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Biomedical subjects

Jukka Peltola

Publications and source records attributed to Jukka Peltola.

At least 19 recordsLinked to original sources

Changes in plasma amino acids after electroconvulsive therapy of depressed patients.

There are indications that mood disorders may be related to perturbations in the amino acid transmitters. The amino acids may thus be targets of treatment of depression. The purpose of this pilot study was to measure the acute effects of a single administration of electroconvulsive therapy (ECT) on the plasma levels of amino acids in depressed patients. ECT was administered to 10 patients with major depressive disorder. Altogether 23 plasma amino acids were analyzed before and at 2, 6, 24 and 48 h after ECT. The levels of glutamate and aspartate increased at 6 h after ECT compared with the baseline. Also the levels of total tryptophan increased 2-24 h after ECT. There were also elevations in other amino acids at 6 and 24 h. The levels of gamma-aminobutyric acid (GABA) decreased at 2 h. In this study the acute effects of single ECT were associated with changes in the levels of glutamate, aspartate, GABA, tryptophan and some other amino acids. The preliminary data suggest that the therapeutic effects of ECT in depression may be due to mechanisms involving these amino acid transmitters.

Adult↗

A quantitative method for the assessment of intraepidermal nerve fibers in small-fiber neuropathy.

OBJECTIVES: The purpose of this paper is to present an easy-to-use and reproducible morphometrical method of determining the density of intraepidermal nerve fibers (IENF) per epidermal area with the corresponding reference range of the IENF-counts. METHODS: Thirty patients and 22 controls were included in this study. The patients were divided into three groups: small-fiber (SFN), diabetic and demyelinating neuropathy. All subjects underwent punch skin biopsy. Specimens were fixed routinely in formalin and thereafter embedded in paraffin. Nerve fibers were revealed using immunoperoxidase staining with panaxonal antibody PGP 9.5. Using light microscopy, immunopositive nerves were counted morphometrically per epidermal area (NPEA) and, for comparison, per epidermal length (NPEL). RESULTS: Both the NPEA and NPEL estimates of SFN and diabetic neuropathy group differed significantly from those of control specimen (p < 0.001 and p < 0.001, Mann-Whitney test). Our method of counting, NPEA, shows a good correlation to NPEL (r = 0.945). CONCLUSIONS: IENF-counting by a new morphometric modification is reproducible and diagnostically sensitive and can easily be adopted in any laboratory familiar with the basic immunohistochemical methodology. The method is less dependent on costly technical support systems and seems to be less time consuming when compared with conventional methods for IENF-counting.

Biopsy, Needle↗

Retention rate of oxcarbazepine monotherapy in an unselected population of adult epileptics.

In a retrospective study we assessed the outcome of oxcarbazepine (OXC) monotherapy in a naturalistic setting. We identified all adult patients who had been treated with OXC at a single neurological outpatient center. A total of 175 patients were identified, 97 of them used OXC as their first AED (Group I), and 78 as second monotherapy (Group II), after failure of a previous AED. The 1-year retention rates of OXC treatment were 91% for Group I and 77% for Group II. Discontinuations were due to adverse effects in 3 patients (3%) in Group I and in 11 patients (14%) in Group II, and due to lack of efficacy in 2 patients (2%) in Group I and in 6 patients (8%) in Group II. We conclude that OXC monotherapy is effective and well tolerated.

Adult↗

Serum IgA, IgG, and IgM concentrations in patients with epilepsy and matched controls: a cohort-based cross-sectional study.

Conflicting reports have been published on serum immunoglobulin (Ig) concentrations in patients with epilepsy. Serum IgA, IgG, and IgM concentrations were determined in a cohort of 958 patients and in a reference population of 581 subjects. Overall, 8.2% of patients with epilepsy and 1.9% of control subjects had low serum IgA concentrations. Low serum IgA levels were measured in 19.1% of patients currently on phenytoin therapy and in 11.9% of patients who had previously been treated with phenytoin, whereas only 3.8% of patients who had never been on phenytoin therapy had low serum IgA. In multivariate analysis low serum IgA concentrations were associated with phenytoin medication and female gender. No differences in serum IgG and IgM concentrations were observed between patients and control subjects. However, in patients with epilepsy, low serum IgG concentrations were associated with concomitant autoimmune diseases, and low IgM levels with older age at the onset of epilepsy, long duration of epilepsy, and autoimmune diseases. In conclusion, the prevalence of low serum IgA concentrations was increased in patients with epilepsy, but serum IgG and IgM concentrations were similar in patients with epilepsy and reference subjects. The low serum IgA concentrations were associated with phenytoin medication. In addition to current phenytoin medication, previous phenytoin therapy also was associated with low serum IgA concentrations. This implies that phenytoin medication may have permanent immunological effects in some patients.

Anticonvulsants↗

Celiac disease-related antibodies in an epilepsy cohort and matched reference population.

Celiac disease (CD) is a common immunologically mediated enteropathic condition manifesting in genetically predisposed individuals after exposure to wheat gluten. CD may be associated with a number of neurological disorders, and the prevalence of epilepsy is reported to be increased in patients with CD. We studied the prevalence of CD-associated antibodies in a cohort of 968 patients with epilepsy and in a population-based reference group of 584 subjects. There was no difference in the prevalence of IgA and IgG class antigliadin antibodies (AGAbA and AGAbG, respectively), endomysial antibodies (EMA), and tissue transglutaminase antibodies (tTGAbA) between patients with epilepsy and the control population. This suggests the presence of CD to be the same in patients with epilepsy and the reference population. However, AGAbA was more prevalent in patients with primary generalized epilepsy (19.6%) than in the reference population (10.6%, relative risk 1.8, 95% confidence interval 1.1-3.0, P=0.012).

Antibodies↗

Antimitochondrial antibodies in patients with epilepsy.

Immune mechanisms have been implicated in the pathogenesis of epilepsy. An increased prevalence of autoantibodies, as well as changes in serum immunoglobulin concentrations, has been reported in patients with epilepsy. The presence of unspecific antimitochondrial antibodies (AMAs) and their possible associations with other immunological markers were evaluated in a cohort of 1386 adult patients with epilepsy and population-based reference subjects. Unspecific AMAs were more frequent in epilepsy patients than in the reference group. Thirty-seven epilepsy patients (3.9%) and eleven control subjects (1.9%) had unspecific AMAs (RR 2.1, CI 1.05-4.1, P=0.03). These antibodies were associated with long duration of epilepsy and old age at the onset of epilepsy among patients with epilepsy. Their presence was independent of other immunological markers, comorbidity, and epilepsy medications.

Adult↗

Intranasal administration of human IL-6 increases the severity of chemically induced seizures in rats.

Here we study the role of a pleiotropic pro-inflammatory cytokine, interleukin-6 (IL-6), in epilepsy. To examine this problem, we used human recombinant IL-6 applied intranasally (400 ng/40 microl) to rats 1h before seizures induced by systemic injection of pentylenenetrazole (PTZ, 75 mg/kg). Overall, compared to the saline-treated control animals (n = 11 in each group), IL-6-treated rats demonstrated elevated levels of IL-6 in the frontal lobe (measured by ELISA) and increased severity of PTZ-induced seizures (shorter latency, longer duration and higher mortality). Our findings show that IL-6 plays a pro-convulsant role in the brain and suggest that the IL-6 system may be a novel target for the development of anticonvulsant drugs.

Administration, Intranasal↗

Increased serum matrix metalloproteinase 9 levels in systemic lupus erythematosus patients with neuropsychiatric manifestations and brain magnetic resonance imaging abnormalities.

OBJECTIVE: To evaluate whether serum matrix metalloproteinase 9 (MMP-9) levels are associated with neuropsychiatric manifestations, particularly cognitive dysfunction, as evaluated by neuropsychological testing and brain magnetic resonance imaging (MRI) abnormalities in patients with systemic lupus erythematosus (SLE). METHODS: MMP-9 determinations were made in 44 patients with SLE and 43 healthy controls who underwent a clinical neurologic and neuropsychological investigation in order to identify neuropsychiatric manifestations. Cerebral MRI scans with volumetric estimation of intracranial cerebrospinal fluid spaces, T1-weighted lesions, and T2-weighted lesions were performed for all subjects. SLE activity was assessed by the European Consensus Lupus Activity Measure (ECLAM) index, and accumulated neuropsychiatric abnormality was assessed by the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index. RESULTS: No significant difference was found in serum MMP-9 levels between the overall group of SLE patients and controls. However, SLE patients who had at least 1 neuropsychiatric manifestation (NPSLE patients) had significantly higher serum MMP-9 concentrations than did SLE patients without neuropsychiatric syndromes (P = 0.009). Among patients with NPSLE, those with cognitive deficits had significantly higher concentrations of serum MMP-9 than did those with normal cognitive function (P = 0.027). Furthermore, serum MMP-9 levels had a significant positive correlation with the volumes of T1-weighted and T2-weighted lesions in the brain MRI (P = 0.031 and P = 0.015, respectively). The concentration of serum MMP-9 correlated significantly with the SLICC index but not with the ECLAM index. CONCLUSION: Elevated levels of serum MMP-9 in patients with SLE may reflect neuropsychiatric involvement, particularly cognitive dysfunction. The serum MMP-9 concentration may be associated with small- vessel cerebral vasculopathy and increased risk of cerebral ischemic events in patients with SLE.

Adult↗

Outcome after prolonged convulsive seizures in 186 children: low morbidity, no mortality.

Prolonged convulsive seizures are a common neurological emergency and a potential cause of neuronal damage and functional sequelae. We explored the role of seizure duration and various background factors for neurological sequelae in children with prolonged convulsive seizures. The population-base of this study was all children (age < 16 years) who had been admitted to the Tampere University Hospital, Finland between 1993 and 1999 with convulsive seizures lasting more than 5 minutes. Patients were followed up individually (mean length of follow-up 2 years 1 month, range 0 to 7 years 8 months). All available data on the prolonged seizure episodes and clinical follow-up were analyzed retrospectively by a detailed review of all medical charts and records. In 186 children (94 males, 92 females; mean age 4 years 5 months, SD 3 years 10 months, range 1 month to 15 years 4 months) there were 279 separate convulsive seizure episodes lasting over 5 minutes, yielding an annual incidence of 47.5 out of every 100000 episodes. Seizure aetiology was idiopathic in 26.2% of episodes, febrile in 41.9%, remote symptomatic in 28%, and acute symptomatic in 3.9% of episodes. Mean duration of all seizure episodes was 42.5 minutes (SD 46.1 minutes) and was significantly correlated with the aetiology: shortest in the febrile group (mean 35.4 minutes) and longest in the acute symptomatic group (mean 88.6 minutes; p < 0.001). There was no mortality related directly to these acute seizure episodes. The most common sequela was an onset of epilepsy in 40 children (22%). Permanent neurological sequelae were noted in only four patients (2.2%; mean seizure duration 16 minutes) and non-permanent sequelae in six patients (3.2%; mean seizure duration 38 minutes). Neurological sequelae of prolonged convulsive seizures in children are rare and are related to aetiological factors rather than the duration of a single seizure. The role of acute seizures in the evolution of epilepsy in children remains obscure.

Adolescent↗

Plasma and cerebrospinal fluid amino acids in epileptic patients.

Altered plasma and cerebrospinal fluid amino acid levels may be associated with human epilepsy. We studied three groups of patients, those with a generalized epileptic syndrome, juvenile myoclonic epilepsy, patients with refractory localization-related epilepsies, and patients with acute seizures (within 24 h). Plasma levels of amino acids were studied in all patient groups, as were those in the cerebrospinal fluid (CSF) of patients with acute seizures. After acute seizures, the amino acid changes in the CSF were limited to a reduction in the level of taurine, whereas the levels of most amino acids in plasma were decreased. On the other hand, levels of the excitatory amino acids glutamate and aspartate were increased. The most notable finding in the juvenile myoclonic epilepsy patients was an increase in glutamate level in the plasma. Our study supports the conception of an altered metabolism of glutamate in generalized epilepsies.

Adult↗

Uptake of GABA and activity of GABA-transaminase in platelets from epileptic patients.

The aim of the present study was to assess the activity of GABA-transaminase (GABA-T) and the kinetic parameters of GABA uptake in platelets from patients with distinct epileptic syndromes. We studied 14 patients with juvenile myoclonic epilepsy (JME), 19 patients with refractory localization-related epilepsy (RLE) and 20 healthy volunteers who were matched for age and sex. Acute effects of valproate (VPA) and lamotrigine (LTG) on the uptake of GABA and the activity of GABA-T in platelets in vitro were also analyzed. The mean activity of GABA-T in JME patients was significantly higher than in control subjects, whereas RLE patients did not significantly differ from controls. The capacity of GABA uptake was least in JME patients, intermediate in RLE patients and highest in controls. In vitro VPA (concentrations 150-1200 microM) or LTG (concentrations 1-100 microM) had no significant effects on GABA uptake. Our results indicate marked differences in the platelet uptake of GABA and the activity of catabolic enzyme GABA-T between patients with generalized and localization-related epileptic syndromes. The observed peripheral alterations may indicate an impairment in the function of brain GABAergic systems.

4-Aminobutyrate Transaminase↗

Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: a population-based neuropsychological study.

We present a cross-sectional, population-based neuropsychological study of systemic lupus erythematosus (SLE) patients identified within Tampere University Hospital district, Finland with 440,000 inhabitants. Patients with definite SLE in the age range of 16-65 years (n = 46) and matched controls (n = 46) underwent neurological examination and comprehensive neuropsychological testing. On the basis of medical examination, the SLE patients were divided into neuropsychiatric (NP+; n = 15) and nonneuropsychiatric (NP-; n = 31) cases. The neuropsychological test results revealed more prevalent cognitive impairment in the NP+ patients, indicating that this subgroup mostly accounts for neuropsychological changes in SLE. Most characteristic changes in NP+ were observed in domains of memory, psychomotor speed, and complex attention. This suggests nonspecific CNS involvement, which is in line with neurological manifestations of the disease.

Adolescent↗

Naturally occurring human autoantibodies recognize a fetal brain antigen identified as microtubulus associated protein 1B.

We have recently reported naturally occurring autoantibodies against a large fetal brain antigen (FBA). Now we describe the process of purification and identification of this particular FBA. The brains of newborn rabbits were solubilized and purified with preparative gel electrophoresis. The protein fractions were concentrated and desalted and the fractions were tested by a known positive serum. On membrane digestion of the FBA-band gave a twelve amino acid sequence that resulted in best identity score for mouse, rat and human microtubule-associated protein (MAP) 1B: a member of the microtubule-associated protein family. Monoclonal anti-MAP1B recognized a band in immunoblots of the brain homogenate and of the partially purified fractions with the same electrophoretic mobility as that recognized by a known anti-FBA positive serum. When adult rabbit brain was used as an antigen, the anti-MAP1B failed to recognize any bands on immunoblots. MAP lB has not been previously known as an autoantigen, even though many structural proteins of the neuronal cytoskeleton are known to be targets of naturally occurring autoantibodies. MAP 1B is a functionally important regulatory protein in the developing brain; thus autoantibodies against MAP1B may affect the normal development.

Animals↗

The usefulness of video-EEG monitoring in elderly patients with seizure disorders.

The purpose of this paper was to evaluate the use of inpatient video-EEG (VEEG) monitoring in the evaluation of seizure disorders in elderly subjects. We retrospectively identified 36 patients aged 60 years old or over from a total of 849 patients studied at the VEEG unit of the Tampere University Hospital. Sixteen of the patients (44%) experienced at least one habitual seizure during the recording. Seven patients had epileptic seizures including two cases with status epilepticus. Nine patients had various non-epileptic disorders. VEEG had a clinically significant impact on the diagnosis and treatment in 14 of the 16 patients in whom paroxysmal events were recorded and proved to be useful in the evaluation of seizure disorders in elderly subjects.

Aged↗

The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients.

PURPOSE: Excessive neuronal activity and seizures directly stimulate cytokine expression. In this study we investigated cytokine production in circulating blood and peripheral blood mononuclear cells (PBMC) in order to assess the cellular origin of these cytokines in patients with therapy resistant epilepsy. METHODS: We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10 patients with therapy resistant localization-related epilepsy and in healthy volunteers. The spontaneous and exogenously stimulated production of these cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific cytokine production was studied using flow cytometry. RESULTS: Highly pro-inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS stimulated cytokine release was similar in PBMC cultures of patients and control subjects. When cells were stimulated with OKT3 the cytokine response profiles in patients with epilepsy were almost opposite (anti-inflammatory) to the profile which was observed in circulating blood. Low IL-6 was observed in cell cultures of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar in patients and control subjects. CONCLUSIONS: Patients with therapy resistant epilepsy display a pro-inflammatory profile of plasma cytokines without any evidence of increased production from PBMC. These results suggest that the most likely origin for these cytokines is the brain, where cytokines can exert neuromodulatory functions.

Adolescent↗