PubMed HealthSearch

Biomedical subjects

P Arlien-Søborg

Publications and source records attributed to P Arlien-Søborg.

At least 19 recordsLinked to original sources

A new mitochondrial tRNA(Met) gene mutation in a patient with dystrophic muscle and exercise intolerance.

A 30-year-old woman with a novel heteroplasmic U4409C mtDNA mutation in the tRNA(Met) gene presented with growth retardation, muscle weakness, severe exercise intolerance, and lactic acidosis. Muscle biopsy showed unusually severe dystrophic features. The mutation was not present in maternal relatives or 25 healthy subjects. Single-fiber PCR-RFLP analysis of mtDNA showed higher proportion of the mutation in COX-negative than in COX-positive muscle fibers.

Adult

Neuronal loss in hippocampus in rats exposed to toluene.

Both clinical and epidemiological studies of the effects of exposure to toluene have shown that long-term exposure may result in chronic toxic encephalopathy, where one of the major symptoms is memory deficits. We have attempted to identify the structural basis of the toxic effects of toluene in the hippocampus, a region of the brain known to be involved in learning and memory processes and well suited for stereological analysis. Rats were exposed to 1500 ppm of toluene, six hours per day, five days per week for six months. This was followed by a four-month-period without exposure prior to sacrifice. The total number of neurons in each of the five subdivisions of hippocampus of six exposed and six control rats was estimated with the optical fractionator. A statistically significant neuron loss of 16% was found in regio inferior (CA3 and CA2) of the exposed rats.

Animals

Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy.

INTRODUCTION: The effect of antiepileptic drugs (AED) on cognitive function was studied in 87 patients with epilepsy. MATERIAL AND METHODS: Group A: (n = 52) started AED treatment (carbamazepine, oxcarbazepine, sodium-valproate, phenobarbital or phenytoin). Group B: (n = 27) had AED monotherapy withdrawn (carbamazepine or sodium-valproate). Group C: (n = 8) was switched from phenytoin to carbamazepine monotherapy. The patients were tested before and 4 months after change of the treatment. RESULTS: In group A the test performances were in general unchanged. Patients who had their drug treatment withdrawn (group B) and the patients who were switched from phenytoin to carbamazepine (group C) improved in single tests. The predominant changes in performance seem to be due to practice effect. CONCLUSION: Cognitive functions are only minimally influenced by AEDs after short-term treatment whereas there is a slight improvement after discontinuation of long-term administration of carbamazepine and valproate. A lack of practice effect might be the first indicator of a negative effect of AED on cognitive function.

Adolescent

Long-term follow-up of cerebral infarction patients with proton magnetic resonance spectroscopy.

BACKGROUND AND PURPOSE: With proton magnetic resonance spectroscopy it is possible to measure the content of various brain metabolites in vivo, including N-acetylaspartate (which may be used as a neuronal marker), creatine, choline, and lactate. The content of these brain metabolites was measured serially from the acute stage to the chronic stage of infarction. Regional cerebral blood flow was also measured within the affected areas. These factors were compared with the clinical outcome. METHODS: Six patients with ischemic stroke were examined serially from the acute stage (< or = 2 days) to the chronic stage (> 6 months) with proton magnetic resonance spectroscopy. Cerebral blood flow was measured with single-photon emission-computed tomography with 99mTc-labeled d,l-hexamethylenepropyleneamine oxime as flow tracer. RESULTS: Lactate was found in all patients in the acute stage of stroke. Lactate was also found in the 3 largest lesions in the chronic stage; in 2 of these patients lactate was not found in the subacute stage. Reduced levels of N-acetylaspartate were found in 5 patients; in the sixth patient with a small lesion no reduction was found. In all lesions reduced blood flow was found in the acute and chronic stage, whereas hyperemia was found in 4 patients in the subacute stage. CONCLUSIONS: In this preliminary study no clear correlation was found between the level of N-acetylaspartate or lactate in the acute stage of stroke and the clinical outcome; however, there does appear to be some connection between the reduction of cerebral blood flow and the spectroscopic findings in the chronic stage and to some extent the clinical outcome. Studies of larger clinical groups will be necessary to further elucidate the prognostic potential of proton magnetic resonance spectroscopy in human stroke.

Adult

[Magnetic resonance spectroscopy of acute cerebral infarctions].

Eight patients with brain infarction were examined serially in the acute phase and one week and two to four weeks after stroke with water-suppressed proton magnetic resonance spectroscopy. Ten healthy volunteers served as controls. The time courses of N-acetylaspartate (NAA), total creatine (Cr), choline containing compounds (Cho), lactate content, and regional cerebral blood flow (rCBF) measured by SPECT were studied. A high lactate level was found in the acute phase. The lactate content decreased to barely detectable levels during the following two to four weeks, while rCBF increased during this period. The content of NAA in infarcted tissue was significantly reduced (p < 0.01) compared to healthy controls, Cr was also reduced (p < 0.02), whereas Cho content did not change. The inverse relationship between lactate level and cerebral blood flow suggests that lactate plays no substantial role in the vasodilatation underlying the hyperaemia that follows reperfusion. The amount of lactate present in the acute phase reflects the severity of ischaemia in the affected region. The content of NAA may be used as a neuronal marker, and thus perhaps as a marker of the effect of future treatment procedures.

Acute Disease

Myelography, CT, and MRI of the spinal canal in patients with myelopathy: a prospective study.

A prospective study including myelography, CT, and MRI was performed on 36 patients with clinical signs of myelopathy. Evoked potentials and spinal fluid examinations were also carried out. Based on our findings, the patients could be classified as suffering from cryptogenic myelopathy (n = 12), multiple sclerosis (n = 6), spinal stenosis (n = 6), or miscellaneous myelopathies (n = 12). The diameter of the spinal cord was normal in the 2 first groups of patients and of same magnitude evaluated by myelography and CT, while MRI constantly gave higher figures. In only four of the patients important new information was added by CT and MRI (syringomyelia, myelitis, lipomatosis) compared with myelography, although a more precise visualization was often provided. Further diagnostic progress in patients with myelopathy of undetermined etiology may be obtained by including supplementary MRI of the brain disclosing multiple sclerosis in several cases.

Adult

Clinical neurological findings among metal degreasers exposed to chlorinated solvents.

Among industrial solvents in present use trichloroethylene belongs to those which have been the concern of most neurological and occupational investigations since the beginning of this century. Reports on a broad spectrum of neurotoxicity are however mostly based on case-studies and accidental circumstances. The object of this study was to examine clinical neurological manifestations after long-term exposure to degreasing solvents, mainly trichloroethylene. The population was 99 metal degreasers, the design a historical cohort study. The most marked finding was a highly significant dose-response relation between solvent exposure and motor dyscoordination--a finding that was retained after multivariate control of relevant confounders. Vibration thresholds increased by solvent exposure at bivariate level, but the multivariate analysis showed that age was explaining most of the increase. No significant cranial nerve dysfunction was found.

Cohort Studies

Brain autopsy in organic solvent syndrome.

General autopsy findings, brain weight and brain pathology were studied in 98 men and five women who had been exposed occupationally to organic solvents over several years and assessed by the Danish National Board of Industrial Injuries for chronic toxic encephalopathy. The findings were compared with a forensic control material and a hospital control material. As in the general population, the most common causes of death among the exposed workers were heart failure and other vascular diseases. Due to the composition of the material (forensic cases), the number of suicides and violent deaths was high. Atherosclerosis was the most common CNS finding, but in comparison with the two control materials, no increase in the frequency of atherosclerosis or of Alzheimer's disease was found. Brain weights of the exposed workers corresponded closely to brain weights in the control materials, after correction for body height, body weight and age. Chronic alcoholism was correlated with slightly reduced brain weight.

Adult

Effects of six months' white spirit inhalation exposure in adult and old rats.

In two separate experiments in rats the irreversible effects of six months' exposure to white spirit (0, 400 p.p.m., and 800 p.p.m.) were studied. In one experiment the exposure started at the age of three months, in the other the rats were 15 months at the beginning of the exposure. After an exposure-free period of several months neurobehavioural, pathological, and neurochemical examinations were performed. A marked difference in motor activity between young and aged animals was found. A slight effect on kidney function was seen at 800 p.p.m. No macroscopic or histopathological changes related to dosing were found. The concentrations of noradrenaline, dopamine, and 5-hydroxytryptamine in various brain regions and in whole brain were irreversibly changed. In conclusion, the study revealed different changes within the CNS, but failed to demonstrate neurobehavioural white spirit-induced neurotoxicity.

Administration, Inhalation

Thrombolytic therapy in acute ischemic stroke. A Danish pilot study.

BACKGROUND AND PURPOSE: In a feasibility and safety study of thrombolytic therapy in acute ischemic stroke, we explored the usefulness of measurements of regional cerebral blood flow. METHODS: Twenty-three patients with acute ischemic stroke were treated with 100 mg recombinant tissue plasminogen activator infused intravenously over 1 hour. Thrombolytic therapy was initiated 78 to 355 minutes after onset of symptoms. RESULTS: Angiography 16 to 24 hours after treatment in 17 patients showed patient intracranial arteries in 12, partial occlusion of the middle cerebral artery in 3, and total occlusion of the middle cerebral artery in 2. rCBF with 99mTc-hexamethylpropyleneamine oxime intravenously was measured 5 minutes before and within 24 hours after thrombolytic therapy in 12 patients. 10 of the 12 patients showed brain tissue reperfusion and 2, with angiographically documented middle cerebral artery occlusion, showed no reperfusion, thus documenting a relationship between reperfusion measured by regional cerebral blood flow and angiographic patency (P = .015). Three patients died. Patients who were reperfused within 24 hours (documented by repeated regional cerebral blood flow measurements) showed greater clinical improvement on the Scandinavian Stroke Scale the sooner their thrombolytic therapy was started and the more severe their neurological deficits. CONCLUSIONS: Acute cerebral ischemia can be documented by rCBF measurements without delay of thrombolytic therapy, and repeated rCBF measurements can reveal whether cerebral reperfusion has occurred. In our study, early reperfusion was associated with clinical improvement.

Adult

Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study.

BACKGROUND AND PURPOSE: The early time course after acute stroke of cerebral N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline was studied in vivo by means of localized water-suppressed proton magnetic resonance spectroscopy. METHODS: Eight patients with acute stroke were studied serially in the acute phase, 1 week after, and 2-4 weeks after the onset of clinical symptoms. Ten healthy volunteers served as controls. A stimulated echo (STEAM) sequence was used for measurement of the brain metabolites in a volume of interest located within the infarcted area as visualized by magnetic resonance imaging. For quantification, the unsaturated water signal was used as the internal standard. Regional cerebral blood flow in the infarcted area was measured relative to a symmetrically located unaffected area by means of single-photon emission computed tomographic scanning, using 99mTc-labeled d,l-hexamethylenepropyleneamine oxime as the flow tracer. RESULTS: Relative regional cerebral blood flow was considerably reduced in the infarcted area in the acute phase. After 1 week, hyperemia was seen in all but one patient. The N-acetylaspartate content was significantly reduced, with the loss appearing to occur between 6 and 24 hours after the stroke incident. The reduction in N-acetylaspartate content was greater in the central part than in the peripheral part of the infarcted area. Creatine and phosphocreatine were also reduced in the infarcted area, whereas no significant change was seen in the choline content. CONCLUSIONS: Assuming that N-acetylaspartate content reflects neuronal survival or loss, our results may suggest that treatment procedures with restoration of blood flow to severely ischemic areas should be initiated within the first 6 hours after stroke onset.

Acute Disease

Irreversible effects in rats of toluene (inhalation) exposure for six months.

The irreversible CNS effects of six months' exposure to toluene (0, 500, and 1500 p.p.m.) in rats was studied applying a multi-disciplinary approach. After an exposure-free period, neurobehavioural, morphometric, pathological, and biochemical examinations were performed. No neurobehavioural or gross pathological changes were found. Morphometric measurements did not show loss of neurones. At 500 p.p.m. the mean nuclear volume and mean perikaryonal volume and the variation of the values of these parameters was increased in the exposed groups compared to the controls. Noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) levels were significantly changed in various brain regions. It is concluded that this investigation failed to reveal overt toluene-induced CNS-neurotoxicity, however, certain irreversible effects were found which further add to the accumulating evidence of the chronic CNS-neurotoxicity of toluene.

Administration, Inhalation

Central nervous system involvement in human immunodeficiency virus disease. A prospective study including neurological examination, computerized tomography, and magnetic resonance imaging.

Sixty-seven patients with different stages of human immunodeficiency virus (HIV) infection (47 CDC group IV, 20 CDC groups II or III) were followed prospectively for a median of 18 months with neurological examination, magnetic resonance imaging (MRI), and computerized tomography (CT) to evaluate the incidence of the AIDS dementia complex (CDC definition) and other neurological complications. Ten patients developed CNS opportunistic infection or malignancy. Among the remaining 57 patients, 12 of 37 (32%) belonging to CDC group IV, and 1 of 20 (5%) belonging to CDC groups II/III developed the AIDS dementia complex (p = 0.03). MRI white matter lesions occurred in 32% of CDC group IV patients and 5% of CDC groups II/III patients (p = 0.03). The corresponding figures for brain atrophy at CT were 71% and 30% (p less than 0.01) and for neurologic signs 49% and 20% (p = 0.06). The development of the AIDS dementia complex was significantly associated with the occurrence of MRI white matter lesions and a CD4 cell count of less than 200 x 10(6)/l, whereas it was not statistical significantly associated with brain atrophy at baseline. It is concluded that the AIDS dementia complex is a common feature of late stage HIV infection. Brain atrophy occurs in a large percentage of HIV infected patients, but the clinical significance of this atrophy is not clear.

AIDS-Related Complex

An efficient method for estimating the total number of neurons in rat brain cortex.

An efficient method for the unbiased estimation of the total number of neurons in rat brain cortex is presented. The method is reasonable fast, the counting procedure takes 2-3 h per rat, and gives an estimate of the total neuron number in cortex cerebri with an CE of 0.10. The rat cerebral cortex is found to have a mean volume of 253 mm3 and to contain a mean of 21 million neurons. The method has been used in a neurotoxicologic study, in which rats were given toluene perorally in doses of 200, 400 and 800 mg/kg/day, respectively, for 12 weeks, followed by an exposure-free period of 4 weeks. The total number of neurons in rat brain cortex cerebri showed no significant difference between exposed and non-exposed animals. The applicability of the method is discussed.

Animals

A Fabry's disease heterozygote with a new mutation: biochemical, ultrastructural, and clinical investigations.

A Fabry heterozygote with early clinical manifestations of this X linked disorder is described. Her symptoms, including febrile attacks, arthralgia, abdominal pain, and neurological signs, were characteristic of Fabry's disease hemizygotes. The neurological findings were compatible with a brain stem infarction. The diagnosis was confirmed by the finding of low activities of alpha-galactosidase A (alpha-galA) in plasma, lymphocytes, and cultured fibroblasts, and by the observation of typical lamellar inclusions in the lysosomes of cultured fibroblasts. Increased levels of ceramide trihexoside were also found by TLC of urine sediment. The family history gave no indication of Fabry's disease in the patient's relatives, and biochemical and ultrastructural investigations of their cells were also normal. Our findings therefore suggest that the defective gene in the heterozygote has resulted from a new mutation.

Adolescent

Cerebral ventricular enlargement relates to neuropsychological measures in unselected AIDS patients.

In a cross-sectional study of unselected Danish AIDS patients various linear measures of cerebral ventricular size obtained by computed tomography were compared with results of neuropsychological test performances. Third ventricular width as well as right and left septum-caudate distances were enlarged in the patients (P less than 0.01). Of 20 patients 15 had at least one abnormal ventricular measurement. Although only one patient was demented, ventricular size correlated inversely with neuropsychological function (r = -0.61, P less than 0.02). The correlation between ventricular size and variation of the reaction time was even closer (r = 0.74, P less than 0.01). It is concluded that neuroradiological signs of central atrophy often occur in AIDS patients.

Acquired Immunodeficiency Syndrome