tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of hydroxyurea in sickle cell anemia
Authors: Richard D. Moore, Samuel Charache, Michael L. Terrin, Franca B. Barton, Samir K. Ballas
Journal: American Journal of Hematology (2000)

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) demonstrated the efficacy of hydroxyurea in reducing the rate of painful crises compared to placebo. We used resource utilization data collected in the MSH to determine the cost-effectiveness of hydroxyurea. The MSH was a randomized, placebo-controlled double-blind clinical trial involving 299 patients at 21 sites. The primary outcome, visit to a medical facility, was one of the criteria to define occurrence of painful crisis. Cost estimates were applied to all outpatient and emergency department visits and inpatient hospital stays that were classified as a crisis. Other resources for which cost estimates were applied included hospitalization for chest syndrome, analgesics received, hydroxyurea dosing, laboratory testing, and clinic visits for management of patient care. Annualized differential costs were calculated between hydroxyurea- and placebo-receiving patients. Hospitalization for painful crisis accounted for the majority of costs in both arms of the study, with an annual mean of $12,160 (95% CI: $9,440, $14,880) for hydroxyurea and $17,290 (95% CI: $13,010, $21,570) for placebo. The difference in means was $5,130 (95% CI: $60, $10,200; P = 0.048). Chest syndrome was the next largest cost with a mean difference of $830 (95% CI: $−340, $2,000; P = 0.16). The hydroxyurea arm was also associated with lower costs for emergency department visits, transfusion, and use of opiate analgesics. In total, the annual average cost per patient receiving hydroxyurea was $16,810 (95% CI: $13,350, $20,270) and the annual average costs per patient receiving placebo was $22,020 (95% CI: $17,340, $26,710). The difference in means was $5,210 (95% CI: $−610, $11,030; P = 0.21). The cost of hydroxyurea with the more intensive monitoring required when using this drug appears to be more than offset by decreased costs for medical care of painful crisis and analgesic use. Although the total cost difference was not significant statistically, these results suggest that hydroxyurea therapy is cost-effective compared to placebo in the management of adult patients with sickle cell anemia. If hydroxyurea can prevent development of chronic organ damage, long-term savings may be even greater. Am. J. Hematol. 64:26–31, 2000. © 2000 Wiley-Liss, Inc.
Evaluation of diagnostic criteria for atopic dermatitis: validity of the criteria of Williams et al. in a hospital-based setting
Authors: H. Gu, X.S. Chen, K. Chen, Y. Yan, H. Jing, X.Q. Chen, C.G. Shao, G.Y. Ye
Journal: British Journal of Dermatology (2001)

Surveys of the prevalence of atopic dermatitis (AD) have been carried out world-wide, but the results vary widely. The differences probably result from the use of different diagnostic criteria. Williams et al. proposed minimum, simplified, diagnostic criteria that require no invasive test and are easy to use. Pilot studies in European countries showed their suitability for implementation both in hospitals and in the community, and their high sensitivity and specificity.To evaluate the potential practical value of the criteria of Williams et al. in the Chinese population.The criteria of Hanifin and Rajka (gold standard), Williams et al. and Kang and Tian were applied and compared in 111 patients with AD and 121 control subjects with other skin diseases in three out-patient centres in China.The criteria of Williams et al. showed a similar diagnostic efficiency to that of the gold standard, with the sensitivity, specificity and kappa value reaching 95.50%, 97.52% and 0.93, respectively. No significant difference was found between the criteria of Williams et al. and those of Kang and Tian (chi2 = 0.69, P > 0.05). 'Onset under the age of 2 years', a criterion of Williams et al. could be used in subjects of any age.The diagnostic efficiency of the criteria of Williams et al. was basically similar to those of Hanifin and Rajka and of Kang and Tian in our out-patient settings. However, those of Williams et al. were easier to apply and required no invasive tests.
ET-10 * THE SYNERGISTIC EFFECT OF INHIBITOR OF INHIBITOR OF APOPTOSIS PROTEINS- LCL161 AND STANDARD ANTI-CANCER AGENTS ON MEDULLOBLASTOMA CELLS
Authors: S.-M. Chen, Y.-Y. Li, T.-N. Lui, L.-a. L. Hsieh
Journal: Neuro-Oncology (2014)

Medulloblastoma is the most common malignant pediatric brain tumor, comprising 15-20% of intracranial tumor in children. Most metastatic and recurrent medulloblastoma cells are resistant to current therapeutic approaches including radiation and high-dose chemotherapy. In addition, some studies indicate that subsets of medulloblastomas exhibit loss of caspase-8 expression and therefore they can resist TRAIL-induced apoptosis.A chemo-drug, LCL161, has a mimic structure of Smac/DIABLO, which can inhibit XIAP and cIAP, and then enhance caspse-3, caspase-7 and caspase-9 activation. Our study purpose is to determine whether LCL161 induce cell apoptosis and activate caspases cascade through inhibition of IAPs in medulloblastoma cells(DAOY and d283) and to examine whether LCL161 can sensitize standard anti-cancer agents(vincrstine, or cisplatin) induced apoptosis. Based on prior data, DAOY cells had higher, and d283 cells had lower caspase-8 expressions respectively. LCL161 alone did not inhibit tumor growth for both medulloblastoma cells. Our data showed synergistic effect of LCL161-combined vincrstine, or cisplatin can be observed in DAOY cells. For d283 med cells, synergistic effect still exist but was not as significant as that of DAOY cells. LCL161-combined vincristine decreased around 40% and 20% cell viability in DAOY cells and d283 med cells compared to vincrisitne alone. LCL-combined cisplatin inhibited 20% growth rate in DAOY cells. Nevertheless, synergistic effect did not work in d283 cells. DNA flow and Annexin V/PI assay were indicated LCL 161 alone increased 16% of apoptotic cells. In addition, LCL161 enhanced 18% of apoptotic cells treated with vincristine, and the combined treatment approached to IC50 for medulloblastoma cells. LCL161-combined cisplatin increased 18% of apoptotic cells compared to cisplatin alone. Overall, the synergistic effect of LCL161 and standard anti-cancer agents was more significant on DAOY cells, which express higher caspase-8. The finding indicated that loss of caspase 8 play an important role in this therapeutic strategy.
Clinical disorders associated with autoantibodies to the insulin receptor. Simulation by passive transfer of immunoglobulins to rats.
Authors: R F Dons, R Havlik, S I Taylor, K L Baird, S S Chernick, P Gorden
Journal: Journal of Clinical Investigation (1983)

Patients with autoantibodies to the insulin receptor (Anti-R) may exhibit either fasting hypoglycemia or hyperglycemia and extreme insulin resistance. Occasionally, both these phenomena are observed in the same patient at different times in the clinical course. In an effort to understand what determines the patient's response to Anti-R, we developed an animal model of these clinical disorders by passive transfer of Anti-R IgG to rats. IgG fractions from the plasma of Anti-R patients and control subjects were prepared by affinity chromatography with staphylococcal protein A-Sepharose. Anti-R IgG, injected into fasting rats, induced severe and persistent hypoglycemia (plasma glucose 30-60 mg/dl). Rats injected with control IgG maintained a plasma glucose within the range of 75 (fasting) to 165 mg/dl (feeding). In comparison with the effects of insulin, the hypoglycemic response to Anti-R IgG had a slower onset (2-4 h) and lasted longer (8-24 h). Similar, dose-dependent hypoglycemic responses were observed in rats whether the Anti-R IgG was derived from an insulin-resistant or hypoglycemic patient. When Anti-R IgG was administered in sufficiently high doses for several days to fed rats, persistent hyperglycemia (plasma glucose 200-400 mg/dl) developed. Based on these in vivo and previous in vitro studies, we attribute the hypoglycemic response to an insulin-like effect of Anti-R, and the hyperglycemic response to a desensitization of host tissues to the effects of insulin, with more prolonged exposure to higher levels of Anti-R.
Cardiovascular Events and Intensity of Treatment in Polycythemia Vera
Authors: Roberto Marchioli, Guido Finazzi, Giorgina Specchia, Rossella Cacciola, Riccardo Cavazzina, Daniela Cilloni, Valerio De Stefano, Elena Elli, Alessandra Iurlo, Roberto Latagliata, Francesca Lunghi, Monia Lunghi, Rosa Maria Marfisi, Pellegrino Musto, Arianna Masciulli, Caterina Musolino, Nicola Cascavilla, Giovanni Quarta, Maria Luigia Randi, Davide Rapezzi, Marco Ruggeri, Elisa Rumi, Anna Rita Scortechini, Simone Santini, Marco Scarano, Sergio Siragusa, Antonio Spadea, Alessia Tieghi, Emanuele Angelucci, Giuseppe Visani, Alessandro Maria Vannucchi, Tiziano Barbui
Journal: New England Journal of Medicine (2012)

Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial.We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit, <45%) (low-hematocrit group) or less intensive treatment (target hematocrit, 45 to 50%) (high-hematocrit group). The primary composite end point was the time until death from cardiovascular causes or major thrombotic events. The secondary end points were cardiovascular events, cardiovascular hospitalizations, incidence of cancer, progression to myelofibrosis, myelodysplasia or leukemic transformation, and hemorrhage. An intention-to-treat analysis was performed.After a median follow-up of 31 months, the primary end point was recorded in 5 of 182 patients in the low-hematocrit group (2.7%) and 18 of 183 patients in the high-hematocrit group (9.8%) (hazard ratio in the high-hematocrit group, 3.91; 95% confidence interval [CI], 1.45 to 10.53; P=0.007). The primary end point plus superficial-vein thrombosis occurred in 4.4% of patients in the low-hematocrit group, as compared with 10.9% in the high-hematocrit group (hazard ratio, 2.69; 95% CI, 1.19 to 6.12; P=0.02). Progression to myelofibrosis, myelodysplasia or leukemic transformation, and bleeding were observed in 6, 2, and 2 patients, respectively, in the low-hematocrit group, as compared with 2, 1, and 5 patients, respectively, in the high-hematocrit group. There was no significant between-group difference in the rate of adverse events.In patients with polycythemia vera, those with a hematocrit target of less than 45% had a significantly lower rate of cardiovascular death and major thrombosis than did those with a hematocrit target of 45 to 50%. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT01645124, and EudraCT number, 2007-006694-91.).
Determination of the chelatable iron pool of isolated rat hepatocytes by digital fluorescence microscopy using the fluorescent probe, phen green SK
Authors: Frank Petrat, Ursula Rauen, Herbert de Groot
Journal: Hepatology (1999)

The intracellular pool of chelatable iron is considered to be a decisive pathogenetic factor for various kinds of cell injury. We therefore set about establishing a method of detecting chelatable iron in isolated hepatocytes based on digital fluorescence microscopy. The fluorescence of hepatocytes loaded with the fluorescent metal indicators, phen green SK (PG SK), phen green FL (PG FL), calcein, or fluorescein desferrioxamine (FL–DFO), was quenched when iron was added to the cells in a membrane–permeable form. It increased when cellular chelatable iron available to the probe was experimentally decreased by an excess of various membrane–permeable transition metal chelators. The quenching by means of the ferrous ammonium sulfate + citrate complex and also the “dequenching” using 2,2′–dipyridyl (2,2′–DPD) were largest for PG. We therefore optimized the conditions for its use in hepatocytes and tested the influence of possible confounding factors. An ex situ calibration method was set up to determine the chelatable iron pool of cultured hepatocytes from the increase of PG SK fluorescence after the addition of excess 2,2′–DPD. Using this method, we found 9.8 ± 2.9 μmol/L (mean ± SEM; n = 18) chelatable iron in rat hepatocytes, which constituted 1.0% ± 0.3% of the total iron content of the cells as determined by atomic absorption spectroscopy. The concentration of chelatable iron in hepatocytes was higher than the one in K562 cells (4.0 ± 1.3 μmol/L; mean ± SEM; n = 8), which were used for comparison. This method allowed us to record time courses of iron uptake and of iron chelation by different chelators ( e.g. , deferoxamine, 1,10–phenanthroline) in single, intact cells
Common variants near TERC are associated with mean telomere length
Authors: Veryan Codd, Massimo Mangino, Pim van der Harst, Peter S Braund, Michael Kaiser, Alan J Beveridge, Suzanne Rafelt, Jasbir Moore, Chris Nelson, Nicole Soranzo, Guangju Zhai, Ana M Valdes, Hannah Blackburn, Irene Mateo Leach, Rudolf A de Boer, Masayuki Kimura, Abraham Aviv, Alison H Goodall, Willem Ouwehand, Dirk J van Veldhuisen, Wiek H van Gilst, Gerjan Navis, Paul R Burton, Martin D Tobin, Alistair S Hall, John R Thompson, Tim Spector, Nilesh J Samani
Journal: Nature Genetics (2010)
Selected CD133 <sup>+</sup> Progenitor Cells to Promote Angiogenesis in Patients With Refractory Angina
Authors: Pilar Jimenez-Quevedo, Juan Jose Gonzalez-Ferrer, Manel Sabate, Xavier Garcia-Moll, Roberto Delgado-Bolton, Leopoldo Llorente, Esther Bernardo, Aranzazu Ortega-Pozzi, Rosana Hernandez-Antolin, Fernando Alfonso, Nieves Gonzalo, Javier Escaned, Camino Bañuelos, Ander Regueiro, Pedro Marin, Antonio Fernandez-Ortiz, Barbara Das Neves, Maria del Trigo, Cristina Fernandez, Teresa Tejerina, Santiago Redondo, Eulogio Garcia, Carlos Macaya
Journal: Circulation Research (2014)

Rationale: Refractory angina constitutes a clinical problem. Objective: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133 + cells to foster angiogenesis in patients with refractory angina. Methods and Results: In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133 + cells or no treatment. The primary end point was the safety of transendocardial injection of CD133 + cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, −8.5 [95% confidence interval, −15.0 to −4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, −1.0 [95% confidence interval, −1.9 to −0.1]) but not in the control arm. Conclusions: Our findings support feasibility and safety of transendocardial injection of CD133 + cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.
CRL4B Catalyzes H2AK119 Monoubiquitination and Coordinates with PRC2 to Promote Tumorigenesis
Authors: Huili Hu, Yang Yang, Qinghong Ji, Wei Zhao, Baichun Jiang, Ruiqiong Liu, Jupeng Yuan, Qiao Liu, Xi Li, Yongxin Zou, Changshun Shao, Yongfeng Shang, Yan Wang, Yaoqin Gong
Journal: Cancer Cell (2012)
Guide to Interpreting 12-Lead ECGs
Authors: I. Martin Grais
Journal: JAMA (1985)

This book is really an atlas and probably merits a different title. It fills a gap among the numerous books on electrocardiography. In 1962, when I first began reading elementary ECG texts, I found a two-volume atlas of 119 ECGs published by the American Heart Association, edited by Dr Travis Winsor, and entitled<i>Electrocardiographic Test Book</i>.<sup>1</sup>Each ECG had a short paragraph of clinical correlation, multiple-choice questions, and a brief interpretation. It was a delightfully useful learning system for neophytes. Unfortunately Dr Winsor's book is out of print, and I had not discovered a suitable substitute for practicing ECG interpretation until the arrival of this text by Drs Wharton and Goldschlager. Indeed, the authors have provided an adequate replacement. The clinical correlations employ modern noninvasive testing, the ECG descriptions use current terminology, and the differential diagnoses are more complete. There is also a series of detailed tables and diagrams
Sliding Board for Severely Disabled Patients
Authors: R. E. Jowett
Journal: BMJ (1967)

Sugar Consumption and Acne SIR,-I was interested in the study by Dr. D. G. G. Bett and others (15 July, p. 153) in which they found raised sugar consumption in patients with seborrhoeic dermatitis but not in those with acne.In a study of 2,720 soldiers it was estab- lished that there is no correlation between the incidence or severity of acne and dandruff.'There was also no correlation between acne and obesity in men under 20 years old--the age group studied by Bett et al.However, in older men (age 20-40) there was a signifi- cant correlation between acne and obesity.It appears, therefore, that perhaps Bett et al. should extend their study to see if there is raised sugar intake in this older group before it can be settled that sugar intake in acne is not raised.-Iam, etc.,
Effect of Insulin Pump Treatment for One Year on Renal Function and Retinal Morphology in Patients with IDDM
Authors: H Beck-Nielsen, B Richelsen, C E Mogensen, T Olsen, N Ehlers, C B Nielsen, P Charles
Journal: Diabetes Care (1985)

The effect of strict metabolic control for 1 yr on renal function and retinal morphology was estimated in 24 insulin-dependent diabetic individuals (age 29 ± 8 yr, diabetes duration 10 ± 6 yr) with Albustix negative urine and minimal or no background retinopathy before the study. They were randomized to conventional insulin treatment (CIT) or continuous subcutaneous insulin infusion (CSII) with a portable pump. During CSII treatment the metabolic status was significantly improved and glomerular filtration rates (GFR) were found to decline (from 130 ± 18 to 116 ± 15 ml/min/1.73 m2, P &amp;lt; 0.01). The mean value of urinary albumin excretion (UAE) was not statistically significantly reduced (from 15.3 ± 24.1 to 6.8 ± 1.5 mg/24 h, P &amp;gt; 0.1). In the CIT group both GFR and UAE values were unchanged. In all subjects before treatment we found a positive correlation between the metabolic status, estimated by the HbA1c values, and GFR as well as UAE values, respectively (r = 0.64, P &amp;lt; 0.01 and r = 0.42, P &amp;lt; 0.05). We conclude that elevated GFR values can be reduced toward normal level by insulin pump treatment for 1 yr. Retinal morphology was found to deteriorate in four of 12 CIT subjects and in three of 12 CSII subjects. However, the progression was mild and in most individuals only due to a slight increase in the number of microaneurysms. Pump treatment did not induce proliferation and “cotton-wool” exudates were not detectable in any pump subject after 1 yr of treatment. We conclude that CSII treatment for 1 yr was unable to stop the progression of retinopathy in individuals with minimal or no retinopathy on entering the study. On the other hand, pump treatment did not induce cotton-wool exudates or proliferation in these subjects as previously reported in subjects with more severe retinopathy before CSII treatment.
Adenosine Mediates Sustained Adrenergic Desensitization in the Rat Heart via Activation of Protein Kinase C
Authors: Stefano Perlini, Edmon P. Khoury, Gavin R. Norton, Eugene S. Chung, Richard A. Fenton, James G. Dobson, Theo E. Meyer
Journal: Circulation Research (1998)

Abstract —Adenosine attenuates the myocardial metabolic and contractile responses induced by β-adrenergic stimulation. Our study was conducted to investigate the longevity of this antiadrenergic action after adenosine exposure. Adenosine (33 μmol/L) was infused into isolated perfused rat hearts for 1, 5, 30, or 60 minutes, and the adrenergic responsiveness (AR) to isoproterenol (10 −8 mol/L) was determined at the end of each infusion period and during a 45-minute adenosine washout period. Interstitial levels of adenosine, as determined from epicardial surface transudates, returned to preinfusion levels within 10 minutes of washout. The duration of adenosine infusion had no effect on the extent of attenuation of AR at the end of the infusion. Whereas AR returned to preadenosine levels with washout of shorter adenosine infusions (1 and 5 minutes), there was a slow and incomplete recovery of AR after the longer exposures (30 and 60 minutes) to adenosine. The magnitude of this persistent antiadrenergic effect (PAE) of adenosine at 15 minutes of washout was proportional to the epicardial concentration of adenosine during infusion of the nucleoside. Infusion of adenosine either with the nonselective adenosine receptor antagonist 8- p -sulfophenyl theophylline or with the selective A 1 -receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine, abolished the PAE during the washout period. In addition, the PAE could be demonstrated only with the selective A 1 -receptor agonist 2-chloro-N 6 -cyclopentyladenosine and not with the selective A 3 -receptor agonist 4-aminobenzyl-5′-N methylcarboxamido-adenosine. When the protein kinase C (PKC) inhibitor chelerythrine was coadministered with adenosine, the PAE of adenosine was not apparent during adenosine washout. A 30-minute infusion of phenylephrine, an α-adrenergic agonist that enhances PKC activity, produced a PAE that lasted for up to 30 minutes of washout. This effect was prevented by the coinfusion of chelerythrine. Thus, it is concluded that the PAE of adenosine is determined by the myocardial concentration of this nucleoside and is manifested when myocardial concentrations of adenosine returned to baseline levels. Moreover, a 5-minute duration of adenosine exposure is required for the expression of the PAE. This latter effect seems to be dependent on adenosine-induced PKC activation via A 1 -receptors.
In Defense of the Autopsy
Authors: Robert R. Wilson
Journal: JAMA (1966)

The "Symposium on the Autopsy"<sup>1-6</sup>prompted the presentation of the results of a study done in London, and reported verbally to the Royal Society of Medicine<sup>7</sup>but never actually printed. The writer was at that time concerned because the autopsy was in some influential quarters "out of fashion," as Bohrod<sup>4</sup>puts it. Indeed, one notable physician had said that he never learned anything at postmortem examination, except what the patient did not die of, and he really did not care whether a postmortem examination were done or not. From the autopsy's former position of preeminence, the pendulum had swung too far the other way. An attempt was therefore made to assess the usefulness of autopsies by doing a survery of a year's postmortem examinations and comparing the clinical diagnosis with the postmortem diagnosis. This impliesno disrespect to clinical colleagues. Medicine is one of the most difficult disciplines,