tbuckley/cabot-search huggingface dataset:
Impact of Total Knee Arthroplasty as Assessed Using Patient‐Reported Pain and Health‐Related Quality of Life Indices: Rheumatoid Arthritis Versus Osteoarthritis
Authors: Anand Dusad, Sofia Pedro, Ted R. Mikuls, Curtis W. Hartman, Kevin L. Garvin, James R. O'Dell, Kaleb Michaud
Journal: Arthritis & Rheumatology (2015)

Objective To assess and compare the impact of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). Methods Patients with rheumatologist‐diagnosed arthritis undergoing primary TKA during 1999–2012 were identified. Indices of pain (overall, index knee, and contralateral knee) and health‐related quality of life (HRQOL) were obtained in 3 consecutive 6‐month intervals: preoperative (baseline), perioperative, and postoperative (recovery). Descriptive statistics and one‐way analysis of variance were used to compare TKA outcomes by diagnosis. Effect sizes and standardized response means (SRMs) were calculated between baseline and recovery. Results Of the participating 18,897 patients, 834 of those with RA (5.3%) and 315 of those with OA (10.2%) had undergone index TKA at similar mean ages (65 and 68 years). Post‐TKA, significant improvements were observed for most domains of pain, function, and HRQOL within both disease groups, with greater impact in OA. Based on the SRM, the maximum improvement was shown in index knee pain (SRM −1.33 in RA and −1.34 in OA; effect size −1.75 and −1.94, respectively). The Health Assessment Questionnaire II and the Short Form 36 physical component summary were the most responsive HRQOL indices in detecting post‐TKA improvement in RA. A diagnosis of RA, lower income, and preoperative anxiety were independently associated with a lower degree of improvement in index knee pain following TKA. Conclusion TKA is highly effective in reducing clinically relevant knee pain (to a greater extent than its effect on other subjective HRQOL indices in patients with RA), although this improvement is less marked as compared to that among patients with OA. TKA serves as a “time machine” via which patients can return to a lifestyle with less disability, before the arthritis process catches up in RA.
Length of Stay, Functional Outcome, and Mortality Following Medical Rehabilitation
Authors: Pamela W Duncan, Gerben Dejong, Helen Hoenig, Bruce Vogel
Journal: JAMA (2005)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
946. Combined E1B-Mutant Adenovirus and Radiotherapy Generates Synergistic Anti-Tumor Effects
Authors: Jaesung Kim, Jung-Hee Choi, Jing-Hua Huang, Pyung Hwan Kim, Beom-Seok Suh, Jin-Sil Seong, Chae-Ok Yun
Journal: Molecular Therapy (2004)

Adenovirus (Ad) has been genetically modified to exhibit various functions. The replication competent adenovirus is exemplary, being used as an effective anti-tumor agent in cancer gene therapy. Two E1B-mutant adenovirus strains, Ad-ΔE1B, Ad-ΔE1B55, have been previously developed, both of which undergo selective replication in cancer cells, ultimately killing them. The E1B 55kDa-deleted adenovirus Ad-ΔE1B55 replicates selectively in tumor cells with dysfunctional tumor suppressor gene p53. On the other hand, the E1B 19kDa protein was shown to confer anti-apoptotic function, possibly repressing inherent apoptosis in tumor cells. Ad-ΔE1B, with both its E1B 19kDa and E1B 55kDa deleted, showed, in addition to tumor-selective replication, a supplemental anti-tumor effect, allowing apoptosis in the tumor cells. Recently, the application of replication competent adenovirus in combination with radiotherapy or chemotherapy has shown optimistic preclinical and clinical trial results. In this study, we evaluated Ad-ΔE1B or Ad-ΔE1B55-mediated cytotoxicity in combination with irradiation treatment. Hepatocellular carcinoma (Hep3B), lung cancer (A549), and cervical cancer (C33A) cell lines were treated, in vitro, with Ad-ΔE1B or Ad-ΔE1B55, followed by irradiation treatment. The highest cytotoxicity was observed in cancer cell lines treated with Ad-ΔE1B and irradiation. Apoptosis was synergistically increased in cancer cell lines treated with Ad-ΔE1B and irradiation, demonstrated by flow cytometry and TUNEL assay. Established C33A xenografts were treated with 108 plaque forming unit (PFU) of Ad-ΔE1B or Ad-ΔE1B55, in conjunction with 10 Gray (Gy) of single fraction local tumor radiation. Individually, Ad-ΔE1B, Ad-ΔE1B55, and 10 Gy irradiation caused moderate decrease in tumor size, and after 31 days, the tumors were 44.2%, 76.3%, and 36.9%, in volume (mm3), respectively. In contrast, a sharp decrease in tumor size was observed when the adenovirus treatment was combined with 10 Gy irradiation; at 31 days, the tumor was measured 10.0% and 18.9% in size respectively. Overall, this study presents strong evidence for a synergistic effect when treatment of E1B-mutant adenovirus strains is combined with irradiation exposure.
Abstract 19588: Angiotensin Converting Enzyme Inhibitors and Mortality Benefit in Systolic Heart Failure Patients With Glomerular Filtration Rate &lt;30 ml/min/1.73 m2
Authors: Chakradhari Inampudi, Vladimir Cotarlan
Journal: Circulation (2014)

Introduction: Randomized controlled trials have shown beneficial effect of Angiotensin converting enzyme inhibitors (ACEI) in reducing mortality in patients with systolic heart failure (HF) and chronic kidney disease (CKD) with glomerular filtration rate (GFR) between 30-59 ml/min/1.73m2 but weak evidence exists in patients with GFR &lt; 30 Hypothesis: We hypothesize that ACEI use is associated with lower mortality in CKD patients with GFR &lt; 30. Methods: Using electronic medical records, we identified 2578 patients with advanced CKD defined as GFR &lt; 30 but not on dialysis. We required a GFR &lt; 30 on two occasions over a 60 day period to insure stability of CKD. Clinical outcomes were reviewed following the index date which was the date of first GFR &lt; 30. Results: Of 2,578 patients (mean age 66+/-15, 61% males) with advanced CKD (GFR&lt;30), 1,064 (41%) have been treated with an ACEI while 1,514 (59%) never received an ACEI. Kaplan Meyer Survival showed reduced mortality in the group of patients treated with an ACEI compared to those never treated with an ACEI despite more comorbidities present in the former group (mean survival 3.9 vs 4.8 years, p&lt;0.001, Fig 1). Of the patients treated with an ACEI, 232 (22%) continued the ACEI till the end of follow up while 832 (78%) patients discontinued the drug: 93 (9%) prior to index date and 739 (69%) after index date. Survival was significantly better in patients who continued the ACEI than those who discontinued the drug late (after the index date) and those who discontinued early (prior to index date) than in those never treated with an ACEI (Fig 2). Conclusion: Treatment with ACEIs is associated with improved survival in CKD patients with GFR &lt; 30ml/min/1.73m2
Effect of Different Corticosteroid Regimens on Hypothalamic-pituitary-adrenal Axis and Growth in Juvenile Chronic Arthritis
Authors: M A Byron, J Jackson, B M Ansell
Journal: Journal of the Royal Society of Medicine (1983)

Linear growth was recorded in 36 children with juvenile chronic arthritis. In 20, the hypothalamic-pituitary-adrenal axis (HPA axis) was assessed by insulin-induced hypoglycaemia, the results of which correlated well with resting cortisol levels. Three groups were identified according to type of corticosteroid regimen administered. Group 1 (6 children), receiving daily corticosteroid therapy, were clearly suppressed and failing to grow. Group 2 (13 children) had received an alternate-day regimen from the initiation of corticosteroid therapy; they were not suppressed and growth was satisfactory in 11. Group 3 (17 children) were receiving alternate-day therapy, but had had daily corticosteroid in the past; they showed no clear pattern of suppression or growth. Factors influencing the recovery of the HPA axis and resumption of growth were assessed. No difference was found in the individual growth of 7 children who commenced alternate-day therapy before the age of 5, compared with matched controls. It is suggested that daily divided doses of corticosteroid should not be used. Ideally, a single morning dose (up to 2 mg/kg) alternate-day regimen should be employed, as this regimen has minimal effects on HPA function and growth, even in young children. For very severe systemic features, it may be necessary to add a small single dose on the alternate day.
CLINICAL DESENSITIZATION TO WHEAT BY USE OF AN ACETYLCHOLINE DERIVATIVE
Authors: Emmet F. Pearson
Journal: Annals of Internal Medicine (1940)

Article1 June 1940CLINICAL DESENSITIZATION TO WHEAT BY USE OF AN ACETYLCHOLINE DERIVATIVEEMMET F. PEARSON, F.A.C.P.EMMET F. PEARSON, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-12-2241 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe focal reactions which result in the clinical syndromes of bronchial asthma, vasomotor rhinitis, eczema, urticaria and angioneurotic edema occur in tissue which is supplied by the cholinergic division of the autonomic nervous system. The peripheral mechanism which produces these symptoms may be initiated or exaggerated by different stimuli such as the antigen-antibody reaction of allergy, local irritation, infection, autonomic nervous reflex, and emotion or psychogenic stimuli. It is frequently possible to reproduce at will the particular symptom to which a hypersensitive individual is susceptible by small doses of acetylcholine or its derivatives. Hundreds of methods of altering the status... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Springfield, Illinois*Delivered before the Central Society for Clinical Research, Chicago, November 6, 1938.Mecholyl for this work was supplied through the courtesy of the Merck Laboratories, Rahway, N. J. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNature and Causation of Insect Bite ReactionsInhalant sensitization and shock in guinea pigs under controlled atmospheric conditionsMecholyl desensitization in the treatment of asthma 1 June 1940Volume 13, Issue 12Page: 2241-2245KeywordsAcetylcholineAllergy and immunologyAutonomic nervous systemCholinergicsEczemaEdemaEmotionsReflexesRhinitisUrticaria ePublished: 1 December 2008 Issue Published: 1 June 1940 PDF downloadLoading ...
619. Augmentation of Anti-Tumor Activity of a Recombinant Adeno-Associated Virus 2 Carcinoembryonic Antigen Vaccine with Plasmid Adjuvants
Authors: Selvarangan Ponnazhagan, Gandham Mahendra, Jose Lima, Wayne Aldrich, Connie Jenkins, Changchun Ren, Sanjay Kumar, Lisa Kallman, Theresa V. Strong, Denise R. Shaw, Pierre L. Triozzi
Journal: Molecular Therapy (2004)

RECOMBINANT adeno-associated virus (rAAV) vectors have been successfully used for sustained expression of therapeutic genes. We investigated the potential of using rAAV-2 as a cancer vaccine vector and the impact of plasmid adjuvants on this activity. C57BL/6 mice received a single intramuscular injection of rAAV expressing the human tumor-associated antigen, carcinoembryonic antigen (CEA). Three weeks later, when CEA expression was optimal, plasmids encoding either mouse granulocyte macrophage-colony stimulating factor (pGM-CSF) or stromal-derived factor (pSDF) 1a or an empty plasmid vector was injected into the same muscle. Mice were challenged one week after the plasmid delivery with syngeneic MC38 tumor cells stably expressing CEA. Immunization with rAAV-CEA alone resulted in sustained transgene expression and the elicitation of a humoral immune response to CEA. Cellular immune response, however, was weak, and tumor protection was not observed. In contrast, immunization with rAAV-CEA and any of the plasmid adjuvants resulted in stronger cellular immune responses to CEA and tumor protection. The addition of plasmid adjuvants increased dendritic cell recruitment in situ. Infiltration of myeloid dendritic cells was observed when either pGM-CSF or the empty vector was applied as adjuvant. Infiltration of plasmacytoid dendritic cells was observed in rAAV-CEA and pSDF-1a immunized mice. The addition of the plasmid adjuvants also increased the production of interferon-gamma in cytokine release assay. These data indicate that robust rAAV transgene expression of a tumor antigen followed by transient plasmid delivery to recruit and activate dendritic cells is an effective method of eliciting anti-tumor cellular immune responses.
Pathogenesis of Mucosal Injury in the Blind Loop Syndrome
Authors: Anita Jonas, Peter R. Flanagan, Gordon G. Forstner
Journal: Journal of Clinical Investigation (1977)

The effect of intestinal bacterial over-growth on brush border hydrolases and brush border glycoproteins was studied in nonoperated control rats, control rats with surgically introduced jejunal self-emptying blind loops, and rats with surgically introduced jejunal self-filling blind loops. Data were analyzed from blind loop segments, segments above and below the blind loops, and three corresponding segments in the nonoperated controls. Rats with self-filling blind loops had significantly greater fat excretion than controls and exhibited significantly lower conjugated:free bile salt ratios in all three segments. Maltase, sucrase, and lactase activities were significantly reduced in homogenates and isolated brush borders from the self-filling blind loop, but alkaline phosphatase was not affected. The relative degradation rate of homogenate and brush border glycoproteins was assessed by a double-isotope technique involving the injection of d-[6-(3)H]glucosamine 3 h and d-[U-(14)C]glucosamine 19 h before sacrifice, and recorded as a (3)H:(14)C ratio. The relative degradation rate in both homogenate and brush border fractions was significantly greater in most segments from rats with self-filling blind loops. In the upper and blind loop segments from rats with self-filling blind loops, the (3)H:(14)C ratios were higher in the brush border membrane than in the corresponding homogenates, indicating that the increased rates of degradation primarily involve membrane glycoproteins. Incorporation of d-[6-(3)H]glucosamine by brush border glycoproteins was not reduced in rats with self-filling blind loops, suggesting that glycoprotein synthesis was not affected. Polyacrylamide gel electrophoresis of brush border glycoproteins from the contaminated segments indicated that the large molecular weight glycoproteins, which include many of the surface hydrolases, were degraded most rapidly. Brush border maltase, isolated by immunoprecipitation, had (3)H:(14)C ratios characteristic of the most rapidly degraded glycoproteins. The results indicate that bacteria enhance the destruction of intestinal surface glycoproteins including disaccharidases. Since alkaline phosphatase, a glycoprotein, is not affected, the destruction is selective and presumably involves only the most exposed membrane components.
704. Ex Vivo and In Vivo Expansion of HoxB4-Transduced CD34+ Cells from Dogs, Baboons, Macaques and Humans
Authors: Andre Larochelle, Allen Krouse, Donald Orlic, Robert E. Donahue, Cynthia E. Dunbar, Peiman Hematti
Journal: Molecular Therapy (2004)

AMD3100 (AMD) has recently been shown to rapidly mobilize primitive hematopoietic cells in mice and humans, but little is known about the properties of cells mobilized with this agent. We initiated a study to determine retroviral (RV) in vivo gene marking efficiency in AMD-mobilized CD34+ cells in rhesus macaques. CD34+ cells collected 3 hours after administration of AMD to 2 animals were transduced using RV vectors containing the Neo® gene. Animals were irradiated and cells reinfused immediately after transduction. By molecular analysis, the levels of PB MNC and granulocyte Neo® gene marking at steady-state (up to 12 months post-transplantation) was 1–2% in animal RC909 and 30–40% in RQ2851.
Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia
Authors: Amar Gajjar, Patricia L. Harrison, John T. Sandlund, Gaston K. Rivera, Raul C. Ribeiro, Jeffrey E. Rubnitz, Bassem Razzouk, Mary V. Relling, William E. Evans, James M. Boyett, Ching-Hon Pui
Journal: Blood (2000)
Hair follicle stem cell differentiation is inhibited through cross‐talk between Wnt/β‐catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia
Authors: G.J. Leirós, A.I. Attorresi, M.E. Balañá
Journal: British Journal of Dermatology (2012)

Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells.To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells.HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt/β-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens.In a coculture model with human DPC from patients with AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition.These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.
The effect of green tea polyphenols on macrophage migration inhibitory factor-associated steroid resistance
Authors: S.U. Noh, Y.M. Park
Journal: British Journal of Dermatology (2011)

Recently, evidence has been obtained to suggest that inflammation is provoked through upregulation of macrophage migration inhibitory factor (MIF) expression by steroids. However, little is known regarding the effect of steroids on MIF expression in human keratinocytes and the counter-effect of epigallocatechin-3-gallate (EGCG), a member of the class of green tea polyphenols.We determined whether or not steroids cause the upregulation of MIF in human keratinocytes, and if so, whether or not EGCG suppresses MIF upregulation in keratinocytes by steroids. We then assessed the effects of EGCG on MIF-induced Th-related chemokine and cytokine expression in keratinocytes.HaCaT keratinocytes were first treated with dexamethasone in the presence or absence of EGCG in the culture medium. The keratinocytes were then treated with recombinant human (rh)-MIF in the presence or absence of EGCG in the culture medium. The expression of mRNA and protein in Th-related cytokines and chemokines, including MIF in the keratinocytes, was measured by real-time reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay.Dexamethasone significantly enhanced MIF expression in human keratinocytes, and EGCG significantly downregulated the expression of dexamethasone-induced MIF. EGCG also significantly downregulated rh-MIF-induced expression of Th-related cytokines and chemokines, such as interleukin (IL)-6, IL-18, transforming growth factor-β, CCL17, CCL22 and CXCL10, in human keratinocytes.These results demonstrated that EGCG may have a novel pharmacological effect to prevent steroid-induced tachyphylaxis and inflammation by suppressing the expression of MIF in human keratinocytes.
Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth
Authors: David Lyden, Koichi Hattori, Sergio Dias, Carla Costa, Pamela Blaikie, Linda Butros, Amy Chadburn, Beate Heissig, Willy Marks, Larry Witte, Yan Wu, Daniel Hicklin, Zhenping Zhu, Neil R. Hackett, Ronald G. Crystal, Malcolm A.S. Moore, Katherine A. Hajjar, Katia Manova, Robert Benezra, Shahin Rafii
Journal: Nature Medicine (2001)
Safra Kanalı Taşı için Endoskopik Papiller Balon Dilatasyonu: 1 Hastadaki Yakın ve Uzun-Dönem Sonuçlar
Authors: Takeshi Tsujino, Takao Kawabe, Yutaka Komatsu, Haruhiko Yoshida, Hiroyuki Isayama, Takashi Sasaki, Hirofumi Kogure, Osamu Togawa, Toshihiko Arizumi, Saburo Matsubara, Yukiko Ito, Yousuke Nakai, Natsuyo Yamamoto, Naoki Sasahira, Kenji Hirano, Nobuo Toda, Minoru Tada, ve Masao Omata
Journal: Clinical Gastroenterology and Hepatology (2007)
Expression of MDR1 P-glycoprotein and MRP-1 proteins in melanoma
Authors: Naomi Walsh, Susan Kennedy, Annemarie Larkin, Jo Ballot, Wei Ooi, Giuseppe Gullo, Martin Clynes, John Crown, Lorraine O'Driscoll
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

B5 

Background: Multiple drug resistance (MDR) is a phenomenon whereby cancer cells are resistant to a broad range of structurally and mechanistically unrelated drugs; either inherently or acquired, following exposure to chemotherapy (CRx) drug(s). ATP-dependent membrane-bound drug efflux pumps (EP), including MDR1 P-glycoprotein (MDR1 P-gp) and MRP-1, may be mediators of clinically relevant MDR. Here we studied the prevalence of MDR1 P-gp and MRP-1 in melanomas which are highly CRx-resistant.    Methods: In this retrospective study we analysed the expression of MDR1 P-gp and MRP-1 protein in 191 melanoma specimens by immunohistochemistry (IHC). Anti-MDR1 P-gp monoclonal antibody, 6/1C, and anti-MRP-1 monoclonal antibody, P2A8(6), generated in our laboratory, were used for this analysis. IHC staining was evaluated semi-quantitatively by two independent observers.    Results: EP expression is common in melanoma. 96.3% (184/191) of cases were positive for MRP-1, 82.7% (158/191) expressed MDR1 P-gp, with approx. 79.5% expressing both MRP-1 and MDR1 P-gp. Only 1/191 specimens analysed expressed neither of these EP.    Conclusions: Expression of one or both EP is common in melanoma. These observations do not prove causality, but they are consistent with the hypothesis that EP might be, at least partly, responsible for MDR in this form of cancer.