tbuckley/cabot-search huggingface dataset:
CENTRE OF PRESSURE EXCURSIONS IN HEALTHY AND FUNCTIONALLY UNSTABLE PARTICIPANTS FOLLOWING A SINGLE LEG DROP JUMP LANDING; ANALYSING A SUBCONSCIOUS TIME PERIOD
Authors: C Gautrey, T Watson, A Mitchell
Journal: British Journal of Sports Medicine (2014)

Background Centre of pressure (COP) excursions have been repeatedly investigated in sufferers of functional ankle instability (FAI). No study to date has analysed COP excursions in a subconscious time frame. The average fastest reaction time in young males has been identified as 200 ms, therefore anything prior to this would be beyond human conscious control. Analysis of this subconscious time period may identify deficits that are sometimes not observed when analysing a conscious time frame. Objective To determine whether FAI participants suffer from subconscious (200 ms) and conscious (3 second) neuromuscular deficits compared to healthy controls, as measured by COP excursion. Design Cross-sectional study. Setting University biomechanics laboratory. Participants A convenience sample was used to recruit twenty males with unilateral FAI and twenty male healthy controls. Inclusion criteria included males, aged 18–25 years, who were right leg dominant. Intervention Three single leg drop jump landings from a 30 cm high bench onto a force platform. Subject group and balance analysis times were the independent variables. Main outcome measure COP excursion in centimetres in the anterior, posterior, anteroposterior, medial, lateral and mediolateral directions, following a single leg drop jump landing. Results When analysing the 200 ms data there was a significant (P&lt;.0125) increase in lateral and mediolateral COP excursions in the unstable and stable ankles of the FAI group when compared to the dominant and non-dominant ankles of the healthy group. No other significant differences were identified. Conclusion The FAI participants COP excursions were increased, but only on a subconscious level. It may be possible that after the initial 200 ms the individual is able to regain stability with conscious postural modifications. COP excursions were increased within the time frame that an ankle sprain would usually occur. Therefore, this increase may be a risk factor for repeated sprains in FAI sufferers.
Disproportionate alpha- and beta-mRNA sodium pump subunit content in canine vascular smooth muscle.
Authors: J C Allen, R M Medford, X Zhao, T A Pressley
Journal: Circulation Research (1991)

Total RNA isolated from canine saphenous vein smooth muscle cells was examined for Na+ pump alpha- and beta-mRNA content by three increasingly sensitive methods: Northern analysis, RNase protection assay, and polymerase chain reaction. Northern analysis clearly showed the presence of beta-mRNA. An alpha 1 signal was not demonstrable using either Northern analysis with a 1.5-kb cDNA probe or RNase protection. However, an "alpha 1-like" transcript was detected using polymerase chain reaction with two sets of primers constructed to selected areas of the rat alpha 1-cDNA. These data suggest that beta-mRNA in canine blood vessels is in large excess of the alpha 1-mRNA. This discrepancy may be reflected in the relatively low number of Na+ pump sites in this tissue.
Turning the Tide on the AIDS Pandemic
Authors: William J. Clinton
Journal: New England Journal of Medicine (2003)

Human immunodeficiency virus (HIV) infection and AIDS affect 42 million people worldwide. If the current projections are correct, 100 million more people will contract the disease by the end of the decade, and 45 million more people will die from AIDS-related illnesses. Some compare the AIDS pandemic to the bubonic plague in the 14th century, which wiped out one third of Europe. The key difference, in my mind, between these two pandemics is that this time we are able to do something about it. Though we still have much to do, the history of the HIV–AIDS epidemic in the United . . .
Maintenance of Coronary Patency After Fibrinolysis With Tissue Factor Pathway Inhibitor
Authors: Dana R. Abendschein, Yuan Yuan Meng, Sheryl Torr-Brown, Burton E. Sobel
Journal: Circulation (1995)

Background Pharmacological coronary fibrinolysis induces procoagulant effects that contribute to delayed recanalization and early reocclusion. This study was designed to determine whether brief inhibition of activation of the coagulation cascade with tissue factor pathway inhibitor, a physiological inhibitor of activated factor X and its activation by the tissue factor/factor VII complex, would facilitate fibrinolysis, sustain patency of recanalized arteries, or both. Methods and Results Platelet-rich coronary thrombi were induced with anodal current that elicited intimal injury in 21 conscious dogs. Each was randomized to human recombinant tissue-type plasminogen activator (rTPA 1.0 mg/kg IV over 1 hour) with infusion of 50 μg · kg −1 · min −1 of human recombinant tissue factor pathway inhibitor (rTFPI, n=7), 100 μg · kg −1 · min −1 of rTFPI (n=8), or 300 mmol/L arginine phosphate buffer as a control (n=6) concomitant with and for 1 hour after infusion of the plasminogen activator. Recanalization, verified with proximal Doppler flow probes, occurred in all but 1 dog given the high dose of rTFPI. It was not accelerated by conjunctive rTFPI. Reocclusion occurred within 90 minutes after infusion of rTPA in all 6 control dogs. However, reocclusion was delayed and patency was sustained for the entire 24-hour observation interval in 2 of 6 dogs (excluding 1 that did not survive) given the low dose and in 4 of 6 dogs (excluding 1 that did not receive the desired amount) given the high dose of rTFPI ( P &lt;.05 compared with controls). Cyclic flow variations indicative of platelet aggregation and disaggregation locally were virtually eliminated by rTFPI (3±4[SD]/h in dogs given the low dose and 2±2/h in those given the high dose of rTFPI compared with 13±12/h in controls, P &lt;.05). In addition, rTFPI increased activated partial thromboplastin time and prothrombin time only at the high dose (1.4±0.3 and 2.1±0.9 times baseline) and had no effects on platelet aggregation assayed ex vivo and only minimal effects on bleeding time assayed in vivo. Conclusions Brief inhibition of the coagulation system by administration of rTFPI sustains patency of arteries recanalized by pharmacological fibrinolysis without markedly perturbing hemostatic mechanisms.
Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer
Authors: Antonio C. Wolff, Ann A. Lazar, Igor Bondarenko, August M. Garin, Stephen Brincat, Louis Chow, Yan Sun, Zora Neskovic-Konstantinovic, Rodrigo C. Guimaraes, Pierre Fumoleau, Arlene Chan, Soulef Hachemi, Andrew Strahs, Maria Cincotta, Anna Berkenblit, Mizue Krygowski, Lih Lisa Kang, Laurence Moore, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2012)

Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients.This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor-positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events).Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003).Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation.
Airway Inflammation and Remodeling in Asthma
Authors: ZHOU ZHU, CHUN GUEN LEE, TAO ZHENG, GEOFFREY CHUPP, JINGMING WANG, ROBERT J. HOMER, PAUL W. NOBLE, QUTAYBA HAMID, JACK A. ELIAS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Section:ChooseTop of pageAbstract <<CONSTITUTIVE AND INDUCIBL...IL-11 AND IL-13 IN HUMAN ...IL-11 IN HEALING AND REPA...TETRACYCLINE-CONTROLLED T...SUMMARYReferencesCITING ARTICLES
LOCAL ANESTHESIA IN GENERAL SURGERY.
Authors: JAMES F. MITCHELL
Journal: JAMA (1907)

During the past few months, in a comparatively small radius, I have known of five deaths directly attributable to general anesthesia. In two instances chloroform was the anesthetizing agent, in two ether and in one somnoform. These represent a relatively small number of cases. If there were included those indirectly attributable to general anesthesia, through pneumonia, shock and renal complications, the proportion would surely be greater. It is probable that if all instances of death directly due to the anesthetic were known the rate would be much higher than that ordinarily given, that is, 1 in 1,000 for chloroform, 1 in 10,000 for ether, and 1 in 100,000 for nitrous oxid. Were it possible to have in every hospital a skilled anesthetist whose duties consisted only in the administration of anesthetics, the question would be simpler and the danger would undoubtedly be lessened. For many reasons this is impossible in
Thirst: Proceedings of the First International Symposium on Thirst in the Regulation of Body Water Held at the Florida State University in Tallahassee, May, 1963
Authors: A. V. Wolf
Journal: JAMA (1964)

In spite of their long history, theories of thirst rich in introspective analysis continue to multiply. The "dry mouth" theory, for example, has been attributed in one form or another to Cannon, Hippocrates, and<i>Pithecanthropus erectus,</i>and has present day adherents. And yet the actual investigation of thirst has been a relatively neglected province, especially among physiologists. Publication of the 30 papers in this volume appears to signal a new climate of scientific interest. No small credit for the successful conference whose proceedings are recorded here belongs to Dr. Wayner, who gathered its distinguished participants. Nominally concerned with thirst, this book necessarily deals also with drinking and satiety, the other two elements of the triad which endlessly repeats its cycle in water metabolism. The work of the neurophysiologist (thirst spots in the hypothalamus), the psychologist (behavior), and the applied scientist (problems of the castaway at sea) are all represented in
p27 <sup>kip1</sup> –838C&gt;A Single Nucleotide Polymorphism Is Associated With Restenosis Risk After Coronary Stenting and Modulates p27 <sup>kip1</sup> Promoter Activity
Authors: Claudia M. van Tiel, Peter I. Bonta, Saskia Z.H. Rittersma, Marcel A.M. Beijk, Edward J. Bradley, Anita M. Klous, Karel T. Koch, Frank Baas, J. Wouter Jukema, Douwe Pons, M. Lourdes Sampietro, Hans Pannekoek, Robbert J. de Winter, Carlie J.M. de Vries
Journal: Circulation (2009)

Background— The cyclin-dependent kinase inhibitor p27 kip1 is a key regulator of smooth muscle cell and leukocyte proliferation in vascular disease, including in-stent restenosis. We therefore hypothesized that common genetic variations or single nucleotide polymorphisms in p27 kip1 may serve as a useful tool in risk stratification for in-stent restenosis. Methods and Results— Three single nucleotide polymorphisms concerning the p27 kip1 gene (−838C&gt;A, rs36228499; −79C&gt;T, rs34330; +326G&gt;T, rs2066827) were determined in a cohort of 715 patients undergoing coronary angioplasty and stent placement. We discovered that the p27 kip1 -838C&gt;A single nucleotide polymorphism is associated with clinical in-stent restenosis; the −838AA genotype decreases the risk of target vessel revascularization (hazard ratio, 0.28; 95% confidence interval, 0.10 to 0.77). This finding was replicated in another cohort study of 2309 patients (hazard ratio, 0.61; 95% confidence interval, 0.40 to 0.93). No association was detected between this end point and the p27 kip1 -79C&gt;T and +326G&gt;T single nucleotide polymorphisms. We subsequently studied the functional importance of the −838C&gt;A single nucleotide polymorphism and detected a 20-fold increased basal p27 kip1 transcriptional activity of the −838A allele containing promoter. Conclusions— Patients with the p27 kip1 -838AA genotype have a decreased risk of in-stent restenosis corresponding with enhanced promoter activity of the −838A allele of this cell-cycle inhibitor, which may explain decreased smooth muscle cell proliferation.
Double isotype production by a neoplastic B cell line. I. Cellular and biochemical characterization of a variant of BCL1 that expresses and secretes both IgM and IgG1.
Authors: Y W Chen, C J Word, S Jones, J W Uhr, P W Tucker, E S Vitetta
Journal: The Journal of Experimental Medicine (1986)

We have subcloned the in vitro-adapted murine B cell leukemia, BCL1.B1, to obtain a variant that expresses both IgM and IgG1. By fluorescence analysis, radioiodination, and immunoprecipitation of cell surface Ig, and by RIA of medium from limiting dilution cultures, we have shown that: (a) all the cells express and secrete both isotypes. The heavy chains of both IgG1 and IgM have the apparent molecular weights of membrane mu and gamma 1 chains; (b) both isotypes bear the same idiotype as determined by immunoprecipitation with antiidiotypic antibody, and both use the same VDJ rearrangement as shown by Southern blotting; and (c) the cells express the membrane and secreted forms of mRNA for both mu and gamma 1 but not gamma 2b or gamma 3. Taken together, the data suggest that all the cells are synthesizing, expressing on their surface, and secreting two isotypes that use the same VDJ rearrangement in the DNA and express the same serologically-defined idiotype. The molecular basis responsible for the production of the two isotypes in a single cell is the subject of the accompanying paper.
Prospective Randomized Trial of Intrapleural Bleomycin Versus Interferon Alfa-2b via Ultrasound-Guided Small-Bore Chest Tube in the Palliative Treatment of Malignant Pleural Effusions
Authors: Sergio Sartori, Davide Tassinari, Piercarlo Ceccotti, Paola Tombesi, Ingrid Nielsen, Lucio Trevisani, Vincenzo Abbasciano
Journal: Journal of Clinical Oncology (2004)

To compare bleomycin pleurodesis and immunotherapy with intrapleural interferon alfa-2b (IFN) in the palliation of malignant pleural effusions.One hundred sixty patients with rapidly recurrent malignant pleural effusion were randomly assigned to intrapleural bleomycin (83 patients) or IFN (77 patients). A 9-French intrapleural catheter was placed under sonographic guidance, and pleural effusion was completely drained before starting the treatment. Bleomycin 0.75 mg/kg was administered as a single dose. An additional dose was given if daily fluid output did not drop to less than 100 mL/d within 3 days. IFN 1 million units/10 kg was administered for six courses at 4-day intervals. Thirty-day and long-term responses were evaluated under the intention-to-treat principle.Thirty-day response was 84.3% in the bleomycin arm and 62.3% in IFN arm (P =.002). Median time to progression was 93 days (range, 12 to 395 days) in bleomycin group, and 59 days (range, 7 to 292 days) in the IFN group (P <.001). Median survival was 96 days (range, 15 to 395) and 85 days (range, 16 to 292) in the bleomycin and IFN groups, respectively. Twenty-three patients received two doses of bleomycin, as their daily fluid output remained higher than 100 mL after the first dose. Thirteen of them had complete response, which lasted until death.Intrapleural bleomycin is more effective than IFN and is a valid option for the palliative treatment of massive, rapidly recurrent malignant pleural effusions. The administration of a second dose of bleomycin to patients not responding to the first one can remarkably improve the overall outcome of the treatment.
p16INK4a deficiency promotes IL-4–induced polarization and inhibits proinflammatory signaling in macrophages
Authors: Céline Cudejko, Kristiaan Wouters, Lucía Fuentes, Sarah Anissa Hannou, Charlotte Paquet, Kadiombo Bantubungi, Emmanuel Bouchaert, Jonathan Vanhoutte, Sébastien Fleury, Patrick Remy, Anne Tailleux, Giulia Chinetti-Gbaguidi, David Dombrowicz, Bart Staels, Réjane Paumelle
Journal: Blood (2011)
Familial Hypercholesterolaemia Regression Study: a randomised trial of low-density-lipoprotein apheresis
Authors: G.R. Thompson, V.M.G. Maher, Y. Kitano, C. Neuwirth, V.M.G. Maher, G. Davies, S. Matthews, M.B. Shortt, A. Rees, A. Mir, A. Henderson, R.J. Prescott, P. de Feyter
Journal: The Lancet (1995)
Peripheral Arterial Surgery
Authors: R. Clement Darling
Journal: New England Journal of Medicine (1969)

Arterial EmbolismArteriosclerotic heart disease is the basis of most arterial embolisms. Of the quarter of patients who present without atrial fibrillation, half will have had previous myocardial infarction to account for the embolus. Extracardiac sources of peripheral emboli are becoming better recognized, particularly aneurysms of the aorta or subclavian vessels, the latter commonly associated with cervical rib. In a recent review of 426 arterial emboli in 260 patients, approximately one tenth involved visceral organs, about one fifth were lodged in cerebral vessels, and more than two thirds were to major limb arteries. Despite the advanced age of these patients, . . .
A CONTRIBUTION TO THE SUBJECT OF TUMORS OF THE HYPOPHYSIS
Authors: DEAN D. LEWIS
Journal: JAMA (1910)

rise to no subjective symptoms.The overlying epidermis was normal in color.Two centimeters farther back was a second lesion, smaller than the first, and of a purplish hue.It was- quite soft to the touch.Immediately below the anterior fold of the elbow-joint was a larger tumor (Fig. 2) (1.5 by 2 cm. in diameter, and 1 cm. in height), which was also purplish in color, and soft and compressible.Higher up, on the inner surface of the upper arm, were four mor.ulules, arranged in ah irregular chain.In only one of these could fluctuation be obtained.The epitroelilear ami axillary glands were not palpable.Tho signs which commonly mark the presence of an ascending cellulitis were absolutely lacking.The patient's temperature was normal, and she slated that if she had not seen the nodules on the wrist she would mil know they were present.Permission to excise one of the smaller lesions was firmly refused.liaeieriologie Kicaminaiion.-Aclinical diagnosis of sporo- triehosis was made, and the case referred lo Dr. W. K. Trimble, of this city, for bactériologie examination, 'fhe large lesion near the elbow-joint was incised, under the usual precautions, and two agar and four glycerin-agar tubes inoculated.The pus was of a mahogany color, thick, stringy, and of the con¬ sistency of syrup.The tubes were placed in an incubator at 37 C. Four days later, there were abundant growths on all six.On investigation, it, was found that pure cultures of the organism had developed on five of the slants (Fig. 3) (one glycerin-agar tube having become contaminated).Some of the patient's blood was secured, and an effort made to prove the feasibility of the sporo-agglutination test, 'fhe method was found, however, to he of more theoretical than practical value.Treatment.-Potassium¡odid, in doses of from 2.0 to 3.0 gm. per day, has been found to be almost a specific in this disease (I am unable to discover who first suggested its use).Locally, a saturated aqueous solution of the same salt, or one of the iodin, potassium iodid, and oil mixtures, is of great value.The patient was placed on this line of treatment, with extremely satisfactory results.When I last saw her, ten days after the first consultation, the lesions had almost entirely disappeared.
DOES NEUROMUSCULAR BLOCKING AGENT HELP FOR THERAPEUTIC HYPOTHERMIA? RESULTS OF A MULTICENTER REGISTRY STUDY FOR OUT OF HOSPITAL CARDIAC ARREST IN JAPAN: J-PULSE-HYPO REGISTRY
Authors: Hideki Arimoto, Hiroshi Rinka, Arito Kaji, Naohiro Yonemoto, Hiroyuki Yokoyama, Ken Nagao, Hiroshi Nonogi
Journal: Journal of the American College of Cardiology (2011)
Phase I Pharmacokinetic/Pharmacodynamic Study of EKB-569, an Irreversible Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Combination with Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in First-Line Treatment of Patients with Metastatic Colorectal Cancer
Authors: Gunnar Folprecht, Josep Tabernero, Claus-Henning Köhne, Charles Zacharchuk, Luis Paz-Ares, Federico Rojo, Susan Quinn, Esther Casado, Ramon Salazar, Richat Abbas, Chantal Lejeune, Irene Marimón, Jordi Andreu, Ulrike Ubbelohde, Hernan Cortes-Funes, Jose Baselga
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To determine the recommended dose (RD) of EKB-569, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer (mCRC). Methods: Patients with previously untreated mCRC received FOLFIRI and EKB-569 at doses of 10, 25, 50, and 75 mg/day (EKB started on day 3). Three sequential skin biopsies were obtained in selected patients to assess the pharmacodynamic effects on EGFR signaling of FOLFIRI alone and with EKB-569. Complete pharmacokinetic sampling and tumor biopsies, when feasible, were conducted. Results: Forty-seven patients were enrolled. Dose-limiting toxicities (grade 3 diarrhea or asthenia) were observed in 1/7 patients at 50 mg EKB-569 and in 2/3 at 75 mg. Two additional dose levels (35 mg EKB-569/day and 50 mg EKB-569/day plus modified FOLFIRI) were evaluated. The RD was 25 mg EKB-569/full dose FOLFIRI. Grades 3 to 4 toxicities in &amp;gt;10% of patients were diarrhea (30%), neutropenia (21%), and asthenia (17%). Twenty-one patients had an objective response [48%; 95% confidence interval (95% CI), 32-65%]. The median time to tumor progression was 7.7 months. At the RD, EKB-569 resulted in complete inhibition of phosphorylated EGFR (pEGFR) and downstream receptor signaling in skin and tumor samples. FOLFIRI alone did not affect pEGFR, but inhibited epidermal proliferation and activated mitogen-activated protein kinase (MAPK) and induced p27 expression in the skin. Conclusion: The RD of EKB-569 is 25 mg/day when combined with FOLFIRI and results in complete EGFR inhibition. Chemotherapy alone interferes with pharmacodynamic markers, an observation to be taken into account in future studies of targeted agents with chemotherapy.