tbuckley/cabot-search huggingface dataset:
Helicase–Primase Inhibitor Pritelivir for HSV-2 Infection
Authors: Anna Wald, Lawrence Corey, Burkhard Timmler, Amalia Magaret, Terri Warren, Stephen Tyring, Christine Johnston, John Kriesel, Kenneth Fife, Lawrence Galitz, Susanne Stoelben, Meei-Li Huang, Stacy Selke, Hans-Peter Stobernack, Helga Ruebsamen-Schaeff, Alexander Birkmann
Journal: New England Journal of Medicine (2014)

Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection.We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding.HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups.Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes. (Funded by AiCuris; ClinicalTrials.gov number, NCT01047540.).
RETRACTED ARTICLE: Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease
Authors: Barbara Nuvoli, Sabrina Germoni, Carlotta Morosetti, Raffaela Santoro, Giancarlo Cortese, Serena Masi, Iole Cordone, Rossella Galati
Journal: Molecular Cancer (2014)

Abstract Background Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models. Results We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin. Conclusion The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment.
Diagnostic accuracy of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis
Authors: O Kasapcopur
Journal: Annals of the Rheumatic Diseases (2004)

To correlate serum anti-cyclic citrullinated peptide antibodies (anti-CCP) levels with juvenile idiopathic arthritis (JIA) subtypes and with an erosive disease course.The study group comprised 122 children with JIA; 16 were evaluated during both active disease and remission. Nineteen children with systemic lupus erythematosus (SLE), 27 with rheumatoid arthritis (RA), and 15 healthy children were also included in the study. Twelve children with JIA were rheumatoid factor (RF) positive, and 34 patients had persistent erosive joint disease. Anti-CCP antibody levels were determined by ELISA; values above 5 relative units were regarded as positive.Three girls with seropositive polyarticular JIA and erosive joint disease had positive anti-CCP values. Children evaluated during active disease and remission, patients with SLE, and healthy children all had negative anti-CCP antibody levels. However, 19/27 (70%) adult patients with RA had positive anti-CCP antibody values.In contrast with RA, anti-CCP positivity is only rarely found in patients with JIA. In patients with RF positivity and/or in patients with erosive joint disease, anti-CCP can be detected.
General Internal Medicine and Geriatrics: Building a Foundation To Improve the Training of General Internists in the Care of Older Adults
Authors: C. Seth Landefeld, Christopher M. Callahan, Nancy Woolard
Journal: Annals of Internal Medicine (2003)

Internists--"doctors for adults"--provide most of the medical care given to older Americans, especially those with serious chronic disease. Nonetheless, the United States lacks an adequate physician workforce with mastery in caring for older persons and with expertise in building knowledge about how best to provide this care. This supplement aims to strengthen the physician workforce by fostering incremental and sustained improvements in the training of internal medicine residents in the care of older adults and in the development of geriatrics-oriented general internal medicine faculty. It identifies 3 major barriers to these improvements: lack of adequately trained teachers and mentors, the belief that explicit training in geriatrics has little to offer the generalist, and inadequate funding. Three strategies offer particular promise in overcoming these barriers: engaging directors of internal medicine residency programs, funding centers to promote collaboration between teaching and research programs in general internal medicine and geriatrics, and providing substantial incremental funding on the national level to pay for the time required to care for frail older patients and to teach and do research about this care. The barriers and strategies identified in this supplement may also inform efforts to enhance the skills of practicing physicians and improve training and faculty development in family medicine and other disciplines.
A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis
Authors: M D Noble, J Romac, S R Vigna, R A Liddle
Journal: Gut (2008)

<h3>Background:</h3> Endoscopic retrograde cholangiopancreatography (ERCP) has a high risk of pancreatitis although the underlying mechanisms are unclear. Transient receptor potential vanilloid 1 (TRPV1) is a cation channel expressed on C and Aδ fibres of primary sensory neurons and is activated by low pH. TRPV1 activation causes release of inflammatory mediators that produce oedema and neutrophil infiltration. We previously demonstrated that neurogenic factors contribute to the pathogenesis of pancreatitis. Resiniferatoxin (RTX) is a TRPV1 agonist that, in high doses, defunctionalises C and Aδ fibres. When we discovered that the pH of radio-opaque contrast solutions used for ERCP was 6.9, we hypothesised that low pH may contribute to the development of contrast-induced pancreatitis via activation of TRPV1. <h3>Methods:</h3> Rats underwent equal pressure pancreatic ductal injection of contrast solutions at varying pH with or without RTX. <h3>Results:</h3> Contrast solution (pH 6.9) injected into the pancreatic duct caused a significant increase in pancreatic oedema, serum amylase, neutrophil infiltration, and histological damage. Solutions of pH 7.3 injected at equal pressure caused little damage. The severity of the pancreatitis was significantly increased by injection of solutions at pH 6.0. To determine if the effects of low pH were mediated by TRPV1, RTX was added to the contrast solutions. At pH levels of 6.0 and 6.9, RTX significantly reduced the severity of pancreatitis. <h3>Conclusions:</h3> Contrast solutions with low pH contribute to the development of pancreatitis through a TRPV1-dependent mechanism. It is possible that increasing the pH of contrast solution and/or adding an agent that inhibits primary sensory nerve activation may reduce the risk of post-ERCP pancreatitis.
In Vivo&lt;char aid="99756086" id="sup"&gt; 1&lt;/char&gt;H-Magnetic Resonance Spectroscopy Study of Amygdala-Hippocampal and Parietal Regions in Autism
Authors: Lisa Page
Journal: American Journal of Psychiatry (2006)

The neural basis for autistic spectrum disorders is unclear, but abnormalities in the development of limbic areas and of glutamate have been suggested. Proton magnetic resonance spectroscopy ((1)H-MRS) can be used to measure the concentration of brain metabolites. However, the concentration of glutamate/glutamine in brain regions implicated in autistic spectrum disorders has not yet been examined in vivo.The authors used (1)H-MRS to investigate the neuronal integrity of the amygdala-hippocampal complex and a parietal control region in adults with autistic spectrum disorders and healthy subjects.People with autistic spectrum disorders had a significantly higher concentration of glutamate/glutamine and creatine/phosphocreatine in the amygdala-hippocampal region but not in the parietal region.Abnormalities in glutamate/glutamine may partially underpin the pathophysiology of autistic spectrum disorders, and the authors confirm earlier reports that limbic areas are metabolically aberrant in these disorders.
Deleted in breast cancer–1 regulates SIRT1 activity and contributes to high-fat diet–induced liver steatosis in mice
Authors: Carlos Escande, Claudia C.S. Chini, Veronica Nin, Katherine Minter Dykhouse, Colleen M. Novak, James Levine, Jan van Deursen, Gregory J. Gores, Junjie Chen, Zhenkun Lou, Eduardo Nunes Chini
Journal: Journal of Clinical Investigation (2010)

The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As SIRT1 activity in vitro was recently found to be negatively regulated by interaction with the deleted in breast cancer–1 (DBC1) protein, we set out to investigate whether DBC1 regulates SIRT1 activity in vivo. We found that DBC1 and SIRT1 colocalized and interacted, and that DBC1 modulated SIRT1 activity, in multiple cell lines and tissues. In mouse liver, increased SIRT1 activity, concomitant with decreased DBC1-SIRT1 interaction, was detected after 24 hours of starvation, whereas decreased SIRT1 activity and increased interaction with DBC1 was observed with high-fat diet (HFD) feeding. Consistent with the hypothesis that DBC1 is crucial for HFD-induced inhibition of SIRT1 and for the development of experimental liver steatosis, genetic deletion of Dbc1 in mice led to increased SIRT1 activity in several tissues, including liver. Furthermore, DBC1-deficient mice were protected from HFD-induced liver steatosis and inflammation, despite the development of obesity. These observations define what we believe to be a new role for DBC1 as an in vivo regulator of SIRT1 activity and liver steatosis. We therefore propose that the DBC1-SIRT1 interaction may serve as a new target for therapies aimed at nonalcoholic liver steatosis.
PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer
Authors: Jyoti D. Patel, Mark A. Socinski, Edward B. Garon, Craig H. Reynolds, David R. Spigel, Mark R. Olsen, Robert C. Hermann, Robert M. Jotte, Thaddeus Beck, Donald A. Richards, Susan C. Guba, Jingyi Liu, Bente Frimodt-Moller, William J. John, Coleman K. Obasaju, Eduardo J. Pennella, Philip Bonomi, Ramaswamy Govindan
Journal: Journal of Clinical Oncology (2013)

PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).
Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis
Authors: Christopher J. Cooper, Timothy P. Murphy, Donald E. Cutlip, Kenneth Jamerson, William Henrich, Diane M. Reid, David J. Cohen, Alan H. Matsumoto, Michael Steffes, Michael R. Jaff, Martin R. Prince, Eldrin F. Lewis, Katherine R. Tuttle, Joseph I. Shapiro, John H. Rundback, Joseph M. Massaro, Ralph B. D'Agostino, Lance D. Dworkin
Journal: New England Journal of Medicine (2013)

Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain.We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy).Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03).Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).
Promiscuous T-cell responses to drugs and drug-haptens
Authors: Fiazia S. Yaseen, Katy Saide, Seung-Hyun Kim, Manal Monshi, Arun Tailor, Sally Wood, Xiaoli Meng, Rosalind Jenkins, Lee Faulkner, Ann K. Daly, Munir Pirmohamed, B. Kevin Park, Dean J. Naisbitt
Journal: Journal of Allergy and Clinical Immunology (2015)
Does an ‘autoimmune’ profile affect the severity of chronic hepatitis C? Results of an Italian survey
Authors: T. Stroffolini, G. Colloredo, G.B. Gaeta, A. Sonzogni, S. Angeletti, M. Marignani, G. Pasquale, G. Venezia, A. Craxi, P.L. Almasio
Journal: Journal of Hepatology (2003)
P1017 : Circulating sclerostin and DICKKOPF-1 in patients with Nonalcoholic Fatty Liver Disease
Authors: S.A. Polyzos, A.D. Anastasilakis, E. Terpos, P. Makras, A. Papatheodorou, P. Kokkoris, J. Kountouras
Journal: Journal of Hepatology (2015)
A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E.
Authors: C Traversari, P van der Bruggen, I F Luescher, C Lurquin, P Chomez, A Van Pel, E De Plaen, A Amar-Costesec, T Boon
Journal: The Journal of Experimental Medicine (1992)

We have reported the identification of human gene MAGE-1, which directs the expression of an antigen recognized on a melanoma by autologous cytolytic T lymphocytes (CTL). We show here that CTL directed against this antigen, which was named MZ2-E, recognize a nonapeptide encoded by the third exon of gene MAGE-1. The CTL also recognize this peptide when it is presented by mouse cells transfected with an HLA-A1 gene, confirming the association of antigen MZ2-E with the HLA-A1 molecule. Other members of the MAGE gene family do not code for the same peptide, suggesting that only MAGE-1 produces the antigen recognized by the anti-MZ2-E CTL. Our results open the possibility of immunizing HLA-A1 patients whose tumor expresses MAGE-1 either with the antigenic peptide or with autologous antigen-presenting cells pulsed with the peptide.
Association Between Placebo-Activated Neural Systems and Antidepressant Responses
Authors: Marta Peciña, Amy S. B. Bohnert, Magdalena Sikora, Erich T. Avery, Scott A. Langenecker, Brian J. Mickey, Jon-Kar Zubieta
Journal: JAMA Psychiatry (2015)

High placebo responses have been observed across a wide range of pathologies, severely impacting drug development.To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD).In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) were studied with positron emission tomography and the µ-opioid receptor-selective radiotracer [11C]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect.Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of µ-opioid receptor binding.Higher baseline µ-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r = 0.48; P = .02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, were associated with increased placebo-induced µ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala (nucleus accumbens: r = 0.6; P < .001). Placebo-induced endogenous opioid release in these regions was associated with better antidepressant treatment response, predicting 43% of the variance in symptom improvement at the end of the antidepressant trial.These data demonstrate that placebo-induced activation of the µ-opioid system is implicated in the formation of placebo antidepressant effects in patients with MDD and also participate in antidepressant responses, conferring illness resiliency, during open administration.clinicaltrials.gov Identifier:NCT02178696.
Effectiveness of Aromatherapy Massage in the Management of Anxiety and Depression in Patients With Cancer: A Multicenter Randomized Controlled Trial
Authors: Susie M. Wilkinson, Sharon B. Love, Alex M. Westcombe, Maureen A. Gambles, Caroline C. Burgess, Anna Cargill, Teresa Young, E. Jane Maher, Amanda J. Ramirez
Journal: Journal of Clinical Oncology (2007)

To test the effectiveness of supplementing usual supportive care with aromatherapy massage in the management of anxiety and depression in cancer patients through a pragmatic two-arm randomized controlled trial in four United Kingdom cancer centers and a hospice.Two hundred eighty-eight cancer patients, referred to complementary therapy services with clinical anxiety and/or depression, were allocated randomly to a course of aromatherapy massage or usual supportive care alone.Patients who received aromatherapy massage had no significant improvement in clinical anxiety and/or depression compared with those receiving usual care at 10 weeks postrandomization (odds ratio [OR], 1.3; 95% CI, 0.9 to 1.7; P = .1), but did at 6 weeks postrandomization (OR, 1.4; 95% CI, 1.1 to 1.9; P = .01). Patients receiving aromatherapy massage also described greater improvement in self-reported anxiety at both 6 and 10 weeks postrandomization (OR, 3.4; 95% CI, 0.2 to 6.7; P = .04 and OR, 3.4; 95% CI, 0.2 to 6.6; P = .04), respectively.Aromatherapy massage does not appear to confer benefit on cancer patients' anxiety and/or depression in the long-term, but is associated with clinically important benefit up to 2 weeks after the intervention.
Induced Abortion: An Overview for Internists
Authors: David A. Grimes
Journal: Annals of Internal Medicine (2004)

Internists care for many women who have had abortions and many who will seek abortions in the future. Each year, about 2% of all women of reproductive age have an abortion. Women having abortions tend to be young, white, unmarried, and early in pregnancy. Most abortions are done by suction curettage under local anesthesia in a freestanding clinic. However, medical abortion is growing in popularity as a nonsurgical alternative. The regimen approved by the U.S. Food and Drug Administration specifies mifepristone, 600 mg orally, followed 2 days later by misoprostol, 400 µg orally (within 49 days from last menses). Recent studies have recommended alternative approaches, such as mifepristone, 200 mg orally, followed in 1 to 3 days by misoprostol, 800 µg vaginally (up to 63 days). Medical abortion can be provided by a broader variety of physicians than can surgical abortion. The overall case-fatality rate for abortion is less than 1 death per 100 000 procedures. Infection, hemorrhage, acute hematometra, and retained tissue are among the more common complications. Referral back to the original abortion provider for management is advisable. Overall, induced abortion does not lead to late sequelae, either medical or psychiatric. Of importance, no link exists between induced abortion and later breast cancer. For physicians who are asked to help with a referral, the National Abortion Federation and Planned Parenthood Federation of America have helpful Web sites and networks of high-quality clinics. The cost of abortion (currently about $372 at 10 weeks) has decreased in recent decades. Provision of ongoing contraception and encouragement of emergency contraception can reduce unintended pregnancies and the need for abortion.