tbuckley/cabot-search huggingface dataset:
CT screening helps to detect resectable lung cancers and may improve survival
Authors: Helen Liddicoat
Journal: Thorax (2007)

▴ Henschke CI, Yankelevitz DF, Libby DM, et al . Survival of patients with stage I lung cancer detected on ct screening the international early lung cancer action programme investigators. N Engl J Med2006;355:1763–71.

[OpenUrl][1][CrossRef][2][PubMed][3]



This international uncontrolled prospective study screened 31 567 asymptomatic individuals using low dose CT scan between 1993 and 2005. Positive tests were defined on baseline screening as the identification of a least one solid or partly solid non-calcified pulmonary nodule >5 mm in diameter, at least one non-solid non-calcified pulmonary …

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Paclitaxel-Associated Hypersensitivity Reactions: Experience of the Gynecologic Oncology Program of the Cleveland Clinic Cancer Center
Authors: Maurie Markman, Alexander Kennedy, Kenneth Webster, Barbara Kulp, Gertrude Peterson, Jerome Belinson
Journal: Journal of Clinical Oncology (2000)

PURPOSE: : This study expands the existing limited data as to whether patients developing clinically significant paclitaxel-induced hypersensitivity reactions can continue to be treated with this important antineoplastic agent and how such retreatment might be undertaken. PATIENTS AND METHODS: More than 450 patients received paclitaxel, either as a single agent or in a combination regimen, for a female pelvic malignancy in the Gynecologic Oncology Program of the Cleveland Clinic Cancer Center from January 1995 through December 1998. RESULTS: Of the more than 450 patients, 44 (approximately 9%) developed at least one episode of a clinically relevant hypersensitivity reaction to the cytotoxic drug. All 43 individuals (plus an additional four patients referred to our center after having previously experienced a severe paclitaxel-associated hypersensitivity reaction at another institution) who were retreated with paclitaxel were ultimately able to receive the agent. Five patients required treatment with a standardized desensitization regimen, developed by our group, to successfully receive paclitaxel. DISCUSSION: On the basis of this large single-institution study of paclitaxel-associated hypersensitivity reactions, we conclude that with appropriate precautions essentially all individuals experiencing these reactions can be safely treated with this agent.
The effect of intravenous phenylephrine on airway calibre in asthma
Authors: BM Grandordy, J Paiva de Carvalho, J Regnard, D Florentin, D de Lauture, J Marsac, A Lockhart
Journal: European Respiratory Journal (1995)

Tracheobronchial vasoconstriction and subsequent reduction of airway wall thickness due to the alpha 1-agonist methoxamine, might be responsible for prevention of exercise-induced asthma, and reduction of bronchial hyperresponsiveness to methacholine increase in exercise performance in patients with impaired left ventricular function. Since bronchial wall oedema plays an important role in asthma, we have now investigated the bronchial response to the intravenously administered alpha 1-agonist, phenylephrine, in asthma of various severity. Increasing noncumulative intravenous phenylephrine doses (100 to 600 micrograms) were injected in 18 asthmatic subjects (three groups: mild asthma, mild asthma with recent acute attack, severe obstructive asthma) and in 11 control subjects. Changes in specific airways resistance (sRaw) on phenylephrine were linearly related to the dose administered in 16 out of 18 asthmatic subjects, and in only 3 out of 11 control subjects. In the asthmatic subjects, sRaw increased in 10 patients whose asthma was mild, or bronchial obstruction mild to moderate, and decreased in the remaining 8 asthmatic subjects with more severe disease or with a higher degree of bronchial obstruction. Changes in forced expiratory volume in one second (FEV1) were consistent with those of sRaw. In the five asthmatic subjects who underwent the protocol twice, results were reproducible. There was no difference in the responses of heart rate between the three groups of asthmatic subjects. It is likely that phenylephrine acts both via airway smooth muscle contraction, an effect which might predominate in mild asthma, and via mucosal vasoconstriction, which might overcome the effect on smooth muscle in more severe asthma with bronchial wall oedema.(ABSTRACT TRUNCATED AT 250 WORDS)
Circulating collagen indices indicative of disease severity in pulmonary arterial hypertension
Authors: Zeenat Safdar
Journal: European Respiratory Journal (2012)

Procollagen deposition occurs in explanted pulmonary arterial hypertension (PAH) lungs. Biochemical monitoring of collagen synthesis may provide a non-invasive method of determining vascular remodeling. However, there is lack of data regarding circulating procollagen indices in PAH. We obtained circulating levels of carboxyl-terminal of procollagen type III (PIIINP), carboxy-terminal telopeptide of collagen type I (CITP), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) from 87 PAH subjects and 37 age- and gender-matched controls (Baylor PH Center). Serum was separated and stored at -80 oC. CITP, MMP-1 and TIMP-1 levels were measured by ELISAs. PIIINP was measured by antibody radioimmunoassay. PAH patients had elevated PIIINP, CITP, MMP-9 and TIMP-1 levels suggesting active collagen metabolism (Table 1). PIIINP levels were higher in WHO FC III-IV as compared to WHO FC I-II PAH patients (p=0.011). PIIINP levels negatively correlated with six-minute walk distance (R=-0.3, P=0.008), and positively correlated with right atrial pressure (R=0.35, P=0.002) and BNP levels (R=0.25, P=0.02). Circulating procollagen markers may provide a novel non-invasive method of documenting active collagen synthesis reflective of severe disease in PAH.
Abstract 16452: Safety and Diagnostic Yield of Cardiac MRI in Patients with ICD
Authors: Timm Dickfeld, Jing Tian, Ghada Ahmad, Alejandro Jimenez, Richard Kuk, Martha McClane, Robert Peters, Magdi Saba, Anastasios Saliaris, Stephen Shorofsky, Jean Jeudy
Journal: Circulation (2010)

Background: An increasing number of patients with ICD would benefit from cardiac MRI. However, MRI in general, and especially cardiac MRI is still considered contra-indicated and the artifacts can ...
A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis
Authors: Joel M. Dulhunty, Jason A. Roberts, Joshua S. Davis, Steven A. R. Webb, Rinaldo Bellomo, Charles Gomersall, Charudatt Shirwadkar, Glenn M. Eastwood, John Myburgh, David L. Paterson, Therese Starr, Sanjoy K. Paul, Jeffrey Lipman
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing.To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis.We conducted a randomized controlled trial in 25 intensive care units (ICUs). Participants commenced on piperacillin-tazobactam, ticarcillin-clavulanate, or meropenem were randomized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge. The primary outcome was the number of alive ICU-free days at Day 28. Secondary outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation, alive organ failure-free days at Day 14, and duration of bacteremia.We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20. There was no difference in ICU-free days: 18 days (interquartile range, 2-24) and 20 days (interquartile range, 3-24) in the continuous and intermittent groups (P = 0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63-1.31; P = 0.61). Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12 (95% confidence interval, 0.77-1.63; P = 0.56). There was no difference in organ failure-free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24).In critically ill patients with severe sepsis, there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion. Australian New Zealand Clinical Trials Registry number (ACT RN12612000138886).
Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients
Authors: Marta Milano, Alessio Aghemo, Rosellina Margherita Mancina, Janett Fischer, Paola Dongiovanni, Stella De Nicola, Anna Ludovica Fracanzani, Roberta D'Ambrosio, Marco Maggioni, Raffaele De Francesco, Silvia Fargion, Thomas Berg, Felix Stickel, Jochen Hampe, Stefano Romeo, Massimo Colombo, Luca Valenti
Journal: Hepatology (2015)

Steatosis and inherited host factors influence liver damage progression in chronic hepatitis C (CHC). The transmembrane 6 superfamily member 2 (TM6SF2) gene E167K variant increases liver fat and risk of progressive steatohepatitis by interfering with lipoprotein secretion. Our aim was to determine whether the E167K variant affects histological severity of steatosis, necroinflammation, and fibrosis in a cross-sectional cohort of 815 Italian therapy-naïve CHC patients. The association with clinically significant fibrosis was replicated in 645 Swiss/German patients. The TM6SF2 E167K variant was genotyped by TaqMan assays, steatosis graded according to the nonalcoholic fatty liver disease activity score, and necroinflammation and fibrosis graded and staged according to Ishak in Italian, and to Metavir in Swiss/German patients. The E167K variant was detected in 69 (9%) Italian patients and was associated with more severe steatosis, independently of confounders (P = 0.038). The association between E167K and steatosis severity was present in patients not infected by genotype 3 (G3) HCV (P = 0.031), but not in those infected by G3 HCV (P = 0.58). Furthermore, the E167K variant was associated with more severe necroinflammation (Ishak grade; adjusted P = 0.037) and nearly associated with more severe fibrosis (Ishak stage; adjusted P = 0.058). At multivariate logistic regression analysis, the E167K variant was independently associated with histologically probable or definite cirrhosis (Ishak stage S6; odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.18-3.93; P = 0.010). After further conditioning for steatosis and necroinflammation, the E167K variant remained associated with cirrhosis (OR, 3.15; 95% CI: 1.60-5.99; P < 0.001). In Swiss/German patients, the E167K variant was independently associated with clinically significant fibrosis Metavir stage F2-F4 (OR, 1.81; 95% CI: 1.12-3.02; P = 0.016).TM6SF2 E167K variant impacts on steatosis severity and is associated with liver damage and fibrosis in patients with CHC.
Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity.
Authors: D B Corry, H G Folkesson, M L Warnock, D J Erle, M A Matthay, J P Wiener-Kronish, R M Locksley
Journal: The Journal of Experimental Medicine (1996)

Reversible airway hyperreactivity underlies the pathophysiology of asthma, yet the precise mediators of the response remain unclear. Human studies have correlated aberrant activation of T helper (Th) 2-like effector systems in the airways with disease. A murine model of airway hyperreactivity in response to acetylcholine was established using mice immunized with ovalbumin and challenged with aerosolized antigen. No airway hyperractivity occurred in severe combined immunodeficient mice. Identically immunized BALB/c mice developed an influx of cells, with a predominance of eosinophils and CD4+ T cells, into the lungs and bronchoalveolar lavage fluid at the time that substantial changes in airway pressure and resistance were quantitated. Challenged animals developed marked increases in Th2 cytokine production, eosinophil influx, and serum immunoglobulin E levels. Neutralization of interleukin (IL) 4 using monoclonal antibodies administered during the period of systemic immunization abrogated airway hyperractivity but had little effect on the influx of eosinophils. Administration of anti-IL-4 only during the period of the aerosol challenge did not affect the subsequent response to acetylcholine. Finally, administration of anti-IL-5 antibodies at levels that suppressed eosinophils to &amp;lt; 1% of recruited cells had no effect on the subsequent airway responses. BALB/c mice had significantly greater airway responses than C57BL/6 mice, consistent with enhanced IL-4 responses to antigen in BALB/c mice. Taken together, these data implicate IL-4 generated during the period of lymphocyte priming with antigen in establishing the cascade of responses required to generate airway hyperractivity to inhaled antigen. No role for IL-5 or eosinophils could be demonstrated.
RETRACTED ARTICLE: HGF and TGFβ1 differently influenced Wwox regulatory function on Twist program for mesenchymal-epithelial transition in bone metastatic versus parental breast carcinoma cells
Authors: Paola Bendinelli, Paola Maroni, Emanuela Matteucci, Maria Alfonsina Desiderio
Journal: Molecular Cancer (2015)

Much effort has been devoted to determining how metastatic cells and microenvironment reciprocally interact. However, the role of biological stimuli of microenvironment in controlling molecular events in bone metastasis from breast carcinoma for mesenchymal-epithelial transition (MET) is largely unknown. The purpose of the present paper was to clarify (1) the influence of hepatocyte-growth factor (HGF) and transforming growth factorβ1 (TGFβ1) on the phenotype of bone-metastatic 1833 and parental MDA-MB231 cells; (2) the hierarchic response of Twist and Snail controlled by Wwox co-factor, that might be critical for the control of 1833-adhesive properties via E-cadherin. We studied under HGF and TGFβ1 the gene profiles—responsible for epithelial-mesenchymal transition (EMT), versus the revertant MET phenotype—making the correspondence with 1833 morphology and the relation to HGF-dependent control of TGFβ1 signalling. In particular, the activation of Twist program and the underlying molecular mechanisms were investigated, considering the role of endogenous and exogenous Wwox with siRNAWWOX and the expression vector transfection, to clarify whether Twist affected E-cadherin transactivation through a network of transcription factors and regulators. HGF and TGFβ1 oppositely affected the expression of Wwox in 1833 cells. Under HGF, endogenous Wwox decreased concomitant with Twist access to nuclei and its phosphorylation via PI3K/Akt pathway. Twist activated by HGF did not influence the gene profile through an E-box mechanism, but participated in the interplay of PPARγ/Ets1/NF-kB-transcription factors, triggering E-cadherin transactivation. Altogether, HGF conferred MET phenotype to 1833 cells, even if this was transient since followed by TGFβ1-signalling activation. TGFβ1 induced Snail in both the cell lines, with E-cadherin down-regulation only in 1833 cells because in MDA-MB231 cells E-cadherin was practically absent. Exogenous Wwox activated metastatic HIF-1, with Twist as co-factor. HGF and TGFβ1 of bone-metastasis microenvironment acted co-ordinately, influencing non redundant pathways regulated by Twist program or Snail-transcription factor, with reversible MET switch. This process implicated different roles for Wwox in the various steps of the metastatic process including colonization, with microenvironmental/exogenous Wwox that activated HIF-1, important for E-cadherin expression. Interfering with the Twist program by targeting the pre-metastatic niche stimuli could be an effective anti-bone metastasis therapy.
Book: Plague Wars
Authors: F. B Charatan
Journal: BMJ (2001)

Tom Mangold, Jeff Goldberg Pan, £7.99, pp 416 ISBN 0 330 36753 6 Rating ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> P lague Wars begins with an imaginary attack on the airport in Houston, Texas, by terrorists, who spray the area with anthrax and botulinum toxin. It goes on to describe the history of biological warfare, with the main focus on the former Soviet Union. The authors' credentials are impressive: Tom Mangold is the senior correspondent in London for the BBC documentary series Panorama, and Jeff Goldberg is an award winning independent television producer and investigative journalist based … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Effect of Phosphonoacetate on Marek's Disease Virus Replication
Authors: Lucy F. Lee, K. Nazerian, Susan S. Leinbach, J. M. Reno, J. A. Boezi
Journal: JNCI Journal of the National Cancer Institute (1976)

Phosphonoacetate (PA), but not any of its analogues tested, effectively inhibited avian herpesvirus replication and viral DNA synthesis in cell cultures. At 100 mug/ml culture medium, PA completely inhibited the replication of Marek's disease virus (MDV), herpesvirus of turkeys, and owl herpesvirus, but had no measurable effect on normal cell growth. PA also inhibited DNA polymerases induced by these avian viruses. Enzyme inhibition was 50% at a PA concentration of 0.2 mug/ml. At a concentration of 3-6 mug/ml, the compound also effected a 50% inhibition of alpha (maxi) enzyme of the host DNA polymerase. It had no effect on the host beta (mini) enzyme. When administered to chickens, PA did not inhibit the replication of MDV, nor did it prevent the development of lymphoma.
Abstract 64: Establishing Microdialysis for Combined Cerebral and Peripheral Monitoring of Cell Metabolism in a Cardiac Arrest Setting in Rats
Authors: Arthur Hosmann, Andreas Schober, Andreas Gruber, Fritz Sterz, Christoph Testori, Alexandra-Maria Warenits, Wolfgang Weihs, Sandra Högler, Thomas Scherer, Andreas Janata, Anton Laggner, Markus Zeitlinger
Journal: Circulation (2014)

Introduction:  Commonly effects of resuscitative measures are monitored by peripheral functions like ECG or blood pressure (BP). However, it is unknown if these effects will transfer to the brain, the ultimate target of resuscitation. Therefore we set out to establish a model allowing for concomitant determination of cerebral and peripheral metabolism in a complex cardiac arrest setting in rodents.   Methods:  In vitro experiments were performed to determine the most reliable flow rate of microdialysis in order to balance temporal resolution and recovery of measures of ischemia, and to specify the inter-assay variability and concentration linearity of our analytic System (CMA600, Sweden).  For in vivo testing male Sprague-Dawley rats underwent multimodality monitoring, including ECG, arterial BP, CVP, EtCO2, SpO2 and core temperature. A microdialysis probe (CMA11; 2mm) was introduced into a guide cannula, which was stereotactically implanted 3 days before the experiment into the right hippocampus (histologically verified after necropsy). As reference for peripheral metabolism a second probe was inserted into the right femoral vein.   Results:  In vitro testing indicated that a flow rate of 1μl/min is sufficient to achieve acceptable recovery values (10-20%) and a temporal resolution of 8 minutes for the most reliable metabolic parameters, i.e. lactate, pyruvate, glutamate and glucose. By introducing this flow rate in our cardiac arrest model we were able to identify 3 main phases: initial surgical trauma, baseline conditions (after preparation and at least 1 hour after probe insertion) and ischemia during cardiac arrest. Compared to peripheral metabolism, cerebrally major deviations were observed during ischemia.   Conclusion:  Based on this optimized setting we established a reliable and solid model to investigate the impact of resuscitation methods on cerebral metabolism, highlighting the importance of concomitant peripheral and cerebral monitoring.
Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study.
Authors: E A Perez, P Hesketh, J Sandbach, J Reeves, S Chawla, M Markman, J Hainsworth, W Bushnell, C Friedman
Journal: Journal of Clinical Oncology (1998)

PURPOSE The antiemetic effectiveness and safety of single-dose oral granisetron were compared with intravenous (I.V.) ondansetron in chemotherapy-naive patients who received moderately emetogenic chemotherapy. PATIENTS AND METHODS In this double-blind, parallel-group study, patients naive to emetogenic chemotherapy (N = 1,085) who were scheduled to receive cyclophosphamide- (500 to 1,200 mg/m2) or carboplatin (&gt; or = 300 mg/m2) based chemotherapy, were randomized to receive either oral granisetron (n = 542) or I.V. ondansetron (n = 543). Efficacy assessments included the proportion of patients in each treatment group with total control over the 24 and 48 hours following chemotherapy initiation, as well as incidence and severity of nausea and emesis and use of antiemetic rescue medication. Prophylactic corticosteroids were allowed. Safety assessment was based on patients' reports of adverse experiences. RESULTS Approximately 80% of patients received prophylactic corticosteroids. Single-dose oral granisetron (2 mg) and I.V. ondansetron (32 mg) resulted in equivalent levels of total emetic control during the first 48 hours after chemotherapy. The proportion of nausea- and emesis-free patients at 24 and 48 hours were also approximately equivalent. The most commonly reported adverse experiences were headache, asthenia, and constipation. More patients who received ondonsetron than granisetron reported dizziness (9.6% v 5.4%, respectively; P = .011) and abnormal vision (4.2% v 0.6%, respectively; P &lt; .001). CONCLUSION A single oral dose of granisetron (2 mg) resulted in equivalent levels of antiemetic protection as I.V. ondansetron (32 mg). Both agents were well tolerated, although more dizziness and abnormal vision were reported with ondansetron. Because the two antiemetic regimens exhibited equivalent efficacies, additional factors such as convenience and cost of therapy should be considered.