Differential generation of class I H-2D- versus H-2K-restricted cytotoxicity against a demyelinating virus following central nervous system infection

Despite the fact that both H-2K and D molecules are up-regulated in the central nervous system (CNS) following Theiler's murine encephalomyelitis virus (TMEV) infection, resistance in this virus model of multiple sclerosis maps exclusively to D. To address this paradox, we examined the ability of the K and D molecules to present viral antigens to cytotoxic T lymphocytes (CTL). Whereas no virus-specific CTL were detected in the CNS of susceptible B10.Q and B10.S mice 7 days post-infection, D-restricted CTL were identified readily in the CNS of resistant B10 animals. There was no evidence of K-restricted CTL in the CNS of B10 mice at day 7 post-infection. The presence of both K- and D-restricted virus-specific CTL in the spleen of immunized B10 mice demonstrates that the exclusive use of D molecules by CTL in the CNS of mice 7 days post-infection is not due to the inability of the K molecules to present viral peptides to lymphocytes. We conclude that the prominent role of the D locus in determining resistance or susceptibility to TMEV-induced demyelination is determined by factors governing the regulation of the immune response, and not by the presence or absence of CTL precursors capable of recognizing viral peptides presented by the K and D antigen-presenting molecules, or by differences in the ability of the K and D molecules to present viral peptides.     

Febrile seizures - treatment and outcome

Assessment of treatment strategies in febrile seizures should be based on short- and long-term outcomes, with and without acute, intermittent, or chronic medical intervention, as well as short- and long-term side effects. Febrile seizures are a benign condition with a normal neurological, motor, intellectual, and cognitive long-term outcome and have a low risk of later epilepsy in most cases. Even many complex febrile seizures have a benign outcome. Prophylaxis may or may not reduce the recurrence rate, but does not appear to improve the long-term outcome as compared to acute treatment of seizures in progress. All agree that chronic prophylaxis with anti-epileptic agents is justified only in highly selected cases, if at all. Treatment with benzodiazepines during febrile episodes appears to effectively reduce the recurrence rate, provided adequate doses are given and compliance problems minimized. A selective approach to intermittent diazepam prophylaxis seems rational, as the recurrence risk and response to treatment are highly variable. An attractive alternative is acute treatment at seizure onset with rectal diazepam in solution given by the parents at home in order to prevent prolonged recurrent seizures. This regimen has the potential of moving the first line of anti-convulsant defence close to the child. It appears to be effective, inexpensive, feasible even for non-professionals, has few side effects and is well accepted by the parents. A reasonable policy would be to treat simple febrile seizures solely with acute rectal diazepam in solution and reserve intermittent diazepam prophylaxis for selected cases including those with multiple or prolonged recurrences, several risk factors for recurrent febrile seizures and other special situations.     

BCL—2蛋白在癫痫过程中海马细胞内的变化

癫痫全面性强直阵挛发作（ＧＴＣＳ）可诱导脑细胞的损伤与修复过程。ＢＣＬ—２蛋白是具有介导多种细胞外信号保护细胞存活的重要的细胞浆蛋白之一。应用流式细胞免疫荧光技术对马桑内酯（ＣＬ）致痫大鼠海马细胞中ＢＣＬ—２蛋白进行检测。结果显示：ＣＬ诱导癫痫发作海马细胞中ＢＣＬ—２蛋白表达增高，发作６小时以内荧光指数（ＦＩ）（１．１２９±０．０４７，ｎ＝７）明显高于对照组（０．９９９±０．０９６，ｎ＝９），Ｐ＜０．００５，６～２４小时组（１．０２６±０．０６５，ｎ＝３）及２４小时以后组（０．９８２±０．０４３，ｎ＝６）ＦＩ回落，Ｐ＞０．０５。提示这种ＢＣＬ—２变化可能对损伤和凋亡细胞具有保护作用。     

Frequency and causes of shunt revisions in different cerebrospinal fluid shunt types

Summary Shunt complications and revisions are common in hydrocephalic patients treated with a ventriculo-atrial or a ventriculo-peritoneal shunt. The reported revision rate differs very much but the rate of revision is close to 50% in many papers. Data from 884 hydrocephalic patients treated with various shunt types in the period 1958–1989 were recorded retrospectively in order to evaluate the frequency of revision for various shunt types and secondly to analyse the specific reasons for the shunt revisions.The rate of shunt revision was 45%. The Pudenz shunt was revised more often (62%) than the remaining shunt types. The Hakim and the Orbis-Sigma shunts had fewer revisions (35% and 27%, respectively) than the other observed shunt types. A defect of or an obstruction in the ventricular catheters was a frequent cause of revision followed by a defect or an obstruction of the distal catheter, a displacement of the distal catheter and an acute infection. Because of the higher rate of revision for the Pudenz shunt the rate of the above mentioned specific complications is also higher in most of the subgroups for that specific shunt type. Driven by these experiences it is reasonable to seek to develop and introduce new shunt types in an attempt to reduce the complication rate.     

Assessment of MRI criteria for abnormal brain MRI in acute monosymptomatic optic neuritis. Comparison to findings in healthy persons

To evaluate various MRI criteria we studied a representative group of 149 consecutive patients below 50 years with acute monosymptomatic optic neuritis (AMON), a frequent first manifestation of multiple sclerosis (MS). The presence, number, size, and localization of areas of increased signal (AIS) on T₂-weighted brain MRIs obtained at 1.5 T were described and compared with findings in 71 healthy persons aged 21–50 years without diabetes, cerebrovascular or neurologic diseases. MRI was performed within 2–145 days, median 16 days from onset of AMON and showed from 0 to 26 AIS, sized 2–30 mm, in 79 of 149 (53%) patients compared to 0–18 AIS, sized 2–12 mm, in 31 of 71 (44%) healthy persons. In patients, AIS were significantly more frequent in women than in men (χ² = 4.67, p > 0.05). Periventricular AIS were revealed in 70 (47%) patients and in 14 (20%) healthy persons. Subcortical AIS were present in 5 (3%) patients and in 18 (25%) healthy persons. Infratentorial AIS were present in only 3 (2%) patients. The sensitivity and specificity of previously proposed diagnostic MRI criteria for MS were unsatisfactory in our group of patients and have previously only been validated in definite MS. We therefore constructed and tested four new sets of criteria. The set with the best relation between sensitivity (e.g. 41%) and specificity (e.g. 93%) was the following: presence of two or more AIS, of which at least one is periventricular or infratentorial, combined with the absence of subcortical AIS. These criteria are recommended for patients with AMON and might be used in other patients with possible or probable MS.     

Acute hemodynamic responses to electroconvulsive therapy are not related to the duration of seizure activity

Study Objective: To test the hypothesis that the magnitude of the acute hemodynamic response to electroconvulsive therapy (ECT) is related to the duration of the seizure activity in patients receiving different dosages of intravenous (IV) lidocaine.

Design: Randomized, double-blind, placebo-controlled, cross-over study.

Setting: University-affiliated hospital.

Patients: 21 ASA physical status I, II, and III patients undergoing four consecutive maintenance ECT treatments for chronic depression.

Interventions: Patients received lidocaine 50 mg, 100 mg, 200 mg IV, or saline prior to induction of anesthesia via a standardized anesthetic technique.

Measurements and Main Results: Noninvasive blood pressure (BP) and heart rate (HR), as well as the duration of motor and electroencephalographic (EEG) seizure, were measured. The duration of motor and EEG seizures (means ± SD) were 37 ± 13 sec and 64 ± 21 sec, 25 ± 11 sec and 52 ± 43 sec, 17 ± 12 sec and 32 ± 17 sec, 1 ± 3 sec and 18 ± 10 sec in the saline, lidocaine 50 mg, 100 mg, 200 mg groups, respectively. Although the duration of seizure activity was decreased in a dose-related fashion after lidocaine pretreatment, the peak increases in BP and HR were similar in the lidocaine and saline treatment groups.

Conclusions: Despite producing dose-related decreases in the duration of both motor and EEG seizure activity, lidocaine failed to attenuate the acute hemodynamic response to ECT. Thus, the acute hemodynamic response to ECT is not related to the duration of seizure activity.     

多发性硬化患者血清和脑脊液中sIL-2R及sIL-6R的研究

目的　探讨可溶性白细胞介素 2受体 (sIL 2R)和可溶性白细胞介素 6受体 (sIL 6R)在多发性硬化(MS)发病过程中的作用。方法　采用双体夹心ELISA法对 2 9例MS急性期患者及 2 0例炎性神经病患者、39例非炎性神经病患者、2 0例健康对照者脑脊液和血清中sIL 2R和sIL 6R的含量进行检测。结果　MS患者血清和脑脊液中sIL 2R、sIL 6R含量明显高于非炎性神经病组 (P <0 .0 5 )及健康对照组 (P <0 .0 1) ;MS组sIL 2R和血清sIL 6R含量与炎性神经病组比较 ,无显著性差异 ,但脑脊液中sIL 6R水平明显低于炎性神经病组 (P <0 .0 1)。结论　sIL 2R和sIL 6R在MS急性期患者体内明显升高 ,进一步证实了MS有关免疫学的发病机制 ,并为临床诊断MS提供了具有参考价值的实验室指标     

Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

健康志愿者１０名，随机交叉口服硫酸吗啡控释片（ＣＲＭＳ）３０ｍｇ（３０ｍｇ×１）和硫酸吗啡普通片（ＩＲＭＳ）２０ｍｇ（１０ｍｇ×２），分别于服药前后各时点取静脉血，用ＧＣＭＳ测定血浆中吗啡含量。以药代软件程序处理，分别求得ＣＲＭＳ和ＩＲＭＳ的Ｃｍａｘ为１９．３８±３．８０和２１．２７±６．２１ｎｇ／ｍｌ；ｔｍａｘ为２．３６±０．３７ｈ和０．５５±０．１６ｈ；ｔ１／２β为３．５３±０．８７ｈ和３．０３±０．７４ｈ，曲线下面积ＡＵＣ为１４５．１５±１７．６５和９３．０８±１６．６５ｎｇ·ｈ／ｍｌ。癌症病人多次口服硫酸吗啡至稳态，ＣＲＭＳ和ＩＲＭＳ的峰浓度分别为２７．４３±０．３３ｎｇ／ｍｌ，２２．６８±０．１６ｎｇ／ｍｌ；谷浓度分别为１９．４５±１．４４ｎｇ／ｍｌ；１８．１４±０．４９ｎｇ／ｍｌ。     

Fatigue in multiple sclerosis is not due to sleep apnoea

Fatigue is a frequent and disabling phenomenon among patients with multiple sclerosis (MS). Daytime sleepiness is a typical symptom of the sleep apnoea/hypopnoea syndrome due to nocturnal hypoxia and recurrent arousals causing sleep fragmentation. Since MS plaques are often found in the midbrain, brain stem and upper cervical cord on magnetic resonance imaging (MRI) we hypothesized that fatigue in MS patients might be caused by a central respiratory dysfunction. We investigated 10 patients with definite MS by oligography, two questionnaires assessing fatigue (Fatigue Severity Scale, FSS) and daytime sleepiness (Epworth Sleepiness Scale, ESS), MRI and pulmonary function tests. A total of six patients had either an elevated FSS and/or an elevated ESS. None of the six patients with an elevated FSS and/or ESS has an apnoea index > 5/hour. CT₉₀ was normal in nine patients. We conclude that fatigue and daytime sleepiness in MS cannot be explained by nocturnal apnoeas or oxygen desaturations. The Fatigue Severity Scale should be integrated to the extended Barthel index, which is a new instrument for disability assessment in MS patients.     

Magnetization transfer imaging of multiple sclerosis

While conventional magnetic resonance imaging (MRI) measures signal primarily from the hydrogen nuclei of water, magnetization transfer (MT) MRI indirectly detects macromolecular associated hydrogen nuclei via their magnetic interaction with the observable water. In the normal adult CNS, white matter exhibits the largest MT effect due to the macromolecular content of the highly structured and lipid rich myelin. Pathologies which alter the structural integrity and the relative macromolecular-water composition, such as multiple sclerosis (MS), therefore show abnormal MT. Conventional MRI, which has a high MS lesion detection sensitivity but poor specificity in terms of differentiating the pathological state of a plaque, can thus be supplemented by MT to provide more specific information on the extent of demyelination and axonal loss. In this paper we review the basic concepts of MT imaging and its role in MS lesion characterization.Financial support was provided by the Medical Research Council of Canada, Fonds de la Recherche en Santé du Québec, and the Killam Foundation.