tbuckley/cabot-search huggingface dataset:
Reply to S.D. Richman et al
Authors: Valérie Boige, David Malka, Jean-Pierre Pignon, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2011)

We thank Richman et al for their interest in our work and provision of additional pharmacogenetic data from patients included in the FOCUS (Fluorouracil [FU], Oxaliplatin and CPT11 [irinotecan]: Use and Sequencing) trial. Of the 2,135 patients enrolled onto the FOCUS trial—in which one of three patients was randomly assigned to receive first-line FU alone and one of six to receive first-line FU plus oxaliplatin—the authors analyzed TS-5 UTR polymorphism in 938 patients (44%) for whom DNA was available. First, they saw no effect on overall survival, which is in accordance with our results. Second, in 910 patients (43%) with complete data, the authors showed a prognostic effect of the polymorphism on progression-free survival (PFS), the 2R allele being protective, whereas in the FFCD (Federation Francophone de la Cancerologie Digestive) 2000-05 trial, we saw no overall prognostic effect on PFS. However, this effect was weak (perallele hazard ratio [HR], 0.9; 95% CI, 0.82 to 0.99; P .03). Third, they failed to validate our finding that genotyping of TS-5 UTR may be a valuable tool in identifying patients who will and will not benefit from first-line combination therapy. This was mainly because of the observed results in patients with 3R/3R genotype (HR for PFS with first-line FU plus oxaliplatin v FU alone, 0.68; 95% CI, 0.48 to 0.96, in FOCUS trial compared with HR, 0.96; 95% CI, 0.66 to 1.40 in FFCD 2000-05 trial). However, it is not possible to assert that the results of the two trials are discordant, because of the large overlap of the CIs (Fig 1). This was confirmed by the absence of significant heterogeneity between the two trials. Furthermore, we pooled the results of the two trials. A significant trend (P .02) was observed between TS-5 UTR genotype and treatment effect on PFS. The addition of oxaliplatin to first-line FU had no significant impact on PFS in patients with the 3R/3R genotype (HR, 0.80; 95% CI, 0.62 to 1.03). We have no clear explanation for the differences observed between the pharmacogenetic analyses in the FOCUS and FFCD 2000-05 trials. In particular, we do not know whether these differences may be the result of differences in FU dosage (2,400 mg/m in FFCD 2000-05 trial v 2,800 mg/m in FOCUS trial), oxaliplatin dosage (100 mg/m v 85 mg/m), prior history of adjuvant FU-based chemotherapy (11% v 23% to 27%), number of disease sites (single-disease site, 52% v 29% to 36%), tumor assessment periodicity (every 8 weeks v 12 weeks), or pattern of DNA extraction (blood v normal bowel mucosa; normal tissue not available in 25% of patients in pharmacogenetic analysis of FOCUS trial). In conclusion, because the FOCUS pharmacogenetic analysis failed to validate our results, additional large prospective studies are mandatory to determine definitively the predictive impact of TS-5 UTR genotype and the effect (or absence of effect) on PFS of the addition of oxaliplatin to FU in 3R/3R patients.
GROUP PSYCHOTHERAPY WITH PATIENTS' RELATIVES
Authors: W. D. ROSS
Journal: American Journal of Psychiatry (1948)

An attempt has been made to supplement psychiatric treatment of patients by concurrent group psychotherapy of their relatives. Weekly discussion meetings have been held of 4 to 30 relatives attending on general invitation or selected because of particular interpersonal difficulties with the patient. The technique was between repressive-inspirational and analytic, involving didactic explanations and group ventilation of interpersonal maladjustments. More resistance was encountered than in psychotherapy with patients, and many of the relatives were quite rigid, defensive individuals. Many of them reported relief at being able to participate, however, and many were able to change attitudes which had been deleterious to the patient. Younger relatives seem to have been influenced more than older ones. A few individual experiences have been described. Some suggestions have been made for the conduction of future projects of this type. No results can be reported separate from the effects of other treatment, but the impression is favorable for the addition of this technique to the battery of psychiatric therapy.
Vorinostat Enhances the Activity of Temsirolimus in Renal Cell Carcinoma Through Suppression of Survivin Levels
Authors: Devalingam Mahalingam, Ernest C. Medina, Juan A. Esquivel, Claudia M. Espitia, Sabrina Smith, Kelli Oberheu, Ronan Swords, Kevin R. Kelly, Monica M. Mita, Alain C. Mita, Jennifer S. Carew, Francis J. Giles, Steffan T. Nawrocki
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus has exhibited promising anticancer activity for the treatment of renal cell cancers (RCC). Survivin expression has been implicated in drug resistance and reducing its levels with the histone deacetylase (HDAC) inhibitor vorinostat may enhance the anticancer activity of temsirolimus. Experimental Design: The sensitivity of RCC cell lines to the combination of temsirolimus and vorinostat was determined by measuring cell viability, clonogenic survival, and apoptosis. The effects of this combination on survivin levels were determined in vitro and in vivo. Survivin expression was silenced using small interfering RNA to evaluate its role in determining sensitivity to temsirolimus and vorinostat. The effect of the combination on angiogenesis was also determined in RCC xenograft models. Results: Vorinostat synergistically improved the anticancer activity of temsirolimus in a panel of RCC cell lines in vitro and in two xenograft models in vivo. While each single agent led to a modest decrease in survivin levels, the combination dramatically reduced its expression, which correlated with an induction of apoptosis. Silencing survivin levels induced apoptosis and significantly improved the efficacy of temsirolimus and vorinostat. In addition, the temsirolimus/vorinostat combination led to a strong reduction in angiogenesis. Conclusions: Vorinostat augmented the anticancer activity of temsirolimus in both in vitro and in vivo models of RCC. The effectiveness of the combination was due to a decrease in survivin levels and corresponding induction of apoptosis, and enhanced inhibition of angiogenesis. Targeting survivin may be a promising therapeutic strategy to improve RCC therapy. Clin Cancer Res; 16(1); 141–53
THE FUNCTION OF BRÜCKE'S MUSCLE.
Authors: V. FUKALA
Journal: JAMA (1899)

In 1864 Brücke published his views in regard to what he calls the "ciliary muscle." As is well known, this muscle consists of two parts, one circular, and one longitudinal. The circular portion escaped his observation, but he correctly apprehended the longitudinal part, and to it his name has been applied. Brücke first demonstrated that the ciliary muscle was unstriated. It had hitherto been designated the "ligamentum scleroticum," "plexus ciliaris," or "ganglion ciliare," according to the different views of its structure. Brücke failed to correctly understand the function of the longitudinal muscle, and this error, to a degree, still prevails. In his "Anatomic Description of the Human Eyeball" he states: "the muscle discovered by me extends from the corneo-scleral junction to the roots of the ciliary process." Unfortunately he did not follow the muscle farther into the choroid, and consequently there escaped him the important fact that it extends nearly
Listerism and the Development of Operative Surgery
Authors: W. W. Cheyne
Journal: BMJ (1902)

1.85x'.ao far as possible to place before you simple facts4 trusting that in estimating their significance you will be ever guided by that which our dear master has so constantly striven to inculcate as our leading principle-the love of truth."When I compare the surgery of my student days with the *urgery of to-day the outstanding impression on my mindis the -amount of physical suffering, which Lister has saved the human race.It is, in my opinion, incalculable.We hear .-often of lives and limbs saved; to my mind the pain saved is -even more striking.Anaesthesia saved pain during, asepsis after, an operation.. From first to last Lister's aim. in Glasgow,.Edinburgh, and in London has been to obtain if possible,.a method whereby .-openwounds would follow the painless and safe course of -a eubcutaneous wound, in other words, follow an aseptic:course.I sincerely trust that I have said nothing that will for a single *moment give my dear master a passing thought that these -reminiscencetlOf past days had been -better unsaid.eiftainl.yI feel that they could have been better said, but I trust they may be looked upon simply as an expression, however incom- plete, of the love and loyalty of a pupil for his master, .
Intravesical Chemotherapy of High-Grade Bladder Cancer with HTI-286, A Synthetic Analogue of the Marine Sponge Product Hemiasterlin
Authors: Boris A. Hadaschik, Hans Adomat, Ladan Fazli, Yves Fradet, Raymond J. Andersen, Martin E. Gleave, Alan I. So
Journal: Clinical Cancer Research (2008)

Abstract Purpose: HTI-286 is a fully synthetic analogue of the natural tripeptide hemiasterlin that inhibits tubulin polymerization and has strong cytotoxic potential. In this study, we evaluate the inhibitory effects of HTI-286 on human bladder cancer growth, both in vitro and as an intravesical agent in an orthotopic murine model. Experimental Design: Various bladder cancer cell lines were treated with HTI-286 and mitomycin C (MMC) in vitro. Human KU-7 bladder tumor cells that stably express firefly luciferase were inoculated in female nude mice by intravesical instillation and quantified using bioluminescence imaging. Mice with established KU-7-luc tumors were given HTI-286 or MMC intravesically twice a week for 2 h. Pharmacokinetic data was obtained using high-performance liquid chromatography–mass spectrometry analyses. Results: In vitro, HTI-286 was a potent inhibitor of proliferation in all tested cell lines and induced marked increases in apoptosis of KU-7-luc cells even after brief exposure. In vivo, HTI-286 significantly delayed cancer growth of bladder tumors in a dose-dependent fashion. HTI-286, at a concentration of 0.2 mg/mL, had comparable strong cytotoxicity as 2.0 mg/mL of MMC. The estimated systemic bioavailability of intravesically given HTI-286 was 1.5% to 2.1% of the initial dose. Conclusions: Intravesical HTI-286 instillation therapy showed promising antitumor activity and minimal toxicity in an orthotopic mouse model of high-grade bladder cancer. These findings provide preclinical proof-of-principle for HTI-286 as an intravesical therapy for nonmuscle-invasive bladder cancer and warrant further evaluation of efficacy and safety in early-phase clinical trials.
THE CLINICAL THERMOMETER IN THE PREVENTION OF PULMONARY TUBERCULOSIS
Authors: E. Clark-Jones
Journal: BMJ (1922)

THE CLINICAL THERMOMETER AND PHTHISIS.[ THE Brm of those tested were pathogenic to these animals.Diphtheroids were present in 30 per cent. of the cases.They were obtained from the superficial surface of 24 per cent. of the tonsils and 9 per cent; of the adenoids, and from the depths of the crypts of 15 per cent. of the tonsils and 11 per cent. of the adenoids.Streptococci.
A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis
Authors: Andrew D. Mumford, Ban B. Dawood, Martina E. Daly, Sherina L. Murden, Michael D. Williams, Majd B. Protty, Jennifer C. Spalton, Mark Wheatley, Stuart J. Mundell, Steve P. Watson
Journal: Blood (2009)
A 20-Year Forecast for Academic Medical Centers
Authors: John A. DiBiaggio
Journal: New England Journal of Medicine (1981)

IT is impossible to predict the events of the next two decades in the medical sciences. Technologic advances are occurring so rapidly that the character of medical practice may change dramatically in that time. No one knows what the next CAT scanner will be, but it is certain that there will be comparable technologic breakthroughs in the near future. Any attempt to make absolute predictions about medical education would be foolhardy and dangerous, but certain assumptions can be made, and they are the subject of this discussion.First of all, we can expect college and university enrollments to stabilize or . . .
William Albert Dunnet
Authors: Dianora Bond
Journal: BMJ (2005)

Neurologist who discovered and gave his name to a hereditary form of amyloidosis While working at the Santo António General Hospital in Porto (which had hired him as an unpaid neurologist to head the hospital's first department of neurology) Corino de Andrade noticed patients presenting with features that were characteristic of a peripheral neuropathy but did not fit any established clinical entity.During the next decade he came across dozens of similar cases and did extensive research on the epidemiology and pattern of transmission of this as yet unidentified disease.In 1942 the autopsy of one of his patients revealed the presence of an amyloid substance in several body tissues.This led him to describe a new hereditary amyloid polyneuropathy-particularly prevalent not only in the fishing areas of northern Portugal, but also in coastal regions of other countries, including Japan and Sweden.This familial amyloid polyneuropathy type I (Portuguese) also became known as Corino de Andrade's disease.Andrade's efforts were widely acknowledged by the international scientific community and attracted leading neurology gurus to Portugal.At a reception in Lisbon, Corino de Andrade met the editor of the British journal Brain, who expressed extreme interest in his research, prompting him to start writing his landmark 1952 paper.Politically, Corino de Andrade was a bothersome opponent of the repressive fascist regime that ruled Portugal at the time.He belonged to the Movement of Democratic Unity, and advocated the free discussion of ideas and projects that could lead to a fair and developed society.Having tapped his phone, the political police arrested him in 1951, just when he had finished writing his paper.He was jailed on charges of "subversive activities" and secret links with the Communist Party.He remained in prison for several months, which slowed the publication of his paper.Nevertheless, he managed to review the paper while behind bars, and some of his colleagues submitted two short versions of the article to other international publications.He was released after a few months, possibly thanks to the diligence of an influential colleague and of his English second wife, Gwendoline, a teacher at the British Institute in Porto.The paper remains today the most
Psychological Disturbances Among 47 Croatian Prisoners of War Tortured in Detention Camps
Authors: Dragica Kozarić-Kovačlć
Journal: JAMA (1993)

To the Editor.  —As medical professionals providing immediate health care to Croatian prisoners of war (POWs) released from detention camps in Serbia or occupied parts of Croatia, 1 we witnessed grave violations of their human rights. Of the 5261 POWs released by February 1993, the majority reported being tortured.  We present a few of our findings, regarding a group of 47 POWs. These were members of the Croatian Army from Vukovar who had been severely tortured, both physically and psychologically, in a detention camp in the occupied area of Croatia. All were beaten and denied any information about their families. Most experienced other classic forms of torture 2 including forced body position, mock executions, hard labor, and blackmail. Half were forced to eat salt without being allowed to drink water, or they had salt put in incision wounds made on their thighs. Twenty-three percent were tortured by exposure to cold,
"FALLACIES OF THE 'YEAST METHOD' OF DETECTING GLUCOSE IN THE URINE"
Authors: Max Einhorn
Journal: JAMA (1926)

<h3>To the Editor:</h3> —InThe Journal, February 20, there is a paper by Drs. Aldo Castellani and F. A. Taylor, entitled "Fallacies of the 'Yeast Method' of Detecting Glucose in the Urine," which begins with the sentence: "In several of the best known manuals of pathology and clinical methods, it is stated that the fermentation test by means of yeast is the only absolutely certain and specific test for glucose." This statement is correct, excepting that "sugar" should be substituted for the word "glucose." The authors mention experiments demonstrating that yeast ferments with gas formation not only glucose but also levulose, maltose, galactose and saccharose. Then they say: "When urine is fermented by bakers' yeast, we cannot therefore come definitely to the conclusion that the fermentable substance is glucose; it might be galactose, maltose or other sugars. To detect glucose, recourse should be made to the really specific germs for
Two Cases of Post Partum Haemorrhage Treated by the Injection of Perchloride of Iron
Authors: W. P. Swain
Journal: BMJ (1874)

THE BRITISH MEDICAL 70URNAL.30I substance.A section from a nodule upon the heart showed the same material infiltrating the muscular fibres.And in one from the root of the lung the pulmonary tissue was infiltrated with similar small cells.There can be little doubt, I think, that the tumour was a sarcoma, com- mencing in the mediastinal connective tissue, spreading by continuity along the pericardium, pleura, and heart; in each case being more de- veloped wvhere more connective tissue naturally existed, as along the vessels, costal pleura, etc., but also infiltrating the subjacent tissues.
Pyloric stenosis in adults: A clinical and radiological study of 100 consecutive patients
Authors: L. Kreel, H. Ellis
Journal: Gut (1965)

EDITORIAL SYNOPSIS The causes of obstruction in 100 cases diagnosed clinically as 'pyloric stenosis' showed that the majority of cases were duodenal ulcer stenosis, with prepyloric carcinoma as second in frequency.In the earlier stages the obstruction is overcome by hyperactivity of the gastric muscle but later on muscular failure occurs with gastric atony and retention of food.This is reversible and should be corrected before surgical treatment.PAIN The length of history of indigestion and epigastric pain, not unnaturally, tended to be 253 on August 18, 2023 by guest.
Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy
Authors: Carolyn J. Owen, Cynthia L. Toze, Anna Koochin, Donna L. Forrest, Clayton A. Smith, Jane M. Stevens, Shannon C. Jackson, Man-Chiu Poon, Gary D. Sinclair, Brian Leber, Peter R. E. Johnson, Anthony Macheta, John A. L. Yin, Michael J. Barnett, T. Andrew Lister, Jude Fitzgibbon
Journal: Blood (2008)
Elucidation of Epigenetic Inactivation of <b> <i>SMAD8</i> </b> in Cancer Using Targeted Expressed Gene Display
Authors: Kuang-hung Cheng, Jose F. Ponte, Sam Thiagalingam
Journal: Cancer Research (2004)

Abstract To address the challenge of identifying related members of a large family of genes, their variants and their patterns of expression, we have developed a novel technique known as targeted expressed gene display. Here, we demonstrate the general application of this technique by analyzing the SMAD genes and report that the loss of SMAD8 expression is associated with multiple types of cancers, including 31% of both breast and colon cancers. Epigenetic silencing of SMAD8 expression by DNA hypermethylation in cancers directly correlates with loss of SMAD8 expression. The SMAD8 alteration in a third of breast and colon cancers makes it a significant novel tumor marker as well as a potential therapeutic target. The utility of targeted expressed gene display for the analysis of highly homologous gene families as demonstrated by its application to the SMAD genes suggests that it is an efficient tool for the identification of novel members, simultaneous analysis of differential expression patterns, and initial discovery of alterations of expressed genes.
Severe thrombotic tendency associated with a type I plasminogen deficiency
Authors: Frank W. G. Leebeek, Eduard A. R. Knot, Jan Wouter Ten Cate, Daan W. Traas
Journal: American Journal of Hematology (1989)

Abstract We report a 45‐year‐old female patient with recurrent spontaneous deep vein thrombosis associated with an isolated hypoplasminogenemia (plasminogen activity and antigen level of 42% and 37%, respectively). The plasminogen molecule was normal as demonstrated by a normal activation by tissue plasminogen activator, electrophoretic mobility on crossed immunoelectrophoresis, molecular weight, and binding to lysine sepharose. All other hemostatic parameters predisposing to recurrent thrombosis were normal. A stimulation test with desmopressin acetate (DDAVP) showed a normal plasma rise of both tissue plasminogen activator and factor VIIIR:WF. This isolated plasminogen deficiency apparently is due to a decreased synthesis of a normal plasminogen molecule and is associated with a severe thrombotic tendency.
Absence of a lateral border zone of intermediate creatine phosphokinase depletion surrounding a central infarct 24 hours after acute coronary occlusion in the dog.
Authors: H O Hirzel, E H Sonnenblick, E S Kirk
Journal: Circulation Research (1977)

Myocardial creatine phosphokinase (CPK) activity was measured as an indicator of cell viability 24 hours after ligation of the left anterior sescending coronary artery (LAD) in normal myocardium, the entire region supplied by the LAD, and individual samples from the border and center of the infarct. Tissue supplied by the LAD and delineated by dye was carefully dissected from normal tissue along the stained border, CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in normal myocardium interdigitating with ischemic tissue at the border. Normal tissue was marked prior to occlusion with microspheres injected into the left atrium, whereas the distal portion of the LAD was perfused separately with unlabeled blood from a reservoir. With this correction, the CPK activity in the ischemic tissue from the lateral border of the infarct was essentially the same as in samples from the center, whereas that in the normal tissue immediately adjacent to the stained border was equal to values in remote normal myocardium. Thus, CPK depletion throughout the entire ischemic myocardium was nearly equal to CPK depletion in the center of the infarct. The uncorrected intermediate CPK levels in the individual samples from the border of the stained region correlated with the amount of normal tissue contaminating these samples. However, differences in CPK depletion across the heart wall resulted in the most depletion in the subendocardium and the least in the epicardium. Further more, coronary collateral blood flow measured 10 minutes after occlusion correlated well with the subsequent extent of CPK depletion.
THE ASSESSMENT OF FOUR NEW FLUOCORTOLONE ANALOGUES BY A MODIFIED VASOCONSTRICTION ASSAY
Authors: HARVEY BAKER, H. A. SATTAR
Journal: British Journal of Dermatology (1968)

Journal Article THE ASSESSMENT OF FOUR NEW FLUOCORTOLONE ANALOGUES BY A MODIFIED VASOCONSTRICTION ASSAY Get access HARVEY BAKER, HARVEY BAKER Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar H. A. SATTAR H. A. SATTAR Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 1, 1 January 1968, Pages 46–53, https://doi.org/10.1111/j.1365-2133.1968.tb11905.x Published: 01 January 1968 Article history Accepted: 03 October 1967 Published: 01 January 1968