tbuckley/cabot-search huggingface dataset:
Evaluation of Prolonged Antithrombotic Pretreatment ("Cooling-Off" Strategy) Before Intervention in Patients With Unstable Coronary Syndromes
Authors: Franz-Josef Neumann, Adnan Kastrati, Gisela Pogatsa-Murray, Julinda Mehilli, Hildegard Bollwein, Hans-Peter Bestehorn, Claus Schmitt, Melchior Seyfarth, Josef Dirschinger, Albert Schömig
Journal: JAMA (2003)

In unstable coronary syndromes, catheter intervention is frequently preceded by antithrombotic treatment to reduce periprocedural risk; however, evidence from clinical trials to support antithrombotic pretreatment is sparse.To test the hypothesis that prolonged antithrombotic pretreatment improves the outcome of catheter intervention in patients with acute unstable coronary syndromes compared with early intervention.Randomized controlled trial conducted from February 27, 2000, to April 8, 2002, and including patients admitted to 2 German tertiary care centers with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levels.Patients were randomly allocated to antithrombotic pretreatment for 3 to 5 days or to early intervention after pretreatment for less than 6 hours. In both groups, antithrombotic pretreatment consisted of intravenous unfractionated heparin (60-U/kg bolus followed by infusion adjusted to maintain partial thromboplastin time of 60 to 85 seconds), aspirin (500-mg intravenous bolus followed by 100-mg twice-daily oral dose), oral clopidogrel (600-mg loading dose followed by 75-mg twice-daily dose), and intravenous tirofiban (10- microg/kg bolus followed by continuous infusion of 0.10 microg/kg per min).Composite 30-day incidence of large nonfatal myocardial infarction or death from any cause.Of the 410 patients enrolled, 207 were allocated to receive prolonged antithrombotic pretreatment and 203 to receive early intervention. Elevated levels of cardiac troponin T were present in 274 patients (67%), while 268 (65%) had ST-segment depression. The antithrombotic pretreatment and the early intervention groups were well matched with respect to major baseline characteristics and definitive treatment (catheter revascularization: 133 [64.3%] vs 143 [70.4%], respectively; coronary artery bypass graft surgery: 16 [7.7%] vs 16 [7.9%]). The primary end point was reached in 11.6% (3 deaths, 21 infarctions) of the group receiving prolonged antithrombotic pretreatment and in 5.9% (no deaths, 12 infarctions) of the group receiving early intervention (relative risk, 1.96 [95% confidence interval, 1.01-3.82]; P =.04). This outcome was attributable to events occurring before catheterization; after catheterization, both groups incurred 11 events each (P =.92).In patients with unstable coronary syndromes, deferral of intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate intervention accompanied by intense antiplatelet treatment.
Endogenous interferon γ protects against cholestatic liver injury in mice
Authors: Miguel E. Sewnath, Tom Van Der Poll, Cornelis J. F. Van Noorden, Fiebo J. W. Ten Kate, Dirk J. Gouma
Journal: Hepatology (2002)

Cholestatic patients suffer from high perioperative morbidity and mortality, but the pathophysiology is still unknown. Interferon gamma (IFN-gamma) may play a role during cholestasis. Therefore, bile duct ligation (BDL) was induced in IFN-gamma alpha-chain receptor-deficient (IFN-gammaR(1)-/-) and wild-type (IFN-gammaR(1)+/+) mice. BDL elicited increased IFN-gamma messenger RNA and protein levels in the liver. One week after BDL, IFN-gammaR(1)+/+ mice showed less severe jaundice and liver injury than IFN-gammaR(1)-/- mice, as reflected by lower bilirubin and liver enzyme levels. In accordance, livers of IFN-gammaR(1)+/+ mice displayed smaller areas of necrosis by two-thirds than IFN-gammaR(1)-/- mice on histopathologic examination (P <.05), whereas mitotic activity and proliferating cell nuclear antigen (PCNA) labeling index was more than twice as high in IFN-gammaR(1)+/+ mice (P <.05). Livers of IFN-gammaR(1)+/+ mice displayed higher rates of apoptosis as indicated by DNA fragmentation rate, the number of apoptotic bodies, and poly ADP-ribose polymerase (PARP) immunostaining. BDL was not associated with lethality in IFN-gammaR(1)+/+ mice; IFN-gammaR(1)-/- mice, however, died from 10 days onward and survival after 2 weeks was 62% (10 of 16). In conclusion, these data suggest that IFN-gamma protects against liver injury during extrahepatic cholestasis by stimulation of apoptosis and subsequent proliferation of hepatocytes, leading to elegant removal of damaged hepatocytes, thus preventing necrosis and concomitant inflammatory responses.
PICOT Inhibits Cardiac Hypertrophy and Enhances Ventricular Function and Cardiomyocyte Contractility
Authors: Dongtak Jeong, Hyeseon Cha, Eunyoung Kim, Misuk Kang, Dong Kwon Yang, Ji Myoung Kim, Pyoung Oh Yoon, Jae Gyun Oh, Oliver Y. Bernecker, Susumu Sakata, Le Thi Thu, Lei Cui, Young-Hoon Lee, Do Han Kim, Sun-Hee Woo, Ronglih Liao, Roger J. Hajjar, Woo Jin Park
Journal: Circulation Research (2006)

Multiple signaling pathways involving protein kinase C (PKC) have been implicated in the development of cardiac hypertrophy. We observed that a putative PKC inhibitor, PICOT (PKC-Interacting Cousin Of Thioredoxin) was upregulated in response to hypertrophic stimuli both in vitro and in vivo. This suggested that PICOT may act as an endogenous negative feedback regulator of cardiac hypertrophy through its ability to inhibit PKC activity, which is elevated during cardiac hypertrophy. Adenovirus-mediated gene transfer of PICOT completely blocked the hypertrophic response of neonatal rat cardiomyocytes to enthothelin-1 and phenylephrine, as demonstrated by cell size, sarcomere rearrangement, atrial natriuretic factor expression, and rates of protein synthesis. Transgenic mice with cardiac-specific overexpression of PICOT showed that PICOT is a potent inhibitor of cardiac hypertrophy induced by pressure overload. In addition, PICOT overexpression dramatically increased the ventricular function and cardiomyocyte contractility as measured by ejection fraction and end-systolic pressure of transgenic hearts and peak shortening of isolated cardiomyocytes, respectively. Intracellular Ca(2+) handing analysis revealed that increases in myofilament Ca(2+) responsiveness, together with increased rate of sarcoplasmic reticulum Ca(2+) reuptake, are associated with the enhanced contractility in PICOT-overexpressing cardiomyocytes. The inhibition of cardiac remodeling by of PICOT with a concomitant increase in ventricular function and cardiomyocyte contractility suggests that PICOT may provide an efficient modality for treatment of cardiac hypertrophy and heart failure.
The information needs and preferred roles in treatment decision‐making of parents caring for infants with atopic dermatitis: a qualitative study
Authors: C. Gore, R. J. Johnson, A. L. Caress, A. Woodcock, A. Custovic
Journal: Allergy (2005)

Information needs and preferences in treatment decision-making of parents caring for infants with atopic dermatitis (AD) are unknown, despite emphasis on quality information-giving and involvement of health-care users in treatment decisions.To explore information needs and decisional role-preferences of parents caring for infants with AD.Qualitative study. Purposive sample: 31 parents caring for infants with AD. Tape-recorded focussed conversation-style interviews. Interview topic-guide literature-derived. Control Preferences Scale (5 sort-card vignettes 'very active' to 'very passive' role) adapted for use with parents; used to facilitate discussion. Thematic analysis of verbatim transcripts.Nine core information needs identified: AD-causation, role of diet, medication-use, medication-side-effects, exacerbating factors, new/alternative medication, nonpharmacological treatments, AD-prevention, AD and other atopic conditions. Parents desired verbal and written information. Many felt their baby's condition was not taken seriously, leading to delayed diagnosis and treatment. They had to be more active than they wished to obtain information/treatment. Parents preferred sharing decisions with their doctor.Parents caring for infants with AD have clearly defined, unmet information needs, forcing them into more active roles in the treatment decision-making process than they desire. The study-findings may inform the development of written information specifically for these parents and improve partnership during consultations.
Safety, Efficacy, and Biomarkers of Nivolumab With Vaccine in Ipilimumab-Refractory or -Naive Melanoma
Authors: Jeffrey S. Weber, Ragini Reiney Kudchadkar, Bin Yu, Donna Gallenstein, Christine E. Horak, H. David Inzunza, Xiuhua Zhao, Alberto J. Martinez, Wenshi Wang, Geoffrey Gibney, Jodi Kroeger, Cabell Eysmans, Amod A. Sarnaik, Y. Ann Chen
Journal: Journal of Clinical Oncology (2013)

Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma. Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in ipilimumab-refractory and -naive melanoma.In this phase I study, 90 patients with unresectable stage III or IV melanoma who were ipilimumab naive and had experienced progression after at least one prior therapy (cohorts 1 to 3, 34 patients) or experienced progression after prior ipilimumab (cohorts 4 to 6, 56 patients) received nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine.Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both ipilimumab-refractory and -naive patients was 25%. Median duration of response was not reached at a median of 8.1 months of follow-up. High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease. At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression. PD-L1 tumor staining was associated with responses to nivolumab, but negative staining did not rule out a response. Patients who experienced progression after nivolumab could respond to ipilimumab.In patients with ipilimumab-refractory or -naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks. Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refractory patients support combination or sequencing of nivolumab and ipilimumab.
A NEW SCHOOL FOR THE STUDY OF HEART DISEASE
Authors: F. J. Poynton
Journal: BMJ (1917)

most part of members of each university, for service over- seas in whatever field they could be of most use.The offers of the last two universities mentioned were not accepted, but units have been mobilized, equipped, and sent across the seas by each of the other universities, and an decount of: their formation was published in this JOURNAL at the time of their departure from Canada.In addition, in most cases funds have been established for their maintenance.The suggestion that.permanence should be given to such units, and that they should take the name of the university from which they came instead of a number, is one which, if put into effect, would be received with the greatest enthusiasm in Canada.
The status of PD-L1 and tumor-infiltrating immune cells predict resistance and poor prognosis in BRAFi-treated melanoma patients harboring mutant BRAFV600
Authors: D. Massi, D. Brusa, B. Merelli, C. Falcone, G. Xue, A. Carobbio, R. Nassini, G. Baroni, E. Tamborini, L. Cattaneo, V. Audrito, S. Deaglio, M. Mandalà
Journal: Annals of Oncology (2015)
Deprivation, distance and death in lung cancer
Authors: Michael D Peake
Journal: Thorax (2014)

There are wide differences in survival rates for lung cancer both within the UK1 and when comparing the UK with many countries in the western world.2 Socio-economic inequalities have been shown to have a significant impact on survival for the large majority of cancers in adults in the UK,3 and many studies have reported lower lung cancer survival rates in patients of lower socio-economic status.4––7 There is also wide variation in treatment rates of patients with lung cancer by geographical region,1 ,8 ,9 and the paper by Forrest et al 10 in this issue adds to the broadly consistent finding of lower treatment rates in patients from lower socio-economic backgrounds.11 In addition, many patients with lung cancer die very soon after diagnosis, a significant proportion with a particularly poor prognosis first presenting to secondary care as an emergency admission,12 a route to diagnosis that is more common in patients of lower socio-economic status.13 This would imply opportunities for earlier recognition of patients at high risk of lung cancer in primary care. Four important studies appear in this issue of Thorax , three from the UK and one from Australia, that address the issues of earlier diagnosis, early death, undertreatment and geographical distance from specialist centres, all of which have significant implications for optimising service provision for patients with lung cancer.10 ,14–16

Despite major improvements to cancer care in England over the last 15 years, the ‘deprivation gap’, in other words, the survival difference between individuals from the least-deprived compared with the most-deprived groups, has not improved significantly in recent years,17 a finding confirmed and startlingly quantified in a recent report from Public Health England's National Cancer Intelligence Network.18 This analysis estimated that both …
Fertility Preservation: A Vital Survivorship Issue for Young Women With Breast Cancer
Authors: Ann H. Partridge
Journal: Journal of Clinical Oncology (2008)

Improvements in the diagnosis and treatment of early breast cancer have led to an increased number of women living with a history of the disease. There are now more than 2.4 million breast cancer survivors in the US alone, and an estimated 10% of these women are of childbearing age. 1,2 In a landmark essay on cancer survivorship, Fitzhugh Mullen wrote: “The challenge in overcoming cancer is not only to find therapies that will prevent or arrest the disease quickly, but also to map the middle ground of survivorship and minimize medical and social hazards.’’ 3 For young adults with cancer, the threat or experience of infertility may be a particularly distressing consequence of a cancer diagnosis. In recognition of this concern, and with an awareness of the recent advances in the reproductive sciences, the American Society of Clinical Oncology (ASCO) has published guidelines recommending that oncologists discuss with patients the possibility of infertility when treated during their reproductive years. 4 Furthermore, ASCO suggests that oncologists be prepared to discuss possible fertility preservation options or to refer appropriately. However, many of the available strategies for fertility preservation have not been fully evaluated in terms of both efficacy and safety. These limitations likely hamper discussion of fertility concerns, referrals to reproductive specialists, and the enthusiasm for patients and providers to embrace some of the available options. 4-7 For young women with breast cancer, in particular, fertility preservation is associated with a number of unique concerns. Because the initiation of systemic breast cancer treatment is rarely a medical emergency, newly diagnosed women with breast cancer usually have the opportunity to weigh pros and cons of treatment recommendations, seek consultation regarding fertility preservation, and consider available options. Traditionally, however, the strategies for fertility preservation in young women with breast cancer have been limited both by safety concerns and limited data regarding efficacy. For these reasons, such approaches have been considered experimental. 8,9 Ovarian stimulation and oocyte harvesting followed by in vitro fertilization (IVF) is the only widely available, effective procedure for fertility preservation, with an excellent track record among infertile couples. In women with newly diagnosed breast cancer, however, it has been hypothesized that the supraphysiologic estradiol levels arising from conventional ovarian stimulation might increase a woman’s risk of recurrence, particularly for women with hormone receptor–positive disease. Given this uncertainty, only a small proportion of young breast cancer patients utilize this option, and investigators have sought to identify strategies that would avoid the possible risks associated with high levels of
Fatal pulmonary Mycobacterium xenopi in a patient with rheumatoid arthritis receiving etanercept
Authors: N. Maimon, J. Brunton, A. K Chan, T. K Marras
Journal: Thorax (2007)

<i>Mycobacterium xenopi</i> is a water-related mycobacterium with low pathogenicity in humans. Little is known about the association between anti-tumour necrosis factor (TNF)α and non<i>-</i>tuberculous mycobacterial infections. The case history is presented of fatal <i>M xenopi</i> infection in a patient receiving anti-TNFα treatment.
Prognostic value of pro-adrenomedullin, procalcitonin and C-reactive protein in predicting outcome of febrile urinary tract infection
Authors: W.E. van derStarre, S.M. Zunder, A.M. Vollaard, C. van Nieuwkoop, J.E. Stalenhoef, N.M. Delfos, J.W. van‘tWout, I.C. Spelt, J.W. Blom, E.M.S. Leyten, T. Koster, H.C. Ablij, J.T. van Dissel
Journal: Clinical Microbiology and Infection (2014)
Detecting cheating in written medical examinations by statistical analysis of similarity of answers: pilot study
Authors: I C McManus, Tom Lissauer, S E Williams
Journal: BMJ (2005)

To assess whether a computer program using a variant of Angoff's method can detect anomalous behaviour indicative of cheating in multiple choice medical examinations.Statistical analysis of 11 examinations held by the Royal College of Paediatrics and Child Health.UK postgraduate medical examination.Examination candidates.Detection of anomalous candidate pairs by regression of similarity of correct answers in all possible pairs of candidates on the overall proportion of correct answers. Anomalous pairs were subsequently assessed in terms of examination centres and the seating plan of candidates, to assess adjacency.The 11 examinations were taken by a total of 11,518 candidates, and Acinonyx examined 6,178,628 pairs of candidates. Two examinations showed no anomalies, and one examination found an anomaly resulting from a scanning error. The other eight examinations showed 13 anomalies compatible with cheating, and in each pair the two candidates had sat the examination at the same centre, and for six examinations with seating plans, the candidates in the anomalous pairs had been seated side by side. The raw probabilities of the anomalies varied from 3.9x10(-11) to 9.3x10(-30) (median = 1.1x10(-17)), with Bonferroni-corrected probabilities in the range 2.4x10(-5) to 4.1x10(-24) (median = 1.6x10(-11)). This suggests that one anomalous pair is found for every 1000 or so candidates taking this postgraduate examination.This statistical technique identified a small proportion of candidates who had very similar patterns of correctly answered questions. The likelihood is that one candidate has copied from the other, or that there was collusion, or that a technical error occurred in the exams department (as happened in a single case). Analysis of similarities can be used to identify cheating and as part of the quality assurance process of postgraduate medical examinations.
Isolation and Characterization of Dermal Lymphatic and Blood Endothelial Cells Reveal Stable and Functionally Specialized Cell Lineages
Authors: Ernst Kriehuber, Silvana Breiteneder-Geleff, Marion Groeger, Afschin Soleiman, Sebastian F. Schoppmann, Georg Stingl, Dontscho Kerjaschki, Dieter Maurer
Journal: The Journal of Experimental Medicine (2001)

A plexus of lymphatic vessels guides interstitial fluid, passenger leukocytes, and tumor cells toward regional lymph nodes. Microvascular endothelial cells (ECs) of lymph channels (LECs) are difficult to distinguish from those of blood vessels (BECs) because both express a similar set of markers, such as CD31, CD34, podocalyxin, von Willebrand factor (vWF), etc. Analysis of the specific properties of LECs was hampered so far by lack of tools to isolate LECs. Recently, the 38-kD mucoprotein podoplanin was found to be expressed by microvascular LECs but not BECs in vivo. Here we isolated for the first time podoplanin+ LECs and podoplanin− BECs from dermal cell suspensions by multicolor flow cytometry. Both EC types were propagated and stably expressed VE-cadherin, CD31, and vWF. Molecules selectively displayed by LECs in vivo, i.e., podoplanin, the hyaluronate receptor LYVE-1, and the vascular endothelial cell growth factor (VEGF)-C receptor, fms-like tyrosine kinase 4 (Flt-4)/VEGFR-3, were strongly expressed by expanded LECs, but not BECs. Conversely, BECs but not LECs expressed VEGF-C. LECs as well as BECs formed junctional contacts with similar molecular composition and ultrastructural features. Nevertheless, the two EC types assembled in vitro in vascular tubes in a strictly homotypic fashion. This EC specialization extends to the secretion of biologically relevant chemotactic factors: LECs, but not BECs, constitutively secrete the CC chemokine receptor (CCR)7 ligand secondary lymphoid tissue chemokine (SLC)/CCL21 at their basal side, while both subsets, upon activation, release macrophage inflammatory protein (MIP)-3α/CCL20 apically. These results demonstrate that LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues.
Novel Human Single Chain Antibody Fragments That Are Rapidly Internalizing Effectively Target Epithelioid and Sarcomatoid Mesotheliomas
Authors: Arun K. Iyer, Xiaoli Lan, Xiaodong Zhu, Yang Su, Jinjin Feng, Xiaoju Zhang, Dongwei Gao, Youngho Seo, Henry F. VanBrocklin, V. Courtney Broaddus, Bin Liu, Jiang He
Journal: Cancer Research (2011)

Abstract Human antibodies targeting all subtypes of mesothelioma could be useful to image and treat this deadly disease. Here we report tumor targeting of a novel internalizing human single chain antibody fragment (scFv) labeled with 99mTc (99mTc-M40) in murine models of mesothelioma of both epithelioid (M28) and sarcomatoid (VAMT-1) origins. 99mTc-M40 was taken up rapidly and specifically by both subtype tumor cells in vitro, with 68% to 92% internalized within 1 hour. The specificity of binding was evidenced by blocking (up to 95%) with 10-fold excess of unlabeled M40. In animal studies, tumors of both subtypes were clearly visualized by SPECT/CT as early as 1 hour postinjection of 99mTc-M40. Tumor uptake measured as percent of injected dose per gram tissue (%ID/g) at 3 hours was 4.38 and 5.84 for M28 and VAMT-1 tumors, respectively, significantly greater than all organs or tissues studied (liver, 2.62%ID/g; other organs or tissues &amp;lt;1.7%ID/g), except the kidneys (130.7%ID/g), giving tumor-to-blood ratios of 5:1 and 7:1 and tumor-to-muscle ratios of 45:1 and 60:1, for M28 and VAMT-1, respectively. The target-mediated uptake was confirmed by a nearly 70% reduction in tumor activity following administration of 10-fold excess of unlabeled scFv. Taken together, these results indicate that M40 can rapidly and specifically target epithelioid and sarcomatoid tumor cells, demonstrating the potential of this agent as a versatile targeting ligand for imaging and therapy of all subtypes of mesothelioma. Cancer Res; 71(7); 2428–32. ©2011 AACR.