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Biomedical subjects

M Dam

Publications and source records attributed to M Dam.

At least 19 recordsLinked to original sources
PubMed2002

A short review of cognitive and functional neuroimaging studies of cholinergic drugs: implications for therapeutic potentials.

In the last 20 years a cholinergic dysfunction has been the major working hypothesis for the pharmacology of memory disorders. Cholinergic antagonists and lesions impair and different classes of cholinomimetics (i.e. acetylcholine precursors, cholinergic agonists and acetylcholinesterase inhibitors) enhance attention and memory in experiment animals, healthy human subjects and Alzheimer disease patients. In addition, acetylcholinesterase inhibitors improve different cognitive (i.e. visuospatial and verbal) functions in a variety of unrelated disorders such as dementia with Lewy bodies, Parkinson disease, multiple sclerosis, schizoaffective disorders, iatrogenic memory loss, traumatic brain injury, hyperactivity attention disorder and, as we recently reported, vascular dementia and mild cognitive impairment. In animals, different cholinomimetics dose-dependently increased regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF), two indices of neuronal function, more markedly in subcortical regions (i.e. thalamus, hippocampus and visual system nuclei). In both healthy human subjects and Alzheimer disease patients acetylcholinesterase inhibitors increased rCMRglc and rCBF in subcortical and cortical brain regions at rest but attenuated rCBF increases during cognitive performances. Hence, acetylcholinesterase inhibitors may enhance cognition and rCMRglc by acting primarily on subcortical regions that are involved in attentional (i.e. thalamus) and memory (i.e. hippocampus) processes; such an effect probably is not specific for Alzheimer disease and can be beneficial in patients suffering from a wide array of neuropsychiatric disorders.

Alzheimer Disease↗
PubMed2002

Atrio-ventricular block: a possible explanation of sudden unexpected death in epilepsy.

INTRODUCTION: This is the third case report describing the occurrence of total atrio-ventricular (AV)-block as a life threatening cardiac arrhythmia complicating epileptic seizures. CASE REPORT: A 56-year-old right-handed man was admitted to our hospital for surgical assessment of his medically intractable epilepsy. During the hospitalization he was enrolled in a study investigating cardiac complication of epileptic seizures as the possible cause of sudden unexplained death among epileptics. DISCUSSION: To the best of our knowledge, we are the first to employ simultaneous video-electroencephalogram-, Holter- and pulse oximetry-recordings of our patients in the description of this complication. These recordings allowed us to discuss the evidence and consequences of this particular cardiac abnormality as an explanation of sudden unexplained death in epileptic seizures, especially those of temporal origin.

Death, Sudden, Cardiac↗
PubMed2001

Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view.

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or--in rare cases--has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.

Anticonvulsants↗
PubMed2001

Removal of 10-hydroxycarbazepine by plasmapheresis.

Removal of the oxcarbazepine metabolite 10-hydroxycarbazepine (MHD) by plasmapheresis was evaluated during a series of six plasmaphereses of a 13-year-old boy with Rasmussen encephalitis. Plasmapheresis was performed after steady-state concentrations of MHD had been achieved with a dose of 2550 mg oxcarbazepine daily. The mean amount of MHD removed per plasmapheresis was 78.9 mg (SD: 6.0 mg), representing 3% to 4% of the daily oxcarbazepine dose and approximately 5% to 6% of body stores of MHD. The mean steady-state trough MHD concentration was 33.3 mg/L (SD: 1.8 mg/L), and this was remarkably stable during the entire plasmapheresis period. The serum concentration of MHD was only mildly reduced by the procedure. The areas under the concentration curve of MHD on the first and sixth day of plasmapheresis were 99% and 94%, respectively, of the pre-plasmapheresis values. The results are in agreement with studies on other anticonvulsant medications (carbamazepine, valproic acid, phenobarbital, and phenytoin), indicating that minor fractions (2% to 10%) of body stores of these drugs are depleted during plasmapheresis. The authors conclude that it is unnecessary to adjust the oxcarbazepine dosage when performing single-volume plasma exchanges or even multiple exchanges during an extended period. It is further proposed that plasmapheresis is unlikely to be of therapeutic benefit in the treatment of an oxcarbazepine overdose.

Adolescent↗
PubMed2001

Plasma concentration of topiramate correlates with cerebrospinal fluid concentration.

The authors examined the ratio between the plasma and the cerebrospinal fluid (CSF) concentration of topiramate in 14 adults with epilepsy. Simultaneous trough samples of venous blood and CSF were collected and analyzed as total and unbound concentrations. Concomitant levels were also analyzed of lamotrigine (n = 5) and the relevant oxcarbazepine metabolite, 10-hydroxycarbazepine (n = 3). There was a close correlation between the plasma and the CSF concentration for both the total and unbound concentration of topiramate. The median CSF/plasma ratio of total topiramate was 0.85. The free topiramate concentration in plasma was not different from the free topiramate concentration in CSF. The CSF/plasma ratios showed little variation and were independent of the plasma level for both the total and the unbound levels. The unbound fraction of topiramate was 84% in plasma and 97% in CSF. The CSF concentrations of lamotrigine and 10-hydroxycarbazepine were 50% and 61% of the plasma concentrations, respectively. For topiramate, there is a close correlation between the plasma concentration and the CSF concentration. There does not seem to be a saturable carrier mechanism restricting topiramate transport across the blood-brain barrier. The concentration of topiramate in CSF is equal to the unbound proportion of topiramate in plasma, implying that the delivery of topiramate to the brain occurs via transfer from the unbound plasma pool. Plasma is thus a relevant matrix for therapeutic drug monitoring of topiramate.

Adolescent↗
PubMed2001

Virtual Reality as an assessment tool for arm motor deficits after brain lesions.

The currently used assessment techniques for measuring neurological deficits are time consuming and may lack of sensibility and repeatability. Previous studies suggested that the cinematic analysis of the movement, might represent a reliable alternative instrument for documenting the degree of motor impairment. To verify this hypothesis we investigated motor/functional progress in 20 post-stroke patients, undergoing rehabilitation therapy, by means of a widely used clinical test (Fugl-Meyer scale), and by evaluating kinematics of arm motion. After rehabilitation therapy, velocity and duration of reaching movements significantly improved with respect to baseline values. Before and after rehabilitation there was a significant correlation between each cinematic parameter and the clinical scale scores. These results, suggests that the cinematic analysis of movement can be proposed as a precise and objective assessment tool to be used in clinical practice.

Aged↗
PubMed2000

Effects of acute and chronic treatment with fluoxetine on regional glucose cerebral metabolism in rats: implications for clinical therapies.

The wide therapeutic spectrum of fluoxetine (e.g., antidepressant, antipanic, antiphobic, antiobsessive, analgesic, antimigraine) requires long-term administration and adaptive changes. To test whether adaptation involves the serotonin (5-HT) transporters, we measured the effects of fluoxetine on the regional cerebral metabolic rate for glucose (rCMRglc) in control rats or in rats pretreated for 2 weeks with fluoxetine (8 mg/kg, i.p., daily, 2 days wash out); rCMRglc was measured in 56 brain regions, using the quantitative [14C]deoxyglucose technique, at 30 min after i.p. administration of fluoxetine 0.4, 4 or 40 mg/kg, i.p., to non-pretreated rats or fluoxetine 4 mg/kg to pretreated rats. In non-pretreated rats, fluoxetine reduced rCMRglc in a dose-dependent fashion in 4 (7%, mean decrease 11%), 28 (50%, mean decrease 23%) and 37 (66%, mean decrease 32%) brain regions. In chronic fluoxetine-pretreated rats, fluoxetine decreased rCMRglc to a substantially lesser degree (eight regions, 14%; mean decrease, 10%). Subcortical brain regions (i.e., hypothalamic paraventricular, locus coeruleus and basal ganglia nuclei) that mediate the physiological responses to stress were very sensitive to fluoxetine acutely and subsensitive after chronic treatment. As kinetic tolerance to fluoxetine does not occur during chronic administration, the diminished rCMRglc responsivity to fluoxetine reflects dynamic, adaptive tolerance of 5-HT transporters and, consequently, increased synaptic 5-HT concentrations; the findings suggest that fluoxetine may be therapeutic by increasing the 5-HT-negative modulation upon areas that drive the abnormally hyperactive responses to stress found in several neuropsychiatric conditions.

Animals↗
PubMed2000

Epilepsy and pregnancy: effect of antiepileptic drugs and lifestyle on birthweight.

OBJECTIVE: To investigate the impact of epilepsy and antiepileptic drugs on length of gestation and anthropometric measures of the newborn. DESIGN: Cohort study based on questionnaires mailed to all pregnant women who attended for prenatal care at our department from August 1989 to January 1997. SETTING: Department of Obstetrics and Gynaecology at Aarhus University Hospital, Denmark. PARTICIPANTS: One hundred and ninety-three singleton pregnancies in women with epilepsy were compared with 24,094 singleton pregnancies in women without epilepsy. MAIN OUTCOME MEASURES: Preterm delivery, small for gestational age, mean gestational age, gestational age-adjusted birthweight, head circumference, and body length. RESULTS: Children of women with epilepsy who smoked had lower gestational age and were at increased risk of preterm delivery (OR 3.4; 95% CI 1.8-6.5), compared with children born by nonepileptic women who smoked. Birthweight adjusted for gestational age was reduced by 102 g (95% CI 40-164) in women with epilepsy, and the risk of delivering a child who was small for gestational age was increased (adjusted OR 1.9, 95% CI 1.3-2.7), compared with women without epilepsy. Newborn babies of women with epilepsy treated by drugs had a reduced adjusted birthweight (208 g, 95% CI 116-300), head circumference (0.4 cm, 95% CI 0.0-0.7), and body length (0.5 cm, 95% CI 0.1-1.0), compared with the newborn infants of women without epilepsy. CONCLUSIONS: Women with epilepsy who smoked were at increased risk of preterm delivery compared with healthy smokers. Children of women with drug treated epilepsy had lower birthweight, length, and head circumference than children of women without epilepsy.

Adolescent↗
PubMed1999

Identification of 19 polybrominated diphenyl ethers (PBDEs) in long-finned pilot whale (Globicephala melas) from the Atlantic.

Nineteen tetra- to hexabrominated diphenyl ethers were identified at ppb concentration in the blubber of pilot whale caught off the coast of the Faroe Islands in 1994 and 1996. Higher total concentrations were found in the pooled samples of young males (3,160 ng/g lipid) and females (3,038 ng/g lipid) compared to adult females (843 ng/g and 1,048 ng/g lipid) and males (1,610 ng/g lipids). The predominant isomers in all samples were 2,2',4,4'-TeBDE (PBDE #47) and 2,2',4,4', 5-PeBDE (PBDE #99) accounting for some 70% of the sum of the 19 isomers.

Adipose Tissue↗
PubMed1999

Fracture risk is increased in epilepsy.

OBJECTIVES: To study fracture rates and risk factors for fractures in non-institutionalized patients with epilepsy. MATERIAL AND METHODS: Historical follow-up. Self-administered questionnaires were issued to 755 patients with epilepsy (ICD 10: G40.0 to G40.9) and 1000 randomly selected controls from the background population. RESULTS: A total of 345 patients (median age: 45, range 17-80 years) and 654 control subjects (median age: 43, range 19-93 years) returned the questionnaire. Before epilepsy was diagnosed there was no difference in overall fracture rate between patients and controls (RR = 1.0, 95% CI: 0.8-1.3). After the diagnosis the overall fracture rate was significantly higher in the patients (RR = 2.0, 95% CI: 1.6-2.5). Fractures of the spine, forearms, femurs, lower legs, and feet and toes were significantly increased. Fractures related to seizures accounted for 33.9% (95% CI: 25.3-43.5%) of all fractures. After elimination of seizure related fractures the increase in fracture frequency was only borderline significant: RR = 1.3 (95% CI: 1.0-1.7, P = 0.042). No difference in fracture energy between patients and controls was observed (low energy fractures: 1.7/1.4%, medium energy fractures: 59.8/52.0%, and high energy fractures: 38.3/46.6%). Use of phenytoin (OR = 2.4, 95% CI: 1.1-5.4) and a family fracture history (OR = 2.4, 95% CI: 1.3-4.6) was associated with an increased fracture risk. CONCLUSIONS: Fractures were more common in epileptics than in controls especially among users of phenytoin. Most of the increase in fracture frequency was related to seizures and not to low bone biomechanical competence.

Adolescent↗
PubMed1999

Electroencephalography in dogs with epilepsy: similarities between human and canine findings.

OBJECTIVES: To investigate the diagnostic value of electroencephalography (EEG) in dogs with epilepsy, applying human criteria for EEG abnormalities observed with this disorder. MATERIAL AND METHODS: Twenty-six dogs with a clinically established diagnosis of epilepsy were investigated with electroencephalography (EEG) in order to evaluate the diagnostic yield of EEG in canine epilepsy. RESULTS: Of 23 dogs with evaluable EEGs 15 (65%) demonstrated abnormal activity. The most common abnormalities were focal low frequency patterns without spikes (48%), followed by focal epileptiform activity (22%) and generalized epileptiform activity (17%). The distribution between focal and generalized activity were 73% and 27%, respectively. Consistency were demonstrated between the clinical- and the EEG-diagnosis in 13 dogs (87%). A relationship was demonstrated between the number of abnormal EEGs and the proximity of a seizure to the EEG examination. CONCLUSION: A marked consistency was demonstrated between the clinical diagnosis of seizure type and the type of abnormalities observed in the EEG, thus indicating that EEG is a valuable diagnostic aid in confirming the diagnosis of epilepsy in dogs. EEG findings in dogs with epilepsy and humans with this disorder were markedly similar.

Animals↗
PubMed1998

Regional cerebral blood flow changes in patients with cirrhosis assessed with 99mTc-HM-PAO single-photon emission computed tomography: effect of liver transplantation.

BACKGROUND/AIMS: Previous studies showed contrasting results with regard to alterations of regional cerebral blood flow/metabolism in subjects with liver cirrhosis. The aim of the study was to extend these findings in a larger series of patients. In addition, we wanted to determine whether such alterations are reversed by successful liver transplantation. METHODS: The study group comprised 23 patients with liver cirrhosis and 13 normal controls. At entry to the study, all subjects underwent a complete neurological examination, EEG recordings and SPECT scanning. The severity of liver disease was determined according to the Child-Pugh score. Fourteen patients underwent a second SPECT examination 1 year after liver transplantation. RESULTS: Significant rCBF reductions, ranging from 6% to 7%, were found in the majority of the cortical regions of the whole group of patients with cirrhosis, as compared to controls. These reductions were more diffuse in patients with alcoholic liver disease, comprising almost all the assayed regions. Liver transplantation normalized cortical rCBF deficits so that postoperative perfusion indexes were superimposable on control values. However, the frontal cortex remained significantly more impaired in patients with alcoholic cirrhosis than in those with non-alcoholic cirrhosis. The differences in frontal rCBF between the two groups of patients ranged from 6 to 11%. CONCLUSIONS: Liver cirrhosis was associated with rCBF defects that depend upon the etiology of liver disease and that subsided after successful liver transplantation. The frontal defects in alcoholic cirrhosis either before or after surgery may imply a neurotoxic, possibly irreversible, action of ethanol.

Adult↗
PubMed1998

Pregnancy and epilepsy: a retrospective study of 151 pregnancies.

OBJECTIVE: We studied the course of pregnancy in women with epilepsy to identify possible risk factors which might complicate the epilepsies and pregnancy outcomes. MATERIAL AND METHODS: Data were collected retrospectively from the records of 151 pregnancies in 124 women with epilepsy from 1978-1992. Epilepsy variables were compared with that of non-pregnant women with epilepsy matched for age. Obstetric and neonatal variables were compared with those of all deliveries in the same unit from 1979-1992 (n=38,983). RESULTS: Pregnancy among patients with epilepsy was more likely to occur in women with relatively mild epilepsy. In 12% of the pregnancies, the women were untreated while 71% were on monotherapy. Twenty-one percent had increased seizure frequency during the pregnancy. Perinatal deaths among newborns of epileptic mothers (1.3%) was more frequent but not significantly increased compared to the background population of 0.5% (95% CI 0.2-4.7). A total of 5.3% had congenital malformations compared to 1.5% in the controls (95% CI 2.3-10.3). No neural tube defects were observed. Maternal treatment with phenytoin was significantly related to the occurrence of congenital malformations, P=0.04. CONCLUSIONS: Most women with epilepsy have an uncomplicated pregnancy and normal healthy offsprings. Maternal treatment with phenytoin might be associated with congenital malformations. No other risk factors could be identified.

Abnormalities, Drug-Induced↗
PubMed1998

Anticipation in familial cavernous angioma: ascertainment bias or genetic cause.

OBJECTIVES: Anticipation has been linked to unstable trinucleotide repeats in many neurological disorders. We examined the hypothesis of genetic anticipation in familial cavernous angioma (FCA) of the central nervous system. MATERIAL AND METHODS: The mean ASO of affected individuals was compared between successive generations in 55 families. Intergenerational pair-wise comparisons were employed to avoid several ascertainment biases. Regarding severity of disease both type of manifestation and number of cavernous angiomas were compared between generations. RESULTS: The mean ASO decreased significantly both from the first to the second generation (31.6 vs 17.8 years; P = 0.000) and from the second to the third generation (17.8 vs 6.7 years; P = 0.002). The pair-wise comparisons also showed significantly earlier ASO. No clear evidence for anticipation with regard to severity of disease was found. CONCLUSIONS: Molecular genetic studies will determine whether trinucleotide repeats are the underlying mechanism for our observation of anticipation in FCA.

Adolescent↗
PubMed1997

The effects of propofol on cerebral high energy metabolites, lactate, and glucose in normoxic and severely hypoxic rats.

Study was performed in Fischer-344 rats to test the effects of the intravenous anesthetic propofol on cerebral content of high-energy metabolites, glucose, and lactate in normoxic and severely hypoxic rats. General and local anesthetics (isoflurane, N(2)O 70%, pancuronium bromide, bupivacaine hydrochloride) were used for surgery (tracheostomy, femoral artery and vein cannulation, skull exposure, ligature of right-sided carotid and EEG needle electrodes only in rats devoted to the hypoxia study). For normoxia study, four groups of 7 rats each were treated for 60 min as it follows: the control group with N(2)O plus propofol vehicle and the other three with propofol 12.5, 25, or 50 mg x kg(-1) x h(-1) respectively. For the hypoxia-study five groups of 7 rats each were planned to have two control (one normoxic) and three propofol-treated groups, drug treatments being the above indicated and of 80 min. During the last 20 min Pa(O(2)) was lowered to 15-20 mmHg. Pa(CO(2)) was maintained between 35-40 mmHg, rectal temperature at 37 degrees C, MABP near to 100 mmHg and pH on the basal values during the whole procedure. Then brains were frozen in vivo, and cortical tissue was excised and analyzed for labile metabolites using fluorometric techniques. Propofol, at all the doses tested, did not alter the concentrations of adenine nucleotides, phosphocreatine, lactate, pyruvate, or glucose in normoxic rats. In rat brain, hypoxia did not produce significant changes in the concentrations of adenine nucleotides. PCr concentration was decreased both in the ligated and unligated side, and lactate levels exceeded 21 and 18 micromol/g in the right and left cortices, respectively. While the lowest dose of propofol was ineffective in preventing PCr decrease and lactate increase, both 25 and 50 mg x kg(-1) x h(-1) significantly reduced those adverse effects of hypoxia.

Adenine Nucleotides↗
PubMed1997

ECG changes in epilepsy patients.

OBJECTIVES: To investigate the frequency of ECG abnormalities suggestive of myocardial ischaemia in patients with severe drug resistant epilepsy and without any indication of previous cardiac disease, assuming that these changes may be of significance for the group of epileptic patients with sudden unexpected death. MATERIAL AND METHODS: Twelve patients with medically intractable epilepsy were investigated with simultaneous long ECG and EEG recordings while attending either epilepsy surgery investigational procedures or the investigational programme for diagnostic purposes, and one while having an episode of status epilepticus. RESULTS: The ECG recording failed in 1 patient. This patient had chest pain and minor yet morphologically conspicuous changes in the ECG, suggestive of myocardial infarction. He died in heart arrest. Eight epilepsy patients had episodes of ST segment depression in the ECG, many of which coincided with video- and EEG documented epileptic seizures. Two patients experiencing simple partial seizures and 1 patient experiencing absence seizures had no ST segment depressions in the ECG. One patient had an episode of status epilepticus secondary to brain damage and no ST segment deviation was seen during the ECG recording which continued until 3 h before the patient died. CONCLUSION: Patients with severe drug resistant epilepsy have episodes of ST segment changes, some of which are closely related to epileptic seizures. Further studies are needed to confirm the present results and to investigate the nature of these changes and document the effect of prophylactic treatment with cardioactive drugs to reduce the risk of sudden death.

Adolescent↗
PubMed1996

Mutations in domain II of 23 S rRNA facilitate translation of a 23 S rRNA-encoded pentapeptide conferring erythromycin resistance.

Mutations in domain II of Escherichia coli 23 S rRNA that cause resistance to erythromycin do so in a manner fundamentally different from mutations at the drug binding site in domain V of the 23 S rRNA. The domain II mutations are located in a hairpin structure between nucleotides 1198 and 1247. This is close to a short open reading frame in the 23 S rRNA that encodes a pentapeptide (E-peptide) whose expression in vivo renders cells resistant to erythromycin. Therefore, a possible mechanism of resistance caused by domain II mutations may be related to an increased expression of the E-peptide. To test this hypothesis, a range of point mutations was generated in domain II of 23 S rRNA in the vicinity of the E-peptide open reading frame. We find a correlation between erythromycin resistance of the mutant clones and increased accessibility of the ribosome binding site of the E-peptide gene. Furthermore, the erythromycin resistance determinant in the mutants was shown to be confined to a small 23 S rRNA segment containing the coding region and the ribosome binding site of the E-peptide open reading frame. It thus appears that the domain II mutations mediate erythromycin resistance by increasing expression of the 23 S rRNA-encoded E-peptide.

Base Sequence↗