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Biomedical subjects

M Koskiniemi

Publications and source records attributed to M Koskiniemi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo.

OBJECTIVE: To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy. METHODS: Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day. RESULTS: Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient. CONCLUSIONS: This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage.

Activities of Daily Living↗
PubMed1998

Clinical features and genetics of progressive myoclonus epilepsy of the Univerricht-Lundborg type.

Progressive myoclonus epilepsy of the Unverricht-Lundborg type is the most common cause of progressive myoclonus epilepsy worldwide. Typical features include onset at the age of 6-15 years, stimulus-sensitive myoclonus, tonic-clonic seizures, a progressive course and characteristic electroencephalographic findings with an exceptionally high sensitivity to photic stimulation. With modern anticonvulsive therapy the symptoms are relatively well controlled, and the disease may not always progress. Previously, no biochemical or pathological marker existed for the diagnosis of Unverricht-Lundborg disease. The positional cloning strategy was applied to identify the genetic defects that are responsible for this disease. The underlying gene encodes cystatin B, a cysteine protease inhibitor. The major mutation worldwide is an unstable expansion of a dodecamer minisatellite repeat unit in the promoter region of the cystatin B gene. In addition, five 'minor' mutations have been described. In the majority of patients, a reduced level of the cystatin B gene product seems to be the primary mechanism in the pathology, but the pathogenetic mechanisms are yet unknown. The molecular genetic findings have made a specific diagnosis possible and are the basis for understanding the molecular pathogenesis of the disease. This understanding may lead to the development of specific therapies for Unverricht-Lundborg disease.

Adolescent↗
PubMed1997

Epidemiology and prognosis of acute myelitis in Southern Finland.

In this study we analyzed all acute adult (>15 years) myelitis cases in the province of Uusimaa in Southern Finland during the years 1981-1993. Only cases with acute infectious myelitis were included. Demyelinating diseases, and medullopaties due to degeneration, traumatic, toxic, hereditary, nutritional or metabolic causes were excluded. A total of 45 patients fulfilled the criteria. The mean incidence was 3.5 cases/million inhabitants/year. The mean latency time from the initial infection to the beginning of neurological symptoms was 11 days. Motor paraparesis was found in 62% and tetraparesis in 13%. Sensory symptoms were found in 82% and bowel disturbances were experienced by 71% of patients. Normal cerebrospinal fluid (CSF) leukocytes were seen in 18% of patients, and CSF protein was elevated in 70% of patients. Case fatality was 6.7%. Permanent care in hospital needed by 13% of patients, and after 24 months 88% were ambulatory. Prognosis is quite good in myelitis, and normal CSF leukocytes do not exclude myelitis.

Acute Disease↗
PubMed1997

Seroprevalence and coprevalence of HIV and HBsAg in Nigerian children with/without protein energy malnutrition.

In order to assess the seroprevalence and coprevalence of hepatitis-B surface antigen (HBsAg), human immunodeficiency virus-1 and -2 (HIV-1 and -2) antibodies in Nigerian children with/without protein energy malnutrition (PEM), we studied plasma specimens of 206 children with PEM and 200 apparently healthy reference children aged between 1 and 3 years by enzyme-linked immunosorbent assays (ELISA). HIV-seropositive cases were confirmed by immunoblotting (IB). Of the children studied, eight (4%) of the healthy and four (1.9%) of the malnourished (P = 0.22, Fisher's exact test) were positive for HIV-1 antibodies, 40 (20%) of the healthy and 54 (26%) of the malnourished (P = 0.14) were positive for HBsAg, and five (2.5%) of the healthy and four (1.9%) of the malnourished (P = 0.70) were positive for both HIV-1/HBsAg. No case of HIV-2 antibodies was found. While the seroprevalence of HBsAg was higher in the malnourished subjects, the reverse was the case with HIV antibodies. However, all the four HIV-1-positive malnourished children and five of eight of the HIV-1-positive reference children were simultaneously positive for HBsAg. This is the first epidemiological report on the seroprevalence and coprevalence of HIV and HBsAg in apparently healthy and malnourished Nigerian children.

Child, Preschool↗
PubMed1997

Radiological signs in newborns exposed to primary Toxoplasma infection in utero.

A total of 44 181 serum samples from 16 733 pregnant women were analyzed for findings suggesting primary Toxoplasma infection. Thirty-seven newborns exposed to maternal primary Toxoplasma infection in utero were studied prospectively with ultrasound, CT, and MRI for signs of intrauterine infection. Their mothers had been treated during pregnancy, and all infants were treated. The children were assigned to three groups according to their mothers' serological status, and the radiological results were compared with the clinical outcome. Although radiological signs were scarce, ultrasound findings combined with maternal serology were found to be significantly related to clinical outcome.

Abdomen↗
PubMed1997

Epidemiology of encephalitis in children. A prospective multicentre study.

UNLABELLED: We found 175 cases with acute encephalitis in a population of 791,712 children aged 1 month-15 years during a 2-year surveillance period in 1993-1994. The overall incidence was 10.5/100,000 child-years with the highest figure in children < 1 year of age, 18.4/100,000 child-years. The microbial diagnosis was considered proven or suggested in 110 cases (63%); varicella zoster, respiratory and enteroviruses comprised 61% of these, and adeno, Epstein Barr-, herpes simplex and rota viruses comprised 5% each. A clearcut change seems to have occurred in the aetiology of encephalitis. Mumps, measles, and rubella virus associated encephalitides have been almost eliminated. Varicella zoster, respiratory, and enteroviruses have increased in frequency and occur in younger age groups. New causes were identified, especially Chlamydia pneumoniae and HHV-6. Our data should assist in making a specific diagnosis and defining appropriate antimicrobial therapy. CONCLUSIONS: The spectrum of encephalitis in children has changed due to vaccination programs. The incidence, however, appears to be about the same due to increasing frequency of other associated old and new microbes.

Acute Disease↗
PubMed1997

Luminometric microplate hybridization for detection of varicella-zoster virus PCR product from cerebrospinal fluid.

We modified and optimized a new microplate hybridization assay to detect the varciella-zoster virus (VZV) PCR product, and studied cerebrospinal fluid (CSF) samples of 287 patients with meningitis, encephalitis or other neurological diseases or symptoms. Specific antibodies to VZV and reference antigens were determined by enzyme immunoassay from serum and CSF, they were then compared with clinical findings and with the results obtained by VZV-PCR using different detection methods for VZV-specific amplified DNA. VZV DNA was found in the CSF of 25 patients using the microplate hybridization assay and chemiluminescence detection for amplified DNA. All 25 CSF samples were also positive in Southern blotting. Among the patients, 10 had chickenpox, 4 had shingles, and 11 had no rash at all. The detection rate of VZV-specific DNA by microplate hybridization was 30% higher than that obtained by conventional agarose gel electrophoresis. In most patients the diagnosis was confirmed by demonstrating specific intrathecal antibody production to VZV but not to other viruses. These results indicate the presence of VZV in the central nervous system (CNS) in many patients with chickenpox or shingles, and even in patients without a rash. The microplate hybridization assay based on chemiluminescence detection improves considerably the detection rate of the VZV-PCR product compared to agarose gel electrophoresis and will add to the list of recognized VZV infections in the CNS. It is especially useful in cases where there is no cutaneous manifestation.

Chickenpox↗
PubMed1997

Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1.

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder that occurs with a low frequency in many populations but is more common in Finland and the Mediterranean region. It is characterized by stimulus-sensitive myoclonus and tonic-clonic seizures with onset at age 6-15 years, typical electroencephalographic abnormalities and a variable rate of progression between and within families. Following the initial mapping of the EPM1 gene to chromosome 21 (ref. 6) and the refinement of the critical region to a small interval, positional cloning identified the gene encoding cystatin B (CST6), a cysteine protease inhibitor, as the gene underlying EPM1 (ref. 10). Levels of messenger RNA encoded by CST6 were dramatically decreased in patients. A 3' splice site and a stop codon mutation were identified in three families, leaving most mutations uncharacterized. In this study, we report a novel type of disease-causing mutation, an unstable 15- to 18-mer minisatellite repeat expansion in the putative promoter region of the CST6 gene. The mutation accounts for the majority of EPM1 patients worldwide. Haplotype data are compatible with a single ancestral founder mutation. The length of the repeat array differs between chromosomes and families, but changes in repeat number seem to be comparatively rare events.

Cystatin B↗
PubMed1997

Assessment of plasma fibronectin in malnourished Nigerian children.

BACKGROUND: Severe malnutrition is associated with septic infections. The concentrations of fibronectin, albumin, and transferrin in plasma were measured in three groups of children with protein-energy malnutrition, aged 1-3 years, each group comprising 20 children. The aim of which was to test whether plasma fibronectin, being an opsonic protein, was reduced in such children, and if it was a useful index for assessing the severity of malnutrition. METHODS: The concentrations of fibronectin, albumin, and transferrin in plasma were studied by enzyme immunoassay/ immunoblotting, spectrophotometry and immunoturbidimetry respectively. RESULTS: All values were significantly lower in the patients with malnutrition than in the age- and sex-matched well-nourished Nigerian reference children. Within the malnourished group, the fibronectin value was evenly reduced in all subgroups. Albumin and transferrin values were lowest in the patients with kwashiorkor, highest in the marasmic patients, and intermediate in the patients with marasmic kwashiorkor; the values correlated mutually in individual cases as well, but not with the fibronectin levels. Neither plasma fibronectin fragmentation nor tissue fibronectin was detected in any patient with malnutrition or in the reference subjects. CONCLUSIONS: The reduced plasma fibronectin values in these patients may be due to reduced synthesis by the liver, as evidenced by the equally reduced albumin and transferrin concentrations and/or to the multiple infections characteristic of the patients.

Biomarkers↗
PubMed1997

Cerebrospinal fluid plasminogen activator inhibitor-1 in patients with neurological disease.

AIM: To study cerebrospinal fluid (CSF) concentrations of plasminogen activator inhibitor type-1 (PAI-1) in patients with neurological disease. METHODS: CSF PAI-1 concentrations were measured in 51 patients with neurological disease and 20 reference subjects using an ELISA. The patient group comprised three patients with viral meningitis, 20 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia (with central nervous system involvement), and 19 with multiple sclerosis. RESULTS: Raised PAI-1 concentrations were observed in patients with leukaemia, encephalitis and multiple sclerosis. There was no difference in the mean concentrations of PAI-1 in patients with meningitis when compared with the reference subjects. The highest mean (SEM) PAI-1 concentration was found in patients with leukaemia (1.28 (0.36) ng/ml), and the next highest in those with encephalitis (1.19 (0.20) ng/ml). these values were much higher than those in patients with viral meningitis. In a previous report, raised CSF tissue-type plasminogen activator (tPA) activities were detected in patients with multiple sclerosis, leukaemia and encephalitis, with mean activities in decreasing order. PAI-1 concentrations in the same patients were the reverse of their corresponding tPA activities, being higher in those with leukaemia and encephalitis, than in patients with multiple sclerosis. There was no association between CSF PAI-1 concentrations and age in either patients or controls. Similarly, there was no association between CSF PAI-1 concentrations and urokinase-type plasminogen activator (uPA). CONCLUSIONS: Raised CSF PAI-1 concentrations may be used as a non-specific marker of neurological disease. Moreover, PAI-1 may play an important role in regulating the functions tPA, and probably uPA, in CSF.

Adolescent↗
PubMed1996

Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1)

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is an autosomal recessive inherited form of epilepsy, previously linked to human chromosome 21q22.3. The gene encoding cystatin B was shown to be localized to this region, and levels of messenger RNA encoded by this gene were found to be decreased in cells from affected individuals. Two mutations, a 3' splice site mutation and a stop codon mutation, were identified in the gene encoding cystatin B in EPM1 patients but were not present in unaffected individuals. These results provide evidence that mutations in the gene encoding cystatin B are responsible for the primary defect in patients with EPM1.

Amino Acid Sequence↗
PubMed1996

Cerebrospinal fluid activity of tissue plasminogen activator in patients with neurological diseases.

AIM: To study cerebrospinal fluid (CSF) activity of tissue plasminogen activator (tPA) in patients with neurological diseases. METHODS: CSF tPA and urokinase (uPA) activities were studied using an immunocapture assay and zymography in 44 patients with neurological disease and 20 reference subjects. The patient group comprised three patients with meningitis, 21 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia, seven with multiple sclerosis, three with facial paresis, and one with polyradiculitis. RESULTS: Raised tPA activities were observed in patients with multiple sclerosis, leukaemia and encephalitis. In contrast, there were no differences in the mean activities of tPA in patients with meningitis or other diseases compared with the reference subjects. The highest tPA activities were found in patients with multiple sclerosis. The mean activity in patients with leukaemia was higher than in those with meningitis and polyradiculitis, but not encephalitis and facial paresis. Although the CSF tPA activity correlated positively with age in reference subjects, no correlation was observed in patients. Samples were qualitatively screened for both tPA and uPA activity by zymography and positive samples were quantitated. Some of the samples had quantifiable levels of uPA activity: three of seven multiple sclerosis samples, 10 of 21 samples from patients with encephalitis and five of nine leukaemic samples. The highest activities were recorded in patients with leukaemia. uPA was not detected in the CSF of the patients with meningitis, facial paresis or polyradiculitis. CONCLUSIONS: Plasminogen activator activity can be measured reliably in CSF and the assessment of tPA activity may be useful for studying the pathogenesis of neurological diseases.

Adolescent↗
PubMed1996

Herpes encephalitis is a disease of middle aged and elderly people: polymerase chain reaction for detection of herpes simplex virus in the CSF of 516 patients with encephalitis. The Study Group.

OBJECTIVE: To assess the diagnostic potential of the polymerase chain reaction (PCR) in herpes simplex virus (HSV) encephalitis. METHODS: Samples of CSF from 516 patients with encephalitis were studied for HSV-DNA by PCR. RESULTS: Samples taken one to 29 days from the onset of symptoms from 38 patients (7.4%) were positive, 32 (6.2%) for HSV-1 and six (1.2%) for HSV-2. At follow up, eight of 28 patients studied were still HSV-PCR positive. A diagnostic serum:CSF antibody ratio to HSV but not to other viruses was detected in 25 of the 38 HSV-PCR positive patients thus supporting the initial PCR findings. Patients positive by HSV-PCR were concentrated in the age group > or = 40 years, and especially in patients aged 60-64 years, of whom nine of 24 (37.5%) were positive. The HSV-PCR was negative in all other patients with encephalitis of known or unknown aetiology. This group included 34 patients with a diagnostic serum:CSF antibody ratio to other viruses. A dual infection, HSV and another microbe, was considered possible in seven patients. CONCLUSIONS: The HSV-PCR is a rapid and useful diagnostic method during the early phase of encephalitis. It may be useful in monitoring the efficacy of treatment and allowing the recognition of new features in the appearance of herpes encephalitis. The HSV-PCR test and antibody determinations from serum and CSF are complementary methods, which should both be applied in pursuit of clinical laboratory diagnosis of these conditions.

Age Distribution↗
PubMed1996

Chlamydia pneumoniae associated with central nervous system infections.

We identified 15 patients with serological evidence of current Chlamydia pneumoniae infection when we studied 263 patients with central nervous system infections among an adult population of 3 million in 1993. In 9 of the 15 patients no other associated or etiological agents were found. One patient died. Sequelae appeared in 7 patients. In neurological infections, C. pneumoniae may be more prevalent as an associated agent than appreciated, and adequate antibiotic therapy may be life-saving.

Adolescent↗
PubMed1996

Stillbirths and maternal antibodies to Chlamydia trachomatis. A new EIA test for serology.

OBJECTIVE: The relationship between stillbirths and infections during pregnancy. METHODS: Antibodies to 13 different viruses and to Mycoplasma pneumoniae, Treponema pallidum, Toxoplasma gondii, and Chlamydia trachomatis, psittaci, and pneumoniae were studied from sera of 42 mothers with stillbirth and of matched case-control pregnancies. RESULTS: Elevated antibody levels to Chlamydia trachomatis and human parvovirus B19 were observed in seven mothers with stillbirth as compared with one in matched case controls (p-0.03 and p < 0.06, Fisher's exact one- and two-tailed p values). By a novel EIA test for C. trachomatis, based on synthetic polypeptide, 15 positive cases were detected in patients compared to seven in controls. Placental calcifications and fetal growth retardation appeared more often (p < 0.001 and p < 0.05, respectively) in the C. trachomatis- associated cases than in the others. There was no significant relation between stillbirth and the other antibodies. CONCLUSIONS: We suggest C. trachomatis as a hitherto unrecognized possible cause of still-births besides human parvovirus B19. A new EIA test for C. trachomatis, one covering all strains, is promising and makes the future assays more convenient, and may thus make it possible to reduce the rate of stillbirths.

Adult↗
PubMed1995

Long-term outcome after severe brain injury in preschoolers is worse than expected.

OBJECTIVE: To determine the long-term outcome after severe brain injury at preschool age. DESIGN: Follow-up until adult life. SETTING: A centralized guidance center for all traffic-associated injuries. PATIENTS: Children with severe brain injury at preschool age between January 1959 and December 1969. MAIN OUTCOME MEASURE: Final evaluation in adulthood was performed by our team. The capability to work and live independently was rated. RESULTS: Twenty three (59%) of 39 children attended a typical school, eight (21%) attended a school for the physically disabled, and seven (18%) attended a school for the mentally retarded; information was not available for one child. In adulthood, nine patients (23%) were able to work full-time, 10 (26%) worked at sheltered workplaces, 14 (36%) lived independently at home, and six (15%) needed physical and/or psychotherapeutic support. The difference between normal school performance (59%) and capability to work full-time (23%) was significant (P < .05). In evaluating different aspects after the severe brain injury, the sense of identity was the best indicator of final outcome. CONCLUSIONS: The final evaluation of severe brain injury at preschool age should be performed in adulthood. Normal school performance or normal intelligence functioning is not a guarantee for good long-term prognosis. To let the child develop a firm identity is essential for good outcome.

Accidents, Traffic↗
PubMed1995

Chlamydia trachomatis seropositivity during pregnancy is associated with perinatal complications.

Sera from the mothers of all children from the greater Helsinki area who were treated in the Neonatal Intensive Care Unit (NICU) of Children's Hospital (University of Helsinki) during a 22-month period were studied serologically, and antibody levels for mothers were compared with those for matched controls. IgM to Chlamydia trachomatis serotype GFK was detected more often in sera from mothers with children in the NICU than in that from controls; IgM was detected in sera from 39 of 264 mothers vs. 15 of 274 controls (P < .001; two-tailed test). The gestational age of children born to mothers in the IgM-seropositive group was 32.4 weeks whereas that of children born to mothers in the IgG/IgM-seronegative group was 34.3 weeks (all children were treated in the NICU). The frequency of signs of maternal infection (i.e., fever and vaginal discharge), the frequency of meconium-stained amniotic fluid, the frequency of chorioamnionitis, and the mortality rate were higher in the IgM-seropositive group than in the IgM-seronegative group; pneumonia, atelectasis, and pneumothorax occurred more frequently in the seronegative group. Thus, in terms of birth weight and perinatal infections, the outcome was better for children whose mothers did not have antibodies to C. trachomatis.

Adult↗