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Biomedical subjects

O Henriksen

Publications and source records attributed to O Henriksen.

At least 19 recordsLinked to original sources

The effect of exercise on regional adipose tissue and splanchnic lipid metabolism in overweight type 2 diabetic subjects.

AIMS/HYPOTHESIS: To test the hypothesis that adipose tissue lipolysis is enhanced in patients with Type 2 diabetes mellitus, we examined the effect of exercise on regional adipose tissue lipolysis and fatty acid mobilisation and measured the acute effects of exercise on the co-ordination of adipose tissue and splanchnic lipid metabolism. METHODS: Abdominal, subcutaneous adipose tissue and splanchnic lipid metabolism were studied by conducting measurements of arterio-venous concentrations and regional blood flow in six overweight Type 2 diabetic subjects before, during and after exercise. RESULTS: Exercise induced an increase in adipose tissue lipolysis and fatty acid release. However, the increase in adipose tissue blood flow was small, limiting fatty acid mobilisation from this tissue. Some of the fatty acids were released in excess in the post-exercise phase. The splanchnic fatty acid uptake was unchanged during the experiment but splanchnic ketogenesis increased in the post-exercise phase. The arterial glucose concentration decreased during exercise and continued to decrease afterwards, indicating an imbalance between splanchnic glucose production and whole-body glucose utilisation. CONCLUSIONS/INTERPRETATION: Regional subcutaneous, abdominal adipose tissue lipolysis is no higher in patients with Type 2 diabetes than in young, healthy subjects. Exercise stimulates adipose tissue lipolysis, but due to an insufficient increase in blood flow, a high fraction of the fatty acids liberated by lipolysis cannot be released to the blood. Splanchnic glucose release is smaller than whole-body glucose utilisation during exercise and post-exercise recovery.

Adipose Tissue↗

[Chronic intermittent vagal nerve stimulation--a new therapeutic approach in epilepsy].

BACKGROUND: Vagal nerve stimulation is a new non-pharmacological therapy for patients with refractory epilepsy. Introduced in USA in 1988, the treatment is based on animal experiments demonstrating that intermittent stimulation of the vagal nerve could prevent or reduce the frequency and/or duration of seizures. MATERIAL AND METHODS: At the National Hospital in Norway, 47 therapy-resistant patients have had a vagal nerve stimulator implanted since June 1993. We have used the Neuro-Cybernetic Prosthesis system from Cyberonics, consisting of a programmable pulse generator, a bipolar vagal nerve stimulator lead, a programming wand with accompanying software, and a hand-held magnet. The mean age of the population was 34.4 years (12-70 years). All had a long-standing epilepsy with frequent seizures, 36 (77%) had seizures every day. The majority (89%) had localization-related epilepsy. Mean follow-up time was 2.7 years (0.4-6.5 years). RESULTS: 16 patients (34%) responded to the treatment with > 50% reduction in seizure frequency. No one, however, became seizure free. 20 patients (43%) had no seizure reduction. 24 of the patients (51%) benefited from extra stimulation triggered by the magnet. The stimulation affected several types of seizures; most often a reduction in frequency of secondary generalised tonic-clonic seizures was noted. Hoarseness, coughing and a tingling sensation in the throat were the most frequently reported side effects occurring during stimulation. The patients tended to habituate to these side effects. In 14 patients (30%), the device has been explanted, mostly due to lack of efficacy. INTERPRETATION: Considering the fact that this patient group belongs to the most refractory part of the epilepsy population, the results are regarded as promising and they are in keeping with results from other studies. However, the role of vagal nerve stimulation in the future treatment of epilepsy is still not settled. Several questions remain unanswered, e.g. what are the exact mechanisms of action behind the seizure reducing effect, and which patients are most suitable for this treatment?

Adolescent↗

Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.

OBJECTIVE: This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. METHODS: Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures were enrolled in this 28-day double-blind, placebo-controlled, weekly rising dose (400-1600 mg/day) trial. PK profiles were obtained after administration of single-dose rufinamide prior to and after the Double-blind phase. RESULTS: In the evaluable patient population, seizure frequency decreased by 41% in the rufinamide group and increased by 52% in the placebo group (P=0.040). Thirty-nine percent (39%) of rufinamide-treated and 16% of placebo-treated patients experienced reduction in seizure frequency of at least 50% relative to baseline (P=0.096). SAFETY: Treatment-emergent adverse events (AEs) consisted mainly of neurologic signs and symptoms commonly associated with antiepileptic drugs (AEDs). PHARMACOKINETICS: At steady state, rufinamide reached a peak plasma concentration with a mean time (Tmax) of 3.4 h and a mean half-life (t1/2) of 7.3 h. No autoinduction of rufinamide metabolism occurred. Rufinamide did not influence the plasma concentration of carbamazepine, phenytoin or valproate when added to these single AED regimens. CONCLUSION: Rufinamide has been shown, in this proof of principle trial, to be safe and effective in reducing seizure frequency in epileptic patients with no relevant influence on the metabolism of other AEDs.

Adult↗

The effects of refractory epilepsy on intellectual functioning in children and adults. A longitudinal study.

The aim of this study was to compare the long-term consequences of refractory epileptic seizures for intellectual functioning in pediatric and adult patients, taking the severity of the epilepsy into consideration. Thirty-four patients, 17 children (mean age 10.2 years) and 17 adults (mean age 24.4 years) were tested twice with the age-appropriate version of Wechsler's Intelligence Scales. The mean test-retest interval in the two groups was 3.5 and 6.0 years, respectively. There were no statistically significant differences between the groups with respect to severity of the epilepsy at Test 1, as indicated by retrospective assessments of seizure severity, interictal EEG pathology, and number of antiepileptic drugs received per patient. Assessments of changes in these variables during the test-retest interval did not indicate different courses of the disease in the two groups. Despite these similarities, a statistically significant difference was found between the children and the adults regarding changes in intellectual functioning. In the children, there was a decline in mean intelligence quotient (IQ) scores during the test-retest interval, while the IQ scores increased in the adult group. It is concluded that recurrent seizures may represent a considerable risk for intellectual decline in children, while intellectual functioning seem to be less vulnerable in adults with early onset of epilepsy.

Adolescent↗

[Epilepsy and pregnancy].

Based on recent international consensus conferences and a literature search, a brief summary is given of current knowledge about epilepsy in pregnancy. We suggest new Norwegian guidelines based on international recommendations for handling pregnant women with epilepsy. There is a slightly increased risk for malformations in children born of women with epilepsy. The main reason is probably teratogenic effects of antiepileptic drugs. Nevertheless, the overall chance of giving birth to a healthy child is 92-96%, compared to about 98% in the general population. Counselling all fertile women with epilepsy is important in order to reduce the risk of malformations. Before a planned pregnancy, medication should be re-evaluated, and the lowest dose of the drug most likely to give satisfactory seizure control is preferable. The women should have regular neurological follow-up throughout the pregnancy, and they should be given extra vitamin D, K, and folate. Women using carbamazepine, valproate or the new generation of antiepileptic drugs should be offered amniocentesis and comprehensive ultrasound examination in the 14th and 17th week, respectively. The newly approved drugs should be prescribed only if they provide a considerable better seizure control and/or fewer side effects than the traditional antiepileptic drugs.

Abnormalities, Drug-Induced↗

Rectal diazepam: pitfalls of excessive use in refractory epilepsy.

INTRODUCTION: The rectal administration of diazepam (DZP) has provided a safer existence to many epilepsy patients and their carers, when prolonged or serial seizures are present. However, in patients with frequent seizures, chronic, intermittent over-administration may occur, particularly in the presence of multihandicaps. METHODS: Six patients who experienced untoward effects from excessive rectal DZP are reported. In two patients, serial plasma levels of DZP and its active metabolites were monitored. RESULTS: Three patients exhibited a pattern of cyclic reappearance of seizures, interrupted by rectal DZP, followed by sedation and gradual awakening. The intervals were approximately 4 days. The three other patients had variable and complex symptoms with serial seizures and alternating states of tension, apathy, and sleepiness. The plasma levels of DZP and desmethyl-DZP showed rapid fluctuations. CONCLUSION: When rectal DZP is prescribed, chronic and excessive administration should be avoided. Fluctuating plasma-levels may probably support a cyclic reappearance of seizures in some patients. The combination of high bolus doses and a rapid drug clearance due to enzyme inducing co-medication may probably increase the risk for rebound reactions. Toxic, withdrawal, and epileptic symptoms may be intermingled and difficult to manage. A replacement strategy in the form of a prophylactic, oral, low dose benzodiaepine regimen may facilitate the discontinuation of this prescription pattern. Adequate counselling and medically appropriate, written directions for the use of rectal DZP is mandatory.

Administration, Rectal↗

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

Electroencephalography↗

Prediction of epileptic seizures from two-channel EEG.

Multivariate spectral estimation based on parametric modelling has been applied to epileptic surface EEG in order to detect EEG changes that occur prior to the clinical outbreak of the seizure. A better time/frequency resolution has been achieved using residual energy ratios (Dickinson's method). Prediction of oncoming seizures was based on detection of increased preictal synchronisation by calculation of coherence and pole trajectories. The method has been tested on simulated EEG data and on real EEG data from patients with primary generalised epilepsy. Prediction times of 1-6 s have been found in several seizures from five patients.

Adolescent↗

Absolute metabolite quantification by in vivo NMR spectroscopy: I. Introduction, objectives and activities of a concerted action in biomedical research.

By utilizing achievements and results of two previous concerted research projects on magnetic resonance imaging and spectroscopy (MRS), the EU BIOMED 1 Concerted Action on "Cancer and brain disease characterization and therapy assessment by quantitative MRS" was specifically aimed at: 1) developing at a multicentre level harmonized methodologies and protocols for quantitative and reproducible MRS measurements, as a basis for validating these procedures in well controlled clinical and experimental conditions; and 2) providing multicentre critical reviews on the present understanding of the significance of MRS parameters as possible new markers of diagnosis, prognosis and response to therapy. The programme comprised the following main areas of collaborative research and multicentre evaluation: a) development of methods and protocols for quality assessment, calibration and absolute metabolite quantification in in vivo localized, volume-selective MRS; b) design and validation of a new method for assessing localization performance in spectroscopic imaging (MRSI); c) interlaboratory comparison of different methods of signal processing and data analysis, for improving signal quantification in vivo and in vitro MRS spectra; d) quality assessment of high resolution MRS analyses of biological fluids; e) protocol for assembling a pilot data base of MR spectra of tumour extracts for pattern recognition analysis; f) multicentre review on evaluation of the significance of MRS parameters in monitoring lipid metabolism and function in cancer; and g) multicentre review on evaluation of drug pharmacokinetics and metabolism using MRS. The main results and conclusions of four multi-centre trials on items (a), (b) and (c), which involved 24 teams, are reported in the accompanying papers of this series.

Brain↗

A two-compartment phantom for VOI profile measurements in small-bore 31P MR spectroscopy.

A two-compartment gel phantom for VOI profile measurements in volume-selective 31P spectroscopy in small-bore units is presented. The phantom is cylindrical with two compartments divided by a very thin (30 microm) polyethene film. This thin film permits measurements with a minimum of susceptibility influences from the partition wall. The phantom was used for evaluation of the volume selection method ISIS (image-selected in vivo spectroscopy). The position of the phantom was fixed in the magnet during the measurements, while the volume of interest (VOI) was moved stepwise over the border. The signal from the two compartments was measured for each position and the data were evaluated following differentiation. We have found this phantom suitable for VOI profile measurements of ISIS in small-bore systems. The phantom forms a useful complement to recommended phantoms for small bore-spectroscopy.

Biophysical Phenomena↗

Focal, continuous spikes suggest cortical developmental abnormalities. Clinical, MRI and neuropathological correlates.

OBJECTIVES: Widespread use of MRI now gives us increased insights into the different expressions of malformations of cortical development (MCD). The heterogeneity of these disorders are reflected by their varied clinical and neuroimaging features. Characteristic and intense scalp EEG abnormalities have been described in some patients. MATERIAL AND METHODS: We report the MRI and clinical findings of 3 adult patients (age 32-36) with a peculiar EEG pattern of distinct, localized, fast, continuous spiking. These patients represent all patients with such EEG findings that have been recognized by the first author during 9 years. RESULTS: MRI showed MCDs in all, respectively hemimegalencephaly, a subcortical heterotopion, and a focal cortical dysgenesis. The EEG findings had been stable since childhood and were posteriorly located. Two patients had fairly well controlled epilepsy in adult age. The third patient was incapacitated by persistent seizures and was treated with surgery. Histologically cortical dysplasia with neuronal clusters was found in this patient. Variable degrees of cognitive dysfunction were present in all. CONCLUSION: Focal, continuous, fast spiking is an unusual scalp EEG pattern. It is not an inevitable sign of severe epilepsy. It may suggest an MCD. It is not yet clear to what extent such findings are predictive of a dysgenetic etiology of epilepsy.

Action Potentials↗

[Volumes of synovial membrane and joint effusion determined by MR imaging. Markers of severity and/or activity in rheumatoid arthritis?].

Volumes of synovial membrane and joint effusion were determined by MRI in 36 knees with gonarthritis and five healthy knees. In 18 knees MRI was performed before and immediately after arthrocentesis. The difference between MRI-determined and syringe-determined volumes of aspirated joint fluid was 0-7 ml, median 2 ml, corresponding to 0-18%, median 7%, of the pre-aspiration effusion volume. Synovial membrane volumes, determined before and after arthrocentesis varied 0-10 ml, median 3 ml (0-17%, median 7%). No significant systematic misinterpretation of the borderline between joint fluid and synovium was found. The interobserver variation was < 15% in all measurements of synovial volumes > 10 ml and effusion volumes > 5 ml. Patient repositioning resulted in variations < 10%. The synovial volumes in clinically active, clinically inactive and healthy knees were statistically significantly different (median 79 ml, 21 ml and 3 ml, respectively). We conclude that effusion volumes, and in all probability also synovial membrane volumes, can be determined by MRI with a maximal error of approximately 20%. The synovial volume is related to the inflammatory activity of the joint. The results encourage further studies of the value of effusion and synovial membrane volumes as markers of the activity and/or severity of joint inflammation.

Arthritis, Rheumatoid↗

Does a sedative dose of chloral hydrate modify the EEG of children with epilepsy?

Chloral hydrate (CH) is used to sedate children unable to cooperate during investigations such as EEG requiring the patient to be still. It is not known if CH or its metabolites modify the EEG and our aim was to answer this question. Recordings of the EEG before, during and after rectal administration of CH (50-77 mg/kg) in 13 children aged 1.5-13.5 years with severe epilepsy and additional neurological impairments were made. All children had frequent spike-wave activity before CH. In 9 children CH had no effect on the EEG. In 3 children there was a significant reduction in epileptic activity after 20-50 min and in one a significant increase. Cardiovascular parameters were stable throughout. At sedative doses, CH can generally be used before an EEG recording without loss of information but in 4 out of 13 children there were changes which could alter interpretation.

Brain↗

[Diagnostic imaging in suspected lumbar disk prolapse. A controlled comparison of myelography, CT and magnetic resonance imaging].

Eighty patients with monoradicular sciatica were examined by myelography, computed tomography (CT) and magnetic resonance imaging (MRI) and all had subsequent surgery. The images were evaluated by a decision-analytic regret function. The largest amount of diagnostic information was gained from CT followed by MRI and myelography. Myelography was not significantly informative. The results suggest that CT or MRI should be the first choice examination in patients with suspected lumbar disc herniation.

Adult↗

Myocardial perfusion modeling using MRI.

In the present study, it is shown that it is possible to quantify myocardial perfusion using magnetic resonance imaging in combination with gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA). Previously, a simple model and method for measuring myocardial perfusion using an inversion recovery turbo-FLASH (fast low-angle shot) sequence and Gd-DTPA has been presented. Here, an extension of the model is presented taking into account fast and slow water exchange between the compartments, enabling the calculation of the unidirectional influx constant (Ki) for Gd-DTPA, the distribution volume of Gd-DTPA (lambda), the vascular blood volume (Vb), and the time delay through the coronary arteries (delta T). The model was evaluated by computer simulation and used on experimental results from seven healthy subjects. The results in the healthy volunteers for a region of interest placed in the anterior myocardial wall were (mean +/- SD) Ki = 54 +/- 10 ml/100 g/min, lambda = 30 +/- 3 ml/100 g, Vb = 9 +/- 2 ml/100 g, delta T = 3.2 +/- 1.1 s. These results are in good agreement with similar results obtained by other methods.

Adult↗

Measurement of the arterial concentration of Gd-DTPA using MRI: a step toward quantitative perfusion imaging.

A noninvasive method using an inversion recovery turbo-FLASH for dynamic measurement of the arterial input function represented by the bolus passage of Gd-DTPA in the descending aorta is presented, and the results are compared with the input function obtained by arterial blood samples. A good accordance between the two input functions was found, indicating that it is possible to measure the input function to the myocardium using MRI. A variation between the two concentration curves of 5% at upslope, 2.7% at peak point, and < 7% at downslope was found. The study also indicates that a short inversion time < 250 ms has to be used to ensure correct measurement of peak concentration.

Adult↗