tbuckley/cabot-search huggingface dataset:
SP0092 Latest advances in connective tissue disorders
Authors: S.J. Bowman
Journal: Annals of the Rheumatic Diseases (2013)

The licensing of belimumab for use in active systemic lupus erythematosus (SLE) has ushered in a new era for the connective tissue diseases (CTDs) based on a better understanding of disease pathogenesis. Genome-wide association studies have been used to identify a number of new therapeutic pathways. Anti-B-cell therapy is proposed for other CTDs such as primary Sjogren's syndrome (PSS) and inflammatory myositis. Other biological therapies – for example targeted at interferons and the innate immune system may also be on the horizon for several of these conditions. Eculizumab, a complement inhibitor has been used successfully in cases of catastrophic anti-phospholipid syndrome. One theme across the connective tissue diseases is to optimize existing therapies and reduce corticosteroid and cyclophosphamide usage. In SLE for example, the use of mycophenolate mofetil to replace cyclophosphamide in many cases of lupus nephritis and steroid-free regimes are also being evaluated. IVIG may also have a role in reducing steroid usage e.g. in myositis flare. In scleroderma, regular screening has improved survival, particularly with regard to earlier intervention for lung fibrosis and pulmonary hypertension. Interstitial lung disease is also common in myositis. Careful attention to nutrition and other gastrointestinal complications have improved patients' general health. Another theme is improved classification of patients into more specific subgroups for targeted management. New antibodies with clinical relevance continue to be discovered: For example - in myositis anti-TIFF antibodies are associated with cancer associated dermatomyositis and anti-MDA5 antibodies with interstitial lung disease. In scleroderma anti-U11/U12 RNP antibodies identify patients with lung fibrosis. International collaborations have been an important driver of new approaches to assessment and therapies. In SLE the SLICC and BILAG groups have been long-established. EUSTAR in scleroderma, EUMYONET in myositis and the UKPSSR and EULAR working group in Sjogren's are all examples of this trend. <h3>Acknowledgements</h3> With thanks to: Dr David D'Cruz, Prof Chris Denton, Prof Caroline Gordon, Dr Patrick Gordon and Dr Voon Ong. <h3>Disclosure of Interest</h3> S. Bowman Consultant for: Merck-Serono
Y a-t-il une répercussion de la variation saisonnière sur la survenue des hémorragies digestives hautes et leurs étiologies
Authors: K Saada, N Aqodad, M El Yousfi, I Mellouki, M El Abkari, DA Benajah, A Ibrahimi
Journal: Endoscopy (2012)

L'hémorragie digestive haute (HDH) est une urgence médicale fréquente. Elle est souvent due à une pathologie ulcéreuse gastro duodénale. Certaines études avaient démontré l'existence d'une variation saisonnière dans la survenue des HDH, alors que d'autres n'avaient pas relevé de différence au cours de l'année. Le but de ce travail est de déterminer les caractéristiques épidémiologiques et étiologiques des HDH ainsi que les fluctuations saisonnières de leur incidence.
Abstract 4488: Inflammation-related biomarkers and risk of epithelial ovarian cancer
Authors: Elizabeth M. Poole, I M. Lee, Julie E. Buring, Susan E. Hankinson, Shelley S. Tworoger
Journal: Cancer Research (2012)

Abstract Introduction: Chronic inflammation caused by ovulation-related wound healing is theorized to cause ovarian carcinogenesis. We examined associations between three plasma biomarkers of inflammation, CRP, IL-6, and TNFαR-2, and risk of epithelial ovarian cancer in a nested case-control study of ovarian cancer cases and controls from the Nurses’ Health Study (NHS) and NHSII as well as in the Women's Health Study (WHS) cohort (CRP only). We further performed a meta-analysis with previously published studies of these biomarkers and ovarian cancer. Methods: Associations between quartiles of CRP, IL-6, and TNFαR-2 and risk of epithelial ovarian cancer were calculated using unconditional logistic regression (NHS/NHSII) or Cox proportional hazards regression (WHS); NHS/NHSII and WHS were combined using random effects meta-analysis. All analyses were adjusted for age, menopausal status/post-menopausal hormone use, duration of oral contraceptive use, tubal ligation, parity, and body mass index. The NHS/NHSII analyses were additionally adjusted for blood draw characteristics (fasting status, time of day and month of draw). Random effects meta-analysis was used to combine these results with previously published results. Results: In the NHS/NHSII (n=218 cases) and WHS (n=159 cases), a 59% increased ovarian cancer risk was observed in the 4th quartile of CRP compared to the 1st quartile (95% CI: 1.08-2.34). Further, CRP &amp;gt;10mg/L compared to &amp;lt;1 mg/L, was associated with a 2.21-fold increased ovarian cancer risk (95% CI: 1.29-3.80). In meta-analyses with previously published studies, the 3rd compared to the 1st tertile of CRP was associated with a 41% increased risk (95% CI: 1.14-1.74) (Table). There were no statistically significant associations between quartiles of IL-6 or TNFαR2 and ovarian cancer risk in the NHS/NHSII or in a meta-analysis with a previous publication. Conclusion: Our results suggest that higher levels of circulating CRP, but not IL-6 or TNFαR2, are associated with increased risk of ovarian cancer. 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 4488. doi:1538-7445.AM2012-4488
SP0191 The ILAR-east africa initiative
Authors: R. Moots
Journal: Annals of the Rheumatic Diseases (2013)

The International League of Associations for Rheumatology (ILAR) East Africa initiative was established in 2009 with the support of the International League of Associations for Rheumatology (ILAR) and the volunteer work of rheumatologists from the international academic community to stimulate the development of clinical rheumatology in East African countries where there is a large burden of rheumatic diseases yet poor infrastructure to support the care of these conditions. Over the past year, rheumatologists from a variety of countries have visited Nairobi, to support training programmes within this scheme. A polarising microscope has been donated and medical and technical staff trained in its use. Two new themes have been identified for 2012. First, the development of a modular training programme with supporting teaching material - to facilitate the transfer of knowledge to local physicians. Second, a programme is being devised to identify the needs of patients and clinicians and provide appropriate support in the form of, for example, teleclinics and email consultations for difficult cases and the provision of patient information on disease and treatment, appropriate to their needs. <h3>Disclosure of Interest</h3> None Declared
Abstract 5369: AN019 in combination with ionizing radiation retards intracranial tumor growth and inhibits angiogenic induction <i>in vitro</i> and <i>in vivo</i>
Authors: Christopher S. Gondi, Bharathi Gorantla, A.K.S. Bhujanga Rao, K. Amala, M.U.R. Naidu, K.V. Jogi, G.V. Ramana, M. Praveen Chowdary, Jasti S. Rao
Journal: Cancer Research (2010)

Abstract Successful treatment of malignant glioma is hampered by the development of resistance to alkylating agents such as Temozolomide (TMZ). The addition of radiation to a TMZ treatment regime has shown promising results with reported survivability of up to 5 years. One of the side effects of Temozolomide is the increased activation of angiogenic factors which may work contrary to the desired result. In this report we demonstrate the development of a novel compound AN019, showing specific VEGF suppression accompanied with anti-angiogenic and anti-proliferative properties in gliomas. We used U87, a glioma cell line, and EGFRvIII over-expressing glioma xenograft 4910 cells for this study. Deduced IC50 values indicated that AN019 had greater anti-proliferative effect than Temozolomide (U87: AN019=103µM, TMZ=768µM; 4910: AN019=169µM, TMZ=582µM). Matrigel invasion assay indicated that AN019 retarded the invasive potential of both U87 and 4910 glioma cells over TMZ treated cells which was enhanced after radiation treatment. In-vitro angiogenic and migration assays showed an almost complete inhibition of angiogenic induction and migration in U87 and 4910 cells after AN019 treatment when compared to TMZ. Cell cycle analysis revealed that 100µg/ml concentration of AN019 was sufficient to achieve &amp;gt;70% apoptosis in both U87 and 4910 cells, whereas 150µg/ml of TMZ was required to achieve the same response. Western blot and ELISA for the expression of VEGF levels indicated that lower concentrations of AN019 (U87=86±3µg/ml and 12±1µg/ml with radiation; 4910=100±1µg/ml and 6µg/ml with radiation) were required for 50% inhibition of VEGF expression. TMZ treatment required a higher concentration to achieve similar 50% inhibition of VEGF expression (U87=80±10µg/ml and 12±3µg/ml with radiation; 4910=100±3µg/ml and 27±3µg/ml with radiation). Animal studies showed that oral doses of AN019 (20mg/kg) regressed tumors in all animals and 70% of the animals showed complete absence of intracranial tumors, whereas TMZ (100mg/kg) treated animals also showed regression of tumors with a 30% cure rate. Overall, our results demonstrate that AN019 has anti-angiogenic, anti-proliferative and anti-tumorogenic properties which may have clinical implications. 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 5369.
Inhibition of Gastric Acid Secretion by Cimetidine in Patients with Duodenal Ulcer
Authors: Ronald M. Henn, Jon I. Isenberg, Vernon Maxwell, Richard A. L. Sturdevant
Journal: New England Journal of Medicine (1975)

Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer. Oral doses of 100, 200, and 300 mg were tested. Each dose significantly inhibited basal and meal-stimulated secretion. After 300 mg, basal acid secretion was essentially zero for at least five hours. The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01). Cimetidine did not affect meal-stimulated gastrin release. No toxicity was observed after serial doses given during these tests. Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing.
Protecting Finances and Improving Access to Care with Medicaid
Authors: Richard Kronick, Andrew B. Bindman
Journal: New England Journal of Medicine (2013)

On the eve of a substantial expansion in health insurance coverage through the implementation of the Affordable Care Act (ACA), there is still much to learn about the effects of health insurance — particularly about the effects of Medicaid coverage.Insurance has three main purposes: to protect financial assets in the event of illness, to improve access to care, and to protect health.1 Some analysts have expressed skepticism about whether having Medicaid is any better than being uninsured.2 However, in this issue of the Journal, Baicker et al.3 report the results of a study of a Medicaid waiver program in . . .
782 IMPAIRED CD4+ T CELL-MEDIATED STIMULATION OF NK CELL ANTI-FIBROTIC ACTIVITY MAY CONTRIBUTE TO ACCELERATED PROGRESSION TOWARDS HCV-ASSOCIATED LIVER FIBROSIS IN HIV/HCV CO-INFECTED PATIENTS
Authors: A. Glässner, M. Eisenhardt, B. Krämer, F. Wolter, P. Kokordelis, B. Sibbing, H.D. Nischalke, J. Rockstroh, T. Sauerbruch, U. Spengler, J. Nattermann
Journal: Journal of Hepatology (2012)
The effect of heritability and host genetics on the gut microbiota and metabolic syndrome
Authors: Mi Young Lim, Hyun Ju You, Hyo Shin Yoon, Bomi Kwon, Jae Yoon Lee, Sunghee Lee, Yun-Mi Song, Kayoung Lee, Joohon Sung, GwangPyo Ko
Journal: Gut (2016)

<h3>Objective</h3> Metabolic syndrome (MetS) arises from complex interactions between host genetic and environmental factors. Although it is now widely accepted that the gut microbiota plays a crucial role in host metabolism, current knowledge on the effect of host genetics on specific gut microbes related to MetS status remains limited. Here, we investigated the links among host genetic factors, gut microbiota and MetS in humans. <h3>Design</h3> We characterised the gut microbial community composition of 655 monozygotic (n=306) and dizygotic (n=74) twins and their families (n=275), of which approximately 18% (121 individuals) had MetS. We evaluated the association of MetS status with the gut microbiota and estimated the heritability of each taxon. For the MetS-related and heritable taxa, we further investigated their associations with the apolipoprotein A-V gene (<i>APOA5</i>) single nucleotide polymorphism (SNP) rs651821, which is known to be associated with triglyceride levels and MetS. <h3>Results</h3> Individuals with MetS had a lower gut microbiota diversity than healthy individuals. The abundances of several taxa were associated with MetS status; <i>Sutterella</i>, <i>Methanobrevibacter</i> and <i>Lactobacillus</i> were enriched in the MetS group, whereas <i>Akkermansia</i>, <i>Odoribacter</i> and <i>Bifidobacterium</i> were enriched in the healthy group. Among the taxa associated with MetS status, the phylum Actinobacteria, to which <i>Bifidobacterium</i> belongs, had the highest heritability (45.7%). Even after adjustment for MetS status, reduced abundances of Actinobacteria and <i>Bifidobacterium</i> were significantly linked to the minor allele at the <i>APOA5</i> SNP rs651821. <h3>Conclusions</h3> Our results suggest that an altered microbiota composition mediated by a specific host genotype can contribute to the development of MetS.
Vascular Metastatic Lesion in the Pelvis Mimicking Gastrointestinal Bleeding
Authors: MELIHA KORKMAZ, E. EDMUND KIM, FRANKLIN C. WONG, DONALD A. PODOLOFF
Journal: Clinical Nuclear Medicine (1996)

Nuclear venogram of the lower extremity using Tc-99m labeled RBCs was performed in a 62-year-old man with prostate cancer, and suggested active bleeding in the left descending colon and sigmoid. However, the patient had a follow-up bone scan using Tc-99m MDP, which revealed markedly increasing diffuse radioactivity in the left pelvic bone, indicating progressive metastasis. Increasing osteoblastic lesion involving the entire left iliac bone was also found on follow-up CT scan of the pelvis. The patient's low hemoglobin and hematocrit levels were stabilized after transfusion with one pint of blood. However, the patient died 6 months later because of disseminated metastases.
Abstract 529: Impaired NF-κB signaling in myeloid cells enhances urethane-induced lung carcinogenesis
Authors: Allyson G. McLoed, Rinat Zaynagetdinov, Taylor Sherrill, Fiona E. Yull, Timothy S. Blackwell
Journal: Cancer Research (2012)

Abstract Nuclear Factor κB (NF-κB) regulates airway inflammation and has been implicated in lung tumorigenesis. We and others have previously described a pro-tumorigenic role for NF-κB activity in airway epithelial cells. However, the role of NF-κB signaling in other cell types, including myeloid cells, in modulation of lung tumorigenesis is unknown. The goal of these studies is to determine the role of myeloid cell-specific NF-κB in lung tumorigenesis. In mice with myeloid cell-targeted IKKβ deletion (IKKβΔmye mice), we observed increased inflammatory mediator expression at 1 week after intraperitoneal injection of urethane (1 μg/g). At 6 weeks post-urethane injection, lungs of IKKβΔmye mice exhibited an increased atypical adenomatous hyperplastic lesion burden, which was accompanied by an increased inflammatory cell influx into the lungs of IKKβΔmye mice compared to wild-type (WT) controls. No difference in total macrophages or the proportion of M2 polarized macrophages in whole lungs was observed by flow cytometry at 6 weeks post-urethane; however, the proportion of CD11b+Gr1hi cells was increased in IKKβΔmye mice. At 4 months after urethane injection, we found an increase in lung tumor numbers (5.6±0.6 in WT, 10.0±1.5 in IKKβΔmye) and a trend towards decreased tumor size in IKKβΔmye mice compared to WT controls. IKKβΔmye mice contained significantly higher numbers of neutrophils in bronchoalveolar lavage at this time point compared to WT controls. In addition, lungs of IKKβΔmye mice exhibited more CD11b+Gr1hi cells in whole lungs as measured by flow cytometry. Our data indicate that inhibition of NF-κB signaling in myeloid cells results in a paradoxical increase in lung inflammation accompanied by enhanced urethane-induced lung tumorigenesis. We conclude that the impact of NF-κB signaling on lung tumorigenesis is cell type specific and that NF-κB activation in myeloid cells functions to limit urethane-induced inflammation and reduce tumor formation in the lungs. 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 529. doi:1538-7445.AM2012-529
The Relation of Post-Dialysis Plasma Calcium and Magnesium to the Dialysate Levels and to Changes in Blood pH
Authors: B. J. N. Z. Danesh, C. H. M. Walker, N. P. Mathers
Journal: New England Journal of Medicine (1970)

The mechanism of the rise in plasma calcium and magnesium reported after hemodialysis was investigated by in vitro equilibrium dialysis using a combined membrane lung and kidney. Correction of 0.1 pH unit by dialysis resulted in an average rise of 0.8 mg in total plasma calcium, owing to the increase in the protein-bound fraction, whereas the decrease in the pH to below normal had the opposite effect. The fall in Pco2 with a rising blood pH during dialysis seemed to exert the major influence in increasing the protein-bound calcium and magnesium. The relation between dialysate and post-dialysis plasma calcium and magnesium at the normal pH may be expressed by the ratios 1:1.70 and 1:1.46 respectively. The rise in plasma calcium and magnesium after dialysis is caused by the correction of blood pH during hemodialysis or by the use of high concentrations of these ions in the dialysate.
Gamma-Beta Thalassemia: A Cause of Hemolytic Disease of the Newborn
Authors: Yuet Wai Kan, Bernard G. Forget, David G. Nathan
Journal: New England Journal of Medicine (1972)

A full-term female infant had hemolytic hypochromic anemia at birth. Blood morphology was consistent with thalassemia. Neither hemoglobin H nor hemoglobin Barts was detected. Studies of globin-chain synthesis in peripheral blood revealed a deficiency of synthesis of gamma and beta chains in relation to alpha-chain synthesis. As the infant matured, her peripheral smear morphology improved and became indistinguishable from that of her father and six other relatives who had beta thalassemia proved by measurement of globin-chain synthesis. Gamma-beta thalassemia is therefore an evanescent disease that may be severe during the normal period of dependence on gamma-chain synthesis.
Postoperative Resolution of 123I-Iomazenil Uptake and Metabolic Rate of Oxygen in the Cerebral Cortex Accompanied by Postoperative Improvement of Cognition in a Patient Undergoing Extracranial-Intracranial Arterial Bypass Surgery for Internal Carotid Artery Occlusion
Authors: Kohei Chida, Kuniaki Ogasawara, Kenta Aso, Hiroki Kuroda, Hideo Saito, Masakazu Kobayashi, Kenji Yoshida, Akira Ogawa
Journal: Clinical Nuclear Medicine (2011)

The distribution of central benzodiazepine receptors in the human brain has been characterized by single-photon emission computed tomography (SPECT) using 123I-iomazenil, and it may dynamically change. We present the case of a 52-year-old man with left internal carotid artery occlusion, who underwent extracranial-intracranial arterial bypass surgery and exhibited postoperative improvement of cognition. Although preoperatively decreased cerebral blood flow and decreased cerebrovascular reactivity to acetazolamide on SPECT in the affected cerebral hemisphere resolved after surgery, preoperatively decreased cerebral metabolic rate of oxygen on positron emission tomography and decreased 123I-iomazenil uptake on SPECT in the affected frontal lobe also resolved after surgery.
QL-05 * SELF-REPORTED COGNITIVE DIFFICULTIES AND ASSOCIATED MEDICAL CHARACTERISTICS IN PATIENTS WITH ADULT-ONSET GLIOMA
Authors: P. Banerjee, T. Cloughesy, J. Pham, S. Cervantes, P. Nghiemphu, A. Lai, D. Wellisch
Journal: Neuro-Oncology (2014)

INTRODUCTION: Neurocognitive functioning and other aspects of quality of life have become increasingly important in the clinical care of patients with glioma. While regular monitoring of neurocognitive functioning with thorough evaluations would be ideal for patients, this is often impractical due to time, cost, and resource considerations. Instead, a measure of self-reported cognitive symptoms can be administered to identify the patients who perceive themselves to be experiencing cognitive difficulties, allowing for rapid detection of patients in need. Recently, a self-report measure of neurocognitive functioning was developed to target the cognitive domains affected by cancer treatments. However, to our knowledge, studies of this questionnaire in adults have only included adult survivors of childhood cancers. METHODS: In the present study, 299 patients with adult-onset WHO Grade II-IV glioma completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. This 25-item measure has four subscales representing different cognitive functions: Task Efficiency, Emotional Tolerance, Organization, and Memory. RESULTS: Overall scores, primary areas of concern, and relationships with medical characteristics were identified. Subtest scores were: Task Efficiency T score (M = 42.8, SD = 15.9), Emotional Tolerance T score (M = 51.6, SD = 11.7), Organization T score (M = 48.6, SD = 11.7), and Memory T score (M = 44.0, SD = 15.3), demonstrating task efficiency to be the cognitive function of greatest concern. Individual item responses were then analyzed, with 188 patients (61.6%) endorsing the highest ranked item: "I have difficulty recalling things I had previously learned" (M = 0.81, SD = 0.74). Chi-square tests, t-tests, and regression were also performed, and these analyses identified statistically significant effects of tumor laterality, radiochemotherapy, recurrence, and KPS score (p < .05), but not tumor grade, on each of the four subscale scores. CONCLUSION: These findings demonstrate that difficulties with memory and task efficiency are frequently endorsed by adult-onset glioma patients, and that several medical characteristics play a role in the level of cognitive dysfunction that patients experience.
Danger of Rectal Examination in Patients with Acute Myocardial Infarction — Fact or Fiction?
Authors: David L. Earnest, Gerald F. Fletcher
Journal: New England Journal of Medicine (1969)

Rectal examination is believed dangerous and is commonly deferred or omitted in patients with acute myocardial infarction. To evaluate the safety and specific usefulness in this clinical setting of an otherwise routine procedure, a gentle digital rectal examination was performed on 86 patients with acute myocardial infarction within 24 hours after admission to the hospital. No adverse clinical or electrocardiographic effects were observed, and no angina pectoris was produced. The unsuspected presence of fecal occult blood, prostatic enlargement and voluminous, hard stool was encountered frequently enough to make rectal examination a useful adjunct in planning of anticoagulation, bladder and bowel care for this patient group.