tbuckley/cabot-search huggingface dataset:
S-nitrosoglutathione-containing hydrogel increases dermal blood flow in streptozotocin-induced diabetic rats
Authors: A.B. Seabra, E. Pankotai, M. Fehér, Á. Somlai, L. Kiss, L. Bíró, C. Szabó, M. Kollai, M.G. de Oliveira, Z. Lacza
Journal: British Journal of Dermatology (2007)

Endothelial dysfunction is characterized by decreased vasodilatory capacity of the arterioles mainly due to the reduced release of nitric oxide (NO). Application of NO donors may prevent or even reverse the consequences of endothelial dysfunction, such as diabetic leg ulcers.To investigate the vasodilatory capacity and the possible side-effects of topical application of an NO donor-containing hydrogel in diabetic rats.S-nitrosoglutathione (GSNO) was incorporated in Pluronic F127 hydrogel and applied on the foot sole skin of healthy and streptozotocin-induced diabetic rats. Blood flow was monitored using a laser-Doppler probe. Nitrotyrosine formation, a possible side-effect of GSNO action, was evaluated by Western blotting of skin protein extracts. Systemic circulatory side-effects were investigated by monitoring blood pressure and heart rate during the application.The hydrogel alone did not induce any changes in microvascular flow, while GSNO-containing hydrogel caused a twofold increase in perfusion. This effect was similar in diabetic and healthy animals. Topical GSNO application did not increase the nitrotyrosine content of skin proteins, nor did it have any effect on blood pressure or heart rate.Dermal application of GSNO may be an effective treatment for promoting the local vasodilation in both healthy and diabetic states, without inducing protein nitration or alterations in blood pressure or heart rate.
Abstract A01: KRAS molecular profiling in non-squamous non-small cell lung cancer (NSCLC).
Authors: Nagla Abdel Karim, Sandra Starnes, John Morris, Peter Pathrose, Ashley Perry, Hassana Fathallah
Journal: Clinical Cancer Research (2014)

Abstract Recent studies suggest that patients with KRAS-mutant NSCLC fail to benefit from standard systemic therapies and do not respond to EGFR inhibitors. Therefore, there is a clear need for therapies specifically developed for these patients. Molecular profiling has the potential to identify potential targets that might provide a better treatment and novel targeted therapy for KRAS-mutated NSCLC. In this study, we purified RNA from archived tumor and normal lung tissue obtained from 20 patients with wild type (wt) and 17 patients with mutant (mt) KRAS tumors undergoing resection for stage I and stage II NSCLC, and assessed by reverse transcriptase-real time polymerase chain reaction (RT-PCR) the expression of four genes involved in DNA synthesis and repair including thymidylate synthase (TS), BRCA1, ECCR1 and RAP80, and the proto-oncogene SRC. Our results show that in mt KRAS tumors, the levels of expression of ERCC1, TS and SRC were significantly increased in comparison to paired-normal lung tissue (p ≤ 0.04). Expression of BRCA1 and RAP80 were similar in both mt KRAS tumors and paired-normal tissue. Furthermore, the expression of BRCA1, TS and SRC were significantly increased in wt KRAS tumors relative to their expression in normal lung (p ≤ 0.044). Expression of ERCC1 and RAP80 was similar in wt KRAS tumors and paired normal tissue. Interestingly, SRC expression in mt KRAS tumors was decreased in comparison to wt KRAS tumors. Our results suggest that greater ERCC1 expression in mt KRAS tumors might increase platinum resistance in this group of patients, whereas the greater expression of BRCA1 in wt KRAS tumors might be suggestive for the sensitivity to taxanes. Our data also suggests that the combination of a SRC inhibitor with a TS inhibitor such as pemetrexed might improve the outcome of patients with wt KRAS tumors. In conclusion, these results suggest that the most effective treatment strategy for KRAS-mutant NSCLC is combined targeting of oncogenic KRAS in addition to other therapeutic agents specific to the molecular profile of the tumor. Citation Format: Nagla Abdel Karim, Sandra Starnes, John Morris, Peter Pathrose, Ashley Perry, Hassana Fathallah. KRAS molecular profiling in non-squamous non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A01.
Spinal Extradural Metastasis: Review of Current Treatment Options
Authors: R. H. M. A. Bartels, Y. M. van der Linden, W. T. A. van der Graaf
Journal: CA A Cancer Journal for Clinicians (2008)

Bone metastases, especially to the spine, are frequently encountered during the course of a malignancy. Due to a worldwide increase of cancer incidence and to a longer life expectancy of patients with cancer, a rise in incidence of bone metastases is observed. A brief historical overview is the base of a review of current treatment options. Despite new developments in the surgical and radiotherapeutic fields, as well as in medical oncology, external beam radiotherapy is the cornerstone of the treatment of spinal metastases. In selected cases, surgical treatment is a proven option. Vertebroplasty or kyphoplasty can also be considered. Supportive medical care does not differ from that given for symptomatic lesions to the skeletal system elsewhere in the body. After discussing the treatment options, an algorithm is given.
Endothelial Dysfunction Plays Dynamic Role in Coronary Artery Disease
Authors: Marsha F. Goldsmith
Journal: JAMA (1990)

THE INSIDE STORY on coronary artery disease has come to center on the role of the endothelium. Various hypotheses have been advanced in the past concerning what might ensue, for example, after damage to the blood vessels' lining. At the most recent Scientific Sessions of the American Heart Association (AHA) held in New Orleans, La, several presentations showed that endothelial dysfunction, whatever its cause, appears to play an important role as a harbinger of atherosclerosis and subsequent adverse coronary events. Evidence from experimental and clinical investigation points toward three major mechanisms of action by which the blood vessels' cellular lining, because of its unique position between the blood and the vessel wall, may influence the development of lesions in the coronary arteries. It may do so, say researchers, by causing altered vasomotor responses, by promoting increased growth of other blood vessel elements such as smooth-muscle cells, or by predisposing to
EMR using dextrose solution versus sodium hyaluronate for colorectal Paris type I and 0-II lesions: a randomized endoscopist-blinded study
Authors: D. Hurlstone, K. Fu, S. Brown, M. Thomson, R. Atkinson, N. Tiffin, S. Cross
Journal: Endoscopy (2008)

See also: Commentaire de travail de D. P. Hurlstone et al., pp. 110Endoscopy 2008; 40(02): 233-233DOI: 10.1055/s-0032-1306805
Approaches to Screening for Intimate Partner Violence in Health Care Settings
Authors: Harriet L. MacMillan
Journal: JAMA (2006)

A][7] An ongoing question in the field is whether health care professionals should routinely screen their female patients for exposure to IPV. 8 Previous studies have demonstrated that women will disclose experiences of violence in response to screening [3][4][5][6][7] ; however, few studies have compared methods of administration.In a review of IPV screening in the primary care setting, Chuang and Liebschutz 9 identified 2 main approaches to screening: (1) verbal methods (questions asked by a clinician) and (2) self-administered meth-ods, including written or computerbased questionnaires.The limited amount of research to date has generally compared IPV prevalence on faceto-face questioning with a written selfcompleted questionnaire.
Deficient Cutaneous Antibacterial Competence in Cutaneous T-Cell Lymphomas: Role of Th2-Mediated Biased Th17 Function
Authors: Kerstin Wolk, Hiroshi Mitsui, Katrin Witte, Sylke Gellrich, Nicholas Gulati, Daniel Humme, Ellen Witte, Melanie Gonsior, Marc Beyer, Marshall E. Kadin, Hans-Dieter Volk, James G. Krueger, Wolfram Sterry, Robert Sabat
Journal: Clinical Cancer Research (2014)

Primary cutaneous T-cell lymphomas (CTCL) are neoplastic disorders of skin-homing T cells. Affected skin areas show morphologic similarities with alterations in other T-cell-mediated dermatoses. Furthermore, as in atopic dermatitis but in contrast with psoriasis, patients with CTCL are frequently afflicted by cutaneous bacterial infections that support the survival of lymphoma cells. Our aim was to investigate the mechanisms of elevated susceptibility to cutaneous infections in patients with CTCL.Skin samples from CTCL, psoriasis, and atopic dermatitis patients were used to illuminate the antibacterial competence status and the presence of its modulating cytokines. For substantiation of findings, 3-dimensional epidermis models, isolated and in vitro generated Th-subpopulations, were applied. Parameters were analyzed via qPCR and IHC.CTCL lesions compared with psoriatic lesions presented an impaired upregulation of antibacterial proteins (ABPs), with levels even below those in atopic dermatitis. This was associated with a relative deficiency of the ABP-inducing cytokine IL-17 and a strong presence of the ABP-downregulating cytokine IL-13. The simultaneous presence of the Th17-cell cytokine IL-26 indicated that IL-17 deficiency in CTCL lesions results from functional deviation of Th17 cells. Accordingly, IL-17 but not IL-26 production by Th17 cells in vitro was inhibited by IL-4Rα ligand. Levels of other ABP inducers were comparable between CTCL and psoriasis lesions. The same was true about IL-22/TNF-α targets, including the keratinocyte hyper-regeneration marker K16 and the matrix-degrading enzyme MMP1.Our results suggest that the cutaneous bacterial infections in CTCL are caused by impaired ABP induction as consequence of Th2-mediated biased Th17-cell function.
Minerals, fibrosis, and the lung.
Authors: A G Heppleston
Journal: Environmental Health Perspectives (1991)

Determinants of pulmonary fibrosis induced by inhaled mineral dusts include quantity retained, particle size, and surface area, together with their physical form and the reactive surface groups presented to alveolar cells. The outstanding problem is to ascertain how these factors exert their deleterious effects. Both compact and fibrous minerals inflict membrane damage, for which chemical mechanisms still leave uncertainty. A major weakness of cytotoxicity studies, even when lipid peroxidation and reactive oxygen species are considered, lies in tacitly assuming that membrane damage suffices to account for fibrogenesis, whereas the parallel occurrence of such manifestations does not necessarily imply causation. The two-phase procedure established that particles, both compact and fibrous, induce release of a macrophage factor that provokes fibroblasts into collagen synthesis. The amino acid composition of the macrophage fibrogenic factor was characterized and its intracellular action explained. Fibrous particles introduce complexities respecting type, durability, and dimensions. Asbestotic fibrosis is believed to depend on long fibers, but scrutiny of the evidence from experimental and human sources reveals that a role for short fibers needs to be entertained. Using the two-phase system, short fibers proved fibrogenic. Other mechanisms, agonistic and antagonistic, may participate. Growth factors may affect the fibroblast population and collagen production, with cytokines such as interleukin-1 and tumor necrosis factor exerting control. Immune involvement is best regarded as an epiphenomenon. Downregulation of fibrogenesis may follow collagenase release from macrophages and fibroblasts, while augmented type II cell secretion of lipid can interfere with the macrophage-particle reaction.
A Breath of Fresh Air
Authors: M. J. Friedrich
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 2527: Antibody-dependent cellular cytotoxicity of cetuximab against colorectal cancer cells with wild-type and mutant KRAS
Authors: Yusuke Nakadate, Yuka Kitamura, Tomohide Tamura, Fumiaki Koizumi
Journal: Cancer Research (2012)

Abstract Cetuximab is a chimeric IgG1 monoclonal antibody (mAb) that targets the extracellular domain of epidermal growth factor receptor (EGFR). In addition to direct EGFR inhibition, antibody-dependent cellular cytotoxicity (ADCC) is considered to be an important mechanism of action of cetuximab. Recently, KRAS mutations in tumors have been shown to be a negative predictive factor for response to cetuximab treatment for colorectal cancer (CRC). KRAS activating mutations constitutively transduce RAS/RAF/MEK/ERK pathway signaling, which theoretically cannot be suppressed by inhibition of the upstream receptor through the use of cetuximab. Thus, KRAS mutations potentially contribute to the resistance to the direct inhibitory effect of cetuximab. However, the influence of KRAS mutations on cetuximab induced ADCC is not fully understood. In this study, we investigated cetuximab-mediated ADCC against human CRC lines, HCT116 and DLD-1, which carry mutated KRAS, and their derivative cell lines, HKh2 and DKO-4 respectively, in which the mutated KRAS allele was deleted by targeted disruption (KRAS wild-type). Peripheral blood mononuclear cells (PBMCs) from healthy volunteers and NK92, a natural killer cell line, exogenously expressing Fcα3A (CD16a) were used as effector cells. We first determined the growth-inhibitory effect of cetuximab alone using a WST-8 assay. Growth inhibition was observed only in KRAS wild-type cell lines, but its effect was only slight. In a standard short-term (4hr) ADCC assay that mainly evaluated lytic activity via perforin/granzyme, ADCC activities were exhibited to a similar extent against CRC cell lines regardless of the KRAS mutation status. We also examined a long-term (24hr) ADCC assay under the perforin-inhibited condition to evaluate the death receptor ligand-induced apoptosis, which is another major mechanism of ADCC. In this assay, cetuximab-mediated ADCC was induced in wild-type but not mutant KRAS cell lines. Similar to a previous report, Hkh2 and DKO-4 displayed a higher sensitivity to recombinant human Fas ligand (FasL) and TRAIL than did HCT116 and DLD-1, respectively. Furthermore, blocking experiments with neutralizing antibodies revealed that induction of apoptosis via Fas-FasL interaction is involved in perforin-independent cetuximab-mediated ADCC against KRAS wild-type cells. In conclusion, these results suggest that mutated KRAS may contribute to the resistance to the antitumor effects of cetuximab not only through direct receptor inhibition but also through ADCC mediated by Fas-FasL interaction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2527. doi:1538-7445.AM2012-2527
Assessing the association of early life antibiotic prescription with asthma exacerbations, impaired antiviral immunity, and genetic variants in 17q21: a population-based birth cohort study
Authors: Aida Semic-Jusufagic, Danielle Belgrave, Andrew Pickles, Aurica G Telcian, Eteri Bakhsoliani, Annemarie Sykes, Angela Simpson, Sebastian L Johnston, Adnan Custovic
Journal: The Lancet Respiratory Medicine (2014)

The relationship between early-life antibiotic use and the development of wheeze and asthma has been reported in several studies but might arise as a consequence of bias rather than causal relationship. We investigated the association between antibiotic prescription and subsequent development of atopy, wheeze, and asthma exacerbations, and the relation of early life antibiotic prescription with anti-infective immunity and genetic variants on asthma susceptibility locus 17q21.Children in a population-based birth cohort were followed from birth to age 11 years. Information on antibiotic prescription, wheeze, and asthma exacerbations was extracted from medical records, and the effect of antibiotic prescription assessed with longitudinal analyses. We assessed immune responses of peripheral blood mononuclear cells, taken at age 11 years, to viruses (rhinovirus and respiratory syncytial virus; RSV) and bacteria (Haemophilus influenzae and Streptococcus pneumoniae) in children who either received at least one or no antibiotic prescriptions in infancy. Finally, we assessed the association of 17q21 polymorphisms with antibiotic prescription.Of 984 families who gave consent, we extracted data for 916 children. We noted significantly higher risk of physician-confirmed wheezing after antibiotic prescription (hazard ratio [HR] 1·71, 95% CI 1·32-2·23; p<0·0001) and severe wheeze or asthma exacerbation after antibiotic prescription (HR 2·26, 95% CI 1·03-4·94; p=0·041). In children who wheezed, the hazards of exacerbations (2·09, 1·51-2·90; p<0·0001) and admissions to hospital (2·64, 1·49-4·70; p=0·0009) were significantly increased in the 2 years after the first antibiotic prescription. Children who received antibiotics in infancy had significantly lower induction of cytokines, which are important in host defence against virus infections to both RSV and rhinovirus; there were no differences in antibacterial responses. Variants in 17q21 were associated with an increased risk of early life antibiotic prescription.The association between antibiotics and asthma might arise through a complex confounding by indication. Hidden factors that may increase the likelihood of both early life antibiotic prescription and later asthma are an increased susceptibility to viral infections consequent upon impaired antiviral immunity and genetic variants on 17q21.Moulton Charitable Foundation and Medical Research Council.
Tensions in the Racial Integration of Health Care, Then and Now
Authors: Samir K. Ballas
Journal: Annals of Internal Medicine (1998)

Letters15 January 1998Tensions in the Racial Integration of Health Care, Then and NowSamir K. Ballas, MD and Roy N. Gay, MDSamir K. Ballas, MDJefferson Medical College; Philadelphia, PA 19107Misericordia Hospital; Philadelphia, PA 19143Search for more papers by this author and Roy N. Gay, MDJefferson Medical College; Philadelphia, PA 19107Misericordia Hospital; Philadelphia, PA 19143Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-2-199801150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with interest the paper on hospitals and civil rights from 1945 to 1963 [1] and its accompanying editorial [2]. We wish to indicate that a subset of African-American patients-those with sickle cell disease-continue to be the target of discrimination. Recent studies [3, 4] suggest the existence of a two-tier system of health care in the United States: one for the affluent and another for the poor. Subcategories exist within each system that are based on such factors as race, diagnosis, disease chronicity, and treatment. Patients with sickle cell disease seem to occupy the lowest rank ...References1. Reynolds PP. Hospitals and civil rights, 1945-1963: The case of Simkins v Moses H. Cone Memorial Hospital. Ann Intern Med. 1997; 26:898-906. Google Scholar2. Thomson GE. Discrimination in health care [Editorial]. Ann Intern Med. 1997; 26:910-2. Google Scholar3. Kahn KL, Pearson ML, Harrison ER, Desmond KA, Rogers WH, Rubenstein LV, et al. Health care for black and poor hospitalized Medicare patients. JAMA. 1994; 271:1169-74. Google Scholar4. Gronick ME, Eggers PW, Reilly TW, Mentnech RM, Fitterman LK, Kucken LE, et al. Effects of race and income on mortality and use of services among Medicare beneficiaries. N Engl J Med. 1996; 335:791-9. Google Scholar5. Ballas SK. Treatment of pain in adults with sickle cell disease. Am J Hematol. 1990; 34:49-54. Google Scholar Author, Article, and Disclosure InformationAuthors: Samir K. Ballas, MD; Roy N. Gay, MDAffiliations: Jefferson Medical College; Philadelphia, PA 19107Misericordia Hospital; Philadelphia, PA 19143 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEthical issues in the management of sickle cell pain 15 January 1998Volume 128, Issue 2Page: 158KeywordsBehaviorDrugsEmergency departmentHabitsHealth careOpioidsPatientsPerceptionRacial and ethnic issuesSickle cell disease ePublished: 15 August 2000 Issue Published: 15 January 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Catheter-Based Cryoablation Permanently Cures Patients With Common Atrial Flutter
Authors: Randy Manusama, Carl Timmermans, Froylan Limon, Suzanne Philippens, Harry J.G.M. Crijns, Luz-Maria Rodriguez
Journal: Circulation (2004)

Cryoablation (cryo) has a high success rate in the short-term treatment of atrial flutter (AFL), but evidence of long-term efficacy is lacking. The present study reports the long-term effect of cryo of the cavotricuspid isthmus (CTI) in patients with common AFL.Thirty-five consecutive patients (28 men; mean age, 53 years) underwent cryo of the CTI. In 34 patients, the AFL had a counterclockwise rotation (cycle length, 242+/-43 ms). Eleven patients had structural heart disease. Cryo was performed with a 10F catheter with a 6-mm-tip electrode (CryoCor). Applications (3 to 5 minutes each) were delivered by use of a point-by-point technique to create the ablation line. The acute end point of the procedure was creation of bidirectional isthmus conduction block and noninducibility of AFL. A median of 14 applications (range, 4 to 30) at 10 sites (range, 4 to 19) was given along the CTI with a mean temperature of -80.0+/-5.0 degrees C. Mean fluoroscopy and procedure times were 40+/-26 minutes and 3.2+/-1.3 hours, respectively. Of the 35 patients, 34 were acutely successfully ablated (97%). After a mean follow-up of 17.6+/-6.2 months (range, 9.6 to 26.1 months), 31 patients (89%) did not have recurrence of AFL. Three of the 4 patients with recurrence had a second successful procedure. One patient had transient ST elevation in the inferior leads during cryoapplication.Cryo produces permanent bidirectional isthmus conduction block of the CTI. Short- and long-term success rates are comparable to those for radiofrequency ablation.