tbuckley/cabot-search huggingface dataset:
FRI0290 Clinical and immunological features of elderly onset sjögren’s syndrome: a comparison with onset disease in adults
Authors: M. Oliver, A. secco, S. fernandez nacul, M. gauna, D. puente trigo, S. velez, F. zazzetti, J. C. barreira, M. rivero, P. pucci, C. amitrano, C. crow, A. nitsche, F. caeiro, M. haye salinas, L. encinas, O. rillo, N. tamborenea, S. papasidero, L. raiti, J. hofman, G. salvatierra, B. busamia, A. catalan pellet
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare histological and serological features and clinical manifestations of Primary Sjögren`s Syndrome (pSS) diagnosed at the elderly age to those diagnosed at an early age. <h3>Methods</h3> It was analyzed GESSAR's (Argentine Study Group of Sjögren's Syndrome) data base of patients diagnosed with pSS according to 2002 American-European criteria, older than 18 years of age. It was used the chi-square test or Fisher's exact test for categorical variables, according to the expected frequency distribution table. It was performed a logistic regression multivariate analysis. <h3>Results</h3> Out of 330 patients, 236 were diagnosed under the 60 years of age (Group 1) and the remaining 94 were diagnosed over 60 years of age (Group 2). There were no significant differences regarding gender in both groups (95% vs. 98.7% were women in groups 1 and 2 respectively; <i>p</i>:0.361). The patients' median age at the time the diagnosis was made was 47 in group 1 (riq: 37-54), 67 years of age in group 2 (riq: 63-70). The median age at the onset of the symptoms was 41 in group 1 (riq: 31-51) and 64 in group 2 (riq: 58-69). We found significant differences between both groups regarding xerostomia, 215 (91,4%) vs 92 (97%): <i>p</i> 0.048; pulmonary fibrosis, 4 (1,9%) vs 7 (8,33%): <i>p</i> 0.014; antinuclear antibodies, 196 (86%) vs 67 (74%): <i>p</i> 0.01; Anti Ro 183 (78.8%) vs 57 (64.6%): <i>p</i> 0.009 and Anti La 122 (53,5%) vs 31 (35,6%): <i>p</i> 0.005; respectively. We did not find significant differences between both groups regarding the following variables: xerophthalmia (<i>p</i>: 1.0), parotid gland enlargement (<i>p</i>: 0.86), arthralgias (<i>p</i>: 0.82), arthritis (<i>p</i>: 0.10), purpura (<i>p</i>: 0.98), Raynaud's syndrome (<i>p</i>: 0.39), active interstitial pneumonia (<i>p</i>: 0.15), renal tubular acidosis (<i>p</i>: 0.62), glomerulonephritis (<i>p</i>: 1.0), peripheral neuropathy (<i>p</i>: 0.19), lymphoma (<i>p</i>: 0.36), leukopenia (<i>p</i>: 0.78), anemia of chronic diseases (<i>p</i>: 0.85), polyclonal hypergammaglobulinemia (<i>p</i>: 0.28) and Rheumatoid Factor (<i>p</i>: 0.37). In the multivariate analysis, only the anti La was associated in a significant and independent way with the age at the time of the diagnosis (OR: 0.48. IC95%: 0.29-0.80, <i>p</i>: 0.005). <h3>Conclusions</h3> pSS diagnosed under the 60 years of age presented more frequency of seropositivity of the ANA, anti Ro and anti La with a statistically significant difference. In the group diagnosed over the 60 years of age, the xerostomia and the pulmonary fibrosis were significantly more frequent. <b>Disclosure of Interest</b>: None Declared
Abstract 5291: Non-coding satellite RNAs are highly expressed in cancer adjacent lesions of human pancreatic carcinoma and may promote oncogenesis .
Authors: Takahiro Kishikawa
Journal: Cancer Research (2013)

Abstract It was believed that most satellite repeats in pericentric heterochromatin region were silenced and rarely transcribed into RNAs. However, a few reports suggest that non-coding satellite RNAs may play a significant role in cell division, heterochromatin remodeling or DNA damage such as other well-researched non-coding RNAs. In fact, a next generation digital gene expression method recently revealed that human satellite II (HSATII) transcripts are highly and specifically upregulated in human pancreatic tumors. To further explore these findings, we examined the precise localization of HSATII transcripts in human clinical pancreatic tissues by in situ hybridization using highly sensitive locked nucleic acid-modified oligonucleotide probes. Unexpectedly, HSATII RNAs were not detected in pancreatic ductal cancerous lesions, in almost all cases examined. Instead, HSATII RNAs were clearly expressed in non-cancerous adjacent acinar cells, surrounding carcinoma tissues. On the other hand, none of normal or inflammatory pancreatic tissues derived from the ones without cancer expressed HSATII RNAs. While, HSATII transcript expression in normal pancreatic ductal cells could not be induced in vitro even under stress conditions which mimic the tumor-adjacent environments, the cells with ectopic expression of HSATII transcripts showed the increase foci of gH2AX, which may reflect the increased genomic instability. These results suggest that the expression of HSATII may not be phenotypic changes in cancers but may directly contribute to the oncogenesis in the cells in precancerous lesions. Citation Format: Takahiro Kishikawa. Non-coding satellite RNAs are highly expressed in cancer adjacent lesions of human pancreatic carcinoma and may promote oncogenesis . [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 5291. doi:10.1158/1538-7445.AM2013-5291
Litigation authority set up for the NHS GPs in inner London to get 35m Reducing GPs' paperwork Juniors' contracts will be held by trusts in Scotland MPs debate merits of commissioning and fundholding Government updates health statistics
Authors: L. Beecham
Journal: BMJ (1995)

# Litigation authority set up for the NHS {#article-title-2}

A new NHS body, called the Litigation Authority, is being set up to administer the clinical negligence scheme for NHS trusts,a financial pooling arrangement to spread the cost of malpracticesettlements. Regulations to set the body up as a special healthauthority were laid before parliament last month (p 1250).

Sir Bruce Martin QC was named as chairman designate of the authority,with Dr Oscar Craig and Mr Ronald Bradshaw as non-executivemembers. The authority will help with the establishment of theclinical negligence scheme (BMJ 1995;310:896) and be responsiblefor its operational effectiveness on behalf of the secretaryof state for health.

The authority will be small, consisting of four non-executivemembers, a full time chief executive, part time finance andclinical directors, and about six support staff. It will receiveadvice on general policy issues from a policy steering groupelected by, and consisting of, representatives of the scheme.Day to day management has been subcontracted to the MedicalProtection Society.

The health minister, Mr Gerald Malone, said that the majorityof problems about clinical standards were resolved at locallevel, but in those cases where patients wished to take thematter further the authority would be responsible for ensuringthat claims were handled sensitively and fairly. He added, “Thiswill safeguard patients' legitimate interests, while allowingNHS trusts to plan ahead with greater security.”

Medical negligence costs in the NHS now exceed £150m ayear and are rising at an annual rate of 25%, due mainly toa rising …
Abstract 1712: Transmembrane domain required for MCL1 function.
Authors: Guo Wei, Xiaohua Wu, Todd R. Golub
Journal: Cancer Research (2013)

Abstract MCL1 is an anti-apoptotic family member of the BCL2 family of proteins that exerts its anti-apoptotic function at least in large measure by sequestering BH3 domain containing pro-apoptotic proteins within the outer mitochondrial membrane. Several lines of evidence point to MCL1 as an important oncology target. MCL1 is among the top 10 most frequently amplified genes in human cancer. Consistent with its frequent amplification, MCL1 is highly expressed in many tumor types, and high expression levels of MCL1 contribute to tumor development and resistance to chemotherapy. MCL1 is required for survival of a sub-group of tumor cells that are characterized by low levels of expression of another anti-apoptotic BCL2 family protein, BCL-xL. Despite the important role of MCL1 in cancer, no inhibitors of MCL1 have reached the clinic. We employed mutagenesis to further explore the anti-apoptotic mechanism of MCL1. Deletion of the N-terminus portion of MCL1, including the PEST domain, did not significantly affect its anti-apoptotic function. However, deletion of the transmembrane (TM) domain of MCL1 abolished the anti-apoptotic function of MCL1. Furthermore, an MCL1 point mutation within the TM domain impaired its anti-apoptotic function, however, it could still bind to the pro-apoptotic proteins BIM and BAK. Therefore, the TM domain may represent an alternative site for pharmaceutical targeting of MCL1. Citation Format: Guo Wei, Xiaohua Wu, Todd R. Golub. Transmembrane domain required for MCL1 function. [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 1712. doi:10.1158/1538-7445.AM2013-1712
Lung Cancer Metastasis to an Adrenal Myelolipoma Detected by PET/CT
Authors: Morgan C. Althoen, Alan Siegel, Michael J. Tsapakos, Marc A. Seltzer
Journal: Clinical Nuclear Medicine (2011)

The patient is a 54-year-old woman with squamous cell lung carcinoma, diagnosed bronchoscopically at the bronchus intermedius. Initial staging F-18 fluorodeoxyglucose PET/CT revealed the hypermetabolic primary perihilar right lower lobe malignancy, and a 13-mm hypermetabolic nodule located within a 45-mm fat density structure at the expected location of the right adrenal gland. No normal-appearing adrenal gland was present. This PET/CT demonstrates metastatic squamous cell carcinoma to an adrenal myelolipoma. A CT-guided biopsy of the nodule confirmed squamous cell carcinoma. This is the patient's only PET-evident site of disease beyond the primary tumor, compatible with T2N0M1 disease.
Use of Endoscopic Ultrasound-Guided Injection in Endoscopic Resection of Solid Submucosal Tumors
Authors: S Sun, M Wang, S Sun
Journal: Endoscopy (2002)

Submucosal tumor (SMT) is a common disease. We used endoscopic ultrasound (EUS)-guided puncture to inject saline before resection of SMTs, and evaluated the usefulness of this method.We selected 16 symptomatic patients with solid SMTs in the upper gastrointestinal tract, confirmed by endoscopy and EUS. We first used EUS-guided puncture to inject saline to separate the submucosal lesions from the deeper normal tissues. Lesions in the muscularis mucosa and submucosa were then removed directly by snare cauterization. Lesions in the muscularis propria were treated by means of a two-step approach: first, we incised the superficial tissue of the tumors using an electrosurgical needle, and second, we enucleated SMTs as much as possible by tightening the snare around them and creating pseudo-stalks. After snare excision of SMTs, the cleavages of the superficial tissues were closed using metal clips.Among the 16 patients, one lesion was in the muscularis mucosa, six were in the submucosa, and nine were in muscularis propria. All the lesions were resected thoroughly. No perforation occurred nor had any recurrences been observed at follow-up of 12 - 17 months.EUS-guided puncture to inject saline before resection is a safe and accurate procedure in the treatment of submucosal tumors.
Abstract 911: Genetic variations in the one-carbon transfer pathway and aberrant DNA methylation in prostate cancer
Authors: Masatoshi Watanabe, Yoshifumi Hirokawa, Hiroyoshi Suzuki, Tomohiko Ichikawa, Takahiko Katoh, Yoshiki Sugimura, Taizo Shiraishi
Journal: Cancer Research (2010)

Abstract Many molecular studies have indicated that genetic and epigenetic alterations are important for carcinogenesis in the prostate. Alterations in the one-carbon metabolism pathway can influence DNA synthesis and DNA methylation. Polymorphisms in the genes for the methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), serine hydroxymethyltransferase (SHMT) have been reported to be associated with some forms of malignancies. In a case-control study of 300 cases and 240 controls, we investigated whether four common polymorphisms in the MTHFR (C677T and A1298T), MTR (A2756G), SHMT1 (C1420T), MTRR (A66G), reduced folate carrier (RFC-1, A80G), and methylenetetrahydrofolate-dehydrogenase (MTHFD, G1958A) may have a role in altering prostate cancer susceptibility. The genotype was mainly determined by the PCR-RFLP method. The MTHFR 677TT genotype was associated with a significant decrease in the risk with an adjusted odds ratio of 0.57 (95% confidence interval: 0.34-0.94). The RFC-1 80GG genotype was associated with a significant increase in the risk with an adjusted odds ratio of 1.75 (95% confidence interval: 1.07-2.87). However, the MTHFR A1298C, MTR A2756G and SHMT1 C1420T, MTRR A66G and MTHFD G1958A were not associated with prostate cancer risk. We also analyzed CpG island hypermethylation in five genes (GSTP1, RARβ2, AR, DAPK, TIMP-3 and hMLH1) and its association with these polymorphisms in 100 prostate cancers. However no significant association was detected. These findings suggest that polymorphism of the MTHFR may be involved in carcinogenesis of the prostate. 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 911.
Risk of Recurrent Seizures after Two Unprovoked Seizures
Authors: W. Allen Hauser, Stephen S. Rich, Ju R.-J. Lee, John F. Annegers, V. Elving Anderson
Journal: New England Journal of Medicine (1998)

Patients with a single unprovoked seizure have about a 35 percent risk of recurrence in the subsequent five years. We studied the risk of recurrence after two unprovoked seizures.
The Effect of a Keto Acid–Amino Acid Supplement to a Restricted Diet on the Progression of Chronic Renal Failure
Authors: William E. Mitch, Mackenzie Walser, Theodore I. Steinman, Sylvia Hill, Scott Zeger, Kriang Tungsanga
Journal: New England Journal of Medicine (1984)

We treated 24 patients who had chronic renal failure with a low-phosphorus diet containing 20 to 30 g of mixed-quality protein, supplemented by amino acids and their keto analogues. Seventeen patients had well-defined rates of progression before treatment, as assessed by serial determinations of serum creatinine levels. By extrapolating these rates of progression, we found that 10 of the 17 (59 per cent) had a clinically important slower rise in creatinine levels during long-term treatment (average, 20 months) than predicted; none had a faster rise than predicted. Seven of the 17 patients began treatment before creatinine reached the level of 8 mg per deciliter; in six of the seven, followed for an average of 22 months, creatinine has remained at or below the level at the start of treatment. Nutrition, as assessed by body weight, nitrogen balance, serum albumin, and serum transferrin, has been well maintained. This regimen slowed or arrested the rise in creatinine levels and thus must have slowed or halted the progression of renal insufficiency in a majority of cases, especially when treatment was initiated before creatinine had reached the level of 8 mg per deciliter. The mechanism underlying this effect remains to be determined.
OP0183 Rebamipide: A potential useful therapeutic addition in the treatment of recurrent oral ulcers in behÇet’s disease
Authors: A. Abou-Raya, S. Abou-Raya, N. Sallam
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recurrent oral ulceration is one of the hallmarks of Behçet's disease (BD). To date, various clinical manifestations, including aphthous ulcers are treated with limited success. Rebamipide is an anti-ulcer, gastro-protective drug, that increases mucous and stimulates endogenous prostaglandin biosynthesis and has anti-inflammatory actions including inhibition of neutrophilic leukocyte activation. <h3>Objectives</h3> To assess the efficacy of rebamipide in the therapy of recurrent oral aphthous ulcers in BD patients. <h3>Methods</h3> Fifty four BD patients (50 males; 4 females) of mean age 34.1 years and mean disease duration 6.14 years fulfilling the criteria of the International Study Group for Behçet's disease were recruited. Exclusion criteria included aphthous ulcers due to other inflammatory conditions. All subjects were from a homogenous ethnic background. Inclusion criteria included presence of oral ulcers within 4 weeks prior to recruitment. Clinical activity was assessed at the time of entry into the study. All 54 patients had recurrent oral aphthous ulcers despite ongoing therapy (colchicine, systemic and/or topical corticosteroids, azathioprine). In this single centre double-blind placebo controlled study, the 54 BD patients were randomized into two groups: 37 were assigned to receive rebamipide 100mg x 3/day and 14 patients received placebo in addition to their standard therapy provided dosages were kept constant throughout the study for 16 weeks. Oral aphthous ulcer count and pain scores were recorded daily by patients and weekly by one of the physicians. Physicians assessed the global improvement in ulcer count and pain using a visual analogue scale (VAS) 0-10. Safety and tolerability were recorded. <h3>Results</h3> Improvement in oral ulcer count was found in 4/14 (29%) of the placebo group and in 26/37 (70%) rebamipide group respectively, p=0.006. No new ulcers were recorded in the rebamipide group whereas 29% of the placebo group showed new ulcers. Patient-recorded pain scores decreased significantly in the rebamipide group compared to the placebo group. Physician global assessment of the pain score was statistically different in the intervention group compared to the placebo group, p&lt;0.05. <h3>Conclusions</h3> Rebamipide showed improvement in oral aphthae count and pain scores in BD patients compared to placebo. The findings of the present study indicate that rebamipide, a gastro-protective drug, displayed an anti-inflammatory action. Rebamipide may thus be a useful addition in the therapeutic armamentarium of recurrent oral ulcers in BD. <h3>Disclosure of Interest</h3> None Declared
SP0005 Novel Imaging Markers for Oa: Costly or Effective?
Authors: A.L. Tan
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Most of the novel work in imaging marker for OA is in MRI, a non-invasive way of assessing structural changes which, in recent years, has made significant contribution to our improved understanding of pathology, and has helped with insights into diagnosis and therapy monitoring. With increasing number of potential new DMOADs on the horizon for OA, it has become prudent that a reliable, reproducible and validated marker of response is developed that can measure change sensitively and accurately, especially in early disease. Large cohort studies like the Osteoarthritis Initiative provide the opportunity to identify sensitive imaging markers. However, the complex relationship between structural changes in OA and symptoms continue to add another dimension of challenge in interpreting the relevance of changes observed. MRI has the advantage over other imaging modality in assessing OA due to its capability in visualising all joint structures including bone, cartilage, meniscus, tendons, ligaments and synovium, all of which can be affected in OA. Various sophisticated novel MRI techniques and scoring systems have been devised for OA, mainly focussing on measuring and characterising the morphology and physiology of cartilage changes. To date, MRI as an imaging marker for OA is mainly explored as a research tool and awaits translation into clinical practice, currently largely limited by its cost and the relative complexity of image interpretation. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6143
REPEATED INTRANASAL APPLICATION OF NEURAL STEM CELL-MEDIATED ENZYM/PRODRUG THERAPY USING A NOVEL HSV-THYMIDINE KINASE VARIANT IMPROVES THERAPEUTIC EFFICIENCY IN AN INTRACRANIAL GLIOBLASTOMA MODEL
Authors: N. O. Schmidt, L. Duhrsen, M. Reitz, M. Henze, J. Sedlacik, K. Riecken, B. Fehse, M. Westphal
Journal: Neuro-Oncology (2014)

BACKGROUND: Neural stem cells (NSCs) have an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive gliomas. We have recently introduced the concept of intranasal application of NSCs as a noninvasive and direct alternative delivery method for glioma-targeting NSCs. Here, we demonstrate that the repeated non-invasive intranasal administration of tumor-targeting NSC is able to deliver a novel suicide gene (TK.007) to intracerebrally growing human glioblastoma xenografts. METHODS: Murine NSC were genetically modified to stably express a novel, codon-optimized HSVtk(A168H) mutant (TK.007). The biological activity of the NSC-mediated TK.007/ganciclovir (GCV) system was assessed in cell survival and bystander assays using various human glioma cell lines. Therapeutic effects of intratumoral and intranasal NSC-TK007 applications alone and the sequential combinations of both was tested using an intracranial U87 human glioblastoma model in nude mice. All animals received 50 mg/kg GCV i.p. for five consecutive days. In all experiments two control groups received either NaCl instead of GCV or NSC containing the control vector instead of NSC-TK.007. Therapeutic efficiency was determined by assessment of tumor size by 7T MR-imaging and by establishment of Kaplan-Meier survival curves. RESULTS: Cell survival and bystander assays confirmed the GCV catalytic activity of NSC-expressed TK007 in a GCV dose dependent manner and a significant bystander effect at 12.5% of cells. Tumor targeted migration was demonstrated by intravital imaging of luciferase-expressing NSC. In glioma-bearing mice a single intratumoral application of NSC-TK007 followed by systemic prodrug application of GCV lead to a significant tumor growth inhibition of 72% versus the control groups at day 22 and translated in a prolonged survival time. Mice recieving a cyclic intranasal application of NSC-TK.007 alone displayed a signifcant longer survival than the controls. This effect was significantly enhanced when cyclic intranasal NSC-TK.007 therapy was preceded by a single intratumoral application of NSC-TK007 and led to a significant tumor growth inhibition of >95% and improved survival time. CONCLUSIONS: Our data demonstrates that the NSC-mediated TK.007/GCV therapy, which is based on the clinically most widely used suicide system to date, is safe, nontoxic, and effective in glioblastoma-bearing mice. Most importantly, our findings establish that the intranasal application of therapeutically-modified NSC is a safe and non-invasive application method which allows a chronic treatment during the disease course. SECONDARY CATEGORY: Clinical Neuro-Oncology.