tbuckley/cabot-search huggingface dataset:
Effects of platelet-modifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition.
Authors: S R Hanson, L A Harker, T D Bjornsson
Journal: Journal of Clinical Investigation (1985)

To resolve questions of drug actions, efficacy, and interactions for platelet-modifying agents used clinically, we have compared the relative capacities and mechanisms of aspirin, dipyridamole, sulfinpyrazone, and dazoxiben to prevent arterial thromboembolism in a baboon model. In 136 studies the agents were given twice daily by oral administration both singly and in combination. The antithrombotic efficacy of a given therapy was determined by its capacity to interrupt steady-state platelet utilization induced by thrombogenic arteriovenous cannulae. When given alone, dipyridamole and sulfinpyrazone reduced the rate at which platelets were utilized by thrombus formation in a dose-dependent manner with essentially complete interruption by dipyridamole at 10 mg/kg per d. In contrast, neither aspirin (2-100 mg/kg per d) nor dazoxiben (20-100 mg/kg per d) decreased cannula platelet consumption detectably despite the striking reduction in the capacity of platelets to produce thromboxane B2. However, aspirin, but not dazoxiben, potentiated the antithrombotic effects of dipyridamole and sulfinpyrazone in a dose-dependent fashion without changing the pharmacokinetics for any of the agents. Complete potentiation required aspirin at 20 mg/kg per d to be given with each dose of dipyridamole. Because dazoxiben's blockade of platelet thromboxane A2 production was not associated with antithrombotic potentiation, and because complete potentiation by aspirin required a dose that fully inhibited vascular production of prostaglandin I2 (PGI2), we conclude that aspirin's potentiating effect on dipyridamole is independent of PGI2 production or inhibition of thromboxane A2 formation. In addition, because frequent repeated and synchronous dosing of aspirin was necessary, aspirin's potentiating effects appear to be produced by mechanism(s) unrelated to its potent, irreversible inhibition of platelet cyclooxygenase.
A New Cell-penetrating Peptide That Blocks the Autoinhibitory XIP Domain of NCX1 and Enhances Antiporter Activity
Authors: Pasquale Molinaro, Anna Pannaccione, Maria José Sisalli, Agnese Secondo, Ornella Cuomo, Rossana Sirabella, Maria Cantile, Roselia Ciccone, Antonella Scorziello, Gianfranco di Renzo, Lucio Annunziato
Journal: Molecular Therapy (2014)

The plasma membrane Na(+)/Ca(2+) exchanger (NCX) is a high-capacity ionic transporter that exchanges 3Na(+) ions for 1Ca(2+) ion. The first 20 amino acids of the f-loop, named exchanger inhibitory peptide (XIP(NCX1)), represent an autoinhibitory region involved in the Na(+)-dependent inactivation of the exchanger. Previous research has shown that an exogenous peptide having the same amino acid sequence as the XIP(NCX1) region exerts an inhibitory effect on NCX activity. In this study, we identified another regulatory peptide, named P1, which corresponds to the 562-688aa region of the exchanger. Patch-clamp analysis revealed that P1 increased the activity of the exchanger, whereas the XIP inhibited it. Furthermore, P1 colocalized with NCX1 thus suggesting a direct binding interaction. In addition, site-directed mutagenesis experiments revealed that the binding and the stimulatory effect of P1 requires a functional XIP(NCX1) domain on NCX1 thereby suggesting that P1 increases the exchanger activity by counteracting the action of this autoinhibitory sequence. Taken together, these results open a new strategy for developing peptidomimetic compounds that, by mimicking the functional pharmacophore of P1, might increase NCX1 activity and thus exert a therapeutic action in those diseases in which an increase in NCX1 activity might be helpful.
EXPERIMENTS ON THE EPIDEMIOLOGY OF PSEUDORABIES
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1935)

Study of the pseudorabies virus-neutralizing antibody content of pooled and individual samples of swine serum have led to the conclusion that pseudorabies is a highly prevalent, unrecognized, disease in middle western hogs. It has been shown that wild brown rats develop a fatal infection following ingestion of pseudorabies virus and that their carcasses, in turn, give rise to the disease in swine to which they are fed. It is believed that rats play a rôle in the epidemiology of porcine pseudorabies, serving as the initial source of infection for a swine herd and also as one means by which virus can be spread from farm to farm in swine herds. The experiments presented furnish further evidence that swine may serve as the source of infection for cattle.
Copper Chelation Enhances Antitumor Efficacy and Systemic Delivery of Oncolytic HSV
Authors: Ji Young Yoo, Jason Pradarelli, Amy Haseley, Jeffrey Wojton, Azeem Kaka, Anna Bratasz, Christopher A. Alvarez-Breckenridge, Jun-Ge Yu, Kimerly Powell, Andrew P. Mazar, Theodoros N. Teknos, E. Antonio Chiocca, Joseph C. Glorioso, Matthew Old, Balveen Kaur
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Copper in serum supports angiogenesis and inhibits replication of wild-type HSV-1. Copper chelation is currently being investigated as an antiangiogenic and antineoplastic agent in patients diagnosed with cancer. Herpes simplex virus–derived oncolytic viruses (oHSV) are being evaluated for safety and efficacy in patients, but several host barriers limit their efficacy. Here, we tested whether copper inhibits oHSV infection and replication and whether copper chelation would augment therapeutic efficacy of oHSV. Experimental Design: Subcutaneous and intracranial tumor-bearing mice were treated with oHSV ± ATN-224 to evaluate tumor burden and survival. Virus replication and cell killing was measured in the presence or absence of the copper chelating agent ATN-224 and in the presence or absence of copper in vitro. Microvessel density and changes in perfusion were evaluated by immunohistochemistry and dynamic contrast enhanced MRI (DCE-MRI). Serum stability of oHSV was measured in mice fed with ATN-224. Tumor-bearing mice were injected intravenously with oHSV; tumor burden and amount of virus in tumor tissue were evaluated. Results: Combination of systemic ATN-224 and oHSV significantly reduced tumor growth and prolonged animal survival. Immunohistochemistry and DCE-MRI imaging confirmed that ATN-224 reduced oHSV-induced blood vessel density and vascular leakage. Copper at physiologically relevant concentrations inhibited oHSV replication and glioma cell killing, and this effect was rescued by ATN-224. ATN-224 increased serum stability of oHSV and enhanced the efficacy of systemic delivery. Conclusion: This study shows that combining ATN-224 with oHSV significantly increased serum stability of oHSV and greatly enhanced its replication and antitumor efficacy. Clin Cancer Res; 18(18); 4931–41. ©2012 AACR.
Adjuvant trastuzumab for breast cancer: Assessing HER2/neu status incurs more costs for treatment
Authors: Malcolm R Kell, Colm P Power
Journal: BMJ (2005)

Adjuvant trastuzumab for breast cancer Assessing HER2/neu status incurs more costs for treatmentEditor-The results of recent trials are likely to continue to fuel the demand for trastuzumab in the adjuvant setting of early breast cancer, 1 as well as a possible neoadjuvant treatment in the near future.However, Dent and Clemons did not discuss the difficulty in obtaining accurate and reproducible assessment of HER2/neu gene overexpression.Immunohistochemical testing measures HER2/neu protein expression whereas in situ hybridisation measures gene amplification.Patients with equivocal immunohistochemical results require in situ hybridisation to determine definitive status because interobserver variability using immunohistochemical testing is appreciable.At least 20% of patients with positive immunohistochemical results will be truly negative for HER2/neu gene amplification; these patients would not benefit from trastuzumab. 2 These difficulties in assessing HER2/ neu status have been encountered in studies testing trastuzumab, and in situ hybridisation testing has been used as the gold standard. 3 As the clinical utility of trastuzumab widens guidelines on HER2/neu testing must be clear to ensure appropriate use of trastuzumab.Clearly this testing will incur additional costs to trastuzumab treatment.
Combined Effect of Sodium Warfarin and Phenylbutazone
Authors: Milton J. Eisen
Journal: JAMA (1964)

IN THE COURSE of long-term ambulatory management of cardiac patients with an anticoagulant, sodium warfarin, five individuals also received phenylbutazone for various arthritic manifestations. In all patients a significant dramatic increase in the prothrombin time was observed, at times accompanied by hemorrhagic episodes. In each case, the unexpected effects occurred rapidly at the end of the usual course of treatment with 200 to 300 mg of phenylbutazone daily for five to seven days. A relationship of phenylbutazone to some factors of the coagulation mechanism has been suggested by several investigators, though the available reports do not support consistently positive ideas. For example, Humble<sup>1</sup>stated that the clotting of blood was diminished by phenylbutazone alone, but that the prothrombin time was also lengthened in 30% of the patients receiving this drug. In two individuals it was prolonged as much as two minutes. These findings have not been duplicated by other
Cost-effectiveness of Alternative Triage Strategies for Atypical Squamous Cells of Undetermined Significance
Authors: Jane J. Kim
Journal: JAMA (2002)

ContextEvery year approximately 2 million US women are diagnosed as having a cervical cytological result of atypical squamous cells of undetermined significance (ASC-US).Objective To determine the most efficient and cost-effective management strategy for women in the United States diagnosed as having ASC-US. Design and SettingCost-effectiveness analysis of data from clinical trials, prospective studies, and other published literature.A computer-based model was used to compare 4 management strategies for a cytological result of ASC-US: immediate colposcopy; human papillomavirus (HPV) triage, which includes colposcopy if high-risk HPV types are detected; repeat cytology, which includes follow-up cytology at 6 and 12 months and referral for colposcopy if a repeat abnormal result occurs; and reclassifying ASC-US as normal in which a cytological result of ASC-US is ignored.Reflex HPV DNA testing uses either residual liquid-based cytological specimens or samples cocollected at the time of the initial screening for conventional cytology.Another method, referred to as the 2-visit HPV DNA triage, requires a woman with an ASC-US result to return within 1 month to provide another speciman sample.Main Outcome Measures Years of life saved (YLS), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. ResultsThe least costly strategy for biennial screening was to reclassify ASC-US as normal, resulting in a reduction in total cancer incidence of 75% for conventional cytology and 84% for liquid-based cytology compared with no screening.The next least costly strategy was HPV DNA testing resulting in a reduction in total cancer incidence of 86% for conventional cytology and 90% for liquid-based cytology, followed by immediate colposcopy with a reduction of 87% and 91%, respectively.Compared with reflex HPV DNA testing, a strategy of repeat cervical cytology or delayed HPV testing costs more but is less effective.When all strategies were compared simultaneously, varying frequency and type of cytological test, biennial (vs every 3 years) liquid-based cytology with reflex HPV testing had a cost of $174200 per YLS.In a similar comparison, liquid-based cytology with reflex HPV testing conducted every 3 years (vs every 5 years) had a cost of $59600 per YLS and was more effective and less costly than a strategy of conventional cytology incorporating repeat cytology or immediate colposcopy conducted biennially. ConclusionReflex HPV DNA testing provides the same or greater life expectancy benefits and is more cost-effective than other management strategies for women diagnosed as having ASC-US.
Body weight and arterial hypertension.
Authors: E. O'Brien, K. O'Malley
Journal: BMJ (1989)

except in a hope that domiciliary fetal monitoring will promote more rational and convenient moni- toring policies.56We agree that there is a risk of overuse,4 and we are sure the debate on the value of antenatal cardiotocographs and the mission to deliver healthy babies should continue in the widest context.Meanwhile, we fully support any call for further evaluation of domiciliary fetal monitoring, and we have recently embarked on a major collaborative research programme in the south Wales valleys.This new application is potentially useful and deserves a fair hearing.
Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging.
Authors: D Dardevet, C Sornet, D Taillandier, I Savary, D Attaix, J Grizard
Journal: Journal of Clinical Investigation (1995)

We studied glucocorticoid-induced muscle wasting and subsequent recovery in adult (7-mo-old) and old (22-mo-old) rats, since the increased incidence of various disease states may result in glucocorticoids hypersecretion in aging. Adult and old rats received dexamethasone in their drinking water and were then allowed to recover. Muscle wasting occurred more rapidly in old rats and the recovery of muscle mass was impaired, suggesting that glucocorticoids may be involved in the emergence of muscle atrophy with advancing age. According to measurements in incubated epitrochlearis muscles, dexamethasone-induced muscle wasting mainly resulted from increased protein breakdown in the adult, but from depressed protein synthesis in the aged animal. Increased expression of cathepsin D, m-calpain, and ubiquitin was observed in the muscles from both dexamethasone-treated adult and old rats. By contrast, the disappearance of the stimulatory effect of glucocorticoids on protein break-down in aging occurred along with a loss of ability of steroids to enhance the expression of the 14-kD ubiquitin carrier protein E2, which is involved in protein substrates ubiquitinylation, and of subunits of the 20 S proteasome (the proteolytic core of the 26 S proteasome that degrades ubiquitin conjugates). Thus, if glucocorticoids play any role in the progressive muscle atrophy seen in aging, this is unlikely to result from an activation of the ubiquitin-proteasome proteolytic pathway.
P1-180: Protein expression and gene amplification of epidermal growth factor receptor in non:small cell lung cancer: correlation with chemoresponse to gefitinib therapy
Authors: Jinyoung Yoo, Sonya Y. Park, Byoung Y. Shim, Sung W. Kim, Deog G. Cho, Myeong I. Ahn, Chi H. Kim, Kyu Cho, Hoon K. Kim
Journal: Journal of Thoracic Oncology (2007)
Dermatomyositis and metastatic malignant melanoma, with complete regression of the primary lesion
Authors: G. Sais, I. Marcoval, A. Jucgla, N. Curgo, O. Servitje
Journal: British Journal of Dermatology (1994)

Journal Article Dermatomyositis and metastatic malignant melanoma, with complete regression of the primary lesion Get access G. Sais, G. Sais Department of Dermatology, Hospital Princeps D'Espanya, Feixa Llarga, s/n. 08907 Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar I. Marcoval, I. Marcoval Department of Dermatology, Hospital Princeps D'Espanya, Feixa Llarga, s/n. 08907 Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Jucgla, A. Jucgla Department of Dermatology, Hospital Princeps D'Espanya, Feixa Llarga, s/n. 08907 Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar N. Curgo, N. Curgo Department of Dermatology, Hospital Princeps D'Espanya, Feixa Llarga, s/n. 08907 Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar O. Servitje O. Servitje Department of Dermatology, Hospital Princeps D'Espanya, Feixa Llarga, s/n. 08907 Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 6, 1 June 1994, Pages 796–797, https://doi.org/10.1111/j.1365-2133.1994.tb03424.x Published: 01 June 1994
London Edition of NEJM
Authors: F. J. Ingelfinger
Journal: New England Journal of Medicine (1973)

The Journal is written everywhere (well, perhaps not in Tristan da Cunha or Komsomolets), raked and assembled in Boston, but printed in and mailed from Chicago. The indefatigable but not always infallible printer (American Can Company — Printing Division) has in his 10 years of association with the Journal invariably mailed every issue on time — i.e., two or three days before the official Thursday date displayed on the cover. North American subscribers, therefore, may occasionally receive an issue on Wednesday, but Thursday through Saturday is more likely, and even after the weekend is possible. It all depends on the . . .
Diagnosis of cystinosis from a bone marrow aspirate
Authors: Abbas Hashim Abdulsalam, Mohammed Haseb Khamis, Barbara J. Bain
Journal: American Journal of Hematology (2012)

A bone marrow aspirate was performed to investigate the pancytopenia and revealed numerous clear cystine crystals, apparently free and within macrophages (images). This rare lysosomal storage disease is readily diagnosed from a bone marrow aspirate because of the presence of distinctive non-staining crystals. The crystals have straight edges and, when seen end on, are hexagonal (lower image).
Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial
Authors: Heinz Gisslinger, Mirjana Gotic, Jerzy Holowiecki, Miroslav Penka, Juergen Thiele, Hans-Michael Kvasnicka, Robert Kralovics, Petro E. Petrides
Journal: Blood (2013)
Visual and Auditory Neurotoxicity in Patients Receiving Subcutaneous Deferoxamine Infusions
Authors: Nancy F. Olivieri, J. Raymond Buncic, Emily Chew, Tsvi Gallant, Robert V. Harrison, Nancy Keenan, William Logan, David Mitchell, Geri Ricci, Barry Skarf, Margot Taylor, Melvin H. Freedman
Journal: New England Journal of Medicine (1986)

Of 89 patients receiving nightly subcutaneous deferoxamine for transfusion-dependent thalassemia major or Diamond-Blackfan anemia, 13 presented with visual loss or deafness of acute onset or both. Detailed ophthalmologic, audiologic, and evoked-potential studies uncovered abnormalities caused by neurotoxicity in 27 more. Four patients with visual loss had optic neuropathy, with a marked decrease in acuity, loss of color vision, and delayed visual evoked potentials. Five asymptomatic patients had changes in the pigment of the retinal epithelium. The hearing loss was characterized by a high-frequency sensorineural deficit, which necessitated hearing aids in six patients. When deferoxamine was stopped, recovery of vision was complete in 2 patients and partial in 2, and in 22 patients with abnormal audiograms, reversal of the hearing deficit was complete in 4 and partial in 1. An analysis of the clinical data showed that members of the affected group were younger, had lower serum ferritin values, and were self-administering higher doses of deferoxamine per kilogram of body weight. Significantly lower doses of deferoxamine were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged evoked potentials (P less than 0.001, less than 0.006, and less than 0.04, respectively). The data implicate high-dose deferoxamine as a central factor in the pathogenesis of the neurotoxicity. We strongly recommend careful regulation of the deferoxamine dosage and serial audiovisual monitoring in all patients receiving the drug.
Thrombus Formation on a Transvenous Pacemaker Electrode
Authors: James J. Sidd, Lawrence I. Stellar, Paul F. Gryska, Arthur E. O'Dea
Journal: New England Journal of Medicine (1969)

THROMBOEMBOLISM has not been a clinical problem after insertion of transvenous pacemaker electrodes despite the presence of an intracardiac foreign body. This report documents the presence of a large thrombus on the electrode, with subsequent pulmonary infarction.Case ReportB.P. (N.W. 68–15885), a 74-year-old woman with intermittent 2nd-degree heart block for 3 years, was admitted to the hospital because of syncopal episodes during the preceding month. On the 3d hospital day complete heart block with a ventricular rate of 25 per minute developed. A permanent demand transvenous pacemaker electrode§ was positioned at the apex of the right ventricle. Episodes of . . .
Detection of Entamoeba histolytica by Fluorescent Microscopy
Authors: T. Doxiades, N. Candreviotis
Journal: BMJ (1962)

Securing pensions relates to careful planning, which in turn requires adequate predictions. Among the many factors in an increasingly globalized world that impede adequate predictions is the factor of migrant flows. To date, most pension models do not consider migrant worker cohort flows. This has critical implications, particularly for pension planning in small open economies with a high inflow and outflow of migrant workers. To close that gap, the article provides a highly innovative model that considers not only population aging but also the cohort of cross-border workers and their entitlement to a partial pension in the future. It is doing that through forecasting pension cohorts annually for the native population, cross-border workers, and net migrations. Based on demographic variables, the article develops an enabling framework for policymakers. This framework outlines a set of scenarios for the long-term sustainability of pension systems in small open economies. The framework also offers important insights for larger economies with high levels of migrant flows. <b>TOPICS:</b>Pension funds, emerging markets, retirement
A burning question
Authors: Theodore Dalrymple
Journal: BMJ (2007)

Great works of literature have meanings beyond the most obvious, and judged by this standard Max Frisch's play The Fire Raisers is a great work. Frisch was a Swiss who worked for a number of years as an architect before turning full time to writing. No doubt unfairly, we do not normally associate the Swiss with literature: who ever uses the phrase “Swiss literature,” for example? Nor do we expect the best societies always to produce the best literature; for what is good for people is not necessarily good for writing.

In The Fire Raisers , an entire town is subject to a rash of arson attacks, so that everyone is terrified by the prospect of further attacks. The action of the play takes place in the …
Marginal Ulcer After Subtotal Gastrectomy—A Medical or Surgical Problem?
Authors: Theodore Balsam
Journal: JAMA (1963)

In the belief that marginal ulcer that develops after subtotal gastrectomy is a distinct clinical entity, a study that evaluates the medical versus the surgical management of this disease was undertaken. Sixty-four patients with marginal ulcer were followed-up through a 10-year period. Most of the patients were managed on medical therapy alone. Seven of the 28 patients operated on represented medical failures. There was one surgical death and a recurrence of symptoms in nine of the 28 patients operated upon for marginal ulcer. In the medically treated group there was no mortality nor major morbidity such as gastrojejunocolic fistulas. We suggest that a reappraisal of the management of marginal ulcer after sub-total gastrectomy is in order.