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.     

Measurement of axial edge lift of rigid corneal lenses*

A simple but reliable method was used to measure the axial edge lift at the total diameter over a range of back optic zone radii of several proprietary designs of rigid gas-permeable corneal lens. One of these was found to have a constant axial edge lift construction.     

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.     

A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

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。     

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.     

MANAGEMENT OF SEMINOMA OF THE TESTIS: RECOMMENDATIONS BASED ON TREATMENT RESULTS

Background : The results of management of seminoma of the testis at the Department of Radiation Oncology St Vincent's Hospital, Sydney were evaluated retrospectively to: (i) establish that outcomes were in keeping with published results from centres in Australia and overseas; (ii) assess the impact of chemotherapy on management; and (iii) to determine ‘best practice’ management protocols based on our results and a review of the relevant literature. Methods : (i) Assessment of treatment results for stage I and II seminoma of the testis treated by post-orchidectomy radiotherapy and/or chemotherapy at St Vincent's Hospital between 1979 and 1993; (ii) literature review of published data from Australian and overseas centres on the management of seminoma of the testis, and in particular the use of surveillance or chemotherapy either alone, at time of relapse or combined with radiotherapy; and (iii) development of recommendations for use as management protocols in our department. Results : Our data and a review of the literature suggest that post-orchidectomy radiotherapy with chemotherapy for relapse in stage I and IIA disease results in long-term cure rates approaching 100%. Treatment with chemotherapy either routinely or selectively or using a surveillance policy is unlikely to show any improvement in outcome and may be less cost-effective and/or produce increased morbidity and the risk of secondary leukaemia. For stage IIB disease (5–10 cm) the use of initial combination chemotherapy with or without subsequent radiotherapy did not appear to give better outcomes than initial radical radiotherapy alone, reserving chemotherapy or further radiotherapy for relapse. For bulkier stage IIB disease (> 10cm). the use of initial chemotherapy plus consolidation radiotherapy appeared to be an appropriate treatment. Conclusions : Management protocols for seminoma of the testis at St Vincent's Hospital, Sydney Department of Radiation Oncology currently are (i) stage I, IA and IIB (5–10 cm): post-orchidectomy radiotherapy alone with chemotherapy or further radiotherapy for relapse; and (ii) stage IIB (> 10 cm) disease: initial chemotherapy post-orchidectomy followed by radiotherapy to sites of initial disease involvement.