tbuckley/cabot-search huggingface dataset:
Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis
Authors: Reinhild Klein, Joseph Eisenburg, Paul Weber, Frank Seibold, Peter A. Berg
Journal: Hepatology (1991)

Antibodies against neutrophils have been detected in sera from patients with primary sclerosing cholangitis and inflammatory bowel diseases either by immunofluorescence or by enzyme-linked immunosorbent assay. To assess primary sclerosing cholangitis-specific antibodies, we examined sera from 30 patients with clinically and morphologically well-established primary sclerosing cholangitis by Western blotting against neutrophils and compared these results with those obtained by testing sera from patients with inflammatory bowel diseases. By Western blot using sonified neutrophils, 24 (80%) of 30 primary sclerosing cholangitis sera were positive. Five antigenic determinants at 95, 60, 55, 40 and 30 kD were visualized. Twenty-eight of the primary sclerosing cholangitis sera also showed the characteristic perinuclear fluorescence pattern by immunofluorescence on neutrophils. Thus a serological diagnosis of primary sclerosing cholangitis could be made in 80% of patients based on these two methods. In contrast, only 9% of 23 patients with ulcerative colitis and 10% of 60 patients with Crohn's disease were positive by Western blot, and these patients also showed positive perinuclear fluorescence pattern by immunofluorescence, suggesting an overlap between inflammatory bowel diseases and primary sclerosing cholangitis. Although some patients with classical primary biliary cirrhosis and autoimmune chronic active hepatitis had antibodies against primary sclerosing cholangitis epitopes, none of the patients with obstructive bile duct disorders, collagen diseases, Wegener's granulomatosis or other hepatic and nonhepatic disorders were positive by Western blot, indicating the specificity of these five primary sclerosing cholangitis-related neutrophilic epitopes.
Endoscopic Management of Acute Colonic Pseudo-Obstruction
Authors: M. D. Saunders, M. S. Cappell
Journal: Endoscopy (2005)

Acute colonic pseudo-obstruction (ACPO), also referred to as Ogilvie’s syndrome, is a clinical condition that presents with the symptoms, signs, and radiographic appearance of acute large-bowel obstruction without a mechanical cause (Figure [1]). ACPO is an important cause of morbidity and mortality. Early detection and prompt, appropriate management are critical to minimize morbidity and mortality. The decision to intervene with active therapy is dictated by the patient’s clinical status. The risk of spontaneous colonic perforation in ACPO is estimated to be approximately 3 %. The mortality rate in ACPO is approximately 40 % when ischemia or perforation is present, compared with 15 % in patients with intact and viable bowel [1].
The case against memory consolidation in REM sleep
Authors: Robert P. Vertes, Kathleen E. Eastman
Journal: Behavioral and Brain Sciences (2000)

We present evidence disputing the hypothesis that memories are processed or consolidated in REM sleep. A review of REM deprivation (REMD) studies in animals shows these reports to be about equally divided in showing that REMD does, or does not, disrupt learning/memory. The studies supporting a relationship between REM sleep and memory have been strongly criticized for the confounding effects of very stressful REM deprivation techniques. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. The MAOIs virtually abolish REM sleep, and the TCAs and SSRIs have been shown to produce immediate (40–85%) and sustained (30–50%) reductions in REM sleep. Despite marked suppression of REM sleep, these classes of antidepressants on the whole do not disrupt learning/memory. There have been a few reports of patients who have survived bilateral lesions of the pons with few lingering complications. Although these lesions essentially abolished REM sleep, the patients reportedly led normal lives. Recent functional imaging studies in humans have revealed patterns of brain activity in REM sleep that are consistent with dream processes but not with memory consolidation. We propose that the primary function of REM sleep is to provide periodic endogenous stimulation to the brain which serves to maintain requisite levels of central nervous system (CNS) activity throughout sleep. REM is the mechanism used by the brain to promote recovery from sleep. We believe that the cumulative evidence indicates that REM sleep serves no role in the processing or consolidation of memory.
Heart Failure Practice Guidelines: Guidance, Not Proscription
Authors: Marvin A. Konstam
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Dr Parmley<sup>1</sup>recently commented on our recommendations for medical management,<sup>2</sup>based on the published clinical practice guideline for heart failure.<sup>3</sup>I largely agree with Parmley's delineation of the value and limitations of such guidelines. These opinions are my own. Guidelines are intended to reduce gaps between scientific knowledge and clinical practice, which may be particularly prevalent among primary care physicians who must follow advances in numerous specialties. As Parmley states, the value of guidelines stems from the authors' having "carefully evaluated the world's literature... as the basis for decision making." So much for the easy part. The hard part is implementing guidelines prudently. It is tempting to transform guideline recommendations into dictum, assigning penalties or rewards based on compliance, but one must choose between the following two perceptions of guidelines: (1) they are declarations of standard care that require rigid adherence, or (2) they
Influence of Tangeretin on Tamoxifen's Therapeutic Benefit in Mammary Cancer
Authors: M. E. Bracke, H. T. Depypere, T. Boterberg, V. L. Van Marck, K.'l M. Vennekens, E. Vanluchene, M. Nuytinck, R. Serreyn, M. M. Mareel
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Tamoxifen and the citrus flavonoid tangeretin exhibit similar inhibitory effects on the growth and invasive properties of human mammary cancer cells in vitro ; furthermore, the two agents have displayed additive effects in vitro . In this study, we examined whether tangeretin would enhance tamoxifen's therapeutic benefit in vivo. METHODS: Female nude mice (n = 80) were inoculated subcutaneously with human MCF-7/6 mammary adenocarcinoma cells. Groups of 20 mice were treated orally by adding the following substances to their drinking water: tamoxifen (3 × 10 −5 M ), tangeretin (1 × 10 −4M ), tamoxifen plus tangeretin (3 × 10 −5M plus 1 × 10 −4 M ), or solvent. RESULTS AND CONCLUSIONS: Oral treatment of mice with tamoxifen resulted in a statistically significant inhibition of tumor growth compared with solvent treatment (two-sided P = .001). Treatment with tangeretin did not inhibit tumor growth, and addition of this compound to drinking water with tamoxifen completely neutralized tamoxifen's inhibitory effect. The median survival time of tumor-bearing mice treated with tamoxifen plus tangeretin was reduced in comparison with that of mice treated with tamoxifen alone (14 versus 56 weeks; two-sided P = .002). Tangeretin (1 × 10 −6M or higher) inhibited the cytolytic effect of murine natural killer cells on MCF-7/6 cells in vitro, which may explain why tamoxifen-induced inhibition of tumor growth in mice is abolished when tangeretin is present in drinking water. IMPLICATIONS: We describe an in vivo model to study potential interference of dietary compounds, such as flavonoids, with tamoxifen, which could lead to reduced efficacy of adjuvant therapy. In our study, the tumor growth-inhibiting effect of oral tamoxifen was reversed upon addition of tangeretin to the diet. Our data argue against excessive consumption of tangeretin-added products and supplements by patients with mammary cancer during tamoxifen treatment.
Echocardiographic evaluation of left ventricular size and performance during handgrip and supine and upright bicycle exercise.
Authors: M H Crawford, D H White, K W Amon
Journal: Circulation (1979)

We used M-mode echocardiography to measure left ventricular dimensions in diastole (Dd) and systole (Ds) and to assess ventricular performance by computing the percent dimensional shortening (%AD) and the normalized rate of dimensional shortening (Vd) during isometric and isotonic exercise in nor- mal subjects.In 27 subjects, isometric handgrip exercise at 50% of maximum grip until fatigue produced a significant increase in Ds (33 ± 3.4 (SD) vs 30.6 i 3.7 mm, p < 0.001), and a reduction in %AD (34 ± 4 vs 39 ± 5%,p < 0.001) and Vd (1.15 ± 0.15 vs 1.28 0.19 sec-',p < 0.001).Handgrip exercise at 15% of max- imum grip produced similar but less marked changes in the 27 subjects, and acute pressure loading with phenylephrine caused similar but more marked changes in 10 of the subjects.In the 20 subjects who performed at least 12 minutes of supine bicycle exercise, Ds decreased significantly (25.6 ± 4.0 vs 31.7 ± 2.8 mm, p < 0.001) and %AD increased (49 ± 6 vs 36 ± 5%,p < 0.001).We observed similar results in the 12 subjects also studied during upright bicycle exercise.Dd was smaller in the upright position but unchanged during either isometric or isotonic exercise.We conclude that: 1) end-diastolic left ventricular size is maintained dur- ing isometric exercise and moderate dynamic exercise, even in the upright position; 2) isometric exercise leads to a mild decrease in left ventricular shortening, whereas dynamic exercise results in marked increases in shortening; this difference may be related to the relatively greater increase in blood pressure than in heart rate during isometric exercise; and 3) M-mode echocardiography can be successfully accomplished in selected sub- jects during various forms of exercise.
Acceleration of re-endothelialization and inhibition of neointimal formation using hybrid biodegradable nanofibrous rosuvastatin-loaded stents
Authors: Cheng-Hung Lee, Shang-Hung Chang, Yu-Huang Lin, Shih-Jung Liu, Chao-Jan Wang, Ming-Yi Hsu, Kuo-Chun Hung, Yung-Hsin Yeh, Wei-Jan Chen, I-Chang Hsieh, Ming-Shien Wen
Journal: Biomaterials (2014)
Declining Stroke and Vascular Event Recurrence Rates in Secondary Prevention Trials Over the Past 50 Years and Consequences for Current Trial Design
Authors: Keun-Sik Hong, Sharon Yegiaian, Meng Lee, Juneyoung Lee, Jeffrey L. Saver
Journal: Circulation (2011)

It is widely supposed, but not well-demonstrated, that cumulative advances in standard care have reduced recurrent stroke and cardiovascular events in secondary prevention trials.Systematic search identified all randomized, controlled trials of medical secondary stroke prevention therapies published from 1960 to 2009. Randomized, controlled trials narrowly focused on single stroke mechanisms, including atrial fibrillation, cervical carotid stenosis, and intracranial stenosis, were excluded. From control arms of individual trials, we extracted data for baseline characteristics and annual event rates for recurrent stroke, fatal stroke, and major vascular events and analyzed trends over time. Fifty-nine randomized controlled trials were identified, enrolling 66 157 patients in control arms. Over the 5 decade periods, annual event rates declined, per decade, for recurrent stroke by 0.996% (P=0.001), fatal stroke by 0.282% (P=0.003), and major vascular events by 1.331% (P=0.001). Multiple regression analyses identified increasing antithrombotic use and lower blood pressures as major contributors to the decline in recurrent stroke. For recurrent stroke, annual rates fell from 8.71% in trials launched in the 1960s to 6.10% in the 1970s, 5.41% in the 1980s, 4.04% in the 1990s, and 4.98% in the 2000s. The sample size required for a trial to have adequate power to detect a 20% reduction in recurrent stroke increased 2.2-fold during this period.Recurrent stroke and vascular event rates have declined substantially over the last 5 decades, with improved blood pressure control and more frequent use of antiplatelet therapy as the leading causes. Considerably larger sample sizes are now needed to demonstrate incremental improvements in medical secondary prevention.
Cecocolic Intussusception — A Postoperative Complication of Appendectomy
Authors: Kenneth S. Danielson
Journal: New England Journal of Medicine (1969)

THE removal of the nonperforated appendix has been associated with a low mortality and morbidity in recent years. The present report focuses on a rare but clinically distinct and potentially lethal complication after appendectomy.Case ReportA 19-year-old boy was admitted to the Emergency Department with symptoms of acute appendicitis. At operation an acutely inflamed appendix was removed, with inversion of the appendiceal stump. The terminal ileum appeared normal. The immediate postoperative period was satisfactory except for mild crampy abdominal pain, which began on the 4th day. Abdominal examination remained unremarkable, and he was discharged on the 7th day.At . . .
Nasal Packs for Epistaxis
Authors: William H. Saunders
Journal: JAMA (1971)

ABSTRACT To the Editor.— The article by Herzon in the Archives of Otolaryngology (94:317, 1971), recommending the use of an ointment containing oxytetracycline and polymyxin B in packs left in the nose of patients with nosebleeds is timely. I have used the same antibiotic preparation in all types of intranasal and sinal packs for the past 15 years, and although I have mentioned the matter in several publications it never has seemed to catch on with the profession. The complete absence of odor when these packs are removed (some having been left in place as long as two weeks) means to me that there also is lack of infection.
Intra-amniotic Delivery of CFTR-expressing Adenovirus Does Not Reverse Cystic Fibrosis Phenotype in Inbred CFTR-knockout Mice
Authors: Suzanne MK Buckley, SN Waddington, S Jezzard, A Bergau, M Themis, LJ MacVinish, AW Cuthbert, WH Colledge, C Coutelle
Journal: Molecular Therapy (2008)

Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero-injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (Cftr(tmlCam)) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr(-/-) mice treated with the CFTR-adenovirus and those treated with the control vector.
Angiotensin II-induced atrial natriuretic factor release in dogs is not related to hemodynamic responses.
Authors: M Volpe, S A Atlas, R E Sosa, D E Marion, F B Mueller, J E Sealey, J H Laragh
Journal: Circulation Research (1990)

Angiotensin II (Ang II) and atrial natriuretic factor (ANF) appear to act as functional antagonists in the regulation of fluid and electrolyte homeostasis and blood pressure. To further define the relations between these hormones in vivo, we investigated the effect of low doses of Ang II (1-10 ng/kg/min) on plasma ANF levels. We also evaluated the influence of ANF release on the renal and hormonal responses to ANG II. Studies were performed in anesthetized and conscious instrumented dogs during sustained saline load and converting enzyme inhibition. In the anesthetized dogs, Ang II significantly increased plasma ANF levels and ANF arteriovenous difference without changing either atrial pressures or hematocrit. In both conscious and anesthetized dogs, ANF increases were not correlated with blood pressure responses to Ang II and did not occur in control groups when Ang II was replaced by vehicle. Ang II-induced sodium retention and stimulation of aldosterone production were attenuated, and renin suppression was enhanced in dogs having the largest changes in plasma ANF in response to converting enzyme inhibition or Ang II. These results demonstrate that in volume-replete dogs Ang II can promote ANF release independently of changes in atrial pressures or systemic hemodynamics, suggesting that Ang II may exert a significant modulatory effect on ANF secretion. The results also show significant relations between ANF and renal and adrenal responses to Ang II, which may suggest that, in turn, endogenous ANF modulates the effects of Ang II.
Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas
Authors: Misu Lee, Tobias Wiedemann, Claudia Gross, Ines Leinhäuser, Federico Roncaroli, Rickmer Braren, Natalia S. Pellegata
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats). Experimental Design: Organotypic cultures of rat primary NFPAs were incubated with NVP-BEZ235 and assessed for cell viability, proliferation, apoptosis, and PI3K/mTOR inhibition. NVP-BEZ235, or placebo, was administered to MENX rats and tumor response was monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tumor tissues were investigated for cell proliferation, apoptosis, and PI3K/mTOR inhibition. Genes mediating the cytotoxic activity of NVP-BEZ235 were identified by gene-expression profiling. Among them, Defb1, encoding beta-defensin 1, was further studied for its role in pituitary cells and in human pancreatic neuroendocrine tumor (NET) cells. Results: NVP-BEZ235 showed antiproliferative and pro-cell death activities against NFPAs both in vitro and in vivo, and the response to the drug correlated with inhibition of the PI3K pathway. DW-MRI identified early functional changes (decreased cellularity) in the adenomas before their size was affected and emerged as a useful modality to assess therapy response. The cytotoxic effect of PI3K/mTOR blockade in NFPA was mediated by several genes, including Defb1. NVP-BEZ235 treatment induced Defb1 expression in NFPAs in vitro and in vivo, and in pancreatic NET cells. High Defb1 levels sensitized NET cells to PI3K/mTOR inhibition. Conclusions: Our findings provide rationale for clinical investigation of PI3K/mTOR inhibition in NFPAs and identify novel effectors of PI3K-mediated neuroendocrine cell survival. Clin Cancer Res; 21(14); 3204–15. ©2015 AACR.
601 CLINICAL FEATURES OF ADVANCED HEPATOCELLULAR CARCINOMA WITH EXTRAHEPATIC METASTASIS
Authors: K. Uchino, R. Tateishi, S. Shiina, T. Arano, K. Enooku, E. Goto, R. Masuzaki, H. Nakagawa, Y. Kondo, T. Goto, M. Omata, H. Yoshida, K. Koike
Journal: Journal of Hepatology (2010)
Aftershocks hamper rescue efforts in Chile
Authors: P. Moszynski
Journal: BMJ (2010)

Although the earthquake that struck Chile last week was some 350 times more powerful than the one that recently devastated Haiti, its immediate effects were far less disastrous. The total number of confirmed dead has been revised downwards to less than 500—a fraction of the estimated 220 000 deaths in Haiti—and most government installations and infrastructure remain functioning.

Yet some two million people are temporarily homeless and many still lack electricity, clean water, and sanitation, leading to fears of outbreaks of hepatitis A and other waterborne diseases as well as infections from contaminated injuries. The health ministry has begun vaccination campaigns against hepatitis A and tetanus.

The area affected by the earthquake …
Erbium--169 versus triamcinolone hexacetonide in the treatment of rheumatoid finger joints.
Authors: A Ruotsi, M Hypen, A Rekonen, M Oka
Journal: Annals of the Rheumatic Diseases (1979)

Erbium--169 was compared with triamcinolone hexacetonide in the topical treatment of 32 patients suffering from rheumatoid arthritis. Erbium--169 was injected into 83 and triamcinolone hexacetonide into 54 proximal interphalangeal or metacarpophalangeal joints. Both treatments produced alleviation of joint pain and swelling and improvement of grip strength. At every check-up (1--18 months) the percentage of remissions was higher after triamcinolone hexacetonide injection than after erbium--169. The difference was significant at 1, 3, and 6 months.
Proof that Sn-protoporphyrin inhibits the enzymatic catabolism of heme in vivo. Suppression of 14CO generation from radiolabeled endogenous and exogenous heme sources.
Authors: S A Landaw, S Sassa, G S Drummond, A Kappas
Journal: The Journal of Experimental Medicine (1987)

Sn-protoporphyrin (SnPP) suppresses generation of 14CO from hepatic heme labeled with delta-aminolevulinic acid (5-[14C]ALA) or from infused [14C]hemin in rats. SnPP administered 1 h before administration of 5-[14C]ALA virtually abolished the peak output of 14CO occurring 2-3 h after injection of this heme precursor, and during the succeeding 12 h reduced 14CO excretion by approximately 61% compared with controls. When [14C]hemin was infused, SnPP diminished 14CO excretion by approximately 50%. These findings, derived from experiments using radiolabeled endogenous and exogenous heme sources, establish conclusively that the synthetic metalloporphyrin SnPP inhibits the oxidative degradation of heme in the intact animal.
Translating Cancer Genomics into Clinical Oncology
Authors: Sridhar Ramaswamy
Journal: New England Journal of Medicine (2004)

Clinical medicine is in the midst of a revolution that is being driven by an increasing understanding of the human genome and advances in molecular biotechnology. This revolution promises to transform clinical practice from population-based risk assessment and empirical treatment to a predictive, individualized model based on the molecular classification of disease and targeted therapy. The expectation is, of course, that personalized approaches to clinical care will increase the efficacy of treatment while decreasing its toxicity and cost.Nowhere is this transformation more apparent than in oncology. Cancer is a complex disease. Our current taxonomy of cancers, which is based . . .