tbuckley/cabot-search huggingface dataset:
Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients
Authors: Sari Pesonen, Iulia Diaconu, Lotta Kangasniemi, Tuuli Ranki, Anna Kanerva, Saila K. Pesonen, Ulrike Gerdemann, Ann M. Leen, Kalevi Kairemo, Minna Oksanen, Elina Haavisto, Sirkka-Liisa Holm, Aila Karioja-Kallio, Satu Kauppinen, Kaarina P. L. Partanen, Leena Laasonen, Tima Joensuu, Tuomo Alanko, Vincenzo Cerullo, Akseli Hemminki
Journal: Cancer Research (2012)

The immunosuppressive environment of advanced tumors is a primary obstacle to the efficacy of immunostimulatory and vaccine approaches. Here, we report an approach to arm an oncolytic virus with CD40 ligand (CD40L) to stimulate beneficial immunologic responses in patients. A double-targeted chimeric adenovirus controlled by the hTERT promoter and expressing CD40L (CGTG-401) was constructed and nine patients with progressing advanced solid tumors refractory to standard therapies were treated intratumorally. No serious adverse events resulting in patient hospitalization occurred. Moderate or no increases in neutralizing antibodies were seen, suggesting effective Th1 immunologic effects. An assessment of the blood levels of virus indicated 17.5% of the samples (n = 40) were positive at a low level early after treatment, but not thereafter. In contrast, high levels of virus, CD40L, and RANTES were documented locally at the tumor. Peripheral blood mononuclear cells were analyzed by IFN-γ ELISPOT analysis and induction of both survivin-specific and adenovirus-specific T cells was seen. Antitumor T-cell responses were even more pronounced when assessed by intracellular cytokine staining after stimulation with tumor type-specific peptide pools. Of the evaluable patients, 83% displayed disease control at 3 months and in both cases in which treatment was continued the effect was sustained for at least 8 months. Injected and noninjected lesions responded identically. Together, these findings support further clinical evaluation of CGTG-401.
Adjuvant Chemotherapy Use for Medicare Beneficiaries With Stage II Colon Cancer
Authors: Deborah Schrag, Sheryl Rifas-Shiman, Leonard Saltz, Peter B. Bach, Colin B. Begg
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Clinical trials have not demonstrated that adjuvant chemotherapy improves survival for patients with resected stage II colon cancer. Nevertheless, patients may receive this treatment despite its uncertain benefit. The objective of this study was to determine the extent to which adjuvant chemotherapy is used for patients with stage II colon cancer. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 3,151 patients aged 65 to 75 with resected stage II colon cancer and no adverse prognostic features. The primary outcome was chemotherapy use within 3 months of surgery ascertained from claims submitted to Medicare. Relationships between patient characteristics and adjuvant chemotherapy use were measured and their significance was assessed using multivariable logistic regression. Survival for treated and untreated patients was compared using a Cox model. RESULTS: Twenty-seven percent of patients received chemotherapy during the 3 postoperative months. Younger age at diagnosis, white race, unfavorable tumor grade, and low comorbidity were each associated with a greater likelihood of receiving treatment. Sex, the number of examined lymph nodes in the tumor specimen, the urgency of the surgical admission, and median income was each unrelated to treatment. Five-year survival was 75% for untreated patients and 78% for treated patients. After adjusting for known between-group differences, the hazard ratio for survival associated with adjuvant treatment was 0.91 (95% confidence interval, 0.77 to 1.09). CONCLUSION: A substantial percentage of Medicare beneficiaries with resected stage II colon cancer receive adjuvant chemotherapy despite its uncertain benefit.
Abstract B72: Serine/threonine kinase MLK4 is a master regulator for proneural-mesenchymal transformation of glioma stem cells
Authors: Kim Sunghak, Rosenstiel-Goidts Violaine, Shi-Yuan Cheng, Nakano Ichiro
Journal: Cancer Research (2015)

Abstract High-grade glioma is a highly aggressive form of brain cancer associated with a poor prognosis. Recently, we identified that mesenchymal glioma stem cells (Mes GSCs) of HGG are linked to radiation resistance and proneural (PN) GSCs acquire Mes identity via radiation treatment. Here we performed a combined kinome-wide RNA interference screen with genome wide expression analysis to identify kinase-encoding genes that are essential for mesenchymal identity of GSCs. Through this stepwise screening with patient-derived GSC samples, we identified the serine/threonine kinase MLK4 as a key regulator for Mes GSC survival and cell cycle progression in vitro and tumor initiation and propagation in vivo. In addition, overexpression of MLK4 promotes, while both its gene-specific shRNA and pharmacological inhibition attenuate, proneural-mesenchymal transformation (PMT) of GSCs. In patient-derived GSCs, expression of MLK4 protein positively correlated with endogenous EGFRvIII expression and the in vivo growth of mouse xenografts derived from glioma cells with EGFRvIII expression was prominently inhibited by MLK4 knockdown. MLK4-overexpressing PN GSCs acquired radiation resistance, while MLK4 elimination by shRNA radiosensitized Mes GSCs. Patients with a higher MLK4 expression showed reduced survival in CD44-high populations. Collectively, these data indicate that MLK4 as a plausible target for therapy against Mes GBM as well as post-irradiation PN GBM. Citation Format: Kim Sunghak, Rosenstiel-Goidts Violaine, Shi-Yuan Cheng, Nakano Ichiro. Serine/threonine kinase MLK4 is a master regulator for proneural-mesenchymal transformation of glioma stem cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B72. doi:10.1158/1538-7445.CHTME14-B72
Anal endosonography in faecal incontinence.
Authors: C I Bartram, A H Sultan
Journal: Gut (1995)

Leading article Anal endosonography in faecal incontinenceThe application of neurophysiological techniques to the pelvic floor highlighted the role of nerve damage in idio- pathic faecal incontinence, and electromyographic needle mapping provided a means of defining traumatic defects in the external sphincter.'Internal sphincter damage could be
Drug Interaction of Terfenadine and Carbamazepine
Authors: Steven Hirschfeld
Journal: Annals of Internal Medicine (1993)

Letters1 June 1993Drug Interaction of Terfenadine and CarbamazepineSteven Hirschfeld, MD and Paul Jarosinski, MDSteven Hirschfeld, MDSearch for more papers by this author and Paul Jarosinski, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-11-199306010-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We observed a drug interaction between the antihistamine terfenadine (Seldane, Marion Merrell Dow, Kansas City, Missouri) and the anticonvulsant carbamazepine (Tegretol, Basel Pharmaceuticals, Summit, New Jersey) that warrants the attention of practitioners.An 18-year-old woman (weight, 39.3 kg) who had had hip disarticulation for osteosarcoma and who was on anticonvulsant therapy after treatment of brain metastases came to the hospital with symptoms of confusion, disorientation, visual hallucinations, nausea, and ataxia. Her history was unremarkable for recent infections, ingestion, or trauma. She had a history of atopy, and her symptoms began shortly after taking terfenadine, 60 mg twice ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByClinically Significant Drug-Drug Interactions Involving Medications Used for Symptom Control in Patients With Advanced Malignant Disease: A Systematic ReviewCarbamazepineCarbamazepineRecent Advances in the Pharmacologic Treatment of Bipolar IllnessDrug Interactions with Agents Used in Respiratory DiseaseDrug Interactions with Agents Used in the Treatment of CNS DisordersThe Emerging Role of Cytochrome P450 3A in PsychopharmacologyMechanism of block of a human cardiac potassium channel by terfenadine racemate and enantiomersCarbamazepine interactionClinical pharmacokinetics: current requirements and future perspectives from a regulatory point of view 1 June 1993Volume 118, Issue 11Page: 907-908KeywordsAnticonvulsantsDrug interactionsHallucinationsHipIngestionMouthNauseaProteinsResearch laboratoriesRhinitis Issue Published: 1 June 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Issues and Challenges With Integrating Patient-Reported Outcomes in Clinical Trials Supported by the National Cancer Institute–Sponsored Clinical Trials Networks
Authors: Deborah Watkins Bruner, Charlene J. Bryan, Neil Aaronson, C. Craig Blackmore, Michael Brundage, David Cella, Patricia A. Ganz, Carolyn Gotay, Pamela S. Hinds, Alice B. Kornblith, Benjamin Movsas, Jeff Sloan, Lari Wenzel, Giles Whalen
Journal: Journal of Clinical Oncology (2007)

The objective of this report is to provide a historical overview of and the issues and challenges inherent in the incorporation of patient-reported outcomes (PROs) into multinational cancer clinical trials in the cancer cooperative groups.An online survey of 12 cancer cooperative groups from the United States, Canada, and Europe was conducted between June and August of 2006. Each of the cooperative groups designated one respondent, who was a member of one of the PRO committees within the cooperative group.There was a 100% response rate, and all of the cancer clinical trial cooperative groups reported conducting PRO research. PRO research has been conducted in the cancer cooperative groups for an average of 15 years (range, 6 to 30 years), and all groups had multidisciplinary committees focused on the design of PRO end points and the choice of appropriate PRO measures for cancer clinical trials. The cooperative groups reported that 5% to 50% of cancer treatment trials and an estimated 50% to 75% of cancer control trials contained PRO primary and secondary end points. There was considerable heterogeneity among the cooperative groups with respect to the formal and informal policies and procedures or cooperative group culture towards PROs, investigator training/mentorship, and resource availability for the measurement and conduct of PRO research within the individual cooperatives.The challenges faced by the cooperative groups to the incorporation of PROs into cancer clinical trials are varied. Some common opportunities for improvement include the adoption of standardized training/mentorship mechanisms for investigators for the conduct of PRO assessments and data collection and the development of minimal criteria for PRO measure acceptability. A positive cultural shift has occurred in most of the cooperative groups related to the incorporation of PROs in clinical trials; however, financial and other resource barriers remain and need to be addressed.
REFORM IN MEDICAL EXPERT TESTIMONY.
Authors: S. S. HERRICK
Journal: JAMA (1895)

The disagreement of doctors is both a proverb and a reproach: a proverb, as if it were constant and axiomatic; a reproach, as if it were needless, unreasonable and peculiar. If medicine were an exact science, men with equal opportunities for acquiring it might be expected to agree substantially, as they do in chemistry and physics; but the personal equation is a disturbing element in the mind of both physician and patient, of a variability defying the power of the differential calculus. That other people should disagree is a matter of course, and generally of no consequence. Clergymen disagree widely in doctrines believed to affect supremely the eternal welfare of mankind, and in this land of liberty and toleration a large fraction look on with indifference, and the remainder with serenity. Lawyers are paid to disagree; their clients are not satisfied unless they are radical and stormy in variance; yet
Alan Douglas Lower
Authors: M. Helliwell
Journal: BMJ (2014)

Born and educated in Oxford, Alan Douglas Lower returned from the Middlesex Hospital after qualifying, to complete his house jobs in Oxford. After brief spells in general practice in Rugeley and Cambridgeshire, he joined a partnership in Stowmarket in 1961. He and his colleagues soon realised the value and benefits of working together and moved into the first health centre in Suffolk in 1972, bringing together all the primary health care team under one roof. They also understood the importance of preventive medicine and set up their own screening programmes long before they were …
The Genetic Difference Principle
Authors: Colin Farrelly
Journal: The American Journal of Bioethics (2004)

In the newly emerging debates about genetics and justice three distinct principles have begun to emerge concerning what the distributive aim of genetic interventions should be. These principles are: genetic equality, a genetic decent minimum, and the genetic difference principle. In this paper, I examine the rationale of each of these principles and argue that genetic equality and a genetic decent minimum are ill-equipped to tackle what I call the currency problem and the problem of weight. The genetic difference principle is the most promising of the three principles and I develop this principle so that it takes seriously the concerns of just health care and distributive justice in general. Given the strains on public funds for other important social programmes, the costs of pursuing genetic interventions and the nature of genetic interventions, I conclude that a more lax interpretation of the genetic difference principle is appropriate. This interpretation stipulates that genetic inequalities should be arranged so that they are to the greatest reasonable benefit of the least advantaged. Such a proposal is consistent with prioritarianism and provides some practical guidance for non-ideal societies--that is, societies that do not have the endless amount of resources needed to satisfy every requirement of justice.
Use of Temperature-Sensitive Mutants for Live, Attenuated Influenza-Virus Vaccines
Authors: Douglas D. Richman
Journal: New England Journal of Medicine (1979)

THE protective value of killed influenza-virus vaccines is well documented; however, these vaccines depart from the ideal in several respects.1 , 2 In most studies vaccine protects only about 70 per cent of those vaccinated. Immunity is often transient, necessitating the annual revaccination of high-risk groups. Parenteral administration is required, and stimulation of local respiratory-tract immunity, which may be of high protective value, is poor. There is a low but statistically significant incidence of local and systemic reactions that appears to be intrinsic to the administered viral antigens. Children, who are important as both victims and vectors of influenza, respond relatively poorly . . .
Collagen Disease in Children
Authors: William P. Coleman
Journal: JAMA (1977)

Seventy-one children with the diagnosis of systemic lupus erythematosus (SLE) (39 cases), dermatomyositis (25 cases), or scleroderma (7 cases) were studied retrospectively. The children with SLE were much sicker than those with the other two diseases and were found to have a poorer prognosis than adults with SLE. In general, the earlier the age of onset, the poorer the prognosis. Early gastrointestinal bleeding, abnormal renal findings, and cardiac abnormalities heralded early death from SLE. The peak incidence of SLE near the time of puberty suggests hormonal influence on this disorder in children. Survival rates and morbidity improved as the treatment improved. Corticosteroids were the main therapeutic agents. The patients with scleroderma also received varying doses of vitamin E, penicillamine, chloroquine hydrochloride, and salicylates. The antimetabolites were used to treat SLE starting in the late 1960s.
"THE LOCALIZATION IN ANIMALS OF BACTERIA ISOLATED FROM FOCI OF INFECTION"
Authors: W. L. Holman
Journal: JAMA (1927)

<h3>To the Editor:</h3> —A recent article by Allen C. Nickel (The Journal, Oct. 2, 1926, p. 1117) enthusiastically supports the theory of Rosenow on "elective localization." Zinsser, referring to this theory, says: "It is an interesting thought, yet a dangerous one to spread broadcast, since it has influenced clinical thinking to an extent not warranted by experimental fact" (Textbook of Bacteriology, ed. 5, 1923, p. 424). Nickel has confused the issue of elective localization (a theory with little if any experimental basis) with that of secondary infections arising from primary foci, a sequence of events, the main features of which are largely accepted. I fully appreciate the important work Rosenow and his co-workers have done in emphasizing the importance of chronic infected foci in many types of disease, and they are deserving of the highest praise. Although the etiologic significance of the streptococci found in all these cases is not
Rubeosis Iridis in Aphakic Diabetics
Authors: Harold Beasley
Journal: JAMA (1970)

<h3>To the Editor:—</h3> Rubeosis iridis is a common ocular complication of diabetes mellitus. Its pathogenesis is no better understood than diabetic retinopathy. It is generally known that reducing the ocular pressure below normal, or systemic hypertension, exerts a deleterious influence on the evolution of diabetic retinopathy. Duane has suggested that this pressure differential between the inside and the outside of a normal retinal arteriole is a critical factor in determining the development of diabetic retinopathy. He defines this as the index of net vascular pressure (intra-arterial pressure/intraocular pressure) and the greater the index the more susceptible the retinal tissues are to retinopathy in diabetes.<sup>1</sup> If this mechanism can be used to explain exacerbations of diabetic retinopathy, it would seem reasonable that it would also explain the aggravation of vessels in the anterior segment, manifested by rubeosis iridis. In the past six months, two diabetics were seen with a rather
UREA CRYSTALS IN CANCER
Authors: William M. Millar
Journal: JAMA (1933)

The peculiarly penetrating fetor of a sloughing cancer is one of the horrible aspects of this disease. For the past year at the Tumor Clinic of the Cincinnati General Hospital, urea crystals<sup>1</sup>have been advocated and prescribed in such cases. If they are packed into the wound the odor will be stopped to a great extent. Although they dissolve in a few minutes, the offensive character of the ulcer becomes less with each application. The crystals are cheap, they possess a considerable antiseptic value, and there is no fear of a systemic reaction. The danger of burning the surrounding skin, which is considerable when the average dispensary patient attempts to use surgical solution of chlorinated soda at home, is avoided. There is one objection. After several days' treatment an occasional patient will complain of pain in the wound after packing. This can readily be relieved by morphine or other
P100 Liver transplantation (LT) results in reduced recipient Natural Killer (NK) cell activation with associated down regulation of activating receptors NKp30 and NKp46 but not NKG2D
Authors: K. M. Jamil, K. S. Cheent, K. Agarwal, G. J. Alexander, M. A. Heneghan, S. I. Khakoo
Journal: Gut (2011)

<h3>Introduction</h3> In solid organ transplantation, the effect of the allograft on recipient NK cell function is poorly understood. NK cells recognise self through inhibitory receptors for HLA class I, so that they lyse target cells that do not express self HLA class I molecules (the “missing-self” model). As liver transplants are not matched for HLA, significant NK cell alloreactivity is expected, but is not seen in practise. <h3>Aim</h3> This aim of this study is to investigate the effect of LT on recipient NK cell reactivity. <h3>Method</h3> Whole blood was collected from 16 liver transplant patients and 10 controls. The transplant patients were all on calcineurin inhibitor-based immunosuppression. NK cells from the peripheral blood were analysed for expression of the cell surface inhibitory receptors CD158a/b (killer cell immunoglobulin-like receptors (KIR) specific for HLA-C), and the activating receptors NKp30, NKp46 and NKG2D. Following overnight incubation with IL-15 NK cell function was assessed using a flow cytometry-based killing assay. <h3>Results</h3> There was significantly reduced expression of NKp30 and NKp46 in post LT patients compared with controls (p&lt;0.001 for both, Student t test), but no reduction in NKG2D expression (Abstract P100 figure 1). There was no difference in KIR expression or segregation of activating receptor expression with expression of specific KIR. However, consistent with the phenotyping results there was a significant reduction of NK cell killing of target cells in post LT patients compared with controls as shown in Abstract P100 figure 2 (p=0.011, Student t test). <h3>Conclusion</h3> Following liver transplantation there is down-regulation of activating NK cell receptors and suppression of NK cell activity. We propose that this suppression helps to maintain tolerance of the HLA-mismatched liver allograft.
P134 CYTOMEGALOVIRUS INFECTION MK2-DEPENDENTLY LEADS TO A DECREASED IFN-γ/IL-10 RATIO WHICH LIMITS MHC CLASS I/II EXPRESSION AND PREVENTS FORMATION OF MONONUCLEAR CELL INFILTRATES WITHIN THE LIVER
Authors: C. Ehlting, M. Trilling, C. Tiedje, A. Zimmermann, V.T.K. Le, M. Gaestel, H. Hengel, D. Häussinger, J.G. Bode
Journal: Journal of Hepatology (2014)
Impact of Collaborative Care Management of Depression Among Patients With Cancer
Authors: Kevin J. Patel, Francesca Dwamena
Journal: Journal of Clinical Oncology (2009)

It was with great interest that we read the article by Ell et al 1 regarding the role of collaborative care management of depression among predominately female patients with nonadvanced cancer.We congratulate the authors for their first large-scale trial of collaborative care, with intervention protocols specifically designed for minority patients with low income and nonadvanced cancer.However, we were struck by a few unacknowledged limitations.First, the high number of patients lost to follow-up (214 patients [45%] after 12 months) raises questions about the validity of the findings.We were surprised not to find any attempt to account for the fact that patients receiving intervention were more likely than patients of the control group to be foreign born; cultural differences may have rendered them more receptive to intervention, 2 resulting in an overestimation of the benefits of intervention.Furthermore, there was no mention of the proportion of foreign-born patients who were lost to follow-up in the intervention group compared with that in the control group.The authors reported that the percentage of patients at 12-month follow-up with 50% reduction in Patient Health Questionnaire-9 score was 63% in the intervention group and 50% in the control group, with a significant odds ratio of 1.98 (95% CI, 1.16 to 3.38; P ϭ .01).However, the 50% reduction in Patient Health Questionnaire-9 score at 12-month follow-up, when adjusted for certain patient demographics (adjusted mean score, Ϫ0.74 [95% CI, Ϫ1.74 to Ϫ0.27; P ϭ .15]),did not reflect significant results.This was contrary to the authors' inference that the adaptation of the collaborative care model results in significant reduction in depressive symptoms in patients with nonadvanced cancer.Finally, no information on patients with cancer that went into remission was provided.Patients who attained remission would have been less likely to be depressed and consequently more likely to have relatively better quality-of-life outcomes, as compared with their counterparts.