tbuckley/cabot-search huggingface dataset:
Interim [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography Scan in Diffuse Large B-Cell Lymphoma Treated With Anthracycline-Based Chemotherapy Plus Rituximab
Authors: Violaine Safar, Jehan Dupuis, Emmanuel Itti, Fabrice Jardin, Christophe Fruchart, Stéphane Bardet, Pierre Véra, Christiane Copie-Bergman, Alain Rahmouni, Hervé Tilly, Michel Meignan, Corinne Haioun
Journal: Journal of Clinical Oncology (2011)

The prognostic value of [(18)F]fluorodeoxyglucose-positron emission tomography (PET), interpreted according to visual criteria, is a matter of debate for diffuse large B-cell lymphoma (DLBCL). Moreover, most published studies do not differentiate between patients treated with or without rituximab. We retrospectively investigated the prognostic value of PET performed in patients with DLBCL receiving chemotherapy plus rituximab. Images were interpreted both visually and by computing maximum standardized uptake value (SUV(max)) between PET performed at baseline and after two cycles of chemotherapy.One hundred twelve patients newly diagnosed with DLBCL were treated with an anthracycline-based regimen plus rituximab. A PET was performed after two cycles of treatment. PET positivity or negativity was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier analysis.Visual analysis showed that 70 patients (62.5%) presented with a negative PET scan after two cycles of treatment. The 3-year PFS and OS rates were 84% and 88%, respectively, in patients with PET-negative results versus 47% and 62%, respectively, in patients with PET-positive results (P < .0001 and P < .003, respectively). A second analysis was performed on 85 patients by using interim PET in a quantitative approach on the basis of a ΔSUV(max) evaluation of more than 66%. The 3-year PFS was 77% for patients with PET-negative results and 37.5% for patients with PET-positive results (P = .002).An early PET scan after two cycles of treatment can effectively predict the outcome in patients with DLBCL treated with rituximab and anthracycline-based chemotherapy by using either a visual or quantitative approach.
Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose?
Authors: Jane E.B. Reusch
Journal: Journal of Clinical Investigation (2003)

Glycemic control is the primary mediator of diabetic microvascular complications and also contributes to macrovascular complications. A new study (see related article beginning on page 1049) reveals a previously unrecognized association between oxidant activation of poly(ADP ribose) polymerase (PARP) and upregulation of known mediators of glycemic injury. Inhibitors of PARP may have potential therapeutic roles in the prevention of diabetic complications.
Gene Expression Signature in Urine for Diagnosing and Assessing Aggressiveness of Bladder Urothelial Carcinoma
Authors: Lourdes Mengual, Moisès Burset, María José Ribal, Elisabet Ars, Mercedes Marín-Aguilera, Manuel Fernández, Mercedes Ingelmo-Torres, Humberto Villavicencio, Antonio Alcaraz
Journal: Clinical Cancer Research (2010)

To develop an accurate and noninvasive method for bladder cancer diagnosis and prediction of disease aggressiveness based on the gene expression patterns of urine samples.Gene expression patterns of 341 urine samples from bladder urothelial cell carcinoma (UCC) patients and 235 controls were analyzed via TaqMan Arrays. In a first phase of the study, three consecutive gene selection steps were done to identify a gene set expression signature to detect and stratify UCC in urine. Subsequently, those genes more informative for UCC diagnosis and prediction of tumor aggressiveness were combined to obtain a classification system of bladder cancer samples. In a second phase, the obtained gene set signature was evaluated in a routine clinical scenario analyzing only voided urine samples.We have identified a 12+2 gene expression signature for UCC diagnosis and prediction of tumor aggressiveness on urine samples. Overall, this gene set panel had 98% sensitivity (SN) and 99% specificity (SP) in discriminating between UCC and control samples and 79% SN and 92% SP in predicting tumor aggressiveness. The translation of the model to the clinically applicable format corroborates that the 12+2 gene set panel described maintains a high accuracy for UCC diagnosis (SN = 89% and SP = 95%) and tumor aggressiveness prediction (SN = 79% and SP = 91%) in voided urine samples.The 12+2 gene expression signature described in urine is able to identify patients suffering from UCC and predict tumor aggressiveness. We show that a panel of molecular markers may improve the schedule for diagnosis and follow-up in UCC patients.
Metabolic characteristics of the deltoid muscle in patients with chronic obstructive pulmonary disease
Authors: J.G. Gea, M. Pasto, M.A. Carmona, M. Orozco-Levi, J. Palomeque, J. Broquetas
Journal: European Respiratory Journal (2001)

The purpose of this study was to analyse key enzyme activities of the deltoid muscle (DM) in chronic obstructive pulmonary disease (COPD) patients. The activities of one oxidative enzyme (citrate synthase (CS)), two glycolytic enzymes (lacatate dehydrogenase (LD); and phosphofructokinase (PFK)) and one enzyme related to the use of energy stores (creatine kinase (CK)) were determined in the DM of 10 patients with COPD and nine controls. Exercise capacity (cycloergometry) and the handgrip strength were also evaluated. Although exercise capacity was markedly reduced in COPD (57 +/- 20% predicted), their handgrip strength was relatively preserved (77 +/- 19% pred). The activity of LD was higher in the COPD patients (263.9 +/- 68.2 versus 184.4 +/- 46.5 mmol x min(-1) x g(-1), p<0.01), with a similar trend for CS (67.3 +/- 33.3 versus 46.0 +/- 17.4 mmol x min(-1) x g(-1), p = 0.07). Interestingly, the activity of the latter enzyme was significantly higher than controls if only severe COPD patients were considered (81.8 +/- 31.2 mmol x min(-1) x g(-1), p < 0.01). PFK and CK activities were similar for controls and COPD. Chronic obstructive patients show a preserved or even increased (severe disease) oxidative capacity in their deltoid muscle. This coexists with a greater capacity in the anaerobic part of the glycolysis. These findings are different to those previously observed in muscles of the lower limbs.
Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD
Authors: Daniel R. Couriel, Chitra Hosing, Rima Saliba, Elizabeth J. Shpall, Paolo Anderlini, Beverly Rhodes, Veronica Smith, Issa Khouri, Sergio Giralt, Marcos de Lima, Yvonne Hsu, Shubhra Ghosh, Joyce Neumann, Borje Andersson, Muzzafar Qazilbash, Sharon Hymes, Stella Kim, Richard Champlin, Michele Donato
Journal: Blood (2005)
DNA hypermethylation regulates the expression of members of the Mu-class glutathione S-transferases and glutathione peroxidases in Barrett's adenocarcinoma
Authors: D F Peng, M Razvi, H Chen, K Washington, A Roessner, R Schneider-Stock, W El-Rifai
Journal: Gut (2008)

<h3>Background:</h3> The accumulation of reactive oxygen species and subsequent oxidative DNA damage underlie the development of Barrett's oesophagus (BO) and its progression to Barrett's dysplasia (BD) and adenocarcinoma (BAC). <h3>Methods:</h3> The promoter regions of 23 genes of the glutathione <i>S</i>-transferase (GST) and glutathione peroxidase (GPX) families were systematically analysed. Quantitative bisulfite pyrosequencing, real-time RT-PCR, western blot and immunohistochemical (IHC) analysis methods were utilised in this study. <h3>Results:</h3> 14 genes were identified that have CpG islands around their transcription start sites: GSTs (<i>GSTM2–M5</i>, <i>GSTA4</i>, <i>GSTP1</i>, <i>GSTZ1</i>, <i>GSTT2</i>, <i>GSTO1</i> and <i>GSTO2</i>) and GPXs (<i>GPX1</i>, <i>GPX3</i>, <i>GPX4</i> and <i>GPX7</i>). Analysis of an initial set of 20 primary samples demonstrated promoter DNA hypermethylation and mRNA downregulation of <i>GPX3</i>, <i>GPX7</i>, <i>GSTM2</i>, <i>GSTM3</i> and <i>GSTM5</i> in more than half of the BAC samples. Further analysis of 159 primary human samples (37 normal, 11 BO, 11 BD and 100 BACs) indicated frequent hypermethylation (⩾10% methylation) of <i>GPX3</i> (62%), <i>GPX7</i> (67%), <i>GSTM2</i> (69.1%) and <i>GSTM3</i> (15%) in BACs. A significant inverse correlation between DNA methylation and mRNA expression level was shown for <i>GPX3</i> (p&lt;0.001), <i>GPX7</i> (p = 0.002), <i>GSTM2</i> (p&lt;0.001) and <i>GSTM5</i> (p = 0.01). Treatment of oesophageal cancer cell lines with 5-aza-2′-deoxycytidine and trichostatin-A led to reversal of the methylation pattern and re-expression of these genes at the mRNA and protein levels. The IHC analysis of GPX3, GPX7 and GSTM2 on a tissue microarray that contained 75 BACs with normal squamous oesophageal samples demonstrated an absent to weak staining in tumours (52% for GPX3, 57% for GPX7 and 45% for GSTM2) and a moderate to strong immunostaining in normal samples. <h3>Conclusion:</h3> Epigenetic inactivation of members of the glutathione pathway can be an important mechanism in Barrett's tumourigenesis.
Response to Antihypertensive Therapy in Older Patients With Sustained and Nonsustained Systolic Hypertension
Authors: Robert H. Fagard, Jan A. Staessen, Lutgarde Thijs, Jerzy Gasowski, Christopher J. Bulpitt, Denis Clement, Peter W. de Leeuw, Jurij Dobovisek, Matti Jääskivi, Gastone Leonetti, Eoin O’Brien, Paolo Palatini, Gianfranco Parati, José L. Rodicio, Hannu Vanhanen, John Webster
Journal: Circulation (2000)

Background —The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. Methods and Results —Patients who were ≥60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of &lt;95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (&lt;140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (≥160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages ( P &lt;0.001) and, during follow-up, a lower incidence of stroke ( P &lt;0.05) and of cardiovascular complications ( P =0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension ( P &lt;0.001). The influence of active treatment on ECG voltages ( P &lt;0.05) and on the incidence of stroke ( P &lt;0.05) and cardiovascular events ( P =0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. Conclusions —Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.
Failure to tackle refugees' health needs increases risk of exclusion
Authors: Sara de Albornoz
Journal: BMJ (2006)

The lack of GPs' clinics willing to deal with refugees in London is one of several factors threatening community relations and increasing the risk of social exclusion, warned Angela Burnett speaking at a conference last week.

Dr Burnett, a GP from east London, was addressing the third annual international mental health conference—“People on the move”—in London, which highlighted the consequences for mental health of displacement and conflict.

One in 300 people in the United Kingdom are of refugee background, according to the United Nations High …
The Use of Biothesiometry to Detect Neuropathy in Children and Adolescents With IDDM
Authors: E A Davis, T W Jones, P Walsh, G C Byrne
Journal: Diabetes Care (1997)

OBJECTIVE To develop clinically useful reference ranges for vibration perception thresholds (VPTs), using biothesiometry in children and adolescents and to assess the reliability of the technique to identify subclinical neuropathy in subjects with IDDM at this age and to examine a large population-based sample of pediatric patients. RESEARCH DESIGN AND METHODS VPTs were measured using a handheld biothesiometer at the medial malleolus and hallux in 232 nondiabetic children and adolescents aged 7–18 years (12.9 ± 4.2 years) and a population-based sample of 307 young IDDM patients (13.3 ± 4.6 years of age). The mean of three readings at each site was correlated with height, pubertal status, and age for all subjects and, in addition for the IDDM sample, with the duration of IDDM, ambient blood glucose, and mean HbA1c from diagnosis. Those IDDM subjects found to have elevated VPTs (&amp;gt; 97th percentile), and a control group of patients with IDDM underwent nerve conduction studies to determine the sensitivity and specificity of biothesiometry to detect abnormal neural function in children. Interoperator reliability was assessed in a separate trial in which two operators measured VPTs independently in the same 11 children. RESULTS In the nondiabetic control subjects, height demonstrated the best correlation with VPT measures, and a reference range was thus established with percentile charts, using mean VPT and height. VPTs were higher in the diabetic sample, compared with the nondiabetic sample (P &amp;lt; 0.05). Of the children, 28 (9.1%) had VPT values &amp;gt; 97th percentile developed from studies of the nondiabetic subjects; of these, 11 were younger than 11 years and 8 were prepubertal. Nerve conduction studies confirmed reduced conduction velocity and prolonged distal latencies in those with abnormal VPTs, compared with normal control subjects and IDDM patients with normal VPTs. Sensitivity of biothesiometry to reflect abnormal nerve function was estimated as 82% and specificity as 75% at this age. Interoperator variation was small (7.25% of total variance). CONCLUSIONS Biothesiometry is a useful noninvasive tool for the detection of subclinical neuropathy in children and adolescents. The use of height-related reference ranges may make screening for neuropathy more feasible in younger patients and allow large-scale longitudiral analysis of its development.
Ryanodine receptors: physiological function and deregulation in Alzheimer disease
Authors: Dolores Del Prete, Frédéric Checler, Mounia Chami
Journal: Molecular Neurodegeneration (2014)

Perturbed Endoplasmic Reticulum (ER) calcium (Ca2+) homeostasis emerges as a central player in Alzheimer disease (AD). Accordingly, different studies have reported alterations of the expression and the function of Ryanodine Receptors (RyR) in human AD-affected brains, in cells expressing familial AD-linked mutations on the β amyloid precursor protein (βAPP) and presenilins (the catalytic core in γ-secretase complexes cleaving the βAPP, thereby generating amyloid β (Aβ) peptides), as well as in the brain of various transgenic AD mice models. Data converge to suggest that RyR expression and function alteration are associated to AD pathogenesis through the control of: i) βAPP processing and Aβ peptide production, ii) neuronal death; iii) synaptic function; and iv) memory and learning abilities. In this review, we document the network of evidences suggesting that RyR could play a complex dual “compensatory/protective versus pathogenic” role contributing to the setting of histopathological lesions and synaptic deficits that are associated with the disease stages. We also discuss the possible mechanisms underlying RyR expression and function alterations in AD. Finally, we review recent publications showing that drug-targeting blockade of RyR and genetic manipulation of RyR reduces Aβ production, stabilizes synaptic transmission, and prevents learning and memory deficits in various AD mouse models. Chemically-designed RyR “modulators” could therefore be envisioned as new therapeutic compounds able to delay or block the progression of AD.
Unintended Consequences of Health Information Technology: Evidence From Veterans Affairs Colorectal Cancer Oncology Watch Intervention
Authors: John Bian, Charles L. Bennett, Deborah A. Fisher, Maria Ribeiro, Joseph Lipscomb
Journal: Journal of Clinical Oncology (2012)

We evaluated the Colorectal Cancer (CRC) Oncology Watch intervention, a clinical reminder implemented in Veterans Integrated Service Network 7 (including eight hospitals) to improve CRC screening rates in 2008.Veterans Affairs (VA) administrative data were used to construct four cross-sectional groups of veterans at average risk, age 50 to 64 years; one group was created for each of the following years: 2006, 2007, 2009, and 2010. We applied hospital fixed effects for estimation, using a difference-in-differences model in which the eight hospitals served as the intervention sites, and the other 121 hospitals served as controls, with 2006 to 2007 as the preintervention period and 2009 to 2010 as the postintervention period.The sample included 4,352,082 veteran-years in the 4 years. The adherence rates were 37.6%, 31.6%, 34.4%, and 33.2% in the intervention sites in 2006, 2007, 2009, and 2010, respectively, and the corresponding rates in the controls were 31.0%, 30.3%, 32.3%, and 30.9%. Regression analysis showed that among those eligible for screening, the intervention was associated with a 2.2-percentage point decrease in likelihood of adherence (P < .001). Additional analyses showed that the intervention was associated with a 5.6-percentage point decrease in likelihood of screening colonoscopy among the adherent, but with increased total colonoscopies (all indicators) of 3.6 per 100 veterans age 50 to 64 years.The intervention had little impact on CRC screening rates for the studied population. This absence of favorable impact may have been caused by an unintentional shift of limited VA colonoscopy capacity from average-risk screening to higher-risk screening and to CRC surveillance, or by physician fatigue resulting from the large number of clinical reminders implemented in the VA.
Left Atrial Mechanical Functions, Atrial Electromechanical Delay and P Wave Dispersion in Patients with Mild to Moderate Psoriasis
Authors: Fatma Özlem Arıcan Özlük, Mustafa Yılmaz, Serkan Yazıcı, Tezcan Peker, Dursun Topal, Kemal Karaagac, Fahriye Vatansever, Alkame Akgumus, Erhan Tenekecioglu
Journal: Journal of the American College of Cardiology (2013)
CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression
Authors: Dachuan Jin, Jie Fan, Long Wang, Linda F. Thompson, Aijie Liu, Benjamin J. Daniel, Tahiro Shin, Tyler J. Curiel, Bin Zhang
Journal: Cancer Research (2010)

CD73, originally defined as a lymphocyte differentiation antigen, is thought to function as a cosignaling molecule on T lymphocytes and an adhesion molecule that is required for lymphocyte binding to endothelium. We show here that CD73 is widely expressed on many tumor cell lines and is upregulated in cancerous tissues. Because the ecto-5'-nucleotidase activity of CD73 catalyzes AMP breakdown to immunosuppressive adenosine, we hypothesized that CD73-generated adenosine prevents tumor destruction by inhibiting antitumor immunity. We confirmed this hypothesis by showing that combining tumor CD73 knockdown and tumor-specific T-cell transfer cured all tumor-bearing mice. In striking contrast, there was no therapeutic benefit of adoptive T-cell immunotherapy in mice bearing tumors without CD73 knockdown. Moreover, blockade of the A2A adenosine receptor with a selective antagonist also augmented the efficacy of adoptive T-cell therapy. These findings identify a potential mechanism for CD73-mediated tumor immune evasion and point to a novel cancer immunotherapy strategy by targeting the enzymatic activity of tumor CD73.
Association of Dopamine Transporter Loss in the Orbitofrontal and Dorsolateral Prefrontal Cortices With Methamphetamine-Related Psychiatric Symptoms
Authors: Yoshimoto Sekine, Yoshio Minabe, Yasuomi Ouchi, Nori Takei, Masaomi Iyo, Kazuhiko Nakamura, Katsuaki Suzuki, Hideo Tsukada, Hiroyuki Okada, Etsuji Yoshikawa, Masami Futatsubashi, Norio Mori
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors examined dopamine transporter density in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in methamphetamine users and assessed the relationship of these measures to the subjects' clinical characteristics. METHOD: Positron emission tomography with [11C]WIN 35,428 was used to examine the regions of interest in 11 methamphetamine users and nine healthy comparison subjects. Psychiatric symptoms were evaluated with the Brief Psychiatric Rating Scale. RESULTS: Dopamine transporter density in the three regions studied was significantly lower in the methamphetamine users than in the comparison subjects. The lower dopamine transporter density in the orbitofrontal and dorsolateral prefrontal cortex was significantly correlated with the duration of methamphetamine use and the severity of psychiatric symptoms. CONCLUSIONS: Chronic methamphetamine use may cause dopamine transporter reduction in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in the brain. Psychiatric symptoms in methamphetamine users may be attributable to the decrease in dopamine transporter density in the orbitofrontal cortex and the dorsolateral prefrontal cortex.
Does biological therapy affect interferon-γ release assay response? A long-term follow-up of patients with psoriasis using QuantiFERON-TB
Authors: G. Lombardi, V. Tengattini, P. Dal Monte, A. Denicolò, M.L. Bacchi Reggiani, A. Patrizi, M.P. Landini, F. Bardazzi
Journal: British Journal of Dermatology (2014)

Funding sources: This study was partially supported by the contribution of the 'Fondazione del Monte di Bologna e Ravenna'. Conflicts of interest: none declared. Dear Editor, Patients with psoriasis treated with biological drugs are at increased risk of reactivation of latent tuberculosis infection (LTBI). Therefore screening for active or latent TB is mandatory before initiating therapy.1 Interferon (IFN)‐γ release assays (IGRAs) are in vitro tests approved for the detection of LTBI and are based on the measure of IFN‐γ secreted by T lymphocytes sensitized to Mycobacterium tuberculosis (MTB) antigens.2 Furthermore, IGRAs provide both a negative and a positive (T‐cell mitogen phytohaemagglutinin) control, thus allowing a more comprehensive evaluation of the host immune reactivity. Published evidence suggests that IGRAs maintain their diagnostic sensitivity for LTBI better than the tuberculin skin test (TST) in patients with chronic inflammatory diseases.3 However, few studies on the performance of IGRAs in patients with psoriasis have been carried out, most of them analysing agreement with TST.4 5