tbuckley/cabot-search huggingface dataset:
Impact of alpha-adrenergic coronary vasoconstriction on the transmural myocardial blood flow distribution during humoral and neuronal adrenergic activation.
Authors: D Baumgart, T Ehring, P Kowallik, B D Guth, M Krajcar, G Heusch
Journal: Circulation Research (1993)

Increased heart rate and left ventricular pressure during humoral and neuronal adrenergic activation act to restrict blood flow preferentially in the subendocardium. The hypothesis was advanced that alpha-adrenergic coronary vasoconstriction preferentially in the subepicardium may counterbalance the enhanced extravascular compression in the subendocardium and serve to maintain blood flow transmurally uniform. In 40 anesthetized dogs, regional myocardial blood flow was determined with colored microspheres; wall function, with sonomicrometry. Humoral adrenergic activation (HAA) was induced by a combination of intravenous atropine, intravenous norepinephrine, and atrial pacing during baseline coronary vasomotor tone (group 1, n = 6) and in the presence of maximal coronary vasodilation with intravenous dipyridamole (group 2, n = 6). In an additional group, HAA was induced by intravenous norepinephrine in the presence of dipyridamole but without atropine and atrial pacing in order to increase end-diastolic left ventricular pressure (group 3, n = 6). Measurements were performed at rest, during HAA, and during ongoing HAA with the intracoronary infusion of the alpha-antagonist phentolamine (Phen). At unchanged mean aortic pressure, Phen improved blood flow particularly to the inner layers as follows: from 1.42 +/- 0.40 (mean +/- SD) to 1.90 +/- 0.40 mL/(min.g) (group 1, P < .05), from 4.99 +/- 2.31 to 5.53 +/- 2.56 mL/(min.g) (group 2, P < .05), and from 6.01 +/- 1.41 to 6.29 +/- 1.27 mL/(min.g) (group 3, P < .05), associated with a decrease in outer layer blood flow in groups 2 and 3. In 16 additional dogs, beta-adrenoceptors were blocked by propranolol and muscarinic receptors by atropine. Neuronal adrenergic activation (NAA) was induced by cardiac sympathetic nerve stimulation (CSNS) during baseline coronary vasomotor tone (group 4, n = 8) and in the presence of maximal vasodilation (group 5, n = 8). Measurements were performed at rest, during a first CSNS, and 20 minutes later during a second CSNS+Phen. The reproducibility of two consecutive episodes of CSNS 20 minutes apart was demonstrated in a separate set of experiments (n = 6). At matched mean aortic pressures, Phen improved blood flow to all myocardial layers in group 4, whereas in group 5, Phen induced a redistribution of myocardial blood flow toward subepicardial layers [from 4.44 +/- 0.96 to 4.81 +/- 0.83 mL/(min.g), P < .05] at the expense of inner layers. With the addition of Phen, there was no change in regional wall function in any group of dogs studied. Thus, during HAA, alpha-adrenergic coronary vasoconstriction does not exert a beneficial effect on transmural blood flow distribution. During NAA, a beneficial effect of alpha-adrenergic coronary vasoconstriction becomes apparent only under conditions of maximal coronary vasodilation.
Changes in cartilage proteoglycan aggrecan after intra-articular injection of interleukin-1 in rabbits: studies of synovial fluid and articular cartilage.
Authors: C Lundberg, I Asberg, M Ionescu, A Reiner, G Smedegard, A R Poole
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To determine how acute but transient inflammation affects the cartilage proteoglycan aggrecan and the value of analyses of synovial fluid to study this. METHODS: For 96 hours after a single intra-articular injection of rabbit knees with human interleukin-1 alpha (IL-1 alpha) or vehicle, articular cartilage and synovial fluid were examined using a putative indicator of aggrecan synthesis (aggrecan chondroitin sulphate epitope 846), immunoreactive keratan sulphate, and total glycosaminoglycan (GAG) content. Aggrecan extractability (with 0.5 M NaCl) followed by 4 M guanidine hydrochloride extraction permitted analyses of cartilage damage, total content and aggrecan heterogeneity. Aggrecan epitopes as well as GAG were assayed in synovial fluid. Changes were related to total joint leucocyte content in synovial fluid. RESULTS: At 10 ng, IL-1 alpha produced a transient increase in synovial fluid leucocytes at six hours and 24 hours. This accompanied a reduction in content and increased extractability of GAG, which was greatest in the tibial medial compartment of the knee. Further studies of this compartment showed no change in keratan sulphate epitope content, but a transient increase in extractability in 0.5 M NaCl. Epitope 846 content and extractability were unchanged. Total contents and extractability for GAG were inversely correlated in both controls and joints injected with IL-1 alpha. These changes were accompanied by transient increases in GAG, keratan sulphate epitope, and 846 content in synovial fluid. CONCLUSION: According to the aggrecan component measured, damage to the matrix of articular cartilage was sometimes reflected by a transient increased extractability and a net loss of aggrecan. There was always an increased release of GAG, and keratan sulphate, and 846 epitopes into synovial fluid. These studies show that changes in aggrecan epitopes and GAG in synovial fluid reflect changes in cartilage metabolism induced by acute transient inflammation.
Designing case-control studies.
Authors: T Yanagawa
Journal: Environmental Health Perspectives (1979)

Identification of confounding factors, evaluation of their influence on cause-effect associations, and the introduction of appropriate ways to account for these factors are important considerations in designing case-control studies. This paper presents designs useful for these purposes, after first providing a statistical definition of a confounding factor. Differences in the ability to identify and evaluate confounding factors and estimate disease risk between designs employing stratification (matching) and designs randomly sampling cases and controls are noted. Linear logistic models for the analysis of data from such designs are described and are shown to liberalize design requirements and to increase relative risk estimation efficiency. The methods are applied to data from a multiple factor investigation of lung cancer patients and controls.
Mutagenic/carcinogenic potential of DEHP and MEHP.
Authors: I Tomita, Y Nakamura, N Aoki, N Inui
Journal: Environmental Health Perspectives (1982)

The mutagenic/carcinogenic activities of DEHP and MEHP were studied in bacteria and mammalian cells. MEHP but not DEHP exerted a dose-dependent DNA damaging effect to B. subtilis in Rec-assay. DEHP and MEHP showed mutagenic activities to S. typhimurium TA-100, with and without S-9 mix, respectively. MEHP produced not only the mutation in E. coli WP2B/r but also sister chromatid exchanges (SCE) in Chinese hamster V79 cells. It also induced 8AG/6TG-resistant gene mutations and chromosomal aberrations in the V79 cells. Transplacental administration of DEHP or MEHP to the Syrian golden hamster embryos was carried out by administering DEHP or MEHP to gravid animals on day 11 of gestation, followed by the cultivation of embryonic cells for 15-20 days. Both DEHP and MEHP induced 8AG/6TG-resistant mutation, chromosomal aberrations and morphological transformation in the embryonic cells of the Syrian golden hamster.
Plasma apolipoprotein CI correlates with increased survival in patients with severe sepsis
Authors: Jimmy F. P. Berbée, Caroline C. van der Hoogt, Carla J. C. de Haas, Kok P. M. van Kessel, Geesje M. Dallinga-Thie, Johannes A. Romijn, Louis M. Havekes, Henk J. van Leeuwen, Patrick C. N. Rensen
Journal: Intensive Care Medicine (2008)
Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas
Authors: H Brem, S Piantadosi, P.C Burger, M Walker, R Selker, N.A Vick, K Black, M Sisti, S Brem, G Mohr, P Muller, R Morawetz, S.C Schold
Journal: The Lancet (1995)

Chemotherapy for brain tumours has been limited because of difficulty in achieving adequate exposure to the tumour without systemic toxicity. We have developed a method for local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumour site allows prolonged local exposure with minimal systemic exposure. We conducted a randomised, placebo-controlled, prospective study to evaluate the effectiveness of biodegradable polymers impregnated with carmustine to treat recurrent malignant gliomas. In 27 medical centres, 222 patients with recurrent malignant brain tumours requiring re-operation were randomly assigned to receive surgically implanted biodegradable polymer discs with or without 3·85% carmustine. Randomisation balanced the treatment groups for all of the prognostic factors examined. Median survival of the 110 patients who received carmustine polymers was 31 weeks compared with 23 weeks for the 112 patients who received only placebo polymers (hazard ratio=0·67, p=0·006, after accounting for the effects of prognostic factors). Among patients with glioblastoma, 6-month survival in those treated with carmustine-polymer discs was 50% greater than in those treated with placebo (mortality=32 of 72 [44%] vs 47 of 73 [64%], p=0·02). There were no clinically important adverse reactions related to the carmustine polymer, either in the brain or systemically. Interstitial chemotherapy delivered with polymers directly to brain tumours at the time of surgery seems to be a safe and effective treatment for recurrent malignant gliomas
17β-Estradiol Inhibits IL-8 in Cystic Fibrosis by Up-Regulating Secretory Leucoprotease Inhibitor
Authors: Sanjay H. Chotirmall, Catherine M. Greene, Irene K. Oglesby, Warren Thomas, Shane J. O'Neill, Brian J. Harvey, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

An unexplained gender gap is observed in cystic fibrosis (CF). Females have poorer lung function, decreased survival, and earlier Pseudomonas colonization.To evaluate the effect of 17beta-estradiol (E(2)) on CF bronchial epithelial cells in vitro and in vivo.On exposure of CFBE41o- cultures to physiological concentrations of E(2), there was a significant dose-dependent inhibition of IL-8 release induced by toll-like receptor agonists, CF bronchoalveolar lavage fluid, or Pseudomonas-conditioned media. Estrogen receptor (ER)-alpha and -beta expression was quantified in cell lines and bronchial brushings from CF and non-CF patients.Both receptors were expressed in vitro and in vivo, although ERbeta expression was significantly higher in CF. Using ER isoform-specific agonists and antagonists, we established that ERbeta mediates the inhibition of CF bronchoalveolar lavage fluid-induced IL-8 release. We also showed that secretory leucoprotease inhibitor gene expression and protein localization to the nucleus increased in response to E(2). Secretory leucoprotease inhibitor knockdown abrogated the inhibitory effects of E(2).E(2) inhibits IL-8 release by ERbeta in CF bronchial epithelial cells through up-regulation of secretory leucoprotease inhibitor, inhibition of nuclear factor (NF)-kappaB, and IL-8 gene expression. These data implicate a novel anti-inflammatory mechanism for E(2) in females with CF, which predisposes to infection and colonization. This could, in part, account for the observed gender dichotomy in CF.
Norethindrone-Mestranol in Hidradenitis Suppurativa
Authors: Marvin I. Lepaw
Journal: JAMA (1966)

<h3>To the Editor:—</h3> I would like to report an interesting case of hidradenitis suppurativa that responded to cyclic administration of a combination of norethindrone and mestranol. A 27-year-old white woman was seen at the Cleveland Clinic in June 1963 complaining of severe recurrent axillary hidradenitis suppurativa. The patient had had this disease, which recurred only between pregnancies for four years. She stated that at the onset of each of her four pregnancies (gravida-4, para-4, abort-0) she noticed the beginning of resolution of all lesions until the mid trimester of her pregnancy when the activity of the lesions appeared to be arrested. In the past she had been given sodium oxacillin, procaine penicillin injections, various tetracycline products by mouth, low doses of x-ray therapy, and injection of staphylococcus toxin. At no time during the course of her recurrences did there seem to be any relief from the condition. Routine urine analysis,
Pleural and Pericardial Pressures Limit Fetal Right Ventricular Output
Authors: Daniel A. Grant, Adrian M. Walker
Journal: Circulation (1996)

Background The chest wall, lungs, and pericardium limit diastolic filling of the left ventricle in the fetus, neonate, and adult. To determine the effect that these tissues have on the fetal right ventricle (RV), we studied six fetal lambs (142 days of gestation). Methods and Results Pregnant ewes were anesthetized (ketamine and α-chloralose), and the fetuses were partially delivered by cesarean section. Fetuses were instrumented to record RV stroke volume, RV end-diastolic pressure (Prved), intrapericardial pressure (Pip), and pleural pressure. Prved was varied between 2 and 20 mm Hg under three conditions: initially with a closed chest and a closed pericardium (CCCP); subsequently with an open chest (chest wall and lungs retracted) and a closed pericardium (OCCP); and finally after the chest wall, lungs, and pericardium were retracted (OCOP). At equal Prved, stroke volume increased substantially when the chest wall and lungs were retracted from the heart and increased further on subsequent retraction of the pericardium (eg, at Prved of 9 mm Hg, stroke volume increased from 1.2±0.2 mL [mean±SEM] in the CCCP condition to 2.9±0.4 and 4.2±0.3 mL in the OCCP and OCOP conditions, respectively, P ≤.05). The limitation of stroke volume in the CCCP and OCCP conditions occurred because Pip increased in an almost one-to-one fashion as Prved increased; as a consequence, RV preload (RV end-diastolic transmural pressure, Prved minus Pip) was relatively unchanged. Conclusions The chest wall–lung combination and the pericardium each significantly constrain the fetal RV and together limit RV stroke volume.
Predictive factors for early cardiac events and angiographic restenosis after coronary stent placement in small coronary arteries
Authors: Jörg Hausleiter, Adnan Kastrati, Julinda Mehilli, Helmut Schühlen, Jürgen Pache, Franz Dotzer, Josef Dirschinger, Albert Schömig
Journal: Journal of the American College of Cardiology (2002)
P309 PROGNOSTIC MODEL FOR PREDICTING DRUG-INDUCED ACUTE LIVER FAILURE
Authors: R.J. Andrade, M. Robles-Díaz, C. Stephens, I. Medina-Cáliz, A. González-Jiménez, A.F. González, N. Kaplowitz, M.C. Fernández, M. Romero-Gómez, M. Jiménez-Pérez, M. Bruguera, M. Prieto, F. Bessone, N. Hernández, M. Arrese, M.I. Lucena
Journal: Journal of Hepatology (2014)
Effect of Altitude and Cobalt Polycythemia, Hypoxia, and Cortisone on Susceptibility of Rats to Endocarditis
Authors: BENJAMIN HIGHMAN, PAUL D. ALTLAND
Journal: Circulation Research (1955)

Rats with polycythemia induced by exposures to simulated high altitudes developed a significantly higher incidence of endocarditis following intravenous bacterial injections than rats with cobalt polycythemia or ground level controls. No increase occurred in altitude rats when polycythemia was prevented by repeated bleedings. These findings suggest that both polycythemia and hypoxia are necessary to explain increased susceptibility of altitude rats. Cortisone increased susceptibility of ground level rats injected with Streptococcus faecalis . Unlike altitude exposures, however, cortisone did not render rats susceptible to endocarditis due to Hemophilus parainfluenza.
Extrahepatic Biliary Obstruction: Magnetic Resonance Imaging Compared With Endoscopic Ultrasonography
Authors: R. Materne, B. Van Beers, J. Gigot, J. Jamart, A. Geubel, J. Pringot, P. Deprez
Journal: Endoscopy (2002)

Background and Study Aims: The aim of this study was to compare prospectively the diagnostic efficacy of magnetic resonance (MR) imaging and endoscopic ultrasonography (EUS) in extrahepatic biliary obstruction.
ABC of Asthma: CHRONIC ASTHMA--GENERAL MANAGEMENT
Authors: J. Rees, J. Price
Journal: BMJ (1995)

Obvious precipitating factors should be sought and avoided when practicable.This is possible for specific allergens such as animals and foods, but is not usually feasible with more widespread allergens such as pollens and house dust mites.A common non-specific stimulus is cigarette smoking.Up to a fifth of asthmatics continue to smoke and strenuous efforts should be made to discourage smoking in both asthmatic patients and their families.Precipitating factors should be carefully explored on one of the first visits but they should also be reassessed periodically.Fortunately most asthmatic patients can have their disease controlled by safe drug treatment with minimal side effects.Education of the patient in understanding the disease and treatment is often helped by home peak flow recording and written explanations of the purpose and practical details of treatment.In particular, the differences between symptomatic bronchodilator treatment and regular maintenance treatment must be emphasised.It is all too common to find asthmatic patients using their dose of inhaled steroid or sodium cromoglycate only to treat an acute attack.Trained nurses can be helpful in continuing education and supervision. Asthma clinics.
695 Prevalence and risk factors for non-alcoholic fatty liver disease in potential living liver donors in Korea: 589 consecutive biopsies review in single center
Authors: J.Y. Lee, K.M. Kim, S.G. Lee, Y.S. Lim, H.C. Lee, Y.H. Chung, Y.S. Lee, D.J. Suh
Journal: Journal of Hepatology (2006)
Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing
Authors: Seung-Young Lee, Myung Sook Huh, Seulki Lee, So Jin Lee, Hyunjin Chung, Jae Hyung Park, Yu-Kyoung Oh, Kuiwon Choi, Kwangmeyung Kim, Ick Chan Kwon
Journal: Journal of Controlled Release (2009)
Bevacizumab combined with chemotherapy significantly improves pathologic complete response in patients with operable or locally advanced breast cancer.
Authors: I Makhoul, KS Vicki, S Korourian, RS Henry-Tillman, ER Siegel, KC Westbrook, LF Hutchins
Journal: Cancer Research (2009)

Abstract Abstract #5114 Bevacizumab (B) improved progression free survival in metastatic breast cancer (BC) when added to chemotherapy (CT) and was relatively safe in the adjuvant setting. This study evaluated pathologic complete response (pCR) and safety of B with CT in the neoadjuvant setting.&amp;#x2028; Methods: This is a single arm, single institution phase II trial. Patients (Pts) eligible for the study were women with proven BC (T1-4 and/or positive axillary LN -excluding inflammatory BC). Pts received CT with docetaxel (T, 75 mg/m2), cyclophosphamide (C, 500 mg/m2) and B (15 mg/kg), TCB every 3 wks x 4 cycles followed by doxorubicin (A, 60 mg/m2) every 3 wks for 4 cycles. After CT, Pts were evaluated clinically (clinical complete or partial response cCR or cPR), by mammogram and for their heart function by MUGA. Breast conserving surgery was considered if the response was deemed satisfactory, otherwise mastectomy was performed and pCR was evaluated. 28 to 84 days after surgery and after documented healing of the operative incision, B was restarted at 15 mg/kg x 9 cycles. XRT, herceptin and endocrine therapy were given as indicated concurrently with B.&amp;#x2028; Results: As planned, 40 Pts were enrolled. Average age 46 (range 27-73). One patient withdrew consent after 2 cycles of TCB. Average tumor size was 5.26 cm (range 1.8 - 15 cm). Lobular 7/ductal 32. Grade I/II/III: 3/12/24. ER +/PR +: 11; ER+/PR-8; ER-/ PR +: 3, ER-/PR-:17. HER2 +: 8. Triple negative: 14. Lymph nodes were + in 25 patients. 32 Pts completed all pre-op CT cycles. One Pt died after 2 cycles of TCB of bilateral PE, 4 Pts received a truncated doxorubicin course due to side effects, 2 Pt received TCB x 2 followed by A x 4. The most common grade 3/4 AEs (#): diarrhea (4), febrile neutropenia (4), musculoskeletal pain (10), fatigue (8), mucositis (3), nausea (2), hypertension (5), syncope (2) infection (3). No clinically significant change in LVEF was noticed (Pre-CT EF 63.3% (55-76%); post-CT EF 61.2% (49-72%)). 4 Pts had a decrease of EF &amp;gt; 10. 21 cCR and 16 cPR were seen.1 Pt had progression and 1 Pt had no change. 38 Pts underwent surgery. 10 had lumpectomy (average pre-CT size 4.8 cm) and 28 had mastectomy (average pre-CT size 6.1 cm). One Pt had infusaport infection and another had breast implant infection, both required device removal and had delayed wound healing. 16 pCR/39 in the breast and 13 pCR/39 in the breast and axilla were seen (pCR breast 41%, pCR breast and axilla 33%). Several Pts had near pCR. Post-operative B safety data will be presented.&amp;#x2028; Conclusions: When added to CT, B improved pCR in a poor prognostic BC Pts and was associated with manageable toxicity. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5114.
Paracrine Coronary Endothelial Control of Left Ventricular Function in Humans
Authors: Walter J. Paulus, Pascal J. Vantrimpont, Ajay M. Shah
Journal: Circulation (1995)

Background Similar to endothelial modulation of vascular tone, myocardial contraction may be modulated by cardioactive agents released from the coronary endothelium. To investigate such modulation in humans, we performed invasive assessment of left ventricular (LV) function before, during, and after bicoronary infusion of substance P, which releases nitric oxide from the endothelium. Methods and Results Eight healthy subjects were investigated during diagnostic coronary angiography and eight transplant recipients during annual catheterization. Tip-micromanometer LV pressure was recorded before, during, and after bicoronary (n=16) and right atrial (n=14) infusion of substance P (20 pmol/min). LV angiograms (n=11) were obtained before and at the end of the substance P infusion. At the end of the intracoronary substance P infusion, we observed (1) a fall in LV peak systolic pressure from 147±16 to 139±15 mm Hg ( P &lt;.01) in healthy subjects and from 147±25 to 141±22 mm Hg ( P &lt;.05) in transplant recipients; (2) a downward and rightward shift of the average LV end-systolic pressure-volume point consistent with depressed systolic performance; and (3) a rise in LV end-diastolic volume at comparable end-diastolic pressure, consistent with increased end-diastolic distensibility. Five minutes after the substance P infusion, LV peak systolic pressure was higher than at baseline in healthy subjects (154±18 mm Hg; P &lt;.05). Right atrial infusion of substance P did not reproduce these changes. Conclusions Bicoronary infusion of substance P modulates LV function in humans, probably through paracrine myocardial action of cardioactive agents released from the coronary endothelium.