tbuckley/cabot-search huggingface dataset:
Effects of Catecholamines and Atropine on Cardiovascular Response to Exercise in the Dog
Authors: ERNST W. O. KECK, MICHAEL J. ALLWOOD, ROBERT J. MARSHALL, JOHN T. SHEPHERD
Journal: Circulation Research (1961)

The manner in which the administration of epinephrine, norepinephrine, isoproterenol, and atrophic modifies the cardiovascular response to exercise has been studied in 12 dogs. In control observations, exercise increased the cardiac output by 116 per cent, the heart rate by 102 per cent, and the stroke volume by 8 per cent. When epinephrine was infused during identical exercise, the cardiac output was similar; however, the stroke volume was increased by 50 per cent. During infusion of norepinephrine, the cardiac output was reduced by 11 per cent compared with that during control exercise, and the stroke volume was increased by 25 per cent. With isoproterenol, the cardiac output exceeded that during control exercise, but the stroke volume was unchanged. Prior to administration of atropine, the cardiac output at rest averaged 4.2 L. per minute. After injection of atropine, the cardiac output averaged 3.7 L. per minute, the heart rate increased from 121 to 249 beats per minute, and the stroke volume decreased from 35 to 15 ml. Before atropinization, the cardiac output, heart rate, and stroke volume during exercise were increased by 95, .90, and 2 per cent over the resting values; after atropinization, the corresponding increases were 110, 7, and 100 per cent. Thus, while cardiac output during exercise normally is regulated mainly by changes in the heart rate, the stroke volume may make a major contribution under other circumstances.
Screening for Metastasis From Choroidal Melanoma: The Collaborative Ocular Melanoma Study Group Report 23
Authors: Marie Diener-West, Sandra M. Reynolds, Donna J. Agugliaro, Robert Caldwell, Kristi Cumming, John D. Earle, Donna L. Green, Barbara S. Hawkins, James Hayman, Ishmael Jaiyesimi, John M. Kirkwood, Wui-Jin Koh, Dennis M. Robertson, John M. Shaw, Jonni Thoma
Journal: Journal of Clinical Oncology (2004)

Purpose To describe the predictive value of liver function tests (LFTs), chest x-ray, and diagnostic imaging for detecting melanoma metastasis during routine follow-up after treatment for choroidal melanoma. Materials and Methods Prospective longitudinal follow-up of patients enrolled onto two randomized trials was conducted by the Collaborative Ocular Melanoma Study (COMS) Group. Baseline and annual or semiannual systemic and laboratory evaluations were performed according to a standard protocol for 2,320 patients enrolled on the COMS. Results COMS patients were screened annually for metastasis and new cancers using LFTs (alkaline phosphatase, AST, ALT, or bilirubin). Elevated findings (1.5 to 2 times upper limit of normal) on LFT prompted a diagnostic or imaging test to confirm or rule out cancer recurrence. Of 714 patients with clinical reports of metastasis, 675 patients died. Of these 675 patients, all but four had either histopathologically confirmed or clinically suspected metastatic melanoma present at the time of death. Among all patients, the 5-year cumulative diagnosis rate of metastatic melanoma was 24% (95% CI, 22% to 27%). Based on all patients with reported metastasis, the sensitivity, specificity, positive predictive value and negative predictive value associated with at least one abnormal LFT before first diagnosis of metastasis at any site was 14.7%, 92.3%, 45.7% and 71.0%, respectively. Conclusion Use of LFTs results followed by diagnostic tests has high specificity and predictive values but low sensitivity. Better tests are needed to identify earlier metastatic disease associated with choroidal melanoma.
Psychometric properties of the Knee injury and Osteoarthritis Outcome Score for Children (KOOS-Child) in children with knee disorders
Authors: Maria Örtqvist, Maura D Iversen, Per-Mats Janarv, Eva W Broström, Ewa M Roos
Journal: British Journal of Sports Medicine (2014)

The Knee injury and Osteoarthritis Outcome Score (KOOS) is a self-administered valid and reliable questionnaire for adults with joint injury or degenerative disease. Recent data indicate a lack of comprehensibility when this is used with children. Thus, a preliminary KOOS-Child was developed. This study aims to evaluate psychometric properties of the final KOOS-Child when used in children with knee disorders.115 children (boys/girls 51/64, 7-16 years) with knee disorders were recruited. All children (n=115) completed the KOOS-Child, the Child-Health Assessment Questionnaire (CHAQ) and the EQ-5D-Youth version (EQ-5D-Y) at baseline to evaluate construct validity. Two additional administrations (1-3 weeks and 3 months) were performed for analyses of reliability (internal consistency and test-retest; n=72) and responsiveness (n=91). An anchor-based approach was used to evaluate responsiveness and interpretability.After item reduction, the final KOOS-Child consists of 39 items divided into five subscales. No floor or ceiling effects (≤15%) were found. An exploratory factor analysis on subscale level demonstrated that items in all subscales except for Symptoms loaded on one factor (Eigenvalues 3.1-5.5, Symptom: 2 factors, Eigenvalue >1). Sufficient homogeneity was found for all subscales (Cronbach's α = 0.80-0.90) except for the Symptoms subscale (α = 0.59). Test-retest reliability was substantial to excellent for all subscales (Intraclass Correlation Coefficient 0.78-0.91, Smallest Detectable Change (SDC)ind 14.6-22.6, SDCgroup 1.7-2.7). Construct validity was confirmed, and greater effect sizes were seen in those reporting improved clinical status. Minimal important changes greater than the SDCs were found for patients reporting to be better and much better.The final KOOS-Child demonstrates good psychometric properties and supports the use of the KOOS-Child when evaluating children with knee disorders.
PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2
Authors: Yukiko Aikawa, Takuo Katsumoto, Pu Zhang, Haruko Shima, Mika Shino, Kiminori Terui, Etsuro Ito, Hiroaki Ohno, E Richard Stanley, Harinder Singh, Daniel G Tenen, Issay Kitabayashi
Journal: Nature Medicine (2010)
Regulation of sodium absorption by canine tracheal epithelium.
Authors: J J Cullen, M J Welsh
Journal: Journal of Clinical Investigation (1987)

To regulate the quantity of respiratory tract fluid, the airway epithelium either secretes chloride, Cl-, or reabsorbs sodium, Na+. Many secretagogues inhibit Na+ absorption, but the decrease may result from a fall in the electrochemical gradient for Na+ absorption. We examined regulation of Na+ absorption independent of Cl- secretion, by bathing canine tracheal epithelium in Cl--free, gluconate Ringers solution. Prostaglandin E2, 2-chloroadenosine, and isoproterenol increased short-circuit current (Isc) and the rate of Na+ absorption. In contrast, indomethacin, which inhibits endogenous prostaglandin production, decreased Isc. These agents regulate cellular levels of cAMP; direct addition of 8-Br-cAMP also acutely increased Isc. We examined chronic regulation of Na+ absorption in cell monolayers grown on permeable supports in serum-free media. Exposure to aldosterone for two days increased baseline Isc by 50% and the amiloride-inhibitable current by 55%. These data indicate that Na+ absorption is both acutely and chronically regulated in the airway epithelium.
Phase 1 study of 28-day, low-dose temozolomide and BCNU in the treatment of malignant gliomas after radiation therapy
Authors: Jeffrey J. Raizer, Mark G. Malkin, Martin Kleber, Lauren E. Abrey
Journal: Neuro-Oncology (2004)

We conducted a study to determine the dose-limiting toxicity of an extended dosing schedule of temozolomide (TMZ) when used with a fixed dose of BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea (carmustine), taking advantage of TMZ's ability to deplete O6-alkylguanine-DNA-alkyltransferase and the synergistic activity of these two agents. Patients with malignant gliomas who had undergone radiation therapy were eligible. Patients were treated with TMZ for 28 days, followed by a 28-day rest (1 cycle). The TMZ was started at 50 mg/m2 and increased in 10-mg/m2 increments; a fixed dose of BCNU (150 mg/m2) was given within 72 h of starting TMZ. A standard phase 1 dose-escalation scheme was used with 3 patients per cohort. Fourteen glioblastoma patients and 10 anaplastic astrocytoma patients were treated. The dose-limiting toxicity was myelosuppression at 90 mg/m2 of TMZ. The total number of cycles given was 73 (median number was 2). Six patients (25%) required a dose reduction in BCNU, and six were removed from study for hematologic toxicity after cycle 1; three patients overlapped. The median time to progression and overall survival were, respectively, 82 and 132 weeks for anaplastic astrocytomas and 14 and 69 weeks for glioblastomas. We conclude that the combination of BCNU and the extended dosing schedule of TMZ is feasible and that the maximal tolerated dose of a 28-day course of TMZ is 80 mg/m2 when combined with a fixed dose of BCNU at 150 mg/m2. This is the recommended dose for phase 2, but myelosuppression after cycle 1 suggests that long-term treatment may be difficult.
Modulatory role of tachykinin NK<sub>1</sub>receptor in cholinergic contraction of mouse trachea
Authors: K.G. Tournoy, K.O. De Swert, P.G. Leclere, R.A. Lefebvre, R.A. Pauwels, G.F. Joos
Journal: European Respiratory Journal (2003)

The role of the NK 1 receptor in airway contraction induced by electrical field stimulation (EFS) was evaluated by comparing the response in NK 1 receptor knockout mice (NK 1 R −/− ) with that of NK 1 receptor wild-type controls (WT). A frequency/response curve on tracheas from NK 1 R −/− mice and NK 1 R WT littermates was constructed. After incubation with [ 3 H]choline, [ 3 H]acetylcholine release upon EFS was measured by high-performance liquid chromatography and liquid scintillation counting. The effects of atropine (1×10 −6 M), tetrodotoxin (1×10 −6 M) and a specific NK 1 R antagonist (SR140333, 1×10 −8 M) were studied, as well as the effects of substance P (1×10 −5 M) on precontracted tracheas. Upon EFS, NK 1 R −/− mice had a significant lower trachea contractility than the NK 1 R WT animals, accompanied with less [ 3 H]acetylcholine release. Pretreatment with atropine or tetrodotoxin abolished the EFS-induced contraction in both strains. Pretreatment with the NK 1 R antagonist SR140333 significantly reduced the contractility in the NK 1 R WT but not in the NK 1 R −/− mice. Substance P caused a small contraction in both NK 1 R WT and NK 1 R −/− mice. Substance P induced a relaxation in precontracted tracheas in NK 1 R WT but not in NK 1 R −/− mice. The data presented here provide direct evidence that the NK 1 receptor augments cholinergic neurotransmission in mouse trachea.
Sulforaphane targets pancreatic tumour-initiating cells by NF- B-induced antiapoptotic signalling
Authors: G Kallifatidis, V Rausch, B Baumann, A Apel, B M Beckermann, A Groth, J Mattern, Z Li, A Kolb, G Moldenhauer, P Altevogt, T Wirth, J Werner, P Schemmer, M W Buchler, A V Salnikov, I Herr
Journal: Gut (2008)

<h3>Background and aims:</h3> Emerging evidence suggests that highly treatment-resistant tumour-initiating cells (TICs) play a central role in the pathogenesis of pancreatic cancer. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to be a novel anticancer agent; however, recent studies have shown that many pancreatic cancer cells are resistant to apoptosis induction by TRAIL due to TRAIL-activated nuclear factor-κB (NF-κB) signalling. Several chemopreventive agents are able to inhibit NF-κB, and favourable results have been obtained—for example, for the broccoli compound sulforaphane—in preventing metastasis in clinical studies. The aim of the study was to identify TICs in pancreatic carcinoma for analysis of resistance mechanisms and for definition of sensitising agents. <h3>Methods:</h3> TICs were defined by expression patterns of a CD44<sup>+</sup>/CD24<sup>−</sup>, CD44<sup>+</sup>/CD24<sup>+</sup> or CD44<sup>+</sup>/CD133<sup>+</sup> phenotype and correlation to growth in immunodeficient mice, differentiation grade, clonogenic growth, sphere formation, aldehyde dehydrogenase (ALDH) activity and therapy resistance. <h3>Results:</h3> Mechanistically, specific binding of transcriptionally active cRel-containing NF-κB complexes in TICs was observed. Sulforaphane prevented NF-κB binding, downregulated apoptosis inhibitors and induced apoptosis, together with prevention of clonogenicity. Gemcitabine, the chemopreventive agents resveratrol and wogonin, and the death ligand TRAIL were less effective. In a xenograft model, sulforaphane strongly blocked tumour growth and angiogenesis, while combination with TRAIL had an additive effect without obvious cytotoxicity in normal cells. Freshly isolated patient tumour cells expressing markers for TICs could be sensitised by sulforaphane for TRAIL-induced cytotoxity. <h3>Conclusion:</h3> The data provide new insights into resistance mechanisms of TICs and suggest the combination of sulforaphane with TRAIL as a promising strategy for targeting of pancreatic TICs.
High Court judge criticises Andrew Wakefield for trying to silence his critics
Authors: Clare Dyer
Journal: BMJ (2005)

Andrew Wakefield, the doctor at the centre of the measles, mumps, and rubella (MMR) vaccine controversy, was criticised by a high court judge last week for trying to silence critics by warning them that he was suing for libel while at the same time failing to progress the case.

Mr Justice Eady said that he was quite satisfied that Dr Wakefield, who now works in Austin, Texas, “wished to extract whatever advantage he could from the existence of the proceedings while not wishing to progress them or to give the defendants an opportunity of meeting the claims.”

The judge refused Dr Wakefield's application to …
Sensitive detection of the effects of reperfusion on myocardium by ultrasonic tissue characterization with integrated backscatter.
Authors: S A Wickline, L J Thomas, J G Miller, B E Sobel, J E Perez
Journal: Circulation (1986)

We have shown recently that tissue characterization of myocardium with ultrasound reflects changes associated with contractile function throughout the cardiac cycle. To determine whether ultrasonic tissue characterization can sensitively detect the impact of ischemic injury and reperfusion on contractile properties of the heart, we studied the time course of change of backscatter after 5, 20, and 60 min of coronary occlusion followed by reperfusion in 15 dogs. The time-averaged integrated backscatter (IB) and the amplitude and phase of cyclic variation of IB (phase relative to the left ventricular pressure waveform) were measured. A novel ultrasonic index of acute injury was identified, the phase-weighted amplitude of cyclic variation, and calculated by weighting the amplitude of cyclic variation of IB with respect to the phase. We hypothesized that backscatter variables would change dramatically after occlusion and that their restitution after reperfusion would sensitively reflect the extent and time course of reversibility of ischemic injury. After coronary occlusion, segmental wall thickening decreased from approximately 55% to 5% regardless of the duration of ischemia. Changes in backscatter associated with this decrease included an increase in time-averaged IB of approximately 5 dB, a 5 dB decrease in cyclic variation, an 80 degree phase shift, and a 7 dB decrease in phase-weighted amplitude. Wall thickening after reperfusion immediately after the 5, 20, or 60 min occlusions recovered to 45%, 27%, and 12% of baseline values, respectively. Within 3 hr it recovered to 53%, 44%, and 22%. Time-averaged IB recovered initially by 89%, 61%, and 44% (all p less than .05) and continued to recover subsequently although more slowly. Ultimate recovery was virtually complete. In contrast to the rapid recovery of time-averaged IB, phase-weighted amplitude recovered initially to only 72%, 41%, and -7% of baseline (all p less than .05) and manifested slower and incomplete recovery when ischemia had been present for 20 or 60 min. After reperfusion, the time course of both cyclic variation and phase were reflected by changes in the phase-weighted amplitude. The backscatter variables assessed appear to sensitively delineate the duration, time course of recovery, and reversibility of ischemic injury in response to reperfusion. The results suggest that early recovery of time-averaged IB corresponds in part to the restoration of tissue ultrastructural integrity.(ABSTRACT TRUNCATED AT 400 WORDS)
Treatment of Blood Clots
Authors: Samuel Z. Goldhaber, Nicole Grasso-Correnti
Journal: Circulation (2002)

his Cardiology Patient Page will focus on medical treatment of blood clots that can cause critical illness by blocking the blood supply to the heart, brain, lungs, or legs.Blood clots that develop in the arteries can cause heart attack, stroke, and severe leg pain and difficulty walking.Blood clots in the veins or venous system can cause deep venous thrombosis (DVT) in the pelvic, leg, and upper extremity veins.When these DVTs break off and travel through the bloodstream to the heart and then to the lung blood vessels, they cause acute pulmonary embolism (PE). 1 What Medications Will Be Used to Treat My ArterialBlood Clots?Treatment of arterial clots may include aspirin and clopidogrel (oral antiplatelet agents), intravenous antiplatelet agents, heparin (a blood thinner and anticoagulant), and clot busters (thrombolytic agents).In addition to medications, special interventional catheters may be used to remove or compress these arterial clots.
A <i>Let-7</i> MicroRNA SNP in the <i>KRAS</i> 3′UTR Is Prognostic in Early-Stage Colorectal Cancer
Authors: Kim M. Smits, Trupti Paranjape, Sunitha Nallur, Kim A.D. Wouters, Matty P. Weijenberg, Leo J. Schouten, Piet A. van den Brandt, Fred T. Bosman, Joanne B. Weidhaas, Manon van Engeland
Journal: Clinical Cancer Research (2011)

Colorectal cancer (CRC) is a common cause of death worldwide. Tumor-node-metastasis-system stage is currently used to guide therapy decisions but lacks precision. Prognostic biomarkers are needed to refine stratification of patients for chemotherapy but validated biomarkers are not yet available. Recently, a SNP in a lethal-7 (let-7) miRNA complementary site (LCS6) in the KRAS 3'untranslated region was suggested to affect survival in metastatic CRC. Effects in early-stage CRC are however unknown. We studied KRAS-LCS6 genotype, hypothesizing that it might identify early-stage cases with a poor prognosis, and could potentially be used in therapy decision-making.We studied 409 early stage, 182 stage III, and 69 stage IV cases, and 1,886 subcohort members from the Netherlands Cohort Study. KRAS-LCS6 genotype was assessed with TaqMan PCR. Kaplan-Meier analyses or Cox regression were used to assess associations between genotype and CRC risk or cause-specific survival.Early-stage cases with the KRAS-LCS6 variant had a lower CRC risk (incidence-rate ratio 0.68; 95% CI: 0.49-0.94) and a better survival (log-rank P = 0.038; HR 0.46; 95% CI: 0.18-1.14). In patients with KRAS-mutated CRC carrying the KRAS-LCS6 variant, the better outcome was enhanced as no patients died of CRC (log-rank P = 0.017). In advanced patients, no clear association between genotype and CRC risk or survival was observed.Our results indicate that early-stage CRC cases with the KRAS-LCS6 variant have a better outcome. In advanced disease, the better outcome no longer exists. For early-stage patients, KRAS-LCS6 genotype combined with KRAS mutations merits validation as a prognostic biomarker and consideration in therapy decision-making.
Peripheral Blood Mononuclear Cell Gene Expression Profiles Predict Poor Outcome in Idiopathic Pulmonary Fibrosis
Authors: Jose D. Herazo-Maya, Imre Noth, Steven R. Duncan, SungHwan Kim, Shwu-Fan Ma, George C. Tseng, Eleanor Feingold, Brenda M. Juan-Guardela, Thomas J. Richards, Yves Lussier, Yong Huang, Rekha Vij, Kathleen O. Lindell, Jianmin Xue, Kevin F. Gibson, Steven D. Shapiro, Joe G. N. Garcia, Naftali Kaminski
Journal: Science Translational Medicine (2013)

We aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) by performing microarray experiments of PBMCs in discovery and replication cohorts of IPF patients. Microarray analyses identified 52 genes associated with transplant-free survival (TFS) in the discovery cohort. Clustering the microarray samples of the replication cohort using the 52-gene outcome-predictive signature distinguished two patient groups with significant differences in TFS. We studied the pathways associated with TFS in each independent microarray cohort and identified decreased expression of "The costimulatory signal during T cell activation" Biocarta pathway and, in particular, the genes CD28, ICOS, LCK, and ITK, results confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A proportional hazards model, including the qRT-PCR expression of CD28, ICOS, LCK, and ITK along with patient's age, gender, and percent predicted forced vital capacity (FVC%), demonstrated an area under the receiver operating characteristic curve of 78.5% at 2.4 months for death and lung transplant prediction in the replication cohort. To evaluate the potential cellular source of CD28, ICOS, LCK, and ITK expression, we analyzed and found significant correlation of these genes with the PBMC percentage of CD4(+)CD28(+) T cells in the replication cohort. Our results suggest that CD28, ICOS, LCK, and ITK are potential outcome biomarkers in IPF and should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies.
The Pivotal Role of Integrin β1 in Metastasis of Head and Neck Squamous Cell Carcinoma
Authors: Dongsheng Wang, Susan Müller, A.R.M. Ruhul Amin, Donghai Huang, Ling Su, Zhongliang Hu, Mohammad Aminur Rahman, Sreenivas Nannapaneni, Lydia Koenig, Zhengjia Chen, Mourad Tighiouart, Dong M. Shin, Zhuo G. Chen
Journal: Clinical Cancer Research (2012)

This study aimed to understand the prognostic value of integrin β1 expression in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its association with metastatic HNSCC.