tbuckley/cabot-search huggingface dataset:
Acyclovir for Prevention of Cytomegalovirus Infection and Disease after Allogeneic Marrow Transplantation
Authors: J D Meyers, E C Reed, D H Shepp, M Thornquist, P S Dandliker, C A Vicary, N Flournoy, L E Kirk, J H Kersey, E D Thomas
Journal: New England Journal of Medicine (1988)

Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.
AB1206 Use of questionnaires for life quality assessment of JIA patients in actual clinical practices:
Authors: T. Shelepina, N. Stepanenko, E. Fedorov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Life quality is one of the objective criteria of JIA patients treatment efficiency. <h3>Objectives</h3> To examine comparability of assessment results in terms of the degree of motor disturbance and presence of psychological and school problems related to patient assessment when using various questionnaires. <h3>Methods</h3> 51 pts with several variants of JIA (9 pts suffering from the systemic variant; 27 – polyarticular variant; 5- oligoarticular, JAS-4 pts and 4 pts suffering from psoriatic arthritis. F/M =82/18%. (CHAQ – validated version(1), JAQQ and JAMAR: non-validated version – direct translate(2, 3). Average age is equal to 13.8±3.5 yrs. Average remoteness of the illness is 7.1±3.8 yrs. The following questionnaires were applied: CHAQ(1gr); JAQQ(2gr); JAMAR (3gr); combination (4gr). Clinical courses and time of illness did not differ much. 41 pts were examines by a psychologist. <h3>Results</h3> Serious psychological problems were revealed with 50% of patients (psychologist data). <h3>Conclusions</h3> The above questionnaires provide comparable results in terms of pts number with various degrees of motor disturbances. Comparability in terms of social status is not complete. Multifunctional questionnaires provide an adequate vision of the patient group in general. For individual evaluation of the patient’s state a consultation of a psychologist in required. Combination of questionnaires is not feasible. It is preferable to apply CHAQ and JAMAR. <h3>References</h3> Nikishina I., Ruperto N., Kuzmina N., et al. Clin Exp Rheumatol 2001;19 (suppl.23):131-135 C.M.Duffy et.al J Rheumatol 1997;24:738-746 Q.Filocamo, A.Consolaro et.al J Rheumatol 2011;38:938-953. <h3>Disclosure of Interest</h3> None Declared
Abstract 3976: The role of a novel oncomiR, miR-135b, in lung cancer metastasis and clinical application
Authors: Ching-Wen Lin, Jau-Chen Lin, Yih-Leong Chang, Hsuan-Yu Chen, Szu-Hua Pan, Tse-Ming Hong, Pan-Chyr Yang
Journal: Cancer Research (2011)

Abstract microRNA(miR) may function endogenous siRNA and regulate a diversity of cellular function through translational repression. Dysregulations of miR expression are involved in carcinogenesis and progression in various cancers. By combining the miR microarray and genomic DNA-methylation array, we identified an intronic miR, miR-135b, which is up-regulated in high invasive lung cancer cell CL1-5. The promoter region of miR-135b is highly de-methylated in high invasive cells and its expression in the less invasive lung cancer cells can be induced by demethylating agent 5’-aza-CdR treatment. Ectopically expression of miR-135b enhanced cell invasive and migratory ability in vitro as well as the orthotopic tumor growth and lung metastasis activity in vivo, whereas specific inhibition of miR-135b decreased tumor growth and metastatic activities. Using the bioinformatic prediction tools, we identified and confirmed that miR-135b could directly repress the expression of Lzts1 through 3’UTR seed-binding. Ectopically-expressed Lzts1 inhibited cell invasion and migration activity, implicating that miR-135b may promote lung cancer cell metastasis by down-regulating Lzts1. Moreover, high level of miR-135b and low level of Lzts1 expressions were associated with poor overall survival in lung cancer patients. We also showed that the miR-135b expression was regulated by NF-κB signaling-cascade and synergistically induced by co-treatment of 5’-aza-CdR and TNF-α, implying that the abnormal expression of miR-135b in cancers may result from inflammatory stimulation and epigenetic modulation. Our results support that miR-135b is an oncogenic miR that may contribute to lung cancer progression and metastasis. The miR-135b/Lzts1 pathway is a promising therapeutic target of lung cancer. 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 3976. doi:10.1158/1538-7445.AM2011-3976
Continuous Ambulatory Peritoneal Dialysis
Authors: Karl D. Nolph, Anne S. Lindblad, Joel W. Novak
Journal: New England Journal of Medicine (1988)

CHRONIC renal failure connotes the permanent deterioration of the glomerular filtration rate. A urinary creatinine clearance of 5 to 8 ml per minute generally indicates a glomerular filtration rate of less than 5 percent of normal and is usually considered an indication for dialysis treatment, particularly when symptoms of uremia are present. In suitable candidates, kidney transplantation is the best treatment. In other patients, dialysis treatments are usually needed for months or years; in some they must be provided as lifelong therapy.Hemodialysis, in which an extracorporeal dialyzer removes metabolites from the blood, is currently used by approximately 75,000 Americans . . .
A Tension Bulla Mimicking Tension Pneumothorax
Authors: Maria Elena Vega, Brian Civic
Journal: New England Journal of Medicine (2011)

A 46-year-old male smoker presented to the ER with chest pain and shortness of breath. He was in mild distress, with an oxygen saturation of 97% while breathing ambient air. The physical examination revealed hyperresonance and decreased breath sounds on the left.
Increased FDG Uptake in Scrotal Steatocystoma Multiplex With Calcification
Authors: Aisheng Dong, Changjing Zuo, Zhijun Zhai, Yang Wang, Yuchao Dong
Journal: Clinical Nuclear Medicine (2013)

Steatocystoma multiplex is a rare, benign, sporadic or familial disorder. Steatocystoma multiplex with extensive calcification is extremely rare. A 57-year-old man presented fever and cough with expectoration for 3 weeks. Chest CT showed bilateral pleural effusion. FDG PET/CT showed diffuse FDG uptake of the bone marrow and multiple hypermetabolic calcified nodules in the scrotum with SUVmax of 7.6. Blood culture revealed septicemia. Skin biopsy of the scrotal nodules revealed steatocystoma multiplex with calcification. Histopathologically, there were rich multinucleated giant cells and lymphocytes in the cyst wall of the steatocystoma, which may contribute to the increased FDG uptake.
Abstract 1269: Molecular changes underlying bortezomib sensitization of cancer cells to TRAIL-mediated apoptosis
Authors: Alan D. Brooks, Candace R. Thompson, Thomas J. Sayers
Journal: Cancer Research (2010)

Abstract We have previously shown that the proteasome inhibitor bortezomib (Velcade/PS-341) specifically sensitized certain human renal carcinoma (RCC) lines to apoptosis induced by the TNF family-member TRAIL. A comparison of RCC sensitized by bortezomib with those that remained resistant revealed no major bortezomib-induced changes in the levels of many apoptosis proteins. Also, when bortezomib treatment induced specific changes in protein levels (mcl-1, Bik and survivin) these changes did not directly correlate with subsequent sensitization or resistance to TRAIL apoptosis. In addition changes in surface expression of TRAIL receptors (DR4, DR5, DcR1, DcR2) following bortezomib treatment also did not correlate well with sensitization or resistance. By contrast, enhanced procaspase 8 activation following bortezomib pretreatment and TRAIL exposure was only observed in the sensitized RCC. This increase in procaspase 8 activation in cell extracts of sensitized RCC was observed using both enzyme assays as well as western blotting for activated (cleaved) caspase 8. Use of the apoptosis-resistant MCF-7 cell line demonstrated that bortezomib pretreatment increased caspase-8 activation on exposure to TRAIL even in the absence of subsequent downstream caspase activation and apoptosis. This suggests that bortezomib increases caspase-8 activation upstream at the death-inducing signaling complex (DISC). Furthermore, immunoprecipitation of the DISC demonstrated higher levels of active caspase 8 in the DISC of sensitized but not resistant RCC. Interestingly ACHN (a bortezomib-sensitized RCC) was also sensitized to TRAIL apoptosis when adherence was prevented by coating cell culture dishes with poly-HEMA. In parallel this loss of adherence abolished the sensitizing effects of bortezomib treatment. Bortezomib and poly-HEMA treatment of RCC both result in reduced cellular proliferation, and may change cell adherence properties. Whether both of these treatments sensitize RCC to TRAIL using common or distinct molecular pathways is under further investigation. Funded in part by DHSS #NO1-CO-12400 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 1269.
Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, endoplasmic reticulum stress, and lipogenesis and is regulated by hepatocyte nuclear factor 4 alpha in mice
Authors: Yuanyuan Li, Munaf Zalzala, Kavita Jadhav, Yang Xu, Takhar Kasumov, Liya Yin, Yanqiao Zhang
Journal: Hepatology (2016)

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). So far, the underlying mechanism remains poorly understood. Here, we show that hepatic carboxylesterase 2 (CES2) is markedly reduced in NASH patients, diabetic db/db mice, and high-fat diet (HFD)-fed mice. Restoration of hepatic CES2 expression in db/db or HFD-fed mice markedly ameliorates liver steatosis and insulin resistance. In contrast, knockdown of hepatic CES2 causes liver steatosis and damage in chow- or Western diet-fed C57BL/6 mice. Mechanistically, we demonstrate that CES2 has triglyceride hydrolase activity. As a result, gain of hepatic CES2 function increases fatty acid oxidation and inhibits lipogenesis, whereas loss of hepatic CES2 stimulates lipogenesis by inducing endoplasmic reticulum stress. We further show that loss of hepatic CES2 stimulates lipogenesis in a sterol regulatory element-binding protein 1 (SREBP-1)-dependent manner. Finally, we show that hepatocyte nuclear factor 4 alpha (HNF-4α) plays a key role in controlling hepatic CES2 expression in diabetes, obesity, or NASH.CES2 plays a protective role in development of NAFLD. Targeting the HNF-4α/CES2 pathway may be useful for treatment of NAFLD. (Hepatology 2016;63:1860-1874).
Abstract 2583: LA480, a bivalent humanized c-Met monoclonal antibody, inhibits tumor growth without eliciting significant agonist activity
Authors: Wei Zeng, Mark Wortinger, Wei Jennifer Yang, Victoria Peek, Lei Yan, Jirong Lu, Chi-Kin Chow, Peter Vaillancourt, Julian Davies, Irene Denning, Spring Weir, Don McClure, Sudhakar Chintharlapalli, Ling Liu
Journal: Cancer Research (2010)

Abstract The receptor tyrosine kinase c-Met and its ligand HGF elicit multiple cellular activities including cell proliferation, motility, invasion, tubulogenesis, angiogenesis and anti-apoptosis. Dysregulation of this pathway has emerged as a crucial feature for many human tumors. However, past efforts in developing c-Met therapeutic antibodies that inhibit both ligand-dependent and ligand-independent c-Met activation have been largely unsuccessful due to agonist properties of the antibodies. In fact, c-Met antibodies exhibiting medium to strong agonist activity stimulate proliferation of both normal and tumor cells. We report here that LA480, a bivalent humanized monoclonal c-Met antibody, blocks HGF binding to c-Met and also induces c-Met internalization. Moreover, LA480 inhibits growth of xenograft tumors mediated by HGF-dependent and HGF-independent c-Met pathway activation. In order to evaluate whether LA480 has agonist activity, we tested LA480 in the following HGF-responsive biological assays: proliferation of primary human hepatocytes and tumor cell lines, scattering of DU145 cells, stimulation of HepG2 invasion and tubulogenesis, tube formation in endothelial and stromal cell co-cultures, and protection from apoptosis induced by staurospor in Caki-1 cells. A bivalent c-Met agonist antibody and HGF were included in the assays as positive controls, in addition to antibody isotype negative controls. Our results demonstrate that LA480 does not significantly stimulate cell proliferation, scattering, invasion, tubulogenesis, angiogenesis or apoptosis protection in the above assay systems. Under the same conditions, the agonist positive control c-Met antibody and HGF both significantly induced these biological effects. These unique properties of LA480 suggest that it may be a promising therapeutic reagent for treatment of cancers driven by ligand-dependent and ligand-independent c-Met activation. 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 2583.
AB0157 The secretory activity of abdominal adipose tissue in patients with rheumatoid arthritis
Authors: E. Kontny, A. Zielinska, W. Maslinski, P. Gluszko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate spontaneous adipocytokine secretion by subcutaneous abdominal adipose tissue (SAAT) explants obtained from patients with rheumatoid arthritis (RA). <h3>Methods</h3> SAAT explants were obtained by 18 G needle biopsy form 18 RA patients (16F/2M, the mean age 58,5±3,6 years) dispersed and cultured <i>in vitro</i> (100mg tissue/ml). Select adipocytokines: leptin, adiponectin, IL-6, IL-8 and macrophage migration inhibiting factor (MIF) concentrations were measured in culturesupernatants using ELISA and in sera of patients. Body mass index (BMI), disease activity scores (DAS 28), x-ray Larsen scores, routine blood tests and other demographic and clinical information were obtained. The association of BMI with duration of the disease, DAS 28, CRP levels, ESR, x-ray scores and concentrations of adipocytokines was analysed using linear regression. The spontaneous adipocytokine secretion from SAAT was compared with serum levels of measured variables. <h3>Results</h3> Disease activity of RA patients was high (DAS28 = 5,28±0,27SD, CRP levels 21.0±5,2 mg/l), mean disease duration 11,8±2,5 years, and patients BMI 26,98±1.28. Patients were treated with methotrexate (13) or leflunomide (1) or sulphasalazine (2) with low doses of prednisone (7). None had received biologics. The SAAT concentrations of IL-6 (1042±242 pg/100mg), IL-8 (3044±833 pg/100mg), MIF (2597±614 pg/100mg) were significantly higher (p&lt;0,006) comparing to the serum levels of IL-6 (747±416 pg/ml), IL-8 (49,4±36,9 pg/ml), MIF (476±76 pg/ml). The SAAT leptin (1,828±0,29 ng/100mg) was significantly lower then the serum leptin levels (30,185±5,7 ng/ml, p&lt;0.05). BMI values of patients correlated positively with the SAAT IL-8 concentrations (r=0,57 p&lt;0.05) and with the serum leptin (r=0,58 p&lt;0.05) level, and negatively with x-ray scores ((r= -0,62 p&lt;0.05). We found positive correlation of serum CRP levels with SAAT IL-6 (r=0,66 p&lt;0.05) but not with serum IL-6. X-ray scores correlated positively with the disease duration (r=0,77 p&lt;0.05) and negatively with the SAAT IL-8 (r=-0.53 p&lt;0.05). <h3>Conclusions</h3> Our data suggest that subcutaneous abdominal adipose tissue may modulate the systemic inflammatory processes in RA releasing pro and anti-inflammatory mediators. Further studies are needed to explore potential association between obesity, abdominal fat bioactivity and RA severity and progression <h3>Disclosure of Interest</h3> None Declared
Safety report of a randomized phase II trial to evaluate the combination of cetuximab plus accelerated concomitant boost radiotherapy (RT) followed or not followed by cetuximab monotherapy in patients (pts) with locally advanced squamous cell carcinoma of the oropharynx
Authors: R. Mesia, A. Rueda, R. Vera, A. Lozano, J. Medina, D. Aguiar Bujanda, F. Arias de la Vega, G. Triana, J. Carles, R. Lopez Lopez
Journal: Journal of Clinical Oncology (2008)

6076 Background: The objectives of this prospective, randomized, phase II trial conducted in 18 Spanish hospitals was to evaluate the safety and efficacy of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in pts with locally-advanced oropharyngeal cancer. Methods: Main eligibility criteria: >18 yrs old, Stage III-IVM0 squamous tumors. Group A received concomitant boost RT (69.9 Gy in 28 days) + cetuximab (400 mg/m2 1 wk before RT and 250 mg/m2/wk during RT). Group B received an additional 12 consecutive wks of cetuximab maintenance therapy. Results: Demographics of the 92 enrolled pts (45 [A]; 47 [B]) were (A/B): median age (range), 60(42–75)/61(45–80); males, 80%/92%; Stage IV, 69%/72%. Compliance rates during the concomitant phase were high and similar in both groups (>85% received full dose of RT and cetuximab). In Group B, compliance in the maintenance phase was also high (86% completed >10 wks). Four pts in group B did not receive cetuximab as maintenance therapy (2 consent withdrawals and 2 AEs). Cetuximab was generally well tolerated (most AEs grade 1–2 cutaneous rash, mucositis, and asthenia). The main grade 3–4 AEs were acne-like rash (16%/15% [A/B]), mucositis (47%/64%), radiation dermatitis (31%/19%), and asthenia (2%/6%). Pts on cetuximab maintenance therapy did not have a significant delay in toxicity recovery after combined treatment (table). There were 6 deaths (4 in group, 2 in group B); none was related to study treatment but occurred in the context of disease complications or underlying disease. Conclusions: Cetuximab maintenance therapy is associated with an acceptable safety profile when administered after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma. Eficcacy results are expected by November 2008. Pts with grade 3/4 AEs (%) EndRT (A/B) Wk 4 (A/B) Wk 8 (A/B) Wk12 (A/B) Acne-like rash 8.9/8.5 6.6/4.3 0/2.1 0/0 Mucositis 40/55 6.7/10.6 0/4.3 0/2.1 Radiation dermatitis 17.8/4.3 15.6/14.9 0/0 0/0 Asthenia 0/4.3 0/2.1 0/0 2.2/0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Serono Merck Serono
AB0720 Performance of Referral Parameters of Patients with Chronic Back Pain Included in the Spondyloarthritis Caught Early Cohort (SPACE): Table 1.
Authors: S. Pellegrom, M. de Hooge, T. Huizinga, D. van der Heijde, F. van Gaalen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> A recent study in Dutch primary care shows that axial spondyloarthritis (axSpA) is underdiagnosed1. A possible reason is that the effectiveness of referral parameters recommended by Dutch GP guidelines is not known. <h3>Objectives</h3> To examine the referral parameters to the rheumatologist of patients included in the SPondyloArthritis Caught Early (SPACE) cohort and the extent to which they are associated with axSpA. <h3>Methods</h3> Referral letters to rheumatologists for patients with chronic back pain (≥3 months, ≤2 years, onset ≤45 years) included in the SPACE cohort were used. Referral parameters analysed were the red-flags mentioned in the current back pain guideline from the Dutch GP association (NHG), features from the Assessment of Spondyloarthritis international Society (ASAS) inflammatory back pain (IBP) criteria, and the SpA features in the ASAS axSpA criteria. Arthralgia and myalgia were mentioned often and were added as referral parameters. AxSpA was defined as meeting ASAS classification criteria for axSpA <h3>Results</h3> Clinical and referral data was available for 204 patients, 75 patients had axSpA (36.8%) and 129 patients had no axSpA (63.2%). 155 patients (75.9%) were referred by GPs, 15 patients (7.4%) by orthopaedist and 34 patients (16.7%) by other specialists. Mentioning in the referral letter of Improvement with exercise (OR 3.0; 95%CI 1.1-8.1), family history of SpA (OR 5.1; 95%CI 1.9-13.9) and a positive HLA-B27 (OR 12.2; 95%CI 3.9-37.1) were associated with axSpA. Arthralgia was negatively associated with axSpA (OR 0.4; 95%C I0.2-0.8). All ASAS axSpA features available at baseline in the SPACE cohort were found more often than in the referral letter see table. <h3>Conclusions</h3> Most of the parameters mentioned in referral letters were not associated with axSpA. AxSpA features present in patients were often not mentioned in referral letters. To improve efficiency of referrals, physicians should be made more aware of SpA features. <h3>References</h3> Weel A AC&amp;R 2013 Sep 19 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3367
Signaling Pathways for Cardiac Hypertrophy and Failure
Authors: John J. Hunter, Kenneth R. Chien
Journal: New England Journal of Medicine (1999)

Heart failure is a leading cause of mortality in the United States. As a result of advances in genetic technology, a molecular basis of heart failure is emerging.1,2 This review highlights the ways in which these insights are leading to new therapeutic targets in patients with acquired forms of heart failure.Morphologic Classification of Cardiac HypertrophyMyocardial hypertrophy is an early milestone during the clinical course of heart failure and an important risk factor for subsequent cardiac morbidity and mortality. In response to a variety of mechanical, hemodynamic, hormonal, and pathologic stimuli, the heart adapts to increased demands for . . .