tbuckley/cabot-search huggingface dataset:
Safe per-operative anticoagulation
Authors: J. Wieberdink
Journal: Thorax (1967)

Pre-, per-, and post-operative anticoagulation at the therapeutic level is nowadays the most, if not the only, available effective method to prevent post-operative thrombo-embolism. There is no increased tendency to bleeding to be feared during the operation. The real danger of this prophylaxis consists of a treacherous tendency to acute relative overdosage after the operation. This is explained by the combined indirect action of anticoagulants and influences related to the operation. As its development can accurately be followed by laboratory tests, dangerous levels of anticoagulation can be prevented. Experiences in 242 surgical patients are presented to demonstrate the efficacy of the following post-operative routine: Coagulation studies (prothrombin time or thrombotest) at least twice daily during one week; fractionated administration of anticoagulants and, if necessary, small amounts (0·25-1 mg.) of vitamin K<sub>1</sub>. The results suggest that with this policy the risk of thrombo-embolism in surgery can be considerably reduced, if not abolished.
Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score
Authors: Philip L De Jager, Lori B Chibnik, Jing Cui, Joachim Reischl, Stephan Lehr, K Claire Simon, Cristin Aubin, David Bauer, Jürgen F Heubach, Rupert Sandbrink, Michaela Tyblova, Petra Lelkova, Eva Havrdova, Christoph Pohl, Dana Horakova, Alberto Ascherio, David A Hafler, Elizabeth W Karlson
Journal: The Lancet Neurology (2009)
Screening and monitoring of tuberculosis in patients on biologics treatment
Authors: Sergey Borisov, Galina Lukina, Lydia Guntupova, Kochetkov Yakov, Natalia Makarova
Journal: European Respiratory Journal (2012)

Background. The new class of drugs - biologics (B) - is high effective, but its essential effect is to increase (in different degree) the risk of tuberculosis (TB).  Methods. 600 pts (rheumatoid arthritis - 264, ankylosing spondylitis - 257, psoriasis - 50, other - 29), 303 male and 297 female, 15-80 y.o. (95%CI 42,2, 43,3) were examined before (377 pts) and during (286 pts: infliximab - 159, adalimumab - 58, etanercept - 17, certolizumab - 12, rituximab - 28, abatacept - 11, tocilizumab - 21; 20 pts receive more then one B consecutively) B treatment. Clinical examination, X-ray (CT in any abnormalities), tuberculin skin test (TST), interferon-gamma release assays (IGRA), skin test with recombinant protein ESAT-6/CFP-10 (developed in Russia as DIASKINTEST - DST) were performed.  Results. In all cases by primary screening active TB was rejected, but positive TST was obtained in 82,6%, IGRA - in 34,4% and DST - in 25,8%. Preventive TB treatment (PT) was administrated in patients with residual TB changes (49) or defined latent TB infection (LTB) (positive both NST and IGRA/DST). During the B treatment active pulmonary TB was detected in 8 pts (all - on TNF-alpha inhibitors): in 2 active or LTB was rejected after screening, in 6 - the TB-screening was insufficient. Especially problem was to consider the LTB in patients with TST conversion from negative to positive (63 pts), but new tests were positive only in the one third of such cases (IGRA - 35%, DST - 33,3%).  Conclusion. The procedure of TB screening and monitoring is the essential part of the B treatment program. The tests based on specific M.tuberculosis antigens are very useful as the tools for LTB monitoring and enable to reduce PT at least three times.
Characterizing Vascular Parameters in Hypoxic Regions: A Combined Magnetic Resonance and Optical Imaging Study of a Human Prostate Cancer Model
Authors: Venu Raman, Dmitri Artemov, Arvind P. Pathak, Paul T. Winnard, Stephen McNutt, Anna Yudina, Alexei Bogdanov, Zaver M. Bhujwalla
Journal: Cancer Research (2006)

Abstract The integration of imaging technologies with the capabilities of genetic engineering has created novel opportunities for understanding and imaging cancer. Here, we have combined vascular magnetic resonance imaging (MRI) and optical imaging to understand the relationship between hypoxia and vascularization in a human prostate cancer model engineered to express enhanced green fluorescent protein (EGFP) under hypoxia. Characterization and validation of EGFP expression under hypoxic conditions was done in culture and in solid tumors in vivo. MRI measurements showed that vascular volume was significantly lower in fluorescing regions. These regions also frequently exhibited high permeability. These data were further supported by the detection of low vessel density in EGFP-positive regions, as determined by the distribution of intravascularly administered, fluorescence-labeled Lycopersicon esculentum lectin in frozen tumor sections. These observations are consistent with the possibility that regions of low vascular volumes are hypoxic, which induces increased expression of functionally active vascular endothelial growth factor, a potent vascular permeability factor. (Cancer Res 2006; 12(20): 9929-36)
A Multidisciplinary Approach to Therapy for Unresectable Malignant Thymoma
Authors: Dong M. Shin, Garrett L. Walsh, Ritsuko Komaki, Joe B. Putnam, Jonathan Nesbitt, Jae Y. Ro, Hyung Ju C. Shin, Keun H. Ki, Amanda Wimberly, Katherine M.W. Pisters, David Schrump, Mary Ann Gregurich, James D. Cox, Jack A. Roth, Waun Ki Hong
Journal: Annals of Internal Medicine (1998)

Background: The therapeutic outcome for unresectable, locally advanced, malignant thymoma has been poor. Objective: To improve tumor resectability and patient survival rates by studying a multimodal approach to therapy for unresectable malignant thymoma. Design: Prospective cohort study. Setting: Tertiary care cancer center. Participants: All eligible patients had newly diagnosed, histologically proven, unresectable malignant thymoma. Intervention: The treatment regimen consisted of induction chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone). Tissue samples were taken at the time of surgical resection for assessment of tumor necrosis and Ki-67 expression. Measurements: Tumor response and resectability (both overall and after induction chemotherapy) and disease-free survival rate in patients who received multimodal therapy. Results: 13 patients were consecutively enrolled from February 1990 to December 1996, and 12 evaluable patients were assessed for response. Disease responded to induction chemotherapy completely in 3 patients (25%) and partially in 8 patients (67%); 1 patient had a minor response (8%). Eleven patients had surgical resection; 1 refused surgery. Tumors were removed completely in 9 (82%) and incompletely in 2 (18%) of 11 patients who had been receiving radiation therapy and consolidation chemotherapy. All 12 patients are alive (100% at 7 years), with a median follow-up of 43 months, and 10 patients are disease free (73% disease-free survival at 7 years). A high correlation was seen between tumor necrosis after induction chemotherapy and Ki-67 expression (r = −0.88). Conclusions: Aggressive multimodal treatment is highly effective and may cure locally advanced, unresectable malignant thymoma.
Autologous fascia lata cardiac valve replacement
Authors: W. Welch, P. Potvliege, G. Primo
Journal: Thorax (1971)

During a three-month period, 20 patients had one or more cardiac valves replaced with mounted autologous fascia lata valves. Only six remain alive. Insufficiency of the implanted valve and thromboembolic complications were frequent. Histological examination demonstrates degenerative changes in the fascia lata and explains the thromboembolic phenomena.
Phase II Trial of Alfimeprase, a Novel-Acting Fibrin Degradation Agent, for Occluded Central Venous Access Devices
Authors: Stephan Moll, Peter Kenyon, Luigi Bertoli, James De Maio, Howard Homesley, Steven R. Deitcher
Journal: Journal of Clinical Oncology (2006)

Purpose Alfimeprase is a recombinantly produced, genetically modified variant of the metalloproteinase, fibrolase. Alfimeprase proteolytically cleaves fibrin, independent of plasminogen activation to plasmin, and directly dissolves thrombi. Based on the direct fibrin degradation effect of alfimeprase, rapid activity in patients with occluded central venous access devices (CVADs) was hypothesized. Patients and Methods We performed a phase II, randomized, double-blind, active-control, multicenter, dose-ranging study to compare the safety and efficacy of one or two instillations of three intraluminal doses of alfimeprase (0.3, 1.0, and 3.0 mg) and alteplase 2.0 mg in re-establishing patency to occluded CVADs in 55 adult patients. Results All three alfimeprase doses were more successful than alteplase during the first 15 and 30 minutes of treatment. The alfimeprase 3.0-mg dose resulted in 40%, 50%, and 60% patency restoration rates at 5, 15, and 30 minutes, respectively, compared with 0%, 0%, and 23% for alteplase. The difference at 15 minutes was highly significant (P = .0075). Alfimeprase 3.0 mg produced the highest patency rate at 120 minutes after the first (60%) and second (80%) doses. No major hemorrhagic or embolic events were reported. Conclusion A single 1- or 3-mg dose of alfimeprase has the potential to restore function to occluded CVADs rapidly and safely, and to facilitate on-time infusion of vital therapies.
Genetic Evidence for the Coexistence of Pheromone Perception and Full Trichromatic Vision in Howler Monkeys
Authors: D. M. Webb
Journal: Molecular Biology and Evolution (2004)

Vertebrate pheromones are water-soluble chemicals perceived mainly by the vomeronasal organ (VNO) for intraspecific communications. Humans, apes, and Old World (OW) monkeys lack functional genes responsible for the pheromone signal transduction and are generally insensitive to vomeronasal pheromones. It has been hypothesized that the evolutionary deterioration of pheromone sensitivity occurred because pheromone communication became redundant after the emergence of full trichromatic color vision via the duplication of the X-chromosome–linked red/green opsin gene in the common ancestor of hominoids and OW monkeys. Interestingly, full trichromacy also evolved in the New World (NW) howler monkeys via an independent duplication of the same gene. Here we sequenced from three species of howler monkeys an essential component of the VNO pheromone transduction pathway, the gene encoding the ion channel TRP2. In contrast to those of hominoids and OW monkeys, the howler TRP2 sequences have none of the characteristics of pseudogenes. This and other observations indicate that howler monkeys have maintained both their systems of pheromone communication and full trichromatic vision, suggesting that the presence of full trichromacy alone does not lead to the loss of pheromone communication. We suggest that the ecological differences between OW and NW primates, particularly in habitat selection, may have also affected the evolution of pheromone perception.
Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance
Authors: D. Elias, T. Matsuhisa, L. Sideris, G. Liberale, L. Drouard-Troalen, B. Raynard, M. Pocard, J.M. Puizillou, V. Billard, P. Bourget, M. Ducreux
Journal: Annals of Oncology (2004)
Safety of modern treatment for cervical pre-cancer
Authors: B. Strander, J. Adolfsson
Journal: BMJ (2014)

Most women can be reassured about future pregnancies

“Will this affect my ability to become pregnant?” might be the most common question asked by women recommended treatment for cervical intraepithelial neoplasia (CIN). Attempting to answer this question, among others, two linked papers (doi:10.1136/bmj.g6192, doi:10.1136/bmj.g6223) cover a range of potential harms to human reproduction associated with treatments for CIN, including fertility.1 2

Kyrgiou and colleagues’ meta-analysis of 15 cohort studies found no evidence that large loop excision of the transformational zone or any other procedure impairs fertility or increases the risk of early spontaneous pregnancy loss.1 Treated women did have a higher risk of second trimester miscarriage than controls. They also had more pregnancies, ectopic pregnancies, and terminations than controls, suggesting unadjusted differences between groups in sexual behaviour or other lifestyle confounders.

Finding an appropriate control group is a recurring problem for researchers trying to evaluate the possible reproductive harms of treatments for CIN. Castanon and colleagues report an association between risk of preterm birth and large, but not small, excisions of the cervical transformation zone.2 They attempted to overcome the problem of control groups by …
Genomic Complexity and AKT Dependence in Serous Ovarian Cancer
Authors: Aphrothiti J. Hanrahan, Nikolaus Schultz, Maggie L. Westfal, Rita A. Sakr, Dilip D. Giri, Stefano Scarperi, Manickam Janikariman, Narciso Olvera, Ellen V. Stevens, Qing-Bai She, Carol Aghajanian, Tari A. King, Elisa de Stanchina, David R. Spriggs, Adriana Heguy, Barry S. Taylor, Chris Sander, Neal Rosen, Douglas A. Levine, David B. Solit
Journal: Cancer Discovery (2011)

Abstract Effective oncoprotein-targeted therapies have not yet been developed for ovarian cancer. To explore the role of phosphatidylinositol 3-kinase (PI3K)/AKT signaling in this disease, we performed a genetic and functional analysis of ovarian cancer cell lines and tumors. PI3K pathway alterations were common in both, but the spectrum of mutational changes differed. Genetic activation of the pathway was necessary, but not sufficient, to confer sensitivity to selective inhibition of AKT and cells with RAS pathway alterations or RB1 loss were resistant to AKT inhibition, whether or not they had coexistent PI3K/AKT pathway activation. Inhibition of AKT1 caused growth arrest in a subset of ovarian cell lines, but not in those with AKT3 expression, which required pan-AKT inhibition. Thus, a subset of ovarian tumors is sensitive to AKT inhibition, but the genetic heterogeneity of the disease suggests that effective treatment with AKT pathway inhibitors will require a detailed molecular analysis of each patient's tumor. Significance: A subset of ovarian cancers exhibits AKT pathway activation and is sensitive to selective AKT inhibition. Ovarian tumors exhibit significant genetic heterogeneity and thus an individualized approach based on real-time, detailed genomic and proteomic characterization of individual tumors will be required for the successful application of PI3K/AKT pathway inhibitors in this disease. Cancer Discovery; 2(1); 56–67. ©2011 AACR. Read the Commentary on this article by Bast and Mills, p. 16 This article is highlighted in the In This Issue feature, p. 1
Assessing the reliability of four severity scales depicting skin ageing features
Authors: F. Valet, K. Ezzedine, D. Malvy, J.-Y. Mary, C. Guinot
Journal: British Journal of Dermatology (2009)

Photographic severity scales depicting facial wrinkling are used extensively to assess the severity of skin ageing features, but they have been poorly investigated for their reproducibility.To investigate the reproducibility of ordinal scales depicting four skin ageing features illustrated by reference photographs.A set of 253 images of caucasian women's faces was evaluated independently by four dermatologists using four different skin ageing severity scales: Larnier's overall photodamage, expression lines, glabellar frown lines, and wrinkles under the eyes. For each pair of dermatologists, degree of agreement was estimated using the weighted kappa statistic and degrees of distinguishability between adjacent categories along these scales were estimated using a recently developed log-linear method.The kappa statistic highlighted substantial degrees of agreement between dermatologists for the glabellar frown lines scale, and the log-linear method did not evidence any scale defect. For the three other scales, only fair to moderate degrees of agreement were observed between dermatologists. In addition, difficulties in distinguishing between some adjacent categories were evidenced.The glabellar frown lines scale is a reproducible tool for assessment of the severity of facial wrinkling. The other scales should be redefined to improve their reproducibility, and therefore their quality, in future studies.
Persistent Airway Inflammation but Accommodated Antioxidant and Lung Function Responses after Repeated Daily Exposure to Nitrogen Dioxide
Authors: ANDERS BLOMBERG, MAMIDIPUDI T. KRISHNA, RAGNBERTH HELLEDAY, MARGARETA SÖDERBERG, MAJ-CARI LEDIN, FRANK J. KELLY, ANTHONY J. FREW, STEPHEN T. HOLGATE, THOMAS SANDSTRÖM
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Nitrogen dioxide (NO2) is a common indoor and outdoor air pollutant that may induce deterioration of respiratory health. In this study the effects of repeated daily exposure to NO2 on airway antioxidant status, inflammatory cell and mediator responses, and lung function were examined. Healthy nonsmoking subjects were exposed under controlled conditions to air (once) and to 2 ppm of NO2 for 4 h on four consecutive days. Lung function measurements were made before and immediately after the end of each exposure. Bronchoscopy with endobronchial biopsies, bronchial wash (BW), and bronchoalveolar lavage (BAL) was carried out 1.5 h after the air exposure and after the last exposure to NO2. Repeated NO2 exposure resulted in a decrease in neutrophil numbers in the bronchial epithelium. The BW revealed a twofold increase in content of neutrophils (p < 0.05) and a 1.5-fold increase in myeloperoxidase (MPO) (p < 0.01) indicative of both migration and activation of neutrophils in the airways. After the fourth NO2 exposure, antioxidant status of the airway fluid was unchanged. Significant decrements in FEV1 and FVC were found after the first exposure to NO2, but these attenuated with repeated exposures. Together, these data indicate that four sequential exposures to NO2 result in a persistent neutrophilic inflammation in the airways, whereas changes in pulmonary function and airway antioxidants are resolved. We conclude that NO2 is a proinflammatory air pollutant under conditions of repeated exposure.
Enhanced Monocyte Chemoattractant Protein-3/CC Chemokine Ligand-7 in Usual Interstitial Pneumonia
Authors: Esther S. Choi, Claudia Jakubzick, Kristin J. Carpenter, Steven L. Kunkel, Holly Evanoff, Fernando J. Martinez, Kevin R. Flaherty, Galen B. Toews, Thomas V. Colby, Ella A. Kazerooni, Barry H. Gross, William D. Travis, Cory M. Hogaboam
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Chemokines are increased and may exert effects on both inflammatory and remodeling events in idiopathic pulmonary pneumonia (IIP). Accordingly, we examined the concomitant expression of inflammatory CC chemotactic cytokines or chemokines and their corresponding receptors in surgical lung biopsies obtained at the time of disease diagnosis and pulmonary fibroblasts grown from these biopsies. By gene array analysis, upper and lower lobe biopsies and primary fibroblast lines from patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia, and respiratory bronchiolitis-interstitial lung disease, but not patients without IIP, exhibited CCL7 gene expression. TAQMAN, immunohistochemical, and ELISA analyses confirmed that CCL7 was expressed at significantly higher levels in UIP lung biopsies compared with biopsies from patients with nonspecific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, and from patients without IIP. Higher levels of CCL7 were present in cultures of IIP fibroblasts compared with non-IIP fibroblasts, and CCL5, a CCR5 agonist, significantly increased the synthesis of CCL7 by UIP fibroblasts. Together, these data suggest that CCL7 is highly expressed in biopsies and pulmonary fibroblast lines obtained from patients with UIP relative to patients with other IIP and patients without IIP, and that this CC chemokine may have a major role in the progression of fibrosis in this IIP patient group.
The effect of purity upon the triple-helical stability of collagenous peptides
Authors: David A. Slatter, Dominique G. Bihan, Richard W. Farndale
Journal: Biomaterials (2011)

Collagen is the fundamental structural protein, comprising 25–35% of the total body protein, its rod-like triple helix providing support in many tissues. Our laboratory has synthesised 113 Toolkit peptides, each 63 residues long, covering the entirety of the homotrimeric helix sequence of collagen II and collagen III. These are used primarily to investigate protein–collagen interactions, from which biomedical applications are under development. Upon increasing the temperature of a Toolkit peptide solution, a novel low temperature transition (LTT) as well as a broadening of the helix unfolding higher temperature transition (HTT) was observed. Here, we hypothesized that unfolding of imperfect helices can account for the LTT. Peptides of various purities were isolated by HPLC or gel filtration, and their unfolding measured by polarimetry, CD, and DSC. The resulting temperature transitions were fitted to a kinetic unfolding equation, allowing comparison of the data, and explanation of the observed melting curve complexity as due to peptide imperfections. Finally, using a mathematical model, this data can be replicated by setting a parameter that quantifies the mutual stabilization conferred by helices on each side of a peptide defect within a triple helix.
Influence of Previous Use of Inhaled Corticoids on the Development of Pleural Effusion in Community-acquired Pneumonia
Authors: Jacobo Sellares, Alejandra López-Giraldo, Carmen Lucena, Catia Cilloniz, Rosanel Amaro, Eva Polverino, Miquel Ferrer, Rosario Menéndez, Josep Mensa, Antoni Torres
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Previous use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease has been associated with increased risk of community-acquired pneumonia. However, ICS have been associated with fewer pneumonia complications and decreased risk of pneumonia-related mortality.The objective of the study was to assess the influence of previous use of ICS on the incidence of parapneumonic effusion in patients with different baseline respiratory disorders.We conducted a single-center cohort study of 3,612 consecutively collected patients diagnosed with community-acquired pneumonia. We assessed clinical, radiographic, and pleural-fluid chemistry and microbiologic variables. Patients were classified according to whether or not they received prior ICS treatment.A total of 633 patients (17%) were treated with corticosteroids before the diagnosis of pneumonia (chronic obstructive pulmonary disease, 54%; asthma, 13%). Incidence of parapneumonic effusion was lower in patients with ICS use compared with non-ICS patients (5% vs. 12%; P < 0.001). After matching according to propensity scores (n = 640), prior treatment with corticosteroids was still significantly associated with a lower incidence of parapneumonic effusion (odds ratio, 0.40; 95% confidence interval, 0.23-0.69; P = 0.001) compared with patients without ICS treatment. Prior ICS treatment was associated with higher levels of glucose (P = 0.003) and pH (P = 0.02), and lower levels of protein (P = 0.01) and lactic acid dehydrogenase (P = 0.007) in the pleural fluid.Prior treatment with ICS in a population of patients with different respiratory chronic disorders who develop pneumonia is associated with lower incidence of parapneumonic effusion.
1153 A NOVEL METHOD TO IDENTIFY ROUTES OF HEPATITIS C VIRUS TRANSMISSION IN RURAL EGYPT
Authors: C. Feray, B. Falissard, M. Mohamed, N. Arafa, I. Bakr, E.-H. Mostafa, M. El Daly, S. Plancoulaine, V. Thiers, A. Fontanet
Journal: Journal of Hepatology (2011)