave MI and chronic stable angina diagnosed 7 years earlier, presented to the emergency department with complaints of chest pain while walking. Cardiac examination showed a normal S 1 , S 2 , no S 3 , and a grade 2/4 harsh systolic murmur that was heard best at the right upper sternal border. A 12-lead electrocardiogram (ECG) demonstrated a sinus rhythm with a rate of 92 and right bundle branch block. Laboratory data are
Significance of Research in Cardiopulmonary Disease
Authors: Herman J. Moersch
Journal: JAMA (1961)

TODAY MARKS the beginning of a new adventure by the American Medical Association, an adventure dedicated to the purpose of improving the caliber of its scientific program—of presenting the latest developments in the field of medicine in a more instructive and attractive manner. In order to accomplish this aim, the American Medical Association has invited the American College of Chest Physicians to join with the Section on Diseases of the Chest in preparing a one-day combined program. Should today's undertaking meet with approval, other groups will undoubtedly be invited to participate in similar efforts. It is your officers' sincere hope that the expectations so hopefully initiated will be successfully fulfilled.  Progress in medicine entails a constant search for the new. We as physicians especially must support the high aims of medical research and, above all, utilize the information that it offers us. To do otherwise will inevitably weaken the enviable
Contributions of Sports to Medicine
Authors: Thomas B. Quigley
Journal: JAMA (1966)

Only a few decades ago there was little association between medicine and sports. A few doctors of distinction such as George Bennett at Johns Hopkins University and Carl Badgley of Michigan University had earned the trust of athletes and achieved reputations for managing with efficiency major and minor afflictions of baseball and football players, but in general, professional association with athletes was thought to be a little undignified for a doctor of medicine. This attitude ended with the publication of Augustus Thorndike's<i>Athletic Injuries</i>in 1938.<sup>1</sup>For the first time a long experience with athletes and their medical problems was presented by a member of the faculty of a major university's school of medicine. During the next 25 years three more stages of interrelationship of medicine and athletics followed. Soon after Dr. Thorndike's book appeared, the realization spread widely that the playing field was a splendid laboratory, affording an
Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study
Authors: Suzanne Lentzsch, Amy O'Sullivan, Ryan C. Kennedy, Mohammad Abbas, Lijun Dai, Silvana Lalo Pregja, Steve Burt, Michael Boyiadzis, G. David Roodman, Markus Y. Mapara, Mounzer Agha, John Waas, Yongli Shuai, Daniel Normolle, Jeffrey A. Zonder
Journal: Blood (2012)
Abstract C87: Regulation of stemness by Hippo-YAP pathway under hypoxia in hepatocellular carcinoma
Authors: Ji Su Kim, Ei Yong Ahn, Young Nyun Park
Journal: Cancer Research (2013)

Abstract Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer-related death. The Hippo-YAP signaling pathway is gaining recognition as it plays an important role in both organ size control and tumorigenesis. Liver-specific ablation of WW45 in rodent models (one of the tumor suppressive Hippo pathway components in mammals) has been reported to increase liver size and expand hepatic stem/progenitor cells (oval cells) and to develop HCC eventually. The expression of YAP also has been reported as an independent poor prognostic marker for human HCCs. Amphiregulin is a downstream target of YAP and is a member of the EGF family, which is implicated in cancer stem cells in HCC. Cancer stem cells have the ability to self-renew, differentiate, and proliferate, and have greater tumorigenicity, chemoresistance, and resistance to hypoxia. HCCs expressing stem cell makers have actually been reported to be associated with poor prognosis and aggressive biological behavior. The aim of this study is to investigate the Hippo-YAP pathway and its related oncogenic signaling in HCCs expressing stem cell markers. The effect of amphiregulin on the regulation of the Hippo-YAP pathway was also studied to identify potential molecular therapeutic targets for HCCs expressing stem cell markers. Under hypoxic condition, the expression of cancer stem cell markers (EpCAM, CD133, and CK19) was upregulated in a time dependent manner and the Hippo-YAP pathway was oncogenically activated in four HCC cell lines (HepG2, Hep3B, Huh7, and SK-Hep1). In addition, the treatment of recombinant human amphiregulin dephosphorylated and activated YAP pathway. Therefore, up-regulation of cancer stem cell markers with activation of oncogenic YAP pathway in HCC cell lines might suggest the acquisition of survival advantage of tumor cells under hypoxia. The relationship between the regulatory mechanism of cancer stem cells and the Hippo-YAP pathway can be used for molecular target of chemotherapy for HCC. Citation Format: Ji Su Kim, Ei Yong Ahn, Young Nyun Park. Regulation of stemness by Hippo-YAP pathway under hypoxia in hepatocellular carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C87.
Sources of Cyclic Nucleotides in Plasma
Authors: Robert E. Wehmann, Lawrence Blonde, Alton L. Steiner
Journal: Journal of Clinical Investigation (1974)

In order to determine the sites of net production and removal of the cyclic nucleotides in plasma, various blood vessels were catheterized in 17 anesthetized dogs and arterial and venous concentrations of adenosine 3′,5′-monophosphate (cAMP) and guanosine 3′,5′-monophosphate (cGMP) were measured by radioimmunoassay.
Canadian election focuses on health cuts
Authors: D. Spurgeon
Journal: BMJ (1997)

The Canadian public blames cuts in funding to the provinces for worsening health care, according to a poll by the Canadian Medical Association.

The day before the results were released the Canadian prime minister, Jean Chretien, opened his re-election campaign with a promise not to go ahead with planned funding cuts to the provinces. The move is seen as a bid to repair …
Some Possible Effects of Patient Noncompliance
Authors: Mark E. Cowen
Journal: JAMA (1981)

To the Editor.—  We recently completed a retrospective 12-month survey of 1,200 inpatients and outpatients in a medical clinic that included a pilot study to see if patient noncompliance had any adverse effects on health care costs. Of the 1,200 charts surveyed, 48 patients met the criteria for being noncompliant, where there was physician documentation in either the outpatient chart or hospital discharge summary. A patient is defined as noncompliant if he either (1) did not take all the drugs prescribed or (2) changed doses on his own without approval by a physician or (3) took medications that were not currently prescribed or recommended by the physician. We then compared this group with the remaining 1,075 patients (77 patients with drug abuse problems were excluded). The mean age for the noncompliant group was older (50.7 years vs 42.3 years). Over the one-year period studied, the noncompliant group compared with the
ECG-Gated Three-dimensional Intravascular Ultrasound
Authors: Clemens von Birgelen, Evelyn A. de Vrey, Gary S. Mintz, Antonino Nicosia, Nico Bruining, Wenguang Li, Cornelis J. Slager, Jos R. T. C. Roelandt, Patrick W. Serruys, Pim J. de Feyter
Journal: Circulation (1997)

Background Automated systems for the quantitative analysis of three-dimensional (3D) sets of intravascular ultrasound (IVUS) images have been developed to reduce the time required to perform volumetric analyses; however, 3D image reconstruction by these nongated systems is frequently hampered by cyclic artifacts. Methods and Results We used an ECG-gated 3D IVUS image acquisition workstation and a dedicated pullback device in atherosclerotic coronary segments of 30 patients to evaluate (1) the feasibility of this approach of image acquisition, (2) the reproducibility of an automated contour detection algorithm in measuring lumen, external elastic membrane, and plaque+media cross-sectional areas (CSAs) and volumes and the cross-sectional and volumetric plaque+media burden, and (3) the agreement between the automated area measurements and the results of manual tracing. The gated image acquisition took 3.9±1.5 minutes. The length of the segments analyzed was 9.6 to 40.0 mm, with 2.3±1.5 side branches per segment. The minimum lumen CSA measured 6.4±1.7 mm 2 , and the maximum and average CSA plaque+media burden measured 60.5±10.2% and 46.5±9.9%, respectively. The automated contour-detection required 34.3±7.3 minutes per segment. The differences between these measurements and manual tracing did not exceed 1.6% (SD&lt;6.8%). Intraobserver and interobserver differences in area measurements (n=3421; r =.97 to.99) were &lt;1.6% (SD&lt;7.2%); intraobserver and interobserver differences in volumetric measurements (n=30; r =.99) were &lt;0.4% (SD&lt;3.2%). Conclusions ECG-gated acquisition of 3D IVUS image sets is feasible and permits the application of automated contour detection to provide reproducible measurements of the lumen and atherosclerotic plaque CSA and volume in a relatively short analysis time.
IM-11 * GBM-ASSOCIATED EXOSOME-PULSED AUTOLOGOUS DC VACCINE (DC-VEX(R)) INDUCES D-2 APOPTOTIC-STAGE AND BYSTANDER KILLING-EFFECT IN GBM OF THE MESENCHYMAL TYPE
Authors: J. Giannios
Journal: Neuro-Oncology (2015)

INTRODUCTION: GBM is one of the most lethal cancers due to its resistance to apoptosis or type I PCD after chemo/radiotherapy. Due to its heterogenicity, we must treat this tumour with personalised cancer medicine. METHODS: We obtain relapsed GBM characterised by NF1 deletions and PTEN mutations of the mesenchymal type resistant to chemo/radiation Tx, and then we develop a GBM-model from which we isolate autologous dendritic cells and exosomes expressing CD9/CD91, both of which incubate ex-vivo in culture with granulocyte-macrophage colony stimulating factor,interleukin-4 and tumour necrosis factor-a. RESULTS: Post-treatment with the active specific immunotherapy via the GBM-associated antigen presenting dendritic cells, we observe humoral antibody responses and cellular immunity responses expanding circulating CD4 and CD8 CTLs which express TCRs for the specific GBM antigens which bind to the complex of class I MHC molecule and release IFN-γ,IL-2 and IL-6.RNA sequencing for genomic/epigenomic analysis has exhibited that exosomes carry coding and non-coding genes whose expression was different from the ones detected in the FFPE samples obtained from the initial biopsies exhibiting the most recent gene alterations which take place in the relapsed GBM. The active specific immunotherapy leads to D2 irreversible stage of apoptosis or type-I programmed cell death leading to a bystander killing effect after phagocytosis of the apoptotic bodies by the adjacent relapsed GBM causing their eradication. CONCLUSION: The DC-Vex® autologous dendritic cell vaccine due to pulsed exosomes, it can eradicate with humoral and cellular immunity pathways the relapsed chemo/radioresistant GBM of mesenchymal type.
THE CLINICAL USE OF STROPHANTHUS
Authors: ROBERT A. HATCHER
Journal: JAMA (1910)

The clinical use of digitalis has proved one of the greatest problems of medicine and, despite the advances made in our knowledge of the pharmacology of this group, the problem has been advanced only, not solved, and there are few practitioners who can invariably distinguish the toxic action of digitalis from the symptoms of cardiac disease. The difficulties in the way of the therapeutic use of the digitalis bodies depend on several factors. In the first place, we have no definite knowledge of the rate of absorption of these bodies from the alimentary tract, and this knowledge is the first requisite for correct dosage by the mouth. In the next place, we know little or nothing of the rate of excretion and destruction in the body, and these facts are also of prime importance. Furthermore, except for the well-known vagus stimulation, we do not know whether they act directly on
Interleukin 10 Secretion and Impaired Effector Function of Major Histocompatibility Complex Class II–restricted T Cells Anergized In Vivo
Authors: Jan Buer, Astrid Lanoue, Anke Franzke, Corinne Garcia, Harald von Boehmer, Adelaida Sarukhan
Journal: The Journal of Experimental Medicine (1998)

Continuous antigenic stimulation in vivo can result in the generation of so-called “anergic” CD4+ or CD8+ T cells that fail to proliferate upon antigenic stimulation and fail to develop cytolytic effector functions. Here we show that class II major histocompatibility complex–restricted T cells specific for influenza hemagglutinin (HA) that become anergic in mice expressing HA under control of the immunoglobulin κ promoter exhibit an impaired effector function in causing diabetes in vivo, as compared to their naive counterparts, when transferred into immunodeficient recipients expressing HA under the control of the insulin promoter. Furthermore, HA-specific T cells anergized in vivo contain higher levels of interleukin (IL)-4 messenger RNA (mRNA) than naive and recently activated T cells with the same specificity and more than a 100-fold higher levels of IL-10 mRNA. The higher expression of the IL-10 gene is also evident at the protein level. These findings raise the interesting possibility that T cells rendered anergic in vivo have in fact become regulatory T cells that may influence neighboring immune responses through the release of IL-10.
Slower Progression of HIV-1 Infection in Persons with GB Virus C Co-Infection Correlates with an Intact T-Helper 1 Cytokine Profile
Authors: Giuseppe Nunnari, Luciano Nigro, Filippo Palermo, Massimo Attanasio, Annemarie Berger, Hans W. Doerr, Roger J. Pomerantz, Bruno Cacopardo
Journal: Annals of Internal Medicine (2003)

Background: Progression to AIDS is slower in persons infected with both HIV-1 and GB virus C (GBV-C), also known as hepatitis G virus. Objective: To compare clinical, virologic, and immunologic variables in HIV-1seropositive patients with and without GBV-C co-infection. Design: Subanalysis of a prospective cohort study. Setting: Institute of Infectious Diseases, University of Catania, Catania, Italy. Patients: 80 asymptomatic HIV-1seropositive patients. Measurements: GBV-C RNA level; plasma HIV-1 viral load; CD4+ cell counts; and serum levels of interleukin (IL)-2, IL-4, IL-10, and IL-12. Results: At the start of the study, plasma GBV-C RNA was detected in 17 patients (21%). During follow-up, IL-2 and IL-12 levels decreased significantly (P = 0.005 and P = 0.01, respectively) and IL-4 and IL-10 levels increased significantly (P = 0.01 and P = 0.004, respectively) in the GBV-Cnegative group but did not change substantially in the GBV-Cpositive group. Each measured variable differed significantly between GBV-Cpositive and GBV-Cnegative groups during follow-up (P < 0.001 for IL-12, IL-4, and IL-10; P = 0.002 for IL-2). Conclusion: GB virus C may immunologically interfere with progression of HIV-1 infection to AIDS by maintaining an intact T-helper 1 cytokine profile.
P06.11 * CLINICAL OUTCOME OF WORLD HEALTH ORGANIZATION GRADE II AND III MENINGIOMAS
Authors: J. Moon, E. Kim, J. Chang
Journal: Neuro-Oncology (2014)

OBJECTIVE: Treatment strategy for world health organization (WHO) grade II and III meningiomas has been gross total resection with or without adjuvant radiotherapy, however, subsequent prognosis and optimal management remain unclear. METHODS: We performed a retrospective review of 60 grade II meningiomas and 23 grade III meningiomas operated in our institution from 1992 to 2009. Recurrence and survival were analyzed with Kaplan-Meier analysis, and risk factors were investigated with multivariate Cox regression. RESULTS: The mean clinical follow-up time was 96.5 months (range 9-240 months). The 1-, 5-, and 10-year overall survival rates were 98.3, 87.5, and 78.9% in grade II meningiomas and 82.6, 56.5, and 49.3% in grade III meningiomas, respectively. Survival benefit with repeated operation was clinically significant. The radicality of resection was the only statistically significant risk factor, whereas postoperative radiotherapy, Ki-67 index, anatomical location, sex, age, presence of bony involvement were not. CONCLUSION: Radical resection is essential in the treatment of WHO grade II and III tumors. Postoperative radiotherapy might be recommended in order to reduce recurrence rate and increase survival rate. This should be investigated in prospective fashion for the higher level of evidence.
Relationship of the 24-Hour Pattern of Intraocular Pressure with Optic Disc Appearance in Primary Open-Angle Glaucoma
Authors: Sunil P. Deokule, Amish Doshi, Gianmarco Vizzeri, Felipe A. Medeiros, John H.K. Liu, Christopher Bowd, Linda Zangwill, Robert N. Weinreb
Journal: Ophthalmology (2009)