tbuckley/cabot-search huggingface dataset:
AB0165 Plasma soluble triggering receptor expressed on myeloid cells-1 (strem-1) levels are correlated with disease activity in rheumatoid arthritis
Authors: J.-S. Song, E.-J. Kang, S.T. Choi, Y.-J. Ha, K.-H. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Triggering receptor expressed on myeloid cells 1 (TREM-1) is an immunoglobulin-like cell surface receptor mainly expressed on neurtophils, monocytes and macrophages. TREM-1 serves as a critical amplifier of inflammatory signaling, and its expression is increased in the synovium of rheumatoid arthritis (RA) patients. It can exist as a soluble form. However, the association between plasma sTREM-1 levels and disease activity in RA patients remains unclear. <h3>Objectives</h3> In this study, we investigated whether plasma soluble TREM-1 (sTREM-1) levels are elevated in patients with RA and whether its levels are correlated with disease activity and other parameters. <h3>Methods</h3> This cross-sectional study included 71 patients with RA and 50 age- and sex- matched healthy controls. Plasma samples were obtained from patients with RA during active and inactive disease status and from controls. We assessed clinical characteristics and laboratory parameters including the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score 28 (DAS28). Their plasma levels of sTREM-1 and tumor necrosis factor (TNF)-α were quantitatively measured by enzyme-linked immunosorbent assay (ELISA). <h3>Results</h3> Patients with RA had significantly higher plasma sTREM-1 levels than healthy controls (170.10±84.71 pg/mL vs 97.41±40.64 pg/mL, <i>p</i>&lt;0.001). In RA patients plasma sTREM-1 levels were found to be correlated with DAS28, ESR, CRP, white blood cell counts, neutrophil counts, and plasma TNF-α levels (<i>r</i> =0.329, <i>p</i> =0.005;<i>r</i> =0.241, <i>p</i> =0.043; <i>r</i> =0.314, <i>p</i> &lt;0.001; <i>r</i> =0.261, <i>p</i> =0.028; <i>r</i> =0.278, <i>p</i> =0.019; <i>r</i> =0.313, <i>p</i> =0.009, respectively). Plasma sTREM-1 levels in patients with a active disease status (DAS28 &gt;3.2) were significantly higher than in those with a low disease status (DAS28 ≤3.2) (208.89±100.14 pg/mL vs 150.29±68.70 pg/mL, <i>p</i>=0.005). <h3>Conclusions</h3> RA patients had higher plasma sTREM-1 levels than healthy controls, and plasma sTREM-1 levels were correlated with disease activity parameters, suggesting that plasma sTREM-1 could play a role in the inflammatory process associated with TNF-α, and that it may be a useful disease activity marker in RA. <h3>References</h3> Collins CE, La DT, Yang HT, Massin F, Gibot S, Faure G, et al. Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patients with septic arthritis or rheumatoid arthritis. Ann Rheum Dis 2009;68;1768-74. Kuai J, Gregory B, Hill A, Pittman DD, Feldman JL, Brown T, et al. TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines. Rheumatology 2009:1352-8. <h3>Disclosure of Interest</h3> None Declared
Fate of Orally Ingested Enzymes in Pancreatic Insufficiency
Authors: Eugene P. DiMagno, Juan R. Malagelada, Vay L. W. Go, Charles G. Moertel
Journal: New England Journal of Medicine (1977)

To assess the fate and efficacy of orally ingested enzymes in pancreatic insufficiency, we administered pancreatin to six patients by two schedules--eight tablets with a standard meal or two tablets hourly--and in six normal controls, quantified duodenal enzyme activity and related inactiviation of ingested enzymes to gastric and duodenal pH; in the six patients we measured malabsorption by fecal balance studies. Postprandially, gastric pH was similar in health and pancreatic insufficiency, and below 4 after 40 minutes. Duodenal pH in pancreatic insufficiency declined to approximately 4 beyond 100 minutes--lower than in health (P less than 0.05). Approximately 22 per cent and 8 per cent of trypsin and lipase activity ingested with either schedule was delivered to the ligament of Treitz. Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, we recommend it.
Sensory Perception Thresholds in Patients with Juvenile Diabetes and Their Close Relatives
Authors: Ronald H. Chochinov, G. Leslie E. Ullyot, John A. Moorhouse
Journal: New England Journal of Medicine (1972)

Since a sensory deficit in diabetes might be early and generalized, tactile and special senses were studied in relation to onset and duration of diabetes. Fifty-nine healthy persons 19 to 40 years of age and 53 age-matched and sex-matched persons with juvenile-onset diabetes of four weeks to 27 years' duration had five sensory thresholds measured: light touch and two-point discrimination of the right index finger and great toe, visual flicker fusion, auditory fusion and electric taste. All senses tested were impaired in the diabetic group. Abnormalities were present within two years of onset for light-touch, flicker fusion and electric taste. The abnormalities progressed with time only for two-point discrimination and flicker fusion. Thresholds in the finger correlated with those in the toe. Subjects with an immediate diabetic relative had an abnormally high threshold for two-point discrimination in the finger. Widespread defects in tactile and special sensory perception are present near the onset of juvenile diabetes.
P17.88 * THE CLINICAL SIGNIFICANCE OF EPENDYMAL ENHANCEMENT AT PRESENTATION IN PATIENTS WITH MALIGNANT GLIOMA: SINGLE CENTER EXPERIENCE
Authors: O. K. - Person, A. Eran, F. Darawshe, T. Tzuk-Shina
Journal: Neuro-Oncology (2014)

INTRODUCTION: Data from trials suggest that GBMs adjacent to the subventricular zone and associated with ependymal enhancement on MRI, have a more aggressive and multifocal phenotype which render the patient to a shorter overall survival (OS). The aim of the current study was to re-assess whether ependymal enhancement is associated with a worse outcome. METHODS: After institutional review board approval, a retrospective review of all patients who were treated for GBM in our institution from 2005 to 2011 was conducted. Only patients in whom the pretreatment MRI was available were included in our study. Data extracted from the medical records included age, date of diagnosis, co-morbidities, performance status at time of the first visit prior to initiating treatment, treatment regimen and time of death. All MRI imaging were blindly reviewed by one of the investigators, and were evaluated for distance from the subventricular zone, ependymal enhancement and pial enhancement. The groups were divided according to ependymal enhancement and data extracted was evaluated for association with survival. RESULTS: Between 2005 and 2011, 230 patients were treated at our center. Sixty five patients were excluded from the study due to insufficient data. Sixty seven patients (40.6%) had evidence of ependymal enhancement on MRI (group A). Seventy patients (42.4%) did not have evidence of enhancement (group B). In 28 patients (17%) the imaging was inconclusive, due to involvement of the temporal horn, therefore defined as group C. Median survival of all groups was 15.3 months (range 13.6 to 16.95). Median survival according to ependymal enhancement was 14 months for group A (range 12 to 16), 15.9 months group B (range 14.28 to 17.65) and 11.7 months for group C (range 6.47 to 16.92 ) (P > 0.05). Age <50 yrs, good performance status, pial enhancement, and gross tumor resection were associated with better survival. CONCLUSIONS: Unlike reported by others, in the current study ependymal enhancement on MRI in patients with GBM was not associated with reduced OS.
DIFFERENTIAL RESPONSIVENESS OF HUMAN ATRIAL AND VENTRICULAR FIBROBLASTS TO SERUM-INDUCED PROLIFERATION AND ITS INHIBITION BY SIMVASTATIN
Authors: Farhan Rizvi, Ramail Siddiqui, Alessandra DeFranco, Larisa Emelyanova, Alisher Holmuhamedov, Gracious Ross, Ekhson Holmuhamedov, David Kress, A. Jamil Tajik, Arshad Jahangir
Journal: Journal of the American College of Cardiology (2016)
S77 Comparing the degree of inhibition of TNF- and IL-6 by p38 inhibitors in monocyte derived macrophages (MDMs)
Authors: R. A. Noble, S. Patel, I. Kilty
Journal: Thorax (2011)

<h3>Objective</h3> The activation of p38 MAPK is involved in the increased expression of pro-inflammatory cytokines, such as TNF-α and IL-6, in inflammatory diseases such as chronic obstructive pulmonary disease (COPD). Inhibition of p38 may therefore represent an effective means to combat inflammatory diseases. Inhibitors of p38 such as BIRB796 cause a rapid reduction in the levels of inflammatory cytokines. The aim was to assess the effect of three p38 inhibitors on the lipopolysaccharide (LPS) induced expression of cytokines; TNF-α IL-6 and IL-10 in MDMs. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMCs) were isolated from human peripheral blood taken from healthy human donors. Monocytes were subsequently selected through magnetic bead separation. Following the isolation of monocytes, cells were differentiated to MDMs over 12 days in suspension. BIRB796 and two novel p38 inhibitors, PH797804 and PF03715455 were pre-incubated for 1 h before stimulation with 100 ng/ml LPS. Supernatants were collected after 18 h and the levels of TNF-α IL-6 and IL-10 were determined by ELISA. The effects of the compounds were also assessed over 24 h. Supernatants were collected at several time-points allowing the onset and duration of the inhibitory effect to be observed. <h3>Results</h3> BIRB796, PHA797804 and PF03715455 caused a substantial inhibition in the release of TNF-α (n=3) and IL-6 (n=3) in LPS-stimulated MDMs. The maximum level of inhibition ranged from 50% to 65%. The addition of the anti-inflammatory cytokine, IL-10, enhanced both the maximum level of inhibition and the potency of each compound. Cytokine expression across 24 h showed a dose dependant inhibition of cytokine release = 2 h (TNF-α) and =4 h (IL-6). The IC<sub>50</sub> values in respect to both TNF-α and IL-6 decreased over time. <h3>Conclusion</h3> The method described here is an effective means of comparing the effect of p38 inhibitors in MDMs. All three compounds caused a substantial inhibition of, LPS-stimulated, production of both TNF-α and IL-6. The effect of these compounds on IL-10 production requires further investigation. Since a reduction of the anti-inflammatory cytokine IL-10 may counteract the benefits that may be associated with reduced levels inflammatory cytokines due to p38 inhibition in inflammatory diseases.
Abstract P6-09-03: No Increased Breast Cancer Risk with Hormone Replacement Therapy (HRT) in Women with Benign Breast Disease
Authors: KP McKian, MH Frost, SD Maloney, RA Vierkant, DW Visscher, LC. Hartmann
Journal: Cancer Research (2010)

Abstract The association between hormone replacement therapy (HRT) and breast cancer risk in women with benign breast disease (BBD) is unclear. However, others have shown that HRT use is associated with the development of proliferative breast disease (Rohan et. al, CEBP 2008). To better clarify potential risks associated with postmenopausal hormone use in women with BBD, we performed a nested case control study within the Mayo Clinic Benign Breast Disease Cohort. In the cohort, there are 11,079 women who had benign breast biopsies between 1967 and 1996 and for whom we have outcome and risk factor data, including use of HRT. We studied 947 cases (breast cancer after BBD) and two controls matched to each case based on age and year of BBD. Information on use of HRT was obtained through use of questionnaires and medical record review with a mean time of follow up of 17.4 years. HRT use, histology, involution status, and family history were all evaluated for impact on breast cancer risk in a multivariate model. As shown in Table 1, when looking at effects of histology, involution, and family history, we confirmed previously reported findings of risk (Hartmann LC et. al, NEJM 2005). Specifically, we saw increased risk in women with AH vs. PDWA or NP, decreased risk with complete involution vs. partial or no involution, and increased risk with strong family history vs. weak or no family history. Associations of hormone replacement therapy and other relevant clinical variables with risk of breast cancer Multivariate model simultaneously including all variables listed in the table. HRT=hormone replacement therapy. NP=non-proliferative. PDWA=proliferative disease without atypia. AH=atypical hyperplasia We found that women who had used HRT had no higher risk of developing breast cancer than women who had not used HRT. Specifically, with Never Users as the reference group, those with 5 years or less exposure had OR 0.80 (0.56-1.15); 6-10 years, 0.85 (0.56-1.28) and 11+ years, 0.51 (0.36-0.72), p =0.002. In conclusion, we found that HRT use among postmenopausal women with BBD was not associated with an increased risk of breast cancer. In this case-control set, we confirmed previous findings regarding well established risk factors of histology, involution status, and family history. While HRT use may contribute to the development of proliferative breast disease, we do not see that HRT is associated with additional breast cancer risk, beyond that of the proliferative disease itself. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-09-03.
Abnormal Iodine-131 Uptake in the Mediastinum Caused by Achalasia
Authors: AYSUN ÖZDEMİR, FIRAT GÜNGÖR, ŞULE ÖZUĞUR, METİN ÇUBUK, ADİL BOZ, BINNUR KARAYALÇIN
Journal: Clinical Nuclear Medicine (1998)

A 50-year-old woman who had had surgery 4 years earlier for papillary carcinoma of the thyroid received 30 mCi I-131 for ablation. Follow-up I-131 imaging showed successful thyroid gland ablation; however, persistent activity was present in the mediastinum corresponding to the esophageal projection. The patient had been experiencing dysphagia for approximately 10 years. Esophageal scintigraphy showed delayed transit time. A contrast esophagogram showed a rat tail deformity with narrowing most marked at the gastroesophageal junction and dilatation of the entire esophagus. Although endoscopic examination demonstrated nonperistaltic contractions, an upper gastrointestinal endoscopic examination was normal. Because these findings suggested achalasia, we concluded that the abnormal I-131 uptake was caused by achalasia.
Adjusted versus Fixed-Dose Subcutaneous Heparin in the Prevention of Deep-Vein Thrombosis after Total Hip Replacement
Authors: Pierre F. Leyvraz, Jacques Richard, Fedor Bachmann, Guy van Melle, Jean-Michel Treyvaud, Jean-Jacques Livio, Georges Candardjis
Journal: New England Journal of Medicine (1983)

Venous thromboembolism after total hip replacement continues to be a serious problem. We conducted a study to determine whether adjustment of the dose of subcutaneous heparin to yield partial thromboplastin times in the high-normal range results in a greater reduction of postoperative deep-vein thrombosis than fixed doses of heparin. Seventy-nine patients undergoing elective hip arthroplasty were randomly divided into two groups two days before surgery. Group 1 (41 patients) received a fixed dose of 3500 IU of heparin subcutaneously ever eight hours; 16 of the 41 (39 per cent) had deep-vein thrombosis diagnosed by venography. Group 2 (38 patients) was started on the same dose, which was then adjusted to keep the activated partial thromboplastin time between 31.5 and 36 seconds. From the day of operation to the eighth postoperative day these patients needed progressively more heparin to maintain the activated partial thromboplastin time in the prescribed range. Only 5 of the 38 (13 per cent) had deep-vein thrombosis (P less than 0.01), and the number of thrombi in proximal veins was also lower in this group (P = 0.003). The number of units of blood transfused, the frequency of postoperative wound hematomas, and the drop in hemoglobin levels were identical in the two groups. Adjusted low-dose heparin prophylaxis appears to be a safe and efficacious method to reduce the frequency of deep-vein thrombosis in patients undergoing total hip replacement.
PEDIATRIC CARDIOMYOPATHY MUTATIONS IN A HIGHLY CONSANGUINEOUS POPULATION
Authors: Akl C. Fahed, Şükrü Candan, Alireza Haghighi, Steven DePalma, Barbara McDonough, Betül Erer, Ahmet Ekmekçi, Helen Bornaun, Kazum Öztarhan, Hatip Aydin, Jonathan Seidman, Christine Seidman
Journal: Journal of the American College of Cardiology (2016)
Assessment of lineality in bipolar I linkage studies
Authors: S G Simpson, S E Folstein, D A Meyers, J R DePaulo
Journal: American Journal of Psychiatry (1992)

To assess lineality in families of bipolar I probands, the authors used direct interviews of family members to reclassify families initially categorized as unilineal by family history.The families of 1,800 treated bipolar I probands were screened by the family history method with multiple informants. If the proband had one or more affected sibs and one apparently unaffected parent, the parents (and then other available first- and second-degree relatives) were directly interviewed by psychiatrists.Of the 1,800 families screened, 56 were apparently suitable unilineal families with multiple affected members; 46 families were interviewed directly. After interviews with the parents, 12 families (26.1%) were found to be bilineal. Direct interviews of all available relatives in the 34 remaining families revealed that only 22 (47.8% of the 46 interviewed families) were unilineal or probably unilineal and 12 were probably bilineal. The probably bilineal families had a significantly higher proportion of siblings with unipolar disorder. In addition, the affected sibs from the probably bilineal families tended to have earlier onsets but had significantly fewer symptoms in the most severe depressive episode.Fewer than 50% of bipolar I families appearing unilineal according to family history were found to be unilineal by direct interviews. The phenotypic differences between the affected sibs from the probably bilineal families and those from the unilineal and probably unilineal families suggest differences in genetic mechanisms. These findings highlight the need to systematically assess lineality in all families considered for bipolar I linkage studies and support the preferential inclusion of unilineal families in linkage studies.
P24 Fluticasone propionate/formoterol fumarate combination therapy has a more rapid onset of action than fluticasone propionate/salmeterol xinafoate in the treatment of asthma: a randomised controlled trial
Authors: A. Bodzenta-Lukaszyk, A. Dymek, H. Mansikka
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> A new asthma therapy combining fluticasone propionate and formoterol fumarate (FP/FORM) in a single pressurised metered dose inhaler has been shown to have similar efficacy and safety to fluticasone propionate/salmeterol xinafoate (FP/SAL). Secondary endpoint data for this study are presented here. <h3>Methods</h3> Adults (N = 202) with mild to moderate-severe asthma were randomised 1:1 to 12 weeks of treatment with FP/FORM (100/10 μg or 250/10 μg) or FP/SAL (100/50 μg or 250/50 μg), both twice daily, in an open-label, parallel-group, multicentre study. The starting dose was based on the dose of inhaled corticosteroid the patient received before the study. The primary endpoint was mean morning pre-dose FEV<sub>1</sub> at Week 12. Secondary endpoints included time to onset of action. Time to onset of action was defined as the first time point post-dose at which the FEV<sub>1</sub> value was at least 12% greater than the pre-dose value (Abstract P24 Figure 1). <h3>Results</h3> FP/FORM time to onset of action was more rapid than FP/SAL (HR: 1.64; 95% CI: 1.28 to 2.10; p&lt;0.001; full analysis population; FP/FORM: n = 101; FP/SAL: n = 100). Onset of action was observed on Day 0 in 78 patients in the FP/FORM group and 64 patients in the FP/SAL group. The probability of onset of action occurring was higher in the FP/FORM group than in the FP/SAL group at each post-dose time point on Days 0, 14, 42 and 84. In total, 72.3% (73/101) patients started on FP/FORM 250/10 μg and 75.2% (76/101) on FP/SAL 250/50 μg. Eight patients (FP/FORM: n = 5; FP/SAL: n = 3) required an increase in dose. Overall, the rate of AEs was comparable (23.8%; 24/101 for both groups). Most AEs were mild or moderate. There were only two severe AEs, both in the FP/FORM group. The frequency of treatment-related AEs was very low in both groups (FP/FORM: n = 1; FP/SAL: n = 1). Clinical laboratory results and vital sign assessments showed no abnormal results. No clinically important ECG changes were observed. Overall, FP/FORM and FP/SAL safety and tolerability profiles were similar. <h3>Conclusion</h3> FP/FORM improved lung function more rapidly than FP/SAL.
A1.27 MPGES-1 deletion increases prostacyclin and evades the elevated systemic ADMA associated with COX-2 inhibitors: relevance to cardiovascular safety of mpges-1 inhibitors
Authors: J Raouf, NS Kirkby, B Ahmetaj-Shala, B Liu, SI Mazi, M Korotkova, Y Zhou, JA Mitchell, PJ Jakobsson
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objective</h3> Cyclooxygenase-2 (COX-2) is involved in the generation of prostanoids such as prostaglandin (PG)E<sub>2</sub>, prostacyclin (PGI<sub>2</sub>) and thromboxane (TXA<sub>2</sub>); PGE<sub>2</sub>is involved in inflammation/pain, whereas the second two are involved in cardiovascular homeostasis. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX-2 and are used to treat inflammation, however they cause cardiovascular side effects. The mechanisms for this include reduced vascular and/or renal PGI<sub>2</sub> and, by effects on the renal medulla, increased dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS). Microsomal PGE<sub>2</sub> synthase 1 (mPGES-1) has been intensively investigated as a safer, alternative anti-inflammatory drug-target. We aimed to investigate how mPGES-1 versus COX-2 influences pathways associated with PGI<sub>2</sub>, ADMAand eNOS in order to assess the potential cardiovascular safety of mPGES-1 as a drug-target. <h3>Materials&nbsp;and&nbsp;Methods</h3> Experiments were performed on mPGES-1<sup>+/+</sup> (WT) and mPGES-1<sup>-/-</sup> (KO) mice as well as PGI<sub>2</sub> synthase (PGIS<sup>-/-</sup>) KO mice. In some experiments WT mice were treated orally with the selective COX-2 inhibitor, parecoxib (100mg/kg; 5 days). Plasma was analysed by immunoassay for ADMA and PGI<sub>2</sub>, or by biochemical assay for creatinine. Renal medulla was stimulated with Ca<sup>2+</sup>ionophore and PGE<sub>2</sub> release measured by immunoassay. Gene expression levels were determined using TaqMan assays. Vascular function (eNOS response) was assessed in isolated aorta stimulated with acetylcholine by wire myography. <h3>Results</h3> WT mice treated with parecoxib displayed no change in plasma PGI<sub>2</sub> levels but, in contrast, mPGES-1 KO mice had significantly higher plasma levels of PGI<sub>2</sub>. In the kidney, mPGES-1 gene expression was lower in the renal medullathan the cortex, and in agreement; mPGES-1 deletion did not alter renal medulla PGE<sub>2</sub> production. mPGES-1deletion had no effect on genes responsible for the production/breakdown of ADMA in the kidney (PRMT1, AGXT2, DDAH1/2). Plasma creatinine/ADMA was elevated in mice treated with parecoxib or PGIS KO mice but unaffected in mPGES-1 KO mice. Furthermore, mPGES-1 deletion significantly improved the eNOS-driven dilator response to acetylcholine in aorta. <h3>Conclusions</h3> Targeting mPGES-1 KO avoids the effects of COX-2 inhibition on renal PGI<sub>2</sub>/ADMA pathway and therefore spares vascular eNOS responses. This supports the development of selective inhibitors of mPGES-1 to more safely treat inflammation.