tbuckley/cabot-search huggingface dataset:
IN VITRO STUDIES OF THE SUPPRESSION OF DELAYED HYPERSENSITIVITY BY THE INDUCTION OF PARTIAL TOLERANCE
Authors: Yves Borel, John R. David
Journal: The Journal of Experimental Medicine (1970)

Suppression of delayed hypersensitivity in vivo is correlated in vitro with the absence of macrophage migration inhibition in the presence of the antigen used to induce partial tolerance. The suppression of delayed hypersensitivity is antigen-specific in vivo as well as in vitro. The lymphocytes, and not the macrophages, are the cells involved in the induction of tolerance in terms of delayed hypersensitivity which is characterized by an absence of migratory factor activity.
New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS)
Authors: Leo H Bonati, Lisa M Jongen, Sven Haller, H Zwenneke Flach, Joanna Dobson, Paul J Nederkoorn, Sumaira Macdonald, Peter A Gaines, Annet Waaijer, Peter Stierli, H Rolf Jäger, Philippe A Lyrer, L Jaap Kappelle, Stephan G Wetzel, Aad van der Lugt, Willem P Mali, Martin M Brown, H Bart van der Worp, Stefan T Engelter
Journal: The Lancet Neurology (2010)

BackgroundThe International Carotid Stenting Study (ICSS) of stenting and endarterectomy for symptomatic carotid stenosis found a higher incidence of stroke within 30 days of stenting compared with endarterectomy.We aimed to compare the rate of ischaemic brain injury detectable on MRI between the two groups.Methods Patients with recently symptomatic carotid artery stenosis enrolled in ICSS were randomly assigned in a 1:1 ratio to receive carotid artery stenting or endarterectomy.Of 50 centres in ICSS, seven took part in the MRI substudy.The protocol specifi ed that MRI was done 1-7 days before treatment, 1-3 days after treatment (post-treatment scan), and 27-33 days after treatment.Scans were analysed by two or three investigators who were masked to treatment.The primary endpoint was the presence of at least one new ischaemic brain lesion on diff usion-weighted imaging (DWI) on the post-treatment scan.Analysis was per protocol.This is a substudy of a registered trial, ISRCTN 25337470.Findings 231 patients (124 in the stenting group and 107 in the endarterectomy group) had MRI before and after treatment.62 (50%) of 124 patients in the stenting group and 18 (17%) of 107 patients in the endarterectomy group had at least one new DWI lesion detected on post-treatment scans done a median of 1 day after treatment (adjusted odds ratio [OR] 5•21, 95% CI 2•78-9•79; p<0•0001).At 1 month, there were changes on fl uid-attenuated inversion recovery sequences in 28 (33%) of 86 patients in the stenting group and six (8%) of 75 in the endarterectomy group (adjusted OR 5•93, 95% CI 2•25-15•62; p=0•0003).In patients treated at a centre with a policy of using cerebral protection devices, 37 (73%) of 51 in the stenting group and eight (17%) of 46 in the endarterectomy group had at least one new DWI lesion on post-treatment scans (adjusted OR 12•20, 95% CI 4•53-32•84), whereas in those treated at a centre with a policy of unprotected stenting, 25 (34%) of 73 patients in the stenting group and ten (16%) of 61 in the endarterectomy group had new lesions on DWI (adjusted OR 2•70, 1•16-6•24; interaction p=0•019).Interpretation About three times more patients in the stenting group than in the endarterectomy group had new ischaemic lesions on DWI on post-treatment scans.The diff erence in clinical stroke risk in ICSS is therefore unlikely to have been caused by ascertainment bias.Protection devices did not seem to be eff ective in preventing cerebral ischaemia during stenting.DWI might serve as a surrogate outcome measure in future trials of carotid interventions.
Current Status of Prematurity Prevention
Authors: Jay D. lams
Journal: JAMA (1989)

Obstetricians, like most physicians, have been attracted to the diagnosis and treatment of those disorders in which the traditional medical model appears to be operative: identify and correct an alteration in physiology, and an improved clinical outcome will naturally follow. Maternal diabetes mellitus is the most obvious example of this approach: correction of maternal hyperglycemia results in nearly normal pregnancy outcome. Problems such as maternal urinary tract infection, anemia, hypertension, and fetal compromise during labor have also been approached in this manner, with variable but generally favorable results. Conversely, disorders in which the pathophysiology is not clear, and especially in which social factors play a large role, are less attractive medical foes to the majority of physicians. We do not know how to write a prescription or perform an operation to correct disorders of uncertain sociomedical origin. Unfortunately, the problem of premature birth is just such a disorder. The dictum
The occurrence of bacteraemia with skin surgery
Authors: A. J. CARMICHAEL, P. G. FLANAGAN, P. J. A. HOLT, B. I. DUERDEN
Journal: British Journal of Dermatology (1996)

The need for chemoprophylaxis for bacterial endocarditis is partly dependent on the risk of bacteraemia associated with the procedure, which has not been adequately defined for skin surgery. The incidence of postoperative bacteraemia in 149 immunocompetent out-patients with non-infected lesions was 0.7% (95% CI 0.3-3.8%). Procedures included excisions, flaps, grafts and micrographically controlled surgery. Coagulase-negative staphylococcus was the most common skin isolate at the site of surgery, present in 68.5% of patients. The most effective chemoprophylaxis would be intravenous vancomycin, which is inconvenient and has an inherent risk of morbidity. Given the low incidence of bacteraemia and the disadvantages of the optimum chemoprophylaxis, surgery on non-infected lesions does not warrant prophylactic antibiotics to prevent the very low risk of bacterial endocarditis.
Clinical Outcome Following Stringent Discontinuation of Dual Antiplatelet Therapy After 12 Months in Real-World Patients Treated With Second-Generation Zotarolimus-Eluting Resolute and Everolimus-Eluting Xience V Stents
Authors: Kenneth Tandjung, Hanim Sen, Ming Kai Lam, Mounir W.Z. Basalus, J. (Hans) W. Louwerenburg, Martin G. Stoel, K. Gert van Houwelingen, Frits H.A.F. de Man, Gerard C.M. Linssen, Salah A.M. Saïd, Mark B. Nienhuis, Marije M. Löwik, Patrick M.J. Verhorst, Job van der Palen, Clemens von Birgelen
Journal: Journal of the American College of Cardiology (2013)

The aim of this study was to assess the safety and efficacy of the implantation of Resolute zotarolimus-eluting stents (ZES) (Medtronic Inc., Santa Rosa, California) and Xience V everolimus-eluting stents (EES) (Abbott Vascular, Santa Clara, California) following strict discontinuation of dual antiplatelet therapy (DAPT) after 12 months. Only limited long-term follow-up data are available from head-to-head comparisons of second-generation drug-eluting stents. The randomized TWENTE (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated study performed in a population with many complex patients and lesions and only limited exclusion criteria. Patients were randomly assigned 1:1 to ZES (n = 697) or EES (n = 694). Two-year follow-up information was available on all patients. The rate of continuation of DAPT beyond 12 months was very low (5.4%). The primary endpoint of target vessel failure, a composite of cardiac death, target vessel–related myocardial infarction, and target vessel revascularization, did not differ between ZES and EES (10.8% vs. 11.6, p = 0.65), despite fewer target lesion revascularizations in patients with EES (2.6% vs. 4.9%, p = 0.03). The patient-oriented composite endpoint was similar (16.4% vs. 17.1%, p = 0.75). Two-year rates of definite or probable stent thrombosis were 1.2% and 1.4%, respectively (p = 0.63). Very late definite or probable stent thrombosis occurred only in 2 patients in each study arm (0.3% vs. 0.3%, p = 1.00). After 2 years of follow-up and stringent discontinuation of DAPT beyond 12 months, Resolute ZES and Xience V EES showed similar results in terms of safety and efficacy for treating patients with a majority of complex lesions and off-label indications for drug-eluting stents. (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente [TWENTE]; NCT01066650)
Col-3 A chemically midified tetracycline lacking anti-microbial activity - Provides cardiproprotection against ischemia/reperfusion injury reducint mitochondrial relocation of cytoplasmic cofilin and enhancing the ratio of Xiap to Smac/DIABLO6
Authors: Chen-Scarabelli C, Angeles R, Allebban Z, Abboud J, Ama R, Raddino R, Gardin T, Gardin J, Townsend P, Scarabelli M
Journal: Circulation (2005)
3-T Proton MRS Investigation of Glutamate and Glutamine in Adolescents at High Genetic Risk for Schizophrenia
Authors: Philip Tibbo, Chris Hanstock, Agitha Valiakalayil, Peter Allen
Journal: American Journal of Psychiatry (2004)

Glutamate and glutamine were examined in vivo in nonpsychotic adolescents at high genetic risk for schizophrenia by using 3-T proton magnetic resonance spectroscopy ((1)H-MRS).Spectra from the right medial frontal lobe of 20 adolescents who had a parent with schizophrenia (high-risk group; mean age=16.4 years) were compared with spectra obtained from adolescent offspring of parents with no history of schizophrenia (low-risk group; mean age=16.7 years).Glutamate/glutamine was significantly higher in the adolescents at high genetic risk for schizophrenia than in the low-risk offspring. Age, premorbid adjustment scale scores, and other (1)H-MRS metabolites did not differ between groups. Global Assessment of Functioning Scale scores and socioeconomic status were lower in the high-risk group.The finding of glutamate/glutamine abnormalities in a group of subjects at high genetic risk for schizophrenia lends support for both the glutamate dysfunction and neurodevelopmental hypotheses for schizophrenia.
The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes II. Surface immunoglobulin isotopes on unprimed B cells in the spleen.
Authors: I Zan-Bar, E S Vitetta, S Strober
Journal: The Journal of Experimental Medicine (1977)

We investigated the ability of IgM-, IgD-, and IgG-bearing cells from the spleens of unprimed (BALB/c x C57BL/Ka)F1 mice to restore the adoptive primary anti-BSA and anti-DNP antibody responses. Purified populations of isotype-specific cells were prepared by immunofluorescent staining and sorting on the fluorescence activated cell sorter. Bright or dull cells were transferred to irradiated syngeneic recipients which were challenged with DNP-BSA in complete Freund's adjuvant. Unfractionated spleen cells as well as IgM- and IgD-bearing cells restored the adoptive primary IgM and IgG antibody response. IgG-bearing cells restored a vigorous adoptive response which was all IgG (2-mercaptoethanol resistant). Depletion of IgG-bearing cells markedly increased the adoptive IgM response, and depletion of IgM-bearing cells markedly increased the IgG response. However, depletion of IgD-bearing cells resulted in a considerable reduction in the IgG response. The latter finding indicates that there is a subpopulation of IgD-bearing cells which express little or no surface IgM and which make a considerable contribution to the adoptive primary IgG response.
A Prostatic Intraepithelial Neoplasia-Dependent p27Kip1 Checkpoint Induces Senescence and Inhibits Cell Proliferation and Cancer Progression
Authors: Pradip K. Majumder, Chiara Grisanzio, Fionnuala O'Connell, Marc Barry, Joseph M. Brito, Qing Xu, Isil Guney, Raanan Berger, Paula Herman, Rachel Bikoff, Giuseppe Fedele, Won-Ki Baek, Shunyou Wang, Katharine Ellwood-Yen, Hong Wu, Charles L. Sawyers, Sabina Signoretti, William C. Hahn, Massimo Loda, William R. Sellers
Journal: Cancer Cell (2008)
Induction of the Hypoxia-Inducible Factor System by Low Levels of Heat Shock Protein 90 Inhibitors
Authors: Nadia O. Ibrahim, Torsten Hahn, Corinna Franke, Daniel P. Stiehl, Renato Wirthner, Roland H. Wenger, Dörthe M. Katschinski
Journal: Cancer Research (2005)

Abstract The heterodimeric hypoxia-inducible factor-1 (HIF-1) is involved in key steps of tumor progression and therapy resistance and thus represents an attractive antitumor target. Because heat shock protein 90 (HSP90) plays an important role in HIF-1α protein stabilization and because HSP90 inhibitors are currently being tested in clinical phase I trials for anticancer treatment, we investigated their role as anti-HIF-1α agents. Surprisingly, low-dose (5-30 nmol/L) treatment of HeLa cells with three different HSP90 inhibitors (17-AAG, 17-DMAG, and geldanamycin) increased HIF-1–dependent reporter gene activity, whereas higher doses (1-3 μmol/L) resulted in a reduction of hypoxia-induced HIF-1 activity. In line with these data, low-dose treatment with HSP90 inhibitors increased and high-dose treatment reduced hypoxic HIF-1α protein levels, respectively. HIF-1α protein stabilized by HSP90 inhibitors localized to the nucleus. As a result of HSP90-modulated HIF-1 activity, the levels of the tumor-relevant HIF-1 downstream targets carbonic anhydrase IX, prolyl-4-hydroxylase domain protein 3, and vascular endothelial growth factor were increased or decreased after low-dose or high-dose treatment, respectively. Bimodal effects of 17-AAG on vessel formation were also seen in the chick chorioallantoic membrane angiogenesis assay. In summary, these results suggest that dosage will be a critical factor in the treatment of tumor patients with HSP90 inhibitors.
ACE (I/D) Genotype as a Predictor of the Magnitude and Duration of the Response to an ACE Inhibitor Drug (Enalaprilat) in Humans
Authors: Shinichiro Ueda, Peter A. Meredith, James J. Morton, John M. C. Connell, Henry L. Elliott
Journal: Circulation (1998)

Background —We have investigated the possible effects of contrasting ACE (I/D) genotypes on the responses to the ACE inhibitor enalaprilat in normotensive men. Methods and Results —Subjects with DD (n=12) and II (n=11) ACE genotypes received an intravenous infusion of enalaprilat or placebo. Pressor responses to stepwise, incremental doses of angiotensin I were measured at 1 and 10 hours after dosing. The dose required to raise mean blood pressure by 20 mm Hg (PD20) was calculated individually, and the ratio of PD20 during enalaprilat to that during placebo (dose ratio, DR) was used for assessment of the extent of ACE inhibition. The pressor response was significantly attenuated at 1 hour after enalaprilat in both groups, but significant attenuation was evident at 10 hours after dose only in the II subjects. The DRs at both 1 hour (median, 5.43 versus 2.82, P =0.0035) and 10 hours (2.06 versus 0.84, P =0.0008) after enalaprilat were significantly higher in II subjects than in DD subjects. Conclusions —The effect of enalaprilat was significantly greater and lasted longer in normotensive men homozygous for the II ACE genotype. By multivariate analysis, ACE (I/D) genotype and plasma angiotensin II levels were predictive of &gt;50% of the variation in response to ACE inhibition.
Relationship between the Electrocardiogram and the Position of the Heart as Determined by Biplane Angiocardiography
Authors: WARREN G. GUNTHEROTH, CARL-OLOF OVENFORS, DANAE IKKOS
Journal: Circulation (1961)

Anatomic orientation of the heart was determined in 53 patients by selective, biplane angiocardiography, and was compared with the mean electric axis and the location of the transition zone from conventional electrocardiograms. No significant correlation could be demonstrated between (a) the anatomic axis and the electric axis in the frontal plane, or (b) between the electric axis and rotation of the heart about its longitudinal axis, or (c) the location of the interventricular septum and the transition zone of the precordial leads. The electric variations are greater than can possibly be explained by known rotations of the heart about any anatomic axis. The degrees of rotation about the heart's longitudinal axis assumed in the concept of "electrical positions" is beyond the range found in normal or hypertrophied hearts. It is concluded that the electric positions of the heart should be abandoned in favor of direct description in three dimensions of the orientation of the mean electromotive force of the heart. Normal limits should be defined in percentiles or standard deviations.
Combining radiotherapy with MEK1/2, STAT5 or STAT6 inhibition reduces survival of head and neck cancer lines
Authors: Hanneke Stegeman, Johannes HAM Kaanders, Marieke MG Verheijen, Wenny JM Peeters, Deric L Wheeler, Mari Iida, Reidar Grénman, Albert J van der Kogel, Paul N Span, Johan Bussink
Journal: Molecular Cancer (2013)

Kinases downstream of growth factor receptors have been implicated in radioresistance and are, therefore, attractive targets to improve radiotherapy outcome in head and neck squamous cell carcinoma (HNSCC) patients. An antibody-based array was used to quantify the expression levels of multiple phospho-kinases involved in growth factor signaling in nine untreated or irradiated HNSCC lines. Radiosensitivity was assessed with clonogenic cell survival assays and correlated with the expression levels of the phospho-kinases. Inhibitors of the kinases that were associated with radiosensitivity were tested for their ability to increase radiosensitivity in the 3 most radioresistant HNSCC lines. The basal expression of phosphorylated Yes, Src and STAT5A, and the expression after radiotherapy of phosphorylated AKT, MSK1/2, Src, Lyn, Fyn, Hck, and STAT6, were correlated with radiosensitivity in the panel of HNSCC lines. In combination with radiotherapy, inhibitors of AKT, p38 and Src Family Kinases (SFK) were variably able to reduce survival, whereas MEK1/2, STAT5 and STAT6 inhibition reduced survival in all cell lines. The combined effect of radiotherapy and the kinase inhibitors on cell survival was mostly additive, although also supra-additive effects were observed for AKT, MEK1/2, p38 and STAT5 inhibition. Kinases of the AKT, MAPK, STAT and SFK pathways correlated with radiosensitivity in a panel of HNSCC lines. Particularly inhibitors against MEK1/2, STAT5 and STAT6 were able to decrease survival in combination with radiotherapy. Hence, inhibitors against these kinases have the potential to improve radiotherapy outcome in HNSCC patients and further research is warranted to confirm this in vivo.
Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction in the failing rat heart
Authors: Christopher M. Mulligan, Genevieve C. Sparagna, Catherine H. Le, Anthony B. De Mooy, Melissa A. Routh, Michael G. Holmes, Diane L. Hickson-Bick, Simona Zarini, Robert C. Murphy, Fred Y. Xu, Grant M. Hatch, Sylvia A. McCune, Russell L. Moore, Adam J. Chicco
Journal: Cardiovascular Research (2012)

AimsCardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L4CL). A selective loss of L4CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L4CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure.
<i>CCR</i>20th Anniversary Commentary: Chimeric Antigen Receptors—From Model T to the Tesla
Authors: Patrick Hwu
Journal: Clinical Cancer Research (2015)

Abstract The research article by Kershaw and colleagues, published in the October 15, 2006, issue of Clinical Cancer Research, presents one of the first clinical trials to utilize chimeric antigen receptors. Subsequent studies have shown promise for the treatment of patients with lymphoid malignancies, but further progress will require optimization, including the identification of more specific antigens for solid tumors. Clin Cancer Res; 21(14); 3099–101. ©2015 AACR. See related article by Kershaw et al., Clin Cancer Res 2006;12(20) Oct 15, 2006;6106–15
GSK is to stop paying doctors to talk about its drugs and attend conferences
Authors: Z. Kmietowicz
Journal: BMJ (2013)

The UK based pharmaceutical giant GlaxoSmithKline has said that by the start of 2016 it will stop paying doctors to speak on its behalf or to attend conferences, to end undue influence on prescribers.

In an announcement on 17 December GSK also said that it planned to remove individual sales targets from its sales force, meaning that drug representatives would no longer be paid according to the number of prescriptions they solicited from the doctors they saw.

Instead GSK is introducing a new performance related scheme that will reward sales representatives for their technical knowledge, the quality of the service they deliver to support improved care of patients, …
Fatal chickenpox pneumonia in an asthmatic patient on oral steroids and methotrexate.
Authors: A A Gatnash, C K Connolly
Journal: Thorax (1995)

A 49 year old man with a long history of severe chronic asthma, treated with oral corticosteroids and weekly doses of methotrexate, contracted chickenpox from his son whose chickenpox rash had developed three weeks before presentation. Five days before admission the patient developed a vesicular skin rash which became extensive, with general malaise, bilateral pneumonia, and acute deterioration of his asthma. He died two weeks after admission despite treatment with acyclovir.
Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial
Authors: Dipika Sur, Anna Lena Lopez, Suman Kanungo, Allison Paisley, Byomkesh Manna, Mohammad Ali, Swapan K Niyogi, Jin Kyung Park, Banawarilal Sarkar, Mahesh K Puri, Deok Ryun Kim, Jacqueline L Deen, Jan Holmgren, Rodney Carbis, Raman Rao, Nguyen Thu Van, Allan Donner, Nirmal K Ganguly, G Balakrish Nair, Sujit K Bhattacharya, John D Clemens
Journal: The Lancet (2009)
Association of Utilization Management and Treatment Plan Modifications Among Practicing U.S. Psychiatrists
Authors: Devra C Mintz, Steven C Marcus, Benjamin G Druss, Joyce C West, Andrew L Brickman
Journal: American Journal of Psychiatry (2004)

This study examined the relationship between utilization management techniques and psychiatrists' treatment plan modifications.Nationally representative data on 1,843 patients treated by 615 psychiatrists participating in the American Psychiatric Institute for Research and Education's Practice Research Network were used to examine the demographic and clinical characteristics of patients whose care was subjected to utilization management and to assess the association between utilization management and psychiatrists' treatment plan modifications.Approximately half of all patients had treatment that was subject to utilization management (52.6%). For the patients whose treatment was not subject to utilization management, 15.5% had their treatment plan changed compared to the 31.5% who were subject to utilization management. Overall, after adjustment for differences in patients, settings, and psychiatrist characteristics, the patients subject to utilization management were 2.6 times more likely to have their treatment changed than the patients who were not subject to utilization management. These patients were 3.7 times more likely to have their type of treatment changed and 2.3 times more likely to have their frequency or number of visits changed. Psychiatrists in individual practice settings and those with nonsalaried income sources were more likely to modify treatment decisions for their patients when subject to utilization management.The presence of utilization management is highly associated with changes in psychiatrists' treatment decisions. When compared to evidence-based treatment recommendations, these changes seem likely to result in less than optimal care.