PubMed Health⌕ Search

Biomedical subjects

L I Persson

Publications and source records attributed to L I Persson.

At least 19 recordsLinked to original sources
PubMed2003

A double-blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine: effects on CSF glutamate, aspartate, branched-chain amino acid levels and clinical parameters.

OBJECTIVES: A study was conducted to examine the effect of lamotrigine (LTG) in amyotrophic lateral sclerosis (ALS). MATERIAL AND METHODS: Patients were entered in a double-blind, placebo-controlled, crossover study. None of the patients were treated with riluzole, which was not approved for treatment of ALS in Sweden when the study started. After randomization, each patient was treated with placebo or LTG 300 mg daily, followed by a washout period and a second treatment period. RESULTS: Thirty patients completed the study and were included in the analysis of the primary outcome, which was measured with clinical scales. The cerebrospinal fluid (CSF) levels of glutamate, aspartate, branched-chain amino acids and LTG were also measured. Changes for glutamate, valine and LTG were found during the progression of the disease. The clinical parameters and the levels of CSF amino acids were similar for the two treatment groups. CONCLUSION: No clinical effect of LTG on ALS progression could be found.

Adult↗
PubMed1996

Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF.

In the present study we describe an ELISA to quantify the light subunit of the neurofilament triplet protein (NFL) in CSF. The method was validated by measuring CSF NFL concentrations in healthy individuals and in two well-characterized groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). The levels were increased in ALS (1,743 +/- 1,661 ng/L; mean +/- SD) and AD (346 +/- 176 ng/L) compared with controls (138 +/- 31 ng/L; p < 0.0001 for both). Within the ALS group, patients with lower motor neuron signs only had lower NFL levels (360 +/- 237 ng/L) than those with signs of upper motor neuron disease (2,435 +/- 1,633 ng/L) (p < 0.05). In a second study patients with miscellaneous neurodegenerative diseases were investigated (vascular dementia, olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral infarctions, and multiple sclerosis), and the CSF NFL level was found to be increased (665 +/- 385 ng/L; p < 0.0001). NFL is a main structural protein of axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in general, but particularly in ALS with involvement of the pyramidal tract.

Aged↗
PubMed1995

Seizure frequency and CSF parameters in a double-blind placebo controlled trial of gabapentin in patients with intractable complex partial seizures.

Gabapentin (GBP) is a non-protein-bound gamma amino acid which is not subjected to metabolic degradation in man. As part of a placebo-controlled double-blind study, patients suffering from intractable complex partial seizures with or without secondary generalization were followed with lumbar punctures at baseline and after three months of GBP treatment (900 mg/day or 1200 mg/day). Cerebrospinal fluid (CSF) was analyzed for concentrations of GBP, amino acids including GABA, homovanillic acid (HVA), and 5 hydroxyindoleacetic acid (5-HIAA). The results indicate that there were no changes in the selected amino acids, HVA, or 5-HIAA after GBP treatment. At steady state the CSF/plasma ratios of GBP ranged from 0.056 to 0.34, indicating that there may be some type of active out-transport of GBP across the blood-brain barrier. No linear relationship was observed between plasma and CSF levels in these patients.

Acetates↗
PubMed1994

Inclusion body myositis: clinical, morphological, physiological and laboratory findings in 18 cases.

Eighteen consecutive patients with inclusion body myositis (IBM) were studied. The mean age of onset of symptoms was 60 years. A typical clinical pattern with insidious onset of muscle weakness in knee extensors and finger flexors combined with dysphagia was observed. Serial measurements of the maximal voluntary muscle strength revealed a mean loss of muscle strength of 1.4% per month. Two of the cases had common variable immunodeficiency, and three cases had reduced levels of the IgG3 subclass. Treatment with prednisone resulted in a temporary improvement of muscle function in three patients. No positive effect of azathioprine or cyclosporine A could be documented. The results show that IBM may be associated with immunodeficiency, and that prednisone treatment may temporarily improve the clinical signs. The results from our studies on the progression of the muscle weakness may provide basis for future studies on treatment of IBM.

Adrenal Cortex Hormones↗
PubMed1992

Selected CSF biochemistry and gabapentin concentrations in the CSF and plasma in patients with partial seizures after a single oral dose of gabapentin.

Gabapentin (GBP) is a neutral amino acid and a GABA analog which in animal experimental models has shown a broad anticonvulsant spectrum. To evaluate the penetration of GBP into the CSF in humans as well as its possible effects on free and total GABA, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), a special investigation was performed as part of a placebo controlled add-on study of GBP in partial epilepsy. At the end of the 3-month double-blind period, 5 patients on placebo were given a single oral dose of GBP. Four patients received 600 mg and 1 patient 1200 mg GBP. CSF was collected immediately before and at 6, 24 and 72 h after the single dose. 5 ml of plasma was collected at 1, 2, 3, 6, 12, 24, 48 and 72 h. Plasma concentrations and plasma elimination half-life (4-6 h) of GBP were in agreement with the results of previous studies. The CSF/plasma concentration ratio of GBP 6 h after drug was 0.1. After 24 h, GBP could only be recovered in the CSF of the patient given 1200 mg. The CSF/plasma ratio at that time was 0.3. Free and total GABA concentrations did not change, but CSF 5-HIAA and HVA increased at 24 and 72 h post dose. The CSF/plasma ratio of gabapentin is similar to that of other amino acids.

Acetates↗
PubMed1991

Effect of long-term vigabatrin therapy on selected neurotransmitter concentrations in cerebrospinal fluid.

Ten patients, suffering from drug-resistant complex partial seizures were treated for a period of up to 3 years with vigabatrin (Sabril). Vigabatrin is a novel antiepileptic agent, whose action is based on the inhibition of gamma-aminobutyric acid (GABA) aminotransferase, the enzyme responsible for the catabolism of the neurotransmitter GABA. Samples of lumbar cerebrospinal fluid were obtained from the patients prior to commencing vigabatrin therapy, and thereafter at 6 months, 1 year, 2 years, and up to 3 years following the initiation of vigabatrin treatment. The influence of vigabatrin on the cerebrospinal fluid concentrations of free and total GABA, homocarnosine, homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol, as well as of the drug itself, was assessed. All patients demonstrated a clinical response to vigabatrin, and the drug was well tolerated over the entire observation period. Mean (+/- SD) reduction of seizure frequency was 65% +/- 23% (range, 26% to 100%) when comparing the end of the treatment period to the previgabatrin baseline. The cerebrospinal fluid concentrations of both free and total GABA and of the dipeptide homocarnosine showed approximately 2- to 5-fold increases over baseline values, with free GABA and homocarnosine being the more sensitive variables. Cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were not altered in a significant manner over the observation period. These findings support the concept that the effects of vigabatrin are restricted to an effect on GABA catabolism and do not extend to the neurotransmitters dopamine and norepinephrine. Clinical efficacy and elevation of GABA and homocarnosine concentration were sustained over the period of observation.

Adult↗
PubMed1990

Differences in side effects between a conventional carbamazepine preparation and a slow-release preparation of carbamazepine.

The aim of this double-blind cross-over study was to investigate whether side effects of carbamazepine (CBZ) could be reduced by using a slow-release CBZ preparation. Twenty-one adult patients with epilepsy who had side effects related to the use of CBZ took part in the trial. Patients were randomized to receive either a conventional (C) or slow-release (SR) CBZ preparation for 3 months and were then switched over to the other preparation for another 3 months. The daily dose and dosing frequency of CBZ were kept the same as before the study. The quality and severity of side effects were assessed monthly using a scored questionnaire containing questions about systemic toxicity (STRS) and neurotoxicity (NTRS). Twenty patients could be evaluated. The mean total values of NTRS of 3 monthly visits on each drug were significantly less during SR than during C treatment (P less than 0.05). All the items of NTRS scored lower during SR therapy, and the difference was significant for the occurrence of headache, dizziness and disturbances of vision, speech and coordination. The total score of STRS was also lower during SR, but the difference was not significant. Eleven patients preferred SR, 3 preferred C and 6 patients estimated the periods to be equal. In conclusion, a slow-release preparation of CBZ can render fewer side effects than conventional CBZ preparations.

Adult↗
PubMed1989

Microwave effects on the central nervous system--a study of radar mechanics.

Seventeen radar mechanics and engineers and 12 unexposed referents were examined, using extensive neurological, psychometric and neuropsychiatric techniques to determine whether there were any indications of central nervous system effects of microwave exposure. Pathological neurological findings were not more common in the exposed group than among the referents. In addition, the psychometric tests and the psychiatric rating scales did not reveal any statistically significant adverse effects of microwave exposure. The frequency of the occurrence of an increased protein band with an isoelectric point of 4.5 in the cerebrospinal fluid was higher among the men exposed to microwaves than among the referents. The nature and clinical significance of this or these proteins are still unclear. The time derivative of the magnetic flux density close to some of the transmitter units was surprisingly high (up to 350 T s-1).

Central Nervous System↗
PubMed1989

Changes in CSF and brain soluble proteins following vigabatrin treatment in rats.

1. Following the discovery of vacuoles in the white matter of the brain of small animals treated with vigabatrin (GVG) it was decided to investigate possible reasons for the occurrence of these vacuoles and to explore the possibility of finding CSF markers which could be applicable for monitoring toxicity in humans. 2. An animal model was developed to study the changes of protein synthesis and to assay soluble brain proteins by isoelectric focusing and two-dimensional electrophoretic techniques. 3. Five groups of rats were treated either with 300 mg kg-1 day-1 GVG, 50 mg kg-1 GVG every other day, 300 mg kg-1 day-1 sodium valproate, 100 mg kg-1 day-1 sodium valproate or sham treated. 4. All animals were given the drug in a liquid full nutrient diet. The dietary intake of the different groups was adjusted to the group which showed the smallest dietary intake, to compensate for possible differences between groups due to nutritional factors. 5. The rats on 300 mg kg-1 day-1 GVG had a 30% reduction of body weight and a 6% reduction of their brain weight, compared with the lower GVG dose group, the two valproate groups and the sham treated group. 6. The synthesis of soluble proteins in the cerebral cortex, hippocampus and cerebellum was decreased in rats given GVG at 300 mg kg-1 day-1 and was increased in rats given valproate at 300 mg kg-1 day-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminocaproates↗
PubMed1989

The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients.

1. Vigabatrin, 50 mg kg-1, was administered orally as add-on therapy to 11 patients with drug-resistant complex partial epilepsy as a single dose, then once every third day for 2 months, every other day for 2 months and daily for 1 month. 2. Lumbar punctures were carried out prior to treatment and at the end of each dosage regimen and cerebrospinal fluid (CSF) evaluated for concentrations of free and total GABA, homocarnosine (GABA-histidine dipeptide), homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA) and vigabatrin. 3. Each regimen resulted in significant increases in CSF concentrations of free and total GABA and homocarnosine compared with the immediately preceding regimen. 4. CSF concentrations of HVA significantly increased after a single vigabatrin dose but returned to pre-treatment levels with subsequent dosing schedules. In contrast, 5-HIAA concentrations also increased with the single dose but were significantly decreased, compared with pre-treatment values, following alternate day and daily vigabatrin administration. 5. Seizure frequency progressively decreased with decreasing dosing interval. Daily vigabatrin administration was associated with greater than 50% decrease in seizures in 8 of the 10 patients treated.

Adult↗
PubMed1984

Cellular composition of primary cultures from cerebral cortex, striatum, hippocampus, brainstem and cerebellum.

Primary cultures from newborn rat cerebral cortex, striatum, hippocampus, brainstem and cerebellum were grown for 14 days. There was a linear relationship between the amount of material seeded and the protein content of the respective culture. The amount of tissue material seeded was selected so that the different cultures reached confluence at 6-7 days and contained similar amounts of protein when 7 and 14 days old. The cellular content was evaluated by astroglial markers, such as the glial fibrillary acidic protein (GFAp; alpha-albumin) and the S-100 protein, and by markers for other cells expected to be in the cultures (14-3-2 protein, macrophage acidic protein (MAP), alkaline phosphatase, myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP]. Astroglial-like cells represented 60-70% of the cells present in the different cultures. Quantitation of GFAp (alpha-albumin) showed similar amounts to be present in cultures from cerebral cortex, hippocampus and striatum; however, on lower levels expressed in soluble proteins than in the corresponding brain regions of adult rats. Brainstem of adult rat contained large amounts of GFAp (alpha-albumin), while low levels were found in brainstem culture. Also, phagocytic cells (macrophages), endothelial-like cells, mesenchymal-like cells, ependymal-like cells and oligoblasts were found. Neither mature neurons, nor oligodendroglial cells were observed. It is concluded that although there might be some differences in the degree of maturation or in the cellular composition of the various cultures, they could serve as a good model system for studying the characteristics of astroglial cells from various brain regions.

Animals↗
PubMed1983

Effect of radiologic contrast media and local anaesthetics on the blood-brain barrier and on the leptomeninges.

The leptomeninges of cats were exposed to lidocaine, metrizamide and methiodal sodium and compared with control brains exposed to Ringer's solution. As a sign of blood-brain barrier damage, an increased extravasation of albumin into the cerebral cortex was recorded after exposure to methiodal sodium; lidocaine or metrizamide did not produce such damage. Scanning electron microscopy revealed minor cellular reactions in the mesothelial cells of the leptomeninges after application of metrizamide, lidocaine and Ringer's solution. Methiodal sodium produced an extensive cellular damage of the leptomeningeal cells. The importance of testing the leptomeningeal reactions and the reactions of the blood-brain barrier to all liquid media used on the brain surface is emphasized.

Animals↗
PubMed1982

Exposure of the cat brain surface to neurosurgical irrigation fluids, hydrogen peroxide and air. Quantitative assay of blood-brain barrier dysfunction.

The effect of different irrigation fluids used in neurosurgery and of cortical exposure to air or hydrogen peroxides on the cat brain surface was tested by quantitative assay of extravasated albumen in the cortex and the white matter. Ringer's solution and Elliott's solution B induced no major blood-brain barrier (BBB) dysfunction after closed subdural perfusion for 3 hours. Normal saline induced slight BBB dysfunction extending throughout the cortex into the white matter after the same time of exposure. When these three solutions were applied to the brain surface via pledgets during exposure for 3 hours no further damage was induced. If 15 minutes exposure to air preceded the open perfusion via pledgets with Ringer's solution or Elliott's solution B for 2 hours and 45 minutes, no significant cortical BBB dysfunction was induced. There was a manifold increase in BBB dysfunction after perfusion with Ringer's solution or Elliott's solution B for 2 hours and 45 minutes followed by exposure to three per cent hydrogen peroxide for 5 minutes and a further 10 minutes perfusion with the previous irrigation fluid. Thus, normal saline was found unsuitable for neurosurgical irrigation purposes, due to disturbance of the BBB. Ringer's solution and Elliott's solution B protected the brain adequately even if only applied in pledgets. A short period of exposure to air had no effect on the BBB in the cortex, whilst exposure to hydrogen peroxide was detrimental to the BBB.

Animals↗
PubMed1982

Increased blood-brain barrier dysfunction around cerebral stab wounds in rats immunized to brain antigens. A quantitative study on endogenous albumin and globulin.

The extravasation of serum albumin and immunoglobulin G (IgG) was assayed by electroimmunoassay in cerebral cortex homogenates of rats subjected to stab wound injury either 2 weeks after immunisation to brain antigens or without prior immunisation. The amount of IgG in the brain was significantly higher in immunised than in non-immunised rats 3 and 24 h after injury. A significantly enhanced extravasation of albumin in immunised rats was found only after 24 h. It is concluded that immunisation to brain antigens enhances the vulnerability of the blood-brain barrier in rats subjected to stab wound injury.

Animals↗
PubMed1981

Acidic protein in macrophages.

An antiserum to unstimulated rat peritoneal macrophages was produced in rabbits. The antibodies were directed against an acidic protein with a molecular weight of 35,000 and with an isoelectric point at 4.6. The macrophage acidic protein (MAP) was purified by gel filtration of rat lung soluble proteins, followed by preparative isoelectric focusing. The preparation of MAP was pure as assayed by agar gel electrophoresis and showed one precipitation peak in crossed immunoelectrophoresis against the crude antiserum directed against peritoneal macrophages. The purified MAP was used for immunization of rabbits, and the antiserum obtained was monospecific, assayed by crossed immunoelectrophoresis and Grabar-Williams immunoelectrophoresis. The titre was 4 times higher in the anti-MAP antiserum (1:80) than in the crude antimacrophage antiserum (1:20), tested against MAP by counter-current immunoelectrophoresis. The antigen (MAP) was demonstrated by direct and indirect immunofluorescence microscopy in rat blood monocytes, in spleen and lung monocytic cells, in clusters of cells in the thymus, and in adventitial macrophages around larger blood vessels in liver, kidney, lung and brain. Scattered meningeal macrophages showed fluorescence in the normal, brain. In stab-wounded areas of rat brain MAP was localized to perivascular and perineuronal macrophages with a morphology similar to that of microglial cells. The localization of the fluorescence was the same both for the antiserum against MAP and for the antiserum raised against crude peritoneal macrophages.

Animals↗