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Biomedical subjects

H Frey

Publications and source records attributed to H Frey.

At least 37 records · Page 2Linked to original sources

Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer's disease.

The apoE phenotype of 83 patients with probable Alzheimer's disease (AD) and of 164 non-demented controls was determined by isoelectric focusing and Western blotting. The proportion of the epsilon 4 allele was 0.548 in AD and 0.202 in controls (P < 0.0001). The effect was seen in both early-onset and late-onset AD patients. The risk of AD in epsilon 4 homozygotes was 18-fold greater than in individuals without the epsilon 4 allele. ApoE concentrations were measured in serum and cerebrospinal fluid (CSF) from a subgroup of patients with AD (n = 72) and controls (n = 84) by a sandwich enzyme-linked immunosorbent assay. Although serum apoE concentrations were lower in individuals with the epsilon 4 allele than in those without the epsilon 4 allele, CSF apoE concentrations did not vary in different phenotype groups. However, CSF apoE levels were lower in AD patients than in controls. We conclude that the inheritance of the epsilon 4 allele of apoE is a risk factor for AD in the Finnish population.

Age of Onset↗

Two-dimensional analysis of qualitative and quantitative changes in blood cell proteins in Alzheimer's disease: search for extraneuronal markers.

Numerous abnormalities have been reported to exist in tissues outside the central nervous system in Alzheimer's disease (AD), supporting the conception of the illness as a systemic disorder. Two-dimensional (2-D) polyacrylamide gel electrophoresis with an immobilized pH gradient of 4-8 in the first dimension combined with computer-assisted image analysis was applied in investigation of extraneuronal proteins of blood cell origin in AD to search for extraneuronal markers. No qualitative protein changes specific for the condition could be observed. However, many statistically significant quantitative alterations were detected when AD and control 2-D patterns of extracts prepared from red blood cell membranes, platelets and lymphocytes were compared. One of these spots, with a marked change in mean intensity value, was identified as actin. The concentration of this protein was significantly reduced in AD platelets and lymphocytes.

Aged↗

Soluble amyloid beta-protein in the cerebrospinal fluid from patients with Alzheimer's disease, vascular dementia and controls.

Cerebrospinal fluid (CSF) soluble amyloid beta-protein (sA beta) concentrations from 69 patients with Alzheimer's disease (AD), 23 patients with vascular dementia (VD), and 76 non-demented controls were measured by a sandwich enzyme linked immunosorbent assay using two monoclonal antibodies (4G8 and 6E10) specific for A beta. sA beta concentrations were lower in CSF from patients with AD or VD compared to those in controls. CSF sA beta concentrations did not correlate with the Mini-Mental State Examination scores in patients with AD. VD patients with moderate to severe dementia had lower CSF sA beta concentrations than those with mild dementia. Because a considerable overlap of CSF sA beta levels existed between AD and control groups, the assay is not useful as a diagnostic test for AD.

Aged↗

[Analysis of blood from the inferior sinus petrosus in patients with Cushing syndrome and acromegaly].

Bilateral catheterization of sinus petrosus inferior was performed in ten patients with Cushing's syndrome and five patients with acromegaly. This was done in order to secure the diagnosis (Cushing's syndrome) and localize an adenoma (Cushing's syndrome and acromegaly). Blood from sinus petrosus inferior on both sides and from the peripheral vein was analyzed for concentration of ACTH or growth hormone after injection of ACTH-releasing hormone and growth hormone-releasing hormone respectively. The quotient between the ACTH concentration in blood from sinus petrosus and peripheral blood determines the diagnosis in Cushing's syndrome and the quotient between the concentration of ACTH or growth hormone between right and left sinus petrosus determines localization of the pituitary adenoma. Correct diagnosis and localization of ACTH-producing pituitary adenoma was found in eight of ten patients with Cushing's syndrome. One result was doubtful and one was wrong. In four patients with Cushing's disease (ACTH-producing adenoma) magnetic tomography (MT) was negative, but catheterization showed the presence of adenoma. In acromegalic patients, correct localization of the adenoma was determined in two out of five patients. In the other three patients, anatomical difficulties prevented satisfactory interpretation.

Acromegaly↗

Alzheimer brain proteins investigated by two-dimensional gel electrophoresis with immobilized pH gradients in the first dimension.

Two-dimensional (2-D) gel electrophoresis with immobilized pH gradient 4-8 in the first dimension was applied in the analysis of Alzheimer's disease brain proteins. The silver-stained 2-D maps of extracts from the frontal cerebral cortex were examined. About 800 and 550 protein spots could be observed on the electrophoretograms from the total and buffer-soluble fractions, respectively. In comparing the gels, four protein spots could now be detected which had either been hitherto undetectable (one spot) or which were weaker (two spots) or stronger (one spot) in density (in the controls) [corrected].

Aged↗

Presence of non-fibrillar amyloid beta protein in skin biopsies of Alzheimer's disease (AD), Down's syndrome and non-AD normal persons.

A total of 66 skin biopsies from persons with Alzheimer's disease (AD) or Down's syndrome (DS) and from persons without AD were used in this study. The age range was from 7 to 89 years. Positive immunoreactivity of skin biopsies to monoclonal antibody 4G8, which is reactive to amino acid residue 17-24 of synthetic amyloid beta protein (A beta), and 4G8-Fab (the antigen-binding fragment of 4G8 IgG, reactive only to amyloid plaque) was observed in the epidermis-dermis junction or the basement membrane of the epidermis and in some blood vessels of the biopsy skins of 13/18 (72%) AD, 9/10 (90%) DS, and 14/38 (37%) non-AD control cases. The Fisher exact probability test revealed a significant difference (P = 0.0415 one-tailed) in immunoreactivity between AD and age-matched controls. There was also a significant difference (P = 0.0152 one-tailed; P = 0.0200 two-tailed) between DS and age-matched control in the same test. Immuno-gold electron microscopy examination of these cases with positive immunoreactivity revealed that the gold particles were deposited along the basement membrane of the epidermis. Amyloid fibrils were not observed in the regions with gold particles. Results of this study suggest that A beta is associated with the basement membrane of skin and is present in amorphous, non-fibrillar form as soluble A beta.

Adolescent↗

Evaluation of a computerized system for recognition of epileptic activity during long-term EEG recording.

A new method of recognition of epileptic activity using adaptive segmentation in EEG during long-term intensive monitoring was developed in Tampere. The performance of the system was validated and compared to the commercially available discharge recognition system of Gotman. Twelve approximately 30 min EEG segments recorded during intensive monitoring from 6 patients were analysed. On these EEG segments two EEG specialists marked the occurrence of epileptic activity independently. Later they re-evaluated any differences in their scoring. This consensus file was used as a reference in validating the performance of the two computer programs. We found that the program developed in Tampere detected discharge activity more often than the Gotman system. Both systems performed poorly in spike recognition. In the specificity of the recognized segments, the Gotman system was better.

Computer Systems↗

Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis.

There are several formulas for the quantitative determination of intrathecal IgG production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these formulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) samples from 125 healthy individuals, 18-88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8-30); and 106 patients with definite multiple sclerosis (MS). The relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF (r = 0.95; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two formulas based on a nonlinear relation between the CSF/S albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values in the presence of BBB damage, probably because of incorrect constants in these formulas. There were no significant correlations between the CSF/S albumin ratio (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGGPROD, an empirical formula for the determination of intrathecal IgG production in mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evaluation of Epilepsy Expert--a decision support system.

Epilepsy Expert is a decision support system based on the International Classification of Epilepsies and Epileptic Syndromes (1989). The aim of this study was to evaluate the Epilepsy Expert. First the diagnostic performance was validated. This was done in 3 stages: collection of the patient cases, determination of the 'correct diagnoses' and testing the system. How the users perceived the functionality of the system was studied by using an inquiry. Three physicians, experts of epilepsy, from different hospitals were asked to choose 10 patients. In the patient description was a short history, a detailed description of the seizure, EEG findings and their own diagnosis. Next, each expert made a diagnosis of the cases supplied by other experts by using the International Classification of Epilepsies and Epileptic Syndromes. The 'correct diagnosis' (so-called majority agreement) was the diagnosis given by the majority of the experts. The diagnosis of each expert was compared with the 'correct diagnosis'. The diagnoses obtained by the Epilepsy Expert were then compared with the 'correct diagnoses'. In the evaluation the expert physicians agreed on 37% of cases and all 3 disagreed on 17%. A majority agreed on 25 cases, which were used in the evaluation. In these 25 cases the experts' (A,B,C) diagnoses were correct or partly correct in 100, 64, 80% of cases, respectively. The program's diagnoses were correct or partly correct in 80% (module I) and 76% (modules IV and V) of cases. In the evaluation Epilepsy Expert was found to be only partly successful. The main reason for this was the weakness of the international classification. However, the program seems to be very close to the level of the experts. According to this limited inquiry Epilepsy Expert is not suitable for clinical use, because it is, for example, too simple and does not contain enough information.

Adult↗

Altered blood-brain-barrier function in Alzheimer's disease?

Alzheimer's disease (AD) and vascular dementia (VD) are the two most common causes of dementia. As yet, no definitive biological antemortem marker has been established for differential diagnosis of AD or VD. In this study, proteins of cerebrospinal fluid (CSF) from AD, VD and control patients were analyzed by two-dimensional (2-D) electrophoresis with immobilized pH gradients in the first dimension. No specific changes for AD or VD could be detected in the 2-D CSF patterns. However, a spot of haptoglobin alpha-1 chains (13.5 kDa; approximate pI 4.6) was found to be present in the majority of 2-D CSF maps from the dementia cases, suggesting a high-molecular-weight transudate type of alteration in the blood-brain barrier with considerable frequency in AD.

Aged↗

Second-order stereology of benign and malignant alterations of the human mammary gland.

The purpose of the present study was a quantitative characterization of the three-dimensional arrangement of the epithelial component of benign and malignant alterations of the female breast by combining stereology with stochastic geometry. Twenty cases of fibrous mastopathy and 20 cases of invasive ductal mammary cancer were studied at the light microscopic level. Segmentation of the epithelial tissue component was performed with an image analyser. From the resulting binary images, unbiased estimates of the covariance C(r) and the intensity Vv of the epithelial volume component were obtained automatically by computer. From these data, estimates of the correlation function k(r), of the pair correlation function g(r), of the radial distribution function RDF(r) and of the reduced second moment function K(r) of epithelial volume were determined. The estimates of C(r) and RDF(r) differed between groups, but these functions depend on spatial pattern and Vv. As carcinomas showed a significantly higher epithelial volume density Vv than mastopathies, estimation of C(r) and RDF(r) alone did not permit a safe distinction between possibly different types of spatial arrangement of epithelium in the benign and malignant lesions. Analysis of the estimates of k(r), g(r) and K(r), which are not influenced by Vv, showed definite interaction between epithelial volume elements, with clustering at short distances and repulsion at long distances. In both groups, the null hypothesis of purely random arrangement of epithelium had to be rejected. The clearest distinction between groups was obtained by estimation of g(r), which showed that short-range, tubular pattern as well as long-range, lobular architecture are better preserved in benign than in malignant lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Effect of advanced brain atrophy and vitamin deficiency on cognitive functions in non-demented subjects.

The relationship between the cognitive functions, structural changes of the brain and vitamin levels was evaluated in 36 non-demented subjects with advanced brain atrophy, and 57 age- and sex-matched healthy controls. In the control subjects ageing was associated with mild decline of cognitive skills, but the cognitive changes were not linked to the structural changes of the brain. In contrast, advanced brain atrophy and vitamin deficiency was related to the decline of complex cognitive functions in the atrophy group. Our results indicate that there are limits of normal age-related changes of the brain structure, and advanced brain atrophy on CT scans increase the probability of mild deficits of the cognitive skills.

Aged↗

Central nervous system involvement and psychiatric manifestations in systemic sclerosis (scleroderma): clinical and neurophysiological evaluation.

We evaluated central nervous system and psychiatric involvement in a clinical sample of 32 patients with systemic sclerosis (SSc) (scleroderma). All patients underwent clinical neurological examination. Electroencephalography (EEG) and visual evoked potentials (VEPs) were also recorded. Prominent central nervous system (CNS) or psychiatric symptoms were present in 5 patients (16%), including encephalopathy, psychosis, anxiety disorder, grand mal seizures and transient ischemic attack. In addition, abnormal VEPs were recorded from 5/32 patients (16%), suggesting optic neuropathy. EEGs were mainly normal or showed only slight, nonspecific changes. Primary CNS involvement in scleroderma, however, could not be shown in any of the 5 cases with neuropsychiatric symptoms. Our results suggest that neuropsychiatric symptoms in SSc are, if not coincidental, indirectly caused by internal organ involvement of SSc or by possible overlapping connective tissue diseases. On the other hand, optic neuropathy might be a primary complication of SSc.

Adult↗

Nervous system involvement in systemic lupus erythematosus, Sjögren syndrome and scleroderma.

INTRODUCTION: The purpose of this study was to determine, whether there are any differences in the occurrence of nervous system involvement in different systemic rheumatic diseases. The further aim of the present study was to identify and distinguish primary involvement of the nervous system by these diseases and involvement that may be secondary to confounding factors. MATERIAL AND METHODS: The patient population consisted of 122 patients with a connective tissue disease (42 with systemic lupus erythematosus (SLE), 48 with Sjögren's syndrome and 32 with scleroderma). The methods included neurological examination and standard electrophysiological tests. RESULTS: At least one neurological defect was diagnosed in 69% of SLE patients, in 71% of Sjögren's syndrome patients and in 66% of scleroderma patients. Secondary factors might have contributed to the pathogenesis of neurological symptoms and signs in up to 25-34% of events. CONCLUSION: No significant differences were noted in the occurrence of neurological events in patients with SLE, Sjögren's syndrome and scleroderma. The necessity to differentiate between neurological phenomena directly attributed to the systemic rheumatic disease and those which are totally unrelated or secondary events resulting indirectly from involvement of other organ systems is emphasized.

Adult↗

Brain atrophy in neurodegenerative diseases. Quantitative and qualitative CT analysis.

A quantitative and qualitative analysis was done of 187 CT examinations in 59 healthy subjects and 128 patients with various neurodegenerative diseases. The rates of agreement between quantitative measurements and the qualitative grading by two observers were 76.7% for the evaluation of lateral ventricular size and 66.3% for the assessment of sulcal size. Increase in the width of the 3rd ventricle, in the bi-caudate span, and in the area of the lateral ventricles reflected a pathologic enlargement of the ventricles. The profile of ventricular dilatation in dementia patients was different from that of other patients with brain atrophy. However, the quantitative measurement of brain atrophy by a computer-based method did not increase the differential diagnostic accuracy among dementia patients. The results stress the importance of the selection of valid measures in the evaluation of structural changes of the brain. We suggest the use of reference scans for improving the reliability of the visual evaluation.

Adult↗

The decrease of CD8-positive lymphocytes in Alzheimer's disease.

The aim of this study was to analyze the possible association of the changes in systemic immunity in the neurodegenerative diseases and in brain atrophy per se. Therefore we enumerated the numbers and proportions of the CD3-, CD4- and CD8-positive cells and B-lymphocytes in peripheral blood of 136 patients with various neurodegenerative disorders of the brain and 58 healthy age-matched controls. The selective decrease of the CD8-positive lymphocytes was demonstrated in the patients with Alzheimer's disease. In contrast, in the patients with brain atrophy of unknown origin and in the patients with vascular dementia the number of the CD8-positive cells tended to increase. The results suggest that brain degenerative changes are associated with changes in the systemic immunity and the changes are linked with the underlying disorder more than brain degeneration per se.

Adult↗

Nervous system disease, immunological features, and HLA phenotype in Sjögren's syndrome.

Twenty seven patients with primary or possible Sjögren's syndrome with neurological manifestations were compared immunologically with 21 patients with Sjögren's syndrome with an intact nervous system. Patients with Sjögren's syndrome were divided into seropositive and seronegative subgroups with respect to the occurrence of one or more autoantibodies (antinuclear antibodies, rheumatoid factor, antibodies to SS-B) in their serum samples. This study of 48 patients indicates that the spectrum of nervous system disease in seronegative and seropositive subgroups is almost indistinguishable. No significant differences were found in the occurrence of circulating immune complexes, the levels of serum complement C3 and C4, or serum IgA, IgM, and beta 2 microglobulin with respect to the neurological manifestations. The serum IgG level, however, was significantly higher in the patients with Sjögren's syndrome with intact nervous systems than in those with neurological manifestations. No significant association was found between the HLA phenotype and nervous system disease. The occurrence of HLA-B8 and DR3 antigens was, however, significantly higher in those patients with antibodies to SS-B than in those without. This finding supports the suggestion that HLA-B8/DR3 may modulate autoantibody responses rather than disease expression in Sjögren's syndrome.

Adult↗