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Biomedical subjects

H Askmark

Publications and source records attributed to H Askmark.

At least 19 recordsLinked to original sources
PubMed2005

Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease.

OBJECTIVES: To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL). METHODS: Twenty-four patients with motor fluctuations and dyskinesia were studied in a randomized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/carbidopa gel for 3 + 3 weeks. Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from -3 to 0 to +3 (from severe "off" to "on" to "on" with severe dyskinesia). Patient self-assessment of motor performance and QoL was done using an electronic diary. RESULTS: Median percentage of ratings in a functional "on" interval (-1 to +1) was increased from 81 to 100% by infusion therapy (p < 0.01). This improvement was accompanied by a decrease in "off" state (p < 0.01) and no increase in dyskinesia. Median Unified Parkinson's Disease Rating Scale score decreased from 53 to 35 in favor of infusion (p < 0.05). QoL was improved, using the two instruments: Parkinson's Disease Questionnaire-39 and 15D Quality of Life Instrument (p < 0.01). Adverse events were similar for both treatment strategies. CONCLUSIONS: Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

Administration, Oral↗
PubMed2005

The ALS/MND prevalence in Sweden estimated by riluzole sales statistics.

OBJECTIVES: To determine whether sales statistics for riluzole can be used as a marker for the prevalence of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) in Sweden. MATERIALS AND METHODS: A questionnaire was sent to all neurological units in Sweden asking about the numbers of patients with ALS/MND and whether these patients were treated with riluzole. Sales statistics for riluzole were obtained from the 906 public pharmacies and 89 hospital pharmacies in Sweden. RESULTS: Eighty percent of the neurological units answered the questionnaire. The estimated prevalence in September 2003 from the questionnaire was 5.4/100,000 inhabitants. The sales expressed in defined daily dose/100,000 inhabitants/day was 3.8. For the counties the correlation between these two parameters was 0.83. CONCLUSION: Estimated prevalence is highly correlated with sales statistics for riluzole. Riluzole sales statistics could be used as a crude marker for the prevalence of ALS/MND in Sweden.

Adolescent↗
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↗
PubMed2002

Increased red blood cell polyamines in ALS and Parkinson's disease.

The polyamines spermidine (SPD) and spermine (SPM) are implicated in nerve cell degeneration and regeneration. Over 70% of circulating polyamines are associated with red blood cells (RBC). Against this background we have analysed RBC polyamines in two neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Twenty patients with the sporadic form of ALS, 20 patients with PD, and 20 healthy controls were studied. The highest levels of SPD and SPM were found in the PD group where the mean values were 134 and 115%, respectively, above those of the controls. The patients with PD also presented the lowest levels of the SPD precursor, putrescine (PUTR). In the patients suffering from ALS the SPD and SPM mean levels were increased by 46 and 112%, respectively. The RBC SPD/SPM ratio in the patients suffering from PD was significantly elevated in comparison with that of ALS patient group, suggesting a different involvement of the polyamine system in these disorders. It is at present unknown if raised polyamine levels may contribute to induce the degeneration of susceptible neurons or if the increase represents a compensatory protective reaction, or simply an unspecific epiphenomenon.

Amyotrophic Lateral Sclerosis↗
PubMed2001

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↗
PubMed2001

Parkinsonism and neck extensor myopathy: a new syndrome or coincidental findings?

BACKGROUND: Dropped head in parkinsonism has been attributed to dystonia or unbalanced muscle rigidity. To our knowledge, isolated neck extensor myopathy with parkinsonism has been described in only one patient. OBJECTIVES: To assess the occurrence of neck extension weakness resulting in dropped head in patients with parkinsonism and to explore whether the head drop might be the consequence of neck extensor myopathy. PATIENTS AND METHODS: All patients who were evaluated because of parkinsonism in the Department of Neurology in our hospital between January 1, 1997, and December 31, 1999, and were found to have both parkinsonism and neck extension weakness resulting in head drop were studied. The patients underwent clinical examination, blood tests including the levels of creatine kinase and myoglobin and neurophysiological evaluation with needle electromyography and autonomic tests. Open biopsy on a neck muscle was performed in the patients who could cooperate. RESULTS: Of 459 patients evaluated because of parkinsonism, 7 were found to have neck extensor weakness resulting in head drop. Needle electromyography revealed myopathic changes in all 7 patients. Muscle biopsy, which was performed in 5 patients, disclosed myopathic changes in all 5 patients. Electron microscopy revealed mitochondrial abnormalities in 2 of these 7 patients. Three of the patients had concomitant neck rigidity that could contribute to the neck position. All 7 patients had autonomic dysfunction and 6 responded poorly to levodopa therapy, making a diagnosis of multiple system atrophy probable. CONCLUSION: Parkinsonism may be associated with isolated neck extensor myopathy resulting in dropped head, and this condition should be suggestive of multiple system atrophy.

Aged↗
PubMed2000

GDNF but not BDNF is increased in cerebrospinal fluid in amyotrophic lateral sclerosis.

Cerebrospinal fluid from 15 patients with ALS and 11 controls without neurological disease were analysed for levels of the neurotrophic factors BDNF and GDNF. Analyses were performed using a sensitive sandwich immunoassay (ELISA). There was no significant difference in BDNF levels between the ALS patients and the control subjects studied. Measurable levels of GDNF were found in 12 out of 15 ALS samples. GDNF was not detected in CSF from any of the control subjects. The finding of increased CSF levels of GDNF in ALS compared to controls, together with earlier findings of increased expression of GDNF mRNA in muscle in ALS, indicates that the capacity to synthesize GDNF is enhanced in this disorder.

Adult↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1993

A pilot trial of dextromethorphan in amyotrophic lateral sclerosis.

Assuming the presence of glutamate-induced neurotoxicity in amyotrophic lateral sclerosis 14 patients were treated with dextromethorphan, an N-methyl-D-aspartate receptor antagonist. The patients were treated with 150 mg dextromethorphan or placebo daily for 12 weeks in a double-blind crossover trial, with a wash out period of 4 weeks between the two treatment periods. Thereafter the surviving patients were treated with 300 mg dextromethorphan daily for up to 6 months in an open trial. No positive effects on clinical or neurophysiological parameters (relative number of axons, and compound muscle action potentials in the abductor digiti minimi muscle) were observed either in the double-blind trial or in the open trial.

Aged↗
PubMed1992

Leakage of carbonic anhydrase III from normal and denervated rat skeletal muscle following contractile activity.

Skeletal muscle extracellular carbonic anhydrase III was investigated in anesthetized rats by a microdialysis technique. A small dialysis probe was inserted into the tibialis anterior (TA) muscle and perfused continuously. Perfusates were collected before and during muscle contraction, induced by electrical stimulation of the muscle or of the sciatic nerve. In the perfusate of resting normal and denervated muscle, the concentration of CA III was 10 to 12 ng/mL, as measured by a radioimmunosorbent technique. During contractile activity, the concentrations of CA III increased markedly in the normal and denervated muscle. A TA muscle suspended in physiological saline behaved similarly, even though the leakage before and during contraction was higher than in vivo. The results show that skeletal muscle leaks CA III both in vivo and in vitro, a leakage which was markedly increased by contractile activity. The microdialysis technique should also be useful in humans to study the efflux of various proteins from different kinds of diseased or fatigued muscles.

Animals↗
PubMed1992

Increased binding of 3H-L-deprenyl in spinal cords from patients with amyotrophic lateral sclerosis as demonstrated by autoradiography.

The present investigation has applied quantitative autoradiography and histochemistry to study the regional distribution of MAO-B and its relation to the number of cells in respective regions. L-deprenyl binds irreversibly and quantitatively to the B-form of monoamine oxidase, MAO, and is an ideal 3H-ligand to measure the MAO-B enzyme protein in tissues by means of in vitro autoradiography. The investigation is performed on spinal sections from five controls and five cases with amyotrophic lateral sclerosis (ALS) on cervical, thoracic and lumbar level. The highest density of 3H-L-deprenyl binding was found around the central canal (lamina X). MAO-B was markedly increased (up to 2.5 times of values in controls) specifically in regions of neurodegeneration e.g. motor neuron laminae and corticospinal tracts. There was a high correlation between glial cell count and 3H-L-deprenyl binding with a relation indicating enhanced MAO-B protein in glial cells within areas of neurodegeneration. In contrast the increased microglial cell number in ALS did not show any correlation with 3H-L-deprenyl binding.

Aged↗
PubMed1992

No re-expression of high-affinity nerve growth factor binding sites in spinal motor neurons in amyotrophic lateral sclerosis.

Autoradiographic studies of high-affinity nerve growth factor binding sites in the cervical human spinal cord revealed a high density of binding sites in the dorsal horn and in the tract of Lissauer, which is in agreement with investigations in nonprimates. Very low or no binding was found in the motor neuron areas of controls as well as in amyotrophic lateral sclerosis cases, which indicates that the degeneration of motor neurons in this disease is not accompanied by re-expression of high-affinity nerve growth factor receptors.

Aged↗
PubMed1991

Changes in cholinergic and opioid receptors in the rat spinal cord, dorsal root and sciatic nerve after ventral and dorsal root lesion.

Changes in the distribution of 3H-quinuclidinylbenzilate (3H-QNB), 3H-acetylcholine (3H-ACh) and 3H-alpha-bungarotoxin (alpha-BTx) binding sites were studied with the use of quantitative in vitro autoradiography in the L4-L6 segments of rats 7 days after ventral L4-L6-rhizotomies and 24 hours after ligation of the dorsal roots L4-L6. The changes in the binding sites of these ligands and of 3H-etorphine binding sites were also studied in the dorsal roots of the rats operated with dorsal root ligation and in the sciatic nerves (around a ligature) in the rats operated with ventral rhizotomy. After ventral rhizotomy 3H-QNB binding sites in the ipsilateral motor neuron area were decreased by about 25% from 100 +/- 5 to 73 +/- 5 fmol/mg wet weight. After dorsal root ligation 3H-QNB binding sites in the ipsilateral posterior horn were reduced by about 30% from 91 +/- 5 to 64 +/- 7 fmol/mg wet weight. No significant changes in the binding of the other cholinergic ligands in the spinal cords were observed after the operations. In the dorsal root 3H-alpha-Btx and 3H-etorphine binding sites were higher on the distal side of the ligation (3.5 +/- 0.8 and 14 +/- 4 fmol/mg wet weight, respectively) than on the proximal side (0.7 +/- 0.5 and 2.4 +/- 1.2 fmol/mg wet weight, respectively). The same level of 3H-ACh (total, muscarinic and nicotinic) binding was observed on both sides of the ligation. In the sciatic nerve 3H-QNB and total, muscarinic and nicotinic ACh binding sites were higher on the proximal side of the ligation than on the distal side.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Quantification of extrajunctional acetylcholine receptors in human muscle biopsies.

Extrajunctional acetylcholine receptors were quantified in human muscle biopsies by in vitro autoradiography with 3H-alpha-bungarotoxin (alpha-Btx). Specific alpha-Btx binding was found in seven of eight biopsies with histological and/or histochemical signs of denervation. The highest binding (21 fmol/mg) was seen in the biopsy with the most pronounced signs of denervation. The specimens with co-existing signs of innervation had generally lower binding levels. Four of the control biopsies showed low binding (less than or equal to 1 fmol/mg) while no specific binding could be detected in the other six controls. The findings suggest that this method cannot only be used to demonstrate denervation in muscle biopsy specimens, but also to give a quantitative measure of the changes.

Adolescent↗
PubMed1990

Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine.

The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l.h-1. Volume of distribution, V alpha varied 100-680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6-36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.

Administration, Oral↗