tbuckley/cabot-search huggingface dataset:
Reduced Plasma Pyrophosphate Levels in Hemodialysis Patients
Authors: Koba A. Lomashvili, Wassim Khawandi, W. Charles O’Neill
Journal: Journal of the American Society of Nephrology (2005)

Pyrophosphate (PPi) is a known inhibitor of hydroxyapatite formation and has been shown to inhibit medial vascular calcification in vitamin D-toxic rats. It was demonstrated recently that endogenous production of PPi prevents calcification of rat aorta that are cultured in high concentrations of calcium and phosphate. For determining whether PPi metabolism is altered in hemodialysis patients, plasma levels and dialytic clearance of PPi were measured in stable hemodialysis patients. Predialysis plasma [PPi] was 2.26 +/- 0.19 microM in 38 clinically stable hemodialysis patients compared with 3.26 +/- 0.17 in 36 normal subjects (P < 0.01). Approximately 30% of plasma PPi was protein bound, and this was not altered in dialysis patients. There was a weak inverse correlation with age in normal individuals but not in dialysis patients. Plasma [PPi] in dialysis patients was correlated with plasma [PO4(3-)] (r = 0.56) but not with [Ca2+], parathyroid hormone, or the dose of dialysis, and levels did not vary between interdialytic periods of 2 and 3 d. Plasma [PPi] decreased 32 +/- 5% after standard hemodialysis in 17 patients. In vitro clearance of PPi by a 2.1-m2 cellulose acetate dialyzer was 36%, and the mean PPi removal in five patients was 43 +/- 5 micromol, consistent with a similar in vivo clearance. Cleared PPi was greater than the plasma pool but less than the estimated extracellular fluid pool. Erythrocyte PPi content decreased 24 +/- 4%, indicating that intracellular PPi is removed as well. It is concluded that plasma [PPi] is reduced in hemodialysis patients and that PPi is cleared by dialysis. Plasma levels in some patients were below those that have previously been shown to prevent calcification of vessels in culture, suggesting that altered PPi metabolism could contribute to vascular calcification in hemodialysis patients.
Fusion Gene–Negative Alveolar Rhabdomyosarcoma Is Clinically and Molecularly Indistinguishable From Embryonal Rhabdomyosarcoma
Authors: Daniel Williamson, Edoardo Missiaglia, Aurélien de Reyniès, Gaëlle Pierron, Benedicte Thuille, Gilles Palenzuela, Khin Thway, Daniel Orbach, Marick Laé, Paul Fréneaux, Kathy Pritchard-Jones, Odile Oberlin, Janet Shipley, Olivier Delattre
Journal: Journal of Clinical Oncology (2010)

To determine whether the clinical and molecular biologic characteristics of the alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) subtypes have relevance independent of the presence or absence of the PAX/FOXO1 fusion gene.The fusion gene status of 210 histopathologically reviewed, clinically annotated rhabdomyosarcoma samples was determined by reverse transcriptase polymerase chain reaction. Kaplan-Meier analysis was used to assess event-free survival and overall survival in fusion gene-negative ARMS (ARMSn; n = 39), fusion gene-positive ARMS (ARMSp; n = 94), and ERMS (n = 77). A total of 101 RMS samples were also profiled for whole-genome expression, and 128 were profiled for genomic copy number imbalances. Profiling data were analyzed by supervised and unsupervised methods to compare features related to histopathology and fusion gene status. Results were also projected by meta-analysis techniques across three separate publically available data sets.Overall and event-free survival, frequency of metastases, and distribution of site at initial presentation were not significantly different between ARMSn and ERMS. Consistent with this, analysis of gene expression signatures could not reproducibly distinguish ARMSn from ERMS whereas fusion gene-positive cases were distinct. ARMSn and ERMS frequently show whole-chromosome copy number changes, notably gain of chromosome 8 with associated high levels of expression of genes from this chromosome.The clinical behavior and molecular characteristics of alveolar cases without a fusion gene are indistinguishable from embryonal cases and significantly different from fusion-positive alveolar cases. This implies that fusion gene status irrespective of histology is a critical factor in risk stratification of RMS.
Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension
Authors: Ronald J Raymond, Alan L Hinderliter, Park W Willis, David Ralph, Edgar J Caldwell, William Williams, Neil A Ettinger, Nicholas S Hill, Warren R Summer, Bennett de Boisblanc, Todd Schwartz, Gary Koch, Linda M Clayton, Maria M Jöbsis, James W Crow, Walker Long
Journal: Journal of the American College of Cardiology (2002)
Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa
Authors: T Ishii, J Murakami, K Notohara, H M Cullings, H Sasamoto, T Kambara, Y Shirakawa, Y Naomoto, M Ouchida, K Shimizu, N Tanaka, J R Jass, N Matsubara
Journal: Gut (2006)

<b>Background:</b> Oesophageal squamous cell carcinoma (OSCC) often arises from preceding dysplastic lesions in the oesophageal epithelium. However, the molecular changes occurring in premalignant lesions are not well understood. An epigenetic change is an example of OSCC that may occur within the epithelium. <b>Aim:</b> To investigate the methylation status of multiple promoters in cancer-derived DNA, as well as in the background epithelium of OSCC, including dysplastic lesions and non-neoplastic mucosa. The normal epithelium from patients without cancer was also examined. The findings were correlated with the mutational status of <i>p53</i>. <b>Patients and methods:</b> 56 patients with advanced OSCC, 21 patients with intraepithelial neoplasia (IEN), 56 patients with a background of non-neoplastic epithelium, adjacent to the OSCC, and 42 normal control epithelia from healthy volunteers were studied. The promoter methylation status of <i>SFRP1, SFRP2, DCC, APC, p16<sup>INK4a</sup>, p14<sup>ARF</sup>, MINT1, MINT2, MINT31, CACNA1G, COX2, DAPK, hMLH1</i> and <i>MGMT</i> was examined by methylation-specific single polymerase chain reaction or combined bisulphite restriction analysis. The mutation of p53 by direct sequencing was assessed. <b>Results:</b> DNA methylation was observed in OSCC and in its background epithelium. The frequency of CpG island methylation increased from a baseline level in the background non-neoplastic epithelium, through IEN, to advanced OSCC. However, mutations in <i>p53</i> were almost exclusively observed in IEN and OSCC. More extensive DNA methylation was seen in the neoplastic lesions (OSCC or IEN) having a <i>p53</i> mutation than in those with wild-type <i>p53</i>. <b>Conclusion:</b> DNA methylation is present at low levels in the non-neoplastic oesophageal epithelium and appears to contribute to the progression of the dysplasia–carcinoma sequence in OSCC carcinogenesis.
Role of hepatitis C virus in dual and triple hepatitis virus infection*1
Authors: Y LIAW
Journal: Hepatology (1995)

Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) share same transmission routes, thus dual or triple infection may occur and even persist in the same patients. A significant amount of literature has accumulated since the advent of HCV assays. It is pertinent to review and evaluate the clinical and virological significance of HCV in multiple hepatotropic viral infection. The reported series on seroprevalence of HCV indicate that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide. Of the patients with dual or triple infection involving HCV, those having coreplication of viruses tend to have severe and progressive liver disease that is resistant to interferon therapy, in contrast with patients having a single virus infection. Paradoxically, dual or triple hepatitis virus infections are associated with viral interference. In particular, HCV exerts a suppressive effect on HBV and HDV and may enhance seroclearance of HBV antigens or even usurp the role of preexisting virus as the agent for continuing hepatitis. Although HBV and HDV may also suppress HCV, it appears to be less effective. These findings clearly suggest the necessity of monitoring patients with HBV or HDV infections. In view of complex dynamism of viral interaction in multiple hepatotropic virus infection, the importance of HCV assay in the clinical studies can not be overemphasized. The basic mechanisms that regulate the viral interactions, in particular the impact of HCV in dual or triple virus infections, remain to be investigated.
Randomized Clinical Trial of Long-Acting Somatostatin for Autosomal Dominant Polycystic Kidney and Liver Disease
Authors: Marie C. Hogan, Tetyana V. Masyuk, Linda J. Page, Vickie J. Kubly, Eric J. Bergstralh, Xujian Li, Bohyun Kim, Bernard F. King, James Glockner, David R. Holmes, Sandro Rossetti, Peter C. Harris, Nicholas F. LaRusso, Vicente E. Torres
Journal: Journal of the American Society of Nephrology (2010)

There are no proven, effective therapies for polycystic kidney disease (PKD) or polycystic liver disease (PLD). We enrolled 42 patients with severe PLD resulting from autosomal dominant PKD (ADPKD) or autosomal dominant PLD (ADPLD) in a randomized, double-blind, placebo-controlled trial of octreotide, a long-acting somatostatin analogue. We randomly assigned 42 patients in a 2:1 ratio to octreotide LAR depot (up to 40 mg every 28+/-5 days) or placebo for 1 year. The primary end point was percent change in liver volume from baseline to 1 year, measured by MRI. Secondary end points were changes in total kidney volume, GFR, quality of life, safety, vital signs, and clinical laboratory tests. Thirty-four patients had ADPKD, and eight had ADPLD. Liver volume decreased by 4.95%+/-6.77% in the octreotide group but remained practically unchanged (+0.92%+/-8.33%) in the placebo group (P=0.048). Among patients with ADPKD, total kidney volume remained practically unchanged (+0.25%+/-7.53%) in the octreotide group but increased by 8.61%+/-10.07% in the placebo group (P=0.045). Changes in GFR were similar in both groups. Octreotide was well tolerated; treated individuals reported an improved perception of bodily pain and physical activity. In summary, octreotide slowed the progressive increase in liver volume and total kidney volume, improved health perception among patients with PLD, and had an acceptable side effect profile.
The regulation of T cell homeostasis and autoimmunity by T cell–derived LIGHT
Authors: Jing Wang, James C. Lo, Amy Foster, Ping Yu, Helen M. Chen, Yang Wang, Koji Tamada, Lieping Chen, Yang-Xin Fu
Journal: Journal of Clinical Investigation (2001)

Costimulatory molecules on antigen-presenting cells (APCs) play an important role in T cell activation and expansion. However, little is known about the surface molecules involved in direct T-T cell interaction required for their activation and expansion. LIGHT, a newly discovered TNF superfamily member (TNFSF14), is expressed on activated T cells and immature dendritic cells. Here we demonstrate that blockade of LIGHT activity can reduce anti-CD3–mediated proliferation of purified T cells, suggesting that T cell–T cell interaction is essential for this proliferation. To test the in vivo activity of T cell–derived LIGHT in immune homeostasis and function, transgenic (Tg) mice expressing LIGHT in the T cell lineage were generated. LIGHT Tg mice have a significantly enlarged T cell compartment and a hyperactivated peripheral T cell population. LIGHT Tg mice spontaneously develop severe autoimmune disease manifested by splenomegaly, lymphadenopathy, glomerulonephritis, elevated autoantibodies, and severe infiltration of various peripheral tissues. Furthermore, the blockade of LIGHT activity ameliorates the severity of T cell–mediated diseases. Collectively, these findings establish a crucial role for this T cell–derived costimulatory ligand in T cell activation and expansion; moreover, the dysregulation of T cell–derived LIGHT leads to altered T cell homeostasis and autoimmune disease.
Multiple Operations on a Single Patient
Authors: W. R. Williams
Journal: BMJ (1899)

Providing doctors with information about risks and benefits of treatment options encountered in general practice is likely to help them communicate with patients.Tools for communicating risks should include information on both absolute and relative risk.Graphical presentation of information is one way of achieving this and has the potential to improve the efficiency of the primary care consultation.We are grateful for the commitment of Pat Oliver, Iris McKenzie, and Allan Thomas, who were the simulated patients; for the secretarial work of Claire Darmanin and Diane Thomas in transcribing tapes;
P4 The use of sildenafil to treat pulmonary hypertension associated with sarcoidosis
Authors: G. J. Keir, A. U. Wells, S. J. Wort
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Pulmonary hypertension (PH) is increasingly recognised as a major contributor to poorer outcomes in pulmonary sarcoidosis. Current treatment guidelines for sarcoidosis associated pulmonary hypertension (SAPH) recommend the optimisation of underlying lung disease and use of oxygen when hypoxaemia is present,1 however there is insufficient evidence to recommend advanced therapies. Limited data suggest a benefit following treatment with sildenafil in SAPH, although no randomised controlled treatment trials have been reported. We report our experience of patients with SAPH treated with sildenafil. <h3>Methods</h3> We reviewed 22 patients (mean age 56±12 years; 10 men) with SAPH (mean pulmonary artery pressure 46±9 mm Hg) who received treatment with sildenafil. Haemodynamic measurements were evaluated by right heart catheterisation in all patients. Serial measurements of brain natriuretic peptide (BNP), pulmonary function testing and functional status were collected. <h3>Results</h3> The mean duration of follow-up after the commencement of sildenafil was 21±14 months. Six patients died during follow-up, and four patients required the addition of an endothelin receptor antagonist due to worsening pulmonary hypertension. Patients were dichotomised into responders (those maintained on sildenafil monotherapy; n=12) or non-responders (those who died or required and escalation of PH therapy during follow-up; n=10). Compared to responders, non-responders had a significantly lower % predicted DLco (20% vs 34%; p=0.03) and % predicted Kco (46% vs 62%; p=0.05) at commencement of sildenafil (Abstract P4 table 1). Within 6 months of commencement of sildenafil, non-responders had a 21% increase in median BNP levels, while responders had a 51% reduction in BNP levels. Sildenafil was ceased in one patient after the development of ocular side-effects attributed to the drug. <h3>Conclusions</h3> Our observations suggest that sildenafil is safe and well tolerated in SAPH. At commencement of sildenafil, a lower % predicted DLco and Kco, and an increasing BNP level within the first 6 months of therapy, was associated with increased risk of death or requirement for additional PH therapy. Controlled trials are warranted before therapeutic recommendations can be made.
Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules
Authors: Namita Roy Chowdhury, Mohamed A. Saber, Pulak Lahiri, Peter I. Mackenzie, Phyllis M. Novikoff, Frederick F. Becker, Jayanta Roy Chowdhury
Journal: Hepatology (1991)

The expression of specific UDP-glucuronosyltransferase isoforms in 2-acetylaminofluorane—induced rat liver preneoplastic nodules was studied; livers from pair-fed littermates were used as controls. For comparison, liver and kidney from 3-methylcholanthrene—treated or untreated (control) rats were used. Steadystate UDP-glucuronosyltransferase mRNA levels were determined by Northern blot analysis or in situ hybridization of tissue sections using a 30-mer oligonucleotide specific for the 3-methylcholanthrene—inducible UDP-glucuronosyltransferase (which is active toward 4-nitrophenol) or a double-stranded cDNA probe specific for androsterone—UDP-glucuronosyltransferase. For 3-methylcholanthrene—inducible UDP-glucurono-syltransferase, the mRNA level was very low in control liver; there was a 15-fold increase after 3-methylcholanthrene treatment. This mRNA was present at relatively high concentration in the kidney and there was a threefold increase after 3-methylcholanthrene administration. In livers with preneoplastic nodules 1 mo after cessation of carcinogen administration, this mRNA concentration was approximately 15 times greater than in control liver. Similar changes in the level of the 3-methylcholanthrene—inducible UDP-glucuronosyltransferase were also observed by in situ hybridization of tissue sections. Immunocytochemical studies using an antiserum that recognizes the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase showed a marked increase in the concentration of this isoform in preneoplastic nodules compared with the adjacent nonnodular liver. Consistent with the changes in mRNA levels, there was a threefold increase in 4-nitrophenol-UDP-glucuronosyltransferase activity in 3-methylcholanthrene-treated rat livers and in livers with preneoplastic nodules. In contrast to the 3-methyl-cholanthrene-inducible UDP-glucuronosyltransferase mRNA, the androsterone-UDP-glucuronosyltransferase mRNA was abundant in the liver and nearly absent in the kidney; its concentration was not increased after 3-methylcholanthrene administration or in preneoplastic nodules. Immunocytochemical studies using an antiserum that recognizes androsterone- testosterone- and bilirubin-UDP-glucuronosyltransferase isoforms did not show any increase of the concentration of these antigens in preneoplastic nodules. Similarly, activities for androsterone, testosterone and bilirubin also did not increase after 3-methylcholanthrene administration or in livers bearing the preneoplastic nodules. (HEPATOLOGY 1991;13:38—46).
Treatment of tuberculosis.
Authors: A M Sutherland
Journal: BMJ (1979)

demand expertise.If this is lacking then expert supervision should be at hand.When this is not available, as in practical terms it may not be, then how much wiser it is to stop well short of that critical force.A trial of forceps therefore should still be a laudable and well-recognised procedure, and a "failed forceps" never regarded as an obstetric failure, unless the danger force is exceeded.No amount of experience will always predict the outcome of every instrumental delivery.Perhaps in the electronic age we could design a special type of strain gauge attached to the forceps handles.Failing this, a change in some attitudes towards trials of forceps, and in particular failed forceps, could certainly help.
Potential use of FDG-PET scan after induction chemotherapy in surgically staged IIIa–N2 non-small-cell lung cancer: A prospective pilot study
Authors: J.F. Vansteenkiste, S.G. Stroobants, P.R. De Leyn, P.J. Dupont, E.K. Verbeken
Journal: Annals of Oncology (1998)
P171 Implications Of A Non-constant Resistance-compliance Product In Pulmonary Arterial Hypertension
Authors: C. Hadinnapola, J. Pepke-Zaba, M. Toshner
Journal: Thorax (2014)

<h3>Introduction</h3> Pulmonary vascular resistance (PVR) is traditionally used to describe pulmonary haemodynamic characteristics. However, it does not take into account pulmonary artery compliance (Ca) or pulsatile flow. The product of PVR and Ca is known as RC-time. RC-time reflects the exponential decay of pressure in the pulmonary arteries during diastole. The right ventricle (RV) oscillatory power fraction (RVOPF) is the ratio of oscillatory power to total power generated by the RV. Oscillatory power is not used to generate stroke volume. Consequently the RVOPF is a measure of cardiac inefficiency. Previous small studies have suggested that both RC-time and RVOPF are constant. We hypothesised that RC-time is not constant and changes in RC-time affect cardiac efficiency. <h3>Methods</h3> Right heart catheters performed in PapworthHospital over a 6 year period were analysed. Patients were divided into normal pulmonary haemodynamics (NPH) and pulmonary arterial hypertension (PAH) groups. RC-time and RVOPF (≈ 1 − (mean pulmonary artery pressure/systolic pulmonary artery pressure) were calculated. <h3>Results</h3> RC-time for the NPH group (0.47 ± 0.1s) is lower than the PAH group (0.56 ± 0.2s; p &lt; 0.0001). There is an inverse relationship between RC-time and the RVOPF in both groups (PAH group: r<sup>2</sup> = 0.33; NPH group: r<sup>2</sup> = 0.27). <h3>Conclusions</h3> RC-time is not constant between health and pulmonary vascular disease. A reduction in RC-time, in the context of PAH, is associated with a decrease in cardiac efficiency. RVOPF is lower in the NPH group compared to the PAH group. This implies better cardiac efficiency in the NPH group possibly due to less pulsatile loading of the RV. Haemodynamic assessments which include measures of compliance may be of utility in understanding the progression of right heart failure in PAH.
Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance—the Chennai Urban Rural Epidemiology Study (CURES)
Authors: Raj Deepa, Kaliyaperumal Velmurugan, Kannan Arvind, Pillarisetti Sivaram, Cahoon Sientay, Saxena Uday, Viswanathan Mohan
Journal: Metabolism (2006)