离子型对比剂与非离子型对比剂在螺旋CT增强中的对比研究

目的通过对比研究离子型对比剂与非离子型对比剂在螺旋CT增强扫描中的应用,探讨离子型对比剂临床应用的安全性,以最好的效价比选择对比剂。方法分别观察离子型对比剂泛影葡胺(60%)106例、非离子型对比剂碘海醇(300mg/ml)120例的螺旋CT增强扫描,比较其不良反应发生率和图像增强效果。结果泛影葡胺(60%)、碘海醇(300mg/ml)均未发生严重不良反应。轻、中度不良反应发生率分别为5.7%、1.7%。二者之间无统计学意义(P>0.05)。泛影葡胺(60%)、碘海醇(300mg/ml)所获图像质量均能达到诊断要求,二者之间无统计学意义(P>0.05)。结论离子型对比剂泛影葡胺(60%)在应用于非高危人群时,是相对安全的,能有效降低检查费用。     

The ionic contrast medium ioxaglate interferes with thrombin-mediated feedback activation of factor V, factor VIII and platelets

Summary.  Clinical observation shows that radiographic contrast media (CM) may influence thrombus formation. In the search for the underlying mechanism, we have shown that the ionic CM ioxaglate is a potent inhibitor of thrombin generation in platelet-poor and platelet-rich plasma, whereas the influence of the non-ionic contrast medium iodixanol is minimal. Ioxaglate boosts the inhibitory effect of the platelet GPIIb/IIIa antagonist abciximab and the effects of ioxaglate and heparin are additive. Ioxaglate inhibits the clotting of fibrinogen and the activation of factors V and VIII, and of platelets by thrombin. It does not inhibit hydrolysis of small chromogenic thrombin substrates, nor does it influence the heparin-catalyzed inactivation of thrombin by antithrombin. We assume therefore that ioxaglate interferes with the binding of macromolecular substrates to the anionic exosite I of thrombin. The biological correlation to the observed antithrombotic effect of ioxaglate is then to be found in the inhibition of thrombin generation via inhibition of thrombin-mediated feedback activations.     

Morphological, biochemical, and functional changes in human platelets subjected to shear stress.

Thromboembolic complications associated with cardiovascular prostheses are thought to result from activation of coagulation factors or platelets by surface contact and/or by certain physical forces generated at the interface between the foreign material and blood. Studies of the effects on human platelets of one of these physical forces, shear stress, were made. A rotational viscometer was used to apply graded levels of shear stress to platelet-rich plasma. Very low shear stress (50 dynes per square centimeter) resulted in the liberation of small amounts of ATP, ADP, and serotonin and subsequent platelet aggregation. Stresses of 100 dynes per square centimeter or more resulted in the appearance in plasma of nonstorage nucleotides, indicating cell lysis, and shear stresses of 250 dynes per square centimeter or more resulted in the fragmentation of platelets. Shear-induced platelet aggregation was partially reversible but only those samples subjected to low levels of shear stress recovered their ability to aggregate to the subsequent addition of ADP. These studies indicate that platelets are extremely sensitive to shear stress and raise the possibility that thrombus formation and/or accelerated platelet turnover in patients with rheumatic valvular disease or who possess artificial heart valves or other cardiac prosthetic devices could result from the effects of this physical force on circulating platelets.     

A new macromolecular paramagnetic MR contrast agent binds to activated human platelets

A new functionalized macromolecular magnetic resonance (MR) contrast agent has been developed from a carboxymethyldextran‐Gd(DOTA) devoid of biospecificity. The functionalized contrast agent was synthesized in order to mimic PSGL‐1, the main ligand of P‐selectin, a glycoprotein mainly expressed on the surface of activated platelets. The starting compound, CM1, was first carboxymethylated by monochloroacetic acid leading to a series of 10 derivatives varying in their carboxymethyl content. CM8 derivative, with a degree of substitution in carboxymethyl of 0.84, was chosen for subsequent fluorolabeling and sulfation to give CM8FS. CM8FS has an average number molecular weight of 27 000 ± 500 g/mol, a hydrodynamic radius of 5.7 ± 0.2 nm and a high relaxivity (r₁ = 11.2/mM (Gd)/s at 60 MHz). Flow cytometry experiments on whole human blood or on isolated platelets evidenced in vitro a preferential binding of CM8FS on TRAP‐activated human platelets. Interestingly, CM8FS did not bind to other blood cells or to resting platelets. Pellets of TRAP‐activated human platelets have also been imaged in tubes with a 1.5 T MR imager. A MR signal was observed for activated platelets incubated with CM8FS. Altogether, these in vitro results evidenced the recognition of activated human platelets by a fluorescent paramagnetic contrast agent grafted with carboxyl and sulfate groups. This biomimetic approach associated with the versatile macromolecular platform appears promising for the development of new contrast agents for molecular imaging of activated platelets in cardiovascular diseases such as atherosclerosis and aneurysms. Copyright © 2007 John Wiley & Sons, Ltd.     

Morphological and functional abnormalities pattern in hypertrophy-free HCM mutation carriers detected with echocardiography

To evaluate if morphological or functional abnormalities could be detected with echocardiography in hypertrophic myocardiopathy (HCM) mutation carriers without left ventricle (LV) hypertrophy has developed. HCM is caused by extensive genes mutations found in two-third of patients. Because screening for carriership of a large population is unreasonable, identification of asymptomatic subjects is confined to the use of imaging such as echocardiography, by which subtle abnormalities can be detected. Comprehensive echocardiographic studies including morphological and functional assessment were performed. Asymptomatic HCM mutation carriers without hypertrophy (Phe?/Gen+, n?=?14), and HCM patients (Phe+/Gen+, n?=?17) were compared with healthy control subjects (n?=?32) in a prospective design. Compared to controls, septum thickness was significantly higher with an elongated mitral valve in both groups. Thickened LV muscular band (LVMB) are more likely found in Phe?/Gen+ and Phe+/Gen+. The thickness of LVMB was higher in the Phe?/Gen+ versus controls. A LVMB thickness ≥3.6 mm was associated with HCM mutation carriership (sensitivity: 76.9?%, specificity: 94.1?%). The regional strain was significantly impaired in the basal segments of the septum in the Phe?/Gen+. The GLS was significantly impaired in the Phe+/Gen+ (?16.4?%?±?2.9 vs. ?21.4?%?±?2.3 in control subjects, p?=?0.01). Mitral A wave velocity, septal E/e′, averaged E/e′ were increased in both groups. E/A ratio was significantly lower in Phe+/Gen+. Morphological and functional abnormalities in hypertrophy-free HCM mutation carriers could be detected with echocardiography. Anomalous thickened LVMB could be representing a morphological marker for the HCM disease without overt hypertrophy has developed or in patients with an ambiguous diagnosis.     

In vitro studies on the development of a high-density contrast medium for double contrast of the colon

Investigations with an electron microscope and phantom imaging studies showed, that from micro-particle barium sulphate a high-density contrast medium can be produced for double-contrast-investigations of the colon. As stabilizing agent a substance with the same physical and chemical action as 0.6 g CMC (Sodium-Carboxy-Methyl-Cellulose) per 100 g barium sulphate should be used. With a second stabilizer, having the same effect as mixed pectin, the thickness of the contrast film can be modified, while the flow time of the contrast medium remains constant. Flow curves lead to the conclusion, that a maximum concentration of 140 GV% can be used for patients. The measurement of density and flow time of the suspension allow to check the high density and low viscosity requirements. The density of the barium sulphates used for investigation was 4,000 g/l.     

强直性脊柱炎96例心理健康状况调查与心理干预

目的：探讨强直性脊柱炎患者的心理健康状况及心理干预的效果。方法：采用焦虑自评量表（SAS）和抑郁自评量表（SDS）对96例强直性脊柱炎患者进行心理问卷调查，根据患者存在的焦虑、抑郁心理问题实施心理干预2周，再次进行SAS和SDS自评量表评分。结果：本组心理干预前SAS、SDS评分较国内常模高，两组比较有极显著性差异（P〈0．01）；干预后患者SAS、SDS评分较干预前低，两组比较有极显著性差异（P〈0．01）。结论：强直性脊柱炎患者存在明显的焦虑、抑郁心理，实施心理干预后患者焦虑、抑郁心理有明显改善。     

Effects of ionic and nonionic radiographic contrast agents on endothelial cells in vitro.

Intravenous administration of radiographic contrast agents results in the occasional occurrence of thrombotic complications, which are more common after the use of ionic agents than nonionic agents. To investigate the pathophysiologic basis of this thrombotic tendency, we compared the effects of ionic and nonionic contrast agents on endothelial cells in vitro. Exposure of cultured human umbilical vein endothelial cells to ionic contrast medium for 10 minutes resulted in lifting of 76% +/- 8% of cells, significantly greater than that after exposure to nonionic medium (6% +/- 4%; p less than 0.005). A modified Baumgartner chamber was used to evaluate the effects of contrast agents on adhesion of platelets in anticoagulated whole blood to everted segments of fresh or stored deendothelialized rabbit aorta segments. Exposure of fresh vessels to ionic contrast medium led to a significant increase in platelet adhesion (31% +/- 7%; p less than .01), whereas the increase was smaller after exposure to nonionic contrast medium (25% +/- 3%). Platelet adhesion to stored vessels (41% +/- 4%) was significantly greater than adhesion to fresh aorta segments (15% +/- 2%; p less than 0.001), and contrast agents did not further increase adhesion. Microscopic examination of perfused aorta segments exposed to ionic contrast medium showed platelet adherence to intact endothelial cells, a phenomenon that did not occur without prior exposure of fresh aorta segments to ionic contrast medium. These findings demonstrate that exposure of endothelial cells to ionic contrast medium results in marked changes in cell viability and adhesive properties that may contribute to their thrombotic potential.     

Buffy coat-derived platelets cryopreserved using a new method: Results from in vitro studies

Cryopreservation for the long-term storage of platelets (PLTs) is a useful method to overcome the limits of platelet shortage. This is an in vitro prospective study to evaluate the count, viability, and function of buffy coat-derived pooled platelet concentrates (BC-PLTs), treated with dimethyl sulphoxide (DMSO) and cryopreserved (CRY BC-PLTs) at ?80?°C with a modified Valeri method. PLTs were stored in 6% DMSO with a patented kit. Overall, 49 BC-PLTs from 245 healthy volunteer donors were prepared, cryopreserved, and analysed before and after 3, 6, and 9?months of storage. In flow cytometry, a statistically significant reduction in CD 42b (92.7?±?4.29% at T0 vs. 23.6?±?27.5% at T3, 16.38?±?12.54% at T6, and 17.3?±?9.6% at T9) and PAC-1 (1.9?±?1.34% at T0 vs. 0.62?±?0.4% at T3, 0.63?±?0.83% at T6, and 0.49?±?0.48% at T9) was observed after storage. CRY BC-PLTs showed a good and stable endogenous thrombin generation potential (nM min): 529.25?±?98.64 at T0 vs. 533.04?±?103.15 at T9 months. CRY BC-PLTs showed a good viability in vitro, according to currently accepted criteria for cryopreserved PLTs.     

In vitro antibacterial properties of AT-2266, a new pyridonecarboxylic acid

AT-2266, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3 -carboxylic acid, is a new pyridonecarboxylic acid derivative with broad and potent antibacterial activity. It inhibited some gram-positive bacteria, such as staphylococci and Bacillus subtilis, and most gram-negative bacteria, including Serratia marcescens, Pseudomonas aeruginosa, Haemophilus influenzae, and Campylobacter jejuni, at concentrations of 0.1 to 0.78 microgram/ml, and most gram-positive bacteria, glucose-nonfermenters, and Mycoplasma pneumoniae at concentrations of 1.56 to 12.5 micrograms/ml. Most of the clinical isolates tested were as susceptible to AT-2266 as were laboratory strains. The antibacterial potency of AT-2266 was higher than those of pipemidic acid and nalidixic acid and similar to that of norfloxacin. AT-2266 was not cross-resistant with antibiotics and inhibited most highly nalidixic acid-resistant bacteria at concentrations of 1.56 to 3.13 micrograms/ml. Its activity was barely affected by the addition of horse serum or sodium cholate but weakened by lowering the medium pH or increasing the inoculum size. AT-2266 was bactericidal at concentrations near its minimal inhibitory concentrations. Frequencies of mutants resistant to 10 micrograms of AT-2266 per ml were lower than 4.0 x 10(-9).     

In vitro and in vivo quality of leukoreduced apheresis platelets stored in a new platelet additive solution

BACKGROUND: Platelets (PLTs) stored in additive solutions (PASs) may reduce the risk of several plasma‐associated adverse transfusion reactions such as allergic reactions and potentially transfusion‐associated lung injury. The objective of this study was to determine the in vitro characteristics and the in vivo radiolabeled recovery and survival of apheresis PLTs (APs) stored in a new PAS and compare the latter to Food and Drug Administration (FDA) criteria. STUDY DESIGN AND METHODS: Hyperconcentrated APs were collected from healthy subjects in a paired crossover study comparing PAS (35% plasma) and 100% plasma‐stored APs (Part 1) up to 7 days and, in Part 2, to determine the in vivo recovery and survival of PAS stored AP at 5 days compared to fresh PLT controls. In vitro and in vivo assays were performed following standard methods. RESULTS: Sixty‐six and 25 evaluable subjects successfully completed Parts 1 and 2, respectively. pH for PAS AP was maintained above 6.6 for 5 days of storage. P‐selectin values were consistent with published values for commonly transfused PLT products. The PAS in vivo PLT recovery (54.3 ± 8.1%) was 86.7% of the fresh control, and survival (6.4 ± 1.3 days) was 78.0% of the fresh control, both meeting the FDA performance criteria. CONCLUSION: APs stored in PAS with 35% plasma carryover maintained pH over 5 days of storage and met current FDA criteria for radiolabeled recovery and survival. The use of PAS for storage of single‐donor PLTs in clinical practice represents an acceptable transfusion product that reduces the volume of plasma associated with PLT transfusion.     

大鼠少突胶质前体细胞在化学条件培养基中定向分化的形态学观察

目的:观察体外无血清化学培养条件下少突胶质前体细胞向成熟少突胶质细胞的定向分化。方法:实验于2000-04/07在复旦大学上海医学院解剖学教研室完成。①取新生SD大鼠获取少突胶质前体细胞;前O2A祖细胞原代混合培养7d后,以B104神经胶质瘤细胞株条件培养液犤100mL含:牛血清白蛋白每20mg,胰岛素2.5mg,转铁蛋白20mg,腐胺1.6mg,亚硒酸钠0.5μg,黄体酮0.6μg,生物素0.24μg,T33μg,T40.04mg,溶于DMEM/F12对半配置的培养液中犦增殖并纯化的少突胶质前体细胞,然后将培养基更换为无血清的化学条件培养基。②倒置相差显微镜观察记录24,48和72h细胞的形态变化,分化成熟的少突胶质细胞作扫描电镜观察。结果:少突胶质前体细胞无血清化学条件培养基培养形态学演变:培养24h,少突胶质前体细胞突起增加为三极或四极,胞体增大稍迟;48h后突起明显增多,相互之间连接成网;72h,胞体大且边缘不规则,突起分支更加清晰,分支彼此呈三维立体交错,部分突起之间可见指环状或膜片状结构。结论:化学条件培养基可使在体外培养条件下的少突胶质前体细胞定向分化为成熟的少突胶质细胞,细胞形态呈现渐变的过程。     

大鼠少突胶质前体细胞在化学条件培养基中定向分化的形态学观察

目的：观察体外无血清化学培养条件下少突胶质前体细胞向成熟少突胶质细胞的定向分化。方法：实验于2000-04／07在复旦大学上海医学院解剖学教研室完成。①取新生SD大鼠获取少突胶质前体细胞；前O2A祖细胞原代混合培养7d后，以B104神经胶质瘤细胞株条件培养液f每100mL含：牛血清白蛋白20mg，胰岛素2．5mg，转铁蛋白20mg，腐胺1．6mg，亚硒酸钠0．5μg，黄体酮0．6μg，生物素0.24μg，T33μg，T40．04mg，溶于DMEM／F12对半配置的培养液中1增殖并纯化的少突胶质前体细胞，然后将培养基更换为无血清的化学条件培养基。②倒置相差显微镜观察记录24，48和72h细胞的形态变化，分化成熟的少突胶质细胞作扫描电镜观察。结果：少突胶质前体细胞无血清化学条件培养基培养形态学演变：培养24h，少突胶质前体细胞突起增加为三极或四极，胞体增大稍迟；48h后突起明显增多，相互之间连接成网；72h，胞体大且边缘不规则．突起分支更加清晰，分支彼此呈三维立体交错，部分突起之间可见指环状或膜片状结构。结论：化学条件培养基可使在体外培养条件下的少突胶质前体细胞定向分化为成熟的少突胶质细胞，细胞形态呈现渐变的过程。     

In vitro antibacterial activity of AM-715, a new nalidixic acid analog

AM-715 [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid] is a new nalidixic acid analog. AM-715 has a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria. The antibacterial activity of AM-715 was greater than those of pipemidic acid and nalidixic acid. AM-715 had higher antibacterial activity against Pseudomonas aeruginosa than did gentamicin. Most nalidixic acid-resistant bacteria were susceptible to AM-715, and cross-resistance was not observed between AM-715 and various antibiotics. The minimal concentration of AM-715 required to inhibit the growth of 75% of the total number of clinical isolates was as follows: Escherichia coli, 0.04 μg/ml; Klebsiella pneumoniae, 0.1 μg/ml; Serratia marcescens, 0.88 μg/ml; Enterobacter spp., 0.076 μg/ml; Staphylococcus aureus, 1.10 μg/ml; P. aeruginosa, 0.38 μg/ml; and nalidixic acid-resistant strains of gram-negative bacteria, 0.62 μg/ml. AM-715 at minimal inhibitory concentrations or at slightly higher concentrations had bactericidal activity against various species of bacteria. The effect of inoculum sizes on minimal inhibitory concentrations and minimal bactericidal concentrations of AM-715 against gram-negative bacteria was smaller than on those of pipemidic acid and nalidixic acid. The dose-response curve of AM-715 indicated a steep gradient, and the 50% inhibited doses of AM-715 were 0.014 μg/ml against E. coli ML4707 and 0.21 μg/ml against P. aeruginosa NC-5.     

Response of neonatal platelets to nitric oxide in vitro

OBJECTIVES: Several studies have demonstrated altered platelet function during nitric oxide inhalation (iNO) in adults and neonates. In vitro NO inhibits activation of fibrinogen receptor glycoprotein (GP) IIb/IIIa in a dose-dependent manner. In neonates GPIIb/IIIa response to stimulation is physiologically attenuated during the first days after birth in comparison to adults; the effects of NO on GPIIb/IIIa in neonates, however, are less established. We investigated the response of platelets from neonates, their mothers, and nonpregnant controls to the NO donor SIN-1 in vitro. DESIGN: Umbilical cord and venous (mother, controls) platelet-rich plasma was stimulated in vitro with 10 microM ADP or 0.05 U/ml thrombin in the presence or absence of 10 microM SIN-1. GPIIb/IIIa activation was determined by two-color flow cytometry. SETTING: Delivery department of an university hospital. PATIENTS AND PARTICIPANTS: Ten healthy term neonates, their mothers and nonpregnant controls. MEASUREMENTS AND RESULTS: NO significantly reduced GPIIb/IIIa activation in thrombin- and ADP-stimulated platelets in all groups (p < 0.001). Neonatal platelets were significantly hyporeactive to stimulation (p < 0.05), but the relative response to SIN-1 was similar in all three groups (70 +/- 5 %). CONCLUSIONS: The relative amount of NO-induced inhibition of GPIIb/ IIIa activation in neonates is thus similar to that of adults. However, due to the intrinsic hyporesponsiveness of neonatal platelets and NO-synergistic pharmacodynamic profiles of other drugs (e.g., prostacyclin), possible adverse effects of iNO must be considered.