tbuckley/cabot-search huggingface dataset:
Altered Tissue 3′-Deoxy-3′-[18F]Fluorothymidine Pharmacokinetics in Human Breast Cancer following Capecitabine Treatment Detected by Positron Emission Tomography
Authors: Laura M. Kenny, Kaiyumars B. Contractor, Justin Stebbing, Adil Al-Nahhas, Carlo Palmieri, Sami Shousha, R. Charles Coombes, Eric O. Aboagye
Journal: Clinical Cancer Research (2009)

We showed in preclinical models that thymidylate synthase (TS) inhibition leads to redistribution of the nucleoside transporter, ENT1, to the cell membrane and hence increases tissue uptake of [(18)F]fluorothymidine (FLT). In this study, we assessed for the first time the altered pharmacokinetics of FLT in patients following administration of capecitabine, a drug whose mode of action has been reported to include TS inhibition.We analyzed 10 lesions from six patients with breast cancer by positron emission tomography before and after treatment with capecitabine. Although drug treatment did not alter tumor delivery pharmacokinetic variables (K1 and permeability product surface area) or blood flow, tumor FLT retention variables increased with drug treatment in all but one patient.The baseline average standardized uptake value at 60 minutes, rate constant for the net irreversible transfer of radiotracer from plasma to tumor (Ki), and unit impulse response function at 60 minutes were 11.11 x 10(-5) m(2)/mL, 4.38 x 10(-2) mL plasma/min/mL tissue, and 4.93 x 10(-2)/min, respectively. One hour after capecitabine administration, the standardized uptake value was 13.55 x 10(-5) m(2)/mL (P = 0.004), Ki 7.40 x 10(-2) mL plasma/min/mL tissue (P = 0.004), and impulse response function was 7.40 x 10(-2)/min (P = 0.002). FLT pharmacokinetics did not change in normal tissues, suggesting that the effect was largely restricted to tumors (P = 0.55).We have identified FLT positron emission tomography retention parameters that could be used in future early clinical studies to measure the pharmacodynamics of TS inhibitors, as well as for identifying patients who are unlikely to benefit from TS inhibition.
Metabolism of <sup>14</sup>C‐Histamine Given Intrabronchially to Asthmatic Patients
Authors: G. Granerus, J. Bergmark, O. Löwhagen, G. Thiringer
Journal: Allergy (1980)

14 C‐histamine was administered intrabronchially to asthmatic patients and controls. The urinary excretion of total radioactivity, 14 C‐histamine and its radioactive metabolites was measured. It was found that the excretion of total radioactivity was complete within 24 h. The excretion rate was equal to that observed after intravenous injection of 14 C‐histamine, indicating a rapid penetration of the bronchial mucosa. However, the diuresis seemed to be of importance for the excretion rate. Histamine inactivation by methylation was more pronounced after intrabronchial than after intravenotis administration.
THE RELATION OF ATTITUDE TOWARD MEDICATION TO TREATMENT OUTCOMES IN CHEMOTHERAPY
Authors: DONALD R. GORHAM, LEWIS J. SHERMAN
Journal: American Journal of Psychiatry (1961)

An Attitude Toward Medication Scale was administered before and after treatment to 369 patients in a large-scale chemotherapy study. The hypothesis that the attitude of patients toward medication has an important bearing on treatment effect was not upheld with this population of chronic, apathetic schizophrenics. Medication attitude, however, was significantly related to a cluster of symptoms that tend to characterize paranoid schizophrenics indicating that the more paranoid the patient, the less faith he had that he might be helped by medication.
The Urge to Find Out
Authors: Albert H. Coons
Journal: JAMA (1962)

THE PASSANO AWARD has been bestowed in the past on men chosen with so much jealous care that their names are well-known to every student of medicine. I accept it this year with humble thanks, remembering that such occasions celebrate the whole company of questing men and women. The heady perfume of praise will not intoxicate if breathed cautiously in honor of collective achievement. I would like to recall the names of some of my colleagues who contributed greatly to the accomplishment, and to the spirit of the laboratory where the early work on fluorescent antibody was carried out. I have already recorded my debt to some of them in another place, but it is fitting that they should also be recorded here. First of all, there is Hugh Creech, an organic chemist, now the head of the Laboratory of Chemotherapy of the Institute for Cancer Research in Philadelphia. In
Hyperthermia-triggered intracellular delivery of anticancer agent to HER2+ cells by HER2-specific affibody (ZHER2-GS-Cys)-conjugated thermosensitive liposomes (HER2+ affisomes)
Authors: Brandon Smith, Ilya Lyakhov, Kristin Loomis, Danielle Needle, Ulrich Baxa, Amichai Yavlovich, Jacek Capala, Robert Blumenthal, Anu Puri
Journal: Journal of Controlled Release (2011)
New expert group agrees plan to analyse full data on oseltamivir
Authors: Z. Kmietowicz
Journal: BMJ (2013)

A multidisciplinary group of scientific experts has developed a plan to analyse data on the influenza drug oseltamivir (Tamiflu) that they hope will provide answers to whether current guidelines on its use need to be amended.

The Multiparty Group for Advice on Science (MUGAS) met for the first time in Brussels on 18 June. It was initiated by four academics: Ab Osterhaus, head of the Institute of Virology at Erasmus MC University in Rotterdam, who also works as a scientific adviser to Roche; Arnold Monto, professor of epidemiology at the University of Michigan; Menno de Jong, of Amsterdam’s Institute for Global Health and Development; and Rich Whitley, from the University …
Evidence of hydrogen ion secretion from the human gall bladder in vitro.
Authors: J N Plevris, P C Hayes, D J Harrison, I A Bouchier
Journal: Gut (1992)

Gall bladder bile is more acid that hepatic bile and this has been attributed to bicarbonate absorption by the gall bladder epithelium. The aim of this study was to investigate in vitro the acid base changes that occur across the human gall bladder mucosa. Fresh gall bladder tissue was obtained at cholecystectomy and placed in an Ussing Chamber and perfused with Ringer-Krebs glucose bicarbonate solution. The viability of the gall bladder was assessed by measuring the potential differences across the epithelium and by the morphology of the epithelial cells at the end of the experiments. Aliquots from the solutions were taken at two, 45 and 70 minutes and pCO2, hydrogen ion and bicarbonate concentrations were measured. In the mucosal side of the chamber a consistent and significant decrease was observed from two minutes to 70 minutes in bicarbonate concentration while pCO2 and hydrogen ion concentrations significantly increased. The degree of inflammation correlated well with the ability for acidification, the more inflamed the tissue the less its ability to acidify. When the gall bladder was exposed to amiloride or sodium free solution acidification was abolished in the mucosal side. When tissue metabolism was irreversibly inhibited by exposure to formaldehyde, hydrogen ion concentration and pCO2 were significantly decreased in the mucosal side of the chamber compared with the viable gall bladder. The human gall bladder is capable of secreting acid and this may be an important mechanism for preventing calcium precipitation and gall stone formation.
The effect of substituted sydnonimines on coronary smooth muscle relaxation and cyclic guanosine monophosphate levels.
Authors: G Rinaldi, H Cingolani
Journal: Circulation (1983)

In vitro experiments on precontracted canine coronary arteries were performed to study the direct relaxant effects of molsidomine (MOLS) and its active metabolite, SIN-1, and to determine if there is a relationship between effect and cGMP level elevations. The effects of MOLS and SIN-1 were compared with those of a classic vasodilator, nitroglycerin (NTG). At equimolar doses (10(-6)M) SIN-1 exerted greater relaxant effect than NTG (80 +/- 2% and 60 +/- 5%, respectively) in spite of the fact that it produced less of an increase in cyclic guanosine monophosphate (cGMP) levels. cGMP levels fell rapidly after they peaked, but relaxation was maintained. cGMP elevation preceded the induction of relaxation by NTG but not that induced by SIN-1. Relaxation occurred faster after NTG than after SIN-1. Since SIN-1 has a greater relaxant effect than NTG in spite of the fact that SIN-1 induces less of an increase in cGMP levels and the fact that the peak elevation does not precede the onset of relaxation, the causal nexus between GMP level elevation and relaxation effect after sydnonimines should be challenged.
Whose Death Is It, Anyway
Authors: Shimon Glick
Journal: Annals of Internal Medicine (1997)

Letters1 April 1997Whose Death Is It, AnywayShimon Glick, MDShimon Glick, MDBen-Gurion University Faculty of Health Sciences, Beer Sheva 84105, IsraelSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-7-199704010-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Elisabeth Hansot's sad tale [1] and Gilligan and Raffin's incisive analysis [2] were most moving. But may I suggest that all might have decided too hastily that the mother's death was justified? It seems plausible that failures in communication as well as problematic therapy may have contributed to the patient's premature death, as well as to unnecessary suffering on the part of mother and daughter.How often can one be so confident within the first 24 hours to predict lack of recovery, need for a permanent tracheostomy, and need for placement in a nursing home? Such a ...References1. Hansot E. A letter from a patient's daughter. Ann Intern Med. 1996; 125:149-51. Google Scholar2. Gilligan T, Raffin TA. Whose death is it, anyway? Ann Intern Med. 1996; 125:137-41. Google Scholar Author, Article, and Disclosure InformationAuthors: Shimon Glick, MDAffiliations: Ben-Gurion University Faculty of Health Sciences, Beer Sheva 84105, Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1997Volume 126, Issue 7Page: 586-587KeywordsNursing homesSedationStrokeTracheostomy ePublished: 15 August 2000 Issue Published: 1 April 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dual developmental role of transcriptional regulator Ets1 in Xenopus cardiac neural crest vs. heart mesoderm
Authors: Shuyi Nie, Marianne E. Bronner
Journal: Cardiovascular Research (2015)

Ets1 is an important transcription factor that is expressed in both the cardiac neural crest (NC) and heart mesoderm of vertebrate embryos. Moreover, Ets1 deletion in humans results in congenital heart abnormalities. To clarify the functional contributions of Ets1 in cardiac NC vs. heart mesoderm, we performed tissue-targeted loss-of-function analysis to compare the relative roles of Ets1 in these two tissues during heart formation using Xenopus embryos as a model system. We confirmed by in situ hybridization analysis that Ets1 is expressed in NC and heart mesoderm during embryogenesis. Using a translation-blocking antisense morpholino to knockdown Ets1 protein selectively in the NC, we observed defects in NC delamination from the neural tube, collective cell migration, as well as segregation of NC streams in the cranial and cardiac regions. Many cardiac NC cells failed to reach their destination in the heart, resulting in defective aortic arch artery formation. A different set of defects was noted when Ets1 knockdown was targeted to heart mesoderm. The formation of the primitive heart tube was dramatically delayed and the endocardial tissue appeared depleted. As a result, the conformation of the heart was severely disrupted. In addition, the outflow tract septum was missing, and trabeculae formation in the ventricle was abolished. Our study shows that Ets1 is required in both the cardiac NC and heart mesoderm, albeit for different aspects of heart formation. Our results reinforce the suggestion that proper interaction between these tissues is critical for normal heart development.
Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood
Authors: Stanislas Faguer, Stéphane Decramer, Nicolas Chassaing, Christine Bellanné-Chantelot, Patrick Calvas, Sandrine Beaufils, Lucie Bessenay, Jean-Philippe Lengelé, Karine Dahan, Pierre Ronco, Olivier Devuyst, Dominique Chauveau
Journal: Kidney International (2011)
Expression levels of parvalbumins determine allergenicity of fish species
Authors: U. Griesmeier, S. Vázquez‐Cortés, M. Bublin, C. Radauer, Y. Ma, P. Briza, M. Fernández‐Rivas, H. Breiteneder
Journal: Allergy (2009)

Parvalbumins are the most important fish allergens. Polysensitization to various fish species is frequently reported and linked to the cross-reactivity of their parvalbumins. Studies on cross-reactivity and its association to the allergenicity of purified natural parvalbumins from different fish species are still lacking. In addition, some studies indicate that dark muscled fish such as tuna are less allergenic.Total protein extracts and purified parvalbumins from cod, whiff, and swordfish, all eaten frequently in Spain, were tested for their IgE-binding properties with 16 fish allergic patients' sera from Madrid. The extent of cross-reactivity of these parvalbumins was investigated by IgE ELISA inhibition assays. Additionally, the cDNA sequences of whiff and swordfish parvalbumins were determined.Extractable amounts of parvalbumins from cod were 20 times and from whiff 30 times higher than from swordfish. Parvalbumins were recognized by 94% of the patients in extracts of cod and whiff, but only by 60% in swordfish extracts. Nevertheless, a high cross-reactivity was determined for all purified parvalbumins by IgE inhibition. The amino acid sequence identities of the three parvalbumins were in a range of 62-74%.The parvalbumins of cod, whiff and swordfish are highly cross-reactive. The high amino acid sequence identity among cod, whiff and swordfish parvalbumins results in the observed IgE cross-reactivity. The low allergenicity of swordfish is due to the low expression levels of its parvalbumin.
p21<sup>Waf1/Cip1</sup>revisited: oncogenic function in hepatocellular carcinoma
Authors: Daniel Goldenberg, Robert Eferl
Journal: Gut (2013)

p21Waf1/Cip1 was originally identified as a crucial p53-regulated factor that controls cyclin-dependent kinase 1/2 (CDK1/CDK2) activities and sequesters proliferating cell nuclear antigen. The physical interaction with CDKs prevents binding and phosphorylation of retinoblastoma proteins which is required for the release of E2F transcription factors important for S-phase progression. Consequently, p21Waf1/Cip1 was classified as a tumour suppressor that interferes with cell cycle progression and DNA synthesis.1 ,2 Meanwhile, it has been realised that p21Waf1/Cip1 has a plethora of alternative functions in apoptosis, differentiation, migration, DNA repair, gene regulation, stem cell renewal and oncogenesis.1 ,2 Most of these functions are regulated in a dual and p53-independent manner. Cell proliferation is not exclusively inhibited but can also be promoted by p21Waf1/Cip1 when it is present at certain threshold concentrations. During apoptosis, the cytostatic effect of p21Waf1/Cip1 can protect cells from genotoxic insults (which require cell cycle progression for induction of cell death) or through mechanisms that are based on cytoplasmic interference with caspase activation, suppression of E2F1- or Myc-induced pro-apoptotic gene expression and inhibition of pro-apoptotic stress kinases. Alternatively, p21Waf1/Cip1 can induce apoptosis through p53-dependent or -independent regulation of Bax and death receptors.1 ,2 

p21Waf1/Cip1 is not readily mutated in human cancers and expression is downregulated …
Multiple pyogenic granulomata occurring during etretinate therapy
Authors: D. M. Williamson, Rachel Greenwood
Journal: British Journal of Dermatology (1983)

Journal Article Multiple pyogenic granulomata occurring during etretinate therapy Get access D. M. Williamson, D. M. Williamson Departments of Dermatology, Pontefract General Infirmary and Bradford Royal Infirmary, West Yorkshire, England Search for other works by this author on: Oxford Academic Google Scholar Rachel Greenwood Rachel Greenwood Departments of Dermatology, Pontefract General Infirmary and Bradford Royal Infirmary, West Yorkshire, England Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 5, 1 November 1983, Pages 615–617, https://doi.org/10.1111/j.1365-2133.1983.tb07688.x Published: 01 November 1983
Swine Flu Sequelae
Authors: Lawrence D. Grouse
Journal: JAMA (1980)

THE SEQUELA of an inflammatory neuritis, the Guillain-Barré syndrome (GBS), following administration of the swine flu vaccine, presents a unique opportunity to view the usually submerged world of Poisson statistics. Out of more than 40 million Americans who received swine flu immunization, only about 500 showed development of the neuritis, approximately five times the normal incidence of this disease. In a less massive immunization program (which, following the swine flu debacle, all future programs will probably be), the chances of detecting such a rare complication would have been remote. In fact, even with the large numbers of people immunized with the vaccine, it was almost miraculous that the association was first entertained and then established, particularly since GBS is not a reportable disease. Although the association of the syndrome with influenza immunization is instructive to physicians, the cost to society for this instruction is sobering. Claims approaching $1 billion have
Measurement of splenic blood flow in the anaesthetised dog using electromagnetic flowmetry and indium labelled platelets
Authors: A M PETERS, J R T MATHIE, M J WALPORT, H J REAVY, R N BELL, J P LAVENDER
Journal: Cardiovascular Research (1983)

Splenic blood flow has been measured in the dog using indium labelled autologous platelets (SBFP) and compared with splenic blood flow measured with an electromagnetic flowmeter placed on the splenic vein (SVBF). The overall correlation between SBFP and SVBF was only moderately close (r = 0.54, P<0.01) and SBFp was about half SVBF. When expressed as a change between sequential measurements in an individual animal, the correlation between SBFP and SVBF was closer (r = 0.85, P <0.001). It was concluded that SBFP is a specific measure of splenic pulp blood flow and that the discrepancy between SBFP and SVBF reflects the degree of splenic blood flow bypassing the pulp.
The scatter of research: cross sectional comparison of randomised trials and systematic reviews across specialties
Authors: T. Hoffmann, C. Erueti, S. Thorning, P. Glasziou
Journal: BMJ (2012)

<b>Objective</b> To estimate the degree of scatter of reports of randomised trials and systematic reviews, and how the scatter differs among medical specialties and subspecialties. <b>Design</b> Cross sectional analysis. <b>Data source</b> PubMed for all disease relevant randomised trials and systematic reviews published in 2009. <b>Study selection</b> Randomised trials and systematic reviews of the nine diseases or disorders with the highest burden of disease, and the broader category of disease to which each belonged. <b>Results</b> The scatter across journals varied considerably among specialties and subspecialties: otolaryngology had the least scatter (363 trials across 167 journals) and neurology the most (2770 trials across 896 journals). In only three subspecialties (lung cancer, chronic obstructive pulmonary disease, hearing loss) were 10 or fewer journals needed to locate 50% of trials. The scatter was less for systematic reviews: hearing loss had the least scatter (10 reviews across nine journals) and cancer the most (670 reviews across 279 journals). For some specialties and subspecialties the papers were concentrated in specialty journals; whereas for others, few of the top 10 journals were a specialty journal for that area. Generally, little overlap occurred between the top 10 journals publishing trials and those publishing systematic reviews. The number of journals required to find all trials or reviews was highly correlated (r=0.97) with the number of papers for each specialty/subspecialty. <b>Conclusions</b> Publication rates of speciality relevant trials vary widely, from one to seven trials per day, and are scattered across hundreds of general and specialty journals. Although systematic reviews reduce the extent of scatter, they are still widely scattered and mostly in different journals to those of randomised trials. Personal subscriptions to journals, which are insufficient for keeping up to date with knowledge, need to be supplemented by other methods such as journal scanning services or systems that cover sufficient journals and filter articles for quality and relevance. Few current systems seem adequate.
Johnson &amp; Johnson to pay $2.2bn to settle charges of false marketing on three drugs
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Pharmaceutical giant Johnson & Johnson (JJ €1.6bn) to resolve allegations in the United States of unlawful promotion of three drugs including kickback payments to physicians and pharmacists.

The settlement is one of the largest in US history and follows an extensive investigation by federal and state law enforcers. It includes $485m in criminal fines and $1.72bn in civil settlements with the federal government and states.

Whistleblowers who reported the fraud are set to receive $167.7m between them for their part in uncovering the fraud.

The allegations concern the antipsychotics Risperdal (risperidone) and Invega (paliperidone) and the heart failure drug Natrecor (nesiritide).

In addition to the fines, J&J has signed a five year corporate integrity agreement to change how it does business. Among other actions, the agreement allows J&J to recoup annual bonuses and other incentives from executives who have …
Alectinib Salvages CNS Relapses in ALK-Positive Lung Cancer Patients Previously Treated with Crizotinib and Ceritinib
Authors: Justin F. Gainor, Carol A. Sherman, Kathryn Willoughby, Jennifer Logan, Elizabeth Kennedy, Priscilla K. Brastianos, Andrew S. Chi, Alice T. Shaw
Journal: Journal of Thoracic Oncology (2015)
Realigning Incentives for Developing and Pricing New Anticancer Treatments
Authors: David H. Howard
Journal: JAMA (2011)

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