tbuckley/cabot-search huggingface dataset:
SP0194 Adult primary central nervous system vasculitis
Authors: C. Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

Adult primary central nervous system vasculitis (aPCNSV) is an uncommon disorder of unknown cause that is limited to the brain and spinal cord. The median age of onset is 50 years. The neurological manifestations are diverse, but commonly include headache, altered cognition, focal weakness, or stroke. Serological markers of inflammation are usually normal. Cerebrospinal fluid is abnormal in approximately 80-90% of the cases. The diagnosis is unlikely in the presence of a normal magnetic resonance imaging (MRI) of the brain. Biopsy of central nervous system tissue showing vasculitis is the only definitive test, however angiography has often been used for diagnosis even though it has only moderate sensitivity and specificity. To prevent misdiagnosis, particularly with the reversible cerebral vasoconstriction syndromes, new criteria based on the levels of certainty of the diagnosis of aPCNSV have been proposed. Advances in the neuroimaging techniques visualizing the wall of intracranial blood vessels have improved the capacity to distinguish inflammatory from non-inflammatory vascular lesions. These techniques could play in the future an important role in the diagnosis of aPCNSV. Studies of larger number of cases have revealed a more varied histopathological inflammatory picture and disclosed an association with amyloid angiopathy. It has also been recognized that aPCNSV is a heterogeneous disorder encompassing clinical subsets that differ in terms of prognosis and therapy. Finally, differently from earliest reports that suggested a poor prognosis with a fatal outcome in the majority of the cases, a large recent study from Mayo Clinic has described a more favorable course with good response to therapy and a favorable outcome in 81% of cases. Glucocorticoids alone or in combination with cyclophosphamide constitute the first line of treatment of PCNSV. TNFalpha blockers and mycophenolate mofetil can successfully treat patients with resistant disease.Early recognition is important because treatment with corticosteroids with or without cytotoxic drugs may prevent serious outcomes. A better understanding of the molecular mechanisms associated with the pathogenesis of aPCNSV should provide opportunities to improve therapy. <h3>Disclosure of Interest</h3> None Declared
Abstract 5610: Electric-field assisted delivery of gemcitabine for the treatment of pancreatic cancer.
Authors: James Byrne, Adrian O'Neill, Raheel Jajja, Mary Napier, James C. Luft, William Zamboni, Jen Jen Yeh, Joseph DeSimone
Journal: Cancer Research (2013)

Abstract Pancreatic cancer is the fourth leading cause of cancer death in the world, with an incidence rate approximately equivalent to the death rate. The very poor prognosis for pancreatic cancer can be attributed to late diagnosis and the ineffectiveness of drug delivery to the primary tumor. Poor tissue perfusion plays a substantial role in preventing adequate drug exposure to primary pancreatic tumors. The systemic administration of gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer, has shown limited efficacy for the treatment of pancreatic cancer, with only 5 to 10% of patients demonstrating an objective radiographic response at the primary tumor site. Furthermore, the toxicity associated with systemic chemotherapy has been found to reduce the quality of life of the patient and in extreme cases can be fatal. In an attempt to address the lack of effectiveness of systemically administered chemotherapy and associated toxicity, we have developed modalities for the localized delivery of chemotherapies to pancreatic tumors. These devices rely upon an applied electric potential difference between electrodes to drive chemotherapy into the tumor. This use of an electric potential for local delivery of chemotherapies offers the capability of overcoming considerable flow and pressure gradients. Significant work using an applied electric potential difference for drug transport has been performed in transdermal drug delivery. In the area of oncology, electric field-assisted delivery techniques have been proposed for skin and ocular cancers and have been clinically translated to the treatment of bladder cancers in the electromotive delivery of mitomycin C. This technique, combined with novel device approaches, is particularly well suited for the local treatment of the primary pancreatic tumor. Herein, we report the development of electric field-assisted delivery devices and the testing of these devices in a patient-derived orthotopic xenograft mouse model of pancreatic adenocarcinoma and a healthy canine animal model. The results show that our devices provide a significant increase in the local delivery of gemcitabine while limiting systemic toxicity. Citation Format: James Byrne, Adrian O'Neill, Raheel Jajja, Mary Napier, James C. Luft, William Zamboni, Jen Jen Yeh, Joseph DeSimone. Electric-field assisted delivery of gemcitabine for the treatment of pancreatic 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 5610. doi:10.1158/1538-7445.AM2013-5610
ACS Mobilizes Forces to Keep Record Straight
Authors: J. Flach
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article ACS Mobilizes Forces to Keep Record Straight Get access Jennifer Flach Jennifer Flach Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 14, 15 July 1992, Pages 1071–1073, https://doi.org/10.1093/jnci/84.14.1071 Published: 15 July 1992
Abstract 1430: Activation of WNT pathway in endometrial cancer stromal fibroblasts
Authors: John Palla, Olga Aprelikova, Xiang Yu, Simone John, Ming Yi, Robert Stevens, John Risinger, Amir Jazaeri, John Niederhuber
Journal: Cancer Research (2010)

Abstract The dynamic interactions between tumor cells and their corresponding microenvironment play an important role in carcinogenesis. Fibroblasts are a dominant feature within a tumor stroma and have undergone a “reprogramming” to become cancer-activated fibroblasts (CAFs). In our study we established primary cell cultures of fibroblasts from matched pairs of normal human endometrium and endometrial cancer tissues and analyzed the differential expressions of mRNA and microRNA. We found that the WNT pathway was activated in CAFs and confirmed these results via Topflash luciferase reporter assays. Wingless-type (WNT) proteins are a highly conserved family of secreted glycoproteins that have been implicated in the carcinogenesis of many cancers. We demonstrated that one of the reasons for this WNT pathway activation was the methylation-dependent silencing of the secreted frizzled-related protein 4 (SFRP4), an antagonist to the WNT signaling pathway. An additional reason for WNT pathway activation was found in the microRNA analysis. These experiments showed downregulation of miR-148a, which is a predicted regulator of the founder member of the WNT family, WNT1. We observed that CAFs have increased WNT1 protein expression in three of the five endometrial cancer CAFs. We confirmed that miR-148a directly targets WNT1 by cloning the WNT1 3'UTR into a luciferase reporter construct and showed that co-transfection with miR-148a results in a decrease of luciferase activity. When mutations to the miR-148a binding sites were introduced into the same luciferase reporter construct, the downregulation of luciferase activity by miR-148a was prevented. We conclude that the observed activation of the WNT pathway in endometrial cancer CAFs may be regulated by the miR-148a and contribute to the progression of the endometrial cancer tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1430.
The origins of vaccination: no inoculation, no vaccination
Authors: Arthur Boylston
Journal: Journal of the Royal Society of Medicine (2013)

Edward Jenner attempted to publish the Phipps experiment in a manuscript which was rejected by the Royal Society.1 Why would this august body turn down what we now regard as one of the most important discoveries ever made? Actually, the manuscript was a mess. Although Jenner gave short details of 10 patients who had resisted inoculation several years after having cowpox, Phipps was the only patient he had immunized with cowpox.2 One example was not enough to support replacing inoculation with smallpox with cowpox. When John Haygarth heard of the experiment he thought that it was potentially interesting but that one case provided insufficient evidence; 20 or 30 would be more convincing. The rest of Jenner’s paper consisted of speculations on the animal origin of cowpox; he thought that it was derived from a horse disease called ‘grease’. And he gave a rambling hypothesis that many human diseases were derived from animals and a very confusing observation that immunity seemed to work in only one direction. Cowpox prevented smallpox, but smallpox did not prevent cowpox. By rejecting the paper the Royal Society spared Jenner the criticism and derision that would have followed his weak evidence and unsupported ideas. They actually saved his reputation.
Staphylococcal Infections in an Obstetric Unit
Authors: Donald N. Wysham, Marie E. Mulhern, George C. Navarre, Gerald D. LaVeck, Alfred L. Kennan, W. R. Giedt
Journal: New England Journal of Medicine (1957)

EARLY in 1955, a major outbreak of staphylococcal infections occurred in a nursery in Seattle, Washington.1 This was the first such outbreak reported in this city since the advent of antibiotics. Subsequently, antibiotic-resistant staphylococcal infections of newborn infants and their mothers became a major and continuing problem, affecting the nurseries of nearly all hospitals in the city for varying periods. During a single month in 1956, 6 infant deaths are known to have occurred in this area, presumably as the result of staphylococcal infections acquired in nurseries.The extent of this problem was evaluated in a large general hospital in . . .
A Young Man With Progressive Language Difficulty and Early-Onset Dementia
Authors: Hugo Botha, Bradley F. Boeve, Lyell K. Jones, Joseph E. Parisi, James P. Klaas
Journal: JAMA Neurology (2016)

A man in his late 40s presented with cognitive decline characterized by gradually increasing difficulty expressing his thoughts and ideas. His family noted word-finding difficulty, especially with the names of people, but no problems with his memory for recent events. Initial workup findings were unremarkable, but during the course of the next decade left anterior temporal atrophy was noted on magnetic resonance imaging and the patient developed increasing reasoning difficulty, apathy, and disinhibition. Several degenerative causes were considered. The patient died 22 years after symptom onset, and the final diagnosis was confirmed at autopsy.
Evaluation des performances de l'écho endoscopie pancréatique dans l'indication opératoire des Tumeurs Intracanalaires Papillaires et Mucineuses du Pancréas
Authors: M Barraud, P Grandval, R Garcès, M Giovannini, O Turrini, G Monges, M Barthet, V Moutardier, S Garcia, JP Bernard, S Chopinet, M Ouaissi, J Del-Grande, R Giorgi, R Laugier
Journal: Endoscopy (2014)

Les Tumeurs Intracanalaires Papillaires et Mucineuses du Pancréas (TIPMP) sont des tumeurs kystiques prénéoplasiques qu'il faut dans certains cas surveiller jusqu'à l'apparition éventuelle de signes évocateurs de transformation cancéreuse. Le traitement est alors chirurgical mais il présente une lourde morbidité. Cette surveillance est effectuée grâce à une Imagerie par Résonnance magnétique (IRM) et/ou une écho endoscopie pancréatique (EEP) permettant de rechercher des critères de malignité. L'objectif de l'étude était d'évaluer les performances de l'EEP dans les critères d'indication chirurgicale à partir de l'analyse du compte rendu d'anatomie pathologique des pièces de pancréatectomie de TIPMP.
Leonard Andrew Scheele, M.D. 1907 - 1993
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Leonard Andrew Scheele, M.D. 1907 – 1993 Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 5, 3 March 1993, Pages 342–343, https://doi.org/10.1093/jnci/85.5.342 Published: 03 March 1993
Comparison of Three Immunosuppressive Regimens in Cadaver Renal Transplantation: Long-Term Cyclosporine, Short-Term Cyclosporine Followed by Azathioprine and Prednisolone, and Azathioprine and Prednisolone without Cyclosporine
Authors: Bruce M. Hall, David J. Tiller, Ian Hardie, John Mahony, Timothy Mathew, Geoffry Thatcher, Peter Miach, Napier Thomson, A.G. Ross Sheil
Journal: New England Journal of Medicine (1988)

We conducted a randomized trial in seven Australian hospitals of the efficacy and safety of three immunosuppressive regimens after first transplantation of a cadaver kidney: long-term cyclosporine, short-term (three months) cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine. Patients assigned to long-term cyclosporine (n = 138) or short-term cyclosporine followed by azathioprine and prednisolone (n = 141) had similar actuarial 12-month survival (98.4 vs. 96.4 percent) and graft survival (83.9 vs. 82.1 percent). Patients assigned to receive only azathioprine and prednisolone (n = 138), with optional use of antithymocyte globulin, had a significantly poorer survival rate (91.3 percent, P = 0.015) because of deaths from cardiac causes and infection, but their graft survival of 76.0 percent (P = 0.31) did not differ significantly from that of either group receiving cyclosporine. After the switch from cyclosporine to azathioprine and prednisolone, 15 percent of patients had reversible rejection episodes, but the frequency of rejection and graft loss did not differ from that in the long-term cyclosporine group. After the change to azathioprine and prednisolone, serum creatinine levels declined in nearly all patients, so that after three months they were comparable to those in the group receiving azathioprine and prednisolone only, and significantly lower than those in the group receiving long-term cyclosporine therapy (P<0.003). We conclude that the two cyclosporine regimens result in comparable patient and graft survival, but that changing to azathioprine and prednisolone at three months improves graft function. (N Engl J Med 1988; 318: 1499–507.)
THU0477-HPR Fatigue in psychosocial subgroups of patients with sjÖgren’s syndrome
Authors: N. van Leeuwen, E.R. Bossema, A.A. Kruize, H. Bootsma, J.W. Bijlsma, R. Geenen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fatigue is a prevalent and debilitating problem in the systemic autoimmune disorder Sjögren's syndrome. Psychosocial factors have been indicated to at least partly explain fatigue in this patient group. Insight into these factors and the relation of these factors with fatigue, will indicate the need for tailoring psychological interventions aimed at the reduction of fatigue to individual patients. <h3>Objectives</h3> To identify psychosocial subgroups of patients with Sjögren's syndrome and to examine differences in fatigue between these subgroups. <h3>Methods</h3> 300 patients with primary Sjögren's syndrome (mean age 56 years, 93% female) completed questionnaires on fatigue (MFI), physical activity cognitions (TAMPA-SK), illness cognitions (ICQ), cognitive emotion regulation (CERQ-short), coping strategies (Brief COPE), emotion processing and regulation (TAS-20, ERQ, BEQ), and social support (SSL, ABO). The psychosocial variables were summarized using principal axis factor analysis with oblimin rotation. Psychosocial subgroups were identified using hierarchical cluster analysis (Ward's method) and K-means cluster analysis. Subgroup differences in fatigue were examined with univariate analysis of variance. <h3>Results</h3> Factor analysis yielded eight psychosocial factors: kinesiophobia (KP, fear to exercise), negative thinking (NT), positive thinking (PT), positive disease outcome (PD), alexithymia (AT), emotional expressivity (EE), social support (SS), and spouse engagement (SE). Cluster analyses identified four psychosocial subgroups: 1) an adaptive profile (<i>n</i>=64) with positive scores on all dimensions; 2) a self-reliance profile (<i>n</i>=64), with neutral scores on all dimensions except adaptive scores on positive thinking and positive disease outcomes and maladaptive scores on spouse engagement; 3) a maladaptive profile (<i>n</i>=52), with negative scores on all dimensions except a neutral score on emotional expressivity; and 4) a cognitive reappraisal profile, with adaptive scores on cognitive factors and maladaptive scores on emotional factors. Subgroup 3 reported more fatigue than the other subgroups on four of five fatigue dimensions (<i>p</i>&lt;0.05), except physical fatigue compared to subgroup 2. The other subgroups did not differ from each other, with the exception of subgroup 2 reporting more mental fatigue, i.e. concentration and thought problems, than subgroup 4 (<i>p</i>&lt;0.05). <h3>Conclusions</h3> Patients with Sjögren's syndrome with a generalized maladaptive psychosocial profile experience more fatigue than patients with an adaptive, self-reliance or cognitive reappraisal profile. Thus, besides the identification of a single group with a generalized maladaptive profile, there is little support for tailoring fatigue interventions on the basis of psychosocial risk profiles. <i>Supported by the Dutch Arthritis Association.</i> <h3>Disclosure of Interest</h3> None Declared
Urinary Hydroxyproline and Calcium Metabolism in Patients with Cancer
Authors: Gianni Bonadonna, Mario J. Merlino, W. P. Laird Myers, Martin Sonenberg
Journal: New England Journal of Medicine (1966)

IN the past few years an increasing interest has developed in the determination of urinary hydroxyproline as an index of the metabolism and turnover of collagen. Recent experimental1 , 2 and clinical studies3 4 5 6 7 8 9 10 11 12 13 14 15 16 performed in normal as well as in many endocrine, metabolic and bone diseases have indicated that bone collagen is the major source of this amino acid in urine. The present investigation was undertaken to study the excretion of total urinary hydroxyproline in patients with inoperable or widespread carcinoma, especially those with bone metastases or hypercalcemia or both. Our specific aim was to observe what relation exists between urinary excretion . . .
Visualization of Discrete Sacral Foramina as an Ancillary Sign of Superscan
Authors: Leeanne K. Harshman, Hamid R. Latifi, Landis K. Griffeth
Journal: Clinical Nuclear Medicine (2010)

Objectives: The purpose of this study was to determine if visualization of discrete sacral foramina on bone scintigraphy can be used as an adjunct criterion supportive of a superscan diagnosis. Methods: The Radiology Information System at our institution was queried for all bone scintigraphy reports, during July 1999 to July 2009, containing the words/phrases: normal bone scan, normal bone scintigraphy, superscan, or diffuse osseous metastatic disease. The final study group consisted of 22 normal studies and 8 superscans. All studies were reviewed by 2 nuclear medicine physicians who rated the examinations on a numeric scale of bone-to-soft tissue activity, whether they would classify the study as a superscan (based on previously published criteria), whether sacral foramina were visualized, and, if so, how many? Results: Of the 22 normal studies, no distinct sacral foramen was visualized in 17 cases. Of the 8 superscan patients, 1 patient demonstrated 8 foramina, 4 patients demonstrated 4 foramina, 1 patient demonstrated 3 foramina, and 2 patients demonstrated none. There was a statistically significant difference between the normal and superscan groups (P < 0.0017). Based on statistical analysis, it was determined that visualizing at least 3 distinct sacral foramina could be used as an ancillary finding to support the diagnosis of superscan. Conclusions: The ability to clearly visualize at least 3 sacral foramina is a statistically significant finding that may be useful as an ancillary criterion to differentiate normal bone scintigraphy from a superscan.
A6.30 Activation of inflammasome correlating with the presence of non-degraded cell-free DNA in the peripheral blood and the salivary glands of patients with severe primary SjÖgren’s syndrome
Authors: AG Vakrakou, S Boiu, A Papadopoulou, E Kanavakis, MN Manoussakis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Inflammasomes are intracellular multiprotein complexes that sense pathogenic microorganisms, as well as DNA and other molecules released after tissue injury. Such activation of inflammasome leads to the upregulation of various inflammasome-related molecules and the release of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. We have recently shown that patients with primary Sjögren's syndrome (SS) manifest increased serum levels of circulating nucleosomes and cell-free genomic DNA (CF-DNA) owing to impaired DNA degradation. Herein, we assessed whether the inflammasome is activated in the peripheral blood and salivary glands (SG) of SS patients and whether serum CF-DNA represents a novel IL-1β stimulating agent. <h3>Materials and methods</h3> The mRNA expression of inflammasome-related molecules ASC, NLRP3, AIM2 and IL-1β were evaluated by RT-PCR in PBMC (15 SS, 9 non-SS-controls). Sera were studied for the levels of circulating CF-DNA (by RT-PCR; 8 SS and 5 non-SS-controls) and ASC protein (by ELISA; 39 SS, 21 non-SS-controls). SG biopsies were examined by confocal microscopy for the presence of CF-DNA (anti-dsDNA/TO-PRO-3/membranous-WAG immunostaining; 3 SS, 2 non-SS-controls) and the expression of ASC protein (15 SS, 5 non-SS-controls). To evaluate the immunostimulatory capacity of CF-DNA, healthy PBMC were treated with 5 SS sera-derived CF-DNA and IL-1β produced was measured by ELISA. <h3>Results</h3> Significantly high mRNA expression of ASC, IL-1β, NLRP-3 was detected in the PBMC of SS patients (all for p &lt; 0.05, vs. controls), with ASC highly positively correlating with disease activity scores (ESSDAI; p = 0.007). SS patients manifested high serum levels of ASC protein (p &lt; 0.0001, vs. controls) that were particularly high among SS patients who had developed lymphoma (p = 0.009). High serum levels of CF-DNA were also detected in SS patients (p &lt; 0.05, vs. controls) that correlated positively with serum levels of ASC (r = 0.654, p = 0.015). The SG specimens of SS patients (but not non-SS-controls) manifested ample evidence of CF-DNA, as well as strong ASC protein expression by both epithelial and infiltrating cells, mainly CD68<sup>+</sup> macrophages. The serum CF-DNA of SS patients induced high IL-1β secretion by healthy PBMC (8-fold induction over mock-treated cells). <h3>Conclusions</h3> SS patients manifest evidence of chronic inflammasome activation in the peripheral blood and the salivary glands, likely due to the presence of lingering non-degraded CF-DNA. As supported by its correlation with disease activity and lymphoma development, inflammasome activation in SS patients likely participates in the pathogenesis of the adverse clinical outcomes of the disorder and may specify novel disease biomarkers.