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991.
Simpson ML Goldenberg NA Jacobson LJ Bombardier CG Hathaway WE Manco-Johnson MJ 《Thrombosis research》2011,127(4):317-323
Introduction
Thrombin and plasmin are the key enzymes involved in coagulation and fibrinolysis, respectively. Plasma coagulative and fibrinolytic potentials in normal children and adults, and in representative pathologically altered hemostatic states, were evaluated via simultaneous assessment of thrombin and plasmin generation.Materials and Methods
An assay of Simultaneous Thrombin and Plasmin generation (STP) was developed to measure thrombin and plasmin in plasma using individual fluorometric substrates. Coagulation is initiated with dilute tissue factor, phospholipid, and calcium in platelet-poor plasma; fibrinolysis is accelerated via tissue plasminogen activator (tPA). Abnormal states of hemostasis were investigated.Results
STP assay reproducibility and normal adult and pediatric values for measured and calculated parameters have been established. Onset of both thrombin and plasmin generation was significantly delayed in children relative to adults (p < 0.001) and the maximum amplitudes of thrombin and plasmin generation were less in children than adults (p < 0.01). No significant differences were measured among pediatric age groups. The most profound impairments in thrombin generation were observed for extrinsic and common pathway factor deficiencies, with the exception of afibrinogenemia. Plasmin generation was severely impaired in deficiencies of fibrinogen and plasminogen as well as with decreased tPA reagent concentration and addition of aminocaproic acid. Plasmin generation was greatly enhanced by alpha-2-antiplasmin deficiency and excess tPA reagent.Conclusion
Simultaneous assessment of thrombin and plasmin generation in plasma shows promise for affording an enhanced understanding of overall coagulative and fibrinolytic functions in physiological and pathologically altered states of hemostasis in children and adults. 相似文献992.
The asymmetry of the spectral distribution of ultrasonic Doppler flow velocity signals, assessed using the coefficient of
skewness, is discussed as a criterion of stenosis differentiation. Its performance is compared with that of the index of turbulence
intensity for both in vitro and in vivo flow Doppler signals, recorded distal to a stenosis. The power spectral distributions
are computed using the direct Fourier transform and maximum likelihood method. The asymmetry of spectral distribution has
proved to be a more efficient criterion than the turbulence intensity. The maximum likelihood method ensures better stenosis
differentiation than the direct FFT method. 相似文献
993.
Hiroshi OGISHIMA Satoshi ITO Akito TSUTSUMI Makoto SUGIHARA Daisuke GOTO Isao MATSUMOTO Mana OBATA‐YASUOKA Hiromi HAMADA Hiroyuki YOSHIKAWA Hideto TAKAHASHI Atsuko MURASHIMA Takayuki SUMIDA 《International journal of rheumatic diseases》2010,13(3):e32-e35
A case of a 37‐year‐old pregnant patient with antiphospholipid syndrome (APS), who has a medical history of both thrombosis and recurrent fetal loss, is presented. She was treated with predonisolone and fixed‐dose unfractionated heparin (UFH) infusion, followed by plasmaphereses and fixed‐dose low‐molecular‐weight heparin infusion during her fourth pregnancy. Unfortunately, this treatment did not have beneficial effects, resulting in intrauterine growth restriction and finally neonatal death. Continuous intravenous UFH infusion and low‐dose aspirin were administrated under the monitoring of the activated partial thromboplastin time to achieve a target level of 120 s during her fifth pregnancy. A healthy baby weighing 1818 g at birth was delivered by Cesarean section at the 34th week of pregnancy. High‐dose UFH infusion may be considered to be one of the preferable options to manage pregnant patients with refractory APS. 相似文献
994.
Morio T Atsuta Y Tomizawa D Nagamura-Inoue T Kato K Ariga T Kawa K Koike K Tauchi H Kajiwara M Hara T Kato S;Japanese Cord Blood Bank Network 《British journal of haematology》2011,154(3):363-372
We report the results of umbilical cord blood transplantation (UCBT) performed in 88 patients with primary immunodeficiency (PID) between 1998 and 2008 in Japan; severe combined immunodeficiency (SCID, n = 40), Wiskott-Aldrich syndrome (WAS, n = 23), chronic granulomatous disease (n = 7), severe congenital neutropaenia (SCN, n = 5) and other immunodeficiencies (n = 13). Five-year overall survival (5-year OS) for all patients was 69% [95% confidence interval (CI), 57-78%], and was 71% and 82% for SCID and WAS, respectively. The main cause of death before day 100 was infection (17/19), while that after day 100 was graft-versus-host disease (GVHD) (5/7). Using multivariate analyses, pre-transplant infection, no conditioning, ≥ 2 human leucocyte antigen (HLA) mismatches or diagnosis other than SCID, SCN or WAS were all associated with poor prognosis. Reduced-intensity conditioning was associated with decreased overall mortality compared with myeloablative therapy. The cumulative incidence of grade 2-4 acute GVHD at day 100 was 28% (95% CI, 19-38%), and that of chronic GVHD at day 180 was 13% (95% CI, 7-23%). We conclude that UCBT should be considered for PID patients without an HLA-matched sibling. The control of pre-transplant infection and selection of HLA-matched donors will lead to a better outcome. 相似文献
995.
Mario Kasner Aleksandar S. Aleksandrov Dirk Westermann Dirk Lassner Michael Gross Stephan von Haehling Stefan D. Anker Heinz-Peter Schultheiss Carsten Tschöpe 《International journal of cardiology》2013
Background
Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure–volume loop analysis in HFPEF.Methods
26 HFPEF patients who showed an increase in LV stiffness by pressure–volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin < 100 μg/l or ferritin of 100–299 μg/l in combination with transferrin saturation < 20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies.Results
Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p < 0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r = − 0.636, p < 0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency.Conclusion
In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID. 相似文献996.
l. a. houghton f. cremonini † m. camilleri † i. busciglio † c. fell v. cox d. h. alpers ‡ o. e. dewit § g. e. dukes § e. gray § r. lea a. r. zinsmeister ¶ & p. j. whorwell 《Neurogastroenterology and motility》2007,19(9):732-743
Visceral hypersensitivity is important in the pathophysiology of irritable bowel syndrome and thus a target for modulation in drug development. Neurokinin (NK) receptors, including NK(3) receptors, are expressed in the motor and sensory systems of the digestive tract. The aim of this study was to compare the effects of two different doses (25 and 100 mg) of the NK(3) receptor antagonist, talnetant (SB223412) with placebo on rectal sensory function and compliance in healthy volunteers studied at two centres. Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days. Studies were performed on three occasions: day 1 immediately prior to 1st dose, day 1 4 h postdose, and after 14- to17-day therapy. Compliance, and pressure thresholds for first sensation, urgency, discomfort and pain were measured using ascending method of limits, and sensory intensity ratings for gas, urgency, discomfort and pain determined during four random phasic distensions (12, 24, 36 and 48 mmHg). Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo. In general, the results obtained at the two centres differed minimally, with intensity scores at one centre consistently somewhat lower. At the doses tested, talnetant has no effect on rectal compliance or distension-induced rectal sensation in healthy participants. 相似文献
997.
Standardized volume-rendering of contrast-enhanced renal magnetic resonance angiography 总被引:1,自引:0,他引:1
Smedby O Oberg R Asberg B Stenström H Eriksson P 《Acta radiologica (Stockholm, Sweden : 1987)》2005,46(5):497-504
Purpose: To propose a technique for standardizing volume-rendering technique (VRT) protocols and to compare this with maximum intensity projection (MIP) in regard to image quality and diagnostic confidence in stenosis diagnosis with magnetic resonance angiography (MRA).
Material and Methods: Twenty patients were examined with MRA under suspicion of renal artery stenosis. Using the histogram function in the volume-rendering software, the 95th and 99th percentiles of the 3D data set were identified and used to define the VRT transfer function. Two radiologists assessed the stenosis pathology and image quality from rotational sequences of MIP and VRT images.
Results: Good overall agreement (mean κ = 0.72) was found between MIP and VRT diagnoses. The agreement between MIP and VRT was considerably better than that between observers (mean κ = 0.43). One of the observers judged VRT images as having higher image quality than MIP images.
Conclusion: Presenting renal MRA images with VRT gave results in good agreement with MIP. With VRT protocols defined from the histogram of the image, the lack of an absolute gray scale in MRI need not be a major problem. 相似文献
Material and Methods: Twenty patients were examined with MRA under suspicion of renal artery stenosis. Using the histogram function in the volume-rendering software, the 95th and 99th percentiles of the 3D data set were identified and used to define the VRT transfer function. Two radiologists assessed the stenosis pathology and image quality from rotational sequences of MIP and VRT images.
Results: Good overall agreement (mean κ = 0.72) was found between MIP and VRT diagnoses. The agreement between MIP and VRT was considerably better than that between observers (mean κ = 0.43). One of the observers judged VRT images as having higher image quality than MIP images.
Conclusion: Presenting renal MRA images with VRT gave results in good agreement with MIP. With VRT protocols defined from the histogram of the image, the lack of an absolute gray scale in MRI need not be a major problem. 相似文献
998.
Rahul Ladwa Timothy Kalas Shivanshan Pathmanathan Natasha Woodward David Wyld Jasotha Sanmugarajah 《Clinical breast cancer》2018,18(5):e1181-e1187
Introduction
Maintaining the relative dose intensity (RDI) of adjuvant chemotherapy at ≥ 85% has been associated with improved treatment outcomes in early-stage breast cancer (ESBC). Increasing evidence has suggested that patients aged ≥ 65 years can maintain the optimal RDI for standard chemotherapy regimens. The present study investigated the RDI of newer adjuvant chemotherapy regimens in this demographic.Patients and Methods
We retrospectively analyzed the data from 281 patients aged ≥ 65 years with a diagnosis of ESBC who had received adjuvant chemotherapy across 3 sites in Queensland, Australia from 2010 to 2015. The primary endpoint was the proportion of patients who had received an RDI of ≥ 85%.Results
The median age at diagnosis was 68 years (range, 65-85 years), with 36.3% aged > 70 years. The patient characteristics included tumor stage T3 or T4 in 17% and node-positive disease in 60%. The common chemotherapy regimens included docetaxel/cyclophosphamide (23%), 5-fluorouracil/epirubicin/cyclophosphamide plus docetaxel or paclitaxel (17%); Adriamycin/cyclophosphamide/weekly paclitaxel (38%); and docetaxel/carboplatin/trastuzumab (11%). Primary (15%) and secondary (54%) granulocyte colony-stimulating factor (G-CSF) was used. An RDI of ≥ 85% was achieved in 63% of the patients. Significant associations were noted between a reduced RDI and age ≥ 70 years (P < .001), Charlson comorbidity index ≥ 1 (P = .043), initial dose reductions (P = .01), secondary G-CSF use (P = .45), hospital admission (P < .001), and febrile neutropenia (P = .007). Treatment-related toxicities were the most common reason for noncompletion, with high rates of hospital admissions (46%) and febrile neutropenia (22%).Conclusion
Our findings suggest that patients aged ≥ 65 years with ESBC can maintain an optimal RDI with modern chemotherapy regimens. Appropriate geriatric assessment and the use of supportive measures such as G-CSF could better assist select groups to maintain an optimal dose intensity. 相似文献999.
《Diagnostic and interventional imaging》2020,101(6):335-345
This article was designed to provide a pediatric cardiac computed tomography angiography (CCTA) expert panel consensus based on opinions of experts of the Société Française d’Imagerie Cardiaque et Vasculaire diagnostique et interventionnelle (SFICV) and of the Filiale de Cardiologie Pédiatrique Congénitale (FCPC). This expert panel consensus includes recommendations for indications, patient preparation, CTA radiation dose reduction techniques, and post-processing techniques. The consensus was based on data from available literature (original papers, reviews and guidelines) and on opinions of a group of specialists with extensive experience in the use of CT imaging in congenital heart disease. In order to reach high potential and avoid pitfalls, CCTA in children with congenital heart disease requires training and experience. Moreover, pediatric cardiac CCTA protocols should be standardized to acquire optimal images in this population with the lowest radiation dose possible to prevent unnecessary radiation exposure. We also provided a suggested structured report and a list of acquisition protocols and technical parameters in relation to specific vendors. 相似文献
1000.
《Vaccine》2021,39(45):6601-6613
AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain. 相似文献