Aspirin dose in prevention of transient ischaemic attacks.
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Biomedical subjects
Publications and source records attributed to J E Olsson.
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On a clinical basis it is sometimes impossible to distinguish between small intracerebral hematomas and reversible ischemic strokes (RIND). Analysis of the cerebrospinal fluid (CSF) has been used in ths context for several years and is still of importance even since the introduction of computerized tomography (CT) of the brain. CSF has been examined in 23 patients with intracerebral hematomas. Typical cell changes with an increase of poly- and mononuclear white cells are seen within the first days after the stroke, whereas clearly pathological spectrophotometric changes are not seen until about one week after the stroke. None of the investigated patients had a significant increase of the absorbance values at the wavelenths 406 and 415 nm (met- and oxyhemoglobin) until 5 days after the stroke.
The activities of acid phosphatase and N-acetyl-beta-glucosaminidase have been measured in 171 samples of cerebrospinal fluid from 104 patients suffering from multiple sclerosis. The mean level of activity of these enzymes was lower than of controls. Patients who had the first or second bouts had somewhat higher activity of these enzymes compared to controls. The lowest values of these enzymes were found in patients with severe disability. Patients with late onset of the disease had higher levels of the enzymes compared to patients with an earlier debut of the illness, whereas patients with a short history had higher values than patients with a longer duration.
Experimental portal-systemic shunting is accompanied by a reduction of the soluble brain proteins. Isoelectric focusing does not indicate any selective decrease of one particular protein or group of proteins. The reduction persists with sustained shunting. The interference with brain protein metabolism is compatible with a grossly normal behavior, alterness and locomotion.
Cerebrospinal fluid (CSF) and serum from 139 patients with MS were analyzed with electrophoresis on agar gel (AGE) and isoelectric focusing (IEF) on polyacrylamide gel. In both methods, 82 percent of the patients had abnormal patterns of oligoclonal IgG bands in the gamma globulin and alkaline regions. With IEF, 10 percent of the serum samples contained faint bands corresponding to the bands in CSF. Most of the bands were found in the cathodal part of the alkaline IEF region, but there was no correlation with clinical characteristics. Each patient seems to have a special band pattern which does not change throughout the disease. The gamma-trace protein was seen in 77 percent of the patients on IEF and in 29 percent on AGE. On IEF it appeared at two positions, at pH 8.0 and 9.3, but about 10 other bands were seen in the "normal" alkaline CSF region, making the band pattern of IEF more difficult to interpret than that of AGE. This limits the routine clinical value of IEF, even if the high resolution capacity of this method is useful in research.
In three families with hereditary ataxia, where the inheritance pattern was autosomal and dominant, HLA antigens were determined in 25 members. In two of the families, HLA linkage of disease was suggested, whereas in the third family, the data did not directly support this concept, since two recombinational events between the postulated locus for disease and the HLA region had to be assumed. However, with this assumption, our data are compatible with those of one family described recently (Jackson et al. 1977) implying the presence on the sixth chromosome, outside the HLA region, of a locus that determines the development of spino cerebellar ataxia (SCA). Further tests with definition of enzyme markers will have to be performed before conclusions as to HLA linkage of a postulated SCA gene can be made.
The activities of four lysosomal acid hydrolases, beta-galactosidase, alpha-mannosidase at pH 4.5 and 5.5, N-acetyl-beta-glucosaminidase, and acid phosphatase, have been measured in serum and cerebrospinal fluid from 179 patients with different neurological diseases and from 20 healthy controls. In patients with tumours, decreased activity of beta-galactosidase was found in both serum and cerebrospinal fluid, and in patients with multiple sclerosis and collagen diseases, decreased activities of beta-galactosidase and N-acetyl-beta-glucosaminidase were found in cerebrospinal fluid. The variations of enzyme activities were great between the individual patients even with these groups and analysis of lysosomal enzymes seems to have a very poor clinical value.
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The results of neuro-ophthalmological examination, visual evoked responses (VER) to pattern reversal stimulation and cerebrospinal fluid (CSF) analysis were compared in 25 patients with myelopathy of unknown etiology and without subjective symptoms of involvement of CNS outside the spinal cord. Delayed latencies of VER indicating a disseminated disease were found in 76 per cent of the patients. In 64 per cent of the patients, CSF showed abnormalities similar to those found in MS. Pathological findings at the clinical eye examination consistent with such an etiology was found in 36 per cent of the cases. It is suggested that a large proportion of patients with myelopathy of unknown etiology suffer from a disseminated demyelinating disorder similar to MS. By a combination of neuro-ophthalmological, VER and CSF examinations such as etiology can be established with reasonable certainty, and more troublesome investigations such as myelographies and spinal angiographies may be restricted to patients in whom the etiology still remains unclear.
Brain proteins were analyzed in supra- and infratentorial structures of 6 patients dying from liver failure. An equal number of patients, lacking any evidence of liver disease or neurological disorder, served as controls. The results were related to regional light microscopic findings. Hepatic coma was associated with a marked reduction of soluble brain proteins, particularly in areas of grey matter. The protein loss is probably neuronal and may be secondary to abnormalities in glial function. Implications for the pathogenesis of hepatic encephalopathy are discussed.
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Eight families from southern Sweden having two or more members with multiple sclerosis (MS) were typed for various alleles of the HLA system. The MS patients within each family shared one major histocompatibility system (MHS) haplotype, which was identical to the hitherto-described MS-associated haplotype A3B7Dw2 only in two of the families. Healthy relatives of MS patients were often found to carry the same haplotype as the affected members, which makes an estimate of the degree of penetrance of disease in individuals carrying the MS-predisposing MHS-linked gene possible.
Cerebrospinal fluid (CSF) and serum from 35 pairs of multiple sclerosis (MS) patients were analysed as regards mononuclear pleocytosis, concentrations of total protein, immunoglobulin G and A and beta-trace protein, and kappa:lambda ratios, as well as the serum/CSF ratios of IgG and albumin. The disability of the patients differed, whereas the age and the duration of the disease were similar in each pair. Similar analyses were also performed on CSF and serum from 72 patients, who were subdivided according to age at onset and severity of the disease. The highest mean values of the CSF-IgG and the lowest mean values of the serum/CSF IgG ratios were found in the more disabled patients. CSF immunoglobulin abnormalities were encountered more often and were more pronounced in the patients with the most malignant course of the disease, i.e., in those with severe disability after a short duration of the disease (less than 10 yr) and in severely disabled patients with an early age at onset of the disease(less than 25 yr). Contrarily, normal mean values of CSF-IgG concentrations and serum/CFS/IgG ratios were found in the groups of patients without disability after a duration of the disease of 10 years or more, and patients without disability and an early age at onset of the disease (less than 25 yr). The observations indicate that the immune response is most vigorous in disabled patients with a short duration or with an early age at onset of the disease. MS patients with a late age at onset (greater than 35 yr) showed a less pronouced immune response within the CNS, irrespective of the occurrence of disability. The most disabled patients also showed the most severe blood-brain barrier damage as manifested by high mean values of total protein in CSF and low serum/CSF albumin ratios. The patients with severe disability and a long duration of the disease (greater than 10 yr) had the highest content of beta-trace protein in the CSF, probably as a sign of destruction of brain matter.
Alphafetoprotein (AFP) and beta-trace protein (BTP) concentrations have been measured in amniotic fluids taken from 19 pregnancies where the outcome was an infant with a neural tube defect and from 19 matched controls. There was no significant difference in the mean BTP values for the pathological samples when compared with the controls, and there were no striking differences in the values within individual matched pairs. On the other hand, the mean AFP concentration in the abnormal amniotic fluids was approximately 15 times the mean value found in the controls. Differences within individual pairs were particularly noticeable early in pregnancy. It is concluded that BTP is of no use for the early antenatal diagnosis of anencephaly and spina bifida.
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The sites of synthesis of the low molecular weight beta-trace protein, present in a seven times higher concentration in normal human CSF than in normal human serum, have been studied by means of a radioactive immunoprecipitation method. Adult squirrel monkey tissues were cultured in Eagle's minimum essential medium in the presence of 14C-labelled valine, threonine and leucine for 24 hours. Synthesis could be demonstrated in cultures of white CNS matter, whereas cultures of grey CNS matter, peripheral nerve, skeletal muscle, kidney and ovary did not show any signs of synthesis. Some cultures of spinal cord, basal ganglia, genital organs except ovary, and liver showed a probable synthesis of beta-trace protein. By means of autoradiography, the synthesis of beta-trace protein in white CNS matter could be confirmed.
One hundred seventy-eight patients with transient ischemic attacks (TIAs) or small strokes with slight symptoms persisting for more than 24 hours (incomplete recovery = IR) (TIA-IR) from both the carotid and the vertebrobasilar systems were treated with anticoagulants. Ten patients stopped the treatment because of severe side effects. Only one patient had a lethal cerebral infarction when the thrombotest values were above the therapeutic level; no other infarction happened during the treatment period. Moreover, the frequency of TIA decreased during the treatment, compared with descriptions of the natural course of TIA. One hundred four patients were observed for a mean of 21 months after the anticoagulant treatment ended. During the observation period, six patients had cerebral infarctions. This was a sixfold increase compared with the stroke incidence during treatment, and was almost identical with the incidence of strokes seen during the natural course of TIA. All the cerebral infarctions were in patients who had their initial TIA/TIA-IR from the carotid territory (within the same carotid artery which earlier had given symptoms). The investigation shows that long-term anticoagulant treatment is useful, especially in patients with carotid TIA/TIA-IR, and that this treatment should continue as long as the patients can manage it. In patients with vertebrobasilar symptoms of malignant character, it seems feasible to terminate the treatment after about one year. The mechanism of the anticoagulant treatment is obscure, but it does not appear to influence the progress of the atherosclerotic process.