tbuckley/cabot-search huggingface dataset:
Evidence that Singlet Oxygen-induced Human T Helper Cell Apoptosis Is the Basic Mechanism of Ultraviolet-A Radiation Phototherapy
Authors: Akimichi Morita, Thomas Werfel, Helger Stege, Constanze Ahrens, Karin Karmann, Markus Grewe, Susanne Grether-Beck, Thomas Ruzicka, Alexander Kapp, Lars-Oliver Klotz, Helmut Sies, Jean Krutmann
Journal: The Journal of Experimental Medicine (1997)

Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.
Abandoning babies safely
Authors: J. Taylor
Journal: BMJ (1999)

Cost shiftingHospital at home had little input to the domestic care of patients-with the exception of washing the patient.This may point to hospital at home adopting a role oriented towards patients' personal care, in addition to their nursing needs, leaving domestic support to the usual carer, to patients themselves, or to their relatives.Patients' perceptions of other costs associated with hospital at home varied: 44% reported using more lighting, 30% more laundry, 27% more heating, and 17% more hot water.In general the patients ascribed the use of extra utilities to the actions of night nurses, with patients themselves having little choice in the matter. DiscussionThe economic analyses suggest that care can be provided in patients' homes using the model of hospital at home, to avoid hospital admission, at the same or lower cost than an equivalent admission to hospital.The sensitivity analyses on hospital at home nurses' contact time with patients compared with their non-contact time suggest that the level of recruitment to the trial had an impact on the estimated cost per case for hospital at home.Adopting a balance of nursing work that might be more plausible for an established hospital at home service reduced the estimated cost per day for hospital at home to a level similar to that estimated for hospital care.An examination of the contribution of different services to the costs of care of patients in the trial indicated an important role for acute hospital care in the management of patients in hospital at home.Costs for acute hospital care represented 26% of the costs for the initial episode in patients randomised to hospital at home and 37% of costs at three months.This study shows that hospital at home may provide a viable alternative to acute hospital when viewed in the long term.Currently the service runs as a complement to hospital care, but it may have a role in managing demand for hospital admission and can provide an acceptable form of care for patients who do not want admission to hospital.This study would not have been possible without the cooperation of Fosse NHS Trust, Leicestershire Health, participating general practitioners, the acute hospitals, Leicestershire Bed Bureau, and, most crucially, the Hospital at Home Service itself.Particular thanks are due, in relation to the economic evaluation, to finance and information staff at all participating trusts, managers and staff of physiotherapy, occupational therapy, district nursing services, and the Red Cross, who provided information on services provided to patients, and to patients themselves for information provided in interviews.Contributors: JJ was responsible for the design and collection of data on workload and health economics, was principal writer of the paper, and is its guarantor.AWi was responsible for the design and completion of the study.HP managed the trial, collected data, and assisted in analysis and interpretation.AWy contributed
HER2/neu expression correlates with vascular endothelial growth factor-C and lymphangiogenesis in lymph node-positive breast cancer
Authors: S.F. Schoppmann, D. Tamandl, L. Roberts, G. Jomrich, A. Schoppmann, R. Zwrtek, P. Dubsky, M. Gnant, R. Jakesz, P. Birner
Journal: Annals of Oncology (2009)
Primary role of renal homografts in setting chronic blood pressure levels in rats.
Authors: L K Dahl, M Heine
Journal: Circulation Research (1975)

The genotype of homograft kidneys plays the primary role in determining chronic blood pressure levels in two strains of rats with opposite genetically controlled propensities for hyptertension. In hypertensive rats from the hypertension-prone (S) strain, a renal homograft from the same strain resulted in a slight rise in blood pressure to a level that was equivalent to that in appropriate uninephrectomized S controls. In contrast, a renal homograft from the hypertension-resistant (R) strain led to a sharp fall in blood pressure in hypertensive S recipients. Opposite results were found when the host came from the R strain: R homografts maintained the same low pressure as that seen in controls, whereas S homografts resulted in hypertension. We concluded that genetically controlled factors operating through the kidney can chronically modify the blood pressure up or down. The central role of the kidney in hypertension is thus further documented.
Cardiovascular comorbidities in patients with psoriatic arthritis: a systematic review
Authors: Anna Jamnitski, Deborah Symmons, Mike J L Peters, Naveed Sattar, Iain MciInnes, Michael T Nurmohamed
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Data regarding cardiovascular comorbidity and cardiovascular risk factors in patients with psoriatic arthritis (PsA) are limited. To evaluate the cardiovascular risk profile, a systematic literature search was performed to provide an extensive summary of all studies available on cardiovascular risk in PsA. <h3>Methods</h3> Medline, EMBASE and the Cochrane library were searched from January 1966 to April 2011 for English language articles on data concerning cardiovascular diseases and cardiovascular risk factors in PsA. Review articles, case reports and studies on psoriasis alone were excluded. <h3>Results</h3> Twenty-eight articles were included in this review. Studies on all-cause mortality revealed mixed results. Available data on cardiovascular disease appeared more consistent, indicating an increased cardiovascular mortality and morbidity in PsA. Commensurate with this, surrogate markers of subclinical atherosclerosis, arterial stiffness and cardiovascular risk factors, for example hypertension, dyslipidaemia, obesity and metabolic-related factors, were more prominent in PsA compared with controls. Suppression of inflammation was linked with a favourable effect on cardiovascular surrogate markers, for example carotid intima media thickness and endothelial dysfunction, in several (un)controlled studies. <h3>Conclusion</h3> Most studies point towards an increased cardiovascular risk in PsA, broadly on a par with the risk level in rheumatoid arthritis, emphasising the need for similar cardiovascular risk management in both conditions. Further studies are needed to indicate whether inflammatory suppression or modification of traditional cardiovascular risk factors, or both, will reduce cardiovascular risk.
Radiolabelled lymphocyte migration in rheumatoid synovitis.
Authors: C Jorgensen, I Couret, C Bologna, M Rossi, J Sany
Journal: Annals of the Rheumatic Diseases (1995)

To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA).After isolation of the lymphocytes, the cells were radiolabelled in vitro with 250 MBq 99mTc-HMPAO. The scans were performed 30 minutes, three hours and 20 hours after injection.An increase of the scintigram signal obtained at 20 hours was associated with a high joint swelling and joint pain score (F test = 3.07, p < 0.002), but not with the radiological score. A positive joint scintigram was predictive of active synovitis. Although the scintigram variation over time did not reach statistical significance, the kinetics of the scintigram signal tended to differ according to the disease duration: in early RA, active arthritis could be clearly imaged as early as 30 minutes, increased at three hours and the signal intensity persisted at 20 hours. In contrast, in long standing disease, the affected joints were imaged at 30 minutes, persisted unchanged at three hours, and the scintigram score decreased significantly at 20 hours.The study shows that 99mTc-HMPAO joint scintigraphy may be used to detect and to localise active rheumatoid arthritis.
Cost of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and systemic lupus erythematosus in Germany
Authors: D Huscher, S Merkesdal, K Thiele, H Zeidler, M Schneider, A Zink
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To estimate and compare the direct and indirect costs of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE), and to evaluate the effect of sex, disease duration and functional status on the various cost domains. <b>Methods:</b> Data of outpatients, aged 18–65, with rheumatoid arthritis (n = 4351), ankylosing spondylitis (n = 827), PsA (n = 908) or SLE (n = 844), who were enrolled in the national database of the German collaborative arthritis centres in 2002, were analysed. Data on healthcare consumption, out-of-pocket expenses and productivity losses were derived from doctors and patients. For the calculation of indirect costs, the human capital approach (HCA) and the friction cost approach (FCA) were applied. <b>Results:</b> Mean direct costs amounted to €4737 a year in rheumatoid arthritis, €3676 in ankylosing spondylitis, €3156 in PsA and €3191 in SLE. By using the HCA, total costs were calculated at €15 637 in rheumatoid arthritis, €13 513 in ankylosing spondylitis, €11 075 in PsA and €14 411 in SLE, whereas with the FCA the numbers were €7899, €7204, €5570 and €6518, respectively. Costs increased with disease duration and were strongly dependent on functional status. In patients with the highest disability (&lt;50% of full function), the total costs on applying the HCA were €34 915 in rheumatoid arthritis, €29 647 in alkylosing spondylitis, €37 440 in PsA and €32 296 in SLE. <b>Conclusion:</b> The costs of illness are high in all four diseases, with a strong effect of functional status on total costs. Indirect costs differ by the factor 3, based on whether the HCA or the FCA is used.
Cryoglobulinaemia and rheumatic manifestations in patients with hepatitis C virus infection
Authors: Y. H. Lee, J. D. Ji, J. E. Yeon, K. S. Byun, C. H. Lee, G. G. Song
Journal: Annals of the Rheumatic Diseases (1998)

To investigate the association of cryoglobulinaemia and rheumatic manifestations in Korean patients with hepatitis C virus (HCV) infection.Forty nine Korean patients with HCV infection were recruited. The prevalence, concentration, and type of cryoglobulin (by immunofixation), rheumatoid factor (RF), antinuclear antibody (ANA), and various rheumatological symptoms were investigated and HCV genotype was determined by polymerase chain reaction with genotype specific primer.The prevalence of cryoglobulin was 59% in Korean HCV patients and the concentration of cryoglobulin was 9.8 (7.9) g/l (mean (SD)). The type of cryoglobulinaemia was identified in 23 (80%) of 29 HCV patients with cryoglobulinaemia and they were all type III. There were no differences in age, sex, history of operation and transfusion, proportion of liver cirrhosis between the patients with cryoglobulinaemia and those without cryoglobulinaemia. The frequencies of RF and ANA were 14% and 3.4% respectively in HCV patients with cryoglobulinaemia. There was no difference in HCV genotype between the patients with cryoglobulinaemia and those without cryoglobulinaemia. Clinical features of HCV patients were as follows: arthralgia/arthritis (35%), cutaneous manifestation (37%), Raynaud's phenomenon (8%), paresthesia (44%), dry eyes (22%), dry mouth (10%), oral ulcer (33%), and abdominal pain (14%). However, these rheumatological symptoms did not differ between the two groups.Although the rheumatological symptoms were not different between HCV patients with and without cryoglobulinaemia, HCV patients showed various rheumatological manifestations. These result suggests that HCV infection could be included as one of the causes in patients with unexplained rheumatological symptoms.
Cigarette-smoking is associated with reduced airway compliance and increased volume fraction of extracellular matrix in human bronchi
Authors: Robyn Jones, Alan James, Howard Mitchell, Alvenia Cairncross, John Elliot, Peter McFawn, Peter Noble
Journal: European Respiratory Journal (2013)

Background  Cigarette smoke exposure is likely to account for differences in pathophysiology in chronic obstructive pulmonary disease (COPD) and asthma.   Aim  To examine the relationship between smoking and the mechanical properties and structure of the airway smooth muscle (ASM) layer in human airways.   Methods  Bronchial segments were obtained from subjects (n=12, 66±6yr) undergoing lobectomy for pulmonary neoplasms. Bronchoconstriction (% volume change) to acetylcholine, airway compliance and pressure to collapse were measured in vitro. The area and volume fractions (V V ) of muscle and extracellular matrix (ECM) in the ASM layer were subsequently assessed in the fixed segments.   Results  Pack-years of smoking were inversely related to airway compliance (p V  ECM within the ASM layer (p V  muscle or the size or number of ASM cells.   Conclusions  The fraction of ECM within the ASM layer, rather than changes in ASM cells, is altered by smoking and this restricts radial movement. This may contribute to the functional differences between COPD and asthma.   Supported by:  NHMRC Project Grant #513842  Conflict of interest:  No.
Controlled Trials of Hemoperfusion for Intoxication
Authors: O. S. BETTER
Journal: Annals of Internal Medicine (1979)

Letters and Corrections1 December 1979Controlled Trials of Hemoperfusion for IntoxicationO. S. BETTER, H. J. GURLAND, G. BRUNNER, E. HOFFER, T. M. S. CHANG, K. MAEDA, J. M. COURTNEY, R. MAINI, P. C. FARRELL, J. L. ROSENBAUM, M. C. GELFAND, S. SIDEMAN, A. GIMSON, U. TAITLEMAN, J. F. WINCHESTERO. S. BETTERSearch for more papers by this author, H. J. GURLANDSearch for more papers by this author, G. BRUNNERSearch for more papers by this author, E. HOFFERSearch for more papers by this author, T. M. S. CHANGSearch for more papers by this author, K. MAEDASearch for more papers by this author, J. M. COURTNEYSearch for more papers by this author, R. MAINISearch for more papers by this author, P. C. FARRELLSearch for more papers by this author, J. L. ROSENBAUMSearch for more papers by this author, M. C. GELFANDSearch for more papers by this author, S. SIDEMANSearch for more papers by this author, A. GIMSONSearch for more papers by this author, U. TAITLEMANSearch for more papers by this author, J. F. WINCHESTERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-6-925_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The following summary prepared by participants in the recent International Workshop on Hemoperfusion held in Haifa, Israel, is submitted in response to the report by Lorch and Garella that appeared in the August 1979, issue (1).Conservative medical management with support of vital systems represents the treatment of choice for most patients with toxic ingestions. For patients with serious intoxications fulfilling the following criteria, charcoal or resin hemoperfusion is indicated: [1] severe clinical intoxication leading to hypoventilation, hypothermia, hypotension, and nonresponsiveness despite supportive clinical measures; [2] lethal blood concentration of one or more potentially adsorbable drugs; and...Reference1. LORCHGARELLA JS. Hemoperfusion to treat intoxications. Ann Intern Med. 1979;91:301-4. LinkGoogle Scholar1. LORCHGARELLA JS. Hemoperfusion to treat intoxications. Ann Intern Med. 1979;91:301-4. LinkGoogle Scholar2. SPODICK D. Revascularization of the heart—numerators in search of denominators. Am Heart J. 1971;81:149-57. Editorial. CrossrefMedlineGoogle Scholar3. SPODICKARONOWBARBER DWB. Controlled trials in surgery. Lancet. 1978;1:1213-4. Letter. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByExtracorporeal Treatment of PoisoningsThe Development of a Haemoperfusion Device for Chronic UseHemoperfusion for IntoxicationJONATHAN A. LORCH, M.D., SERAFINO GARELLA, M.D. 1 December 1979Volume 91, Issue 6Page: 925-925KeywordsAttentionBloodDrugsHemoperfusionHypotensionHypothermiaIngestionIntoxication Issue Published: 1 December 1979 PDF DownloadLoading ...
TRKing Down an Old Oncogene in a New Era of Targeted Therapy
Authors: Aria Vaishnavi, Anh T. Le, Robert C. Doebele
Journal: Cancer Discovery (2014)

The use of high-throughput next-generation sequencing techniques in multiple tumor types during the last few years has identified NTRK1, 2, and 3 gene rearrangements encoding novel oncogenic fusions in 19 different tumor types to date. These recent developments have led us to revisit an old oncogene, Trk (originally identified as OncD), which encodes the TPM3-NTRK1 gene fusion and was one of the first transforming chromosomal rearrangements identified 32 years ago. However, no drug has yet been approved by the FDA for cancers harboring this oncogene. This review will discuss the biology of the TRK family of receptors, their role in human cancer, the types of oncogenic alterations, and drugs that are currently in development for this family of oncogene targets.Precision oncology approaches have accelerated recently due to advancements in our ability to detect oncogenic mutations in tumor samples. Oncogenic alterations, most commonly gene fusions, have now been detected for the genes encoding the TRKA, TRKB, and TRKC receptor tyrosine kinases across multiple tumor types. The scientific rationale for the targeting of the TRK oncogene family will be discussed here.
Telomere Dysfunction: A Potential Cancer Predisposition Factor
Authors: X. Wu, C. I. Amos, Y. Zhu, H. Zhao, B. H. Grossman, J. W. Shay, S. Luo, W. K. Hong, M. R. Spitz
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Genetic instability associated with telomere dysfunction (i.e., short telomeres) is an early event in tumorigenesis. We investigated the association between telomere length and cancer risk in four ongoing case–control studies. Methods: All studies had equal numbers of case patients and matched control subjects (92 for head and neck cancer, 135 for bladder cancer, 54 for lung cancer, and 32 for renal cell carcinoma). Telomere length was measured in peripheral blood lymphocytes from study participants. Genetic instability was assessed with the comet assay. Patient and disease characteristics were collected and analyzed for associations with risk for these cancers. All statistical tests were two-sided. Results: Telomeres were statistically significantly shorter in patients with head and neck cancer (6.5 kilobases [kb]) than in control subjects (7.4 kb) (difference = 0.9 kb, 95% confidence interval [CI] = 0.5 to 1.2 kb; P<.001). Nine percent of patients with head and neck cancer were in the longest quartile of telomere length, whereas 59% were in the shortest quartile. Similar patterns were observed for lung, renal cell, and bladder cancer. When subjects were categorized into telomere length quartiles defined by the distribution in control subjects, the following inverse relationship between telomere length and cancer risk was observed: adjusted odds ratios [ORs] for decreasing quartiles = 0.84 (95% CI = 0.36 to 1.97), 1.77 (95% CI = 0.72 to 4.36), and 5.11 (95% CI = 1.90 to 13.77). In stratified analysis, we found a suggestive greater-than-additive interaction between smoking status and telomere length: for ever smokers with short telomeres, OR = 25.05 (95% CI = 6.91 to 90.73); for never smokers with short telomeres, OR = 6.18 (95% CI = 1.72 to 22.13); and for ever smokers with long telomeres, OR = 6.49 (95% CI = 1.54 to 27.38). Telomere length was statistically significantly and inversely associated with baseline and mutagen-induced genetic instability. Conclusion: Short telomeres appear to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers.
General practice premises
Authors: T White
Journal: BMJ (1977)

Relation of lecithin :sphingomyelin ratio (LSR) to presence of vernix in amntiotic fluxid LSR I Total ;2 !2 1-3 >3 No vernix seen 17 12 4 33 Cloudy, with doubtful 0 4 8 12 presence of vernix Vernix definitely present 0 5 29 34 Total 17 21 41 79Z2= 3487; DF 4; P <0(001; contingency coefficient 0-55.LSR is sometimes found in clear amniotic fluid, no immature LSR (> 2) was seen whenever vernix was present.Our findings suggest that amnioscopy might be used to assess fetal maturity before induction of labour.Induction can proceed if vernix is seen in the amniotic fluid and amniocentesis for the measurement of amniotic fluid LSR need be performed only when no vernix is seen.
Improved prediction of prostate cancer recurrence through systems pathology
Authors: Carlos Cordon-Cardo, Angeliki Kotsianti, David A. Verbel, Mikhail Teverovskiy, Paola Capodieci, Stefan Hamann, Yusuf Jeffers, Mark Clayton, Faysal Elkhettabi, Faisal M. Khan, Marina Sapir, Valentina Bayer-Zubek, Yevgen Vengrenyuk, Stephen Fogarsi, Olivier Saidi, Victor E. Reuter, Howard I. Scher, Michael W. Kattan, Fernando J. Bianco, Thomas M. Wheeler, Gustavo E. Ayala, Peter T. Scardino, Michael J. Donovan
Journal: Journal of Clinical Investigation (2007)

We have developed an integrated, multidisciplinary methodology, termed systems pathology, to generate highly accurate predictive tools for complex diseases, using prostate cancer for the prototype. To predict the recurrence of prostate cancer following radical prostatectomy, defined by rising serum prostate-specific antigen (PSA), we used machine learning to develop a model based on clinicopathologic variables, histologic tumor characteristics, and cell type-specific quantification of biomarkers. The initial study was based on a cohort of 323 patients and identified that high levels of the androgen receptor, as detected by immunohistochemistry, were associated with a reduced time to PSA recurrence. The model predicted recurrence with high accuracy, as indicated by a concordance index in the validation set of 0.82, sensitivity of 96%, and specificity of 72%. We extended this approach, employing quantitative multiplex immunofluorescence, on an expanded cohort of 682 patients. The model again predicted PSA recurrence with high accuracy, concordance index being 0.77, sensitivity of 77% and specificity of 72%. The androgen receptor was selected, along with 5 clinicopathologic features (seminal vesicle invasion, biopsy Gleason score, extracapsular extension, preoperative PSA, and dominant prostatectomy Gleason grade) as well as 2 histologic features (texture of epithelial nuclei and cytoplasm in tumor only regions). This robust platform has broad applications in patient diagnosis, treatment management, and prognostication.