tbuckley/cabot-search huggingface dataset:
O5.06 * CYSTIC CRANIOPHARYNGIOMAS: MICROSURGICAL OR STEREOTACTIC TREATMENT?
Authors: W. Rachinger, M. Kunz, N. Thon, J. C. Tonn, F. W. Kreth
Journal: Neuro-Oncology (2014)

OBJECTIVE: The value of microsurgical and stereotactic treatment particularly in cystic craniopharyngiomas is poorly defined. We present outcome data in terms of functional results and progression free survival (PFS) after individualized treatment strategies: Solid tumors were considered eligible for open tumor resection, whereas predominantly cystic lesions were treated by stereotactic catheter placement for internal drainage. The target point for catheter implantation was the prepontine cisterne thereby enabling drainage in both directions the ventricular space (upstream) and the prepontine cisterne (downstream). METHODS: Patients with craniopharyngioma treated between 2001 and 2010 either by open tumor resection or stereotactic drainage were analyzed retrospectively. Reference point of the study was the date of surgical treatment. PFS was estimated with the Kaplan Meier method; prognostic factors were obtained from multivariate regression models including all relevant patient-, radiological-, and functional-related data. Adjuvant radiation therapy was used as second line treatment in case of unresectable recurrences. RESULTS: 68 consecutively treated patients (median age: 53 years) were included. Patients of the microsurgical (N = 44) and stereotactic group (N = 24) did not differ in terms of age, gender, tumor size, functional deficits, and duration of symptoms. Complete tumor resection and complete cyst drainage was obtained in 23/44 and 21/24 patients, respectively. Median PFS after surgical and stereotactic treatment was 51 months and 46 months, respectively (p = 0.1). Endocrinological outcome was significantly better after stereotactic treatment (p = 0.004). The overall transient complication rate was 4.4 % being lower in the stereotactic group (8.1 % vs. 0 %, p < 0.05). However, one patient of the stereotactic group experienced a haemorrhage leading to permanent morbidity (overall permanent morbidity rate: 1.5 %). CONCLUSIONS: For cystic craniopharyngiomas, stereotactic treatment (internal shunt) is safe and effective with very good preservation of the endocrinological function. This hypothesis requires further investigation in the framework of a prospective randomized study.
AB1012 The efficacy and safety of ibandronate in patients with osteoporosis – importance of risk factors and fractures
Authors: B.N. Stamenkovic, S.D. Bozilov, A.M. Stankovic, A.N. Dimic, J.M. Nedovic, S.K. Stojanovic, S.B. Milenkovic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Treatment of osteoporosis may be expected to affect the remodelling phase of bone repair and therefore promote fracture healing. Ibandronat significantly increase bone mineral density (BMD) and reduce the risk of vertebral, hip and non vertebral fractures in women with postmenopausal osteoporosis <h3>Objectives</h3> To confirm the efficacy and safety of 1 year ibandronate in OP pts: 150mg oral monthly or quarterly intravenously; to analyze the impact of risk factors and fractures on the efficacy of ibandronate treatment <h3>Methods</h3> 190 pts with primary OP,average 62.1y, average menopause 16.8y, treated 1 year with oral monthly or quarterly iv injection of ibandronate were included. BMD was measured by DXA Hologic at lumbar spine and proximal femur; OP is defined as the mean BMD expressed as a T-score &lt;-2.5 and&gt; = -5.0. The profil RTG of TH-LS spine was done before and after the therapy. Substitution of the optimal dose of vitamin D and calcium was applied. <h3>Results</h3> Previous fracture (37.6%)and smoking (33.5%) were the most common risk factors;75.1% pts had OP and more than one risk factor. Total number of vertebral and nonvertebral fractures at baseline was 71; 25 vertebral, 46 nonvertebral.After therapy, the number of new fractures was 18; 8 vertebral, 10 nonvertebral. After 1 year of oral monthly ibandronate BMD was increased at the spine for 3.0%,hip 3.5%,after ibandronate injection spine BMD was increased for 4.6%, hip 3.6%. Spine and hip BMD increase was higher in pts with OP and multiple risk factors (spine, p=0.000, hip, p=0.01)than those with one risk factor (spine, p=0.04; hip, p=0.02). Pts with multiple fractures and OP had a greater increase in spine and hipBMD(spine, p=0.000; hip, p=0.001) compared to those with 1 or without fracture (spine, p=0.04; hip, p=0.05). Pts with OP and previous BF treatment had no sign. BMD increase at the spine (p=0.334), nor on the hip (p=0.2)opposed to those not previously treated, with statistically sign. BMD increasing(spine, p=0.000, hip, p=0.006). Adverse events were rare,did not lead to stopped the treatment:7.8%pts had a flu like sy,1.1% LS pain,1.1% SVPT, stopped after medical therapy <h3>Conclusions</h3> Ibandronate is effective,safe drug, orally applied monthly or quarterly iv. in OP pts, especially those with multiple risk factors and multiple fractures <h3>Disclosure of Interest</h3> None Declared
An Epidemic of<i>Shigella sonnei</i>Dysentery Arising in a General Hospital
Authors: N. Joel Ehrenkranz, Michael J. Takos, Warren R. Hoffert, Florence Riemer
Journal: New England Journal of Medicine (1958)

SHIGELLA epidemics occurring in hospitals are sufficiently uncommon to justify the reporting of such an episode. The present report deals with an epidemiologic investigation of an outbreak of Shigella sonnei dysentery primarily involving personnel in a general hospital.Description of the EpidemicBetween July 9 and 14, 1957, there was an explosive outbreak of gastroenteritis involving approximately 80 persons at the Jackson Memorial Hospital of Miami, Florida. The majority of persons affected were hospital employees (Table 1). Gastrointestinal symptoms developed in 78 persons in the hospital community during the week of July 8. Eleven were patients previously hospitalized for another . . .
A9.7 Loss of PTEN in Myeloid Cells Controls Inflammatory Bone Destruction by Regulating the Osteoclastogenic Potential of Myeloid Cells
Authors: Stephan Blüml, Gernot Schabbauer, Martin Friedrich, Antonia Puchner, Victoria Saferding, Emine Sahin, Tobias Lohmeyer, Birgit Niederreiter, Josef Smolen, Kurt Redlich
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Local bone destruction in rheumatoid arthritis, psoriasis arthritis or ankylosing spondylitis is a serious health burden and the major cause of disability and severely reduced quality of life in these diseases. This damage to the bony structures is exclusively mediated by a special cell type, the osteoclast (OC). Therefore, it is important to understand factors and pathways regulating the generation of OCs under inflammatory conditions. As PTEN is a lipid phosphatase and one of the main antagonists of the PI3-kinase, we analysed the impact of the PI3-Kinase/PTEN axis on OC generation and bone biology in an animal model of inflammatory bone loss. <h3>Methods</h3> We induced osteoclastogenesis in wt and PTEN deficient bone marrow cells and measured the generation of OCs, their resorptive capacity and induction of OC differentiation markers in vitro. Moreover, we analysed mice with a monocyte/macrophage-specific deletion of PTEN (myeloid specific PTEN<sup>-/-</sup>) by bone histomorphometry and crossed these mice into hTNFtg animals. <h3>Results</h3> We show that myeloid specific PTEN<sup>-/-</sup> mice have increased osteoclastogenesis in vitro and in vivo when compared to wild-type animals. However, under non-inflammatory conditions, enhanced osteoclastogenesis did not result in systemic bone loss in vivo. However, when we crossed myeloid specific PTEN<sup>-/-</sup> into hTNFtg mice we found significantly decreased grip strength scores in myeloid specific PTEN<sup>-/-</sup>/hTNFtg mice compared to wt hTNFtg mice. Joint swelling scores, however, were not different between both groups. In line, myeloid specific PTEN<sup>-/-</sup>/hTNFtg mice displayed enhanced local bone destruction as well as OC formation in the inflamed joints, whereas the extent of synovial inflammation was not different between the groups. Analysis of the synovial membranes of wt and myeloid specific PTEN<sup>-/-</sup> animals revealed similar relative compositions of the cellular infiltrate including macrophages, which serve as OC precursors. This suggests that increased capacity for osteoclastogenic differentiation rather than enhanced recruitment of precursor cells is responsible for the enhanced local generation of OCs. <h3>Conclusions</h3> Taken together, these data demonstrate that sustained PI3-Kinase activity in myeloid cells specifically elevated the osteoclastogenic potential of these cells, leading to enhanced inflammatory local bone destruction. Therefore, targeting the PI3-Kinase pathway therapeutically may be especially useful for the prevention of structural joint damage.
Effect of HMG-CoA Reductase Inhibitors on Coronary Artery Disease as Assessed by Electron-Beam Computed Tomography
Authors: Tracy Q. Callister, Paolo Raggi, Bruce Cooil, Nicholas J. Lippolis, Donald J. Russo
Journal: New England Journal of Medicine (1998)

Angiographic studies of the regression of coronary artery disease are invasive and costly, and they permit only limited assessment of changes in the extent of atherosclerotic disease. Electron-beam computed tomography (CT) is noninvasive and inexpensive. The entire coronary-artery tree can be studied during a single imaging session, and the volume of coronary calcification as quantified with this technique correlates closely with the total burden of atherosclerotic plaque.
P40 Change in Rectus Femoris Cross Sectional Area (RFcsa) Following an Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD): Abstract P40 Table 1
Authors: S Mandal, E Suh, B Connolly, M Ramsay, Z Puthucheary, J Moxham, N Hart
Journal: Thorax (2012)

<h3>Introduction</h3> Ultrasound (US) is a useful tool in measuring RFcsa. We have previously shown that a curvilinear ultrasound probe (CUP) is equally effective as a linear ultrasound probe in measuring RFcsa (Mandal et al 2011). We therefore used a CUP-US to characterise the trajectory of muscle loss in a cohort of patients with AECOPD. <h3>Methods</h3> Subjects had RFcsa measured at 3/5 of the distance from the anterior superior iliac spine to the superior border of the patella during a hospital admission with AECOPD and at 4 weeks post hospital discharge. Image acquisition was made using real time B-mode ultrasonography using a 2–5MHz curvilinear probe (<i>SonoSite Inc, Japan</i>). RFcsa measurements were calculated offline using the Image J® programme. Subjects also wore an Actiwatch Spectrum device (<i>Phillips Respironics, Murrysville, Pennsylvania</i>) to monitor physical activity levels during exacerbation and recovery. <h3>Results</h3> 10 patients were recruited. 40% were male with an age of 71±11years and FEV1 0.6±0.12L (on admission). RFcsa at admission was 519±359mm2. Mean change in RFcsa between admission and follow up was -90±295mm2 (19.5%). Subjects were divided in to 2 groups based on a 10% reduction in RFcsa (see table 1). Small numbers of patients prevented statistical analysis of the data. However, patients with ≥10% RFcsa loss tended to be older, had a lower BMI and longer length of hospital stay. At discharge this group of patients had lower daily physical activity count and greater time spent immobile. Both groups increased their daily activity count and decreased their immobile time between discharge and follow-up. However, those with preserved RFcsa tended to increase their activity count more than those with RFcsa wasting (table 1). <h3>Discussion</h3> These data suggest RFcsa muscle wasting as a consequence of an AECOPD was more common in older patients with a lower BMI. These patients tended to have a longer hospital stay with lower activity levels both during and immediately after an AECOPD However, more patients are required to confirm these initial observations.
Abstract 2954: The transient receptor potential V6 (TRPV6) calcium channel in breast cancer cell lines and clinical breast cancer tissues
Authors: Amelia Peters, Peter Simpson, Jonathon Bassett, Sunil Lakhani, Sarah Roberts-Thomson, Gregory Monteith
Journal: Cancer Research (2011)

Abstract TRPV6 is an important calcium channel, which is highly selective for Ca2+ and has high basal activity. In prostate tumors TRPV6 over-expression is linked to enhanced invasiveness and proliferation. While some studies have demonstrated that TRPV6 is over-expressed in clinical breast cancer samples and studies from our laboratory have shown that TRPV6 mRNA is up-regulated in a sub-set of breast cancer cell lines, a link between TRPV6 expression and breast cancer aggressiveness has not been demonstrated. Furthermore, the mechanism for the over-expression of TRPV6 in breast cancer is unknown. To explore TRPV6 gene amplification as a possible mechanism for over-expression, we used a real-time PCR copy number assay and identified a sub-set of breast cancer cells lines that exhibited increased TRPV6 gene copy number. To assess the clinical relevance of this finding, we initially used a high throughout, clinically driven approach to examine TRPV6 gene amplification in breast tumors. Our findings showed that the mechanism of TRPV6 over-expression is due to, at least in part, gene amplification and that gene amplification may be pronounced in breast cancer subtypes with a poor prognosis. In clinical breast tumor samples, microarray based comparative genomic hybridization (aCGH) showed that the TRPV6 gene region (7q34) is gained in 0/16 invasive lobular carcinomas and in 11/35 high grade invasive ductal carcinomas. When stratified by estrogen receptor status, 7/13 estrogen receptor negative, high grade invasive ductal carcinomas harbored a gain in this region. To determine whether the copy number increase observed at the gene region 7q34 specifically corresponded with amplification of the TRPV6 gene, we performed chromogenic in situ hybridization (CISH) using a probe specific for the TRPV6 gene and a breast cancer tissue microarray. Our findings suggest that a sub-set of breast cancers may be characterized by TRPV6 gene amplification. 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 2954. doi:10.1158/1538-7445.AM2011-2954
Abstract 1177: The mutational status of the p53 tumor suppressor gene is a determinant of GSTP1 expression and mediates GSTP1-dependent drug resistance in human glioblastoma
Authors: Gamil R. Antoun, R McLendon, H Friedman, A Friedman, D Bigner, F Ali-Osman
Journal: Cancer Research (2012)

Abstract Mutations in the p53 tumor suppressor gene, a transcription factor activated by a variety of cellular stresses, including, those inflicted by anti-cancer agents, is a common genetic abnormality in GBMs. Although, p53 is involved in critical cellular processes, such as, cell cycle arrest, DNA repair and apoptosis, studies of p53 in tumor drug resistance and/or patient response to therapy have yielded mixed results. Thus, in gliomas and other cancers, such as, breast, bladder, and ovarian carcinomas, some studies have associated wild-type p53 with higher tumor drug resistance, while other studies indicate that mutant or functionally inactive p53, rather than wt p53, confers drug resistance. These observations indicate the significant complexity of the role of p53 in tumor response to therapy and suggest that other factors, including, downstream p53 pathways and/or regulation, may be important determinants of the p53 effects on the tumor drug resistance phenotype. We previously reported that the human GSTP1 gene, that encodes a major drug metabolizing protein, cell signaling regulator and a mediator of tumor drug resistance, is transcriptionally activated by p53 via a canonical p53 binding motif located in intron 4 of the GSTP1 gene. Our goal, in this study, is to gain further insight into the relationship between p53-dependent transcriptional control of GSTP1 in GBM and the extent to which it contributes to GSTP1 expression in primary patient tumor and, ultimately, to their response to therapy. For this, we sequenced the p53 gene across exons 2-11 in 42 primary GBM specimens quantified the level of GSTP1 gene expression by RNA-PCR and genotyped the allelic variants in them. The results showed, approx. half of the tumors to harbor wild-type p53. In those with mutant p53, the mutations spanned the entire p53 target region, the majority in the core DNA binding domain with the hot spots in codons 55, 72, 175, 245, 248, and 273. GSTP1 expression was significantly heterogeneous between the tumors, and with a few exceptions, correlated directly with the presence of wild-type p53. In representative tumors, the high GSTP1 gene expression was associated with resistance to cisplatin and temozolomide. These result suggest that, in GBM, transcriptional activation of GSTP1 by wild-type, and some mutant forms of p53, contributes to their resistance to therapy. Supported by NIH grants RO1 CA 153050, RO1CA127872, RO1 CA 112519, P50CA108786 and P30-CA14236. 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 1177. doi:1538-7445.AM2012-1177
Disseminated Lyme Disease
Authors: Nora Regelin, Ernesto Montaruli
Journal: New England Journal of Medicine (2015)

An 8-year-old boy presented with periorbital rash that had been preceded by knee pain, fever, and headache. During a walk in a forest 3 weeks before presentation, he had been bitten on the back of his right knee by two ticks, which were removed 2 days later.
AB0988 Inflammation in hand osteoarthritis remains constant after a period of 3 months
Authors: M. Kortekaas, W.Y. Kwok, M. Reijnierse, T.W. Huizinga, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent studies have shown that inflammatory ultrasound (US) features are frequently present in hand osteoarthritis (HOA) and are associated with pain on joint level. It is not known, however, how these features evolve over time. <h3>Objectives</h3> To study the development of inflammatory features and pain over a 3 months period in HOA patients. <h3>Methods</h3> In 25 consecutive HOA patients (mean age 60 years, 76% women) fullfilling the American College of Rheumatology (ACR)criteria, demographic characteristics and scores of Visual Analogue Scale (VAS) pain were collected at baseline and at 3 months. Pain was assessed by palpation of all 1st CMC, MCP, PIP, DIP and 1st IP joints. With ultrasound (US), grayscale (GS) synovitis and Power Doppler signal were scored in all hand joints using a standardized semi-quantitative scoring method (grade 0-3) by two observers (MCK, WYK). Associations between inflammatory US features and pain per joint were analyzed using Generalized Estimated Equations to account for patient effects with adjustments for age, sex, Body Mass Index (BMI). <h3>Results</h3> Summated inflammatory US features did not change at 3 months; mean (range) GS synovitis 7.5 (0-16) at baseline versus 7.5 (0-18) at 3 months and PDS 3.0 (0-7) at baseline versus 2.0 (0-9) at 3 months. In 125 of 750 joints, GS synovitis was present at both baseline and 3 months, 62 joints showed GS synovitis at baseline only and 77 joints at 3 months only. Eleven of 750 joints showed PDS at both baseline and 3 months, 28 at baseline only, 16 at 3 months only. Overall pain decreased over 3 months time: median VAS pain (range) 49 (1-76) to 39 (1-76) mm; summated tenderjoints median (range) 8 (1-23) to 3 (0-16) respectively. Associations between inflammatory US signs and pain at palpation became stronger especially for GS synovitis: odds ratio (OR) 5.4 (1.9-15.6) and for PDS 3.6 (2.1-6.3) at baseline and OR 21.5 (3.5-117.3) and 4.1 (2.1-7.9) at 3 months, respectively. <h3>Conclusions</h3> In HOA summated inflammatory US features are stable over time, but inflammatory US features on joint level are more variable. In the course of 3 months pain diminished, while the association between painful joints and inflammatory US features grew stronger. This emphasizes the multifactorial etiology of pain, which should be taken into account while studying clinical outcomes in HOA. <h3>Disclosure of Interest</h3> None Declared
CHANGES IN N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE LEVELS PREDICTS MORTALITY AND HEART FAILURE HOSPITALIZATION IN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION
Authors: Gianluigi Savarese, Camilla Hage, Ulf Dahlstrom, Pasquale Perrone-Filardi, Lars Lund, Lars H. Lund
Journal: Journal of the American College of Cardiology (2016)
Abstract 4640: Development of antibody-drug conjugate technology based on novel DNA-interacting agents and unique linker technology
Authors: Vincent F.M.H. De Groot, Patrick Beusker, John Joosten, Henri Spijker, Ruud Coumans, Wiro Menge, Ronald Elgersma
Journal: Cancer Research (2012)

Abstract Antibody-Drug Conjugation (ADC) is gaining momentum as a next generation antibody therapeutics approach in oncology. Tumor specific delivery of the cell-killing agent maximizes the agent's potency while avoiding damage to healthy tissue resulting in a high therapeutic window. Synthon's Potent Payload Technology comprises the combination of highly potent DNA-alkylating duocarmycin derivatives and unique releasable linker technology. Duocarmycin analogs and the CC-1065 derivatives represent a class of highly potent, cell-killing, DNA-alkylating, minor groove binding agents. This class is suitable to target solid tumors and has shown activity in a variety of Multi-Drug Resistant (MDR) models.Synthon SpaceLink technology is the only releasable linker technology for ADC that can couple the toxin via its hydroxyl group to the antibody, validated in vivo. Synthon has combined its linkers with duocarmycin derivatives that have a hydroxyl group crucial for biological activity. The data package to be presented supports that SpaceLink and duocarmycins form an excellent chemical match for ADC therapy, possessing an intrinsic complementarity. Strong in vivo Proof of Concept with Potent Payload ADCs has been obtained against multiple targets. In human tumor xenograft models, substantial efficacies have been obtained based on low, single dose treatments, with minimal or absent side effects. We discuss applicability and several other aspects of multiple, validated Potent Payload-based Antibody-Drug Conjugates (ADCs). Latest results of preclinical development progress (in vivo efficacy, safety, etc.) will be presented, including in vitro drug and ADC potencies, plasma stabilities, cathepsin cleavage kinetics, linker cyclization kinetics and in vivo therapeutic window aspects for ADCs directed against HER2 and potentially other (collaborator) targets. 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 4640. doi:1538-7445.AM2012-4640
Decompression side tube-equipped double-balloon enteroscopy extends intubation depth and reduces patient discomfort
Authors: K. Ikeya, S. Osawa, S. Kuriyama, Y. Hamaya, T. Yamada, M. Sugimoto, T. Furuta, K. Sugimoto
Journal: Endoscopy (2012)

Since the first article introducing double-balloon endoscopy (DBE) was published in 2001 [1], the technique has proven effective for deep intubation of the small bowel and is used in clinical practice worldwide. However, the intubation depth is sometimes limited by the distension of the small bowel due to air insufflation during the procedure. In a recent report [2], the total success rate using a combined (antegrade and retrograde) or antegrade-only approach in DBE was 44.0 % (95 % confidence interval [CI] 35.0 % – 53.3 %). To improve intubation depth, we have developed a modified method for desufflation around the overtube of DBE using a decompression side tube.