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Biomedical subjects

L Gram

Publications and source records attributed to L Gram.

At least 91 records · Page 5Linked to original sources

[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↗

Poisonings from flesh of the Greenland shark Somniosus microcephalus may be due to trimethylamine.

The flesh of the Greenland shark, Somniosus microcephalus, especially in fresh condition, is toxic to both dog and man. Analysis of the toxic fractions indicates the presence of large amounts of trimethylamine oxide (TMAO) but no other substances that could be directly responsible for the poisoning. The symptoms appear to be due to an acute trimethylamine (TMA) poisoning arising from intestinal reduction of TMAO to TMA. TMA stimulates contraction of the guinea-pig ileum (antagonized by atropine but not hexamethonium). Low concentrations of TMA increase contraction of the rat phrenic nerve-diaphragm preparation, whereas higher concentrations cause blockade.

Animals↗

Evaluation of intensified prehospital treatment in out-of-hospital cardiac arrest: survival and cerebral prognosis. The Odense ambulance study.

During a period of 3 years three different types of emergency medical service (EMS) systems were evaluated in a city with about 238,000 inhabitants/population density of 570/km2. Included were 393 out-of-hospital cardiac arrest patients in whom prehospital cardiopulmonary resuscitation was provided by personnel on basic, intermediate, or advanced care training. When ordinary ambulances (basic EMS) were used, 8 (5%) patients were discharged alive. When ambulances with specially trained paramedics (intermediate EMS) were used, 2 (1%) patients were discharged. Finally medically staffed ambulances with doctors collaborating (advanced EMS) were used, and 11 (13%) patients were discharged. The intermediate EMS system was used in another area with 45,000 inhabitants/population density of 340/km2, and in this area 20 (18%) patients were discharged. Among the survivors a psychological assessment in form of a test for dementia was assessed in long-term survivors (n = 30) together with 28 patients surviving acute myocardial infarction and 11 control persons. The results of the investigation demonstrate that the more intensive the prehospital treatment of out-of-hospital cardiac arrest, the more patients survive and the more patients survive with good cerebral function. However, the ambulances with specially trained paramedics were only effective in the area with 340 inhabitants/km2.

Brain Ischemia↗

Oxcarbazepine.

Explore the source record for details and available documents.

Animals↗

Vigabatrin in pediatric epilepsy--an open study.

The antiepileptic effect of vigabatrin in adults has been demonstrated in a number of controlled studies. In children, the effect of vigabatrin has been investigated only to a limited extent. In order to assess the long-term effect and safety of vigabatrin in patients with severe epilepsy, an open, add-on, dose-ranging study was initiated. To date, 27 children with partial epilepsy, two with generalized epilepsy, two with Lennox-Gastaut syndrome, and one with nonclassifiable epilepsy have been enrolled in the trial. Fifty-four percent of patients have experienced a greater than 50% reduction in seizure frequency, and four patients have become seizure free. A significant reduction in seizures was noted across the patient population, although patients who were recorded as seizure free at 3 and 6 months did suffer some recurrence of seizures. However, when seizures recurred, they did so at much lower frequency than recorded at the start of the study. Thirteen patients (39%) reported adverse events attributable to vigabatrin; one was immediately withdrawn from the study, and six had their vigabatrin dose reduced. No physiologic effects were noted on normal growth or clinical physical examination.

Adolescent↗

[Intensified prehospital treatment of heart arrest increases the number of survivors with good cerebral function].

Psychological assessment in the form of a test for dementia was carried out in 69 individuals. Thirty of these were survivors of cardiac arrest outside hospital. Seven of these were brought to hospital in ordinary emergency ambulances, 14 in heart ambulances and nine in medically staffed ambulances. In addition, 28 patients with acute myocardial infarction (AMI) and 11 control persons were examined. The result of the investigation demonstrates that the more intensive the prehospital treatment of cardiac arrest, the more patients survive with good cerebral function. In particular, the percentage of cerebral damage was least in cases where a medically staffed ambulance was employed.

Brain Damage, Chronic↗

The bacteriology of fresh and spoiling Lake Victorian Nile perch (Lates niloticus).

A total of 177 bacterial cultures isolated from Lake Victorian Nile Perch (Lates niloticus) were investigated. The flora on newly caught Nile perch consisted of organisms belonging to the genera Moraxella, Alcaligenes, Acinetobacter, Pseudomonas, Aeromonas, Micrococcus and other Gram-positive organisms. 39% were identified as Gram-positive species and 61% were negative in the Gram-reaction. Three cultures out of 53 investigated caused weak rotten off-odours in sterile fish broth and one culture, an Aeromonas spp. produced strong rotten, fishy, hydrogen sulphide off-odours. From Nile perch spoiled at ambient temperature, 15 of the 42 strains isolated caused rotten, fishy, hydrogen sulphide off-odours. These specific spoilage bacteria were all identified as Aeromonas and all reduced trimethylamine oxide to trimethylamine and produced hydrogen sulphide. From spoiled iced Nile perch, 74 out of 82 (90%) of the bacteria isolated were identified as Pseudomonas. A small proportion of these (13 out of 74) produced off-odours in sterile fish broth resembling the spoiling fish. These specific spoilers could not be separated from the non-spoilers based on biochemical activities used in classical taxonomy. While the Pseudomonas spp. isolated did not produce trimethylamine or H2S, a few of the remaining isolates (two Shewanella putrefaciens and five Aeromonas spp.) did produce these compounds. The role of Shewanella putrefaciens in the iced spoilage of Nile perch was, however, insignificant, since they only very late in the storage reached numbers where their spoilage could be detected.

Amino Acids↗

Pharmacokinetic comparison of two carbamazepine slow-release formulations.

In a single-blind pharmacokinetic study patients being treated with conventional carbamazepine (CBZ) in a t.i.d. regimen were randomly allocated to identical doses of two CBZ slow-release formulations (Trimonil Retard and Tegretol Retard) administered once daily. Statistical analysis involved the following parameters: AUC, Cmin, Cmax and Fluctuation Index (FI). With regard to Cmin and FI statistically significant differences in favour of Tegretol Retard were observed.

Administration, Oral↗

[Cardiac arrest outside of hospital. A retrospective study in Odense].

During the period 1.10.1986-30.9.1987, all patients with cardiac arrest outside hospital brought to the casualty department in Odense Hospital were registered. Out of 160 patients, 133 (83%) could be primarily resuscitated, 19 (12%) were resuscitated but died later in hospital and eight patients (5%) were resuscitated and could be discharged alive from hospital. Out of the eight patients who were discharged alive, only two (1%) had retained reasonable cerebral function as assessed by dementia testing. Treatment of the cardiac arrest prior to the arrival of the ambulance, duration of the cardiac arrest for less than six minutes and staffing of the ambulance with three first-aid men were factors of decisive importance for survival of the patients. The results of this investigation demonstrate that treatment of cardiac arrest outside hospital is unsatisfactory. Proposals for improvement of treatment include: 1. Information to the population. 2. Training of first-aid staff in treatment of cardiac arrest. 3. Quicker arrival of ambulances and 4. Better staffing and training of ambulance staff in the use of a defibrillator possibly with participation of a doctor.

Denmark↗

Experimental studies of the influence of vigabatrin on the GABA system.

1. Studies of the influence of clinically relevant concentrations of vigabatrin on GABA-transaminase and on the release of endogenous GABA were performed in selectively cultured astrocytes and neurons. In addition, the two stereoisomers of vigabatrin were investigated separately. 2. The results indicated a preferential inhibition of neuronal GABA-transaminase by vigabatrin. 3. Only the (S)-form of vigabatrin seems to inhibit GABA-transaminase. This finding corresponds to observations in epileptic animals that the (R)-form exhibits no anticonvulsant effect. 4. Resynthesis of GABA-transaminase, following withdrawal of vigabatrin showed that maximum enzyme activity was obtained within 6 days. This finding corresponds to the persistent effect after withdrawal of the drug in patients, observed in clinical trials. 5. At a concentration of 25 microM, vigabatrin caused a significant increase in the release of endogenous GABA from cultured GABAergic neurons. Although no data on brain levels of the drugs are currently available, judging from vigabatrin blood concentrations in man and from information of brain levels in animals, following chronic treatment, it is conceivable that a sufficiently high concentration of the drug in human brain is obtained to augment GABA release.

4-Aminobutyrate Transaminase↗

Experimental studies and controlled clinical testing of valproate and vigabatrin.

Gamma-aminobutyric acid (GABA) is the most important inhibitory transmitter, quantitatively, in the CNS. Evidence exists that decreased GABAergic neurotransmission may play a role in some forms of epilepsy. Consequently, manipulating the GABA system may be a therapeutic possibility in the treatment of this disease. Inhibition of the major GABA degrading enzyme, GABA-transaminase (GABA-T), seems to be the most promising approach. Currently, 2 antiepileptic drugs, valproate (VPA) and vigabatrin, gamma-vinyl GABA (GVG), are available, which are supposed to inhibit the degradation of GABA. Both drugs cause an increase in the total concentration of GABA in the brain, but to a different extent. VPA produces a moderate elevation, which seems to be the result of a marked increase in the transmitter-related GABA pool, while the pronounced elevation in GABA concentration observed during treatment with GVG seems to be caused mainly by an increase in the non-transmitter-related (glial) GABA pool. In order to investigate this apparently differential influence of VPA and GVG on the GABA system, a number of studies were undertaken in selectively cultured astrocytes and neurons from mice. For both drugs neuronal GABA-T proved far more sensitive with regard to inhibition than glial GABA-T. In order to obtain a more direct measure of a potential GABAergic mechanism of action of VPA and GVG, synaptic release of endogenous GABA was determined after culturing neurons in the presence of clinically relevant concentrations of the drugs. GVG caused a significant increase in GABA release, even at concentrations as low as 25 microM. For VPA only the highest of the investigated concentrations (300 microM) augmented GABA release. It is concluded that the antiepileptic effect of GVG seems to be caused by a direct GABAergic mechanism of action. For VPA an influence on the GABA system may play a role in the antiepileptic effect of the drug. However, the lack of definite data on human brain levels of VPA after chronic treatment, combined with evidence that VPA exhibits a number of other effects that may be relevant for its antiepileptic properties, makes the interpretation of a GABAergic mechanism of action difficult. Controlled clinical trials have been increasingly applied within all areas of medicine. In 1982 a survey of the literature identified 29 studies of antiepileptic drugs, where the design involved randomization, the double-blind principle and a statistical analysis of the results.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminocaproates↗

Differential effect of gamma-vinyl GABA and valproate on GABA-transaminase from cultured neurones and astrocytes.

A preferential effect of valproate on gamma-aminobutyric acid (GABA) in the nerve terminal compartment has been proposed. Gamma-vinyl GABA, an irreversible inhibitor of GABA-transaminase (GABA-T) causes a preferential increase in the GABA compartment of the non-nerve terminal. The aim of the present study was to investigate further this apparent differential effect on GABA-T of these compounds in neurones and glia. The investigations were undertaken in neurones and astrocytes, cultured separately. After incubation with valproate, the IC50 value for astrocytes was found to be 1202 microM of valproate and for neurones 634 microM. Assuming regional differences of concentrations of valproate in the brain, the observed IC50 values might be clinically relevant. Culturing the cells in the presence of gamma-vinyl GABA demonstrated IC50 values for astrocytes and neurones of 89 and 24 microM, respectively. The (S)isomer of gamma-vinyl GABA was the most active inhibitor of GABA-T in both glia and neurones. After withdrawal of gamma-vinyl GABA from the culture media of the cells, in neurones 50% of the activity of GABA-T was regained within 2-4 days. In astrocytes a similar time course was observed. These findings are in agreement with clinical data: the IC50 values correspond to clinically-relevant serum levels of gamma-vinyl GABA in humans only the (S)isomer showed an antiepileptic effect in animal models of epilepsy a delayed antiepileptic effect, after withdrawal of gamma-vinyl GABA, has been established in clinical studies.

4-Aminobutyrate Transaminase↗