Lesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis.

Magnetization transfer ratio (MTR) is a sensitive parameter to quantify the integrity of myelinated white matter in patients with multiple sclerosis. Lesional MTR decreases in the acute phase due to demyelination, and subsequently shows recovery depending on the degree of remyelination in the absence of axonal loss. Recovery of average lesion MTR therefore might prove a viable outcome measure to assess the effect of remyelinating agents. Our objective was to determine the required sample size for phase II multicentre clinical trials using the recovery of average lesion MTR as primary outcome measure. With 7-monthly MRI scans, the MTR evolution of 349 new enhancing lesions before and after enhancement was assessed in 32 MS patients from 5 centres. Multilevel models were fitted to the data yielding estimates for the variance components, which were applied in power calculations. Sample sizes were determined for placebo-controlled, multicentre trials using lesional MTR recovery post-enhancement as primary outcome measure. Average lesion MTR decreased slightly in the build-up to enhancement, decreased dramatically during enhancement and showed recovery in the period after cessation. The power calculations showed that for a power of 80%, approximately 136 patients per trial (mean number of 6 lesions per patient) are required to detect a 30% increase in lesional MTR post-enhancement compared with placebo, whereas 48 subjects are required to detect a 50% increase in lesional MTR compared with placebo. Recovery of lesion MTR is a feasible outcome measure for future multicentre clinical trials measuring the effect of remyelinating agents.

Amnestic mild cognitive impairment: structural MR imaging findings predictive of conversion to Alzheimer disease.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is considered by many to be a prodromal phase of Alzheimer disease (AD). We used voxel-based morphometry (VBM) to find out whether structural differences on MR imaging could offer insight into the development of clinical AD in patients with amnestic MCI at 3-year follow-up. MATERIALS AND METHODS: Twenty-four amnestic patients with MCI were included. After 3 years, 46% had progressed to AD (n = 11; age, 72.7 +/- 4.8 years; women/men, 8/3). For 13 patients (age, 72.4 +/- 8.6 years; women/men, 10/3), the diagnosis remained MCI. Baseline MR imaging at 1.5T included a coronal heavily T1-weighted 3D gradient-echo sequence. Localized gray matter differences were assessed with VBM. RESULTS: The converters had less gray matter volume in medial (including the hippocampus) and lateral temporal lobe, parietal lobe, and lateral temporal lobe structures. After correction for age, sex, total gray matter volume, and neuropsychological evaluation, left-sided atrophy remained statistically significant. Specifically, converters had more left parietal atrophy (angular gyrus and inferior parietal lobule) and left lateral temporal lobe atrophy (superior and middle temporal gyrus) than stable patients with MCI. CONCLUSION: By studying 2 MCI populations, converters versus nonconverters, we found atrophy beyond the medial temporal lobe to be characteristic of patients with MCI who will progress to dementia. Atrophy of structures such as the left lateral temporal lobe and left parietal cortex may independently predict conversion.

Global and local gray matter loss in mild cognitive impairment and Alzheimer's disease.

PURPOSE: Mild cognitive impairment (MCI) is thought to be the prodromal phase to Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to examine what characterizes MCI and what determines the difference with AD. MATERIALS AND METHODS: Thirty-three subjects with AD, 14 normal elderly controls (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR imaging. Global GM volume was assessed using segmentation and local GM volume was assessed using voxel-based morphometry (VBM); VBM was optimized for template mismatch and statistical mass. RESULTS: AD subjects had significantly (12.3%) lower mean global GM volume when compared to controls (517 +/- 58 vs. 590 +/- 52 ml; P < 0.001). Global GM volume in the MCI group (552 +/- 52) was intermediate between these two: 6.2% lower than AD and 6.5% higher than the controls but not significantly different from either group. VBM showed that subjects with MCI had significant local reductions in gray matter in the medial temporal lobe (MTL), the insula, and thalamus compared to NCLR subjects. By contrast, when compared to subjects with AD, MCI subjects had more GM in the parietal association areas and the anterior and the posterior cingulate. CONCLUSION: GM loss in the MTL characterizes MCI, while GM loss in the parietal and cingulate cortices might be a feature of AD.

A comprehensive study of gray matter loss in patients with Alzheimer's disease using optimized voxel-based morphometry.

Voxel-based morphometry (VBM) has already been applied to MRI scans of patients with Alzheimer's disease (AD). The results of these studies demonstrated atrophy of the hippocampus, temporal pole, and insula, but did not describe any global brain changes or atrophy of deep cerebral structures. We propose an optimized VBM method, which accounts for these shortcomings. Additional processing steps are incorporated in the method, to ensure that the whole spectrum of brain atrophy is visualized. A local group template was created to avoid registration bias, morphological opening was performed to eliminate cerebrospinal fluid voxel misclassifications, and volume preserving modulation was used to correct for local volume changes. Group differences were assessed and thresholded at P < 0.05 (corrected). Our results confirm earlier findings, but additionally we demonstrate global cortical atrophy with sparing of the sensorimotor cortex, occipital poles, and cerebellum. Moreover, we show atrophy of the caudate head nuclei and medial thalami. Our findings are in full agreement with the established neuropathological descriptions, offering a comprehensive view of atrophy patterns in AD.

Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry.

Previous cross-sectional MRI studies based on region-of-interest analyses have shown that increased cerebral atrophy is a feature of both Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Relative preservation of the hippocampus and temporal lobe structures in DLB compared to AD has been reported in region-of-interest-based studies. Recently, image processing techniques such as voxel-based morphometry (VBM) have been developed to provide an unbiased, visually informative, and comprehensive means of studying patterns of cerebral atrophy. We report the first study to use the voxel-based approach to assess patterns of cerebral atrophy in DLB compared to control subjects and AD. Regional gray matter volume loss was observed bilaterally in the temporal and frontal lobes and insular cortex of patients with DLB compared to control subjects. Comparison of dementia groups showed preservation of the medial temporal lobe, hippocampus, and amygdala in DLB relative to AD. Significant gray matter loss was also observed in the thalamus of AD patients compared to DLB.

Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages.

The aim of this study was to investigate the relationship between recurrent miscarriages and factor V Leiden, prothrombin G20210A and C677T methylenetetrahydrofolate reductase (MTHFR) mutations. In this case-control study the prevalence of factor V Leiden, prothrombin G20210A and C677T methylenetetrahydrofolate reductase mutations was determined in a consecutive series of 80 recurrent miscarriage patients and 100 controls. Fifteen of 80 recurrent miscarriage patients and four out of 100 controls carried the factor V Leiden mutation (19 versus 4%, P = 0.003, odds ratio 5.5, 95% confidence interval (CI): 1.7-17). Seven of 80 recurrent miscarriage patients and two of 100 controls were carriers of the prothrombin G20210A mutation (9 versus 2%, P = 0.038, odds ratio 4.6, 95% CI: 0.9-23.2). Six of 80 recurrent miscarriage women and 15 of 100 controls were homozygotes for the C677T MTHFR mutation (8 versus 15%, P = 0.134, odds ratio: 0.4, 95% CI: 0.1-1.2). Our results suggest that the presence of factor V Leiden and prothrombin G20210A polymorphism, but not MTHFR C677T homozygosity, could be additional risk factors for recurrent miscarriages. Furthermore, it was suggested that the prevalence of factor V Leiden and prothrombin G20210A mutations is more prominent in second trimester, primary fetal losses and it is independent of the existence of additional pathology predisposing to recurrent fetal losses.

T1 hypointensities and axonal loss.

T1 hypointensities are lesions that are hypointense on moderately T1-weighted conventional spin-echo sequences and serve as markers of matrix destruction and axonal loss. They correlate better with clinical disability than T2-weighted images, are found in patients with progressive multiple sclerosis, and can be used as surrogate outcome measures in treatment trials.

[Use of various bibliometric methods in operative evaluation of research activities of the research institutions of medico- biological profile]. / Ispol'zovanie nekotorykh bibliometricheskikh priemov dlia operativnoi otsenki nauchnoi deiatel'nosti nauchno- issledovatel'skikh uchrezhdenii mediko-biologicheskogo profilia.

Based on the analysis of the indices accepted for the evaluation of scientific work in research institutes, a suggestion was proposed that the putative instead of realized value of the scientific product should be evaluated. This implies employment of such bibliometric techniques of analysis of the volume and quality of the used information as: total number of references in scientific works, reference to the most recent publications and foreign sources, and the interdisciplinary index rated according to the subject-relation of the cited works. Studies of selected indices based on the analysis of one-year scientific journal publications and of manuscripts sent for print, as well as of reports made by the Kiev Research Institute of Otorhinolaryngology of UkrSSR Ministry of Health and by the Research Institute of Hematology of BSSR Ministry of Health, paralleled with a comprehensive consideration of the reference peculiarities and expert evaluation of the scientific material proper, allowed for making a conclusion on the importance of the role played by the bibliometric data in making the expert formal and objective and in operative evaluation of the activity of scientific communities and/or trends. This is of special significance for information and scientific policy making. Such investigations may be carried out by expert information workers.

[Treatment of suppurative-necrotic foot lesions in diabetes mellitus]. / Lechenie gnoino-nekroticheskikh porazhenii stopy pri sakharnom diabete.

On the basis of observation of 103 patients with diabetes mellitus who had angiopathy complicated by pyo-necrotic lesion of the foot, the authors give recommendations on the most effective complex treatment aimed at normalization of carbohydrate metabolism, reduction of intoxication and degree of metabolic disorders which allowed the amount of amputations to be reduced to 28.1%.

[Histochemistry of proteins and their functionally active groups in the skin of the neck and mucous membrane of the oral cavity of white rats in the zone exposed to a helium-neon laser]. / Gistokhimiia belkov i ikh funktsional'nogo aktivnykh grupp v kozh shei i slizistoi obolochke polosti rta belykh krys v zone vozdeistviia gelii-neonovym lazerom

The author made experiments on 49 white rats exposing their cervical skin ano oral cavity mucous membrane to the irradiation beam of a 40 mvt helium-neon laser (lambda 6328A) during 10-15 minutes. The reactive capacity of proteins was found to have intensified and the content of functionally active groups, especially SH. to have increased as well as well as the activity of the cytochromozydase. When the exposition to laser irradiation was raised to 30 minutes pronounced morphohistochemical lesions were noted in the cervical skin and oral cavity mucous membrane. The data received may be useful in clinical practice for the application of low-power laser irradiation of 6328A wave length for stimulation of metabolic processes.

Deldrin toxicity and successive discrimation reversal in squirrel monkeys (Saimiri sciureus).

Seven squirrel monkeys were systematically exposed to dieldrin (C12H10DC16) at two oral doses: 0.10 and 0.01 mg/kg-day. Two zero-dose controls were included. After 55 days of exposure dose assignments were shifted and continued for an additional 54 days. The higher dose group was shifted to zero exposure and lower dose group was shifted to high-dose exposure. Controls continued at zero exposure. The monkeys were presented with a visual nonspatial successive discrimination reversal task. During the first 55 days (preshift), control and low-dose monkeys learned the task; high-dose monkeys did not (p less than 0.001). During the subsequent 54 days (postshift), all groups performances remained at the approximate level achieved at the end of the preshift period. It was concluded that the high dose disrupted learning acquisition. This effect is speculated to be attributed to disruption of hippocampal activity. The low dose had no effect on task acquisition or maintenance.