tbuckley/cabot-search huggingface dataset:
Extended Nortriptyline and Psychological Treatment for Cigarette Smoking
Authors: Sharon M. Hall, Gary L. Humfleet, Victor I. Reus, Ricardo F. Muñoz, Jennifer Cullen
Journal: American Journal of Psychiatry (2004)

Accepted treatments for cigarette smoking rarely achieve abstinence rates of >35% at 1 year. Low rates may reflect failure to provide extended and multifocal treatment for this complex and chronic addiction. Using a chronic disease model of smoking, the authors undertook a study to determine the effects of long-term antidepressant and psychological treatment.One hundred sixty smokers of > or =10 cigarettes/day were randomly assigned to one of four treatment conditions in a two-by-two (nortriptyline versus placebo by brief versus extended treatment) design. All subjects received 8 weeks of a transdermal nicotine patch, five group counseling sessions, and active or placebo treatment. Interventions for subjects in brief treatment ended at this point. Subjects in extended treatment continued taking drug or placebo to week 52 and received an additional 9 monthly counseling sessions, with checkup telephone calls midway through each session. Subjects were assessed at baseline and weeks 12, 24, 36, and 52. The principal outcome variables were repeated abstinence at each assessment after the first over a 1-year period and a point prevalence of 7 days of abstinence.At week 52, point-prevalence abstinence rates with missing subjects imputed as smokers were 30% for placebo brief treatment, 42% for placebo extended treatment, 18% for active brief treatment, and 50% for active extended treatment. With missing subjects omitted, these rates were 32%, 57%, 21%, and 56%, respectively.Comprehensive extended treatments that combine drug and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature.
Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation.
Authors: D M Bissell, S S Wang, W R Jarnagin, F J Roll
Journal: Journal of Clinical Investigation (1995)

Expression of the group of cytokines known as transforming growth factor-beta (TGF-beta 1, -beta 2 and -beta 3) is increased during liver regeneration induced by a 70% partial hepatectomy. The origin of these changes was examined in purified isolates of hepatocytes, sinusoidal endothelial cells, Kupffer cells (liver macrophages), and lipocytes (Ito or stellate cells) from normal and regenerating liver. In normal liver, TGF-beta 1 and -beta 2 levels were relatively high in sinusoidal endothelial cells and Kupffer cells. After partial hepatectomy, an early peak of TGF-beta 2 and -beta 3 was present in all four cell types, followed by a sustained increase in mRNA for TGF-beta 1, -beta 2, and -beta 3 primarily in the hepatocyte population. The specificity of these changes was established by examining a mechanistically different injury model, fibrosis induced by ligation of the biliary duct. In this model, TGF beta mRNA was increased only in lipocytes and the increase was progressive over a 7-d period of observation. Secretion of TGF beta protein was examined in cell isolates placed in short-term primary culture and generally reflected the corresponding mRNA level. The TGF beta released by hepatocytes was entirely in the latent form, whereas the individual nonparenchymal cell isolates released 50-90% active TGF beta. Hepatocyte-conditioned culture medium, after treatment to activate latent TGF beta, inhibited hepatocellular DNA synthesis as did the authentic factor. The data indicate that after injury TGF beta increases selectively in the cells that are the target of the factor, i.e., in hepatocytes after partial hepatectomy and in lipocytes in inflammation and fibrosis. We conclude that the effects of TGF beta in liver regeneration and fibrogenesis are predominantly, if not exclusively, autocrine.
Predictive value of synovial fluid analysis in juvenile chronic arthritis.
Authors: L Punzi, R Ramonda, S Glorioso, F Schiavon, S Mariuz, P F Gambari
Journal: Annals of the Rheumatic Diseases (1992)

To investigate the value of synovial fluid analysis in predicting the articular evolution of juvenile chronic arthritis, synovial fluid from 29 patients with oligoarticular onset juvenile chronic arthritis were examined prospectively. The patients were subsequently classified after a three year period of observation as having polyarticular (10 patients) or pauciarticular (19 patients) disease. The synovial fluid samples were analysed for total and differential white blood cell count, total protein, beta 2 microglobulin, and total complement activity. For comparison, synovial fluid samples from 95 patients with adult onset rheumatoid arthritis were also analysed. In patients with polyarticular disease polymorphonuclear cells and beta 2 microglobulin concentrations were higher than in the patients with pauciarticular disease (80 (29.2) v 58.1 (25.3), and 3.6 (1.2) v 2.2 (0.5) mg/l, respectively), but there was no significant difference from the patients with rheumatoid arthritis. Synovial fluid analysis may be useful in predicting the evolution of juvenile chronic arthritis and improve definition of its subtypes.
A monoclonal antibody recognizing plasminogen and plasmin—altered reactivity in psoriatic lesions
Authors: C. JUSTUS, S. MULLER, M. D. KRAMER
Journal: British Journal of Dermatology (1987)

To study the organization of the plasminogen activator/plasminogen-plasmin (PA/PG-P) system in human epidermis we raised monoclonal antibodies with specificity for human plasminogen and plasmin (PG-P). Monoclonal antibody P2, which appeared most suitable for immunohistology, is a mouse monoclonal antibody of IgG1 subtype, specific for the precursor enzyme plasminogen and for the high molecular weight chain of the active enzyme, plasmin. Immunofluorescence analysis of normal human epidermis revealed that reactivity with P2 was confined to the basal cell layer. In psoriatic lesions, however, this regional organization was not found. Immunoreactivity in this case was scattered throughout all the hyperproliferating cell layers, which is taken as evidence for an altered distribution of PG-P in psoriatic lesions. In psoriasis other components of the PA/PG-P system have previously been found to be altered. In this context our findings add to the hypothesis that this system may be involved in the pathology or the pathogenesis of psoriatic lesions.
Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
Authors: Arjen M Dondorp, Caterina I Fanello, Ilse CE Hendriksen, Ermelinda Gomes, Amir Seni, Kajal D Chhaganlal, Kalifa Bojang, Rasaq Olaosebikan, Nkechinyere Anunobi, Kathryn Maitland, Esther Kivaya, Tsiri Agbenyega, Samuel Blay Nguah, Jennifer Evans, Samwel Gesase, Catherine Kahabuka, George Mtove, Behzad Nadjm, Jacqueline Deen, Juliet Mwanga-Amumpaire, Margaret Nansumba, Corine Karema, Noella Umulisa, Aline Uwimana, Olugbenga A Mokuolu, Olanrewaju T Adedoyin, Wahab BR Johnson, Antoinette K Tshefu, Marie A Onyamboko, Tharisara Sakulthaew, Wirichada Pan Ngum, Kamolrat Silamut, Kasia Stepniewska, Charles J Woodrow, Delia Bethell, Bridget Wills, Martina Oneko, Tim E Peto, Lorenz von Seidlein, Nicholas PJ Day, Nicholas J White
Journal: The Lancet (2010)
Sequencing of Chemotherapy and Radiation Therapy in Early-Stage Breast Cancer: Updated Results of a Prospective Randomized Trial
Authors: Jennifer R. Bellon, Steven E. Come, Rebecca S. Gelman, I. Craig Henderson, Lawrence N. Shulman, Barbara J. Silver, Jay R. Harris, Abram Recht
Journal: Journal of Clinical Oncology (2005)

The optimal integration of chemotherapy with radiation (RT) for patients with early-stage breast cancer remains uncertain. We present the long-term results of a prospective randomized trial to address this question.Two hundred forty-four patients were randomly assigned after conservative breast surgery to receive 12 weeks of cyclophosphamide, doxorubicin, methotrexate, fluorouracil, and prednisone (CAMFP) before RT (CT-first) or after RT (RT-first). Median follow-up for surviving patients was 135 months.There were no significant differences between the CT-first and RT-first arms in time to any event, distant metastasis, or death. Sites of first failure were also not significantly different.Among breast cancer patients treated with conservative surgery, there is no advantage to giving RT before adjuvant chemotherapy. However, this study does not have enough statistical power to rule out a clinically important survival benefit for either sequence.
Pulse Wave Velocity in the Main Pulmonary Artery of the Dog
Authors: JACK D. BARGAINER
Journal: Circulation Research (1967)

Apparent phase velocities in the main pulmonary artery were calculated from simultaneous measurements of pressure at two sites in 11 anesthetized, open-chest dogs, at heart rates ranging from 24 to 240 beat/min. The distribution of apparent phase velocity with harmonic frequency was similar to that reported previously for input impedance and frequency. Phase velocity in the absence of reflections, estimated by averaging apparent phase velocities at frequencies from 9 to 23 cycle/sec, averaged 275 cm/sec in the control state and 417 cm/sec during the infusion of 5-hydroxytryptamine (serotonin). The elastic modulus of the pulmonary arterial wall implied by these velocities was calculated to be approximately 1.2 x 10 6 dyne/cm 2 in the controls and 2.7 x 10 6 dyne/cm 2 during serotonin. These results are consistent with previous observations on normal pulmonary vascular input impedance in the dog under these conditions, and with the relationships predicted by the Womersley equations, and suggest that the effects of serotonin on the input impedance spectrum are due in part to an increase in pulse wave velocity.
A Comparison of Hirudin with Heparin in the Prevention of Restenosis after Coronary Angioplasty
Authors: Patrick W. Serruys, Jean-Paul R. Herrman, Rudiger Simon, Wolfgang Rutsch, Christoph Bode, Gert-Jan Laarman, Rene van Dijk, Arjan A. van den Bos, Victor A.W.M. Umans, Keith A.A. Fox, Philip Close, Jaap W. Deckers
Journal: New England Journal of Medicine (1995)

The likelihood of restenosis is a major limitation of coronary angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin with irreversible effects, would prevent restenosis after angioplasty. We compared two regimens of recombinant hirudin with heparin.
Patterns of Weight Change Preceding Hospitalization for Heart Failure
Authors: Sarwat I. Chaudhry, Yongfei Wang, John Concato, Thomas M. Gill, Harlan M. Krumholz
Journal: Circulation (2007)

Weight gain is used by disease-management programs as a marker of heart failure decompensation, but little information is available to quantify the relationship between weight change in patients with heart failure and the risk for imminent hospitalization.We conducted a nested case-control study among patients with heart failure referred to a home monitoring system by managed care organizations. We matched 134 case patients with heart failure hospitalization to 134 control patients without heart failure hospitalization on the basis of age, sex, duration of home monitoring, heart failure severity, and baseline body weight. Compared with control patients, case patients experienced gradual weight gain beginning approximately 30 days before hospitalization; changes in daily weight between case and control patients were statistically significant (P<0.001). Within the week before hospitalization, when weight patterns in case and control patients began to diverge more substantially, mean increases of more than 2 and up to 5 pounds, more than 5 and up to 10 pounds, and more than 10 pounds (relative to time of enrollment in the monitoring system) were associated with matched adjusted odds ratios for heart failure hospitalization of 2.77 (95% confidence interval 1.13 to 6.80), 4.46 (95% confidence interval 1.45 to 13.75), and 7.65 (95% confidence interval 2.22 to 26.39), respectively, compared with mean increases of 2 pounds or less.Increases in body weight are associated with hospitalization for heart failure and begin at least 1 week before admission. Daily information about patients' body weight identifies a high-risk period during which interventions to avert decompensated heart failure that necessitates hospitalization may be beneficial.
Training with supplemental oxygen in patients with COPD and hypoxaemia at peak exercise
Authors: JM Rooyackers, PN Dekhuijzen, CL Van Herwaarden, HT Folgering
Journal: European Respiratory Journal (1997)

Supplemental oxygen has acute beneficial effects on exercise performance in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate whether oxygen-supplemented training enhances the effects of training while breathing room air in patients with severe COPD. A randomized controlled trial was performed in 24 patients with severe COPD who developed hypoxaemia during incremental cycle exercise (arterial oxygen saturation (Sa,O2) &lt;90% at peak exercise). All patients participated in an in-patient pulmonary rehabilitation programme of 10 weeks duration. They were assigned either to general exercise training while breathing room air (GET/RA group: forced expiratory volume in one second (FEV1) 38% of predicted; arterial oxygen tension (Pa,O2) 10.5 kPa at rest; Pa,O2 7.3 kPa at peak exercise), or to GET while breathing supplemental oxygen (GET/O2 group: FEV1 29% pred; Pa,O2 10.2 kPa at rest; Pa,O2 7.2 kPa at peak exercise). Sa,O2 was not allowed to fall below 90% during the training. The effects on exercise performance while breathing air and oxygen, and on quality of life were compared. Maximum workload (Wmax) significantly increased in the GET/RA group (mean (SD) 17 (15) W, p&lt;0.01), but not in the GET/O2 group (7 (25) W). Six minute walking distance (6MWD), stair-climbing, weight-lifting exercise (all while breathing room air) and quality of life significantly increased in both groups. Acute administration of oxygen improved exercise performance before and after training. Training significantly increased Wmax, peak carbon dioxide production (V'CO2) and 6MWD while breathing oxygen in both groups. Differences between groups were not significant. Pulmonary rehabilitation improved exercise performance and quality of life in both groups. Supplementation of oxygen during the training did not add to the effects of training on room air.
Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy
Authors: Peiman Habibollahi, Jose-Luiz Figueiredo, Pedram Heidari, Austin M Dulak, Yu Imamura, Adam J. Bass, Shuji Ogino, Andrew T Chan, Umar Mahmood
Journal: Theranostics (2012)

Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64±0.14 and 4.50±0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88±0.04 and 0.81±0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions.
United States Food and Drug Administration Approval Summary: Bortezomib for the Treatment of Progressive Multiple Myeloma after One Prior Therapy
Authors: Robert C. Kane, Ann T. Farrell, Rajeshwari Sridhara, Richard Pazdur
Journal: Clinical Cancer Research (2006)

Abstract Purpose: On March 25, 2005, bortezomib (Velcade for Injection; Millennium Pharmaceuticals, Inc., Cambridge, MA, and Johnson &amp; Johnson Pharmaceutical Research &amp; Development, L.L.C.) received regular approval from the U.S. Food and Drug Administration (U.S. FDA) for the treatment of multiple myeloma (MM) progressing after at least one prior therapy. This approval was based on bortezomib's efficacy and safety which was shown in a single, large, comparative international open-label phase 3 trial that randomized 669 patients with MM previously treated with at least one systemic regimen to receive single-agent bortezomib or high-dose dexamethasone. The FDA analysis of the trial data and bortezomib's regulatory development are summarized here. Experimental Design and Results: Following a preplanned interim analysis of time to disease progression (the primary end point), an independent data-monitoring committee advised the sponsor to halt the study and offer bortezomib to all dexamethasone-treated study patients. Time to progression was significantly prolonged in the bortezomib treatment arm (median, 6.2 months) compared with the dexamethasone arm (median, 3.5 months; log-rank test, P &amp;lt; 0.0001; hazard ratio, 0.55; 95% confidence interval, 0.44-0.69). Analysis of overall survival done on the interim database (with 20% of events) showed the superiority of bortezomib for patients (log-rank test, P &amp;lt; 0.05; hazard ratio, 0.57; 95% confidence interval, 0.40-0.81). Using criteria from the European Group for Blood and Marrow Transplantation, the response rate (complete plus partial response) with bortezomib was also superior to dexamethasone (38% versus 18%; P &amp;lt; 0.0001). Adverse events on the bortezomib arm were similar to those previously observed in phase 2 studies; some notable adverse events included asthenia, peripheral neuropathy, thrombocytopenia, and neutropenia. Conclusions: The U.S. FDA had earlier (May 2003) granted bortezomib accelerated approval for the treatment of patients with MM progressing after two prior therapies. The results of the phase 3 trial and the FDA analysis of the data, along with the sponsor's completion of other postmarketing commitments, confirm bortezomib's benefit and support regular approval.
Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury
Authors: Christer Baeck, Alexander Wehr, Karlin Raja Karlmark, Felix Heymann, Mihael Vucur, Nikolaus Gassler, Sebastian Huss, Sven Klussmann, Dirk Eulberg, Tom Luedde, Christian Trautwein, Frank Tacke
Journal: Gut (2011)

<h3>Objective</h3> Monocyte chemoattractant protein-1 (MCP-1, CCL2), the primary ligand for chemokine receptor C–C chemokine receptor 2 (CCR2), is increased in livers of patients with non-alcoholic steatohepatitis (NASH) and murine models of steatohepatitis and fibrosis. It was recently shown that monocyte/macrophage infiltration into the liver upon injury is critically regulated by the CCL2/CCR2 axis and is functionally important for perpetuating hepatic inflammation and fibrogenesis. The structured L-enantiomeric RNA oligonucleotide mNOX-E36 (a so-called Spiegelmer) potently binds and inhibits murine MCP-1. Pharmacological inhibition of MCP-1 with mNOX-E36 was investigated in two murine models of chronic liver diseases. <h3>Methods</h3> Pharmacological inhibition of MCP-1 by thrice-weekly mNOX-E36 subcutaneously was tested in murine models of acute or chronic carbon tetrachloride (CCl<sub>4</sub>)- and methionine–choline-deficient (MCD) diet-induced chronic hepatic injury in vivo. <h3>Results</h3> Antagonising MCP-1 by mNOX-E36 efficiently inhibited murine monocyte chemotaxis in vitro as well as migration of Gr1<sup>+</sup> (Ly6C<sup>+</sup>) blood monocytes into the liver upon acute toxic injury in vivo. In murine models of CCl<sub>4</sub>- and MCD diet-induced hepatic injury, the infiltration of macrophages into the liver was significantly decreased in anti-MCP-1-treated mice as found by fluorescence-activated cell sorting (FACS) analysis and immunohistochemistry. In line with lower levels of intrahepatic macrophages, proinflammatory cytokines (tumour necrosis factor α, interferon γ and interleukin 6) were significantly reduced in liver tissue. Overall fibrosis progression over 6 (CCl<sub>4</sub>) or 8 weeks (MCD diet) was not significantly altered by anti-MCP-1 treatment. However, upon MCD diet challenge a lower level of fatty liver degeneration (histology score, Oil red O staining, hepatic triglyceride content, lipogenesis genes) was detected in mNOX-E36-treated animals. mNOX-E36 also ameliorated hepatic steatosis upon therapeutic administration. <h3>Conclusions</h3> These results demonstrate the successful pharmacological inhibition of hepatic monocyte/macrophage infiltration by blocking MCP-1 during chronic liver damage in two in vivo models. The associated ameliorated steatosis development suggests that inhibition of MCP-1 is an interesting novel approach for pharmacological treatment in liver inflammation and steatohepatitis.
Effect of genioglossus contraction on pharyngeal lumen and airflow in sleep apnoea patients
Authors: A. Oliven, N. Tov, L. Geitini, U. Steinfeld, R. Oliven, A. R. Schwartz, M. Odeh
Journal: European Respiratory Journal (2007)

The purpose of the present study was to quantify the mechanical effect of genioglossus stimulation on flow mechanics and pharyngeal cross-sectional area in patients with obstructive sleep apnoea, and to identify variables that determine the magnitude of the respiratory effect of tongue protrusion. The pressure/flow and pressure/cross-sectional area relationships of the velo- and oropharynx were assessed in spontaneously breathing propofol-anaesthetised subjects before and during genioglossus stimulation. Genioglossus contraction decreased the critical pressure significantly from 1.2±3.3 to -0.7±3.8 cmH<sub>2</sub>O, with individual decreases ranging -0.6–5.9 cmH<sub>2</sub>O. Pharyngeal compliance was not affected by genioglossus contraction. The pharyngeal response to genioglossus stimulation was related to the magnitude of advancement of the posterior side of the tongue, but not to the severity of sleep apnoea, critical pressure, compliance or the shape and other characteristics of the velopharynx. Genioglossus contraction enlarges both the velo- and the oropharynx and lowers the critical pressure without affecting pharyngeal stiffness. The response to genioglossus stimulation depends upon the magnitude of tongue protrusion achieved rather than on inherent characteristics of the patient and their airway.