tbuckley/cabot-search huggingface dataset:
S45 Clinical efficacy of seasonal influenza vaccination in adults with cystic fibrosis
Authors: W. G. Flight, K. J. Mutton, A. K. Webb, R. J. Bright-Thomas, A. M. Jones
Journal: Thorax (2011)

<h3>Introduction</h3> Influenza vaccination produces an adequate serological response in adults with cystic fibrosis (CF)1 and is a recommended part of routine CF care. There is little evidence to date, however, of a clinical benefit from influenza vaccination in this patient group. We compared prospectively the rate of influenza infection with vaccination status among 100 adults with CF over the 2010/2011 UK influenza season. <h3>Methods</h3> 100 adults with CF were enrolled in a prospective observational study of respiratory viruses between December 2010 and March 2011. Sputum, nose- and throat-swabs for PCR-based virological analysis were sent every 2 months and additionally at onset of acute respiratory illness through to June 2011. Prior to enrolment, sputum was sent for virology at onset of pulmonary exacerbations as part of routine care. Details of influenza vaccination status were obtained from the CF centre9s database and GP records. Previous infection with influenza A/H1N1 was determined from clinical records. <h3>Results</h3> Patients had a median age of 28 years (range 18–62). 88% had received the 2010/2011 seasonal influenza vaccine (A/California/7/2009/H1N1, A/Perth/16/2009/H3N2 &amp; B/Brisbane/60/2008). 44% of the cohort had received the 2009 monovalent swine-origin influenza A/H1N1 vaccine and 8 patients had previously had PCR-confirmed swine-origin influenza. Over the study period there were 10 cases of influenza: 5 influenza A/H1N1, 4 influenza B and 1 dual influenza A/B infection. Among patients who received the 2010/2011 seasonal vaccine, 9/88 (10.2%) suffered influenza compared with 1/12 (8.3%) of those who had not been vaccinated (OR 1.25; 95% CI 0.14 to 10.9). All 9/9 patients who developed influenza despite being vaccinated were homozygous for the F508del mutation compared with 43/79 (55.7%) of vaccinated patients who did not develop influenza (p=0.009). No significant difference was seen between these groups with regard to age, gender, BMI, lung function, diabetes mellitus or use of oral corticosteroids. <h3>Conclusions</h3> Influenza vaccination may have limited clinical efficacy in adults with CF. The influence of CF genotype on susceptibility to influenza infection and response to vaccination requires further investigation.
Neural Tuberculosis Detected by F-18 FDG Positron Emission Tomography
Authors: F J Braga, A Maes, P Vanteenkiste, P Flamen, W Peetermans, L Mortelmans
Journal: Clinical Nuclear Medicine (2001)

JOSÉ H. N. BRAGA, FRANCISCO M.D., Ph.D.,*; MAES, ALEX M.D., Ph.D.,*; VANTEENKISTE, PETER M.D.,*; FLAMEN, PATRICK M.D.,*; PEETERMANS, WILLY M.D., Ph.D.†; MORTELMANS, LUC M.D., Ph.D.* Author Information
P17.73 * IN VITRO ANALYSIS OF CYTOTOXIC EFFECTS OF BRIVARACETAM AND LACOSAMIDE ON HUMAN GLIOBLASTOMA CELLS
Authors: A. Rizzo, V. Girgenti, C. Vasco, F. Zucchetti, C. Calatozzolo, A. Salmaggi, G. Blandino, S. Donzelli, M. Maschio, E. Ciusani
Journal: Neuro-Oncology (2014)

RATIONAL AND AIMS: Epilepsy is a frequent side effect in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patient are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of drug-resistant epilepsy affected patients suggesting their involvement in the clearance of antiepileptic medications. In addition to the action anticonvulsant drugs has been documented for some a possible cytotoxic effect. METHODS: The in vitro effects of two new generation antiepileptic drugs, Brivaracetam and Lacosamide, were evaluated on two lines of human glioblastoma (A172 and U87). RESULTS: The results show a cytotoxic effect of Brivaracetam and Lacosamide on the cell line U87. However, the cytotoxic mechanism does not appear to be related to apoptosis, evaluated by annexin V binding. Moreover, by flow cytometric analysis, we observed that exposure of the two cell lines to Brivaracetam or Lacosamide at their IC30 does not contribute to the modulation of the chemoresistance molecules MRP1, MRP3, MRP5, GSTπ and P-Gp. Similar results were obtained by evaluating the modulation of the same molecules on human umbilical vein endothelial cells (HUVEC) after exposure to the two drugs. CONCLUSIONS: The data obtained suggest that Brivaracetam and Lacosamide in vitro play a cytotoxic effect on human glioma cells.
EFFICACY OF FIBRATES OR OMEGA-3 FATTY ACIDS ADDED TO STATIN THERAPY IN ACUTE MYOCARDIAL INFARCTION PATIENTS
Authors: Seung-Woon Rha, Min Shim, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Dong Joo Oh, Myung Ho Jeong
Journal: Journal of the American College of Cardiology (2016)
Abstract 173: Frequent concomitant epigenetic silencing of the <i>SFRPs</i> and <i>SOX1</i>, Wnt/β-catenin regulators, in human hepatocellular carcinoma
Authors: Ya-Wen Lin, Chung-Bao Hsieh, Yu-Lueng Shih, Tsai-Yuan Hsieh, Chun-Ming Tsao, Ming-De Yan
Journal: Cancer Research (2010)

Abstract Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications for carcinogenesis. Recently, we have shown that SFRPs are frequently downregulated through promoter hypermethylation in HCC cell lines and clinical HCC tissues. Furthermore, we have demonstrated that restoration of SFRPs could attenuate Wnt signaling in HCC cells with β-catenin point mutation, decrease abnormal accumulation of free β-catenin in the nucleus, and then suppress cell growth. Sox1 encodes a transcription factor involved in the regulation of embryonic development and cell fate determination. Structurally related to TCF/LEFs, several members of the Sox family, including Sox17, Sox3, Sox7, and Sox9, have also been implicated in repressing β-catenin activity by a mechanism that is not well understood. In this study, we found that the Sox1 was severely down-regulated by quantitative reverse transcription polymerase chain reaction (QRT-PCR). Next, we employed bisulfite modification and methylation-specific PCR (MS-PCR) to analyze the feature of Sox1 promoter methylation in the HCC cell lines and found that the majority of the tested cell lines exhibited hypermethylation. Meanwhile, we also examined sixty primary HCC surgical samples and adjacent nonturmorous liver tissues from Taiwan Liver Cancer Network (TLCN). These results showed that aberrant promoter methylation of SOX1 were found in 32 of 60 HCCs (53.3%), in 13 of 50 cirrhotic livers (26%), and in one of 30 normal control tissues (3.3%). Concomitantly, SFRPs was epigenetically inactivated in HCC cell lines and most of all the tumors with methylated SOX1. A significant correlation between the methylation of both genes was found (p &amp;gt;0.05). Furthermore, overexpression of SOX-1 in HCC cells could suppress TCF-dependent transcriptional activity and suppress colony formation. Taken together, our data suggest that SOX1 is a negative modulator of Wnt/β-catenin signaling, and that SOX1 silencing due to promoter hypermethylation is an early event during tumorigenesis and may contribute to aberrant activation of Wnt signaling in HCC. 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 173.
Is There Any Difference in Overall Response Rate According to Kras Mutation in Advanced Colorectal Cancer (Acrc)?
Authors: Jose Rivadeneira, Antonio Viudez, David Guerrero, Irene Hernandez, Maria Gomez Dorronsoro, Marta Montes, Juan Verdun, Antonio Tarifa, Javier Suarez, Angela Fernandez De Lascoiti, Miguel CIGA Lozano, Ruth Vera
Journal: Annals of Oncology (2013)
P17.89 * EFFECTS OF GLIOBLASTOMA FIRST-LINE TRIALS ON TIME DELAY TO INITIATION OF TREATMENT, SIGNS OF EARLY TUMOR PROGRESSION AND PROGRESSION-FREE SURVIVAL
Authors: D. Sefranek, C. Wendl, M. Hutterer, P. Hau, M. Uhl
Journal: Neuro-Oncology (2014)

Randomized clinical trials based on molecular markers such as MGMT promoter methylation are pivotal to further develop the field of medical therapies in neuro-oncology. However, shipping of material and central review of histology and molecular markers significantly delay treatment start in patients with glioblastoma. To evaluate a possible treatment disadvantage for patients in clinical trials, we performed a retrospective analysis of 3 prospective Phase II and III clinical trials for the treatment of patients with high-grade gliomas in first-line therapy. In this study we examined 23 patients we enrolled during the last 3 years into controlled prospective multicenter European glioblastoma treatment trials for the incidence of an early MRI progression. Pre- and post-surgery MRI, baseline MRI, follow-up MRI, date of operation, date of progression and overall survival were collected for 23 patients, 22 of them with glioblastoma and 1 with gliosarcoma. Early MRI progression was evaluated based on the RANO criteria by 2 independent neuroradiologists and stratified into "no", "unlikely", "possible" and "definite" progression, based on new contrast enhancement distant from the resection site, nodular and eccentric contrast enhancement at the resection site or a combination of both. Progression-free survival (PFS) was defined as the time from resection to treatment failure during first-line therapy, and overall survival (OS) as time from resection to death. We observed a profound delay between resection and treatment start if patients were treated within trials with central histology and molecular marker evaluation with a mean of 30.2 days between surgery and baseline examination. At baseline MRI, 56% of patients had "definite" signs of early progression, whereas 26% had "no" signs of early progression. The 6 patients with "no" signs of early progression had a mean time delay between surgery and study inclusion of 28.3 days, which was not significantly different from the 30.5 days in the group of 13 patients with "definite" signs of early progression (p = 0.210; Mann-Whitney test). However, regarding the PFS of both groups we found a significant difference in favor of the group with “no” early progression signs (“no” signs of early progression: PFS = 188 days, 95% CI (120-255) and “definite” signs of early progression: PFS = 403 days, 95% CI (281-526); p = 0.018; log rank test). In this small pilot dataset, we cannot support a correlation between time delay to treatment and signs of early tumor progression. However, we observe a statistically significant correlation between signs of early tumor progression at baseline MRI and PFS. We plan to expand this analysis to support the hypothesis that a delayed treatment initiation leads to early tumor progression, which negatively influences progression-free survival.
Case 7-2013
Authors: Anne Louise Oaklander, Donlin M. Long, Mykol Larvie, Christian J. Davidson
Journal: New England Journal of Medicine (2013)

A 77-year-old woman sought neurosurgical and neurologic consultation because of a long history of left thoracic pain, for which no cause or effective treatment had been found. Review of imaging studies revealed multiple perineurial cysts in the thoracic spine.
SP0111 The Resolution-Phase Macrophage
Authors: D. Gilroy
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Inflammation is a primordial response to infection and injury that seeks to neutralise and eliminate foreign organisms and/or material. Thus, inflammation is no trivial event. Life depends upon it. In general, the innate inflammatory response initiates within minutes and resolves within hours. Chronic inflammation, on the other hand, persists for weeks, months or even years and, unlike the acute response, is the side of host immunity we need to avoid. Notwithstanding, dispersed among this black and white view of inflammation are shades of grey. We are constantly reminded that defining inflammation is not so easy and that while acute inflammation can resolve, it can also be recurrent and that, over time, chronic inflammation can also resolve or persist with devastating consequences to the host. In this presentation, one of these many aspects of the inflammatory response – how acute inflammation resolves and the role of macrophages in this process will be discussed. I will present new data on so-called resolution-phase macrophages, describe their phenotype in the context of conventional nomenclature and speculate on their function in resolution and homeostasis. <h3>Disclosure of Interest</h3> None Declared
Nerve Glucose, Fructose, Sorbitol,<i>myo</i>-Inositol, and Fiber Degeneration and Regeneration in Diabetic Neuropathy
Authors: Peter James Dyck, Bruce R. Zimmerman, Todd H. Vilen, Sharon R. Minnerath, Jeannine L. Karnes, Jeffrey K. Yao, Joseph F. Poduslo
Journal: New England Journal of Medicine (1988)

We measured the alcohol sugars in sural nerves from 11 controls, 21 conventionally treated patients with diabetes and neuropathy, and 4 diabetics without neuropathy. The results were related to metabolic control and to clinical, neuropathological, and morphometric abnormalities in the nerves. The mean endoneurial glucose, fructose, and sorbitol values were higher in diabetic patients than in controls. Linear regression analysis revealed that nerve sorbitol content in the diabetics was inversely related to the number of myelinated fibers (P = 0.003). Mean nerve levels of myo-inositol were not decreased in the diabetic patients, with or without neuropathy, and were not associated with any of the neuropathological end points of diabetes. Our results indicate that myo-inositol deficiency is not part of the pathogenesis of human diabetic neuropathy, as had been hypothesized. Other accumulated alcohol sugars, however, were increased in diabetes and were associated with the severity of neuropathy. On repeat biopsy, six diabetics, treated for a year with the aldose reductase inhibitor sorbinil, had decreased endoneurial levels of sorbitol (P<0.01) and fructose (0.05<P<0.1), but unchanged levels of myo-inositol. (N Engl J Med 1988; 319:542–8.)
Hereditary Occurrence of Cystic Disease of the Renal Medulla
Authors: Sidney H. Goldman, Samuel R. Walker, Thomas C. Merigan, Kenneth D. Gardner, Joan M. C. Bull
Journal: New England Journal of Medicine (1966)

CYSTIC disease of the renal medulla is an infrequently recognized disease of the human kidney. Strauss1 was able to collect 18 cases from the literature and his personal files, and he presented a review of this condition in 1962. The paucity of cases has not permitted a study of the hereditary aspects of this condition. There is suggestive published evidence that a genetic influence may participate in its development.1 2 3 4 5 In December, 1964, a thirty-three-year-old man was admitted to the Stanford Medical Center. He was in the end stages of renal failure. A family history revealed that 2 of his brothers, . . .
Prevalence and Clinical Outcome of Mitral-Valve Prolapse
Authors: Lisa A. Freed, Daniel Levy, Robert A. Levine, Martin G. Larson, Jane C. Evans, Deborah L. Fuller, Birgitta Lehman, Emelia J. Benjamin
Journal: New England Journal of Medicine (1999)

Mitral-valve prolapse has been described as a common disease with frequent complications. To determine the prevalence of mitral-valve prolapse in the general population, as diagnosed with the use of current two-dimensional echocardiographic criteria, we examined the echocardiograms of 1845 women and 1646 men (mean [±SD] age, 54.7±10.0 years) who participated in the fifth examination of the offspring cohort of the Framingham Heart Study.
Scientific Method and Scientific Attitude
Authors: Jerome M. Schneck
Journal: JAMA (1966)

To the Editor:—  Two statements especially attracted my attention in the editorial, Medicine And  Behavioral Sciences ( 194 :1242, 1965).  first is, The student who engages in research may learn the almost mystical `scientific method.'   second is, ... experimental science is not the only field in which `scientific method' can be learned, nor is it even necessarily the best. I cannot be sure whether the author's use of quotation marks indicates his skepticism about the term scientific method or whether the intention is simply to emphasize it. It is possible that he may share my opinion which I may state as one of doubt about the existence of a scientific method.  I should be more inclined to think in terms of scientific attitude. This may be defined in many ways, and one suitable description may be an attitude of curiosity about new facts and phenomena and their interrelationships. A
Abstract 5060: Discrepancy between MMP-9 and its fibronectin-like domain in tumor growth and invasion.
Authors: Cynthia Dayer
Journal: Cancer Research (2013)

Abstract Tumors are often compared to wounds that do not heal, where the crosstalk between tumor cells and their surrounding stroma is crucial at all stages of development from the initial primary growth to metastasis. Similar to wound healing, fibroblasts in the tumor stroma differentiate into myofibroblasts, also referred to as “cancer-associated fibroblasts” (CAFs), primarily, but not exclusively, in response to transforming growth factor-β (TGF-β). Myofibroblasts in turn enhance tumor progression by remodeling the stroma. Among molecules implicated in stromal remodeling, matrix metalloproteinases (MMPs), and MMP-9 in particular, play a prominent role. However, the mechanisms that regulate MMP-9 activation and function remain poorly understood. Recent evidence indicates that tumor cell surface association of MMP-9 is an important event in its activation, and more generally in tumor growth and invasion. Based on these observations, we addressed the potential association of MMP-9 activity with cell-surface recruitment on human fibroblasts. We show for the first time that recruitment of MMP-9 to the MRC5 fibroblast cell surface occurs through the fibronectin-like (FN) domain, found only in MMP-9 and MMP-2. Functional assays suggest that the active form of MMP-9 triggers α-smooth muscle actin (αSMA) expression in resting fibroblasts that reflects myofibroblast differentiation, possibly through TGF-β activation. Xenograft experiments using HT1080 fibrosarcoma or MDA-MD231 breast adenocarcinoma cells stably expressing the FN domain of MMP-9 in NOD/SCID mice revealed no changes in primary tumor growth. However, in the context of metastasis, expression of the FN domain by these same tumor cells dramatically increases their metastatic proclivity whereas expression of wt MMP-9 either promotes no change or actually reduces the number of metastases. Curiously, xenografts of SW480 colorectal adenocarcinoma cells stably expressing the FN domain of MMP-9 display reduced growth at both the primary (subcutaneous) injection site and the lungs, in experimental metastasis assays, of NOD/SCID mice. This discrepancy is believed to be due to the FN domain that may modulate MMP-9 activity and TGF-β activation in different ways, depending on the tumor cell type. These observations suggest a dual role of MMP-9 and its FN domain in primary tumor growth and metastasis, underscoring the notion that the effect of MMP-9 on tumor cells may depend on their response to TGF-β activation and highlighting possible protective effects of MMPs in tumor progression and invasion. Citation Format: Cynthia Dayer. Discrepancy between MMP-9 and its fibronectin-like domain in tumor growth and invasion. [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 5060. doi:10.1158/1538-7445.AM2013-5060
Examination of the Retina
Authors: Vanessa Y Ng, Shannon M Mentock, Allison B Brantley
Journal: New England Journal of Medicine (2015)

Indications The retinal examination is part of a complete physical examination. It is particularly important in patients with a history of such systemic diseases as diabetes, hypertension, and atherosclerosis. Patients with the human immunodeficiency virus (HIV) or the acquired immunodeficiency syndrome (AIDS) are also at increased risk for retinal diseases. Evaluation of the retina may reveal the initial signs of diabetic retinopathy, hypertensive retinopathy, macular edema, glaucoma, or macular degeneration. Diagnosis and appropriate interventions can help preserve sight and prevent disease progression. 2 Indications for urgent direct ophthalmoscopy include a clinical suspicion of increased intracranial pressure, occluded retinal vessels, and retinal detachment. Any of these conditions, or the sudden loss of vision or a change in vision, constitutes an ophthalmic emergency. The patient should be seen by an ophthalmologist immediately or should be sent to the emergency department. Anatomy The inner structures of the eye can be visualized through the pupil, the central opening in the iris. The light rays from the ophthalmoscope pass through the cornea, pupil, and lens to focus on the retina, producing an upright, magnified image. The retina is located on the inner surface of the globe, opposite the pupillary opening. The color should appear red, orange, or brown and varies from person to person. Direct Ophthalmoscopic Settings The direct ophthalmoscope consists of a handle, which contains the power supply and a light source, and a head, which contains the viewing window and lenses. The on–off switch adjusts the brightness of the light. The apertures include a large circle, a medium circle, a small circle, and a slit beam. To reduce the patient’s pupillary constriction it is best to use the ophthalmoscope at a brightness level of 80 to 90%, with the aperture set to the small or medium circle. The ophthalmoscope contains a range of lenses with positive and negative diopters that compensate for refractive error on the part of the examiner and the patient. If the patient has hyperopia, the retina will be closer to the pupil than normal. If the patient has myopia, the retina will be farther away from the pupil