tbuckley/cabot-search huggingface dataset:
PMO-128 Effects of oral nanoporous carbon therapy in leptin null mice as a model of non-alcoholic steatohepatitis
Authors: J Macnaughtan, J Soeda, A Mouralidarane, S Sandeman, C Howell, S Milkhalovsky, O Kozynchenko, S Tennison, N Davies, R Mookerjee, J Oben, R Jalan
Journal: Gut (2012)

<h3>Introduction</h3> Endotoxaemia is implicated in the pathogenesis of non-alcoholic fatty liver disease. Modulation of intra-luminal factors driving bacterial translocation may have the capacity to impact on the natural history of the disease. Nanoporous carbons are non-absorbable, synthetic materials which are safe with porosity manipulated for adsorption of middle and high molecular weight molecules and surface chemistry modified to alter adsorption capacity for biological molecules. We sought to determine their biological effects in leptin null mice, which are hyperphagic and obese with evident steatohepatitis and to ascertain whether nanoporous carbons can reverse established non-alcoholic steatohepatitis (NASH) in these animals. <h3>Methods</h3> 10 lep<sup>−</sup>/lep<sup>−</sup> null and 10 heterozygote male mice were randomised to receive powdered chow ± carbon (0.4 g/100 g body weight/day) for 4 weeks. Extent of liver injury was assessed by serum levels of ALT. Additionally, non-parenchymal cells were isolated and the Kupffer cell (KC) population characterised by flow cytometry as those cells expressing F4/80, CD68 and CD11b. Reactive oxygen species (ROS) production by isolated KCs was also assayed. Hepatic TLR-4 expression as a surrogate of endotoxaemia was determined by immunohistochemistry. <h3>Results</h3> In lep<sup>−</sup>/lep<sup>−</sup> mice, oral carbon treatment was associated with a significant reduction in ALT 889±280 IU/ml to 408±42 IU/ml (p&lt;0.05). Total KC population was found to be increased in lep<sup>−</sup>/lep<sup>−</sup> mice compared to heterozygote control with a significant reduction observed with carbon treatment (p&lt;0.05). A significant reduction in KCs ROS production was also observed in carbon treated lep<sup>−</sup>/lep<sup>−</sup> mice (p&lt;0.05) compared to untreated lep<sup>−</sup>/lep<sup>−</sup> controls. A significant reduction in the F4/80+, CD68<sup>−</sup>, CD11b+ cell sub-population in lep<sup>−</sup>/lep<sup>−</sup> in the presence of carbon treatment group was also observed (p&lt;0.05). Moreover, hepatic TLR-4 expression was reduced in carbon-treated lep<sup>−</sup>/lep<sup>−</sup> mice compared to non-treated controls. Finally, we observed a trend towards reduction in final body weight in carbon-treated lep<sup>−</sup>/lep<sup>−</sup> mice compared to untreated controls group (p=0.095). <h3>Conclusion</h3> Oral nanoporous carbon through modulating endotoxaemia and KC function may be a promising therapy in NASH. <h3>Competing interests</h3> None declared.
A7.4 Study of psychometric properties of the "medical outcomes Scale (MOS) sleep scale" in the portuguese population with fibromyalgia
Authors: Cristina Mesquita, Sofia Lopes, Alice Vitorino, Filipa Araújo, Inês Neves, Daniela Silva, Patrícia Lopes, Excelsa Moreira, Ana Carneiro
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Sleep is a highly organised biological process that is an important component of functioning and well-being of human. Sleep disorders have been referred as one of the main symptoms of Fibromyalgia. However, after the pain, sleep disorder symptoms is most often referenced by these individuals, including non-restorative sleep, insomnia and poor quality sleep. Recent studies suggest a reciprocal relationship between pain and sleep. Thus, the new diagnostic criteria proposed by American College of Rheumatology (ACR) suggest that sleep should be a central aspect of Fibromyalgia clinical evaluation. The objective of this study is evaluate the psychometric properties of the MOS Sleep Scale in patients with Fibromyalgia. <h3>Materials and Methods</h3> The MOS Sleep Scale was sent by mail to 229 individuals with Fibromyalgia, members of National Association Against Fibromyalgia and Chronic Fatigue Syndrome - MYOS, Northern Region. Individuals who responded (sample test-retest), was sent back after 10 days. Subsequently was tested reliability and validity. Internal consistency was assessed using Cronbach9s alpha reliability and intraobserver reliability by intraclass correlation coefficient. Construct validity was determined by formulating hypotheses developed based on another measure, FIQ-P. <h3>Results</h3> Most subjects were female (94.5%) with a mean age of 52.40 ± 11.05. The Cronbach9s alpha showed acceptable values ​​above 0.70 for all domains. They demonstrated good intra-observer reliability with intraclass correlation coefficient of 0.80 and standard error of measurement of 9.10. <h3>Conclusions</h3> The results of this study demonstrated good levels of reliability and construct validity of the MOS Sleep Scale, which is an appropriate instrument to evaluate sleep disturbances in individuals with fibromyalgia.
FACTORES PRONÓSTICOS DE LAS COMPLICACIONES ASOCIADAS A LA SEDACIÓN CON PROPOFOL DIRIGIDA POR EL ENDOSCOPISTA: EXPERIENCIA DE SEGURIDAD EN UN HOSPITAL GENERAL
Authors: M Pérez Contreras, O Miquel Cusachs, F Mohamed Embarek, S Virolés Torrent, M Figa Francesch, F González-Huix Lladó
Journal: Endoscopy (2012)

Introducción: la Sedación con Propofol dirigida por el endoscopista (SPDE) se utiliza cada vez con mayor frecuencia por su buena relación coste-efectividad. Los efectos adversos de la SPDE se relacionan con alteraciones respiratorias y cardiovasculares. Objetivo: evaluar la seguridad y la tolerancia de la SPDE y determinar los factores predictivos de la aparición de complicaciones graves relacionadas con la sedación. Método: registro prospectivo durante 10 años de la tolerancia y los efectos adversos durante los procedimientos endoscópicos en los que se ha administrado SPDE. Se valoraron parámetros de filiación, tolerancia (escala visual analógica), factores de riesgo para la sedación (grado de ASA, score de Mallampati), variables hemodinámicas incluyendo: TA, FC, Sat O2; dosis de fármacos sedantes, tipo de exploración y de terapéutica endoscópica realizada. Se definió como complicación grave, la aparición de una de las siguientes: sat O2, TAS, crisis convulsivas, broncoaspiración, parada respiratoria y éxitus. Se determinaron las medidas utilizadas para tratarlas: necesidad de ventilación con ambú, intubación endotraqueal y de intervención de anestesiólogos o intensivistas. Se hizo un análisis multivariante de regresión logística, para determinar los factores relacionados con la probabilidad de la aparición de complicaciones graves. Resultados: durante el período de análisis se administró algún tipo de sedación en 39.301 procedimientos endoscópicos. El Propofol como fármaco sedante en 28.385 (72,2%): solo Propofol en 18.579 (65,4%) y asociado a Midazolam en 9.806 (34,5%). La edad media fue de 59,5 +/-; 46,2% mujeres, gastroscopias 51,3%, colonoscopias 38,4%, CPRE/USE 9,3%. El 24,2% fueron endoscopias terapéuticas. Hubo un total de 184 complicaciones graves en 159 pacientes (0,5%) que fueron: desaturación grave (Sat <O2 50% en 12 pacientes, TAS 250mmHg en 8 pacientes. Además hubo 3 de crisis convulsivas, 1 broncoaspiración, 2 espasmos laríngeos y 5 paros respiratorios. Ningún éxitus relacionado con la SPDE. Fue necesario utilizar ventilación con ambú en 15, intubación endotraqueal en 5 e intervención por anestesiólogos/intensivistas en 4 pacientes. Cuatro factores reducían el riesgo de presentar complicaciones graves: grado de ASA, la edad, la endoscopia por vía oral y la monitorización. Conclusiones: la SPDE es un método seguro con un bajo número de complicaciones graves. El grado de ASA ≥3, la aplicación de tratamientos durante la endoscopia, la edad >65 años, el acceso del endoscopio por vía oral y variables hemodinámicas y respiratorias sencillas evaluadas antes de la endoscopia permiten detectar a los pacientes con riesgo elevado de complicaciones graves.
Familial Dysalbuminemic Hyperthyroxinemia
Authors: Miguel Ruiz, Rajata Rajatanavin, Ruth A. Young, Charles Taylor, Rosalind Brown, Lewis E. Braverman, Sidney H. Ingbar
Journal: New England Journal of Medicine (1982)

We investigated 15 euthyroid patients from eight families with a recently recognized syndrome, familial dysalbuminemic hyperthyroxinemia (FDH), that could be mistaken for thyrotoxicosis. The syndrome is characterized by elevations in serum thyroxine and the free-thyroxine index (FT4l), which are due to an abnormal serum albumin that preferentially binds thyroxine. This albumin has an abnormal binding site with a much greater affinity for thyroxine (relative to its affinity for triiodothyronine) than that of the hormone-binding site on thyroxine-binding globulin. Results of thyrotropin-releasing hormone and thyroid-suppression tests, as well as direct measurements of the free-thyroxine concentration by equilibrium dialysis, are normal in these patients, although the serum triiodothyronine concentration may be slightly elevated. Although its prevalence is uncertain, FDH may be more common than suspected; we have seen 26 cases within the past year.
Foreign Medical Aid to South Vietnam
Authors: Alister Brass
Journal: New England Journal of Medicine (1967)

"Of course, it's just bush medicine under those conditions. What Vietnam needs is immunisation schemes, malaria eradication, decent water supplies, sewerage – and a birth control policy. Then you can start on the surgery.""Its been the most stimulating and rewarding three months of my surgical career. I think I've done more really useful work in those few weeks than in several years at home. I'd go back again tomorrow if I could, and so would practically everyone else who's been."THESE are two opinions of Australia's present system of medical aid to South Vietnam – just one part of . . .
RESECCIÓN ENDOSCÓPICA DE TODO EL GROSOR DE LA PARED EN NEOPLASIA COLONICA: DEL LABORATORIO A LA CLINICA
Authors: JR Armengol Miró, J Dot Bach, M Abu-Suboh Abadia, J Armengol Bertroli, A Benages Curell, M Masachs Peracaula, X Zhang, JC Salord Oses, L Rivero, D Castillo, SV Kantsevoy
Journal: Endoscopy (2012)

Introducción: La mucosectomía endoscópica (EMR) y la disección submucosa (ESD), se usan actualmente para la resección de neoplasias precoces del tracto gastrointestinal, limitadas a las capas superficiales de la paret del colon. Estas técnicas son técnicamente dificultosas y laboriosas y no pueden usarse con la lesión no puede elevarse con la inyección submucosa de suero y/o cuando afecta a capas profundas de la pared. Objetivo Valorar la posibilidad y seguridad de realizar resección de colon de todo el grosor de la pared en un modelo porcino vivo y la primera experiencia clínica en humanos. Método: Se realizaron resecciones de todo el grosor de la pared en estomago y colon de 9 cerdos de 50kg. Después de la resección los defectos de la pared fueron suturados con el dispositivo de sutura Overstich (Apollo Endosurgery Inc, Austin, TX). Tres animales fueron sacrificados post-procedimiento y 6 animales sobrevivieron 14días. Pasado este tiempo fueron sacrificados y se realizó examen. Tras esto se realizó resección de todo el grosor de la pared del colon en un paciente, con hemorragia activa por neoplasia de colon, que no era tributario de tratamiento quirúrgico debido a patología concomitante. Resultados: Utilizando hook knife, IT-knife o asa de polipectomía (todas ellas Olympus), se realizaron con facilidad resecciones grandes (3–5cm) de todo el grosor de la pared. Todos los orificios se suturaron utilizando el sistema de sutura endoscópica Overstich. La sutura fue sencilla técnicamente, y se consiguió una sutura firme en todos los animales. El examen postmortem reveló una buena cicatrización del tracto gastro-intestinal en los sitios de resección. Después de conseguir una experiencia significativa en sutura endoscópica se realizó una resección de todo el espesor de la pared del colon en un paciente de 64 años con una neoplasia colónica de ángulo hepático con sangrado activo. El paciente requería tratamiento anticoagulante y no era candidato a cirugía debido a patología severa cardiaca. La lesión colónica tenia un tamaño de 2×4cm y no se elevó con la inyección submucosa de suero salino. Tras la resección endoscópica de un área de 4×6cm, el defecto de la paret se cerró completamente con sutura continua. Tras el procedimiento el paciente no presentó dolor y fue dado de alta tras 72 horas de observación. El seguimiento endoscópico a los 3, 6 y 12 meses reveló una buena cicatrización de la mucosa del colon sin recidiva neoplásica ni estenosis. Conclusión: Esta es la primera resección de toda la paret en el tracto gastrointestinal para tratamiento de neoplasias, realizada de forma completamente endoscópica. Este procedimiento puede usarse incluso cuando la mucosectomía o la disección submucosa no son posibles y puede convertirse en una alternativa a la laparoscopia y la cirugía abierta.
Résection endoscopique des cancers colo-rectaux comportant un envahissement sous-muqueux: évaluation rétrospective monocentrique
Authors: E Bories, F Poizat, F Caillol, C Pesenti, C de Chaisemartin, G Monges, JR Delpero, M Giovannini
Journal: Endoscopy (2014)

Le but de cette étude était d'évaluer l'efficacité de la résection endoscopique (RE) des carcinomes colo-rectaux comportant un envahissement sous-muqueux.
Abstract B35: Dynamics of MHC class II tumor antigen presentation is critical for effector antitumor CD4+ T-cell generation and tumor rejection
Authors: Cristina Bonorino, Fabio Maito, Ana Paula Souza
Journal: Cancer Research (2009)

Abstract Absence of CD4+ T cell help leads to defects in CD8+ T cell memory responses.Although this phenomenon is well characterized in infectious immunity, little is known about the generation of anti-tumor CD4+ T cell responses in vivo, or even how relevant is T cell help for tumor elimination. CD4+ T cells appear differ from CD8+ T cells in their requirements for differentiation, the dynamics of encounter with antigen being critical in this process. We analyzed the relevance of MHC class II antigen presentation for tumor rejection, developing a B16EaRFP line to study class II restricted tumor antigen presentation and the cognate CD4+ T cell help in vivo. We found that, in a tumor heavily infiltrated by dendritic cells (DC), a progressive decline in different cell subpopulations is observed in draining lymph nodes (DLNs), suggesting an interruption of local cell traffic. Artificial increase in precursor frequency of tumor specific CD8+ T cells by adoptive transfer of naïve OT-I cells in C57Bl/6 mice injected with B16OVA tumor was able to delay tumor growth, but was not sufficient to block it completely. While tumor antigen presentation in class II molecules was detected in the DLN, and could be increased by delivery of necrotic or apoptotic tumor cells, tumor specific CD4+ T cells showed proliferation arrest in the DLN. Tumor growth was blocked only when dendritic cells (DCs) were activated by intra-tumoral LPS injection, reestablishing cell traffic to the LN, resulting in expansion of INF-γ producing anti-tumor CD4+ T cells. Our results suggest that CD4+ T cells are a major target of tumor mediated antigen presentation interruption, and that CD4+ T cell help is necessary for rejection of an established tumor. These observations have major implications for the design of cancer immunotherapy strategies. Citation Information: Cancer Res 2009;69(23 Suppl):B35.
Suppression of the Anamnestic Response to Tetanus Toxoid in Man by Chloramphenicol
Authors: Thomas M. Daniel, Leif G. Suhrland, Austin S. Weisberger
Journal: New England Journal of Medicine (1965)

ALTHOUGH chloramphenicol is known to inhibit microbial protein synthesis both in intact cells and in cell-free systems, protein synthesis in analogous mammalian systems has been, in general, resistant to inhibition by chloramphenicol. Recently, however, it was demonstrated that chloramphenicol can inhibit protein synthesis in mammalian cell-free systems as effectively as in analogous microbial systems when mammalian protein synthesis is stimulated by the addition of template RNA.1 It was suggested that chloramphenicol acts by blocking the attachment of messenger RNA to its ribosomal binding site. A similar explanation was offered by Ambrose and Coons,2 who demonstrated the ability of chloramphenicol to . . .
QL-17 * COMMUNITY BRAIN TUMOUR FORUMS: LESSONS FROM THE FRONT LINE
Authors: D. Legge, L. Cher
Journal: Neuro-Oncology (2014)

BACKGROUND: Informational demands of patients and families affected by brain cancer are well documented. Access to accurate well-balanced material is a vital element in ensuring their participation in their healthcare journey. Since 2011, Austin Health has partnered with other organisations to present current, relevant clinical and supportive care information to a self selected community audience. METHODS: Program content was drawn from high prevalence clinical issues, support groups and anecdotal feedback from a variety of sources. Forums have developed from a 3-hour evening session to full day forums with invited speakers and exhibitors. Importantly, it has been vital to promote to buy-in of health institutions, peer support services and charities. We balanced opportunities to hear from experts, specialised support services and consumer sharing experiences. RESULTS: Since 2011, 3 forums have been conducted attracting 205 participants in total. Post forum evaluations were conducted, with a response rate of 52%. All presentations rated greater than 4.76/5. Clinical trials, research and brain tumour science presentations were rated as most valuable. Logistical challenges include competing interests of different organisations, and agendas of attendees. Balancing technical verses layman language, evidence based information verses alternate treatment options, and ensuring effective facilitation of sessions has led to program content revision. The use of post-forum evaluations allowed us to identify a range of areas that were an unmet need, which included such information as role of clinical trials and an understanding of specific cognitive syndromes and their impact on patient and family. CONCLUSION: Community brain tumour education forms a positive step to ensuring patients and families are well resourced, with opportunities to broaden support options. Bringing together of clinicians, consumers and philanthropy has led to coordinated relevant information being available to consumers unable to access neuro-oncology care coordination.
Abstract 4378: Poly(ADP-ribose)glycohydrolase (PARG) is a novel therapeutic target in breast cancer.
Authors: Amanda Lovato, Tiejun Zhao, Qiang Sun, Michael Witcher
Journal: Cancer Research (2013)

Abstract Poly(ADP-ribose)polymerase (PARP) is an enzyme responsible for catalyzing the addition of poly(ADP-ribose) chains onto target proteins in a process known as PARylation. This post-translational modification has been implicated in numerous cellular processes including gene expression, chromatin remodeling, apoptosis and DNA damage repair. In particular, the role of PARP activation in response to DNA damage has been intensely studied. BRCA mutated tumors are highly sensitive to DNA breaks and are therefore critically dependent on alternative repair mechanisms involving PARP. This forms the basis for a synthetic lethal therapeutic approach that has been met with much success in the clinic. BRCA mutated breast and ovarian tumors, in particular, are acutely sensitive to PARP inhibitors. Currently, it is unclear from in vitro and clinical studies to what extent PARP inhibitors can be used as chemotherapeutics to treat tumors beyond those harboring BRCA mutations. Due to the insensitivity of most solid tumors to PARP inhibitors, we have begun to study the role of the dePARylating enzyme poly(ADP-ribose)glycohydrolase (PARG), as a possible target in cancer therapy. PARG, like PARP, maintains a critical role in DNA repair and can therefore be a target in cells with defective repair mechanisms (e.g. BRCA mutant cells). We further hypothesize that targeting this factor may activate the expression of tumor suppressor genes, thus limiting cell proliferation. Thus far, we have novel data indicating that targeting PARG may indeed have therapeutic benefit. We show that PARG knockdowns of the T47D and MDA-MB-468 breast cancer cell lines have dramatically reduced rates of cellular proliferation. Gene expression analyses of the knockdown cells indicated that cell cycle related pathways may be affected. As such, we examined cell cycle profiles by BrdU and PI staining and found that PARG knockdown cells were arrested in S phase. These results are particularly striking given that these cells show resistance to PARP inhibition. Subsequent studies using the PARG inhibitor gallotannin successfully reconstituted the results obtained with the PARG knockdowns. Overall, our data illustrates that PARG has great potential as a new anti-cancer target. Citation Format: Amanda Lovato, Tiejun Zhao, Qiang Sun, Michael Witcher. Poly(ADP-ribose)glycohydrolase (PARG) is a novel therapeutic target in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4378. doi:10.1158/1538-7445.AM2013-4378
Abstract 1429: <i>Apc</i> heterozygosity in the C57BL/6J-Min/+ mouse produces an abnormal exuberant proliferative response in excisional wound healing
Authors: Yvonne Heit, Adelaide M. Carothers, Eric Ross, Hira Rivzi, Dennis Orgill, Monica M. Bertagnolli
Journal: Cancer Research (2011)

Abstract The Min mouse is a model for intestinal tumor formation. Previously, we showed that the ApcMin allele produces a dominant-negative effect on enterocyte migration and stromal interaction in vivo. Tumorigenesis is driven by features of epithelial-mesenchymal interaction that are observed in wound healing, therefore we hypothesized that the Min phenotype also involved abnormalities in the wounding response program. We performed excisional wound assays on female Min mice (10 or 20-week old), comparing response to that of female age-matched Apc+/+ (WT) mice. The healing kinetics of full thickness dorsum wounds were quantified by digital planimetry. Histological cross sections on post-operative day 7 were used to measure granulation tissue thickness, nascent blood vessel density, and cell proliferation. Western blotting was performed using granulation tissue lysates to compare the expression of adhesion and extracellular matrix proteins, as well as α-smooth muscle actin, a marker for the presence of contractile cells. Immunofluorescent histochemistry was performed to detect the co-expression and quantitation of αSMA+, vimentin+, SM22+, desmin− myofibroblasts at wound edges. Wound closure was faster in Min mice relative to WT mice, 88.85% versus 68.86% (P&amp;lt;0.01). Min mice also showed the strongest induction of granulation tissue formation; the relative granulation tissue thickness in the centre of wounds was 171.15±47.53 and 147.96±16 mm (P&amp;lt;0.01) in Min and WT, respectively. Blood vessel density, measured by counting the number of CD31+ cells/high power field, was increased (40.72 + 22.6) in Min mice when compared to WT (19.03 ± 17.6, P&amp;lt;0.01). The number of proliferating cells in granulation tissue (Ki67+ nuclei/all) in Min mice (63.72±16.83) was greater than in WT (41.58±23.46) (P&amp;lt;0.01). Masson's stain demonstrated that more collagen deposition was present in wounds of Min/+ relative to WT. In conclusion, this study showed that wound healing was accelerated in Min/+ mice relative to WT. Therefore, even before the loss of the WT allele, Apc heterozygosity likely promotes tumor formation because it affects wound-induced invasive, homing, and engraftment responses of the epithelial stroma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1429. doi:10.1158/1538-7445.AM2011-1429