Immunization-induced inflammatory infiltration of the central nervous system in transgenic mice expressing a microbial antigen in astrocytes

Transgenic mice expressing a defined microbial antigen from central nervous system (CNS) cell type-specific promoters can be utilized to investigate the consequences of induction of peripheral immune responses to foreign antigens produced by different CNS cell types. Immunization of mice expressing β-galactosidase (β-gal) in astrocytes with this protein resulted in antigen-dependent infiltration of the CNS by mononuclear cells, principally CD4⁺ T lymphocytes and monocyte/macrophages. The perivascular and intraparenchymal infiltrates, which were located predominantly in the hippocampal formation and cerebellum, the areas of highest β-gal expression, were associated with astrocytosis, microgliosis, and a generalized increase in blood-brain barrier permeability. The resemblance of these pathological changes to aspects of human immune inflammatory CNS disorders e.g. multiple sclerosis, suggests that an initiating step in the process by which such complex diseases are produced could be the induction of peripheral immune responses to antigens expressed in astrocytes.     

Validation of impedance cardiography measurements of cardiac output during limited exercise in heart transplant recipients

Abstract. Twenty-one patients were studied at rest and during exercise after heart transplantation to compare cardiac output measured by thermodilution and impedance cardiography. Exercise was performed on a bicycle ergometer over a limited range of work load (25 and 50 watt) whilst metabolic gas exchange was recorded. One patient was studied at rest whilst his circulation was maintained by a Jarvik-7 artificial heart. The values of cardiac output measured by impedance cardiography corresponded closely with the flow rate from the artificial heart. There was also close agreement between the impedance and thermodilution measurements of cardiac output at rest and during exercise. Both measurements followed the changes in heart rate and oxygen consumption. Both thermodilution and impedance cardiography methods elicited good reproducibility of cardiac output measurements at rest and during exercise. These observations suggest that the noninvasive and continuous record of cardiac output obtained by impedance cardiography can be used for the postoperative monitoring of heart transplant recipients.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

Moving beyond empiric continuous positive airway pressure (CPAP) trials for central sleep apnea: a multi-modality titration study

There is no universally accepted method to determine effective therapy for central sleep apnea (CSA). Continuous positive airway pressure (CPAP) applied acutely most often does not eliminate apneas and hypopneas. We hypothesized that the application of two or more therapeutic modalities after the diagnostic phase of polysomnography, a multi-modality titration study (MMTS), would identify a successful CSA treatment more often than a standard split-night study (SNS) and obviate the need for additional polysomnograms to determine a successful therapy. We retrospectively analyzed polysomnograms of patients diagnosed with CSA at our Sleep Disorders Center. We defined a therapy trial that resulted in an apnea–hypopnea index < 10 with at least one treatment modality as a therapeutic success. One hundred fifteen patients with CSA were studied. Sixty-six patients (57.4%) underwent a SNS, and 49 patients (42.6%) underwent a MMTS. SNS yielded only 8/66 (12.1%) successes on the first night, whereas a MMTS yielded 19/49 (38.8%) successes (p = 0.001, two-tailed Fishers exact). Patients who underwent a SNS eventually had similar rate of success as patients studied with MMTS (60.6 vs 63.3%, NS), but required more testing. Adaptive servo-ventilation was the most successful modality tested, yielding 36/46 (78.3%) successes. Trials of additional modalities following a failed trial of CPAP often produce a successful option that may guide therapy in patients with CSA. This approach may lead to establishing the diagnosis and treatment plans faster, while reducing unnecessary testing.     

近视眼的屈光度、眼轴、角膜屈光力的相关性探讨

目的：探讨近视眼的屈光度、眼轴、角膜屈光力之间的相关关系以及近视的成因。方法：将204例(348只眼)近视患者分为三组：低度近视组62眼(屈光度＜-3．0D）；中度近视组159眼(屈光度-3．0D～-6．0D)；高度近视组127眼(屈光度＞-6．0D)。测量患者眼的屈光度、角膜屈光力及眼轴，与近视程度、角膜屈光力、眼轴的关系。结果：在低度近视组，62只眼屈光度与眼轴长度无显著相关性，而屈光度与角膜水平径、垂直径屈光力呈正相关(P＜0．05)，相关具有显著性；在中度近视组和高度近视组屈光度与眼轴长呈正相关(P＜0．05)，相关具有显著性，且随近视度数的增加，与眼轴长的相关系数呈递增趋势，而中、高度组患者眼屈光度与角膜水平径及垂直径屈光力无显著相关性。结论：在近视性屈光不正的影响因素中，低度近视眼患者受角膜屈光力的影响相对较大，而眼轴的作用甚微；在中、高度近视眼患者中，眼轴长是影响近视程度的主要因素，而角膜屈光力几乎不起作用。     

Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline

Summary The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated.Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31–43 and 80–124 pmol·kg^–1·min^–1, respectively. The total-body (ER), pulmonary (ER_p) and forearm (ER_f) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma.ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ER_f. ER_p did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO.Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity. The enhancement by desipramine of the ISO-induced increase in plasma noradrenaline points towards recapture by neuronal uptake of at least 58% of the noradrenaline released in response to ISO.     

病理证实的原发性中枢神经系统淋巴瘤40例临床分析

目的探讨原发性中枢神经系统淋巴瘤（PCNSL）的临床与影像学特点，治疗与预后。方法对40例病理证实的PCNSL的临床与影像学表现、治疗和预后情况进行回顾性分析。结果PCNSL好发于50～60岁男性，急性或亚急性起病。肿瘤单发者占75．0％，多发者占25．0％，多位于脑脊液循环通路附近，即深部结构近脑室（57．5％）或靠近皮质的浅表部位（32．5％）。病理均为B细胞型，有特征性的“血管周围淋巴套”和“星空现象”。临床不具有特异性。头颅MRI多为T1低信号，T2高信号，界限清晰，水肿明显，显著均匀强化占67．6％，厚壁环形强化占13．5％。采用大剂量甲氨蝶呤（HDMTX）化疗者，存活率（75．0％）较未采用者（48．1％）高。平均生存时间14．8个月，复发后69．2％的患者存活不足6个月。结论PCNSL临床表现无特异性，确诊需靠穿刺活体组织检查。治疗首选HDMTX为基础的综合化疗，预后差。     

颅内原发性中枢神经系统淋巴瘤的MRI研究

目的研究颅内原发性中枢神经系统淋巴瘤（PCNSL）的MRI表现特点。资料与方法回顾性分析23例颅内PCNSL的MRI表现。抽取恶性胶质瘤30例、颅内转移瘤30例，共60例归为非PCNSL组作为对照。观察肿瘤部位、分布、信号、形态，并进行统计学分析。结果颅内PCNSL好发于深部脑组织，如胼胝体、丘脑及基底节区，多发病灶多呈区域性分布；肿瘤T2WI多呈等或稍高信号，甚至低信号，扩散加权像（DWI）呈均匀高信号；增强扫描多呈均匀明显强化，肿瘤周围可见“尖突征”。与非PCNSL组之间差异有统计学意义（P〈0．01）。结论颅内PCNSL影像表现多样，但具有一定特征。     

新一代人工牛黄的药理与毒理学研究 Ⅰ.对中枢神经系统的影响

本文比较了新一代人工牛黄和天然牛黄,人工牛黄对中枢神经系统的影响,实验结果:新一代人工牛黄对小鼠中枢神经系统具有抑制作用,对发热大鼠有一定程度的解热作用,它的药理作用与天然牛黄接近,某些药理作用强于人工牛黄,为新一代人工牛黄代替天然牛黄提供了科学依据.