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G W Ellison L W Myers M R Mickey M C Graves W W Tourtellotte K Syndulko M I Holevoet-Howson C D Lerner M V Frane P Pettler-Jennings 《Neurology》1989,39(8):1018-1026
Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS. 相似文献
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Ernest P. Noble Rudolf E. Noble Terry Ritchie Karl Syndulko M. Charlotte Bohlman Lorna A. Noble Yzan Zhang Robert S. Sparkes David K. Grandy 《The International journal of eating disorders》1994,15(3):205-217
The prevalence of Taql A D2 dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high-density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22–q23 region of chromosome 11, confers susceptibility to a subtype of this disorder. © 1994 by John Wiley & Sons, Inc. 相似文献
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The long march of the cerebrospinal fluid profile indicative of clinical definite multiple sclerosis; and still marching 总被引:3,自引:0,他引:3
W.W. Tourtellotte R.W. Baumhefner K. Syndulko P. Shapshak M. Osborne G. Rubinstein L. Newton G. Ellison L. Myers I. Rosario R. Thomsen R. Sloan S. Engelmann 《Journal of neuroimmunology》1988,20(2-3):217-227
Much progress has been made, especially in the last two decades, in laboratory aids to diagnosis and to follow the course of patients with multiple sclerosis (MS). The cerebrospinal fluid (CSF) profile indicative of MS, though not pathognomonic of MS, is present in almost every case of clinical definite MS in a chronic progressive phase (probably also true for early MS). The cardinal aspect of the profile is intra-blood-brain barrier (BBB) IgG synthesis which can be qualitatively detected by determining unique CSF oligoclonal IgG bands and quantitated by rate formula, mg/day. We believe that intra-BBB IgG synthesis is caused by a persistent antigen, most likely a virus, possibly measles. A number of issues about the profile are proposed and opportunities are presented to resolve them. 相似文献
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W W Tourtellotte A R Potvin M Mendez R W Baumhefner J H Potvin B I Ma K Syndulko 《Annals of neurology》1980,8(4):402-408
To study the nature of the multiple sclerosis (MS) central nervous system (CNS) immune reaction, cytarabine (ara-C) was administered intravenously to three patients and intrathecally to another seven. Although intravenous administration severely suppressed circulating leukocytes derived fom the bone marrow, there was no change in de novo CNS IgG synthesis (rate or presence of CSF IgG oligoclones). Therefore, the MS CNS immune reaction can persist in the presence of severe granulocytopenia and severe monocytopenia of one to two weeks' duration. In four patients who were given ara-C intrathecally, cytotoxic levels (> 10 micrograms/ml) were present for a least 24 hours. A brief elevation in CSF albumin indicated transient damage to the blood-brain barrier. Leukopenia did not result in the seven patients treated intrathecally, and de novo CNS IgG synthesis did not change or was transiently increased. Assuming that cytotoxic levels in CSF diffused to the CNS sites responsible for synthesizing IgG, results indicate that CNS IgG synthesis does not depend on in situ rapid turnover of immune cells. None of the ten patients demonstrated neurological improvement or persistent adverse effects. 相似文献
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The CNV, visual AEP and resting EEG were analyzed in sociopaths and controls matched for age and sex. Twenty-seven male sociopaths were selected by psychiatric interview and special rating scale, restricted to Shipley-Hartford IQs of 115-145 and separated into young (x = 20.5 yr) and older (x = 35.3 yr) age groups. Subjects participated in forewarned reaction-time tasks in which the imperative stimulus was either an innocuous or noxious tone that the subject escaped by pressing a response key. Sociopaths and controls did not differ in reaction time, vertex and occipital AEP amplitude or latency, and power spectral density of the EEG. Contrary to previous findings, there also were no significant differences between sociopaths and controls in overall CNV amplitude or topography. However, while most controls showed increased CNV amplitude in the noxious tone condition as compared to the innocuous tone condition, older sociopaths showed no change, or decreased amplitudes. 相似文献
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W W Tourtellotte A R Potvin R W Baumhefner J H Potvin B I Ma K Syndulko Z Petrovich 《Archives of neurology》1980,37(10):620-624
Megavoltage CNS irradiation was given to 20 patients with clinically definite multiple sclerosis (MS) to determine if de novo CNS IgG synthesis could be eradicated. In all five patients given 1,200 rads, a transient reduction in the de novo CNS IgG synthesis rate was noted. In ten patients given 1,800 rads, the following occurred: a reduction in synthesis rate in three patients, a reduction followed by enhancement in two, only enhancement in four, and no change in one. In all five additional patients, a therapy of adrenocorticotropic hormone (ACTH) followed by prednisone in combination with 1,800 rads produced greater and more persistent decreases in CNS IgG synthesis, but did not block the enhancement effect. Only two of 19 patients who had abnormal CNS IgG synthesis rates had reductions to normal; no patients showed changes in the number or pattern CSF IgG oligoclones. Hence, no treatment eradicated de novo CNS IgG synthesis. A persistent decrease in CSF leukocytes occurred in all 20 patients due to the reduction of small lymphocytes (not dose related). The blood-brain-barrier to albumin concentration was transiently damaged in 11 of 15 patients given irradiation, but when patients were premedicated with ACTH/prednisone therapy, no damage was found. None of the patients demonstrated neurological improvement, change in the activity of their disease, or persistent adverse effects. 相似文献
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R W Baumhefner W W Tourtellotte K Syndulko V Waluch G W Ellison L W Meyers S N Cohen M Osborne P Shapshak 《Archives of neurology》1990,47(1):19-26
Magnetic resonance imaging (MRI) of the cerebrum, cerebellum, brain stem, and upper cervical cord was performed in 62 individuals with clinically definite chronic, progressive multiple sclerosis (MS). The total area of MRI-demonstrated lesions was measured from film enlargements for each region using an interactive image analysis system. While the MRI was abnormal in 60 (97%) of 62 patients, the visual-evoked potentials in 51 (85%) of 60 patients, the brain stem auditory-evoked potentials (BAEPs) in 24 (46%) of 52 patients, and the somatosensory-evoked potentials (SSEPs) in 45 (89%) of 54 patients, an abnormal intra-blood-brain barrier (BBB) IgG synthesis rate, IgG oligoclonal bands, or both were found in all 62 patients. The total area of MRI abnormality in the cerebrum was significantly correlated only with the intra-BBB IgG synthesis rate, abnormal visual-evoked potentials, impaired performance on the Symbol Digit Modalities Test (SDMT), and one test of standing duration in the quantitative examination of neurologic function (QENF). The brain stem lesion area correlated with the Kurtzke expanded disability status scale and brain stem functional systems score, the ambulation index, abnormal BAEPs, and impaired performance on the SDMT as well as multiple tests of upper and lower extremity function in the QENF. The cerebellar lesion area correlated with impaired performance on the SDMT and primarily upper extremity testing in the QENF.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Recommendations from the national multiple sclerosis society clinical outcomes assessment task force
Richard Rudick Jack Antel Christian Confavreux Gary Cutter George Ellison Jill Fischer Fred Lublin Aaron Miller John Petkau Stephen Rao Stephen Reingold Karl Syndulko Alan Thompson Joy Wallenberg Brian Weinshenker Ernest Willoughby 《Annals of neurology》1997,42(3):379-382
This article provides recommendations from the National Multiple Sclerosis Society's Clinical Outcomes Assessment Task Force. The Task Force was appointed in 1994 and charged with recommendending improved approaches for clinical outcomes assessment in future controlled clinical trials. The recommendations herein follow extensive deliberation and data analysis during 2.5 years. General principles and desirable measurement attributes were used to assess alternative measurement techniques and clinical scales. On the basis of the analysis of existing multiple sclerosis (MS) data sets, a new measurement approach is proposed. The approach is based on quantitative functional composites that consist of simple quantitative measures from the major clinical dimensions of MS combined into a single score. Quantitative functional composites are likely to provide improved precision and sensitivity in future MS clinical trials. Studies necessary to further refine quantitative functional composites as useful MS clinical trial outcomes are delineated. 相似文献