tbuckley/cabot-search huggingface dataset:
Course of Posttraumatic Stress Disorder 40 Years After the Vietnam War
Authors: Charles R. Marmar, William Schlenger, Clare Henn-Haase, Meng Qian, Emily Purchia, Meng Li, Nida Corry, Christianna S. Williams, Chia-Lin Ho, Danny Horesh, Karen-Inge Karstoft, Arieh Shalev, Richard A. Kulka
Journal: JAMA Psychiatry (2015)

The long-term course of readjustment problems in military personnel has not been evaluated in a nationally representative sample. The National Vietnam Veterans Longitudinal Study (NVVLS) is a congressionally mandated assessment of Vietnam veterans who underwent previous assessment in the National Vietnam Veterans Readjustment Study (NVVRS).To determine the prevalence, course, and comorbidities of war-zone posttraumatic stress disorder (PTSD) across a 25-year interval.The NVVLS survey consisted of a self-report health questionnaire (n = 1409), a computer-assisted telephone survey health interview (n = 1279), and a telephone clinical interview (n = 400) in a representative national sample of veterans who served in the Vietnam theater of operations (theater veterans) from July 3, 2012, through May 17, 2013. Of 2348 NVVRS participants, 1920 were alive at the outset of the NVVLS, and 81 died during recruitment; 1450 of the remaining 1839 (78.8%) participated in at least 1 NVVLS study phase. Data analysis was performed from May 18, 2013, through January 9, 2015, with further analyses continued through April 13, 2015.Study instruments included the Mississippi Scale for Combat-Related PTSD, PTSD Checklist for DSM-IV supplemented with PTSD Checklist for DSM-5 items (PCL-5+), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and Structured Clinical Interview for DSM-IV, Nonpatient Version.Among male theater veterans, we estimated a prevalence (95% CI) of 4.5% (1.7%-7.3%) based on CAPS-5 criteria for a current PTSD diagnosis; 10.8% (6.5%-15.1%) based on CAPS-5 full plus subthreshold PTSD; and 11.2% (8.3%-14.2%) based on PCL-5+ criteria for current war-zone PTSD. Among female veterans, estimates were 6.1% (1.8%-10.3%), 8.7% (3.8%-13.6%), and 6.6% (3.5%-9.6%), respectively. The PCL-5+ prevalence (95% CI) of current non-war-zone PTSD was 4.6% (2.6%-6.6%) in male and 5.1% (2.3%-8.0%) in female theater veterans. Comorbid major depression occurred in 36.7% (95% CI, 6.2%-67.2%) of veterans with current war-zone PTSD. With regard to the course of PTSD, 16.0% of theater veterans reported an increase and 7.6% reported a decrease of greater than 20 points in Mississippi Scale for Combat-Related PTSD symptoms. The prevalence (95% CI) of current PCL-5+-derived PTSD in study respondents was 1.2% (0.0%-3.0%) for male and 3.9% (0.0%-8.1%) for female Vietnam veterans.Approximately 271,000 Vietnam theater veterans have current full PTSD plus subthreshold war-zone PTSD, one-third of whom have current major depressive disorder, 40 or more years after the war. These findings underscore the need for mental health services for many decades for veterans with PTSD symptoms.
Hyperventilation Induces Release of Cytokines from Perfused Mouse Lung
Authors: ALEXANDER NEPOMUK von BETHMANN, FRANK BRASCH, ROLF NÜSING, KATHRIN VOGT, HANS D. VOLK, KLAUS-MICHAEL MÜLLER, ALBRECHT WENDEL, STEFAN UHLIG
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Artificial mechanical ventilation represents a major cause of iatrogenic lung damage in intensive care. It is largely unknown which mediators, if any, contribute to the onset of such complications. We investigated whether stress caused by artificial mechanical ventilation leads to induction, synthesis, and release of cytokines or eicosanoids from lung tissue. We used the isolated perfused and ventilated mouse lung where frequent perfusate sampling allows determination of mediator release into the perfusate. Hyperventilation was executed with either negative (NPV) or positive pressure ventilation (PPV) at a transpulmonary pressure that was increased 2.5-fold above normal. Both modes of hyperventilation resulted in an approximately 1.75-fold increased expression of tumor necrosis factor α (TNF α ) and interleukin-6 (IL-6) mRNA, but not of cyclooxygenase-2 mRNA. After switching to hyperventilation, prostacyclin release into the perfusate increased almost instantaneously from 19 ± 17 pg/ min to 230 ± 160 pg/min (PPV) or 115 ± 87 pg/min (NPV). The enhancement in TNF α and IL-6 production developed more slowly. In control lungs after 150 min of perfusion and ventilation, TNF α and IL-6 production was 23 ± 20 pg/min and 330 ± 210 pg/min, respectively. In lungs hyperventilated for 150 min, TNF α and IL-6 production were increased to 287 ± 180 pg/min and more than 1,000 pg/ min, respectively. We conclude that artificial ventilation might cause pulmonary and systemic adverse reactions by inducing the release of mediators into the circulation. von Bethmann AN, Brasch F, Nüsing R, Vogt K, Volk HD, Müller K-M, Wendel A, Uhlig S. Hyperventilation induces release of cytokines from perfused mouse lung.
The World Trade Center disaster: a tragic source of medical advancement
Authors: Vinicius C. Antao
Journal: European Respiratory Journal (2013)

The history of medicine is full of examples of the determination of scientists when faced with public health disasters. As a result of this strength, many tragedies that occurred in the 20th century were followed by important scientific developments. If World War I marked the advent of chemical weapons, it also provided respiratory specialists with knowledge about the effects of poisonous gases on the lungs and led to the development of the first practical gas mask for mass production. The increased use of aircraft in warfare during World War II prompted Forrest M. Bird to develop oxygen masks to enable pilots to fly at higher altitudes than ever before. Further improvements of this technology led to the invention of the first modern ventilators, such as the Bird Universal Medical Respirator. The legacy of the Vietnam War to the medical field was the identification of acute respiratory distress syndrome (called Da Nang Lung at that time), by Colorado researchers in 1967 [1]. Other tragedies, such as the 1986 catastrophic nuclear accident of Chernobyl, led to a better understanding of the physiology of radiation poisoning, which had been evolving since the Hiroshima bombing, and helped improve treatment for victims of other disasters. There were advances in the creation of sterile hospital rooms, infection prevention, intravenous transfusion, life support systems, plasmapheresis, platelet transfusion, and bone marrow transplants.

The dawn of the 21st century saw another tragedy that will remain in the memory of many generations to come: the terrorist attacks on September 11, 2001 in New York City, NY, …
Hereditary disorders of surfactant homeostasis cause acute and chronic lung disease in infancy
Authors: J. A Whitsett
Journal: Thorax (2008)

In this issue of Thorax , Doan et al 1 report the clinical and pathological findings from nine paediatric patients with severe acute and chronic lung disease caused by mutations in the ATP-binding cassette A3 protein (ABCA3), a lamellar body-associated transport protein expressed selectively in type II epithelial cells in the alveoli ( see page 366 ). Previous reports regarding the mutations in ABCA3 were derived primarily from the analysis of term infants presenting with severe respiratory failure in the neonatal period.2 3 In the study by Doan et al , five of nine infants had respiratory symptoms at birth but only one died during the neonatal period. The others presented with chronic respiratory signs and symptoms at 3 months to 4 years of age, indicating the marked variability in age and severity of presentation of this genetic disease. These infants generally fail to thrive. Clinical, radiographic and pulmonary function testing were consistent with diffuse alveolar disease. Hypoxaemia and pulmonary function studies indicated severe restrictive lung …
Laser treatment for tracheobronchial tumours: local or general anaesthesia?
Authors: P J George, C P Garrett, C Nixon, M R Hetzel, E M Nanson, F J Millard
Journal: Thorax (1987)

Ninety seven patients with tracheobronchial tumours have been treated with the neodymium yttrium-aluminium-garnet (Nd YAG) laser over a period of 33 months. Fifty one of these patients were treated under local anaesthesia and 46 under general anaesthesia. The results obtained with the two methods have been compared retrospectively. The numbers of patients responding to treatment, the magnitude of the response, and the duration of palliation were similar in the two groups; significantly more treatment sessions, however, were required during each course of treatment under local anaesthesia. This advantage of general anaesthesia was thought to arise from the ability to continue treatment for longer and with greater efficiency. The use of the rigid bronchoscope with jet ventilation under general anaesthesia was also thought to provide better control of the airway and to allow more efficient clearance of blood and mucus. Two operative deaths occurred under local anaesthesia, when bleeding led to asphyxiation, but none have occurred under general anaesthesia. Treatment under general anaesthesia is not, however, without risk and is potentially hazardous in patients with severe chronic hypoxic lung disease.
Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis
Authors: Djillali Annane, Eric Bellissant, Pierre Edouard Bollaert, Josef Briegel, Didier Keh, Yizhak Kupfer
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To assess the effects of corticosteroids on mortality in patients with severe sepsis and septic shock. <b>Data sources</b> Randomised and quasi-randomised trials of corticosteroids versus placebo (or supportive treatment alone) retrieved from the Cochrane infectious diseases group9s trials register, the Cochrane central register of controlled trials, Medline, Embase, and LILACS. <b>Review method</b> Two pairs of reviewers agreed on eligibility of trials. One reviewer entered data on to the computer and four reviewers checked them. We obtained some missing data from authors of trials and assessed methodological quality of trials. <b>Results</b> 16/23 trials (n = 2063) were selected. Corticosteroids did not change 28 day mortality (15 trials, n = 2022; relative risk 0.92, 95% confidence interval 0.75 to 1.14) or hospital mortality (13 trials, n = 1418; 0.89, 0.71 to 1.11). There was significant heterogeneity. Subgroup analysis on long courses (≥ 5 days) with low dose (≤ 300 mg hydrocortisone or equivalent) corticosteroids showed no more heterogeneity. The relative risk for mortality was 0.80 at 28 days (five trials, n = 465; 0.67 to 0.95) and 0.83 at hospital discharge (five trials, n = 465, 0.71 to 0.97). Use of corticosteroids reduced mortality in intensive care units (four trials, n = 425, 0.83, 0.70 to 0.97), increased shock reversal at 7 days (four trials, n = 425; 1.60, 1.27 to 2.03) and 28 days (four trials, n = 425, 1.26, 1.04 to 1.52) without inducing side effects. <b>Conclusions</b> For all trials, regardless of duration of treatment and dose, use of corticosteroids did not significantly affect mortality. With long courses of low doses of corticosteroids, however, mortality at 28 days and hospital morality was reduced.
Effects of Decision Aids for Menorrhagia on Treatment Choices, Health Outcomes, and Costs
Authors: Andrew D. M. Kennedy, Mark J. Sculpher, Angela Coulter, Nuala Dwyer, Margaret Rees, Keith R. Abrams, Susan Horsley, Deborah Cowley, Christine Kidson, Catherine Kirwin, Caroline Naish, Gordon Stirrat
Journal: JAMA (2002)

ContextDecision aids can increase patient involvement in treatment decision making. However, questions remain regarding their effects and cost implications.ObjectiveTo evaluate the effects of information, with and without a structured preference elicitation interview, on treatment choices, health outcomes, and costs.Design, Setting, and ParticipantsA randomized controlled trial with 2 years of follow-up. Between October 1996 and February 1998, 894 women with uncomplicated menorrhagia were recruited from 6 hospitals in southwest England. Women were randomized to the control group, information alone group (information), or information plus interview group (interview).InterventionsWomen in both intervention groups were sent an information pack (a booklet and complementary videotape) 6 weeks before their specialist consultation. Immediately before their consultation, women in the interview group underwent structured interview, to clarify and elicit their preferences.Main Outcome MeasuresSelf-reported health status was the main outcome; secondary outcomes included treatments received and costs. Cost analyses adopted a UK health service (payer) perspective, and were based on patient-reported resource use data and are reported in 1999-2000 US dollars.ResultsThe interventions had no consistent effect on health status. Hysterectomy rates were lower for women in the interview group (38%) (adjusted odds ratio [OR], 0.60; 95% confidence interval [CI], 0.38-0.96) than in the control group (48%) and women who received the information alone (48%) (adjusted OR, 0.52; 95% CI, 0.33-0.82). The interview group had lower mean costs ($1566) than the control group ($2751) (mean difference, $1184; 95% CI, $684-$2110) and the information group $2026 (mean difference, $461; 95% CI, $236-$696).ConclusionsNeither intervention had an effect on health status. Providing women with information alone did not affect treatment choices; however, the addition of an interview to clarify values and elicit preferences had a significant effect on women's management and resulted in reduced costs.
Chemoprevention of dietary digitoflavone on colitis-associated colon tumorigenesis through inducing Nrf2 signaling pathway and inhibition of inflammation
Authors: Yang Yang, Xueting Cai, Jie Yang, Xiaoyan Sun, Chunping Hu, Zhanpeng Yan, Xiaojun Xu, Wuguang Lu, Xiaoning Wang, Peng Cao
Journal: Molecular Cancer (2014)

Nuclear factor-erythroid 2-related factor 2 (Nrf2) has emerged as a novel target for the prevention of colorectal cancer (CRC). Many chemopreventive compounds associated with Nrf2 activation are effective in preclinical systems and many on-going clinical trials are showing promising findings. In present study we evaluated the cytoprotective effect and chemopreventive properties of dietary digitoflavone.A cell based Antioxidant Response Element (ARE)-driven luciferase reporter system was applied to screen potential Nrf2 activators. Activation of Nrf2 by digitoflavone was confirmed through mRNA, protein and GSH level assay in Caco-2 cell line. The cytoprotective effect of digitoflavone was evaluated in H2O2-induced oxidative stress model and further signaling pathways analysis was used to determine the target of digitoflavone induced Nrf2 activation. An AOM-DSS induced colorectal cancer model was used to assess the chemopreventive effect of digitoflavone.Micromolarity (10 μM) level of digitoflavone increased Nrf2 expressing, nuclear translocation and expression of downstream phase II antioxidant enzymes. Furthermore, digitoflavone decreased H2O2-induced oxidative stress and cell death via p38 MAPK-Nrf2/ARE pathway. In vivo study, 50 mg/kg digitoflavone significantly reduced AOM-DSS induced tumor incidence, number and size.These observations suggest that digitoflavone is a novel Nrf2 pathway activator, and protects against oxidative stress-induced cell injury. The results of the present study add further evidence of the molecular mechanisms that allow digitoflavone to exert protective effects and reaffirm its potential role as a chemopreventive agent in colorectal carcinogenesis.
Nitric oxide inhibits angiotensin II-induced migration of rat aortic smooth muscle cell. Role of cyclic-nucleotides and angiotensin1 receptors.
Authors: R K Dubey, E K Jackson, T F Lüscher
Journal: Journal of Clinical Investigation (1995)

Nitric oxide (NO) and angiotensin II (AII) can effect vascular smooth muscle cell (SMC) proliferation. However, the effects of such agents on SMC migration, an equally important phenomenon with regard to vascular pathophysiology, have received little attention. The objectives of the present study were: (a) to determine whether NO inhibits AII-induced migration of vascular SMCs; (b) to investigate the mechanism of the interaction of NO and AII on SMC migration; and (c) to evaluate the AII receptor subtype that mediates AII-induced SMC migration. Migration of rat SMCs was evaluated using a modified Boydens Chamber (transwell inserts with gelatin-coated polycarbonate membranes, 8 microns pore size). AII stimulated SMC migration in a concentration-dependent manner, and this effect was inhibited by sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP). In the presence of L-arginine, but not D-arginine, IL-1 beta, an inducer of inducible NO synthase, also inhibited AII-induced SMC migration, and this effect was prevented by the NO-synthase inhibitor, N-nitro-L-arginine methyl ester. The effects of NO donors on AII-induced SMC migration were mimicked by 8-bromo-cGMP. Also, the antimigratory effects of SNAP were partially inhibited by LY83583 (an inhibitor of soluble guanylyl cyclase) and by KT5823 (an inhibitor of cGMP-dependent protein kinase). Although 8-bromo-cAMP (cAMP) also mimicked the antimigratory effects of NO donors, the antimigratory effects of SNAP were not altered by 2',5'-dideoxyadenosine (an inhibitor of adenyl cyclase) or by (R)-p-adenosine-3',5'-cyclic phosphorothioate (an inhibitor of the cAMP-dependent protein kinase). Low concentrations of the subtype AT1-receptor antagonist CGP 48933, but not the subtype AT2-receptor antagonist CGP 42112, blocked AII-induced SMC migration. These findings indicate that (a) NO inhibits AII-induced migration of vascular SMCs; (b) the antimigratory effect of NO is mediated in part via a cGMP-dependent mechanism; and (c) AII stimulates SMC migration via an AT1 receptor.
Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma
Authors: Jennifer A. Quinn, David A. Reardon, Allan H. Friedman, Jeremy N. Rich, John H. Sampson, James M. Provenzale, Roger E. McLendon, Sridharan Gururangan, Darell D. Bigner, James E. Herndon, Nicholas Avgeropoulos, Jonathan Finlay, Sandra Tourt-Uhlig, Mary Lou Affronti, Brandon Evans, Valerie Stafford-Fox, Sara Zaknoen, Henry S. Friedman
Journal: Journal of Clinical Oncology (2003)

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m 2 /d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to ∞ months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced ≥ grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.
Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis
Authors: Catherine MacLean, Sydne Newberry, Margaret Maglione, Maureen McMahon, Veena Ranganath, Marika Suttorp, Walter Mojica, Martha Timmer, Alicia Alexander, Melissa McNamara, Sheetal B. Desai, Annie Zhou, Susan Chen, Jason Carter, Carlo Tringale, Di Valentine, Breanne Johnsen, Jennifer Grossman
Journal: Annals of Internal Medicine (2008)

Background: Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well described. Purpose: To compare the benefits in fracture reduction and the harms from adverse events of various therapies for osteoporosis. Data Sources: MEDLINE (1966 to November 2007) and other selected databases were searched for English-language studies. Study Selection: For the efficacy analysis, investigators selected studies that reported the rate of or risk for fractures. For the adverse event analysis, they selected studies that reported the relationship between an agent and cardiovascular, thromboembolic, or upper gastrointestinal events; malignant conditions; and osteonecrosis. Data Extraction: Using a standardized protocol, investigators abstracted data on fractures and adverse events, agents and comparators, study design, and variables of methodological quality. Data Synthesis: Good evidence suggests that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than placebo; the evidence for calcitonin was fair. Good evidence suggests that alendronate, risedronate, and estrogen prevent hip fractures more than placebo; the evidence for zoledronic acid was fair. The effects of vitamin D varied with dose, analogue, and study population for both vertebral and hip fractures. Raloxifene, estrogen, and estrogen–progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding. Limitation: Few studies have directly compared different agents or classes of agents used to treat osteoporosis. Conclusion: Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, the data are insufficient to determine the relative efficacy or safety of these agents.