tbuckley/cabot-search huggingface dataset:
Fluoxetine After Weight Restoration in Anorexia Nervosa
Authors: B. Timothy Walsh, Allan S. Kaplan, Evelyn Attia, Marion Olmsted, Michael Parides, Jacqueline C. Carter, Kathleen M. Pike, Michael J. Devlin, Blake Woodside, Christina A. Roberto, Wendi Rockert
Journal: JAMA (2006)

Antidepressant medication is frequently prescribed for patients with anorexia nervosa.To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration.Randomized, double-blind, placebo-controlled trial. From January 2000 until May 2005, 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital. Participants regained weight to a minimum body mass index (calculated as weight in kilograms divided by the square of height in meters) of 19.0 and were then eligible to participate in the randomized phase of the trial.Participants were randomly assigned to receive fluoxetine or placebo and were treated for up to 1 year as outpatients in double-blind fashion. All patients also received individual cognitive behavioral therapy.The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment.Forty-nine patients were assigned to fluoxetine and 44 to placebo. Similar percentages of patients assigned to fluoxetine and to placebo maintained a body mass index of at least 18.5 and remained in the study for 52 weeks (fluoxetine, 26.5%; placebo, 31.5%; P = .57). In a Cox proportional hazards analysis, with prerandomization body mass index, site, and diagnostic subtype as covariates, there was no significant difference between fluoxetine and placebo in time-to-relapse (hazard ratio, 1.12; 95% CI, 0.65-2.01; P = .64).This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration. Future efforts should focus on developing new models to understand the persistence of this illness and on exploring new psychological and pharmacological treatment approaches.clinicaltrials.gov Identifier: NCT00288574.
On the association between chromosomal rearrangements and genic evolution in humans and chimpanzees
Authors: Tomàs Marques-Bonet, Jesús Sànchez-Ruiz, Lluís Armengol, Razi Khaja, Jaume Bertranpetit, Núria Lopez-Bigas, Mariano Rocchi, Elodie Gazave, Arcadi Navarro
Journal: Genome biology (2007)

The role that chromosomal rearrangements might have played in the speciation processes that have separated the lineages of humans and chimpanzees has recently come into the spotlight. To date, however, results are contradictory. Here we revisit this issue by making use of the available human and chimpanzee genome sequence to study the relationship between chromosomal rearrangements and rates of DNA sequence evolution.Contrary to previous findings for this pair of species, we show that genes located in the rearranged chromosomes that differentiate the genomes of humans and chimpanzees, especially genes within rearrangements themselves, present lower divergence than genes elsewhere in the genome. Still, there are considerable differences between individual chromosomes. Chromosome 4, in particular, presents higher divergence in genes located within its rearrangement.A first conclusion of our analysis is that divergence is lower for genes located in rearranged chromosomes than for those in colinear chromosomes. We also report that non-coding regions within rearranged regions tend to have lower divergence than non-coding regions outside them. These results suggest an association between chromosomal rearrangements and lower non-coding divergence that has not been reported before, even if some chromosomes do not follow this trend and could be potentially associated with a speciation episode. In summary, without excluding it, our results suggest that chromosomal speciation has not been common along the human and chimpanzee lineage.
A Cophylogenetic Perspective of RNA-Virus Evolution
Authors: A. P. Jackson
Journal: Molecular Biology and Evolution (2003)

The extent to which viruses and their hosts codiverge remains an open question, given that numerous cases of both "cospeciation" and horizontal switching have recently been documented. DNA viruses that form persistent infections are thought to be the most likely candidates for phylogenetic congruence. Phylogenetic reconciliation analysis was used to compare established phylogenies for four RNA viruses and their hosts. The analysis employs a cophylogeny mapping technique, implemented in TreeMap v2.0, to find the most parsimonious combinations of evolutionary events able to reconcile any incongruence. This technique is guaranteed to recover all potentially optimal solutions to the reconciled tree and specifically tests the null hypothesis that an associate phylogeny is no more congruent with a host phylogeny than would be a random tree with the same taxon set. Phylogenies for Hantavirus, Spumavirus, and avian sarcoma leukosis virus were found to be significantly similar to their host trees, whereas Lyssavirus and Arenavirus displayed no significant congruence. These results demonstrate that RNA viruses are able to form stable associations with their hosts over evolutionary time scales and that the details of such associations are consistent with persistent infection being a necessary but not sufficient precondition.
Hemodynamic, biochemical and morphological changes induced by aminoguanidine in normal and septic sheep
Authors: J.A. Lorente, C. Tejedor, M.A. Delgado, P. Fernández-Segoviano, N. Jara, R. Tobalina, A. Rodríguez-Corcos, A. Moscoso, A. Esteban
Journal: Intensive Care Medicine (2000)
A Phase I Trial and Pharmacokinetic Study of Tipifarnib, a Farnesyltransferase Inhibitor, and Tamoxifen in Metastatic Breast Cancer
Authors: Peter F. Lebowitz, Jennifer Eng-Wong, Brigitte C. Widemann, Frank M. Balis, Nalini Jayaprakash, Catherine Chow, Geoff Clark, Susan B. Gantz, David Venzon, JoAnne Zujewski
Journal: Clinical Cancer Research (2005)

Farnesyltransferase (FTase) inhibitors, which were designed to inhibit oncogenic Ras, act synergistically with tamoxifen in preclinical breast cancer models. We studied the safety and toxicity of tipifarnib in combination with tamoxifen in metastatic breast cancer. The pharmacokinetics and pharmacodynamics of tipifarnib were also assessed.Patients with metastatic, hormone receptor-positive breast cancer were enrolled. Two cohorts of patients were treated with tipifarnib at either 200 or 300 mg p.o. twice daily for 21 of 28 days. Tamoxifen (20 mg once daily) was started after 1 week of tipifarnib monotherapy to perform pharmacokinetics and FTase inhibition levels in peripheral blood mononuclear cells with tipifarnib alone and with tipifarnib and tamoxifen.A total of 12 heavily pretreated patients with prior progression on hormonal therapy were enrolled. Minimal toxicity was observed at the 200-mg dose level of tipifarnib. At the 300-mg dose, all six patients required dose reduction of tipifarnib due to toxicities that included grade 2 nausea, rash, and fatigue and grade 3 diarrhea and neutropenia. Tipifarnib pharmacokinetic and pharmacodynamic variables were similar in the presence and absence of tamoxifen. Average FTase inhibition was 42% at 200 mg and 54% at 300 mg in peripheral blood mononuclear cells. Of the 12 patients treated, there were two partial responses and one stable disease for >6 months.Tipifarnib (200 mg twice daily for 21 of 28 days) and tamoxifen (20 mg once daily) can be given safely with minimal toxicity. Tamoxifen does not have a significant effect on tipifarnib pharmacokinetics.
Is Proteinuria Reduction by Angiotensin-Converting Enzyme Inhibition Enough to Prove Its Role in Renal Protection in IgA Nephropathy?
Authors: Daniel C. Cattran
Journal: Journal of the American Society of Nephrology (2007)

IgA nephropathy (IgAN) is the most common biopsy-proven type of glomerulonephritis globally, including children ([1][1]). In the United States alone, it is estimated that as many as 30% of children with IgAN are likely to progress to ESRD ([2][2]). Most pediatric studies that deal with treatment,
Clinical Predictors and Algorithm for the Genetic Diagnosis of Pheochromocytoma Patients
Authors: Zoran Erlic, Lisa Rybicki, Mariola Peczkowska, Henriette Golcher, Peter H. Kann, Michael Brauckhoff, Karsten Müssig, Michaela Muresan, Andreas Schäffler, Nicole Reisch, Matthias Schott, Martin Fassnacht, Giuseppe Opocher, Silke Klose, Christian Fottner, Flavio Forrer, Ursula Plöckinger, Stephan Petersenn, Dimitry Zabolotny, Oleg Kollukch, Svetlana Yaremchuk, Andrzej Januszewicz, Martin K. Walz, Charis Eng, Hartmut P.H. Neumann
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Six pheochromocytoma susceptibility genes causing distinct syndromes have been identified; approximately one of three of all pheochromocytoma patients carry a predisposing germline mutation. When four major genes (VHL, RET, SDHB, SDHD) are analyzed in a clinical laboratory, costs are ∼$3,400 per patient. The aim of the study is to systematically obtain a robust algorithm to identify who should be genetically tested, and to determine the order in which genes should be tested. Experimental Design: DNA from 989 apparently nonsyndromic patients were scanned for germline mutations in the genes VHL, RET, SDHB, SDHC, and SDHD. Clinical parameters were analyzed as potential predictors for finding mutations by multiple logistic regression, validated by bootstrapping. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Results: Of 989 apparently nonsyndromic pheochromocytoma cases, 187 (19%) harbored germline mutations. Predictors for presence of mutation are age &amp;lt;45 years, multiple pheochromocytoma, extra-adrenal location, and previous head and neck paraganglioma. If we used the presence of any one predictor as indicative of proceeding with gene testing, then 342 (34.6%) patients would be excluded, and only 8 carriers (4.3%) would be missed. We were also able to statistically model the priority of genes to be tested given certain clinical features. E.g., for patients with prior head and neck paraganglioma, the priority would be SDHD&amp;gt;SDHB&amp;gt;RET&amp;gt;VHL. Using the clinical predictor algorithm to prioritize gene testing and order, a 44.7% cost reduction in diagnostic process can be achieved. Conclusions: Clinical parameters can predict for mutation carriers and help prioritize gene testing to reduce costs in nonsyndromic pheochromocytoma presentations. (Clin Cancer Res 2009;15(20):6378–85)
Animal Eggs for Stem Cell Research: A Path Not Worth Taking
Authors: Françoise Baylis
Journal: The American Journal of Bioethics (2008)

In January 2008, the Human Fertilisation and Embryology Authority (HFEA) (London, UK) issued two 1-year licenses for cytoplasmic hybrid embryo research. This article situates the HFEA's decision in its wider scientific and political context in which, until quite recently, the debate about human embryonic stem cell research has focused narrowly on the moral status of the developing human embryo. Next, ethical arguments against crossing species boundaries with humans are canvassed. Finally, a new argument about the risks of harm to women egg providers resulting from research involving the creation of humanesque cytoplasmic hybrid embryos is elaborated. Taken together these ethical concerns about the moral status of the human embryo, about the ethics of crossing species boundaries with humans, and about the potential harms to women (concerns that independently are more or less weighty for different constituencies), provide good reason to eschew humanesque cytoplasmic hybrid embryo research in favor of less ethically controversial means to the laudable end of successful regenerative medicine.
Bronchiolitis Obliterans Syndrome in Chemical Workers Producing Diacetyl for Food Flavorings
Authors: Frits G. B. G. J. van Rooy, Jos M. Rooyackers, Mathias Prokop, Remko Houba, Lidwien A. M. Smit, Dick J. J. Heederik
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Workers in microwave popcorn plants are at risk of developing bronchiolitis obliterans associated with exposure to butter flavoring volatiles, including diacetyl.To investigate the risk of bronchiolitis obliterans for chemical workers producing diacetyl, with exposure to less complex mixtures of chemicals.We interviewed and conducted spirometry on 175 of 196 workers from a chemical production plant that produced diacetyl between 1960 and 2003. We used all available historical exposure data to classify all workers into three exposure groups with varying exposure profiles to diacetyl, based on frequency and level of exposure.Workers with fixed airway obstruction underwent further pulmonary function testing (including diffusing capacity and lung volumes) and paired inspiratory and expiratory high-resolution computed tomography studies. We identified three cases consistent with bronchiolitis obliterans syndrome with air trapping on high-resolution computed tomography of the lungs, in the highest exposure group of 102 process operators. Two of these cases were lifelong nonsmokers. Potential exposures included acetoin, diacetyl, acetaldehyde, and acetic acid, with diacetyl exposures in the range previously reported to be associated with fixed airway obstruction in the microwave popcorn industry.Exposure to an agent during diacetyl production appears to be responsible for causing bronchiolitis obliterans syndrome in chemical process operators, consistent with the suspected role of diacetyl in downstream food production.
Phosphorylation of Mitochondrial Elongation Factor Tu in Ischemic Myocardium
Authors: Huaping He, Min Chen, N. Karoline Scheffler, Bradford W. Gibson, Linda L. Spremulli, Roberta A. Gottlieb
Journal: Circulation Research (2001)

The objective of this study was to identify the mitochondrial proteins that undergo changes in phosphorylation during global ischemia and reperfusion in the isolated rabbit heart. We also assessed whether the cardioprotective intervention of ischemic preconditioning affected mitochondrial protein phosphorylation. We established a reconstituted system using isolated mitochondria and cytosol from control or ischemic hearts. We found that phosphorylation of a 46-kDa protein on a serine residue was increased in ischemia and that phosphorylation was reduced in control or preconditioned hearts. Using 2D gel electrophoresis and mass spectrometry, we have identified the 46-kDa protein as mitochondrial translational elongation factor Tu (EF-Tu mt ). These data reveal that ischemia and preconditioning modulate the phosphorylation of EF-Tu mt and suggest that the mitochondrial protein synthesis machinery may be regulated by phosphorylation. Phosphorylation of mitochondrial EF-Tu has not been previously described; however, in prokaryotes, EF-Tu phosphorylation inhibits protein translation. We hypothesized that phosphorylation of mitochondrial EF-Tu would inhibit mitochondrial protein translation and attempted to reproduce the effect with inhibition of mitochondrial protein synthesis by chloramphenicol. We found that chloramphenicol pretreatment significantly reduced infarct size, suggesting that mitochondrial protein synthesis is one determinant of myocardial injury during ischemia and reperfusion.
In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis graft stenosis
Authors: Christi M. Terry, Li Li, Huan Li, Ilya Zhuplatov, Donald K. Blumenthal, Seong-Eun Kim, Shawn C. Owen, Eugene G. Kholmovski, Kirk D. Fowers, Ramesh Rathi, Alfred K. Cheung
Journal: Journal of Controlled Release (2012)
Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer
Authors: Nathan C. Sheets, Gregg H. Goldin, Anne-Marie Meyer, Yang Wu, YunKyung Chang, Til Stürmer, Jordan A. Holmes, Bryce B. Reeve, Paul A. Godley, William R. Carpenter, Ronald C. Chen
Journal: JAMA (2012)

<h3>Context</h3>There has been rapid adoption of newer radiation treatments such as intensity-modulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies.<h3>Objective</h3>To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment.<h3>Design, Setting, and Patients</h3>Population-based study using Surveillance, Epidemiology, and End Results–Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer.<h3>Main Outcome Measures</h3>Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy.<h3>Results</h3>Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score–adjusted analyses (N = 12 976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86-0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65-0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03-1.20). Intensity-modulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73-0.89). In a propensity score–matched comparison between IMRT and proton therapy (n = 1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55-0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy.<h3>Conclusions</h3>Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction; IMRT compared with proton therapy was associated with less gastrointestinal morbidity.
The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC
Authors: Y. Takahashi, P. Sheridan, A. Niida, G. Sawada, R. Uchi, H. Mizuno, J. Kurashige, K. Sugimachi, S. Sasaki, Y. Shimada, K. Hase, M. Kusunoki, S. Kudo, M. Watanabe, K. Yamada, K. Sugihara, H. Yamamoto, A. Suzuki, Y. Doki, S. Miyano, M. Mori, K. Mimori
Journal: Annals of Oncology (2015)
Nonsteroidal Anti-inflammatory Drug Treatment for Postoperative Pericardial Effusion
Authors: Philippe Meurin
Journal: Annals of Internal Medicine (2010)

The incidence of asymptomatic pericardial effusion is high after cardiac surgery. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in this setting, but no study has assessed their efficacy.To assess whether the NSAID diclofenac is effective in reducing postoperative pericardial effusion volume.Multicenter randomized, double-blind, placebo-controlled study. (Clinical trials.gov registration number: NCT00247052)5 postoperative cardiac rehabilitation centers.196 patients at high risk for tamponade because of moderate to large persistent pericardial effusion (grade 2, 3, or 4 on a scale of 0 to 4, as measured by echocardiography) more than 7 days after cardiac surgery.Random assignment at each site in blocks of 4 to diclofenac, 50 mg, or placebo twice daily for 14 days.The main end point was change in effusion grade after 14 days of treatment. Secondary end points included frequency of late cardiac tamponade.The initial mean pericardial effusion grade was 2.58 (SD, 0.73) for the placebo group and 2.75 (SD, 0.81) for the diclofenac group. The 2 groups showed similar mean decreases from baseline after treatment (-1.08 grades [SD, 1.20] for the placebo group vs. -1.36 (SD, 1.25) for the diclofenac group). The mean difference between groups was -0.28 grade (95% CI, -0.63 to 0.06 grade; P = 0.105). Eleven cases of late cardiac tamponade occurred in the placebo group and 9 in the diclofenac group (P = 0.64). These differences persisted after adjustment for grade of pericardial effusion at baseline, treatment site, and type of surgery.The sample was not large enough to find small beneficial effects of diclofenac or assess the cardiovascular tolerance of diclofenac.In patients with pericardial effusion after cardiac surgery, diclofenac neither reduced the size of the effusions nor prevented late cardiac tamponade.French Society of Cardiology.
Hypertension guidelines. Other diseases complicate management.
Authors: J Tudor Hart
Journal: BMJ (1993)

Hypertension guidelines 1B blockers no good for smokers EDITOR,-Though I welcome the British Hyper- tension Society's management guidelines in essential hypertension, I am dismayed that there is no mention of the importance of smoking in the choice of first line antihypertensive drug.'The Medical Research Council's trials in both young and older adults clearly showed that smokers do not benefit from , blockers.23Moreover, the trial in older adults indicated that the excess non- cardiovascular mortality in the treated groups was largely attributable to cancers in the ,B blocker group.3I am not aware of any study of hypertension which has refuted these grave doubts about (B blockade and believe that the rationale for its current use, not restricted to non-smokers, is merely that it lowers blood pressure despite the evidence that smokers would be at least as healthy without the (3blockers and possibly healthier.
Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial
Authors: Raimund Erbel, Carlo Di Mario, Jozef Bartunek, Johann Bonnier, Bernard de Bruyne, Franz R Eberli, Paul Erne, Michael Haude, Bernd Heublein, Mark Horrigan, Charles Ilsley, Dirk Böse, Jacques Koolen, Thomas F Lüscher, Neil Weissman, Ron Waksman
Journal: The Lancet (2007)
HEMOLYTIC STREPTOCOCCUS LYMPHADENITIS IN GUINEA PIGS
Authors: C. V. Seastone
Journal: The Journal of Experimental Medicine (1939)

A group of guinea pigs carrying a chronic streptococcus cervical lymphadenitis has been studied. The chronic disease may be transmitted with pure cultures of streptococci isolated from the naturally occurring abscesses. Its probable mode of transmission under natural conditions was shown to be the ingestion of the infective agent. The spontaneous appearance of an acutely fatal variant was observed. Infection with the chronic strains protected animals against the highly virulent strain. Such immunity could not be passively transferred to either mice or guinea pigs, nor could any opsonizing, precipitating, or bactericidal antibody be associated with it. The presence of allergy could not be correlated with this immunity. The dissociation of the chronic and acute strains was investigated and non-invasive phases isolated. No precipitin reaction attributable to an antigenic virulence factor could be demonstrated. No protection was obtained with vaccines or aggressins.