tbuckley/cabot-search huggingface dataset:
Increased Infarct Size in Uremic Rats
Authors: Ralf Dikow, Lars Philipp Kihm, Martin Zeier, Jolanthe Kapitza, Johannes To[Combining Diaeresis]rnig, Kerstin Amann, Christiane Tiefenbacher, Eberhard Ritz
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. In patients with renal failure, myocardial infarction (MI) is more frequent and the rate of death from acute MI is very high. It has been argued that ischemia tolerance of the heart is reduced in uremia, but direct evidence for this hypothesis has not been provided. It was the purpose of this study (<i>1</i>) to ligate the left coronary artery and to measure the nonperfused area (risk area: total infarction plus penumbra) as well as the area of total infarction in subtotally nephrectomized (SNX) rats compared with sham-operated pair-fed control rats and (<i>2</i>) to examine the effects of potential confounders such as BP, sympathetic overactivity, and salt retention. The left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. For visualizing perfused myocardium, lissamine green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (triphenyltetrazolium chloride stain) were assessed in sections of the left ventricle using image analysis. Groups of SNX rats also received: antihypertensive treatment (nadolol plus hydralazine); moxonidine; high salt diet or low salt diet (1.58% <i>versus</i> 0.015%). In surviving animals, the nonperfused area at risk (as the proportion of total left ventricular area), presumably determined by the geometry of vascular supply, was similar in sham-operated and SNX animals (0.38 ± 0.13 <i>versus</i> 0.45 ± 0.09; NS). In contrast, the infarcted area, given as a proportion of the nonperfused risk area, was significantly (<i>P</i> &lt; 0.003) higher in SNX (0.68 ± 0.09) compared with sham-operated (0.51 ± 0.11) rats and was not altered by any of the above interventions. The finding that a greater proportion of nonperfused myocardium undergoes total necrosis is consistent with the hypothesis of reduced ischemia tolerance of the heart in renal failure. The findings could explain the high rate of death from MI in patients with impaired renal function.
Percutaneous coronary interventional strategies for treatment of in-stent restenosis: a network meta-analysis
Authors: George C M Siontis, Giulio G Stefanini, Dimitris Mavridis, Konstantinos C Siontis, Fernando Alfonso, María J Pérez-Vizcayno, Robert A Byrne, Adnan Kastrati, Bernhard Meier, Georgia Salanti, Peter Jüni, Stephan Windecker
Journal: The Lancet (2015)
Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates
Authors: Katherine L O'Brien, Lara J Wolfson, James P Watt, Emily Henkle, Maria Deloria-Knoll, Natalie McCall, Ellen Lee, Kim Mulholland, Orin S Levine, Thomas Cherian
Journal: The Lancet (2009)
Azacytidine Inhibits RNA Methylation at DNMT2 Target Sites in Human Cancer Cell Lines
Authors: Matthias Schaefer, Sabine Hagemann, Katharina Hanna, Frank Lyko
Journal: Cancer Research (2009)

The cytosine analogues azacytidine and decitabine are currently being developed as drugs for epigenetic cancer therapy. Although various studies have shown that both drugs are effective in inhibiting DNA methylation, it has also become clear that their mode of action is not limited to DNA demethylation. Because azacytidine is a ribonucleoside, the primary target of this drug may be cellular RNA rather than DNA. We have now analyzed the possibility that azacytidine inhibits the RNA methyltransferase DNMT2. We found that DNMT2 is variably expressed in human cancer cell lines. RNA bisulfite sequencing showed that azacytidine, but not decitabine, inhibits cytosine 38 methylation of tRNA(Asp), a major substrate of DNMT2. Azacytidine caused a substantially stronger effect than decitabine on the metabolic rate of all the cancer cell lines tested, consistent with an effect of this drug on RNA metabolism. Of note, drug-induced loss of RNA methylation seemed specific for DNMT2 target sites because we did not observe any significant demethylation at sites known to be methylated by other RNA methyltransferases. Our results uncover a novel and quantifiable drug activity of azacytidine and raise the possibility that tRNA hypomethylation might contribute to patient responses.
Trends of Analgesic Nephropathy in Two High-Endemic Regions with Different Legislation
Authors: PAUL MICHIELSEN, PAUL DE SCHEPPER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Analgesic abuse is related to a specific form of interstitial nephritis, but the exact nature of the causal agent remains controversial and this has resulted in differences in regulation. In Flanders, the free sale of phenacetin was banned, but the consumption of other combined analgesics remained free. In New South Wales, phenacetin was also banned, but 2 yr later the sales of all combined analgesics were also prohibited. This study compared the evolution of end-stage renal disease as a result of analgesic nephropathy (AN) in these two high-endemic regions with different legislation. In both regions, the time trend of the age-specific incidence of end-stage renal disease as a result of AN is similar in the age group 45 to 54 yr. In all age groups combined, the time trend of the percentage of AN among the patients admitted for renal replacement therapy is also similar. This finding does not support the hypothesis that non-phenacetin mixed analgesics play a significant role in the occurrence of AN.
Sudden exertional death in sickle cell trait: Figure 1
Authors: Mike Loosemore, Stephen B Walsh, Emma Morris, Gordon Stewart, John B Porter, Hugh Montgomery
Journal: British Journal of Sports Medicine (2011)

While generally considered benign, sickle cell trait (SCT) is both common and associated with a risk of sudden exertional death. Indeed, all high-level US intercollegiate athletes now face mandatory screening, raising legal and ethical concerns that resonate given the 2012 London Olympics' role in driving universal sports' participation, and increasing public health messaging promoting physical activity. This issue is also of substantial clinical and scientific interest: the pathogenesis of such deaths is unknown and successful management thus impeded.

This article discusses both clinical presentation and relevant (patho)physiology. It also proposes that a vicious cycle of skeletal muscle microvascular occlusion and ‘metabolic failure’ drives potassium efflux from erythrocytes and myocytes and therefore, hyperkalaemic death. Such discussion may be of value to all dealing with subjects with SCT in the community, to emergency/intensive care physicians who treat such cases and to researchers seeking new methods of screening and modes of treatment.

The pathogenesis of exercise-related death among those with SCT is not understood. We hypothesise that potassium efflux from red cells and skeletal muscle causes hyperkalaemic death.

Each of the haemoglobin (Hb) molecule's four subunits contains an oxygen-carrying haem group and a globin molecule. Two α-subunits are bound to two γ-subunits in fetal haemoglobin (HbF, α2γ2) or two β-subunits in adult haemoglobin (HbA, α2β2). The haemoglobin in which two α-subunits are associated with two mutant β-subunits (in which a hydrophobic valine replaces a hydrophilic glutamic acid) is referred to as sickle cell haemoglobin (HbS).

Hypoxia and falling pH cause HbS to polymerise, distorting red blood cell (RBC) shape (‘sickling’), whose extent depends upon the RBC concentration of HbS relative to HbA/HbF. This is lower in heterozygotes (HbAS with SCT) than homozygotes (HbSS with sickle cell disease (SCD)). Sickling-induced vaso-occlusion can lead to so-called ‘sequestration crises’, but …
The pharmacodynamics of GSK961081 in patients with COPD
Authors: Virginia Norris, Chang-Qing Zhu, Claire Ambery
Journal: European Respiratory Journal (2011)

Introduction:  GSK961081 is a dual pharmacophore with both muscarinic antagonist and beta 2  agonist (MABA) activity.   Objective:  To assess the pharmacodynamics of GSK961081.   Methods:  This was a randomised, double-blind, double-dummy, placebo-controlled, incomplete block crossover study in 50 COPD patients. Patients were randomised to 3 of 4 possible treatments: 400μg GSK961081 once daily (OD) (n=29); 1200μg GSK961081 OD (n=32); salmeterol 50μg twice daily+tiotropium 18μg OD (SAL+TIO) (n=41); and placebo (n=43) by inhalation for 14 days. Pharmacodynamics (lung and systemic), safety and tolerability were monitored.   Results:  After 14 days9 dosing there were significant improvements in trough FEV 1  for all active treatments. For 400μg GSK961081, 1200μg GSK961081 and SAL+TIO mean (95% CI) differences vs placebo were 0.115L (0.024,0.205), 0.168L (0.080,0.255) and 0.103L (0.026,0.180), respectively (all p   Conclusions:  GSK961081 was well tolerated and showed significant bronchodilatation, meriting further evaluation as a potential therapy for COPD.  Funded by GSK (MAB104958; NCT00478738)
Usefulness of GOLD classification of COPD severity
Authors: D Kohler
Journal: Thorax (2003)

In 2001 the US National Heart, Lung and Blood Institute (NHLBI) and the World Health Organization announced guidelines for the diagnosis, management, and treatment of COPD (Global Initiative for Chronic Obstructive Lung Disease, GOLD).1 One key aspect of these guidelines is that COPD is classified by severity into five stages which constitute the basis of treatment recommendations. However, to date there has been little evidence for the usefulness of these severity stages.

We retrospectively reviewed 1000 patients with COPD diagnosed clinically in 2001; 500 patients originated from a pulmonary rehabilitation hospital. Patients’ symptoms (based on a standardised interview), findings of a standardised lung examination, lung function data, and chest radiographic findings are routinely documented in a …
Prognostic Value of Apoptosis in Rectal Cancer Patients of the Dutch Total Mesorectal Excision Trial: Radiotherapy Is Redundant in Intrinsically High-Apoptotic Tumors
Authors: Elza C. de Bruin, Cornelis J.H. van de Velde, Simone van de Pas, Iris D. Nagtegaal, J. Han J.M. van Krieken, Marleen J.E.M. Gosens, Lucy T.C. Peltenburg, Jan Paul Medema, Corrie A.M. Marijnen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The combination of radiotherapy and good quality surgery reduces local recurrence rate for rectal cancer patients. This study assesses the prognostic value of both intrinsic and radiotherapy-induced apoptosis and evaluates the relevance of radiotherapy for outcome of rectal cancer patients. Experimental Design: Tumor samples (1,198) were available from the Dutch Total Mesorectal Excision trial, in which rectal cancer patients were treated with standardized surgery and randomized for preoperative short-term radiotherapy or not. Tumor samples were obtained at time of surgery. Tissue microarrays were constructed and stained with the active caspase-specific M30 antibody to determine the amount of apoptotic epithelial tumor cells. Results: Nonirradiated patients with a negative circumferential margin displaying lower than median levels of apoptosis developed more local recurrences (10.5% versus 6.1%; P = 0.06) and more rapidly after surgery than patients with high intrinsic apoptosis in their tumors (median time to recurrence, 13.0 versus 21.3 months; P = 0.04). In multivariate analysis, intrinsic apoptosis was an independent predictor for the development of local recurrences (hazard ratio, 2.0; P = 0.05). Radiotherapy increased apoptosis level (11 versus 23 apoptotic cells/mm2 tumor epithelium; P &amp;lt; 0.001), but this apoptosis did not influence patients' prognosis. Conclusions: Rectal cancer patients with low intrinsic apoptosis will benefit from radiotherapy with respect to the development of local recurrences. Because apoptosis is an inherent characteristic of tumors, patients who do not need radiotherapy may be selected based on the apoptotic index of the primary tumor.
Mitral prosthesis malfunction. Comparative Doppler echocardiographic studies of mitral prostheses before and after replacement.
Authors: U Nellessen, T Masuyama, C P Appleton, T Tye, R L Popp
Journal: Circulation (1989)

To assess the influence of mitral prosthesis malfunction on various Doppler echocardiographic indexes, we studied the changes in the peak mitral flow velocity during early diastolic filling phase (Vmax), the mean transprosthesis pressure drop from the simplified Bernoulli equation, the mitral valve area by the pressure half-time method, and the left ventricular isovolumic relaxation time in 15 patients before and after replacement of the malfunctioning mitral prosthesis using continuous wave Doppler echocardiography. Examination of the 15 replaced prostheses revealed a torn or perforated leaflet in 12 valves and a sewing ring dehiscence in one valve. Additional restricted leaflet motion (classified as mild obstruction) was seen in three of these 13 valves. In the remaining two valves, severe prosthesis obstruction was noted. Changes in the Doppler indexes between the preoperative and postoperative study were present in all patients regarding Vmax (mean, 2.2 +/- 0.3 versus 1.6 +/- 0.2 m/sec; p less than 0.001), mean gradient (mean, 9 +/- 5 versus 5 +/- 0.8 mm Hg; p less than 0.001), and isovolumic relaxation time (mean, 47 +/- 12 msec versus 80 +/- 13 msec; p less than 0.001). The mean mitral valve area remained virtually unchanged (2.3 +/- 0.9 versus 2.6 +/- 0.3 cm2; p = NS) but increased postoperatively in each patient with preoperative mild or severe prosthesis obstruction without concomitant aortic regurgitation. Our conclusion is that the peak mitral flow velocity, the mean gradient, and the isovolumic relaxation time are useful parameters in the differentiation of normal and abnormal mitral prosthesis function but may not define the underlying lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Age-related changes in cell surface antigens of preleukemic AKR thymocytes.
Authors: K Kawashima, H Ikeda, E Stockert, T Takahashi, L J Old
Journal: The Journal of Experimental Medicine (1976)

Thymocytes from preleukemic AKR mice aged 5-6 mo have an altered pattern of cell surface antigens. The expression of four MuLV-related antigens on the cell surface (GIX, GCSA, gp70, p30) is markedly increased in comparison to 2-mo-old AKR mice and approximates the heightened levels of these antigens found on thymic leukemia cells. H-2 and Thy-1 alloantigens also show characteristic modifications in relation to age and leukemia development. In contrast to the high Thy-1/low H-2 levels on 2-mo-old AKR thymocytes, thymocytes from 6-mo-old mice and thymic leukemia cells frequently show a low Thy-1/high H-2 surface phenotype. As thymocytes from mouse strains with a low incidence of leukemia do not show these changes, they appear to represent a stage in the conversion of normal cells to leukemia cells.
Clinical Manifestations and Treatment of Dysfunctional Uterine Bleeding
Authors: Steven R. Bayer
Journal: JAMA (1993)

Dysfunctional uterine bleeding is a common gynecologic disorder that can affect any woman during her reproductive years. It is a diagnosis of exclusion, and the clinician must proceed through a logical stepwise evaluation to rule out all other causes of the abnormal bleeding. In most cases dysfunctional uterine bleeding is associated with anovulation. During the pubertal and perimenopausal periods, anovulatory bleeding is a common occurrence. During these transitional states, the abnormal bleeding has a physiological basis and is secondary to an estrogen withdrawal. Anovulatory bleeding can also be associated with chronic anovulation. The chronic unopposed estrogen that characterizes this disorder causes a continuous proliferation of the endometrium; this can result in abnormal bleeding and place the patient at risk for endometrial cancer. The goals of treatment for anovulatory bleeding are to stop the acute bleeding, avert future episodes, and prevent long-term complications. In some cases surgical intervention is indicated, but the foundation of treatment has been a medical approach. Several progestational agents have demonstrated effectiveness and can be administered either orally or by intramuscular injection. If the patient fails to have resolution of the bleeding with medical therapy, another cause of the bleeding must be suspected, and reevaluation is necessary. (<i>JAMA</i>. 1993;269:1823-1828)
Health USA. A national health program for the United States
Authors: E. R. Brown
Journal: JAMA (1992)

The Health USA Act of 1991 addresses two fundamental health services financing problems: the more than 30 million uninsured persons and the rising costs for health care and for health insurance. Health USA would provide coverage of the entire resident population for comprehensive medical and preventive health and long-term care services through a universal tax-funded financing system. The federal government would contribute an average of 87% of program costs to each state, which would establish, under federal guidelines, a state health program. Each individual or family may enroll in any health plan approved by the state program, including many private plans, or a plan run by the state program. Through the approved plan of their choice, enrollees would receive covered services and obtain their care from participating physicians and other professional practitioners, hospitals, and other facilities. The state program would pay approved plans a capitation payment for every person enrolled. The plans would pay professional providers fees, as part of an all-payer system of fee schedules and expenditure targets, or capitation payments or salary. Hospitals would be financed through global budgets negotiated by the state program with each hospital. The plan run by the state program would pay the health care costs of any person who does not enroll in an approved plan, making the state plan the payer of last resort and eliminating uncompensated care and cost shifting by providers. Health USA would separate health care coverage from employment, ensuring uninterrupted coverage and eliminating employers' administrative role in providing coverage. Federal and state taxes would replace present methods of financing by private insurance premiums and large out-of-pocket expenditures. Building on the present system of health plans, Health USA would offer all persons a wide choice of competing plans in which to enroll and offer professional providers a wide choice of plans in which to practice. It would control costs by increasing financial accountability of providers and health plans, reducing present reliance on intrusive utilization review and on patient cost sharing. By controlling health care and administrative costs, Health USA would cover the entire population and, according to independent cost estimates, reduce national health expenditures by $11.5 billion in 1991.
Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases
Authors: Pedro FC Vasconcelos, Expedito J Luna, Ricardo Galler, Luiz J Silva, Terezinha L Coimbra, Vera LRS Barros, Thomas P Monath, Sueli G Rodigues, Cristina Laval, Zouraide G Costa, Maria FG Vilela, Cecília LS Santos, Cristina MO Papaiordanou, Venancio AF Alves, Liliana D Andrade, Helena K Sato, Elisabeth ST Rosa, Gustavo B Froguas, Ethel Lacava, Leda MR Almeida, Ana CR Cruz, Iray M Rocco, Raimunda TM Santos, Otávio FP Oliva, Brazilian Yellow
Journal: The Lancet (2001)
AMINONUCLEOSIDE NEPHROSIS
Authors: Robert L. Vernier, Benjamin W. Papermaster, Robert A. Good
Journal: The Journal of Experimental Medicine (1959)

Experimental renal disease was produced in young rats by daily subcutaneous injections of 6-dimethylamino purine, 3-amino-d-ribose (aminonucleoside). The physiologic, biochemical, and light microscopic changes were similar to those observed in human nephrosis. Electron microscopy of the glomeruli from animals which received seven or more daily injections of aminonucleoside revealed characteristic abnormalities of the epithelial cells of the glomerular capillaries. These changes consisted of swelling, coalescence, and eventual obliteration of the epithelial cell foot processes and an increase in the number and the size of epithelial cytoplasmic vacuoles. The serial development of the ultramicroscopic pathologic changes in the epithelial cells, as observed by study of animals through the course of the disease, indicated that the smudging of the foot processes occurred at the time of onset of severe proteinuria. Further changes, consisting of hypercellularity due primarily to an increase in the number of endothelial cells and an increase in the amount of basement membrane-like material, were regularly observed by the 12th day after injections were begun. These abnormalities were correlated with the development of uremia in the later stages of the disease process. The distal and proximal renal tubules were abnormal by the 7th day after injections were begun, and showed localized swelling between the cristae of the mitochondria and a decrease in over-all cytoplasmic density, described as hydropic change. Electron microscopy of glomeruli from animals which had partially recovered from aminonucleoside nephrosis revealed areas of normal epithelial cell morphology. This observation was interpreted as evidence of partial reversal of the ultramicroscopic changes in the recovery phase of the disease. These observations of the fine structure of pathologically altered glomeruli and tubules in aminonucleoside nephrosis are similar to our findings in human nephrosis as revealed by electron microscopy of serial renal biopsies.