tbuckley/cabot-search huggingface dataset:
Histamine receptor 2 modifies iNKT cell activity within the inflamed lung
Authors: R. Ferstl, R. Frei, W. Barcik, E. Schiavi, K. Wanke, M. Ziegler, N. Rodriguez‐Perez, D. Groeger, P. Konieczna, S. Zeiter, D. Nehrbass, R. Lauener, C.A. Akdis, L. O'Mahony
Journal: Allergy (2017)

Abstract Background Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H 2 R). The aim of this study was to determine the role of H 2 R in modulating lung inflammatory responses. Methods H 2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin ( OVA ) and house dust mite extract ( HDM ) murine models of respiratory inflammation. H 2 R‐deficient animals and CD 1d/H 2 R‐deficient animals were utilized to examine the CD 1d presentation of lipid antigens (αGalCer or OCH ) to invariant natural killer T ( iNKT ) cells. Results Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM ‐induced airway diseases were more severe in H 2 R‐deficient animals. Flow cytometric analysis of lung tissue from H 2 R‐deficient animals revealed increased numbers of CD 1d + dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer‐stimulated iNKT cells from H 2 R‐deficient mice secreted higher levels of IL ‐4, IL ‐5, and GM ‐ CSF . In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H 2 R‐deficient or famotidine‐treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H 2 R‐deficient ( CD 1d −/− H 2 R −/− ) animals normalized the lung response to HDM. Conclusion The deliberate activation of H 2 R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD 1d‐mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.
X-Box Binding Protein-1 Dependent Plasma Cell Responses Limit the Development of Atherosclerosis
Authors: Andrew P. Sage, Meritxell Nus, Jayashree Bagchi Chakraborty, Dimitrios Tsiantoulas, Stephen A. Newland, Alison J. Finigan, Leanne Masters, Christoph J. Binder, Ziad Mallat
Journal: Circulation Research (2017)

Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies, and their importance in both humans and mouse models is still unclear.To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells.We combined a model of specific antibody deficiency, B cell-specific CD79a-Cre x XBP1 (X-box binding protein-1) floxed mice (XBP1-conditional knockout), with antibody-mediated depletion of CD4+ T cells. Ldlr knockout mice transplanted with XBP1-conditional knockout (or wild-type control littermate) bone marrow were fed western diet for 8 weeks with or without anti-CD4 depletion. All groups had similar levels of serum cholesterol. In Ldlr/XBP1-conditional knockout mice, serum levels of IgG, IgE, and IgM were significantly attenuated, and local antibody deposition in atherosclerotic plaque was absent. Antibody deficiency significantly accelerated atherosclerosis at both the aortic root and aortic arch. T cell and monocyte responses were not modulated, but necrotic core size was greater, even when adjusting for plaque size, and collagen deposition significantly lower. Anti-CD4 depletion in Ldlr/wild-type mice led to a decrease of serum IgG1 and IgG2c but not IgG3, as well as decreased IgM, associated with increased atherosclerosis and necrotic cores, and a decrease in plaque collagen. The combination of antibody deficiency and anti-CD4 depletion has no additive effects on aortic root atherosclerosis.The endogenous T cell-dependent humoral response can be protective. This has important implications for novel vaccine strategies for atherosclerosis and in understanding the impacts of immunotherapies used in patients at high risk for cardiovascular disease.
Translational clinical trial design
Authors: James Abbruzzese
Journal: Clinical Cancer Research (2008)

ED01-01  Our improved understanding of the molecular basis of malignancy has led to the identification of many new biochemical targets for therapy. While some of the drugs developed to affect specific targets have demonstrated activity in clinical trials and have subsequently gained FDA approval, many questions remain about the optimal way to translate basic research observations into clinical practice. These questions include preclinical identification of therapeutically relevant targets with high fidelity and demonstration of clinical benefit in well-designed controlled clinical trials. There are even more vexing concerns as to whether incorporation of biomarkers or imaging studies into our current clinical trial designs will optimize the development of targeted agents and whether a subset of such biomarkers can be validated as surrogate markers for clinical benefit. Such optimization could lead to an increase in the percentage of novel agents entering phase I trials that ultimately gain FDA approval or increasing the speed with which novel agents move through the various phases of drug development. Previous publications (1, 2) suggest that measurement of drug effects in tumor or surrogate tissue or use of functional imaging studies have not improved the efficiency of phase I clinical trials and did not contribute to the selection of a dose for phase II study. Likewise, limited data from phase II efficacy studies of targeted agents typically employed a standard primary endpoint such as objective response with only a limited number of studies qualifying patients for therapy through measurement of target expression or use of enrichment designs. No phase II studies used measurement of a surrogate endpoint to assess anticancer drug effects with, or in place of, clinical endpoints (3). Despite the practical challenges highlighted by these data, effectively incorporating translational endpoints into early clinical trials of novel targeted agents remains appealing and suggests that clinical trials with translational endpoints require more extensive planning to demonstrate their relevance. We will consider how appropriate planning can begin to address the challenges inherent in designing successful translational clinical trials that contribute essential information to drug development and ultimately facilitate the approval of targeted anticancer agents.  References   Parulekar WR, Eisenhauer EA. Phase I trial design for solid tumor studies of targeted, non-cytotoxic agents: Theory and practice. J Natl Cancer Inst 2004;96:990-7.  Goulart BHL, Clark JW, Pien HH, Roberts TG, Finkelstein SN, Chabner BA. Trends in the use and role of biomarkers in Phase I oncology trials. Clin Cancer Res 2007;13:6719-26.  El-Maraghi RH, Eisenhauer EA. Review of Phase II trial designs used in studies of molecular targeted agents: Outcomes and predictors of success in Phase III. J Clin Oncol 2008;26:1346-54.
Spiritual needs and patient satisfaction in a multicultural patient population.
Authors: Alan Bennett Astrow, Nelli Fromer, Shilpa Sambidi, Gary Kwok, Rashmi Sharma, Daniel Sulmasy
Journal: Journal of Clinical Oncology (2014)

e20562 Background: Attention to spiritual needs is an important component of supportive cancer care, but there has been little work to specify what these needs might be or how prevalent they are in ethnically and religiously diverse populations. We have previously reported that unmet spiritual needs are associated with decreased satisfaction with care among oncology outpatients in a single center in Manhattan. We have since improved and validated our spiritual needs assessment instrument and translated and validated it in Chinese, Spanish, and Russian. We are now studying spiritual needs in a multi-cultural group of cancer patients in Brooklyn and report results of the first 171 patients. Methods: We administered the Spiritual Needs Assessment for Patients (SNAP) to a convenience sample of outpatients from the Maimonides Cancer Center and a nearby private practice. The SNAP is a 23 item questionnaire that comprises three domains: psychosocial, spiritual, religious. Patients were also asked to complete a demographic survey, the QUEST satisfaction scale, and to answer questions about physician inquiries regarding their religious and spiritual needs. Results: 74% were female. 42% were white, 9% Hispanic, 23% African-American, and 23% Asian. English was the primary language for 57%, Spanish 9%, Chinese 21%, Russian 8%. 7% were Buddhist, 35% Catholic, 5% Eastern Orthodox, 3% Muslim, 14% Jewish, 24% Protestant. Fifty-five percent considered themselves “spiritual but not religious;” 40% attended religious services at least monthly. At least one specific spiritual need was reported by 60%, 23% reported that their spiritual needs were not being met, 14% would like help getting their spiritual needs met. Half (49%) would feel comfortable having their physician inquire about their religious beliefs and 46% about their spiritual needs. Patients with higher spiritual needs reported lower satisfaction with care (p = .05). Conclusions: Spiritual needs are common in an ethnically, religiously, and linguistically diverse urban cancer patient population. High levels of spiritual need are associated with lower levels of satisfaction with care. We continue to accrue patients and will perform in-depth cross-cultural comparisons at study completion.
Ферментные препараты поджелудочной железы без кишечнорастворимой оболочки: используются ли они сегодня?
Authors: A.V. Savustyanenko
Journal: GASTROENTEROLOGY (2014)

Введение. Для лечения экзокринной недостаточности поджелудочной железы рекомендована заместительная терапия высокодозовыми ферментными препаратами с кишечнорастворимой оболочкой. В связи с этим возникает вопрос о целесообразности клинического применения более старых низкодозовых ферментных препаратов без кишечнорастворимой оболочки (в качестве референсного препарата служил Мезим® форте). Результаты. Ряд анатомо-физиологических особенностей и активное применение средств, подавляющих желудочную секрецию — ингибиторов протонной помпы, антацидов (натрия бикарбоната), позволяют существенно повысить «выживаемость» панкреатических ферментов, не имеющих кишечнорастворимой оболочки, в желудочном соке и их доставку в двенадцатиперстную кишку. Данная лекарственная форма продолжает применяться для купирования болевого синдрома при хроническом панкреатите (препараты с кишечнорастворимой оболочкой неэффективны). Предложено использовать комбинацию обеих лекарственных форм — с кишечнорастворимой оболочкой и без нее — для более эффективной терапии экзокринной недостаточности поджелудочной железы. При функциональных заболеваниях желудочно-кишечного тракта (синдром раздраженного кишечника с функциональной патологией поджелудочной железы, функциональная диспепсия) ферментные препараты без кишечнорастворимой оболочки ускоряли выздоровление пациентов. При воспалительных заболеваниях кишечника (неспецифический язвенный колит, болезнь Крона) и хронической обструктивной болезни легких данная лекарственная форма увеличивала длительность ремиссии, причем при заболеваниях кишечника — и качество жизни во время ремиссии. Ферментные препараты без кишечнорастворимой оболочки применялись и при ряде других заболеваний, сопровождающихся мальдигестией/мальабсорбцией. Кроме того, их применяли для постепенного (мягкого) ухода от терапии высокодозовыми ферментными препаратами. Они также находят свое применение для коррекции экзокринной недостаточности поджелудочной железы при легких перекусах и погрешностях в диете. Финансовые показатели продаж свидетельствуют о высокой востребованности низкодозовых ферментных препаратов без кишечнорастворимой оболочки (Мезим® форте). Выводы. Низкодозовые ферментные препараты без кишечнорастворимой оболочки продолжают широко применяться в современной клинической практике.
Amid FDA Approval Filings, Another CAR-T Therapy Patient Death
Authors: Jennifer Abbasi
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sigmoidoscopy Reimbursement
Authors: Evan Ashkin
Journal: Annals of Internal Medicine (1999)

Letters16 November 1999Sigmoidoscopy ReimbursementEvan Ashkin, MDEvan Ashkin, MDUniversity of North Carolina, Chapel Hill; Chapel Hill, NC 27599-7595 (Ashkin)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-10-199911160-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The article by Lewis and Asch (1) was timely and confirmed my recent experience. I have just opened a community-based family practice office for the Department of Family Medicine at the University of North Carolina, Chapel Hill. In accordance with recommendations for colorectal cancer screening, we wanted to provide office-based screening sigmoidoscopy for our patients. We conducted a break-even analysis, in which we projected our costs and local health maintenance organization and Medicare reimbursement rates, and found that we needed to do approximately seven examinations a month, an estimate very close to that of Lewis and Asch. ...Reference1. Lewis JD, Asch DA. Barriers to office-based screening sigmoidoscopy: does reimbursement cover costs? Ann Intern Med. 1999;131:525-30. LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Evan Ashkin, MDAffiliations: University of North Carolina, Chapel Hill; Chapel Hill, NC 27599-7595 (Ashkin) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBarriers to Office-Based Screening Sigmoidoscopy: Does Reimbursement Cover Costs? James D. Lewis and David A. Asch Metrics 16 November 1999Volume 131, Issue 10Page: 792-793KeywordsBiopsyColorectal cancerColorectal cancer screeningFlexible sigmoidoscopyHealth maintenance organizationsMedicareMotivationPrimary care physicians ePublished: 15 August 2000 Issue Published: 16 November 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Клініко-ендоскопічні аспекти кандидозу слизової оболонки верхнього відділу шлунково-кишкового тракту у пацієнтів з гастроентерологічною патологією
Authors: I.V Kushnirenko, L.M. Mosiychuk, O.O. Krylova, L.I. Belova, L.V. Demeshkina
Journal: GASTROENTEROLOGY (2013)

Стаття присвячена розв’язанню актуальних питань взаємозв’язку клінічних та ендоскопічних аспектів кандидозу слизової оболонки (СО) верхнього відділу шлунково-кишкового тракту. Результати досліджень, проведених у 122 пацієнтів, дозволили виявити превалювання диспептичного синдрому в пацієнтів із даною патологією, при цьому в пацієнтів з ураженням стравоходу інтенсивність синдрому абдомінального болю в 1,5 раза перевищує таку в групі лише з орофарингеальним кандидозом (р &lt; 0,001). Більш глибоке ураження СО асоціюється зі збільшенням частоти виявлення макроскопічних ознак запалення у стравоході (р &lt; 0,05), нальоту на язику (r = 0,220; р = 0,02), утруднення проходження їжі стравоходом (r = 0,235; р = 0,02), болю за грудниною (r = 0,249; р = 0,01) при відсутності впливу таких факторів, як шлунково-стравохідний і дуоденогастральний рефлюкси. Виявлений прямий взаємозв’язок макроскопічних ознак запалення і рубцевої деформації в цибулині дванадцятипалої кишки зі ступенем кандидозу (r = 0,250; р = 0,01). У цілому аналіз отриманих даних показав необхідність подальшого осмислення ролі опортуністичної інфекції у формуванні патологічних процесів і розвитку захворювань.
Impact of modifiable risk factors on clinical outcomes in geriatric patients with breast cancer.
Authors: Sukesh Manthri, Muhammad Iqbal, Meghna R. Desai, Robert S. Mocharnuk, Kathy Robinson
Journal: Journal of Clinical Oncology (2017)

e21546 Background: Tobacco use remains the single largest contributor to preventable death in the U.S. Women who consume alcohol have a 15% higher risk of hormone-receptor-positive breast cancer and obese women are at higher risk of developing breast cancer compared to non-obese women after menopause. There is limited information about the combined impact of smoking, alcohol and BMI on clinical outcomes among elderly patients . The purpose of this study was to analyze the effects of smoking, alcohol and BMI on clinical outcomes in geriatric breast cancer patients. Methods: Among 1659 patients in the institutional Breast Cancer Registry database, a total of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 years or older at the time of diagnosis were reviewed in an IRB approved fashion. Clinical outcomes included assessment of the following risk factors: current/former smoking, current/former alcohol usage and BMI at time of diagnosis. Kaplan-Meyer and Cox proportional hazards methods were used to calculate clinical outcomes which included overall survival (OS) and disease free survival (DFS). Results: There were 110 (40.9%) never smokers, 41 (15.2%) current smokers and 80 (29.7%) former smokers. A total of 129 (48%) of women had never consumed alcohol, 73 (27.1%) currently consumed alcohol, and 19 (17.1%) previously consumed alcohol. Mean BMI at the time of diagnosis was 30.62. The OS and DFS was longer among patients who were never smokers compared to current and former smokers (P = 0.0125, P = .0.0077) (P = 0.0107, P = 0.0146). There was also no statistically significant decrease in OS, DFS among those who never consumed alcohol compared to current and former alcoholic users (P = 0.7516, P = 0.2027) (P = 0.8892, P = 0.2432). Neither was there a statistically significant decrease in OS, DFS based on BMI at time of diagnosis (P = 0.5045) (P = 0.5233). In patients with combined cigarette and alcohol usage with BMI &gt; 25, there was also no statistically significant decrease in OS (P = 0.3572). Conclusions: In patients 65 years old or older diagnosed with breast cancer, prognosis for current or former smokers is worse compared to never smokers. Alcohol consumption and BMI have no impact on DFS or OS.
Повышение информативности эндоскопической диагностики предраковых изменений и рака желудка у больных с атрофическим гастритом
Authors: Yu.M. Stepanov, Ye.V. Simonova
Journal: GASTROENTEROLOGY (2013)

В статье представлены данные об изучении характера эндоскопических изменений слизистой оболочки желудка у больных с атрофическим гастритом с различной выраженностью структурных нарушений. Показано, что эндоскопические проявления атрофического гастрита являются неоднородными и характеризуются, помимо атрофических изменений, наличием изменений рельефа слизистой оболочки (узловатость, бугристость), очаговых гиперплазий, полипов, ксантом. Указанные изменения коррелируют с наличием кишечной метаплазии и дисплазии слизистой желудка. Частота атрофически-гиперпластических гастритов достоверно выше у пациентов с наличием предраковых изменений слизистой желудка.Показано, что применение пеногасителя симетикона повышает диагностическую эффективность эзофагогастродуоденоскопии, способствуя выявлению предраковой патологии и рака желудка.
Hypoxia in the glioblastoma microenvironment: shaping the phenotype of cancer stem-like cells
Authors: Nicole Colwell, Mioara Larion, Amber J. Giles, Ashlee N. Seldomridge, Saman Sizdahkhani, Mark R. Gilbert, Deric M. Park
Journal: Neuro-Oncology (2016)

Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity. This review highlights the interaction of GSCs with the hypoxic tumor microenvironment, exploring the mechanisms underlying the contribution of GSCs to tumor vessel dynamics, immune modulation, and metabolic alteration.