tbuckley/cabot-search huggingface dataset:
Are Electrophysiological Changes Induced by Longer Lasting Atrial Fibrillation Reversible?
Authors: Luz-Maria Rodriguez, Carl Timmermans, Hein J. J. Wellens
Journal: Circulation (1999)

Studies in animal hearts have shown shortening of the atrial effective refractory period (AERP) and loss of the relation between the AERP and heart rate after prolonged periods of atrial fibrillation (AF). The purposes of this study were (1) to evaluate atrial electrophysiology after a long period of sinus rhythm in patients who had longer lasting recurrent AF that was successfully treated with the Metrix Atrioverter and (2) to analyze the effect of prompt cardioversion on subsequent AF episodes and the duration of sinus rhythm.Four patients with recurrent AF (duration, 3 to 21 years; mean+/-SD, 13+/-7.6 years) were studied after the implantation of an Atrioverter. The Atrioverter stores and analyzes 3 minutes of cardiac rhythm every hour. Before implantation, AERP was measured. During a mean follow-up of 14 months, 52 spontaneous (39 treated and 18 nontreated) AF episodes occurred while the patients were on antiarrhythmic drugs. All patients were electrophysiologically studied after they had been in sinus rhythm for at least 1000 hours (range, 1052 to 2675 hours). Before Atrioverter implantation, AF was induced by 1 atrial premature beat in 3 patients and not induced in the remaining patient. After a long period in sinus rhythm (>1000 hours), AF could be induced in the same 3 patients in the same way as before implantation. In the patient in whom no AF was induced, right AERP values measured using the single extrastimulus technique at 3 pacing cycle lengths (600, 500, and 430 ms) were similar to those before implantation.AF was still inducible by a single atrial premature beat after long episodes of sinus rhythm in 3 of 4 patients with previously longer lasting AF. In the patient in whom no AF was induced, AERP behaved like it did before implantation. In these patients with longer lasting recurrent AF, no return to "normal" atrial electrophysiology could be demonstrated.
Antioxidants and the bioactivity of endothelium-derived nitric oxide
Authors: Douglas Tomasian, John F. Keaney, Joseph A. Vita
Journal: Cardiovascular Research (2000)

Time for primary view 21 days. 

Over the past two decades, investigators have increasingly recognized the importance of the endothelium as a central regulator of vascular homeostasis. In 1980, Furchgott and Zawadzki [1] reported that acetylcholine-mediated relaxation of isolated aortic tissue is dependent on release of an ‘endothelium-derived relaxing factor’. Subsequent studies by Ignarro and colleagues identified this factor as nitric oxide (NO) [2] or a closely related NO product [3]. In addition to regulating vascular tone, it is now appreciated that endothelium-derived NO also acts to inhibit platelet activity, vascular smooth muscle cell growth, and adhesion of inflammatory cells to the endothelial surface [4].

Loss of the bioactivity of endothelium-derived NO plays a critical role in the pathogenesis of a number of disease states including atherosclerosis and its risk factors [5]. A large body of work suggests that the impaired NO action in atherosclerosis is related to increased oxidative stress in the vascular wall [6]. Since oxidative stress may be defined as an excess of oxidants relative to antioxidant defenses [7], investigators were prompted to examine the possibility that increasing antioxidant availability would restore NO-dependent responses. This article will review the effects of antioxidants on NO bioactivity and the clinical implications of these observations.

NO is synthesized in endothelial cells from l-arginine by the endothelial isoform of NO synthase (eNOS), which is the product of the NOS3 gene [8]. eNOS is constitutively expressed and located to caveolae in the plasma membrane. When bound to caveolin, eNOS is catalytically inactive. In the presence of calcium, calmodulin displaces caveolin and binds to eNOS, and thereby activates the enzyme [8]. Thus, NO production by endothelial cells is stimulated by factors that increase intracellular calcium concentration including receptor-dependent agonists like acetylcholine, bradykinin, substance P, and … 

* Corresponding author. Boston Medical Center, 88 East Newton Street, Boston, MA 02118, USA. Tel.: +1-617-638-8701; fax: +1-617-638-8712 jvita{at}bu.edu
Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study
Authors: Khaled M Musallam, Hani M Tamim, Toby Richards, Donat R Spahn, Frits R Rosendaal, Aida Habbal, Mohammad Khreiss, Fadi S Dahdaleh, Kaivan Khavandi, Pierre M Sfeir, Assaad Soweid, Jamal J Hoballah, Ali T Taher, Faek R Jamali
Journal: The Lancet (2011)
Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer
Authors: Shailesh Agarwal, Lisa Pappas, Leigh Neumayer, Kristine Kokeny, Jayant Agarwal
Journal: JAMA Surgery (2014)

To our knowledge, there are no recent studies that directly compare survival after breast conservation therapy (BCT) vs mastectomy.To compare the breast cancer-specific survival rates of patients undergoing BCT, mastectomy alone, or mastectomy with radiation using a contemporary cohort of patients.We performed univariate, multivariate logistic regression, and propensity analyses to compare the hazard of death for female patients with early-stage invasive ductal carcinoma treated with BCT, mastectomy alone, or mastectomy with radiation during the period from 1998 to 2008. The data were extracted from the Surveillance, Epidemiology, and End Results database. Early-stage breast cancer was defined as having a tumor size of 4 cm or smaller with 3 or less positive lymph nodes.Breast conservation therapy, mastectomy alone, or mastectomy with radiation.Hazard of death due to breast cancer for patients undergoing BCT, mastectomy alone, or mastectomy with radiation.A total of 132,149 patients were included in this analysis. Breast conservation therapy was used to treat 70% of patients, mastectomy alone was used to treat 27% of patients, and mastectomy with radiation was used to treat 3% of patients. The 5-year breast cancer-specific survival rates of patients who underwent BCT, a mastectomy alone, or a mastectomy with radiation were 97%, 94%, and 90%, respectively (P < .001); the 10-year breast cancer-specific survival rates were 94%, 90%, and 83%, respectively (P < .001). Multivariate analysis showed that women undergoing BCT had a higher survival rate than those undergoing mastectomy alone (hazard ratio, 1.31; P < .001) or mastectomy with radiation (hazard ratio, 1.47; P < .001). When propensity score stratification was used, the effect of treatment method on survival was similar.Patients who underwent BCT have a higher breast cancer-specific survival rate compared with those treated with mastectomy alone or mastectomy with radiation for early-stage invasive ductal carcinoma. Further investigation is warranted to understand what may be contributing to this effect.
Asylums: Essays on the Social Situation of Mental Patients and other Inmates
Authors: S. Mac Suibhne
Journal: BMJ (2009)

“Deinstitutionalisation” has become one of the stated aims of modern, establishment psychiatry. Somewhat like motherhood and apple pie, it seems to have become a concept that is nearly impossible to criticise. Whether institutionalisation was ever exactly like its critics described it is a moot point; another is whether what we have seen since the move to community psychiatry is really “transinstitutionalisation”—with those patients who formerly would have been in asylums now in prison or homeless—rather than deinstitutionalisation. Goffman’s Asylums , a key text in the development of deinstitutionalisation, anticipated and indeed predicted some of these …
Pur α Binds to rCGG Repeats and Modulates Repeat-Mediated Neurodegeneration in a Drosophila Model of Fragile X Tremor/Ataxia Syndrome
Authors: Peng Jin, Ranhui Duan, Abrar Qurashi, Yunlong Qin, Donghua Tian, Tracie C. Rosser, Huijie Liu, Yue Feng, Stephen T. Warren
Journal: Neuron (2007)
Cediranib Plus FOLFOX/CAPOX Versus Placebo Plus FOLFOX/CAPOX in Patients With Previously Untreated Metastatic Colorectal Cancer: A Randomized, Double-Blind, Phase III Study (HORIZON II)
Authors: Paulo M. Hoff, Andreas Hochhaus, Bernhard C. Pestalozzi, Niall C. Tebbutt, Jin Li, Tae Won Kim, Krassimir D. Koynov, Galina Kurteva, Tamás Pintér, Ying Cheng, Brigitte van Eyll, Laura Pike, Anitra Fielding, Jane D. Robertson, Mark P. Saunders
Journal: Journal of Clinical Oncology (2012)

Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signaling with activity against all three VEGF receptors. HORIZON II [Cediranib (AZD2171, RECENTIN) in Addition to Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer] assessed infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (FOLFOX/CAPOX) with or without cediranib in patients with previously untreated metastatic colorectal cancer (mCRC).Eligible patients were initially randomly assigned 1:1:1 to receive cediranib (20 or 30 mg per day) or placebo plus FOLFOX/CAPOX. In an early analysis of this and two other cediranib studies (HORIZON I [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Previously Treated Metastatic Colorectal Cancer] and HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer]), the 20-mg dose met the predefined criteria for continuation. Subsequent patients were randomly assigned 2:1 to the cediranib 20 mg or placebo arms. Progression-free survival (PFS) and overall survival (OS) were coprimary end points.In all, 860 patients received cediranib 20 mg (n = 502) or placebo (n = 358). The addition of cediranib to FOLFOX/CAPOX resulted in PFS prolongation (hazard ratio [HR], 0.84; 95% CI, 0.73 to 0.98; P = .0121; median PFS, 8.6 months for cediranib v 8.3 months for placebo) but had no impact on OS (HR, 0.94; 95% CI, 0.79 to 1.12; P = .5707; median OS, 19.7 months for cediranib v 18.9 months for placebo). There were no significant differences in the secondary end points of objective response rate, duration of response, or liver resection rate. Median chemotherapy dose-intensity was decreased by approximately 10% in patients treated with cediranib. Adverse events (AEs) associated with cediranib were manageable. CONCLUSION Addition of cediranib 20 mg to FOLFOX/CAPOX resulted in a modest PFS prolongation, but no significant difference in OS. The cediranib AE profile was consistent with those from previous studies. Because of the lack of improvement in OS, cediranib plus an oxaliplatin-based regimen cannot be recommended as a treatment for patients with mCRC.
Spleen Cells from Young Donors Eradicate Large Tumors–Response
Authors: Donald A. Rowley, Karin Schreiber, Hans Schreiber
Journal: Clinical Cancer Research (2012)

We are very grateful to Dr. Radvanyi for his keen analysis and stimulating suggestions for possible ways to offset the effects of aging on the immune system. We do not question the desirability for having standardized assays of “immune health” that can be applied to all cancer patients, but the assays must be relevant to the outgrowth of cancer and not to other measurable immune responses.We can construct such assays for mice of various inbred strains where multiple individuals of different ages of each strain are available (1). But we are unable, probably due to lack of imagination, to envision such tests for individuals in outbred populations. Our concern is that assays unrelated to an individual's response to a cancer will be developed and exploited commercially, just as some screening tests for other diseases have been exploited. For this reason, we warn against the misinterpretation of this part of Dr. Radvanyi's letter.See the original Letter to the Editor, p. 6074No potential conflicts of interest were disclosed.
Reference Equations for the Six-Minute Walk in Healthy Adults
Authors: PAUL L. ENRIGHT, DUANE L. SHERRILL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

In order to establish reference equations for prediction of the total distance walked during six minutes (6MWD) for healthy adults, we administered the standardized 6-min walk test to 117 healthy men and 173 healthy women, aged 40 to 80 yr. Oxygen saturation (SaO2 ), pulse rate, and the degree of dyspnea (Borg scale) were determined before and at the end of the walk. The median distance walked was 576 m for men and 494 m for women. The 6MWD was significantly less for men and women who were older and heavier, and for shorter men. The resulting gender-specific regression equations explained about 40% of the variance in the distance walked for healthy adults: for men, 6MWD = (7.57 × heightcm) − (5.02 × age) − (1.76 × weightkg) − 309 m, and for women, 6MWD = (2.11 × heightcm) − (2.29 × weightkg) − (5.78 × age) + 667 m. These reference equations may be used to compute the percent predicted 6MWD for individual adult patients performing the test for the first time, when using the standardized protocol.
Cost-Minimization Analysis of Prophylactic Granulocyte Colony-Stimulating Factor After Induction Chemotherapy in Children With Non-Hodgkin'ss Lymphoma
Authors: Carole Rubino, Agne`s Laplanche, Catherine Patte, Jean Michon
Journal: JNCI Journal of the National Cancer Institute (1998)

Colony-stimulating factors promote the proliferation of certain bone marrow cell populations. The primary objective of treating patients with these factors prophylactically following chemotherapy is to reduce the risk of infection, thereby minimizing the need for hospitalization and parenteral antibiotics. The use of colony-stimulating factors in children is widespread, despite the absence of conclusive supportive data and the high cost of these drugs. Consequently, the cost-benefit ratio of using prophylactic colony-stimulating factors is an important issue in cancer therapy.During the period from January 1994 through June 1996, 149 afebrile children with newly diagnosed non-Hodgkin's lymphoma were randomly assigned either to receive granulocyte colony-stimulating factor (G-CSF) (lenograstim; 5 microg/kg body weight per day subcutaneously) or not to receive it (the control) at the end of the first two courses of induction chemotherapy with cyclophosphamide, vincristine, prednisone, doxorubicin, and methotrexate. A cost-minimization analysis was performed to assess the cost of chemotherapy in each group and to quantify how much could be economized by prescribing G-CSF.The total cost for induction chemotherapy was $29,765 in the G-CSF-treated group and $30,774 in the control group, indicating that the treatment strategy with G-CSF was slightly less expensive than the strategy without G-CSF (mean difference = $1009; 95% confidence interval = -$1474 to $3492).Treatment with G-CSF following chemotherapy in children with non-Hodgkin's lymphoma--previously shown to be of limited clinical benefit--also does not appear to reduce the costs of chemotherapy.
Calcineurin Aβ Is Central to the Expression of the Renal Type II Na/Pi Co-transporter Gene and to the Regulation of Renal Phosphate Transport
Authors: Yulia Moz, Ronen Levi, Vardit Lavi-Moshayoff, Keith B. Cox, Jeffery D. Molkentin, Justin Silver, Tally Naveh-Many
Journal: Journal of the American Society of Nephrology (2004)

The sensing and response to extracellular phosphate (Pi) concentration is preserved from prokaryotes to mammals and ensures an adequate supply of Pi in the face of large differences in its availability. In mammals, the kidneys are central to Pi homeostasis. Renal Pi reabsorption is mediated by a Na/Pi co-transporter that is regulated by a renal Pi sensing system and humoral factors. The signal transduction by which Pi regulates type II Na/Pi activity is largely unknown. It is shown that calcineurin inhibitors specifically and dramatically decrease type II Na/Pi gene expression in a proximal tubule cell line and in vivo. Mice with genetic deletion of the calcineurin Aβ gene had a marked decrease in type II Na/Pi mRNA levels and remarkably did not show the expected increase in type II Na/Pi mRNA levels after the challenge of a low-Pi diet. In contrast, the regulation of renal 25(OH)-vitamin D 1α-hydroxylase gene expression by Pi was intact. This is the first demonstration that calcineurin has a crucial role in the signal transduction pathway regulating renal Pi homeostasis both in vitro and in vivo. These results suggest that the use of calcineurin inhibitors contributes to the renal Pi wasting seen in renal transplant patients.
Influence of age on natriuretic peptides in patients with chronic heart failure: a comparison between ANP/NT‐ANP and BNP/NT‐proBNP
Authors: Jochem Hogenhuis, Adriaan A. Voors, Tiny Jaarsma, Hans L. Hillege, Frans Boomsma, Dirk J. van Veldhuisen
Journal: European Journal of Heart Failure (2004)
GENETIC REGULATION OF CARDIOGENESIS AND CONGENITAL HEART DISEASE
Authors: Deepak Srivastava
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Developmental heart disorders are the most common of all human birth defects and occur in nearly one percent of the population. Survivors of congenital heart malformations are an increasing population, and it is becoming clear that genetic mutations that cause developmental anomalies may result in cardiac dysfunction later in life. This review highlights the progress in understanding the underlying molecular basis for cardiac formation and how disruption of the intricate steps of cardiogenesis can lead to congenital heart defects. The lessons learned from examining the early steps of heart formation are essential for informing the prevention of malformations and their long-term consequences, as well as for approaches to guide stem cells into cardiac lineages.
Analysis of Intrachromosomal Duplications in Yeast Saccharomyces cerevisiae: A Possible Model for Their Origin
Authors: Guillaume Achaz, Eric Coissac, Alain Viari, Pierre Netter
Journal: Molecular Biology and Evolution (2000)

The complete genome of the yeast Saccharomyces cerevisiae was investigated for intrachromosomal duplications at the level of nucleotide sequences. The analysis was performed by looking for long approximate repeats (from 30 to 3,885 bp) present on each of the chromosomes. We show that direct and inverted repeats exhibit very different characteristics: the two copies of direct repeats are more similar and longer than those of inverted repeats. Furthermore, contrary to the inverted repeats, a large majority of direct repeats appear to be closely spaced. The distance (delta) between the two copies is generally smaller than 1 kb. Further analysis of these "close direct repeats" shows a negative correlation between delta and the percentage of identity between the two copies, and a positive correlation between delta and repeat length. Moreover, contrary to the other categories of repeats, close direct repeats are mostly located within coding sequences (CDSs). We propose two hypotheses in order to interpret these observations: first, the deletion/conversion rate is negatively correlated with delta; second, there exists an active duplication mechanism which continuously creates close direct repeats, the other intrachromosomal repeats being the result, by chromosomal rearrangements of these "primary repeats."
Impact of Preanalytic Factors on the Design and Application of Integral Biomarkers for Directing Patient Therapy
Authors: Stephen M. Hewitt, Sunil S. Badve, Lawrence D. True
Journal: Clinical Cancer Research (2012)

Abstract Molecular assays have been routinely applied to improve diagnosis for the last 25 years. Assays that guide therapy have a similar history; however, their evolution has lacked the focus on analytic integrity that is required for the molecularly targeted therapies of today. New molecularly targeted agents require assays of greater precision/quantitation to predict the likelihood of response, i.e., to identify patients whose tumors will respond, while at the same time excluding and protecting those patients whose tumors will not respond or in whom treatment will cause unacceptable toxicity. The handling of tissue has followed a fit-for-purpose approach focused on appropriateness for diagnostic needs, which is less rigorous than the demands of new molecular assays that interrogate DNA, RNA, and proteins in a quantitative, multiplex manner. There is a new appreciation of the importance and fragility of tissue specimens as the source of analytes to direct therapy. By applying a total test paradigm and defining and measuring sources of variability in specimens, we can develop a set of specifications that can be incorporated into the clinical-care environment to ensure that a specimen is appropriate for analysis and will return a true result. Clin Cancer Res; 18(6); 1524–30. ©2012 AACR.
Management of Type 2 Diabetes in Treatment-Naive Elderly Patients
Authors: Richard E. Pratley, Julio Rosenstock, F. Xavier Pi-Sunyer, Mary Ann Banerji, Anja Schweizer, Andre Couturier, Sylvie Dejager
Journal: Diabetes Care (2007)

OBJECTIVE—The purpose of this study was to evaluate the efficacy and safety of vildagliptin in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Efficacy data from five double-blind, randomized, placebo- or active-controlled trials of ≥24 weeks’ duration were pooled. Effects of 24-week vildagliptin monotherapy (100 mg daily) were compared in younger (&amp;lt;65 years, n = 1,231) and older (≥65 years, n = 238) patients. Safety data from eight controlled clinical trials of ≥12-weeks’ duration were pooled; adverse event profiles in younger (n = 1,890) and older (n = 374) patients were compared. RESULTS—Mean baseline A1C and fasting plasma glucose (FPG) were significantly lower in older (70 years: 8.3 ± 0.1% and 9.6 ± 0.1 mmol/l, respectively) than in younger (50 years: 8.7 ± 0.0% and 10.5 ± 0.1 mmol/l, respectively) patients. Despite this, the adjusted mean change from baseline (AMΔ) in A1C was −1.2 ± 0.1% in older and −1.0 ± 0.0% in younger vildagliptin-treated patients (P = 0.092), and the AMΔ in FPG was significantly larger in older (−1.5 ± 0.2 mmol/l) than in younger (−1.1 ± 0.1 mmol/l, P = 0.035) patients. Body weight was significantly lower at baseline in older (83.4 ± 1.0 kg) than in younger (92.0 ± 0.6 kg) patients. Weight decreased significantly in the older subgroup (AMΔ −0.9 ± 0.3 kg, P = 0.007), whereas smaller, nonsignificant decreases occurred in younger patients (AMΔ −0.2 ± 0.1 kg). Adverse event rates were slightly higher in older than in younger subgroups but were lower among older, vildagliptin-treated subjects (63.6%) than in the pooled active comparator group (68.1%). Vildagliptin treatment did not increase adverse events among older patients with mild renal impairment (62.0%). Hypoglycemia was rare (0.8%) in the elderly patients, and no severe events occurred. CONCLUSIONS—Vildagliptin monotherapy was effective and well tolerated in treatment-naive elderly patients.