1,256 research outputs found
Biochemical markers and assessment of cardiotoxicity during preparative regimen and hematopoietic cell transplantation in acute leukemia
Introduction: Cardiotoxicity is a relatively frequent and potentially serious complication of antitumor treatment. Anthracyclines and other high-dose chemotherapy represent the greatest risk. The aim of the study was to assess cardiotoxicity during preparative regimen (PR) and hematopoietic cell transplantation (HCT) in acute leukemia (AL) with biochemical markers — “N-terminal pro brain natriuretic peptide” (NT-proBNP), cardiac troponin T (cTnT) and creatine kinase MB (CK-MB mass). Methods: Nineteen adult AL patients previously treated with anthracyclines — idarubicine, daunorubicine, mitoxantrone with standard doses for a cycle as 3 х 12 mg/m2, 3 х 50 mg/m2, 3 х 10 mg/m2 accordingly were studied. PR consisted of high-dose cyclophosphamide (HD-C) in combination with busulphan or total body irradiation (TBI). Plasma NT-proBNP, cTnT and CK-MB mass concentrations were measured the day before PR, the day after PR, the day after HCT and 14 days after HCT. Results: Before PR, mean plasma NT-proBNP value was 106.3 ± 55.7 ng/l. After PR, it increased to 426.1 ± 391.5 ng/l. After HCT, a further increase to 847.6 ± 780.6 ng/l was observed. Fourteen days after HCT, the mean NT-proBNP was 330.8±236.8 ng/l. The differences were statistically significant in comparison with the baseline values (p < 0.01). The NT-proBNP elevations were more pronounced in patients with cumulative doses (CD) of anthracyclines above 450 mg/m2 (p < 0.05), in patients with PR containing HD-C and TBI (p < 0.05). In all patients, plasma cTnT and CK-MB mass concentrations remained unchangable during PR and HCT. Conclusion: Our results suggest that administration of PR and HCT is in most AL patients associated with acute neurohumoral activation (significant rise in NT-proBNP). Persistent NT-proBNP elevations, in our study in 12 (63.2 %) patients, indicate subclinical cardiotoxicity (risk for development of heart failure) and require further follow-up. More pronounced NT-proBNP elevations in patients with higher CD of anthracyclines and in patients with PR containing combination of HD-C and TBI confirm that these therapeutic procedures seem to be more cardiotoxic and not very appropriate for patients with cumulation of risk factors for cardiotoxicity. Negative plasma cTnT and CK-MB mass concentrations show no detectable damage of cardiomyocyte structure during PR and HCT.Введение: кардиотоксические осложнения — это относительно частые и потенциально опасные последствия противоопухолевой
терапии. Наибольшую кардиотоксичность отмечают при применении высоких доз химиопрепаратов, в частности антибиотиков
антрациклинового ряда. Целью данного исследования была оценка кардиотоксичности при лекарственной подготовке пациентов
с острым лейкозом (ОЛ) и проведении им трансплантации гематопоэтических стволовых клеток (ГСК), а также определение
следующих биохимических маркеров – N-терминального промозгового натрийуретического пептида (NT-proBNP), сердечного
тропонина T (cTnT) и креатинкиназы MB (CK-MB). Методы: обследованы 19 взрослых пациентов с ОЛ, прошедших предварительное
лечение (ПЛ) с применением антрациклиновых антибиотиков (АА) – идарубицина, даунорубицина, митотриксантрона в дозах 3
х 12 мг/м2
, 3 х 50 мг/м2
, 3 х 10 мг/м2
соответственно. Кроме применения АА, ПЛ включало высокие дозы циклофосфамида
(ВД-Ц) в сочетании с бусульфаном или радиолучевой терапией (РЛТ). Концентрацию NT-proBNP, cTnT и CK-MB определяли
в плазме крови за день до и через день после проведения ПЛ, а также за день до и через 14 дней после трансплантации ГСК.
Результаты: уровень NT-proBNP перед проведением ПЛ составил 106,3 ± 55,7 нг/л, а после повышался до 426,1 ± 391,5 нг/л.
После трансплантации ГСК отмечали дальнейшее возрастание исследуемого показателя до 847,6 ± 780,6 нг/л. Через 14 дней
после трансплантации ГСК концентрация NT-proBNP достигла 330,8 ± 236,8 нг/л, при этом разница была статистически
достоверна по сравнению с исходными значениями (p < 0,01). Повышение уровня NT-proBNP в плазме крови более выражено
у пациентов, получавших АА в суммарной дозе (СД) выше 450 мг/м2
(p < 0,05), а также у больных, получавших ВД-Ц и РЛТ (p
< 0,05). Концентрация cTnT и CK-MB при проведении ПЛ и трансплантации ГСК не изменялась по отношению к исходному
уровню. Выводы: показано, что применение ПЛ и трансплантация ГСК у большинства пациентов с ОЛ сопровождается острой
нейрогуморальной активацией, что проявлялось в существенном повышении уровня NT-proBNP. Постоянно высокий уровень NTproBNP,
отмеченный у 12 (63,2%) пациентов, свидетельствует о бессимптомной кардиотоксичности (риске развития сердечной
недостаточности) и требует последующего врачебного наблюдения больных. Более выраженное повышение уровня NT-proBNP
у пациентов с более высокой СД АА и у больных, получавших ВД-Ц и РЛТ, свидетельствует о том, что такое лечение является
более кардиотоксичным и не рекомендовано для применения в случае наличия факторов риска проявления кардиотоксичности
Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia
To assess cardiac toxicity of anthracycline treatment with six biomarkers of cardiac injury: myoglobin, creatine kinase MB (CK-MB mass), cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), glycogen phosphorylase BB (GPBB). Methods: We evaluated anthracycline-induced cardiotoxicity in 12 acute myeloid leukemia patients (mean age 51.3 ± 10.7 years, 7 females). All biomarkers were measured at the baseline, after first chemotherapy (CT) with anthracyclines, after last CT with anthracyclines (total cumulative dose 479.8 ± 106.2 mg/m2) and 6 months thereafter. Values above the reference range were considered elevated. Results: GPBB increased above the cut-off (7.30 µg/L) in 2 (16.7%) patients after first CT, in 3 (25.0%) patients after last CT and remained elevated in 2 (16.7%) patients within 6 months after CT. CTnI became elevated (above 0.40 µg/L) in 1 (8.3%) patient after first and last CT and within 6 months after CT. CTnT remained negative (below 0.01 µg/L) during CT in all patients. Six months after CT, delayed cTnT positivity was found in 1 (8.3%) patient. All patients with cTnI or cTnT positivity had elevated GPBB. Other biomarkers (myoglobin, CK-MB mass, H-FABP) remained within the reference range in all patients. Conclusion: Our preliminary results suggest that GPBB could be a new promising marker for detection of anthracycline-related cardiotoxicity and probably superior to cardiac troponins. The predictive value for development of cardiomyopathy in the future is not clear and will be evaluated during a prospective follow-up.Цель: провести оценку кардиотоксичности, вызываемой антрациклином, с помощью ряда биомаркеров поражения сердца:
миоглобина, креатин-киназы MB (CK-MB mass), кардиального тропонина T (cTnT), кардиального тропонина I (cTnI),
белка, связывающего жирные кислоты (H-FABP), и гликогенфосфорилазы BB (GPBB). Методы: оценку кардиотоксичности
проводили у 12 больных острой миелоидной лейкемией (средний возраст — 51,3 ± 10,7 года, 7 женщин). Измерены
начальные показатели всех биомаркеров, а также таковые после проведения первой и последней химиотерапии (ХT) антрациклинами
(общая накопленная доза — 479,8 ± 106,2 мг/м2
) и через 6 мес после завершения терапии. Значения выше
начальных рассматривали как повышенные. Результаты: уровень GPBB превысил норму (7,30 µg/L) у 2 больных (16,7%)
после первой ХT, у 3 (25,0%) — после последней ХT и оставался повышенным у 2 больных (16,7%) и через 6 мес после ХT.
Уровень CTnI повысился (более 0,40 µg/L) у 1 больного (8,3%) после первой и последней ХT, а также и через 6 мес после
ХT. Значения CTnT оставались в пределах нормы (ниже 0,01 µg/L) во время проведения CT у всех пациентов. Через 6 мес
после ХT отдаленная положительная реакция на cTnT выявлена у 1 больного (8,3%). У всех пациентов с положительными
cTnI или cTnT установлен повышенный уровень GPBB. Другие биомаркеры (миоглобин, CK-MB, H-FABP) оставались в
пределах нормы у всех больных. Выводы: предварительные результаты, полученные в данном исследовании, позволяют
предположить, что GPBB можно рассматривать как новый перспективный маркер для выявления кардиотоксичности,
вызванной антрациклинами, и, возможно, превосходит предложенные ранее тропонины. Возможная прогностическая
ценность этого маркера при развитии кардиомиопатии пока не установлена
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia
Aim: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD-CT) with multiple biomarkers of cardiac injury — glycogen phosphorylase BB (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT, cTnI), creatine kinase MB (CK-MB mass), myoglobin. Methods: A total of 47 adult acute leukemia patients were studied — 24 patients treated with conventional CT containing anthracyclines (ANT) and 23 patients treated with HD-CT (myeloablative preparative regimen) followed by hematopoietic cell transplantation (HCT). Cardiac biomarkers were assessed prior to treatment (before CT/HD-CT), after first CT with ANT, after last CT with ANT in the first group, after HD-CT and after HCT in the second group. Values above the reference range were considered elevated. Results: Before CT/HD-CT, all biomarkers of cardiac injury were below the cut-offs in all patients. GPBB increased above the cut-off (7.30 μg/L) in 4 (16.7%) patients after first CT and in 5 (20.8%) patients after last CT with ANT. GPBB increased above the cut-off in 5 (21.7%) patients after HD-CT and remained elevated in 5 (21.7%) patients after HCT. CTnI became elevated (above 0.40 μg/L) in 2 (8.3%) patients after first and last CT with ANT. Both patients with cTnI positivity had elevated GPBB. Other tested biomarkers remained below the cut-offs during the study. Conclusion: Our results suggest that GPBB could become a sensitive biomarker for detection of acute cardiotoxicity associated with conventional CT containing ANT and HD-CT followed by HCT. The predictive value for development of cardiomyopathy in the future is not known and should be evaluated during a prospective follow-up. Based on our data, a larger prospective and multicenter study would be most desirable to define the potential role of new circulating biomarkers in the assessment of cardiotoxicity in oncology
Metadata and Buckets in the Smart Object, Dumb Archive (SODA) Model
We present the Smart Object, Dumb Archive (SODA) model for digital libraries (DLs), and discuss the role of metadata in SODA. The premise of the SODA model is to push down many of the functionalities generally associated with archives into the data objects themselves. Thus the data objects become smarter , and the archives dumber . In the SODA model, archives become primarily set managers, and the objects themselves negotiate and handle presentation, enforce terms and conditions, and perform data content management. Buckets are our implementation of smart objects, and da is our reference implementation for dumb archives. We also present our approach to metadata translation for buckets
Pseudogap effects induced by resonant pair scattering
We demonstrate how resonant pair scattering of correlated electrons above T_c
can give rise to pseudogap behavior. This resonance in the scattering T-matrix
appears for superconducting interactions of intermediate strength, within the
framework of a simple fermionic model. It is associated with a splitting of the
single peak in the spectral function into a pair of peaks separated by an
energy gap. Our physical picture is contrasted with that derived from other
T-matrix schemes, with superconducting fluctuation effects, and with preformed
pair (boson-fermion) models. Implications for photoemission and tunneling
experiments in the cuprates are discussed.Comment: REVTeX3.0; 4 pages, 4 EPS figures (included
Experimental Metrics for Identifying Origins of Combustion Variability during Spark-Assisted Compression Ignition
Spark-assisted compression ignition, SACI, can be used to control the combustion phasing of compression-ignition gasoline engines. However, implementation of this technique can be confounded by cyclic variability. The purpose of this paper is to define experimental metrics that describe the SACI process and to demonstrate the use of these metrics for identifying the source(s) of cyclic variability during the SACI process. This study focused on a light load condition (7 mg/cycle, 200 kPa i.m.e.p.), where spray-guided direct fuel injection with spark ignition and an exhaust-rebreathing strategy was employed to achieve flame propagation, which led to compression ignition. This study employed a combination of measurements including pressure-based heat-release analysis, spark-discharge voltage/current measurements, and cycle-resolved combustion imaging. Based on these measurements, four distinct combustion periods were identified; namely, the spark discharge, the early kernel growth (EKG), flame propagation, and the compression ignition periods. Metrics were defined to characterize each period and used to identify the contribution of each period to the cyclic variability of the main heat release. For the light load condition studied here, the EKG period had the largest effect on the crank angle (CA) position of 50 per cent mass burned, CA50. The spark-discharge event may affect CA50 indirectly through its influence on EKG. However, this could not be definitively assessed here since the camera was incapable of recording both the spark-discharge event and the flame images during cycles of the same tests.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86770/1/Sick18.pd
Superconducting transitions from the pseudogap state: d-wave symmetry, lattice, and low-dimensional effects
We investigate the behavior of the superconducting transition temperature
within a previously developed BCS-Bose Einstein crossover picture. This
picture, based on a decoupling scheme of Kadanoff and Martin, further extended
by Patton, can be used to derive a simple form for the superconducting
transition temperature in the presence of a pseudogap. We extend previous work
which addressed the case of s-wave pairing in jellium, to explore the solutions
for T_c as a function of variable coupling in more physically relevant
situations. We thereby ascertain the effects of reduced dimensionality,
periodic lattices and a d-wave pairing interaction. Implications for the
cuprate superconductors are discussed.Comment: REVTeX, 11 pages, 6 EPS figures included, Replace with published
versio
Coulomb Correlations and Pseudo-gap Effects in a Pre-formed Pair Model for the Cuprates
We extend previous work on pre-formed pair models of superconductivity to
incorporate Coulomb correlation effects. For neutral systems, these models have
provided a useful scheme which interpolates between BCS and Bose Einstein
condensation with increasing coupling and thereby describes some aspects of
pseudo-gap phenomena. However, charge fluctuations (via the plasmon,
) significantly modify the collective modes and therefore the
interpolation behavior. We discuss the resulting behavior of the pseudo-gap and
thermodynamic quantities such as , and as a function of
.Comment: 4 pages RevTeX, 3 ps figures included (Submitted to Physical Review B
August 27, 1996
Magnetic Field Effects in the Pseudogap Phase: A Competing Energy Gap Scenario for Precursor Superconductivity
We study the sensitivity of T_c and T^* to low fields, H, within the
pseudogap state using a BCS-based approach extended to arbitrary coupling. We
find that T^* and T_c, which are of the same superconducting origin, have very
different H dependences. This is due to the pseudogap, \Delta_{pg}, which is
present at the latter, but not former temperature. Our results for the
coherence length \xi fit well with existing experiments.We predict that very
near the insulator \xi will rapidly increase.Comment: 4 pages, 4 figures, RevTe
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