PubMed Health⌕ Search

Biomedical subjects

U Held

Publications and source records attributed to U Held.

8 recordsLinked to original sources
PubMed2006

MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.

BACKGROUND: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. OBJECTIVE: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. METHODS: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. RESULTS: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. CONCLUSIONS: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.

Adult↗
PubMed2005

Predictors of relapse rate in MS clinical trials.

BACKGROUND: The annual relapse rate has been commonly used as a primary efficacy endpoint in phase III multiple sclerosis (MS) clinical trials. The aim of this study was to determine the relative contribution of different possible prognostic factors available at baseline to the on-study relapse rate in MS. METHODS: A total of 821 patients from the placebo arms of the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database were available for this analysis. The univariate relationships between on-study relapse rate and the baseline demographic, clinical, and MRI-based predictors were assessed. The multiple relationships were then examined using a Poisson regression model. Two predictor subsets were selected. Subset 1 included age at disease onset, disease duration, sex, Expanded Disability Status Scale (EDSS) at baseline, number of relapses in the last 24 months prior to baseline, and the disease course (relapsing remitting [RR] and secondary progressive [SP]). Subset 2 consisted of Subset 1 plus gadolinium enhancement status in MRI. The number of patients for developing the models with no missing values was 727 for Subset 1 and 306 for Subset 2. RESULTS: The univariate relationships show that the on-study relapse rate was higher for younger and for female patients, for RR patients than for SP patients, and for patients with positive enhancement status at entry (Wilcoxon test, p < 0.05). A higher on-study relapse rate was associated with a shorter disease duration, lower entry EDSS, more pre-study relapses, and more enhancing lesions in T1 at entry. The fitted Poisson model shows that disease duration (estimate = -0.02) and previous relapse number (estimate = 0.59 for one, 0.91 for two, and 1.45 for three or more relapses vs no relapses) remain. The authors were able to confirm these findings in a second, independent dataset. CONCLUSIONS: The relapse number prior to entry into clinical trials together with disease duration are the best predictors for the on-study relapse rate. Disease course did not contribute independently because its effect is covered by the pre-study relapse rate. Gadolinium enhancement status, given the other covariates, has no significant influence on the on-study relapse rate.

Age Factors↗
PubMed2005

Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials.

BACKGROUND: Gadolinium enhancement is often used in randomized clinical trials to evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about predictors of enhancement status is important for the selection of patients for MRI monitored trials. METHODS: Data from 17 trials were available in anonymized format through the Sylvia Lawry Centre for MS Research. In an open part containing 1,328 (non primary progressive) patients, two logistic regression analyses were explored, including demographic, clinical, and MRI predictors. The authors examined the area under the curve (AUC) and the increase in positive predictive value (PPV). The final selection of models was validated in a closed part of 848 comparable patients. RESULTS: Age at onset, disease duration, and disease course (CIS/RR/SP) were important predictors from the multivariate models. Further, a multivariate model including T2 burden of disease was more predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p < 0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to 58.5% for the model without (a priori chance 46.4%). These findings were unequivocally confirmed in the closed part of the database. CONCLUSION: Gadolinium status can be predicted by a set of baseline variables, certainly when T2 burden of disease is included. These findings may benefit the design and statistical power of future randomized clinical trials.

Adult↗
PubMed2001

Rec (formerly Corf) function requires interaction with a complex, folded RNA structure within its responsive element rather than binding to a discrete specific binding site.

It was recently reported that the human endogenous retrovirus HTDV/HERV-K encodes the regulatory protein Rec (formerly designated Corf), which is functionally equivalent to the nuclear export adapter proteins Rev of human immunodeficiency virus and Rex of human T-cell leukemia virus. We have demonstrated that the Rec protein interacts with a characteristic 429-nucleotide RNA element, the Rec-responsive element (RcRE), present in the 3' long terminal repeat of HTDV/HERV-K transcripts. In analogy to the Rev and Rex proteins, which have distinct RNA binding sites in their responsive elements, we have proposed that Rec may also have a defined binding site in the RcRE. In this report, we demonstrate that not every HTDV/HERV-K copy present in the human genome contains an active RcRE, and we characterize mutations that abrogate Rec function. In addition, we demonstrate that Rec function requires binding to a complex, folded RNA structure rather than binding to a discrete specific binding site, in contrast to Rev and Rex and their homologous responsive elements. We define four stem-loop structures in the RcRE that are essential for Rec function. Finally, we demonstrate that both Rev and Rex can mediate nuclear export through the RcRE but that their binding sites are different from each other and from that of Rec.

Base Sequence↗
PubMedDate not supplied

[Topographic mapping of retinal function with a scanning laser ophthalmoscope and multifocal electroretinography using short M-sequences].

A new method of multifocal electroretinography making use of scanning laser ophthalmoscope with a wavelength of 630 nm (SLO-m-ERG), evoking short spatial visual stimuli on the retina, is proposed. Algorithm of presenting the visual stimuli and analysis of distribution of local electroretinograms on the surface of the retina is based on short m-sequences. Mathematical cross correlation analysis shows a three-dimensional distribution of bioelectrical activity of the retina in the central visual field. In normal subjects the cone bioelectrical activity is the maximum in the macular area (corresponding to the density of cone distribution) and absent in the blind spot. The method detects the slightest pathological changes in the retina under control of the site of stimulation and ophthalmoscopic picture of the fundus oculi. The site of the pathological process correlates with the topography of changes in bioelectrical activity of the examined retinal area in diseases of the macular area and pigmented retinitis detectable by ophthalmoscopy.

Adult↗