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Biomedical subjects

S M Aquilonius

Publications and source records attributed to S M Aquilonius.

At least 19 recordsLinked to original sources

Objective assessment of cervical dystonia: a pilot study.

OBJECTIVES: The aims were to characterize the movements in cervical dystonia (CD) by using an estimate of the mechanical power and work involved in the movements and to describe this through a movement energy index (MEI). MATERIALS AND METHODS: The subjects (patients n = 6, controls n = 6) were seated in front of a screen with a laser pointer attached to a headband while they performed standardized movements. A three-dimensional motion capture system was used and a test-retest was performed. RESULTS: The mean value of MEI was significantly higher for the patients than for the controls. There was no significant difference between MEI from test to retest for the patients but there was a significant difference between MEI from test to retest for the controls. CONCLUSION: This study suggests that MEI could be a useful measure for the quantification of movement dysfunction in CD and thus an objective outcome measure in comparison of different therapies.

Aged↗

Amyotrophic lateral sclerosis: evidence for intact hepatocyte growth factor/met signalling axis.

Hepatocyte growth factor (HGF) is a secreted cytokine which is expressed in the central nervous system (CNS) together with its specific receptor MET. Since HGF exerts strong neurotrophic activity including motoneurons, we have further analysed whether the HGF/MET axis is defective in patients with amyotrophic lateral sclerosis (ALS). Intrathecal HGF-secretion was measured in cerebrospinal fluid (CSF) from patients with amyotrophic lateral sclerosis and in controls without neurological diseases using a specific sandwich immunoassay (ELISA). MET-expression was analysed by immunohistology in spinal cord cross-sections of ALS patients and unaffected controls. The HGF concentrations in CSF were moderately but significantly increased in ALS patients compared to healthy controls (580 pg/ml vs 348 pg/ml). MET-protein was detectable in spinal cord motoneurons of patients with ALS as well as unaffected controls. The data demonstrate that ALS does not show a lack of the trophic signalling axis, HGF/MET, suggesting that the signalling system itself is not affected. The moderate increase in HGF-secretion may represent a compensatory effect.

Adult↗

High 3H-vesamicol binding in ALS motor neurons--autoradiographic visulalization of hyperactivities?

OBJECTIVES: To evaluate if increased metabolic demand in remaining motor neurons in ALS spinal cord sections can be visualized by 3H-vesamicol binding. MATERIAL AND METHODS: As a presumed marker of the vesicular acetylcholine transporter, 3H-vesamicol was applied in quantitative autoradiography in cervical spinal cord sections from 11 ALS patients and 4 control cases. The regional binding was compared to that of the muscarinic ligand 3H-QNB. RESULTS: Our results demonstrate the same magnitude of H-vesamicol binding in the ventral horn of ALS spinal cord as compared to controls, despite the profound loss of motor neurons in that specific area in ALS. The specificity of 3H-vesamicol binding for the cholinergic transporter is high in the motor neuron area, and sigma-sites constitute a minor proportion. CONCLUSION: The lack of decrease in 3H-vesamicol binding in postmortem ALS spinal cord sections probably reflects an upregulated synthesis of vesicular membranes in remaining and hyperactive motor neurons in vivo.

Autoradiography↗

Duodenal levodopa infusion in Parkinson's disease--long-term experience.

Motor fluctuations in parkinsonian patients can be reduced by intraduodenal infusion of levodopa. Between 1991 and 1998 continuous daytime administration of levodopa through a transabdominal port has been used in 28 very advanced patients over a total period of 1045 months. A stable suspension of levodopa and carbidopa (Duodopa) has been developed. Patients were characterized by early onset, long history of disease and levodopa therapy. The reason for infusion was in all cases related to on-off fluctuations. All patients experienced a general improvement after the introduction of continuous treatment. There have been no severe complications. Six patients have taken the decision to curtail their treatment. The mean daily levodopa consumption has been slightly reduced on infusion as compared to oral therapy. Nine of the first group of patients participating in the new therapy have been regularly evaluated by means of rating scales and movement analyses. Short-term results have already been published and a follow-up showing continued positive effect after 4-7 years of continuous duodenal infusion is presented.

Adult↗

A comparative study of methionine adenosyltransferase activity and regional distribution in mammalian spinal cord.

To provide a background for future studies on neurodegenerative changes in the spinal cord, the present study analysed the distribution of the activity of methionine adenosyltransferase (ATP:L-methionine S-adenosyltransferase, EC 2.5.1.6, MAT), an enzyme that catalyses the synthesis of the biological methyl group donor S-adenosylmethionine (AdoMet), in spinal cords from bovine and pig, and compared the results with those from human spinal cord. The enzyme activity was estimated by a radiochemical method measuring the rate of formation of [(3)H]AdoMet from L-[methyl-(3)H]methionine and ATP. The MAT activity (V(max)) was quite homogeneously distributed between spinal regions and species investigated (19-50 pmol [(3)H]AdoMet/mg protein/minute), with the highest level found in the male bovine group. The bovine group (both males and females) also presented a 20% higher enzymatic activity in the dorsal horn as compared to the ventral horn and white matter areas. In the pig spinal cord, the highest level of activity was found in the white matter. The lowest affinity for methionine (highest K(m)) was found in the human spinal cord. Whole spinal cords of one cat and one rhesus monkey were also analysed and the levels of MAT activity were similar to that of humans and bovine females, respectively. Studies of MAT stability in the rat spinal cord (post-mortem time 0-72 hr) showed a significant decrease in enzyme activity during the interval of 0-8 hr (23 degrees ). From this time point on and up to 72 hr (4 degrees ), the significant decrease in the activity remained at 60% of the initial value.

Animals↗

Gender differences in Parkinson's disease symptom profile.

Gender symptom differences were studied in 948 subjects with Parkinson's disease (PD) using a questionnaire covering the most common symptoms associated with PD at debut (SP-1) and at present (SP-2). The symptoms most frequently reported by both genders were: tremor, fumblingness, writing problems, rigidity and fatigue. At SP-1 females reported neck-pain and low back pain more frequently than males. At SP-2 subjects reported an increased number of symptoms. The following symptoms were more frequent among males than females: writing difficulties, fumblingness, gait problems, speech problems, increased flow of saliva, lack of initiative. Sleep problems were common in both sexes with inability to turn in bed and calf muscle cramps in a high percentage. A majority of female subjects find their symptoms (e.g. depression) constantly distressing. Although depression is not one of primary reported symptoms (36%) attention is called for, due to the problem with compliance to treatment regimes. About 30% do not report having tremor and rigidity. This study indicates the usefulness of a symptom profile instrument capable of capturing the many symptoms involved in PD. Such an instrument could be used to detect apparent mistakes in medication and thereby increase the function and quality of life for the individual.

Aged↗

Palmar and axillary hyperhidrosis treated with botulinum toxin: one-year clinical follow-up.

Focal hyperhidrosis is a common and sometimes handicapping condition for which the presently most effective treatment, sympathectomy, often leads to irreversible side-effects. We aimed to study effectiveness and tolerability of an alternative treatment with botulinum toxin injections over a period of one year for this condition. Twenty-eight patients with palmar (n = 19) and/or axillary (n = 13) hyperhidrosis were treated with intracutaneous injections of botulinum toxin (Botox(R)) 2 U/4 cm2. Sweat function was studied clinically and by objective measurements after treatment of one side. Treated and untreated sides, and pre- and post-treatment skin areas were compared. Subjective evaluation was performed after treatment of one side and 2-5 months after treatment of both sides. Duration of effect was controlled by a one-year follow-up. Sweating disappeared in eight out of 13 patients with axillary and in five out of 19 with palmar hyperhidrosis, and was reduced markedly in another five out of 13 and 10 out of 19 patients. Two-thirds of those treated for hand sweat noticed a slight and transient reduction of power of finger grip. No side-effects were noticed after treatment of axillary hyperhidrosis. We find intracutaneous injections of botulinum toxin with this technique safe and effective, and due to the relatively long duration of effect the treatment should be recommended before sympathectomy for focal hyperhidrosis.

Adult↗

Increased expression of glial cell line-derived neurotrophic factor mRNA in muscle biopsies from patients with amyotrophic lateral sclerosis.

The expression of glial cell line-derived neurotrophic factor (GDNF) mRNA and brain-derived neurotrophic factor (BDNF) mRNA were studied in muscle biopsies from five patients with amyotrophic lateral sclerosis (ALS), six patients with other neuromuscular diseases and eight healthy control persons. All five patients with ALS had higher GDNF mRNA expressions in their biopsies than the healthy control group (almost a three fold increase). Among the other patients only one, who had a rapidly progressing toxic polyneuropathy, showed a GDNF mRNA expression above those of the controls. The BDNF mRNA expressions in the biopsies from the ALS patients were in the same range as those from the healthy controls, although the mean value of the ALS patients was higher. The only biopsy that showed a markedly higher BDNF mRNA expression was taken from one patient with progressive muscular atrophy. These results suggest that increased GDNF mRNA expression in muscle is an unspecific response to ongoing denervation and that this response is maintained in ALS, at least temporarily. If increased GDNF mRNA in muscle proves to be a constant finding in ALS the rationale for the use of GDNF as a therapeutic agent in ALS must be questioned.

Adult↗

Methionine adenosyltransferase activity in erythrocytes and spinal cord of patients with sporadic amyotrophic lateral sclerosis.

The role of transmethylation mechanisms in the etiology of amyotrophic lateral sclerosis (ALS) is hitherto unexplored. The activity of L-methionine S-adenosyltransferase (MAT), a regulatory enzyme of S-adenosylmethionine biosynthesis, was investigated in erythrocytes of 21 patients with ALS, spinal cord specimens of 7 ALS patients, and matched controls. In ALS patients the activity of MAT in erythrocytes was sex-dependent. In comparison with controls, the male group presented a 33% higher V(max) (P < 0.05) and a 41% decrease in the affinity of MAT for methionine (K(m), P < 0.05). The type of ALS onset (limb or bulbar), age, or duration of the disease did not influence erythrocyte MAT activity. In the spinal cord, the activity of MAT was homogeneously distributed through dorsal horn, ventral horn, and white matter. Comparisons between data from controls and ALS patients and analysis of sex effect showed no significant differences. The kinetic difference of erythrocyte MAT in the male group of ALS patients might be interesting to explore since it is well known that there is a male predominance of 1.5 to 2. 5:1 in ALS.

Aged↗

Absorption of L-DOPA from the proximal small intestine studied in the rhesus monkey by positron emission tomography.

Positron emission tomography (PET) seems to be a valuable method for the understanding of intestinal absorption mechanisms, for simultaneous quantitation of absorption rate and distribution kinetics to the tissues of interest after oral drug delivery. PET was evaluated in three Rhesus monkeys for quantitation of the absorption rate from the gastrointestinal tract and the distribution kinetics into different organs. To obtain optimal standardized conditions for the measurement of absorption the drug was administered via a naso-duodenal catheter directly to the absorption site in the proximal small intestine. l-DOPA was used as study drug given in a suspension together with carbidopa and the radiomarker l-[beta-11C]DOPA. The l-DOPA suspension was given into the duodenum without and after administration of a suspension of six l-amino acids (120 mM) in order to investigate any interaction on the intestinal absorption and distribution of l-DOPA into the liver and brain tissue. Intestinal absorption was in general minor during the first study period and higher together with administered l-amino acids. The somewhat contradictory result with increased absorption when amino acids were present in the intestinal lumen, may be a consequence of increased intestinal motility initiated by the nutrient load.

Animals↗

Upregulation of Bax protein and increased DNA degradation in ALS spinal cord motor neurons.

OBJECTIVES: To investigate if degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is related to altered levels of the apoptosis regulating proteins Bcl-2 and Bax. In addition, immunoreactivity of the cysteine protease ICH-IL and detection of motor neurons with DNA fragmentation, indicative of apoptosis, was also studied. MATERIAL AND METHODS: The immunoreactivity of Bcl-2, Bax and ICH-1L were compared in ALS and control spinal cord motor neurons by immunohistochemical analysis and motor neurons with DNA fragmentation were identified by the TUNEL-method. RESULTS: The results demonstrate an increased expression of Bax in the ALS material as compared to controls but no change in Bcl-2 and ICH-1L expressions. Moreover, a larger proportion of motor neurons stained positive for TUNEL in ALS spinal cords. CONCLUSION: Present study suggest an upregulation of the cell death promoting protein Bax and increased DNA degradation, indicative of apoptosis, in spinal motor neurons of ALS patients.

Aged↗

Reversible chorea in primary antiphospholipid syndrome.

A 20-year-old woman with acute chorea induced by primary antiphospholipid syndrome was studied by using fluorodeoxyglucose and positron emission tomography (PET). PET sessions were conducted during an episode of severe chorea and after recovery. The symptoms predominantly affected the right side of her face and body, and PET demonstrated a corresponding increase in lentiform and caudate nucleus metabolism prevailing on the left side. After recovery, PET showed normal values in the regions previously studied. This study adds further evidence to support the theory that acute choreas are somehow the result of striatal hypermetabolism.

Acute Disease↗

Long-term intraduodenal infusion of a water based levodopa-carbidopa dispersion in very advanced Parkinson's disease.

OBJECTIVE: To evaluate the effects of continuous duodenal infusion of levodopa over time on the disabling fluctuations in motor performance in advanced parkinsonian patients. It has earlier been demonstrated that these fluctuations can be reduced by keeping the plasma concentration of levodopa constant. MATERIAL AND METHODS: In view of the low water solubility of levodopa a stable dispersion of the drug was developed and used for continuous intraduodenal infusion in patients with advanced Parkinson's disease. Nine patients were evaluated with respect to an optimal oral treatment, during nasoduodenal infusion by a portable pump and then followed for 6 months to 2 1/2 years when treated via transabdominal infusion. Upon each test occasion, over 2 non-consecutive days, objective movement analysis by means of an opto-electronic system was applied every 15-20 min and video recordings performed twice every h. On several test occasions plasma levodopa concentrations were analysed every 15 min. RESULTS: The patients showed improvement and decreased variance of their motor function. In the 2 patients followed over a period of 2 1/2 years levodopa plasma concentration showed reduced fluctuations on infusion and the levodopa consumption as well as mean levodopa plasma concentration decreased. CONCLUSION: Continuous duodenal infusion of levodopa is an alternative treatment strategy for patients with advanced Parkinson's disease when conventional therapy has failed.

Activities of Daily Living↗

Levels of L-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson's disease.

In the present study, levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in whole blood as well as L-methionine S-adenosyltransferase (MAT) activity in erythrocytes were assayed in a series of 20 patients with Parkinson's disease and 12 healthy control subjects. A significant difference was found with regard to SAM levels between patients and controls, with the detected levels being 383.1 +/- 41.5 nM for the parkinsonian patients and 680.6 +/- 30.9 nM for the controls. With regard to SAH, we found no difference between the groups. The catalytic activity of MAT was increased by 30% in patients compared to controls, with the Vmax for methionine being 17.9 +/- 3.7 and 13.9 +/- 2.2 pmol/mg/h, respectively.

Antiparkinson Agents↗