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Biomedical subjects

M Dam

Publications and source records attributed to M Dam.

At least 73 records · Page 4Linked to original sources

Speech localization using repetitive transcranial magnetic stimulation.

To evaluate whether repetitive transcranial magnetic stimulation (RTMS) may be used for speech localization, we compared the results from RTMS with the intracarotid amobarbital test (IAT) in 21 patients undergoing surgical treatment (amygdalohippocampectomy or anterior temporal lobe resection) for medically intractable partial epilepsy. None of the patients had aphasia. We stimulated the temporal and frontal cortex on each side at a frequency of 30 Hz for 1 second and increased the intensity until speech was inhibited. A list of words and forward and backward counting were used to test speech function. The IAT was performed on the hemisphere of proposed surgery by unilateral injection and simultaneous regional cerebral blood flow (rCBF) recordings. In one patient, there was doubt about hemisphere dominance and a second bilateral IAT was performed. Fifteen patients had left-sided speech dominance; one, left-sided dominance and a moderate right-sided speech inhibition; two, right-sided speech dominance; and one, bilateral speech representations (bilateral injection at the IAT) with both techniques. One patient showed bilateral with right-sided speech dominance by RTMS and showed right-sided speech inhibition with right-sided injection only at the IAT procedure. One patient differed from the rest, showing bilateral representations with right-sided speech dominance with RTMS and left-sided speech inhibition by IAT with left-sided injection only. The concordance was 95%. None of the patients had seizures provoked by the procedure. We conclude that speech localization with RTMS shows a high concordance with the results from the IAT and may be useful in addition to traditional techniques in speech localization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Retention of 99mTc-bicisate in the human brain after intracarotid injection.

99mTc-bicisate (ECD) was injected as a bolus into the internal carotid artery, and cerebral uptake and retention were recorded with fast-rotating single photon emission computed tomography (SPECT) equipment in four patients suffering from temporal lobe epilepsy. Quantitative regional cerebral blood flow (rCBF) was measured tomographically with the 133Xe inhalation technique. We applied a three-compartment kinetic model and algorithms modified from a previous analysis of 99mTc d,l-hexamethylpropyleneamine oxide (HM-PAO) kinetics. The bicisate brain uptake and retention curve was very similar to that of HM-PAO, and it can be described by a triexponential function including an initial steep component representing the vascular transmitted spike, a second less steep component representing back-diffusion from brain tissue to blood, and a third, very slow component, representing the very slow loss due to incomplete retention of the deesterified hydrophilic metabolites. Computerized curve-fitting on data from three patients gave average kinetic values for the first-passage (unilateral) extraction of E = 0.60 (range, 0.59-0.61); the overall retained fraction of the tracer supplied was R = 0.44 (0.43-0.45), and the conversion/clearance ratio was alpha = k3/k2 = 2.59 (2.38-2.77). This alpha is higher than that for HM-PAO, and therefore bicisate uptake as a function of blood flow is more linear than in HM-PAO. Less correction for backdiffusion is therefore needed. From 1 to 24 h there was an average loss of hydrophilic tracer of 3.5%/h, but the late distribution images were essentially unchanged over time, pointing to practically the same rate of loss in all regions.

Adolescent↗

The monosialoganglioside GM1 dose-dependently reduces regional cerebral metabolic rates for glucose in awake rats.

Using the quantitative autoradiographic [14C]2-deoxyglucose technique, regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats at 1, 2, 3, 4 and 6 h after administration of GM1 30 mg/kg and at 3 h after GM1 150 or 300 mg/kg. GM1 is a natural compound that is able to prevent neuron degeneration induced by exposure to excitatory amino acids in vitro and by ischemia or neurotoxins in vivo. GM1 30 mg/kg, a dose very effective in preventing excitatory amino acid-induced neurotoxicity, produced minimal rCMRglc change over a 6 h period. GM1 150 and 300 mg/kg reduced rCMRglc, in 14 (31%) and in 29 (64%) brain regions, respectively. Maximal metabolic effects occurred in hippocampal areas which possess, in specific subfields, the highest brain concentrations of different excitatory amino acid receptor subtypes. This finding suggests an effect by GM1 on postreceptor mechanisms common to different excitatory amino acids.

Animals↗

The tricyclic antidepressant clomipramine dose-dependently reduces regional cerebral metabolic rates for glucose in awake rats.

The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats after administration of clomipramine (CMI), a serotonin (5-HT) uptake inhibitor and clinical antidepressant. rCMRglc was determined, using the quantitative autoradiographic [14C]2-deoxyglucose technique, in 64 brain regions at 20, 40, 60, 120, and 180 min after administration of CMI 50 mg/kg IP and 120 min after CMI 2 and 10 mg/kg IP. The peak metabolic effect was observed at 120 min after CMI. At that time, CMI 2 and 10 mg/kg IP significantly reduced rCMRglc from control values in 12 (19%) and 14 (22%) brain regions, which correspond to areas with high densities of 5-HT reuptake sites (e.g. visual and limbic areas and raphe nuclei). CMI 50 mg/kg produced widespread rCMRglc reductions in 34 (53%) brain regions, including cortical, hippocampal, raphe and cerebellar areas. The topographic distribution and the relation to time and dose of CMI effects on rCMRglc are different from those of 5-HT1A [8-hydroxy-2(di-N-propylamino) tetralin], 5-HT1B-C (m-chlorophenylpiperazine) and 5-HT3 (quipazine) agonists and resemble those produced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist of 5-HT2 receptors, suggesting that CMI may prefentially stimulate this 5-HT receptor subtype.

Animals↗

Effect of barbiturate on epileptiform activity: comparison between intravenous and oral administration. Sphenoidal, zygomatic and temporal recordings.

The present study was performed in order to compare: 1) the differences between oral and intravenous barbiturate on interictal epileptiform activity (sharp-waves and spikes) in the EEG, and 2) interictal epileptiform activity in the sphenoidal electrode compared to the temporal and zygomatic electrodes (an electrode placed at the cutaneous entry of the sphenoidal electrode) during intravenous barbiturate administration in patients with epilepsy. Two procedures were performed: 1) an oral pentobarbital sleep induction with 10-20 electrode placement including a zygomatic electrode, and 2) an intravenous thiopental sleep induction with the same electrode placement including a sphenoidal electrode. Thirty eight patients with complex partial seizures were included. During the oral pentobarbital procedure 34 of 38 (90%) patients showed interictal epileptiform activity compared with 22 of 38 (55%) patients during the intravenous thiopental procedure (p < 0.005). A interictal epileptiform focus was observed in 33 (87%) patients in the oral procedure and in 19 (50%) patients in the intravenous procedure (p < 0.01). Interictal epileptiform activity recorded in the sphenoidal electrode was also recorded in the zygomatic electrode. Except from two patients a good correlation was observed between the zygomatic electrodes and the F7/F8 electrodes. We conclude that administration of intravenous thiopental offers no advantage compared to the administration of oral pentobarbital as an activating procedure, and for standard interictal EEG recordings with sleep activation procedures, suitable places scalp electrodes including a zygomatic electrode with the use of oral pentobarbital may be sufficient.

Administration, Oral↗

Dopamine receptor SPET imaging in Parkinson's disease: a [123I]-IBZM and [99mTc]-HM-PAO study.

Single photon emission tomography (SPET) with the novel ligand [123I]-IBZM was used to image central dopamine D2 receptors in Parkinson's disease (PD) patients. The aim was to assess basal ganglia (BG) receptor densities in relation to the response to L-dopa therapy. To better characterize the clinical potential of [123I]-IBZM SPET, each patient underwent a second study with the regional perfusion tracer [99mTc]-HM-PAO. Tracer activity ratios were calculated for caudate and putamen with mean activity over the cerebellar hemispheres as internal standard. In PD patients we found a significant decline of mean caudate [123I]-IBZM activity, as compared with age-matched control subjects. However, when patients were grouped according to their therapeutic behavior, the [123I]-IBZM uptake in BG ganglia regions of the PD patient group with a poor and fluctuating response to L-dopa was significantly reduced from mean values of patients with a sustained response to L-dopa therapy. [99mTc]-HM-PAO caudate and putamen uptake indexes in PD were similar to control values, even in patients with deteriorated therapeutic response. Our results indicate that BG D2 receptor alterations in PD may contribute to the altered response to L-dopa.

Adult↗

The effects of long-term rehabilitation therapy on poststroke hemiplegic patients.

BACKGROUND AND PURPOSE: Rehabilitation therapy is believed to be useful during the first few months after stroke when recovery usually takes place. However, evidence exists that this may not be the rule for all stroke victims. Therefore, we investigated, in a selected group of poststroke patients, the profile of recovery in response to long-term rehabilitation therapy. METHODS: Fifty-one hemiplegic subjects unable to walk 3 months after stroke were enrolled in this study. Patients underwent consecutive periods of rehabilitation up to 2 years after the cerebrovascular accident. Autonomy in daily living activities and the degree of neurological compromission were periodically assessed with the Barthel Index and a neurological scale designed for hemiplegic subjects. The main features of the patients were also evaluated as a possible predictor of outcome. RESULTS: In a consistent percentage of the patients, significant gains in gait and daily living abilities were observed during the first year and, in individual cases, during the second year after stroke. At the end of the study, 74% of the patients regained their capacity to walk without assistance, and up to 79% had a Barthel Index score above 70. Sphincter function, level of neurological impairments, and capacity in daily living activities are significantly related to the outcome of the patients as a whole but were not useful to anticipate the outcome of each patient. CONCLUSIONS: These results suggest that disabled poststroke subjects may attain significative functional improvements in response to prolonged restorative therapy. However, the possibility of predicting the outcome of individual patients appears the major problem to solve in order to assign to long-term rehabilitation programs only patients who will benefit from the therapy.

Activities of Daily Living↗

Phenytoin-loading: pharmacokinetic comparison between an intravenous bolus injection and a diluted standard solution.

Phenytoin (PHT) is considered a first or second choice in the treatment of status epilepticus that is refractory to benzodiazepines. The use of an intravenous bolus injection of PHT is hazardous due to the risk of cardiac conduction disturbances, dose-dependent side effects in general, as well as the possibility of severe necrotic lesions in case of extravasation. We compared the number and intensity of side effects and serum level profiles of a highly concentrated, non-dilutable bolus (46 mg/ml) of PHT [Fenytoin, DAK] with a dilutable standard solution (1.5 mg/ml) [Phenhydan] administered intravenously in 500 ml saline. Six healthy volunteers received both regiments (9.1 mg/kg). The diluted solution showed a curvilinear saturation curve with a lower concentration maximum (C-max) than the concentrated solution. Lower toxicity of the diluted solution was indicated by a clinical rating of side effects. Based on a higher incidence and degree of side effects following administration of the more concentrated formulation of PHT, compared with the more diluted preparation, we recommend the use of the less concentrated formulation.

Adult↗

Quantitative neuropathology in epilepsy.

Counting of neurons has brought new insight to the mechanism of epilepsy. The reduction in Purkinje cells and neuron loss in hippocampus are related to generalized convulsions in man. Generalized convulsions provoked by electric shock in rats do not result in neuron loss. However, mongolian gerbils from seizure-susceptible strains with "spontaneous" seizures of various types, have a reduced number of H1-neurons and Purkinje cells after only a restricted number of seizures of any type. Loss of neurons is a possible consequence of generalized convulsions. Even "seizure activity", as such, seems to damage nerve cells. The consequence is early effective treatment in such cases where epilepsy is a secondary threat as in febrile convulsions, post-traumatic, post-infectious and post-infarction epilepsy.

Animals↗

Effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites.

The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required.

Administration, Oral↗

[Surgical treatment of epilepsy resistant to drug therapy. A review].

The prevalence of epilepsy is 7-9 cases per 1,000 population, corresponding to 440,000 individuals in Denmark. Approximately 1/4 of these individuals have seizures refractory to anticonvulsant medications and most of them have an epileptic focus in the temporal lobe. Epilepsy refractory to anticonvulsant medication is an incapacitating disease with high costs for the person and the society. The main problems are polypharmacy with side effects, suspicion of neurodegenerative consequences and a higher mortality. The modern era of epilepsy surgery began more than 100 years ago and since then, the developments in neurophysiology and neuroimaging have made it possible to demonstrate the epileptic focus with relatively high precision. As a consequence of this, the volume of the resected tissue has diminished and the operative complications become less frequent. The somatic and neuropsychological effects of a cortical resection are discrete and compensated by a general improvement in performance. Surgical treatment of epilepsy should no longer be considered as a last resort, but as a realistic treatment in cases of medication failure.

Anticonvulsants↗

[3-year experiences with surgical treatment of epilepsy at the Hvidovre hospital].

The results of a retrospective survey of 48 patients submitted to neurosurgery for medically intractable epilepsy are presented. Twenty-eight patients were treated with selective amygdalohippocampectomy, one with temporal lobe resection, 12 with anterior callosotomy and seven with a total callosotomy. Of the amygdalohippocampectomized patients and the one with temporal lobe resection (n = 29), 52% were seizure free, 17% experienced rare seizures, 7% had a worthwhile improvement while 24% observed no worthwhile improvement (follow-up time 6 to 36 months). Of the callosotomized patients, 11% were free from generalized seizures, 69% had a significant seizure reduction and 18% experienced no worthwhile improvement. The observed neurological complications were: one patient had hemianopia, one had superior quadrant anopia, four developed unilateral anosmia and one complete anosmia. The callosotomized patients, with two exceptions, were all mentally and physically handicapped. In the callosotomy group, two patients died, one from a intracerebral hematoma three months after the operation and another patient seven months postoperatively from unknown causes.

Adult↗

Specific structural probing of plasmid-coded ribosomal RNAs from Escherichia coli.

The preferred method for construction and in vivo expression of mutagenised Escherichia coli ribosomal RNAs (rRNAs) is via high copy number plasmids. Transcription of wild-type rRNA from the seven chromosomal rrn operons in strains harbouring plasmid-coded mutant rRNAs leads to a heterogeneous ribosome population, which consequently hinders direct probing of mutant rRNAs. Here, we describe how nonconserved helical regions of plasmid-coded rRNA have been altered in a manner that preserves their secondary structures while creating new sites for primer extension of mutant rRNAs. This facilitates specific biochemical probing of mutagenised rRNA regions despite the background of wild-type molecules. Four priming sites have been made to investigate the structural effects of mutations in the GTPase centre, helix 1200-1250, the peptidyl transferase region and the alpha-sarcin loop of 23S rRNA.

Anti-Bacterial Agents↗

Vigabatrin in refractory epilepsy in adults and its application in children.

Vigabatrin has been studied in adult drug-resistant epilepsy since 1982 in single-blind and double-blind studies followed by long-term, open evaluations. These studies have provided evidence that vigabatrin is a potent and well-tolerated antiepileptic drug and support its potential value in pediatric epilepsy. The lack of any evidence of human neurotoxicity in these patients is also reassuring regarding its use in children.

Adolescent↗

SPECT in the presurgical evaluation of patients with temporal lobe epilepsy--a preliminary report.

Twenty-eight patients with drug resistant temporal lobe epilepsy (DRTLE) were studied using single photon emission computed tomography (SPECT) using xenon-133 inhalation and Tc99m-d, 1-HMPAO with TOMOMATIC 64 as part of a presurgical evaluation programme. The visually evaluated flow-images were studied after blinding and the results subsequently compared to the EEG, MRI and CT scanning studies. In 24 patients a significant low flow region was seen in one temporal lobe. The SPECT result corresponded to the EEG findings in all but 6 patients. In 2 of these patients no side localization was indicated by EEG, while in four patients the EEG suggested that the opposite side was epileptogenic. Ictal SPECT and MRI/CT agreed with the resting SPECT study in three patients, while one patient has remained undiagnosed with respect to side-localization. In 14 patients discordance between SPECT and the CT scan was observed, but in 11 of these patients the SPECT study correlated with the other focal diagnostic tools. In 11 of the 21 patients studied by MRI, the results corresponded to SPECT; in 7 of the 10 which did not correspond, ictal studies of EEG and SPECT defined the side, in four of these 7 patients. Using the neuroimaging tools in concert 16 patients have been selected for surgery. All patients have benefited from surgery. These preliminary results correspond favourably with earlier studies comparing SPECT and PET with CT, MR and EEG.

Adult↗