Evaluation of left ventricular contractile performance from baseline stress-shortening data in humans: comparison with pharmacological afterload challenge

The purpose of this study was to evaluate whether the baseline stress-shortening data reflect the contractile state adequately and give results comparable to the evaluation of the end-systolic stress-shortening relationships using pharmacological manipulation of afterload. Five groups were studied (total 152 patients): a control group of 30 healthy volunteers, 32 patients after surgical correction of infantile tetralogy of Fallot, 50 patients treated for childhood malignancies with doxorubicin, 17 patients with left ventricular hypertrophy due to systemic hypertension, and 23 patients with congestive cardiomyopathy. In all patients except those with congestive cardiomyopathy, afterload was altered pharmacologically to evaluate the individual stress-shortening relationship. In all patients the baseline stress-shortening data were evaluated, as well as their relative positions to two predefined normal ranges for the relationship between end-systolic stress and shortening. Additionally, a slope value was calculated from the baseline data of the five groups studied and compared with the data obtained by pharmacological afterload increment. Our data show that the comparison of individual baseline data of end-systolic wall stress and fractional shortening with predefined normal ranges for the relationship between end-systolic stress and shortening is inadequate. The appropriate normal range to compare with is the 95% confidence interval of baseline stress-shortening data in normal subjects. Also the calculation of a slope value from the baseline stress-shortening data of a group of patients seems to be inappropriate. Such a slope value does not necessarily reflect the contractile state, as the specific conditions leading to variations of end-systolic wall stress are undefined and not standardized, and the correlation between baseline stress-shortening data depends largely on the influence of the end-systolic dimension on both parameters.     

Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells

Low density lipoprotein (LDL) has been found to represent a suitable carrier for cytotoxic drugs that may target them to cancer. This study investigated whether very low density lipoprotein (VLDL), LDL and high density lipoprotein (HDL) can be used to effectively incorporate four cytotoxic drugs, 5-fluorouracil (5-FU), 5-iododeoxyuridine (IUdR), doxorubicin (Dox) and vindesine; characterized the complexes; and examined the effect of incorporation on drug cytotoxicity against HeLa cervical and MCF-7 breast carcinoma cells. Significant drug loading was achieved into all three classes of lipoproteins, consistent with the sizes and hydrophobicity of the drugs. The relative loading efficiency was found to be vindesine>IUdR>Dox>5-FU for all three classes of lipoproteins. As shown by electron microscopy (EM), drug incorporation did not affect the size or morphology of the lipoproteins. Differential scanning calorimetry (DSC) showed that drug loading did not significantly change the thermal transition temperature of core lipids in the lipoproteins. The transition enthalpy was changed only for LDL–Dox and LDL–vindesine. The drugs remained stable in the lipoproteins as determined by high performance liquid chromatography (HPLC). EM, DSC and HPLC data suggest that drugs were incorporated into lipoproteins without disrupting their integrity and drugs remained in their stable forms inside lipoproteins. Compared with free drugs in cytotoxicity assays, the IC₅₀ values of LDL– and HDL–drug complexes were significantly lower (2.4- to 8.6-fold for LDL complexes and 2.5- to 23-fold for HDL complexes). All free or lipoprotein-bound drug formulations were comparably more cytotoxic against MCF-7 than HeLa cells. Upregulating the lipoprotein receptors enhanced, and downregulating them inhibited, the cytotoxicity, indicating the mechanistic involvement of lipoprotein receptor pathways. Complexes of all four drugs with VLDL, in contrast to LDL and HDL, had the same cytotoxicity as the four corresponding free drugs. Our results suggest that further studies are required of the potential of HDL to be a cancer targeting drug carrier.     

Photodynamic therapy of tumours: value of quantum chemical procedures for characterization of new drugs. Prediction of the electronic structure of zinc(II) phthalocyanine with special emphasis on triplet state excitation energies

Zinc(II) phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a high activity in photodynamic therapy in a variety of animal tumours. The photophysical properties of zinc(II) phthalocyanine have been studied in detail and compared to those of Photofrin, the only sensitizing agent approved so far for phase III/IV clinical trials. Since the efficacy of photodynamic therapy intrinsically depends on the spectroscopic features of the sensitizer, quantum chemical methods have proven to be an efficient means for optimizing chemical structures. As will be shown, a simple modification of the time-honoured INDO model of Pople allows a prediction of the singlet and triplet state properties of molecules of the size of zinc(II) phthalocyanine with an rms error of ≤ 1000 cm⁻¹.     

高能聚焦超声刀联合氟脲嘧啶、四氢叶酸治疗晚期胰腺癌临床疗效观察

目的探讨高能聚焦超声刀加氟脲嘧啶、四氢叶酸治疗晚期胰腺癌临床疗效及毒副作用。方法30例经病理学或细胞学确诊的晚期胰腺癌病人先用高能聚焦超声刀(HIFU)治疗，再予氟脲嘧啶、四氢叶酸联合化疗。氟脲嘧啶500mg／m^2加入5％GNS500ml静滴持续6小时以每天1次连用5天，CF(四氢叶酸)100mg／m^2加入生理盐水250ml静滴每天1次连用5天，28天为1周期，至少治疗2个周期。结果CR1例；PR9例；MR9例；NC5例；PD6例。总有效率63％。毒副作用主要消化道反应，其他副作用轻微。结论应用HIFU局部治疗胰腺癌同时合用四氢叶酸加氟脲嘧啶全身化疗近期疗效提高明显，止痛明显达75％，副反应小，值得应用。     

眼球孤立性脉络膜血管瘤的HR-MRI表现

目的　探讨眼球孤立性脉络膜血管瘤的高分辨率磁共振 (HR MRI)影像学特征 ,进一步提高诊断水平。资料与方法　回顾性分析诊断明确的孤立性脉络膜血管瘤 16例共计 17个病灶的位置、数目、形态、大小、MRI信号、强化情况、有无合并视网膜脱离及有无视神经和眼外侵犯等。所有病例均行HR MRI及增强扫描 ,部分病例行脂肪抑制。结果　 17个病灶中的 16个呈扁丘状位于眼球内壁的后极。 15个病灶厚度 <5mm ,平均厚度为2 .9mm。病灶边缘清晰 ,T1WI上呈轻度高信号者 16个 ,T2 WI上呈等信号者 15个 ,增强扫描显著强化者有 12个。 3例合并视网膜脱离 ,在T2 WI上多呈等信号 ,T1WI上呈轻度高信号者 ,均无强化。无视神经及眼外侵犯病例。结论　 94 %孤立性脉络膜血管瘤的HR MRI表现具有特征性 ,表现为位于眼球内壁后极的较小、基底较宽、边缘清晰的扁丘状病灶。其T1WI信号高于玻璃体 ,T2 WI信号等于玻璃体 ,增强扫描瘤体显著强化。明确其HR MRI影像学特征有助于临床与恶性葡萄膜黑色素瘤相鉴别 ,避免不必要的眼球摘除     

A preliminary study of stress symptoms and nutritional state in children

The aim of this work was to examine the occurrence of stressful events in the lives of children, using the ‘Scale of Infantile Social Readjustment’ (SISR), and the ‘Inventory of Symptoms of Infantile Stress’ (ISIS) to identify the presence of stress symptoms. The results of these evaluations were then used to examine the relationship between the levels of stress and the nutritional state of the children, by correlation. Forty 7–10‐year‐old children were included in the evaluation. From the analysed sample 49 per cent of them were eutrophic (weight/height normal to age), 50 per cent were above weight and 1 per cent was undernourished. Whereas 70 per cent of the girls were eutrophic and 30 per cent were above weight, only 35 per cent of the boys were eutrophic, 60 per cent were above weight and 5 per cent were undernourished. The results obtained in this first study indicated that 45 per cent of eutrophic girls demonstrated symptoms of stress, while 20 per cent of them were asymptomatic (with no symptoms of stress). Of the overweight boys, 30 per cent of them showed symptoms of stress and 35 per cent did not. This study indicated a possible relationship between weight and the symptoms of stress. Copyright © 2004 John Wiley & Sons, Ltd.     

Off-resonance effects in the transient response of SSFP sequences.

A previously developed eigenvector formalism is adapted to off-resonance in the transient response of quasiperiodic steady-state free precession (SSFP) sequences, including TrueFISP as a special case. The effective relaxation rates for essentially parallel and perpendicular deviations from the steady state are determined analytically in leading order perturbation theory. The latter are a known cause of oscillatory artifacts and therefore constitute the main target of a variety of preparation techniques. In addition, the former also play a dominating role in applications such as inversion recovery (IR) TrueFISP, which intentionally measure far away from the equilibrium. For both components, the approach toward equilibrium turns out to depend sensitively on field inhomogeneities, especially for smaller ratios of T2/T1. For the perpendicular deviations, the calculations show that--except very close to banding artifacts, where the steady-state signal is almost zero--field inhomogeneities additionally increase their effective relaxation rate almost as much as in the free induction decay (FID). The analytical results are tested against numerical simulation and MR measurements.     

View ordering for magnetization prepared steady state free precession acquisition: application in contrast-enhanced MR angiography.

Magnetization prepared segmented acquisition requires a view order that maximizes signal contrast during the acquisition of the central portion of k-space. Steady state free precession (SSFP) acquisition further requires a view order that minimizes changes in phase-encoding gradients from one repetition to the next in order to minimize eddy current artifacts. In this article, optimal view ordering schemes satisfying these two requirements are formulated and applied to inversion prepared 3D SSFP contrast-enhanced MR angiography (MRA). Experiments on phantoms and pigs demonstrated improved background suppression and reduced image artifacts.     

Steady state of gradient echo sequences with radiofrequency phase cycling: Analytical solution,contrast enhancement with partial spoiling

Spoiled gradient echo sequences can only reach a homogeneous steady state if sufficiently strong crusher gradients are used in combination with RF phase cycling (RF spoiling). However, the signal depends quite sensitively on the chosen phase increment ? and—lacking analytical solutions—numerical simulations must be used to study the transient and steady‐state magnetization. For the steady state an exact analytical solution is derived, which holds for arbitrary sequence and tissue parameters. Besides a considerably improved computation performance, the analytical approach enables a better understanding of the complicated dependence on ?. For short repetition times (TR) the regime of small ? turns out to be particularly interesting: It is shown that the typical ?_c, where RF spoiling starts to become effective, is essentially inversely proportional to T₂. This tissue dependence implies that contrasts can be considerably larger with partial spoiling (? ≈ ?_c) than with conventional RF spoiling (? ? ?_c). As an example, the uptake of contrast agents in tissues is investigated. For typical parameters a considerably improved contrast enhancement can be obtained, both theoretically and experimentally. Magn Reson Med, 2006. © 2005 Wiley‐Liss, Inc.     

急性脑出血患者血清谷氨酸动态变化分析

目的通过观察脑出血（intracerebral hemorrhage，ICH）患者血清中谷氨酸的动态变化来进一步评价谷氨酸对脑出血的作用。方法选择符合条件的30例急性高血压脑实质出血患者，给予神经内科脑出血常规治疗，采用高效液相色谱法检测起病后2d内、5．6d、8-9d和15．16d的血清谷氨酸浓度，同步进行神经功能评定，同时于发病后1．3d、d5-6d及d15．16行头部CT检查了解血肿体积大小。结果脑出血患者血中谷氨酸浓度与血肿体积及神经功能缺损评分之间呈正的直线相关。经治疗后，所有病例谷氨酸水平迅速下降，在5-6d和8—9d下降速度更加明显。结论谷氨酸可能参与了自发性脑出血患者的急性期脑损伤作用。