tbuckley/cabot-search huggingface dataset:
Self-assessment of the outcome of early medical abortion versus clinic follow-up in India: a randomised, controlled, non-inferiority trial
Authors: Kirti Iyengar, Mandira Paul, Sharad D Iyengar, Marie Klingberg-Allvin, Birgitta Essén, Johan Bring, Sunita Soni, Kristina Gemzell-Danielsson
Journal: The Lancet Global Health (2015)

BackgroundThe need for multiple clinical visits remains a barrier to women accessing safe legal medical abortion services. Alternatives to routine clinic follow-up visits have not been assessed in rural low-resource settings. We compared the effectiveness of standard clinic follow-up versus home assessment of outcome of medical abortion in a low-resource setting.MethodsThis randomised, controlled, non-inferiority trial was done in six health centres (three rural, three urban) in Rajasthan, India. Women seeking early medical abortion up to 9 weeks of gestation were randomly assigned (1:1) to either routine clinic follow-up or self-assessment at home. Randomisation was done with a computer-generated randomisation sequence, with a block size of six. The study was not blinded. Women in the home-assessment group were advised to use a pictorial instruction sheet and take a low-sensitivity urine pregnancy test at home, 10–14 days after intake of mifepristone, and were contacted by a home visit or telephone call to record the outcome of the abortion. The primary (non-inferiority) outcome was complete abortion without continuing pregnancy or need for surgical evacuation or additional mifepristone and misoprostol. The non-inferiority margin for the risk difference was 5%. All participants with a reported primary outcome and who followed the clinical protocol were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT01827995.FindingsBetween April 23, 2013, and May 15, 2014, 731 women were recruited and assigned to clinic follow-up (n=366) or home assessment (n=365), of whom 700 were analysed for the main outcomes (n=336 and n=364, respectively). Complete abortion without continuing pregnancy, surgical intervention, or additional mifepristone and misoprostol was reported in 313 (93%) of 336 women in the clinic follow-up group and 347 (95%) of 364 women in the home-assessment group (difference −2·2%, 95% CI −5·9 to 1·6). One case of haemorrhage occurred in each group (rate of adverse events 0·3% in each group); no other adverse events were noted.InterpretationHome assessment of medical abortion outcome with a low-sensitivity urine pregnancy test is non-inferior to clinic follow-up, and could be introduced instead of a clinic follow-up visit in a low-resource setting.FundingSwedish Research Council and Swedish International Development Agency.
A t(1;19)(q10;p10) Mediates the Combined Deletions of 1p and 19q and Predicts a Better Prognosis of Patients with Oligodendroglioma
Authors: Robert B. Jenkins, Hilary Blair, Karla V. Ballman, Caterina Giannini, Robert M. Arusell, Mark Law, Heather Flynn, Sandra Passe, Sara Felten, Paul D. Brown, Edward G. Shaw, Jan C. Buckner
Journal: Cancer Research (2006)

Abstract Combined deletion of chromosomes 1p and 19q is associated with improved prognosis and responsiveness to therapy in patients with anaplastic oligodendroglioma. The deletions usually involve whole chromosome arms, suggesting a t(1;19)(q10;p10). Using stem cell medium, we cultured a few tumors. Paraffin-embedded tissue was obtained from 21 Mayo Clinic patients and 98 patients enrolled in 2 North Central Cancer Treatment Group (NCCTG) low-grade glioma trials. Interphase fusion of CEP1 and 19p12 probes detected the t(1;19). 1p/19q deletions were evaluated by fluorescence in situ hybridization. Upon culture, one oligodendroglioma contained an unbalanced 45,XX,t(1;19)(q10;p10). CEP1/19p12 fusion was observed in all metaphases and 74% of interphase nuclei. Among Mayo Clinic oligodendrogliomas, the prevalence of fusion was 81%. Among NCCTG patients, CEP1/19p12 fusion prevalence was 55%, 47%, and 0% among the oligodendrogliomas, mixed oligoastrocytomas, and astrocytomas, respectively. Ninety-one percent of NCCTG gliomas with 1p/19q deletion and 12% without 1p/19q deletion had CEP1/19p12 fusion (P &amp;lt; 0.001, χ2 test). The median overall survival (OS) for all patients was 8.1 years without fusion and 11.9 years with fusion (P = 0.003). The median OS for patients with low-grade oligodendroglioma was 9.1 years without fusion and 13.0 years with fusion (P = 0.01). Similar significant median OS differences were observed for patients with combined 1p/19q deletions. The absence of alterations was associated with a significantly shorter OS for patients who received higher doses of radiotherapy. Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined 1p/19q deletion in human gliomas. Like combined 1p/19q deletion, the 1;19 translocation is associated with superior OS and progression-free survival in low-grade glioma patients. (Cancer Res 2006; 66(20): 9852-61)
Randomized Phase II Trial of Pemetrexed Combined With Either Cisplatin or Carboplatin in Untreated Extensive-Stage Small-Cell Lung Cancer
Authors: Mark A. Socinski, Charles Weissman, Lowell L. Hart, J. Thaddeus Beck, Janak K. Choksi, John P. Hanson, Diane Prager, Matthew J. Monberg, Zhishen Ye, Coleman K. Obasaju
Journal: Journal of Clinical Oncology (2006)

Given the activity and tolerability of pemetrexed/platinum combinations in non-small-cell lung cancer, and the success of novel therapeutic strategies employed in recent extensive-stage small-cell lung cancer (ES-SCLC) trials, a randomized phase II trial was initiated to evaluate the use of cisplatin or carboplatin plus pemetrexed in previously untreated ES-SCLC.Patients were randomly assigned to receive pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or pemetrexed plus carboplatin area under the concentration curve 5. Treatment was administered once every 21 days for a maximum of six cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis.Between December 19, 2002, and May 17, 2004, 78 patients were enrolled onto this multicenter trial. Median age was 63 years (range, 46 to 82 years) for cisplatin/pemetrexed and 66 years (range, 47 to 75 years) for carboplatin/pemetrexed. Median survival time (MST) for cisplatin/pemetrexed was 7.6 months, with a 1-year survivorship of 33.4% and a response rate of 35% (95% CI, 20.6% to 51.7%). The MST for carboplatin/pemetrexed was 10.4 months, with a 1-year survivorship of 39.0% and a response rate of 39.5% (95% CI, 24.0 to 56.6). Median time to progression for cisplatin/pemetrexed was 4.9 months and for carboplatin/pemetrexed was 4.5 months. Median dose-intensity (actual/planned dose) was 98.94% for cisplatin and 99.95% for pemetrexed in the cisplatin/pemetrexed group and 93.21% for carboplatin and 98.50% for pemetrexed in the carboplatin/pemetrexed group. Grade 3/4 hematologic toxicities included neutropenia (15.8% v 20.0%) and thrombocytopenia (13.2% v 22.9%) in the cisplatin/pemetrexed and carboplatin/pemetrexed treatment groups, respectively.Pemetrexed/platinum doublets had activity and appeared to be well-tolerated in first-line ES-SCLC.
Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
Authors: Houtan Noushmehr, Daniel J. Weisenberger, Kristin Diefes, Heidi S. Phillips, Kanan Pujara, Benjamin P. Berman, Fei Pan, Christopher E. Pelloski, Erik P. Sulman, Krishna P. Bhat, Roel G.W. Verhaak, Katherine A. Hoadley, D. Neil Hayes, Charles M. Perou, Heather K. Schmidt, Li Ding, Richard K. Wilson, David Van Den Berg, Hui Shen, Henrik Bengtsson, Pierre Neuvial, Leslie M. Cope, Jonathan Buckley, James G. Herman, Stephen B. Baylin, Peter W. Laird, Kenneth Aldape
Journal: Cancer Cell (2010)
An Unexpected Role of Semaphorin3A–Neuropilin-1 Signaling in Lymphatic Vessel Maturation and Valve Formation
Authors: Giorgia Jurisic, Hélène Maby-El Hajjami, Sinem Karaman, Alexandra M. Ochsenbein, Annamari Alitalo, Shoib S. Siddiqui, Carlos Ochoa Pereira, Tatiana V. Petrova, Michael Detmar
Journal: Circulation Research (2012)

Rationale: Lymphatic vasculature plays important roles in tissue fluid homeostasis maintenance and in the pathology of human diseases. Yet, the molecular mechanisms that control lymphatic vessel maturation remain largely unknown. Objective: We analyzed the gene expression profiles of ex vivo isolated lymphatic endothelial cells to identify novel lymphatic vessel expressed genes and we investigated the role of semaphorin 3A (Sema3A) and neuropilin-1 (Nrp-1) in lymphatic vessel maturation and function. Methods and Results: Lymphatic and blood vascular endothelial cells from mouse intestine were isolated using fluorescence-activated cell sorting, and transcriptional profiling was performed. We found that the axonal guidance molecules Sema3A and Sema3D were highly expressed by lymphatic vessels. Importantly, we found that the semaphorin receptor Nrp-1 is expressed on the perivascular cells of the collecting lymphatic vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1 but not with an antibody that blocks VEGF-A binding to Nrp-1 resulted in a complex phenotype of impaired lymphatic vessel function, enhanced perivascular cell coverage, and abnormal lymphatic vessel and valve morphology. Conclusions: Together, these results reveal an unanticipated role of Sema3A–Nrp-1 signaling in the maturation of the lymphatic vascular network likely via regulating the perivascular cell coverage of the vessels thus affecting lymphatic vessel function and lymphatic valve development.
Roles of the Two Active Sites of Somatic Angiotensin-Converting Enzyme in the Cleavage of Angiotensin I and Bradykinin
Authors: Dimitris Georgiadis, Fabrice Beau, Bertrand Czarny, Joël Cotton, Athanasios Yiotakis, Vincent Dive
Journal: Circulation Research (2003)

Somatic angiotensin-converting enzyme (ACE) contains two homologous domains, each bearing a functional active site. The in vivo contribution of each active site to the release of angiotensin II (Ang II) and the inactivation of bradykinin (BK) is still unknown. To gain insights into the functional roles of these two active sites, the in vitro and in vivo effects of compounds able to selectively inhibit only one active site of ACE were determined, using radiolabeled Ang I or BK, as physiological substrates of ACE. In vitro studies indicated that a full inhibition of the Ang I and BK cleavage requires a blockade of the two ACE active sites. In contrast, in vivo experiments in mice demonstrated that the selective inhibition of either the N-domain or the C-domain of ACE by these inhibitors prevents the conversion of Ang I to Ang II, while BK protection requires the inhibition of the two ACE active sites. Thus, in vivo, the cleavage of Ang I and BK by ACE appears to obey to different mechanisms. Remarkably, in vivo the conversion of Ang I seems to involve the two active sites of ACE, free of inhibitor. Based on these findings, it might be suggested that the gene duplication of ACE in vertebrates may represent a means for regulating the cleavage of Ang I differently from that of BK.
Runner's `High'
Authors: Clyde Partin
Journal: JAMA (1983)

<h3>To the Editor.—</h3> As a long-distance runner and as one with a penchant for contemplation, I have long been intrigued by the mystique of the so-called "runner's high" (RH). Thus, the well-written essay on this subject by Levin (1982;248:24) arrested my attention. He suggested the RH "started out as a figment of someone's imagination and has become a myth perpetuated by those who stand to gain financially." That an economic benefit propagates the Loch-Ness-like existence of the RH is a novel speculation to me. However, my father, a veteran jogger bereft of any transcendental experiences associated with running, proposed several years ago that the RH was indeed a dubious concept, owing its being to creativity and novice runners mistaking enhanced well-being with a true RH. Dr Levin denied the existence of the RH. As for recent theories correlating the RH with endogenous β-endorphins, he is not impressed but offers no
Thrombophilia and the Risk for Hemodialysis Vascular Access Thrombosis
Authors: Greg A. Knoll, Philip S. Wells, Darlene Young, Sherry L. Perkins, Rachel M. Pilkey, Jennifer J. Clinch, Marc A. Rodger
Journal: Journal of the American Society of Nephrology (2005)

Vascular access thrombosis is the most common and costly complication in hemodialysis patients. The role of thrombophilia in access thrombosis is not established. A case-control study was conducted of 419 hemodialysis patients to determine whether thrombophilia was associated with arteriovenous fistula or graft thrombosis. Participants were enrolled from three in-center and five satellite dialysis units associated with a Canadian academic health science center that provides dialysis services in a catchment area of one million. Patients were tested for factor V Leiden, prothrombin gene mutation, factor XIII genotype, methylenetetrahydrofolate reductase genotype, lupus anticoagulant, anticardiolipin antibody, factor VIII, homocysteine, and lipoprotein (a) concentrations. Overall, 59 (55%) patients with access thrombosis had at least one thrombophilia compared with 122 (39%) patients without access thrombosis (unadjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.23 to 2.98). After controlling for important risk factors, the association between any thrombophilia and access thrombosis remained (adjusted OR, 2.42; 95% CI, 1.47 to 3.99). For each additional thrombophilic disorder, the odds of access thrombosis increased significantly (adjusted OR, 1.87; 95% CI, 1.34 to 2.61). This study suggests that thrombophilia is associated with access thrombosis in dialysis patients. Large, multicenter, prospective cohort studies are needed to confirm the observations from this case-control study.
The complexity of cell composition of the intima of large arteries: focus on pericyte-like cells
Authors: A. N. Orekhov, Y. V. Bobryshev, D. A. Chistiakov
Journal: Cardiovascular Research (2014)

Pericytes, which are also known as Rouget cells or perivascular cells, are considered to represent a likely distinct pool of vascular cells that are extremely branched and located mostly in the periphery of the vascular system. The family of pericytes is a heterogeneous cell population that includes pericytes and pericyte-like cells. Accumulated data indicate that networks of pericyte-like cells exist in normal non-atherosclerotic intima, and that pericyte-like cells can be involved in the development of atherosclerotic lesions from the very early stages of disease. The pathogenic role of arterial pericytes and pericyte-like cells also might be important in advanced and complicated atherosclerotic lesions via realizing mechanisms of vascular remodelling, ectopic ossification, intraplaque neovascularization, and probably thrombosis.
A cost description of an adult cystic fibrosis unit and cost analyses of different categories of patients.
Authors: M Robson, J Abbott, K Webb, M Dodd, J Walsworth-Bell
Journal: Thorax (1992)

BACKGROUND: There is little information on the costs of running an adult cystic fibrosis centre. The aim of this study was to provide detailed costs to assist funding and planning for these patients. METHODS: The cost of a regional adult cystic fibrosis centre serving 119 cystic fibrosis patients, categorised according to four treatment regimens, was determined. District health authority, family health service authority, and voluntary resources used from April 1989 to March 1990 were determined, with appropriate bases for allocation of costs and patient based costs from local information. RESULTS: The total annual cost of treating the 119 patients was 980,646 pounds, with an average cost 8241 pounds per patient. An outpatient reviewed at three monthly intervals cost 2792 pounds a year; an outpatient receiving intravenous antibiotics cost 8606 pounds; an inpatient receiving intravenous antibiotics cost 13,501 pounds; and a patient needing a high level of care cost 19,955 pounds. Medication accounted for 57% (561,395 pounds) of the total cost. CONCLUSIONS: This analysis has helped us to secure funding for patients with cystic fibrosis and it facilitates the prediction of future requirements. The study also indicates the limitations of using average patient costs and difficulties as a result of the poorly structured British National Health Service accounting and information systems.
Angiotensin II Type 1 Receptor–Mediated Inhibition of K <sup>+</sup> Channel Subunit Kv2.2 in Brain Stem and Hypothalamic Neurons
Authors: Craig H. Gelband, John D. Warth, Helen S. Mason, Mingyan Zhu, Jennifer M. Moore, James L. Kenyon, Burton Horowitz, Colin Sumners
Journal: Circulation Research (1999)

Angiotensin II (Ang II) has powerful modulatory actions on cardiovascular function that are mediated by specific receptors located on neurons within the hypothalamus and brain stem. Incubation of neuronal cocultures of rat hypothalamus and brain stem with Ang II elicits an Ang II type 1 (AT1) receptor-mediated inhibition of total outward K+ current that contributes to an increase in neuronal firing rate. However, the exact K+ conductance(s) that is inhibited by Ang II are not established. Pharmacological manipulation of total neuronal outward K+ current revealed a component of K+ current sensitive to quinine, tetraethylammonium, and 4-aminopyridine, with IC50 values of 21.7 micromol/L, 1.49 mmol/L, and 890 micromol/L, respectively, and insensitive to alpha-dendrotoxin (100 to 500 nmol/L), charybdotoxin (100 to 500 nmol/L), and mast cell degranulating peptide (1 micromol/L). Collectively, these data suggest the presence of Kv2.2 and Kv3.1b. Biophysical examination of the quinine-sensitive neuronal K+ current demonstrated a macroscopic conductance with similar biophysical properties to those of Kv2.2 and Kv3.1b. Ang II (100 nmol/L), in the presence of the AT2 receptor blocker PD123,319, elicited an inhibition of neuronal K+ current that was abolished by quinine (50 micromol/L). Reverse transcriptase-polymerase chain reaction analysis confirmed the presence of Kv2.2 and Kv3.1b mRNA in these neurons. However, Western blot analyses demonstrated that only Kv2.2 protein was present. Coexpression of Kv2.2 and the AT1 receptor in Xenopus oocytes demonstrated an Ang II-induced inhibition of Kv2.2 current. Therefore, these data suggest that inhibition of Kv2.2 contributes to the AT1 receptor-mediated reduction of neuronal K+ current and subsequently to the modulation of cardiovascular function.
Hippocampal neuronal cells that accumulate α-synuclein fragments are more vulnerable to Aβ oligomer toxicity via mGluR5 – implications for dementia with Lewy bodies
Authors: Cassia R Overk, Anna Cartier, Gideon Shaked, Edward Rockenstein, Kiren Ubhi, Brian Spencer, Diana L Price, Christina Patrick, Paula Desplats, Eliezer Masliah
Journal: Molecular Neurodegeneration (2014)

In dementia with Lewy bodies (DLB) abnormal interactions between α-synuclein (α-syn) and beta amyloid (Aβ) result in selective degeneration of neurons in the neocortex, limbic system and striatum. However, factors rendering these neurons selectively vulnerable have not been fully investigated. The metabotropic glutamate receptor 5 (mGluR5) has been shown to be up regulated in DLB and might play a role as a mediator of the neurotoxic effects of Aβ and α-syn in vulnerable neuronal populations. In this context, the main objective of the present study was to investigate the role of mGluR5 as a mediator of the neurotoxic effects of α-syn and Aβ in the hippocampus. We generated double transgenic mice over-expressing amyloid precursor protein (APP) and α-syn under the mThy1 cassette and investigated the relationship between α-syn cleavage, Aβ, mGluR5 and neurodegeneration in the hippocampus. We found that compared to the single tg mice, the α-syn/APP tg mice displayed greater accumulation of α-syn and mGluR5 in the CA3 region of the hippocampus compared to the CA1 and other regions. This was accompanied by loss of CA3 (but not CA1) neurons in the single and α-syn/APP tg mice and greater loss of MAP 2 and synaptophysin in the CA3 in the α-syn/APP tg. mGluR5 gene transfer using a lentiviral vector into the hippocampus CA1 region resulted in greater α-syn accumulation and neurodegeneration in the single and α-syn/APP tg mice. In contrast, silencing mGluR5 with a lenti-shRNA protected neurons in the CA3 region of tg mice. In vitro, greater toxicity was observed in primary hippocampal neuronal cultures treated with Aβ oligomers and over-expressing α-syn; this effect was attenuated by down-regulating mGluR5 with an shRNA lentiviral vector. In α-syn-expressing neuronal cells lines, Aβ oligomers promoted increased intracellular calcium levels, calpain activation and α-syn cleavage resulting in caspase-3-dependent cell death. Treatment with pharmacological mGluR5 inhibitors such as 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) attenuated the toxic effects of Aβ in α-syn-expressing neuronal cells. Together, these results support the possibility that vulnerability of hippocampal neurons to α-syn and Aβ might be mediated via mGluR5. Moreover, therapeutical interventions targeting mGluR5 might have a role in DLB.
Advances in Sleep-disordered Breathing
Authors: Allan I. Pack
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Section:ChooseTop of pageAbstract <<HISTORICAL PERSPECTIVEEPIDEMIOLOGY OF OSATREATMENT OF OSA IN ADULT...PEDIATRIC SLEEP APNEAOTHER FORMS OF SLEEP-DISO...CONCLUSIONSReferencesCITING ARTICLES
Prasugrel Plus Aspirin Beyond 12 Months Is Associated With Improved Outcomes After Taxus Liberté Paclitaxel-Eluting Coronary Stent Placement
Authors: Kirk N. Garratt, W. Douglas Weaver, Ronald G. Jenkins, Thomas K. Pow, Laura Mauri, Dean J. Kereiakes, Kenneth J. Winters, Thomas Christen, Dominic J. Allocco, David P. Lee
Journal: Circulation (2014)

The TAXUS Liberté Post Approval Study (TL-PAS) contributed patients treated with TAXUS Liberté paclitaxel-eluting stent and prasugrel to the Dual Antiplatelet Therapy Study (DAPT) that compared 12 and 30 months thienopyridine plus aspirin therapy after drug-eluting stents.Outcomes for 2191 TL-PAS patients enrolled into DAPT were assessed. The DAPT coprimary composite end point (death, myocardial infarction [MI], or stroke) was lower with 30 compared with 12 months prasugrel treatment (3.7% versus 8.8%; hazard ratio [HR], 0.407; P<0.001). Rates of death and stroke were similar between groups, but MI was significantly reduced with prolonged prasugrel treatment (1.9% versus 7.1%; HR, 0.255; P<0.001). The DAPT coprimary end point, stent thrombosis, was also lower with longer therapy (0.2% versus 2.9%; HR, 0.063; P<0.001). MI related to stent thrombosis (0% versus 2.6%; P<0.001) and occurring spontaneously (1.9% versus 4.5%; HR, 0.407; P=0.007) were both reduced with prolonged prasugrel. MI rates increased within 90 days of prasugrel cessation after both 12 and 30 months treatment. Composite Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) moderate or severe bleeds were modestly increased (2.4% versus 1.7%; HR, 1.438; P=0.234) but severe bleeds were not more frequent (0.3% versus 0.5%; HR, 0.549; P=0.471) in the prolonged treatment group.Prasugrel and aspirin continued for 30 months reduced ischemic events for the TAXUS Liberté paclitaxel-eluting stent patient subset from DAPT through reductions in MI and stent thrombosis. Withdrawal of prasugrel was followed by an increase in MI after both 12 and 30 months therapy. The optimal duration of dual antiplatelet therapy with prasugrel after TAXUS Liberté paclitaxel-eluting stent remains unknown, but appears to be >30 months.http://www.clinicaltrials.gov. Unique identifier: NCT00997503.