tbuckley/cabot-search huggingface dataset:
Myocardial energetics in patients with dilated cardiomyopathy. Influence of nitroprusside and enoximone.
Authors: G Hasenfuss, C Holubarsch, H W Heiss, T Meinertz, T Bonzel, U Wais, M Lehmann, H Just
Journal: Circulation (1989)

Cardiotonic agents influence myocardial energy consumption by vasodilation, which may reduce energy demand, and by inotropism, which may increase it. To distinguish between the two effects, myocardial oxygen consumption must be analyzed in relation to its hemodynamic determinants. The coupling of myocardial oxygen consumption with its determinants was investigated in 22 patients with idiopathic dilated cardiomyopathy (NYHA Class II and III). Predicted myocardial oxygen consumption by the pressure-work index, the Bretschneider index, and the pressure-volume area correlated moderately with measured myocardial oxygen consumption (r = 0.57, p less than 0.001; r = 0.52, p less than 0.005; and r = 0.63, p less than 0.001). Multiple regression analysis, including left ventricular peak systolic wall stress, systolic stress-time integral, pressure-volume work, maximum rate of left ventricular pressure rise, and mean velocity of circumferential fiber shortening indicated that systolic stress-time integral is the major determinant of myocardial oxygen consumption (r = 0.75, p less than 0.001) in these patients. Enoximone, a phosphodiesterase inhibitor, has an inotropic and a vasodilating effect. To investigate the inotropic portion of the energy cost of this phosphodiesterase inhibitor, the influence of enoximone on myocardial oxygen consumption and systolic stress-time integral was compared with the effects of nitroprusside, which is a vasodilator only. Nitroprusside (10 patients) and enoximone (12 patients) reduced left ventricular systolic stress-time integral from 109 +/- 22 to 71 +/- 21 (p less than 0.005) and from 104 +/- 23 to 42 +/- 10 (p less than 0.001) 10(3) dynes.sec/cm2, respectively. Myocardial oxygen consumption decreased from 159 +/- 44 to 112 +/- 23 (p less than 0.005) and from 134 +/- 28 to 109 +/- 21 (p less than 0.001) microliters/beat/100 g, respectively. In both groups, there was a significant correlation between the decrease in myocardial oxygen consumption and the decrease in systolic stress-time integral. The slopes of the respective linear regression lines were significantly different (1.27 for nitroprusside and 0.51 nl.cm2/100 g.dynes.sec for enoximone, p less than 0.05), indicating a smaller decrease of myocardial oxygen consumption for a given decrease of stress-time integral with enoximone. Applying the pressure-work index or the pressure-volume area instead of systolic stress-time integral yielded comparable results. Thus, vasodilation reduces myocardial oxygen consumption in proportion to the reduction of stress-time integral. With enoximone, the energy-saving effect of vasodilation is counteracted in part by the increased energy d
Cardiac Sarcotubular Vesicles
Authors: MARY E. CARSTEN
Journal: Circulation Research (1967)

The transport of calcium through the membranes of the sarcoplasmic reticulum plays an important role in the relaxation-contraction cycle of the heart. To study and characterize this system, fragmented sarcotubular vesicles from dog hearts were prepared by ultracentrifugation. The fraction between 15,000 and 40,000 g was partially purified by gradient centrifugation. Calcium accumulation by the vesicles in the presence of ATP, Mg, 45 Ca, and oxalate was studied. The rate of calcium uptake increased with the ATP concentration and was not affected by changes in K or Na concentration nor by substitution of isosmotic amounts of sucrose for 75% of the Na ions. Splitting of ATP was increased upon substitution of sucrose. In aged preparations of vesicles, ouabain or acetylstrophanthidin decreased the rate of their calcium accumulation and partially reversed the inhibition of myofibrillar ATPase by the vesicles. It is suggested that the partial inhibition of calcium uptake increases the concentraton of free calcium, and thus makes more calcium available for contraction of the myofibril.
Treatment of severe atopic dermatitis in childhood with cyclosporin
Authors: I. ZAKI, R. EMERSON, B.R. ALLEN
Journal: British Journal of Dermatology (1996)

Cyclosporin has been shown to be effective in the treatment of adult atopic dermatitis, but there are no clinical trials evaluating its use in childhood. Atopic dermatitis is more common in children and the severe form can be associated with considerable morbidity. We report on 18 children with severe refractory atopic dermatitis who have been treated with cyclosporin on an open basis. The drug was given at an initial daily dose of 5 or 6 mg/kg and in some patients the dose was reduced according to response. Sixteen patients showed a good or excellent response to treatment, one a moderate response and one patient failed to improve. The treatment was well tolerated and there were no significant changes in serum creatinine or blood pressure. Long remission after withdrawal of treatment was seen in some patients, although most relapsed within a few weeks. We suggest that cyclosporin is an effective and safe short-term treatment for severe atopic dermatitis in childhood.
Measurement of thrombopoiesis in rabbits using 75selenomethionine
Authors: Bruce L. Evatt, Jack Levin
Journal: Journal of Clinical Investigation (1969)

Incorporation of (75)selenomethionine ((75)SeM) has been used to study platelet production in rabbits. Radioactivity of platelets was low after the intravenous administration of (75)SeM and rose to a maximum approximately 3 days after administration. Platelet radioactivity was independent of concurrent plasma levels. The life span of rabbit platelets, as estimated with this technique, was 4-5 days. In vivo reutilization of (75)SeM previously incorporated into plasma proteins was not detected. In vitro incorporation of (75)SeM by platelets in platelet-rich plasma was not demonstrated. Acute hemorrhage 24 hr before administration of (75)SeM increased the incorporation of (75)SeM into platelets. Transfusion-induced thrombocytosis reduced the incorporation of (75)SeM to approximately 30% of that observed in control animals. Suppression of bone marrow function with nitrogen mustard resulted in decreased numbers of platelets in the circulation, and a decrease in incorporation of (75)SeM. Delayed appearance of (75)SeM was observed in circulating platelets during recovery from marrow suppression. Injection of 75-225 ml of plasma from thrombocytopenic donors into normal rabbits increased incorporation of (75)SeM into platelets while normal plasma did not have this effect. The rate of appearance of (75)SeM in circulating platelets appears to provide a sensitive and specific method for the study of production of platelets by megakaryocytes. The data suggest more rapid entry of platelets into the circulation, and a sustained increase in incorporation of (75)SeM into platelet protein after stimulation of platelet production. The results are consistent with the concept of a humoral agent (thrombopoietin) that acts on megakaryocytes to regulate platelet production.
Occupational asthma due to liquorice roots
Authors: A. Cartier, J.‐L. Malo, M. Labrecque
Journal: Allergy (2002)

We describe the case of an herbalist who developed occupational asthma due to liquorice roots as confirmed by specific inhalation challenges. Many high-molecular-weight agents have been reported as causes of occupational asthma (OA) (1) (asthmanet.com, asthme.csst.qc.ca) A 33-year-old woman started to work as an herbalist 13 years ago. In her workplace, she was exposed to several natural products. She started suffering from asthma 8–9 years before being referred. She reported that her asthma symptoms were worse at work and improved on weekends and during a maternity leave. She also had rhinoconjunctivitis symptoms at work. She mentioned that several products brought on asthmatic symptoms when she handled them in powder form at work, including liquorice root. Her FEV1 varied from 1.5 to 2.2 L (pred = 3.2 l) and the concentration of methacholine causing a 20% fall in FEV1 (PC20 values), from 0.5 to 2.0 mg/ml (slight to moderate airway hyperresponsiveness (2) when she was assessed while at work. Peak expiratory flows showed greater fluctuations in some instances during periods at work. Skin-prick tests with a liquorice extract showed an 8 mm immediate weal. Skin-prick tests were also positive (= 3 mm weal) to common inhalants (pollens, mites) and to other products handled at her workplace, including echinacea, nettle, hop and thistle. Specific inhalation challenges carried out by exposing the subject with a dry aerosol generator (3,4) to liquorice root powder at concentrations lower than 10 mg/m3 and for progressively increasing periods up to a total of 90 min induced a 25% immediate fall in FEV1 without significant late reaction (Fig. 1). PC20 did not change significantly in the afternoon of the challenge day to liquorice roots (PC20 at 1.3 mg/ml by comparison with a value of 2.0 mg/ml before exposure). The patient was removed from her workplace with improvement in her symptoms. Values of Fev1 as a function of time after exposure to lactose and liquorice roots. This case report shows that liquorice roots can cause OA through an apparently IgE-mediated mechanism as seen by immediate skin reactivity reaction to the diluted powder of liquorice root. Thesubject also presented symptoms of occupational rhinoconjunctivitis, which is commonly encountered in the case of high-molecular-weight agents (5). Herbalists are typically at risk of developing IgE-mediated allergic conditions (6), as they are exposed to several seeds, herbs and derivatives of vegetal products. Other vegetal roots can cause OA. Vandenplas and co-workers indeed described an interesting case of OA due to sarsaparilla root dust (7). The authors thank Lori Schubert for reviewing the manuscript.
Incapacity, work, and benefits
Authors: Miles J Stanger
Journal: BMJ (2008)

An anti-human monoclonal antibody (RFB-1) has been produced that reacts with a group of hemopoietic precursor cells in human bone marrow. These include terminal deoxynucleotidyl transferase-positive (TdT+) cells and myeloid colony-forming unit cells, functionally identifiable progenitor cells of the granulocytic-monocytic series. The expression of RFB-1 antigen on myeloid cells decreases as the cells become more mature; myeloblasts are weakly RFB-1+ but most promyelocytes are RFB-1-. RFB-1 also reacts with TdT+ thymic blast cells and cortical thymocytes but is unreactive with TdT- medullary thymocytes, although the majority of peripheral T cells are weakly RFB-1+. RFB-1 is the first anti-precursor cell reagent that labels human TdT+ cells in both the thymus and bone marrow as well as hemopoietic precursor cells but is unreactive with pre-B blasts and B lymphocytes.
The effect of compression on venous stasis
Authors: P.M. GAYLARDE, I. SARKANY, H.J. DODD
Journal: British Journal of Dermatology (1993)

Skin blood flow in the lower leg is increased by external compression in standing subjects. This prevents the hypoxia induced by standing. The maximum increase in oxygen tension is seen when the external pressure is 40-50 mmHg. Pressures in the range of those produced by lightweight elastic stockings were found to be ineffective. Our results uphold the commonly held clinical opinion that only compression bandages or strong stockings are effective in the treatment of venous ulcers. External compression when the subject is recumbent causes skin oxygen tension to fall. Uniform external pressure exceeding 10 mmHg should therefore be avoided in the prophylactic treatment of post-operative deep-vein thrombosis. This observation suggests that when the patient is confined to bed, only lightweight stockings are safe in the prophylaxis of post-operative deep-vein thrombosis.
Predicting Clinical Outcome in Patients Diagnosed with Synchronous Ovarian and Endometrial Cancer
Authors: Susan J. Ramus, Karim Elmasry, Zhiyuan Luo, Alex Gammerman, Karen Lu, Ayse Ayhan, Naveena Singh, W. Glenn McCluggage, Ian J. Jacobs, John C. Whittaker, Simon A. Gayther
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Patients with synchronous ovarian and endometrial cancers may represent cases of a single primary tumor with metastasis (SPM) or dual primary tumors (DP). The diagnosis given will influence the patient's treatment and prognosis. Currently, a diagnosis of SPM or DP is made using histologic criteria, which are frequently unable to make a definitive diagnosis. Experimental Design: In this study, we used genetic profiling to make a genetic diagnosis of SPM or DP in 90 patients with synchronous ovarian/endometrial cancers. We compared genetic diagnoses in these patients with the original histologic diagnoses and evaluated the clinical outcome in this series of patients based on their diagnoses. Results: Combining genetic and histologic approaches, we were able make a diagnosis in 88 of 90 cases, whereas histology alone was able to make a diagnosis in only 64 cases. Patients diagnosed with SPM had a significantly worse survival than patients with DP (P = 0.002). Patients in which both tumors were of endometrioid histology survived longer than patients of other histologic subtypes (P = 0.025), and patients diagnosed with SPM had a worse survival if the mode of spread was from ovary to endometrium rather than from endometrium to ovary (P = 0.019). Conclusions: Genetic analysis may represent a powerful tool for use in clinical practice for distinguishing between SPM and DP in patients with synchronous ovarian/endometrial cancer and predicting disease outcome. The data also suggest a hitherto uncharacterized level of heterogeneity in these cases, which, if accurately defined, could lead to improved treatment and survival.
Coprescription of Tamoxifen and Medications That Inhibit CYP2D6
Authors: Kostandinos Sideras, James N. Ingle, Matthew M. Ames, Charles L. Loprinzi, David P. Mrazek, John L. Black, Richard M. Weinshilboum, John R. Hawse, Thomas C. Spelsberg, Matthew P. Goetz
Journal: Journal of Clinical Oncology (2010)

Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6 is the key enzyme responsible for the generation of the potent tamoxifen metabolite, endoxifen. Multiple studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-treated women; the majority of studies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence. As a result, practitioners must be aware that some of the most commonly prescribed medications coadministered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentrations and potentially increasing the risk of breast cancer recurrence. After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen.
Primary malignant melanoma of the oesophagus with a left atrial metastasis.
Authors: M Chello, A R Marchese, A Panza, P Mastroroberto, F Di Lello
Journal: Thorax (1993)

A 75 year old man with an eight month history of dysphagia and weight loss underwent pericardiocentesis for a massive pericardial effusion. The echocardiogram showed a mass in the left atrium, and computed tomography also showed distal oesophageal narrowing, which was found to be due to a malignant melanoma. The left atrial mass, investigated by immunoscintigraphy with technetium-99m labelled monoclonal antibody, was diagnosed as metastatic melanoma. This represents a rare case of primary oesophageal melanoma with left atrial metastasis.
Inflammation of Atrium After Cardiac Surgery Is Associated With Inhomogeneity of Atrial Conduction and Atrial Fibrillation
Authors: Yosuke Ishii, Richard B. Schuessler, Sydney L. Gaynor, Kiyomi Yamada, Annabel S. Fu, John P. Boineau, Ralph J. Damiano
Journal: Circulation (2005)

Background— Atrial fibrillation (AF) is common after cardiac surgery. Abnormal conduction is an important substrate for AF. We hypothesized that atrial inflammation alters atrial conduction properties. Methods and Results— Normal mongrel canines (n=24) were divided into 4 groups consisting of anesthesia alone (control group); pericardiotomy (pericardiotomy group); lateral right atriotomy (atriotomy group); and lateral right atriotomy with antiinflammatory therapy (methylprednisolone 2 mg/kg per day) (antiinflammatory group). Right atrial activation was examined 3 days after surgery. Inhomogeneity of conduction was quantified by the variation of maximum local activation phase difference. To initiate AF, burst pacing was performed. Myeloperoxidase activity and neutrophil cell infiltration in the atrial myocardium were measured to quantify the degree of inflammation. The inhomogeneity of atrial conduction of the atriotomy and pericardiotomy groups was higher than that of the control group (2.02±0.10, 1.51±0.03 versus 0.96±0.08, respectively; P &lt;0.005). Antiinflammatory therapy decreased the inhomogeneity of atrial conduction after atriotomy (1.16±0.10; P &lt;0.001). AF duration was longer in the atriotomy and pericardiotomy groups than in the control and antiinflammatory groups ( P =0.012). There also were significant differences in myeloperoxidase activity between the atriotomy and pericardiotomy groups and the control group (0.72±0.09, 0.41±0.08 versus 0.18±0.03 ΔOD/min per milligram protein, respectively; P &lt;0.001). Myeloperoxidase activity of the antiinflammatory group was lower than that of the atriotomy group (0.17±0.02; P &lt;0.001). Inhomogeneity of conduction correlated with myeloperoxidase activity ( r =0.851, P &lt;0.001). Conclusions— The degree of atrial inflammation was associated with a proportional increase in the inhomogeneity of atrial conduction and AF duration. This may be a factor in the pathogenesis of early postoperative AF. Antiinflammatory therapy has the potential to decrease the incidence of AF after cardiac surgery.
Cambodia's AIDS strategy could fail without sustainable financing
Authors: P. Moszynski
Journal: BMJ (2010)

Despite Cambodia’s success in driving down numbers of HIV infections, a new report on the future of the disease in the country argues that further success is not guaranteed and that the government needs to focus on prevention and assume more of the financing of its AIDS programme.

Written by Cambodian experts working with the Results for Development Institute, a non-profit organisation in Washington, DC, that aims to help accelerate social and economic progress in low and middle income countries, the report finds that in a best case scenario Cambodia could reduce the incidence of HIV to 1000 people a year in 2031—down from an estimated 2100 infections in 2009 and …
1245 THE EFFECT OF SEVERE RENAL IMPAIRMENT ON THE PHARMACOKINETICS OF THE INVESTIGATIONAL HCV PROTEASE INHIBITOR TELAPREVIR
Authors: R. van Heeswijk, A. Vandevoorde, G. Boogaerts, E. De Paepe, R. van Solingen-Ristea, V. Garg, M. Beumont
Journal: Journal of Hepatology (2011)
Single cell DNA measurements in benign cutaneous lymphoid infiltrates and in positive patch tests
Authors: ELISABETH RALFKIAER, G.L. WANTZIN, J.K. LARSEN, I.J. CHRISTENSEN, K. THOMSEN
Journal: British Journal of Dermatology (1985)

Cellular DNA in skin biopsies from eighteen patients with positive patch tests and eleven patients with benign lymphocytic skin infiltates (cutaneous lymphocytoma, lymphoplasia or Jessner's lymphotic infiltrate) was estimated by flow cytometry of propidium iodide‐stained dermal cells. Specimens from three patients with patch tests and one with cutaneous lymphocytoma had DNA histograms similar to those of normal blood mononuclear cells. The remaining patients demonstrated DNA histogram abnormalities in the form of hyperdiploid peaks in forty‐two of forty‐five specimens. The estimated proportion of cells in the S‐phase was similar in patch tests (median:9.2%) and in benign lymphocytic skin infiltrates (median: 9.6%). The median number of cells in the G2/M‐phase was 3.1% in both groups of disorders. These data indicate DNA content heterogeneity of the dermal cells in benign lymphocytic skin infiltrates. This may be attributed to DNA replication and/or chromatin dispersion during cellular activation and proliferation. The data also emphasize that hyperdiploid peaks are not necessarily indicative of the presence of separate cell clones.
Abstract A28: Targeting PCL3/PHF19 as an alternative therapeutic strategy to EZH2 inhibition in PRC2-deregulated cancers
Authors: Gerard L. Brien, Emilia Jerman, Matthew Campbell, Bracken P. Adrian
Journal: Cancer Research (2013)

Abstract The Polycomb Repressive Complex 2 (PRC2) is emerging as an attractive therapeutic target for the treatment of cancer. Several functional protein domains that are amenable to small-molecule inhibition exist within the complex and the recent development of chemical inhibitors of the EZH1/2 SET domain now offers a means to therapeutically target the complex. Here we explore the potential of targeting the sub-stoichiometric PRC2 component, PCL3/PHF19, as an alternative to EZH1/2 inhibition. We show, both in normal fibroblasts and in SNF5 deficient malignant rhabdoid sarcoma cells, that targeted depletion of PCL3/PHF19 leads to proliferative defects, owing, at least in part, to a loss of Polycomb binding at and de-repression of the tumour suppressor p16INK4A. Significantly, we show that ectopic expression of PCL3/PHF19 leads to p16INK4A repression and a bypass of cellular senescence. This correlates with increased recruitment of EZH2, accumulation of H3K27me3 and PRC1 components on the INK4A promoter, suggesting a potential oncogenic role for PCL3/PHF19. Consistent with this, PCL3/PHF19 is over-expressed in many cancers. Previously we demonstrated that the TUDOR domain of PCL3/PHF19 is required for the ability of the protein to read epigenetic modifications and facilitate the recruitment of EZH2 to chromatin. Taken together with the data presented here, we propose that the TUDOR domain of PCL3/PHF19 represents a viable alternative functional domain within the PRC2 complex for small-molecule inhibition. Citation Format: Gerard L. Brien, Emilia Jerman, Matthew Campbell, Bracken P. Adrian. Targeting PCL3/PHF19 as an alternative therapeutic strategy to EZH2 inhibition in PRC2-deregulated cancers. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A28.
Success and complication parameters for laparoscopic surgery: a benchmark for natural orifice transluminal endoscopic surgery
Authors: C. Gutt, B. Müller-Stich, M. Reiter
Journal: Endoscopy (2009)

Background: Natural orifice transluminal endoscopic surgery (NOTES) currently represents an issue of particular interest among surgeons and gastroenterologists. The principle of NOTES is the reduction of the operative trauma by using natural orifices of the human body to access the abdominal cavity. Regarding the tendency to further minimization of the surgical trauma, NOTES may be considered as a logical step in the evolution of minimally invasive surgery. Pioneers of this technique regard NOTES as the successor to laparoscopic surgery in enabling surgeons and gastroenterologists to conduct scarless surgery. This might not only lead to better cosmetic results but also enhance the prospect of decreases in wound infections and incisional hernias, as well as reducing operative stress, postoperative immobility, and pain.