tbuckley/cabot-search huggingface dataset:
Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: a dual energy CT study
Authors: Nicola Dalbeth, Meaghan E House, Opetaia Aati, Paul Tan, Christopher Franklin, Anne Horne, Gregory D Gamble, Lisa K Stamp, Anthony J Doyle, Fiona M McQueen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The aim of this study was to compare the frequency and volume of dual energy CT (DECT) urate deposits in people with asymptomatic hyperuricaemia and symptomatic gout. <h3>Methods</h3> We analysed DECT scans of the feet from asymptomatic individuals with serum urate ≥540 µmol/L (n=25) and those with crystal proven gout without clinically apparent tophi (n=33). <h3>Results</h3> DECT urate deposits were observed in 6/25 (24%) participants with asymptomatic hyperuricaemia, 11/14 (79%) with early gout (predefined as disease duration ≤3 years) and 16/19 (84%) with late gout (p&lt;0.001). DECT urate deposition was observed in both joints and tendons in the asymptomatic hyperuricaemia group, but significantly less frequently than in those with gout (p≤0.001 for both joint and tendon sites). The volume of urate deposition was also significantly lower in those with asymptomatic hyperuricaemia, compared with the early and the late gout groups (p&lt;0.01 for both comparisons). Similar urate volumes were observed in the early and late gout groups. <h3>Conclusions</h3> Although subclinical urate deposition can occur in people with asymptomatic hyperuricaemia, these deposits occur more frequently and at higher volumes in those with symptomatic gout. These data suggest that a threshold of urate crystal volume may be required before symptomatic disease occurs.
Oral Everolimus Inhibits In-Stent Neointimal Growth
Authors: Andrew Farb, Michael John, Eduardo Acampado, Frank D. Kolodgie, Margaret Forney Prescott, Renu Virmani
Journal: Circulation (2002)

Background— Rapamycin (sirolimus)-eluting stents are associated with reduced restenosis rates in animal studies and initial human trials. The present study evaluated whether orally administered everolimus (a macrolide of the same family as sirolimus) inhibits in-stent neointimal growth in rabbit iliac arteries. Methods and Results— New Zealand white rabbits were randomized to everolimus 1.5 mg/kg per day starting 3 days before stenting and reduced to 1 mg/kg per day from days 14 to 28 (group 1), everolimus 1.5 mg/kg given 1 day before stenting followed by 0.75 mg/kg per day for 28 days (group 2), or matching placebo for each group. Drugs were administered by oral gavage. Stents were deployed in both iliac arteries, and arteries were harvested 28 days after stenting. Group 1 everolimus-treated rabbits experienced weight loss and anorexia, which resolved after the everolimus dose was lowered on day 14. Group 2 animals were healthy for the duration of everolimus dosing. Both everolimus treatment groups significantly reduced in-stent neointimal growth (46% reduction and 42% reduction in intimal thickness in groups 1 and 2, respectively). In group 2 everolimus-treated animals, the neointima was healed or healing, characterized by stent struts covered by a thin neointima, overlying endothelial cells, and only small foci of fibrin. Scanning electron microscopy showed &gt;80% stent surface endothelialization in group 2 everolimus-treated rabbits. Conclusions— Oral everolimus suppresses in-stent neointimal growth in the rabbit iliac artery. At a dose of 1.5 mg/kg given 1 day before stenting followed by 0.75 mg/kg per day for 28 days, everolimus was well tolerated and was associated with significant neointimal healing.
Common Flaws in Pharmacoepidemiologic Study Design and Analysis
Authors: Jennifer L. Lund, Jonathan Montomoli
Journal: Journal of Clinical Oncology (2013)

PTEN downregulation may contribute to liver disease progression in these patients, possibly increasing the risk of HCC.In HCV infection, a single study has shown a negative impact of PTEN downregulation in HCC tissue on patients' survival. 16 Regrettably, whether the downregulation of PTEN predicts also the occurrence of HCC in the same setting is unknown because of lack of properly conducted prospective studies.However, the fact that the risk of developing HCC is higher in hepatitis C patients infected with the HCV genotype 3 17,18 or who have steatosis 19,20 is indirect evidence supporting this hypothesis.Thus, it would be interesting to have more detailed information on the virological characteristics of the patients included in the study of Tsan et al. 1 In particular, it would be important to know whether patients to whom statins afforded protection from HCC were infected with genotype 3; even a moderate, statin-mediated antiviral effect in these patients would have had as a consequence a reversal of the PTEN downregulation, hence a reduced risk of developing HCC.In addition, we regret that no information was provided concerning the viral load status of the patients included in the study; history of anti-HCV treatment cannot be used as a surrogate marker of viremia or lack thereof because patients with therapy-induced viral eradication would have been considered together with treatment failures.
Fibroblast Growth Factor Signaling during Early Vertebrate Development
Authors: Ralph T. Böttcher, Christof Niehrs
Journal: Endocrine Reviews (2004)

Fibroblast growth factors (FGFs) have been implicated in diverse cellular processes including apoptosis, cell survival, chemotaxis, cell adhesion, migration, differentiation, and proliferation. This review presents our current understanding on the roles of FGF signaling, the pathways employed, and its regulation. We focus on FGF signaling during early embryonic processes in vertebrates, such as induction and patterning of the three germ layers as well as its function in the control of morphogenetic movements.
Curcumin Analogue CDF Inhibits Pancreatic Tumor Growth by Switching on Suppressor microRNAs and Attenuating EZH2 Expression
Authors: Bin Bao, Shadan Ali, Sanjeev Banerjee, Zhiwei Wang, Farah Logna, Asfar S. Azmi, Dejuan Kong, Aamir Ahmad, Yiwei Li, Subhash Padhye, Fazlul H. Sarkar
Journal: Cancer Research (2011)

Abstract The histone methyltransferase EZH2 is a central epigenetic regulator of cell survival, proliferation, and cancer stem cell (CSC) function. EZH2 expression is increased in various human cancers, including highly aggressive pancreatic cancers, but the mechanisms underlying for its biologic effects are not yet well understood. In this study, we probed EZH2 function in pancreatic cancer using diflourinated-curcumin (CDF), a novel analogue of the turmeric spice component curcumin that has antioxidant properties. CDF decreased pancreatic cancer cell survival, clonogenicity, formation of pancreatospheres, invasive cell migration, and CSC function in human pancreatic cancer cells. These effects were associated with decreased expression of EZH2 and increased expression of a panel of tumor-suppressive microRNAs (miRNA), including let-7a, b, c, d, miR-26a, miR-101, miR-146a, andmiR-200b, c that are typically lost in pancreatic cancer. Mechanistic investigations revealed that reexpression of miR-101 was sufficient to limit the expression of EZH2 and the proinvasive cell surface adhesion molecule EpCAM. In an orthotopic xenograft model of human pancreatic cancer, administration of CDF inhibited tumor growth in a manner associated with reduced expression of EZH2, Notch-1, CD44, EpCAM, and Nanog and increased expression of let-7, miR-26a, and miR-101. Taken together, our results indicated that CDF inhibited pancreatic cancer tumor growth and aggressiveness by targeting an EZH2-miRNA regulatory circuit for epigenetically controlled gene expression. Cancer Res; 72(1); 335–45. ©2011 AACR.
A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment
Authors: Norishige Yoshikawa, Koichi Nakanishi, Mayumi Sako, Mari S. Oba, Rintaro Mori, Erika Ota, Kenji Ishikura, Hiroshi Hataya, Masataka Honda, Shuichi Ito, Yuko Shima, Hiroshi Kaito, Kandai Nozu, Hidefumi Nakamura, Takashi Igarashi, Yasuo Ohashi, Kazumoto Iijima
Journal: Kidney International (2014)

In this multicenter, open-label, randomized controlled trial, we determined whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was inferior or not to 6-month therapy despite significantly less steroid exposure. The primary end point was time from start of initial treatment to start of frequently relapsing nephrotic syndrome. The pre-specified non-inferiority margin was a hazard ratio of 1.3 with one-sided significance of 5%. We randomly assigned 255 children with an initial episode of steroid-sensitive nephrotic syndrome to either 2 - or 6-month treatment of which 246 were eligible for final analysis. The total prednisolone exposure counted both initial and relapse prednisolone treatment administered over 24 months. Median follow-up in months was 36.7 in the 2-month and 38.2 in the 6-month treatment group. Time to frequent relaps was similar in both groups; however, the median was reached only in the 6-month group (799 days). The hazard ratio was 0.86 (90% confidence interval, 0.64-1.16) and met the non-inferior margin. Time to first relapse was also similar in both groups: median day 242 (2-month) and 243 (6-month). Frequency and severity of adverse events were similar in both groups. Most adverse events were transient and occurred during initial or relapse therapy. Thus, 2 months of initial prednisolone therapy for steroid-sensitive nephrotic syndrome, despite less prednisolone exposure, is not inferior to 6 months of initial therapy in terms of time to onset of frequently relapsing nephrotic syndrome.
Culture and symptom reporting at menopause
Authors: Melissa K Melby, Margaret Lock, Patricia Kaufert
Journal: Human Reproduction Update (2005)

The purpose of the present paper is to review recent research on the relationship of culture and menopausal symptoms and propose a biocultural framework that makes use of both biological and cultural parameters in future research. Medline was searched for English-language articles published from 2000 to 2004 using the keyword 'menopause' in the journals—Menopause, Maturitas, Climacteric, Social Science and Medicine, Medical Anthropology Quarterly, Journal of Women's Health, Journal of the American Medical Association, American Journal of Epidemiology, Lancet and British Medical Journal, excluding articles concerning small clinical samples, surgical menopause or HRT. Additionally, references of retrieved articles and reviews were hand-searched. Although a large number of studies and publications exist, methodological differences limit attempts at comparison or systematic review. We outline a theoretical framework in which relevant biological and cultural variables can be operationalized and measured, making it possible for rigorous comparisons in the future. Several studies carried out in Japan, North America and Australia, using similar methodology but different culture/ethnic groups, indicate that differences in symptom reporting are real and highlight the importance of biocultural research. We suggest that both biological variation and cultural differences contribute to the menopausal transition, and that more rigorous data collection is required to elucidate how biology and culture interact in female ageing.
The Acquired Immunodeficiency Syndrome in a Cohort of Homosexual Men
Authors: HAROLD W. JAFFE
Journal: Annals of Internal Medicine (1985)

A cohort of 6875 homosexual men, initially seen at the San Francisco City Clinic between 1978 and 1980, were studied to determine the incidence and prevalence of the acquired immunodeficiency syndrome, related conditions, and infection with the human T-lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV). By December 1984, 2.4% of the men had the syndrome; mortality attributable to the syndrome in 1984 was 600/100 000. For each man with the syndrome in a representative sample of 474 cohort members seen in 1984, 7.5 men had generalized lymphadenopathy, 1.1 had other prodromal findings, and 0.8 had hematologic abnormalities. Prevalence of serum antibodies to HTLV-III/LAV, measured by an enzyme-linked immunosorbent assay, increased from 4.5% in 1978 to 67.4% in 1984. Of 31 persons who were seropositive and without the syndrome between 1978 and 1980, 2 developed the syndrome and 8 developed related conditions during a median follow-up of 61 months. Over a 6-year period, two thirds of cohort members were infected with HTLV-III/LAV and almost one third developed related conditions.
Tumour infiltrating lymphocytes and apoptosis are independent features in colorectal cancer stratified according to microsatellite instability status
Authors: J M Michael-Robinson
Journal: Gut (2001)

<h3>BACKGROUND</h3> The presence of high level DNA microsatellite instability (MSI-H) in colorectal cancer is associated with an improved prognosis, as is the presence of tumour infiltrating lymphocytes (TILs). It is not clear if TILs contribute directly to the survival advantage associated with MSI-H cancers through activation of an antitumour immune response. <h3>AIMS</h3> To correlate TIL and apoptosis rates in colorectal cancer stratified by MSI status. <h3>METHODS</h3> The distribution of TILs was characterised and quantified in a selected series of 102 sporadic colorectal cancers classified according to levels of MSI as 32 MSI-H, 30 MSI-low (MSI-L), and 40 microsatellite stable (MSS). Archival blocks were immunostained using the T cell markers CD3 and CD8, and the B cell marker CD20. Apoptosis of malignant epithelial cells was quantified by immunohistochemistry with the M30 CytoDEATH antibody. <h3>RESULTS</h3> Positive staining with anti-CD3 and negative staining with anti-CD20 identified virtually all TILs as T cells. The majority of CD3<sup>+</sup> TILs (&gt;75%) also stained with anti-CD8. TILs were most abundant in MSI-H colorectal cancers in which 23/32 (72%) scored as TIL positive. Only 5/40 (12.5%) MSS tumours and 9/30 (30%) MSI-L cancers were TIL positive (p&lt;0.0001). MSI-H cancers showed a twofold higher rate of apoptosis (mean (SD) 3.52 (0.34)%) than the MSS cancers (1.53 (0.23)%) while the MSI-L subgroup had an intermediate level (2.52 (0.35)%) (p&lt;0.0001). Overall, there was a small (<i>r</i>=0.347) but significant linear correlation between CD3<sup>+</sup> and M30<sup>+</sup> random apoptosis counts (p&lt;0.001). However, TILs and apoptosis showed little colocalisation. <h3>CONCLUSIONS</h3> While TILs might be expected to explain the increased apoptotic rate and improved prognosis of MSI-H cancers, it is likely that TILs and apoptosis are independent characteristics of MSI-H cancers.
Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy
Authors: Thomas S. Uldrick, Kathleen M. Wyvill, Pallavi Kumar, Deirdre O'Mahony, Wendy Bernstein, Karen Aleman, Mark N. Polizzotto, Seth M. Steinberg, Stefania Pittaluga, Vickie Marshall, Denise Whitby, Richard F. Little, Robert Yarchoan
Journal: Journal of Clinical Oncology (2012)

Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T 1 ), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients.
HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans
Authors: Sachie Marubayashi, Priya Koppikar, Tony Taldone, Omar Abdel-Wahab, Nathan West, Neha Bhagwat, Eloisi Caldas-Lopes, Kenneth N. Ross, Mithat Gönen, Alex Gozman, James H. Ahn, Anna Rodina, Ouathek Ouerfelli, Guangbin Yang, Cyrus Hedvat, James E. Bradner, Gabriela Chiosis, Ross L. Levine
Journal: Journal of Clinical Investigation (2010)

JAK2 kinase inhibitors were developed for the treatment of myeloproliferative neoplasms (MPNs), following the discovery of activating JAK2 mutations in the majority of patients with MPN. However, to date JAK2 inhibitor treatment has shown limited efficacy and apparent toxicities in clinical trials. We report here that an HSP90 inhibitor, PU-H71, demonstrated efficacy in cell line and mouse models of the MPN polycythemia vera (PV) and essential thrombocytosis (ET) by disrupting JAK2 protein stability. JAK2 physically associated with both HSP90 and PU-H71 and was degraded by PU-H71 treatment in vitro and in vivo, demonstrating that JAK2 is an HSP90 chaperone client. PU-H71 treatment caused potent, dose-dependent inhibition of cell growth and signaling in JAK2 mutant cell lines and in primary MPN patient samples. PU-H71 treatment of mice resulted in JAK2 degradation, inhibition of JAK-STAT signaling, normalization of peripheral blood counts, and improved survival in MPN models at doses that did not degrade JAK2 in normal tissues or cause substantial toxicity. Importantly, PU-H71 treatment also reduced the mutant allele burden in mice. These data establish what we believe to be a novel therapeutic rationale for HSP90 inhibition in the treatment of JAK2-dependent MPN.
Poliomyelitis and the postpolio syndrome
Authors: Robin S Howard
Journal: BMJ (2005)

In the first half of the 20th century, poliomyelitis was widely feared.It often struck without warning, was highly contagious, and affected large, young populations, causing prolonged or permanent flaccid paralysis or death.There are arresting and disturbing accounts of the explosive nature of polio epidemics and the response of communities to these outbreaks. 1he effective control of poliomyelitis throughout most of the world has been a remarkable story of scientific and social progress.However, "wild" poliomyelitis is still endemic in parts of sub-Saharan Africa and the Indian subcontinent, and it continues to occur sporadically elsewhere.In addition, there is a small incidence of vaccine induced polio in infants and adults.][4] Acute poliomyelitis is now rarely encountered in the United Kingdom, but "imported" poliomyelitis still occurs and it is necessary to distinguish acute poliomyelitis from other causes of acute flaccid paralysis.Despite the obvious success of preventive policies, many patients who had poliomyelitis experience late functional deterioration after periods of prolonged stability-the so called postpolio syndrome.The patterns of disability and their management present unique challenges to the multidisciplinary rehabilitation team.
Metformin reduces endothelial cell expression of both the receptor for advanced glycation end products and lectin-like oxidized receptor 1
Authors: Nadjat Ouslimani, Meriem Mahrouf, Jacqueline Peynet, Dominique Bonnefont-Rousselot, Claudine Cosson, Alain Legrand, Jean-Louis Beaudeux
Journal: Metabolism (2007)
Mechanisms of depressed delayed-type hypersensitivity in rheumatoid arthritis: the role of protein energy malnutrition.
Authors: P Emery, G Panayi, D Symmons, G Brown
Journal: Annals of the Rheumatic Diseases (1984)

The presence of anergy and its relationship to malnutrition was investigated in patients with rheumatoid arthritis (RA) and in controls. A generalised reduction in delayed cutaneous hypersensitivity to 7 recall antigens were found in 104 RA patients compared with 67 controls. No measured of the disease was capable of predicting cutaneous anergy, which was present in 36% of patients but none of the controls. A detailed dietary assessment in 30 RA patients and 30 controls revealed little evidence of clinically important malnutrition. It is therefore concluded that the cutaneous anergy of rheumatoid arthritis is not a consequence of nutritional factors.
Combination of Paclitaxel, Ifosfamide, and Cisplatin Is an Effective Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Tumors
Authors: G. Varuni Kondagunta, Jennifer Bacik, Alessia Donadio, Dean Bajorin, Stephanie Marion, Joel Sheinfeld, George J. Bosl, Robert J. Motzer
Journal: Journal of Clinical Oncology (2005)

The efficacy of paclitaxel was evaluated in combination with ifosfamide and cisplatin as second-line chemotherapy for patients with relapsed testicular germ cell tumors (GCTs).Forty-six patients with progressive metastatic GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. Eligibility required that patients have both a testis primary tumor site and a prior complete response (CR) to a first-line chemotherapy program, which had been identified previously as favorable prognostic factors to conventional-dose salvage chemotherapy.Thirty-two (70%) of 46 patients achieved a CR to treatment. Three patients (7%) who achieved a CR relapsed after TIP chemotherapy. Twenty-nine patients are continuously disease free at a median follow-up time of 69 months, resulting in a 63% durable CR rate and a 2-year progression-free survival rate of 65% (95% CI, 51% to 79%).Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.
High incidence of cardiovascular events in patients with rheumatoid arthritis: Table 1
Authors: K S S Steen, W F Lems, I M Visman, M Heierman, B A C Dijkmans, J W R Twisk, M Boers, M T Nurmohamed
Journal: Annals of the Rheumatic Diseases (2009)

Rheumatoid arthritis (RA) is associated with higher risk for cardiovascular disease (CVD) in comparison with the general population.1 Traditional cardiovascular (CV) risk factors only partially explain the higher risk for CVD.2 There is increasing evidence that inflammation explains the enhanced CV risk in RA, as inflammation has a pivotal role in the development of atherosclerotic disease and this might be the link between increased atherosclerotic CVD and RA.3 Other RA-related factors might be undertreatment of CV comorbidity,1 and the use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase 2 inhibitors.4,5

The objective of this prospective observational study was to determine the incidence of CV events in patients with RA in comparison to the general Dutch population, where the incidence of CV events is …