tbuckley/cabot-search huggingface dataset:
Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease
Authors: Paul S. Chan, Brahmajee K. Nallamothu, Hitinder S. Gurm, Rodney A. Hayward, Sandeep Vijan
Journal: Circulation (2007)

Background— Recent clinical trials found that high-dose statin therapy, compared with conventional-dose statin therapy, reduces the risk of cardiovascular events in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). However, the actual benefit and cost-effectiveness of high-dose statin therapy are unknown. Methods and Results— We designed a Markov model to compare daily high-dose with conventional-dose statin therapy for hypothetical 60-year-old cohorts with ACS and stable CAD over patient lifetime. Pooled estimates for major clinical end points (all-cause mortality, myocardial infarction, stroke, rehospitalization, and revascularization) from relevant clinical trials were incorporated. Incremental benefit was quantified as quality-adjusted life-years (QALYs). Threshold analyses determined at what price difference high-dose statins would yield incremental cost-effective ratios below $50 000, $100 000, and $150 000 per QALY gained. In ACS patients, a high-dose versus conventional-dose statin strategy resulted in a gain of 0.35 QALYs. In threshold analyses, a high-dose statin strategy consistently yielded incremental cost-effective ratios below $30 000 per QALY even under conservative model assumptions. In stable CAD patients, a high-dose statin strategy yielded a gain of only 0.10 QALYs and was sensitive to model assumptions about statin efficacy. The daily cost difference between a high- and conventional-dose statin would need to be &lt;$1.70, $2.65, and $3.55 to yield incremental cost-effective ratios below $50 000, $100 000, and $150 000 per QALY. Conclusions— High-dose statin therapy is potentially highly effective and cost-effective in patients with ACS. In patients with stable CAD, however, the cost-effectiveness of high-dose statin therapy is highly sensitive to model assumptions about statin efficacy and cost. Use of high-dose statins can be supported on health economic grounds in patients with ACS, but the case is less clear for patients with stable CAD.
Cost of anaesthetic drugs and clinical budgeting.
Authors: J R Lethbridge, J S Walker
Journal: BMJ (1986)

In 1980 Astley and Seeker Walker calculated that the average total cost to the National Health Service of one anaesthetic was ?29*98.1 The cost of drugs for the year 1979-80 was ?44032 or 8-6% of the total hospital cost of anaesthesia of ?506459. This paper examines the drugs bill for the University College Hospital group of hospitals between April 1984 and March 1985 and compares it directly with the study of the drugs bill for 1979-80. It highlights the financial consequences of changes in anaesthetic practice. We have also examined the cost of anaesthesia for one hour in 1985 and compared it with the cost of anaesthesia for the same operation (hysterectomy) lasting one hour in 1980. This shows how the choice of the newer anaesthetic drugs in 1985 led to a rise in costs, when compared with 1980, which is above the percentage rise of the Retail Price Index. Medical and nursing staff salaries account for 83% of the cost of anaesthesia, but the cost of anaesthetic drugs is the next most important factor. If the drugs bill were allowed to rise faster than the annual increase for inflation in the departmental budget it would be necessary to make equivalent economies elsewhere in the anaesthetic department's budget.
Renography in Diagnosis and Follow-up of Renal Vein Thrombosis
Authors: ALDRIK J M NIELANDER, WILLEM A. BODE, GUIDO A K HEIDENDAL
Journal: Clinical Nuclear Medicine (1983)

The case of a patient in whom the diagnosis of renal vein thrombosis was supported by renographic and scintigraphic patterns that disappeared several days after the initiation of heparin therapy is reported. This observation suggests that renal investigation with radionuclides can be an important aid in the diagnosis and follow-up of patients with acute renal vein thrombosis.
modeling category coordination: comments and complications
Authors: james a. hampton
Journal: Behavioral and Brain Sciences (2005)

consideration of color alone can give a misleading impression of the three approaches to category coordination: the nativist, empiricist and culturalist models. empiricist models can benefit from a wider range of correlational information in the environment. also, all three approaches may explain a set of perceptual categories within the human repertoire. finally, a suggestion is offered for supplementing the naming game by varying the social status of agents.
Idiotypes of inulin-binding myeloma proteins localized to variable region light and heavy chains: genetic significance.
Authors: R Lieberman, M Vrana, W Humphrey, C C Chien, M Potter
Journal: The Journal of Experimental Medicine (1977)

Idiotypes of inulin-binding myeloma proteins (InuBMP) were determined primarly by variable region light chains (VL) or by variable region heavy chains (VH) but needed both chains to be expressed. Recombinant molecules were used to show that individual idiotypes (IdI) of U61, E109, T957, and A4 InuBMP and cross-specific idiotypes (IdXB) of U61 were primarily determined by VL while cross-specific idiotype (IdXA) of A4 was determined mainly by VH. The assignment of genes controlling idiotypes to VH based on allotype linkage (e.g., IdXB) is dubious until the role of the L chain in determining that idiotype is assessed. IdXB has been shown to be a VL-VH marker which presumably is controlled by two unlinked genes. However IdXB can be used as a L chain marker in combinations of strains differing in their L chain genes but having the same permissive H chain genes. Conversely IdXB can be used as a H chain marker in strains having the same permissive L chain genes but differing in their H chain genes.
Naming names
Authors: Gayatri Vedantam, V.K. Viswanathan
Journal: Gut Microbes (2012)

The constraints imposed by available experimental data, and the need for precision, typically limits the eloquence of researchers. Scientists, however, indulge in their literary and poetic selves in the names that they bestow on genes and proteins, on organisms and diseases. We briefly review some familiar names in the Inside Passage, and explore their historical antecedents.
An Organized Sense of Wonder: From the President's Convocation Address at the American College of Physicians Annual Session, 16 March 1995
Authors: Clifton R. Cleaveland
Journal: Annals of Internal Medicine (1995)

Articles1 September 1995An Organized Sense of Wonder: From the President's Convocation Address at the American College of Physicians Annual Session, 16 March 1995Clifton R. Cleaveland, MDClifton R. Cleaveland, MDImmediate Past President, American College of Physicians, Philadelphia, PA 19106Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-5-199509010-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail One of the unifying characteristics of physicians is, I believe, a restless yet optimistic dissatisfaction with the status quo. We want to know more, to teach better, and to solve more quickly the mystery of disease.Another of our unifying traits is our rigorous pursuit of science. This propels research. In the pursuit of science, we marvel at the rare and the commonplace.A third characteristic is our desire to refine the art of the profession. We know science to be inadequate without compassion, devotion, and continuity of responsibility. We are the human face on a complex biological science.Our ... Author, Article, and Disclosure InformationAuthors: Clifton R. Cleaveland, MDAffiliations: Immediate Past President, American College of Physicians, Philadelphia, PA 19106Corresponding Author: Clifton R. Cleaveland, MD, 960 East Third Street, Suite 200, Chattanooga, TN 37403. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOpportunities and Challenges in Educating Community-Responsive Physicians 1 September 1995Volume 123, Issue 5Page: 385-386KeywordsCardiomyopathiesEmphysemaFearForecastingHealth careHealth insuranceMedical educationMedical servicesSurgeryTobacco control ePublished: 15 August 2000 Issue Published: 1 September 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Adenovirus Type-2 in a Patient with Lethal Hemorrhagic Colonic Ulcers and Chronic Active Epstein-Barr Virus Infection
Authors: MOTOHIKO OKANO
Journal: Annals of Internal Medicine (1988)

An adenovirus type-2 was isolated from peripheral blood lymphocytes and throat washings from a patient with severe chronic active Epstein-Barr virus infection. Despite the Epstein-Barr virus reactivation, attempts to establish spontaneous lymphoblastoid cell lines from peripheral blood lymphocytes and to immortalize cord lymphocytes with throat washings were unsuccessful due to a marked cytopathic effect. The supernatants from the cultures induced cytopathic effect in cultured cord lymphocytes, MRC-5 cells, A-549 cells, or Vero cells. Virus particles with adenovirus morphology were seen by electron microscopy. Using type-specific antisera, the isolate was identified as adenovirus type-2. In addition, both Epstein-Barr virus and adenovirus type-2 genomes were seen in the colonic tissues and spleen. These results suggest that the combination of Epstein-Barr virus and adenovirus type-2 may be etiologic agents in the development of chronic active Epstein-Barr virus infection in this patient.
Hookworm Infection in Great Britain
Authors: L. R. S. MacFarlane
Journal: BMJ (1965)

heights of children of parents whose mean height was 69.5 in.-that is, above average stature.In the frequency series 1, 16, 4, 17, 27, 20, 33, 25, 20, 11, 4, 5, which he quotes, there are three prominent peaks.These he ignores, saying no one has paid any attention to them, that such variation is " natural with such small numbers " (actually the chance of this being so is less than 1: 100), and possibly because they were not what he was looking for.I contend that he should have been look- ing for multimodality, and in 1963 I tested this contention on the heights of 760 univer- sity students and their parents.The results, which supported the view put forward here, were published in the Lancet' in a column adjacent to a letter from Sir George and under the same heading.It is interesting that these results find no place in his recent lecture and bibliography.
Angiotensin II and Other Hypertrophic Stimuli Mediated by G Protein–Coupled Receptors Activate Tyrosine Kinase, Mitogen-Activated Protein Kinase, and 90-kD S6 Kinase in Cardiac Myocytes
Authors: Junichi Sadoshima, Zhihua Qiu, James P. Morgan, Seigo Izumo
Journal: Circulation Research (1995)

Abstract Many hypertrophic stimuli such as angiotensin II (Ang II) activate phospholipases through G protein–coupled receptors in cardiac myocytes. However, it is not known whether these stimuli also activate the tyrosine phosphorylation–dependent signaling pathway, which plays an essential role in growth factor–induced mitogenic responses in other cell types. Serine/threonine kinases such as mitogen-activated protein (MAP) kinases and 90-kD S6 kinase (RSK) are activated in response to many growth stimuli and are important downstream signaling pathways of tyrosine kinases. Therefore, we examined whether Ang II activates these protein kinases in primary cultures of cardiac myocytes and fibroblasts from neonatal rats. Ang II rapidly induced tyrosine phosphorylation of multiple proteins, including 42-, 44-, 75- to 80-, and 120- to 130-kD proteins, in both cardiac myocytes and fibroblasts. This was accompanied by an increase in tyrosine kinase activity. The 42- and 44-kD proteins were immunologically related to an extracellular signal-regulated kinase family (MAP kinases). Ang II rapidly increased kinase activity of MAP kinases and their downstream kinase, RSK. The Ang II–induced tyrosine phosphorylation and activation of MAP kinases and RSK were AT 1 receptor–mediated. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate or an increase in intracellular Ca 2+ by the Ca 2+ ionophore A23187 was sufficient to cause tyrosine phosphorylation of multiple proteins and activation of MAP kinase and RSK. Although downregulation of PKC did not suppress Ang II–induced activation of MAP kinase and RSK, chelating intracellular Ca 2+ by BAPTA-AM completely abolished Ang II–induced activation of these kinases. Activation of MAP kinases and RSK was also observed in myocytes stimulated with other agonists for G q protein–coupled receptors, such as phenylephrine, norepinephrine, and endothelin 1, but not with agonists to G s protein–coupled receptors, such as isoproterenol. These results suggest that Ang II and other hypertrophic stimuli, known to act through G q protein–coupled receptors, rapidly cause tyrosine phosphorylation of several intracellular substrates through activation of tyrosine kinase and activate MAP kinases and RSK in cardiac myocytes as well as in cardiac fibroblasts. Furthermore, intracellular Ca 2+ , rather than PKC, seems to be critical for Ang II–induced activation of these protein kinases in cardiac myocytes.
The cyclophilin inhibitor Debio 025 combined with PEG IFNα2a significantly reduces viral load in treatment-naïve hepatitis C patients
Authors: Robert Flisiak, Saya V. Feinman, Maciej Jablkowski, Andrzej Horban, Wieslaw Kryczka, Małgorzata Pawlowska, Jenny E. Heathcote, Giuseppe Mazzella, Carmen Vandelli, Valérie Nicolas-Métral, Pierre Grosgurin, Jorge S. Liz, Pietro Scalfaro, Hervé Porchet, Raf Crabbé
Journal: Hepatology (2009)

Abstract The anti–hepatitis C virus (HCV) effect and safety of three different oral doses of the cyclophilin inhibitor Debio 025 in combination with pegylated interferon-α2a (PEG IFN-α2a) were investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase II study in treatment-naïve patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN-α2a 180 μg/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 μg/week PEG IFN-α2a. In patients with genotypes 1 and 4, the 600- and 1,000-mg combination treatments induced a continuous decay in viral load that reached −4.61 ± 1.88 and −4.75 ± 2.19 log 10 IU/mL at week 4, respectively. In patients with genotypes 2 and 3, HCV RNA levels at week 4 were reduced by −5.91 ± 1.11 and −5.89 ± 0.43 log 10 IU/mL, respectively, with the same treatment regimens. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with PEG IFN-α2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day). Conclusion: These results confirm that Debio 025 has a potent activity and an additive effect on HCV RNA reduction in genotype 1 and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN-α2a. (Hepatology 2009.)
RIGHT RECTUS RIGIDITY
Authors: Robert J. Ogilvie
Journal: JAMA (1952)

<h3>To the Editor:—</h3> I wish to take exception to a statement inThe Journalof May 3. On page 29, under the heading "Right Rectus Rigidity," the author states, "We know that it is quite impossible to contract one rectus muscle without contracting the other." While on duty at Valley Forge General Hospital in 1945 in the plastic surgery department, I had frequent occasion to observe a patient who delighted in demonstrating his corporeal achievements. He could, at will, alternately contract and relax first one and then the other rectus abdominis so that the surface of his abdomen gave the impression of a revolving door.
Emergency Renal Surgery in the Newborn Infant
Authors: Arnold Porter, Ernest K. Landsteiner
Journal: New England Journal of Medicine (1960)

ABDOMINAL masses in the newborn infant are an intriguing medical phenomenon from the point of view of both diagnosis and selection of treatment. In a recent review by Melicow and Uson1 of 372 cases in infancy and childhood with "surgical" abdominal masses, approximately 50 per cent were of urinary-tract origin. Of these the vast majority involved the kidney. The other 50 per cent consisted of neuroblastomas and teratomas. We. wish here to review only the anomalies of the kidney in the newborn infant that, because of the presence of a palpable abdominal mass, constituted a surgical emergency. These patients all . . .
Studies of Red-Cell Volume and Turnover Using Radiochromium
Authors: Raymond C. Read
Journal: New England Journal of Medicine (1954)

THE successful management of many clinical problems depends on information regarding the total volume of the mass of red cells in the body. The concentration of these cells in the peripheral blood is widely used as an index of total volume. The value of this determination depends on the accuracy with which it measures the over-all distribution of cells and plasma in the circulation. Changes in the hematocrit percentage of the peripheral blood can only reflect alterations in the size of the red-cell mass if the plasma volume remains constant. Keith et al.1 showed in 1921 that the ratio of . . .
Younger diabetes patients receive poorer routine care than older ones, audit finds
Authors: S. Mayor
Journal: BMJ (2014)

<h3>Background</h3> Patients with adrenal insufficiency are required to follow ‘steroid sick day rules’ in illness or stress. Failure to do so, in particular delays in administering intramuscular (IM) hydrocortisone (HC), may precipitate a potentially fatal adrenal crisis. An audit comparing published standards to local patient education on steroid sick day rules was undertaken in 2015, prompted by two local mortality cases related to adrenal insufficiency. Questionnaires were distributed to families for baseline data collection. Subsequent interventions included introducing ‘red flags’ on the electronic patient record and introducing age-banded refresher teaching sessions for families, run by staff, with patient/carer peer support opportunities. <h3>Aims</h3> To evaluate the impact of the teaching intervention on carer knowledge and confidence around IM HC injections. <h3>Methods</h3> Questionnaires were then redistributed to families four years later (2019). Questionnaires involved binary responses for factual questions, five-point Likert scale for opinion-based questions, and a free-text box for further comments. <h3>Results</h3> Response rate was 94% (49/52) in the first audit cycle (C1), where questionnaires were distributed after clinic appointments. Response rate was 36% (39/109) in the second audit cycle (C2), with mail distribution, perhaps reflecting this change. With particular focus on the IM HC injection, in C1, 53% (n=26) received written information on IM HC injections, increasing to 69% (n=26) in C2. Similarly, 61% (n=30) were ‘very confident’ or ‘somewhat confident’ in C1 about when to give IM HC injection, increasing to 72% (n=28) in C2. Respondents recalled demonstration on IM HC administration in 90% (n=44) in C1 and 92% (n=35) in C2. In C1 46% (n=22) were ‘very confident’ or ‘somewhat confident’ with how to give IM HC, increasing to 63% (n=24) in C2. Families have given very positive feedback, and value the opportunity to engage in peer support. There have been no further deaths in our region over the last 4 years relating to adrenal insufficiency. <h3>Conclusion</h3> Following introduction of the refresher teaching sessions, there is a significant increase in confidence and knowledge on administration of the potentially lifesaving IM HC injection. This reflects the positive impact of a patient centred quality improvement initiative. Further work will be done to integrate these sessions into standard care.
A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition
Authors: Santiago Ropero, Mario F Fraga, Esteban Ballestar, Richard Hamelin, Hiroyuki Yamamoto, Manuel Boix-Chornet, Rosalia Caballero, Miguel Alaminos, Fernando Setien, Maria F Paz, Michel Herranz, Jose Palacios, Diego Arango, Torben F Orntoft, Lauri A Aaltonen, Simó Schwartz, Manel Esteller
Journal: Nature Genetics (2006)
Abstract A62: Phosphorylation of Ser205 by the protein kinase CK2 persists on Pax3-FOXO1, but not Pax3, throughout myogenic differentiation
Authors: Kevin N. Dietz, Patrick J. Miller, Andrew D. Hollenbach
Journal: Cancer Research (2009)

Abstract The myogenic transcription factor Pax3 plays an essential role in early skeletal muscle development and is a key component in Alveolar rhabdomyosarcoma (ARMS), a childhood solid muscle tumor. ARMS, which is associated with a four year survival rate of only 17%, is most commonly characterized by a t(2;13) chromosomal translocation resulting in the fusion of the 5′ Pax3 sequences to the 3′ FOXO1 sequences to encode the oncogenic fusion protein, Pax3-FOXO1. Posttranslational modifications such as phosphorylation are common mechanisms by which transcription factors are regulated. Consistent with this fact, we demonstrated in a previous report that Pax3 is phosphorylated on Ser205 in proliferating, but not differentiated, primary myoblasts. However, the kinase that mediates this phosphorylation event has yet to be identified. More recently it was demonstrated that Pax3-FOXO1 is also phosphorylated at unidentified sites in non-physiologically relevant cells. Despite this information, it is not known whether Pax3-FOXO1 is phosphorylated at Ser205 or how the phosphorylation of the fusion protein changes during myogenic differentiation. In this report, we use standard in vitro kinase assays to identify CK2 (formerly termed “casein kinase II”) as the kinase responsible for phosphorylating Pax3 and Pax3-FOXO1 at Ser205 in proliferating mouse primary myoblasts. Furthermore, we use standard Western blot analysis to demonstrate that in contrast to wild-type Pax3, phosphorylation at Ser205 persists on Pax3-throughout early myogenic differentiation. Finally, we use standard Western blot analysis to show that Pax3-FOXO1 is phosphorylated at Ser205 in a variety of translocation-containing ARMS cell lines. The results presented in this report not only suggest a possible mechanism by which the disregulation of Pax3-FOXO1 may contribute to tumorigenesis, but also identifies a novel target for the development of therapies to be used for the treatment of ARMS. Citation Information: Cancer Res 2009;69(23 Suppl):A62.
Insulin: Sixty Years of Use
Authors: Errol B. Marliss
Journal: New England Journal of Medicine (1982)

January 11, 1982, was the sixtieth anniversary of the first injection of exogenous insulin into a diabetic person. The discovery of insulin, credited to two University of Toronto scientists, Frederick G. Banting and Charles H. Best, was reported to the scientific community late in 1921, and the first patients began to receive pancreatic extracts in early 1922. Elsewhere in this issue of the Journal, Burrow et al.1 provide a report of that historic first case, which is instructive in many ways. First of all, the hypoglycemic effect of the extracts in diabetic patients was established (although Banting and Best . . .