tbuckley/cabot-search huggingface dataset:
PTH-096 Oral Ciclopsorin in Steroid Refractory, Acute, Severe Ulcerative Colitis
Authors: S Gaggar, N Thompson
Journal: Gut (2013)

<h3>Introduction</h3> Ciclosporin (CsA) has been shown to be effective in treatment of steroid refractory severe ulcerative colitis and reducing the need for colectomy<sup>1</sup>. Most published evidence concerns intravenous infusions; however oral microemulsion ciclosporin (Neoral®) is well absorbed, more convenient and potentially less toxic. We report our experience with oral ciclosporin for treatment of steroid refractory severe ulcerative colitis. <h3>Methods</h3> 30 consecutive patients receiving oral Ciclosporin for steroid refractory acute severe ulcerative colitis from October 2001 till July 2012 were retrieved from our clinical and pathology database. One patient received therapy twice. Hence, 31 episodes were analysed for this study. <h3>Results</h3> 19/31 patients were males. The median age at diagnosis and at the time of starting CsA was 39 years and 42 years respectively. 19 patients had pancolitis and 11 patients had left sided colitis. 4 patients were not on any treatment at the time of acute flare up. 28 patients were treated as inpatients. CsA was started after a median of 5 days after treatment with intravenous hydrocortisone in admitted patients (range 2–13 days). The mean CsA dose was 7.31 mg/kg on admission (range 5 to 8). The mean ciclosporin trough levels at 48–72hours and days 5–7 were 167ng/ml and 254ng/ml respectively. The mean length of treatment was 23.6 weeks (range 1–123). 50% had no side effects. One patient developed pyrexia of unknown origin necessitating stoppage of CsA. 26/31 (84%) had initial clinical response. 5/31 had colectomies during the same admission while 15/31 (48%) had colectomies within one year of starting ciclosporin treatment. 14/31 (46%) have had no surgery till date after a mean follow up of 46 months (range 2–131). 14/26 who had initial response to CsA were started on azathioprine. Eleven were thiopurine naïve and out of these, 8/11 (72%) are colectomy free till date. 12/26 were on thiopurines in the past. Only 4 of these 12 patients (33%) are colectomy free till date. <h3>Conclusion</h3> 84% of the cohort of patients having steroid refractory severe ulcerative colitis responded to CsA and 52% retained their colon after 1 year. Our experience confirms CsA to be a safe drug with few side effects and should be used as a bridging therapy to azathioprine. Patients who are azathioprine naïve prior to CsA appear to have lower colectomy rates. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Campbell S, Travis S, Jewell D. Ciclosporin use in acute ulcerative colitis: a long term experience. Eur J Gastroenterol Hepatol 2005 Jan; 17(1):79–84
In vivo comparison of electromagnetic and Doppler flowmeters: with special attention to the processing of the analogue Doppler flow signal
Authors: R. S. RENEMAN, H. F. CLARKE, N. SIMMONS, M. P. SPENCER
Journal: Cardiovascular Research (1973)

In acute experiments, instantaneous arterial flow tracings were obtained simultaneously with an electromagnetic (square-wave and pulsed field) and a non-directional Doppler flowmeter at rest, during reactive hyperaemia and during isoprenaline infusion. A wide band Doppler flow signal was processed with a zero-crossing meter preceded with and without a differentiator. The performance of both high and low threshold zero-crossing meters was also examined. The combination of a differentiator with a high threshold zero-crossing meter gave the best results. In this way, the Doppler flowmeter followed the electromagnetic flowmeter without loss of high frequency information. Since the differentiator weights the amplitude with respect to frequency, the low amplitude high frequency components, which normally are riding on the high amplitude low frequencies, can be counted in the zero-crossing meter. The peak velocity readings in the femoral artery, however, were significantly higher than those calculated from the electromagnetic flowmeter readings, both with the differentiator and the band-pass filter preceding the zero-crossing meter, necessitating in situ calibration when absolute flow values are required. Possible causes of this discrepancy are discussed.
Exposure to Juniperus Ashei (Mt. Cedar) and Virginia Live Oak Pollen in a Pollen Challenge Chamber Elicits Similar Symptomology When Compared to Natural Season
Authors: Daniel Ramirez, Cynthia Rather, Nathan Harper, Andrew Carrillo, Weijing He, Charles Andrews, Sunil Ahuja, Robert L. Jacobs
Journal: Journal of Allergy and Clinical Immunology (2013)
In vivo administration of vascular endothelial growth factor (VEGF) and its antagonist, soluble neuropilin-1, predicts a role of VEGF in the progression of acute myeloid leukemia in vivo
Authors: Gunter Schuch, Marcelle Machluf, Georg Bartsch, Masashi Nomi, Henri Richard, Anthony Atala, Shay Soker
Journal: Blood (2002)
Proarrhythmia — Taking the Bad with the Good
Authors: Leonard N. Horowitz
Journal: New England Journal of Medicine (1988)

The usefulness of antiarrhythmic drug therapy has long been appreciated. The elimination of symptoms produced by supraventricular and ventricular arrhythmias is the most obvious benefit. In addition, it is now known that when appropriately directed, such therapy can prolong life in patients with malignant ventricular arrhythmias.1 2 3 Although it is still uncertain, it is possible that suppression of other serious arrhythmias, such as complex ventricular ectopy, including unsustained ventricular tachycardia in patients with severe organic heart disease, may also have beneficial effects. This issue is currently being studied in the Cardiac Arrhythmia Suppression Trial, a multicenter study by the National Institutes . . .
Generation of leukotrienes by purified human lung mast cells.
Authors: D W MacGlashan, R P Schleimer, S P Peters, E S Schulman, G K Adams, H H Newball, L M Lichtenstein
Journal: Journal of Clinical Investigation (1982)

Although mediator release from mast cells and basophils plays a central role in the pathogenesis of human allergic disease, biochemical studies have been restricted to rat peritoneal mast cells and basophilic leukemia cells because they could be easily purified. We have used two new techniques of cell separation to purify human lung mast cells to 98% homogeneity. Lung cell suspensions were obtained by dispersion of chopped lung tissue with proteolytic enzymes. Mast cells were then purified from the suspensions by countercurrent centrifugal elutriation and affinity chromatography. The purified mast cells released both histamine and slow-reacting substance of anaphylaxis (SRS-A) (leukotriene C and D) during stimulation with goat anti-human IgE antibody. Moreover, these preparations were able to generate significant quantities of SRS-A (32 +/- 7 x 10(-17) LTD mole-equivalents/mast cell) at all stages of purification, indicating that a secondary cell is not necessary for the antigen-induced release of SRS.
Inhalation toxicology and carcinogenicity of 1,3-butadiene in B6C3F1 mice following 65 weeks of exposure.
Authors: R L Melnick, J E Huff, J H Roycroft, B J Chou, R A Miller
Journal: Environmental Health Perspectives (1990)

1,3-Butadiene, a large-production volume chemical used mainly in the manufacture of synthetic rubber, was found to induce multiple-organ carcinogenicity in male and female B6C3F1 mice at exposure concentrations (625 and 1250 ppm) equivalent to and below the OSHA standard of 1000 ppm. Since this study was terminated after 60 weeks of exposure because of reduced survival due to fatal tumors, and because dose-response relationships for 1,3-butadiene-induced neoplastic and nonneoplastic lesions were not clearly established, a second long-term inhalation study of 1,3-butadiene in B6C3F1 mice was conducted at lower exposure concentrations, ranging from 6.25 to 625 ppm. Both the histopathological findings from animals dying through week 65 and the results of evaluations of animals exposed for 40 and 65 weeks are presented in this report. Exposure to 1,3-butadiene caused a regenerative anemia at concentrations of 62.5 ppm and higher. Testicular atrophy was induced at 625 ppm, and ovarian atrophy was observed at 20 ppm and higher. During the first 50 weeks of the study, lymphocytic lymphoma was the major cause of death of mice exposed to 625 ppm 1,3-butadiene. Neoplasms of the heart, forestomach, lung, Harderian gland, mammary gland, ovary, and liver were frequently observed in 1,3-butadiene-exposed mice that died between week 40 and week 65 of the study. Studies in which exposure to 1,3-butadiene was stopped after limited periods were also included to assess the relationship between exposure levels and duration of exposures on the outcome of 1,3-butadiene-induced carcinogenicity. In these studies, lymphocytic lymphomas were induced in male mice exposed to 625 ppm 1,3-butadiene for only 13 weeks. The incidence of lymphocytic lymphoma in male mice exposed to 625 ppm 1,3-butadiene for 26 weeks was two times that in mice exposed to 625 ppm for 13 weeks. However, when the exposure concentration was reduced by half to 312 ppm and the exposure duration extended to 52 weeks, the incidence of lymphocytic lymphoma was reduced by 90%. Thus, the multiple of the exposure concentration times the exposure duration did not predict the incidence of lymphocytic lymphoma in mice. The early mortalities resulting from lymphocytic lymphomas in male mice exposed to 625 ppm 1,3-butadiene limited the expression of tumors at other sites. A clearer dose-response for 1,3-butadiene-induced neoplasia should be apparent from experiments in mice exposed to lower concentrations of this chemical for 2 years.
Disinfectant Action of Phenol and of Alcohol in T.A.B.C. Vaccine
Authors: J. C. Cruickshank, B. C. Hobbs, A. M. McFarlan, I. Maier
Journal: BMJ (1942)

The substitution by Felix (1941) of alcohol for phenol in T.A.B.C. vaccine in order to prevent destruction of the Vi antigen represents a considerable advance in the method of prophylactic inoculation against enteric fever.The alcohol, which was employed in a 22.5 % or 25 % concen- tration, was intended to fulfil the double purpose of preserving the activity of the Vi antigen and of guarding against infection by virtue of its antiseptic properties.Doubts, however, were soon raised as to its efficiency in this latter respect.Since Felix in his study of the bactericidal action of this substance worked with only one organism, Staph.aureus, and since he gave no protocols of any of his experiments, it was felt that the only satis- factory way of allaying these doubts was to carry out a series of observations in which the destructive effect of different strengths of alcohol on different organisms was compared with that of 0.5% phenol. TechniqueFour constituent laboratories of the Emergency Public Health Laboratory Service took part in these trials.Bottles containing 25 ml. of the following T.A.B.C. vaccines were distributed to each laboratory: (a) 0.5% phenol, Batch 18, Oct.. 1940, prepared by the Lister Institute; (b) 22.5% alcohol.Batch Al, Sept., 1940, prepared by the Lister Institute; (c) 25% alcohol, Batch AA4, May, 1940, prepared by Dr. Felix.The experiments were carried out during the summer and autumn of 1941.Observations were made on Staph.aureus, Bact.coli, Ps. pyocyanea, and, in three laboratories, on the spores of B. subtilis and Cl.sporogenes.With a few exceptions different strains of these organisms were used by different laboratories.The general plan of the experiments was as follows.The three species of non-sporing organisms were grown overnight on agar; the growth was washed off with
Alternative to neostigmine for megacolon.
Authors: J Neely
Journal: BMJ (1969)

BRirISH 557stopping it, but some months later developed identical chorea again, without having re- started the use of the preparation.When examined it was clear that she was in the early stages of pregnancy.Sydenham's chorea is uncommon in young adults these days, and when it does appear in otherwise healthy young women most careful inquiry should be made to determine if they have been taking one of the progestogenoestrogen preparations, for, as these may be prescribed for purposes other than contra- ceptive, the women may not themselves con- sider that they are on the pill.-Iam, etc.,
Von Ruck's Vaccine-Reply
Authors: R. S. Cummings
Journal: JAMA (1913)

[The preceding letter was shown to Dr. Cummings, whose reply follows:] In my article referred to above by Dr. von Ruck, I published exact details of my experiments, and the conclusions that I drew were that the experiments, as I made them, afforded no evidence that immunity was produced, but rather that there was increased susceptibility to infection by reason of the vaccination. I made no claim to having used the complement-fixation test as a criterion of immunity, and those who are interested must decide for themselves whether or not the test is an essential procedure in these immunity experiments. I did not feel—and the staff of the Barlow Sanitarium agreed with me—that the complement-fixation test offered sufficient promise to employ it, and we were not sufficiently impressed by Dr. von Ruck's laboratory tests to be induced to carry them out. In one of his letters to me Dr. von
SLC2A9 influences uric acid concentrations with pronounced sex-specific effects
Authors: Angela Döring, Christian Gieger, Divya Mehta, Henning Gohlke, Holger Prokisch, Stefan Coassin, Guido Fischer, Kathleen Henke, Norman Klopp, Florian Kronenberg, Bernhard Paulweber, Arne Pfeufer, Dieter Rosskopf, Henry Völzke, Thomas Illig, Thomas Meitinger, H-Erich Wichmann, Christa Meisinger
Journal: Nature Genetics (2008)
Influence of coronary artery disease and coronary revascularization status on outcomes in patients with acute heart failure syndromes: A report from OPTIMIZE‐HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure)*
Authors: Joseph S. Rossi, James D. Flaherty, Gregg C. Fonarow, Eduardo Nunez, Wendy Gattis Stough, William T. Abraham, Nancy M. Albert, Barry H. Greenberg, Christopher M. O'Connor, Clyde W. Yancy, James B. Young, Charles J. Davidson, Mihai Gheorghiade
Journal: European Journal of Heart Failure (2008)
Endotoxin-induced liver necrosis and intravascular coagulation in rats enhanced by portacaval collateral circulation.
Authors: H Liehr, M Grun, H Thiel, D Brunswig, U Rasenack
Journal: Gut (1975)

The effects of intravenously administered endotoxin on the hepatic and systemic circulation as well as on the coagulation system were evaluated in normal rats (n = 26), in rats with experimental portal hypertension (n = 15), and in rats with portacaval anastomosis (n = 22). Endotoxin (1-5 mg/kg) in the normal rat leads to a prompt increase of transaminase activity and to a hyperdynamic circulation with a consequent increase in the total hepatic blood flow. In a later phase (6 h postoperatively) the hepatic artery dilated with a consequent hepatic arterial hyperperfusion. The coagulation system was affected with signs of consumption coagulopathy. In the rats with portal hypertension and portacaval collaterals as well as in those with portacaval anastomosis, the endotoxin injection resulted in acute liver necrosis within 12 to 15 hours. The hepatic artery became overdilated with a cardiac output fraction of 25% (normal 5-5%). Blood extravasates and thrombi, rich in fibrin, were detected in the liver. It is suggested that this exaggeration of the endotoxin effect was due to an impaired clearance function of the reticuloendothelial system, probably as consequence of portacaval collateral circulation. It is concluded that endotoxins (1) damage the liver even in a normal organism; (2) are potent to induce acute liver necrosis, if the reticuloendothelial system is altered; (3) have to be taken into consideration as contribution to the pathogenesis of acute as well as chronic liver diseases.
Abstract 5138: Histone deacetylase 2 and N-Myc reduce p53 protein phosphorylation at serine 46 by repressing gene transcription of tumor protein 53-induced nuclear protein 1
Authors: Jeyran Shahbazi, Christopher J. Scarlett, Murray Norris, Bing Liu, Michelle Haber, Andrew E. Tee, Alice Carrier, Andrew V. Biankin, Wendy B. London, Glenn M. Marshall, Richard Lock, Tao Liu
Journal: Cancer Research (2014)

Abstract Myc oncoproteins and histone deacetylases (HDACs) exert oncogenic effects by modulating gene transcription. Paradoxically, N-Myc induces p53 gene expression. Tumor protein 53-induced nuclear protein 1 (TP53INP1) phosphorylates p53 protein at serine 46, leading to enhanced p53 activity, transcriptional activation of p53 target genes and programmed cell death. We aimed to identify the mechanism through which N-Myc overexpressing p53 wild-type neuroblastoma cells acquired resistance to apoptosis.Gene and protein expression was analysed by real-time RT-PCR and immunoblot. Cell survival/death was examined by flow cytometry study of Annexin V-staining. The prognostic value of TP53INP1 expression in tumor tissues was investigated in three independent cohorts of neuroblastoma patients. TP53INP1 was one of the genes most significantly repressed by HDAC2 and N-Myc according to Affymetrix microarray gene expression datasets. HDAC2 and N-Myc reduced TP53INP1 gene expression by direct binding to the TP53INP1 gene promoter, leading to transcriptional repression of TP53INP1, p53 protein de-phosphorylation at serine 46, neuroblastoma cell proliferation and survival. Moreover, low levels of TP53INP1 expression in human neuroblastoma tissues correlated with high levels of N-Myc expression and poor patient outcome, and the BET bromodomain inhibitors JQ1 and I-BET151 reduced N-Myc expression and reactivated TP53INP1 expression in neuroblastoma cells. These findings identify TP53INP1 repression as an important co-factor for N-Myc oncogenesis, and provide further evidence for the potential application of BET bromodomain inhibitors in the therapy of N-Myc-induced neuroblastoma. Citation Format: Jeyran Shahbazi, Christopher J. Scarlett, Murray Norris, Bing Liu, Michelle Haber, Andrew E. Tee, Alice Carrier, Andrew V. Biankin, Wendy B. London, Glenn M. Marshall, Richard Lock, Tao Liu. Histone deacetylase 2 and N-Myc reduce p53 protein phosphorylation at serine 46 by repressing gene transcription of tumor protein 53-induced nuclear protein 1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5138. doi:10.1158/1538-7445.AM2014-5138
Back to punishment in New South Wales
Authors: Thomas B Hugh
Journal: BMJ (2004)

N ew South Wales in Australia appears to be reverting to its origins as a penal colony, if the interim recommendations of the special commission of inquiry into Campbelltown and Camden Hospitals are any guide.

The hospitals, on the southwestern outskirts of Sydney, serve a population of 800 000 people. In November 2002 four nurses made 71 allegations to the then state health minister, Craig Knowles, about “unsafe” care of patients in the hospitals. The allegations were referred to the Health Care Complaints Commission and were investigated. The commission's report of December 2003 focused on the systemic problems underpinning many of the adverse events, particularly under-resourcing and under-staffing. The report's accounts of individual cases will be familiar to any doctor working in a modern hospital, describing clinical errors of judgment, fumbled handovers, delays in treatment, and poor communication.

> Nurses have been spat at 

The government was incensed that blame had been laid at its feet. The complaints commissioner was sacked, …
<i>DHRS7c</i>, a novel cardiomyocyte‐expressed gene that is down‐regulated by adrenergic stimulation and in heart failure
Authors: Bo Lu, Wardit Tigchelaar, Willem P.T. Ruifrok, Wiek H. van Gilst, Rudolf A. de Boer, Herman H.W. Silljé
Journal: European Journal of Heart Failure (2011)
Financing Health Care — Finding the Money Is Hard and Spending It Well Is Even Harder
Authors: Richard Kronick
Journal: New England Journal of Medicine (2005)

In this issue of the Journal, Mongan and Lee argue persuasively that physicians should lead the way in confronting the unpleasant truth that we cannot achieve universal health care coverage in the United States without tax increases.1 There is a second unpleasant truth that we must confront: if we are going to create a sustainable system of health care financing in which there is a balance between the costs and benefits of care, then the government must become more involved in influencing how the money is spent. And although the difficulties of figuring out desirable ways of raising money are . . .
Intravaginal Estrogen Creams and Endometrial Cancer
Authors: Ralph I. Horwitz
Journal: JAMA (1979)

In two case-control studies of estrogens and endometrial cancer, women were asked about previous use of intravaginal estrogen creams. In a set of cases and controls chosen by conventional procedures from a tumor registry, the odds ratio was 0.90. In an alternative set of cases and controls who had all received dilatation and curettage or hysterectomy, the odds ratio was 0.82. Despite the reported relationship between oral estrogens and endometrial cancer and although intravaginal estrogen creams are readily absorbed by the vaginal mucosa, we detect no causal association for their use. (<i>JAMA</i>241:1266-1267, 1979)
Bitter Medicine: Greed and Chaos in American Health Care
Authors: Bradford Kirkman-Liff
Journal: JAMA (1995)

<i>Bitter Medicine</i>is a report on the condition of American health care from an angry physician's perspective, written to those concerned with the entry of large business into health care delivery and financing. As the health care reform debate continues in a turbulent environment, this book provides useful insight into many of the issues and publics that have shaped medicine today. More important, it also outlines the goals that should be integral to any health care system that is finally adopted. It is a clinician's view of what makes the current system falter. As such, it is at times a diatribe against many recent innovations, but change should be examined critically. Much of Kassler's discussion focuses on the issue of money, where it is and how it affects medicine. She acknowledges that the chief problem in American health care is its costs, and that traditional medical ethics is challenged by