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Biomedical subjects

J De Keyser

Publications and source records attributed to J De Keyser.

At least 55 records · Page 3Linked to original sources

Brachial, radial, or femoral approach for elective Palmaz-Schatz stent implantation: a randomized comparison.

UNLABELLED: From October 1994 to November 1995, 150 male eligible patients were randomly assigned to Palmaz-Schatz stent implantation through 6 French catheters using the femoral (puncture) (n = 56), radial (puncture) (n = 56), or brachial (cutdown) (n = 38) approach at 6 participating Belgian centers. Acenocoumarol was given for 1 month after stenting. END POINTS: Primary-entry site complications (bleeding, haematoma, transfusion, occlusion, surgery) poststent implantation. Secondary-success rate, stent thrombosis, Q or non Q wave MI, repeat PTCA, CABG, CVA, haemorrage, death. There were no statistically significant differences between the three groups for base line and angiographic patient characteristics, procedural characteristics, in hospital outcome, average hospitalisation time after stenting, events during the month after stenting, or local complications at 1 month follow-up. The only statistically significant difference was the arterial time of the procedure: mean +/- SD (minutes) brachial 31.0 +/- 10.02 *P < 0.001, femoral 42.2 +/- 21.8, radial 55.8 +/- 31.3 **P < 0.0001 (*brachial vs. femoral, **brachial vs. radial). There was a clear trend toward more technical difficulties and more problems with the radial approach. In each group: vascular surgery at entry site: 0%, blood transfusion: 0%. In our study, local complications and length of hospital stay were similar with the three possible approaches, and brachial approach was associated with a shorter arterial time.

Adult↗

Early outcome in acute ischemic stroke is not influenced by the prophylactic use of low-dose aspirin.

Aspirin reduces the occurrence of ischemic strokes. In some prophylactic trials it was suggested that aspirin might also lessen stroke severity, and hence improve outcome in patients sustaining an ischemic stroke. We examined stroke severity (by using the Mathew scale) and early outcome (Barthel index and mortality on day 21) in 91 patients with an acute (< 24 h) ischemic stroke in the territory of the middle cerebral artery. Twenty-seven patients were taking low-dose aspirin (100 or 200 mg/day) prior to their stroke, and 64 were not using antiplatelet drugs. There were no significant differences in baseline stroke severity, early (21 days) mortality or early disability between the two groups. The results of this small study suggest that the use of low-dose aspirin prior to an ischemic stroke does not influence the severity of that stroke and early outcome.

Aged↗

Menstrually related worsening of symptoms in multiple sclerosis.

The objective of this study was to investigate whether the menstrual cycle influences multiple sclerosis (MS) symptoms. Seventy-two normally menstruating women (aged 20-50 years) with MS were interviewed. Of the 60 patients with a relapsing-remitting form of MS (RR-MS), 26 (43%) regularly experienced worsening of their MS symptoms in the period just before, or at the beginning of, the menstruation. Significantly more patients of the group reporting no influence of the premenstrual period on MS symptoms were using an oral contraceptive (p=0.041), suggesting a protective effect. There were 12 patients with the primary chronic progressive form of MS (PCP-MS). None of them experienced an influence of the menstrual cycle on their symptoms. Our results suggest that hormonal changes preceding menstruation may worsen symptoms in a subgroup of women with RR-MS.

Adult↗

Risks of multiple sclerosis in relatives of patients in Flanders, Belgium.

OBJECTIVES: To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. METHODS: Lifetime risks were calculated using the maximum likelihood approach. RESULTS: Vital information was obtained on 674 probands with multiple sclerosis in Flanders and a total of their 26225 first, second, and third degree relatives. Full medical information to allow documentation of multiple sclerosis status was available for 21351 (81.4%) relatives. The age adjusted risk for parents was 1.61 (SEM 0.35)%, for siblings 2.10 (SE 0.36)%, and for children 1.71 (SEM 0.70)%. For aunts and uncles, the risk was 0.66 (SEM 0.13)%. CONCLUSIONS: The risk for first degree relatives of patients with multiple sclerosis in Flanders is increased 10-fold to 12-fold; for second degree relatives, it is increased threefold. This information can be used for risk counselling in families and provides additional support for the role of more than one locus contributing to the susceptibility of multiple sclerosis.

Adult↗

Is positron emission tomography useful in stroke?

Positron emission tomography (PET) has been widely used in the study of stroke and related cerebrovascular diseases. It has shown the various stages leading to cerebral infarction and defined the significance of the ischaemic penumbra. PET scan can predict the clinical outcome of patients with acute ischaemic stroke. Several types of diaschisis can also be demonstrated by PET. They reflect different pathophysiological changes in supratentorial infarcts. Post-apoplectic seizures are shown to increase the ischaemic damage in the affected cerebral hemisphere. PET has contributed also to the concept of multi-infarct dementia, although the significance of chronic ischaemia in the pathogenesis of vascular dementia has not been fully investigated.

Brain Ischemia↗

Lubeluzole in acute ischemic stroke. A double-blind, placebo-controlled phase II trial. Lubeluzole International Study Group.

BACKGROUND AND PURPOSE: We aimed to assess the safety and efficacy of lubeluzole in patients with a clinical diagnosis of acute (< 6 hours) ischemic stroke in the carotid artery territory. METHODS: A randomized, double-blind, placebo-controlled multicenter trial was conducted in 232 patients. Because treatment was administered within 6 hours and a CT scan was not mandatory before the start of treatment, 39 patients with either an intracerebral hemorrhage or ischemic stroke in the vertebrobasilar circulation were excluded from the primary efficacy analysis as prespecified in the protocol. Of the 193 patients with acute ischemic stroke in the carotid artery territory (target population), 61 received placebo, 66 lubeluzole 7.5 mg over 1 hour followed by 10 mg/d for 5 days, and 66 lubeluzole 15 mg over 1 hour followed by 20 mg/d for 5 days. RESULTS: The trial, initially aimed at a patient inclusion of 270, was terminated prematurely according to the advice of the Safety Committee because of an imbalance in mortality between the treatment groups. Mortality rates at the final follow-up of 28 days for placebo, lubeluzole 10 mg/d, and lubeluzole 20 mg/d were, respectively, 18%, 6%, and 35% in the target population, results that were confirmed in the intent-to-treat population. Multivariate logistic regression analysis showed that the lower mortality in the lubeluzole 10 mg/d group was significantly in favor of the 10 mg/d treatment (P = .019). The higher mortality rate in the 20 mg/d group could be explained, at least in part, by an imbalance at randomization that led to a higher number of patients in that group with severe ischemic stroke. A total of 26 of 66 patients (39%) who received lubeluzole 10 mg/d had a score on the Barthel Index of > 70 at day 28, indicating no or mild disability, compared with 21 of 61 (34%) in the placebo group and 19 of 66 (29%) in the lubeluzole 20 mg/d group (P = NS). CONCLUSIONS: In patients with acute ischemic stroke, the dosage regimen of 7.5 mg over 1 hour followed by 10 mg/d of intravenous lubeluzole is safe and statistically significantly reduced mortality. Further clinical trials in a larger number of patients are ongoing to confirm efficacy.

Acute Disease↗

Dopamine agonists used in the treatment of Parkinson's disease and their selectivity for the D1, D2, and D3 dopamine receptors in human striatum.

1. It has been suggested that an ideal antiparkinsonian treatment requires stimulation of both D1 and D2 dopamine receptors. Bromocriptine and lisuride are regarded as pure D2 receptor agonists, whereas pergolide and apomorphine are thought to stimulate both D1 and D2 receptors. 2. The aim of this study was to compare the affinities of bromocriptine, lisuride, pergolide, and apomorphine for the D1, D2, and D3 receptors in postmortem human striatum. The dissociation constants (Ki values) of the dopamine agonists were determined from competition binding experiments with selective radioligands. 3. The Ki values of the orally administered agonists--bromocriptine, pergolide, and lisuride--for the D2 receptors were proportional to their optimal doses against parkinsonism. Ki(D1)/Ki(D2) ratios were 23 for lisuride, 67 for pergolide, 60 for bromocriptine, and 2.6 for apomorphine. Ki(D3)/Ki(D2) ratios were 0.4 for lisuride, 1 for pergolide, 5.4 for bromocriptine, and 21 for apomorphine. 4. The present results support the hypothesis that the antiparkinsonian effect of dopamine agonists is mediated primarily by D2 receptors. Apomorphine is a mixed D1/D2 agonist, but pergolide has no more D1 agonist properties than bromocriptine and lisuride. The role of the D3 receptors is unknown, but their activation might either be associated with the generation of psychiatric side-effects or dyskinesias, or alternatively add to antiparkinsonian activity.

Aged↗

Autoradiographic distribution of D3-type dopamine receptors in human brain using [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin.

The regional distribution of D3 dopamine receptors was studied in human brain by quantitative autoradiography with [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT). The highest densities were found in the ventral striatum/nucleus accumbens, followed by the remainder of the neostriatum, cerebral cortex, and cerebellar cortex. Moderate amounts were found in the substantia nigra. Low densities of D3 dopamine receptors were visualized in pituitary gland (posterior lobe > anterior lobe), amygdala, and hippocampus. The globus pallidus and thalamus contained lower densities. The distribution pattern is much more widespread as detected by in situ hybridisation histochemistry for D3 mRNA in human and in rat brain. Our data confirm a predilection of D3 receptors in brain areas involved in cognitive and emotional functions. The presence of D3 receptors in non-limbic parts of the neostriatum and substantia nigra suggests that they also play a role in the dopaminergic control of motor processes. Its precise function in cerebellum and pituitary gland is at present uncertain.

Aged↗

Insulin-like growth factor-I receptor densities in human frontal cortex and white matter during aging, in Alzheimer's disease, and in Huntington's disease.

Using quantitative autoradiography we have investigated insulin-like growth factor (IGF)-I receptors in postmortem-obtained frontal cortex and white matter from 39 individuals without neurological disease, ranging in age from 0 to 95 years, and from 5 patients with Huntington's disease and 4 with Alzheimer's disease. IGF-I receptor densities in white matter were significantly higher in neonates than in adults; during adult life there was no further decline. The higher density of IGF-I receptors in white matter of neonates most likely reflects extensive formation of myelin. There was no significant decrease in IGF-I receptor densities in the cortical mantle with age, suggesting that the cells containing IGF-I receptors in frontal cortex are maintained during the entire life-span. There were no significant alterations in IGF-I receptor densities in frontal cortex and white matter from patients with Huntington's disease and Alzheimer's disease compared with controls from the same age groups.

Adolescent↗

Insulin-like growth factor-I receptors in human brain and pituitary gland: an autoradiographic study.

Insulin-like growth factor (IGF)-I receptors were studied in adult human postmortem brain and pituitary gland using quantitative autoradiography with human recombinant [125I]IGF-I. The highest densities were found in the choroid plexus, pituitary gland--where IGF-I receptors were mainly concentrated in the anterior lobe, pineal gland, glomerular layer of the olfactory bulb, and the molecular layer of the cerebellar cortex. Moderate densities were present in cerebral cortex, caudate nucleus, putamen, accumbens, the CA1, CA2, CA3 fields and dentate gyrus of the hippocampus, the dentate nucleus of the cerebellum, amygdala, thalamus, pontine nuclei, and substantia nigra. All other brain areas, including white matter, contained low densities of IGF-I receptors. The finding that several well-defined brain structures are enriched with IGF-I receptors suggests a neurotrophic/survival or neuromodulatory role of insulin-like growth factors on specific neuronal systems. IGF-I receptors observed in the white matter may be associated with oligodendrocytes.

Adult↗

Hospital referral of stroke patients: a survey of attitudes in general practice, and consideration of entry times for clinical trials.

Two major issues in clinical trials in stroke are the criteria used for the selection of patients expected to benefit from the proposed treatment, and the entry time of those patients. We surveyed 507 Belgian general practitioners (GPs) on their opinions on referral of stroke patients to hospital and also on their actual referral behaviour. The feasibility of a 6-hour entry time was included in the investigation. Stroke is considered to require an urgent response: 88% of GPs visited the patient immediately on concluding that such an event had occurred. The mean time between the onset of the first clinical symptoms and the arrival of the GP at the patient's residence was about 30 minutes. Within 6 h of the insult, 95% of the patients referred to hospital had been admitted. Information on the GP's most recent stroke patient revealed that 72.4% of these stroke patients were admitted to hospital. Patients referred to hospital were significantly younger, had a significantly more severe stroke, and were significantly more likely to have had a first stroke and to have lived independently before the insult than patients not admitted to hospital. We think that Belgian GPs need to change their referral behaviour with respect to stroke patients and refer more of those who have suffered more mildly. There is every reason to be optimistic about this re-education, since the patients whom GPs do refer to hospital are referred rapidly enough to profit from a possibly efficacious treatment.

Adult↗

Miller Fisher syndrome associated with Mycoplasma pneumoniae infection: report of a case.

We report a 38-year-old male patient who developed a Miller Fisher syndrome following a respiratory tract disorder associated with a serologically proven Mycoplasma pneumoniae infection. Although several neurologic manifestations have been reported after Mycoplasma pneumonia infection, Miller Fisher syndrome has not been reported previously. No evidence of CNS involvement could be demonstrated on repeated MRI of the brain.

Adult↗

Imidazoline receptors, non-adrenergic idazoxan binding sites and alpha 2-adrenoceptors in the human central nervous system.

Both [3H]clonidine and [3H]idazoxan bind to alpha 2 adrenoceptors. The former also labels imidazoline receptors, and the latter non-adrenergic idazoxan binding sites. In order to investigate whether the imidazoline receptors and non-adrenergic idazoxan binding sites are identical, we compared the binding characteristics of [3H]clonidine and [3H]idazoxan to these sites by radioligand binding experiments on ultra-thin slices and homogenates of human striatum. A good correlation was found between the effect of different ions on the binding characteristics of [3H]clonidine and [3H]idazoxan, and the affinities of most competing drugs. However, clonidine and rilmenidine displayed a 100- and 10-fold lower affinity, respectively, for the idazoxan binding sites than for the imidazoline receptors. Autoradiography with [3H]clonidine showed that high densities of imidazoline receptors were present in the striatum, pallidum, gyrus dentatus of the hippocampus, amygdala, and substantia nigra. Moderate densities were found throughout the cerebral cortex, thalamus and several brainstem nuclei including the nucleus olivarius inferior. Low densities were seen in the cerebellum, spinal cord and pituitary gland. As for the non-adrenergic sites labelled by [3H]idazoxan, the imidazoline receptors can be found in all major brain areas examined. However, there are some striking differences between the concentrations of imidazoline receptors and non-adrenergic idazoxan binding sites in certain brain regions. To reconcile distribution and pharmacologic data, we propose that imidazoline receptors and non-adrenergic idazoxan binding sites represent different proteins or protein complexes and that at least in the nucleus reticularis lateralis and the striatum, imidazoline receptors and non-adrenergic idazoxan binding sites may be physically associated. The regional distribution of alpha 2 adrenoceptors within the human CNS was determined by quantitative autoradiography with [3H]RX821002. The highest densities of alpha 2 adrenoceptors were found in the cerebral and cerebellar cortex, and certain regions in the medulla oblongata (floor of the IV ventricle, reticular formation, hypoglossal nucleus and nucleus olivarius inferior). No alpha 2 adrenoceptors were detected in the pituitary gland. There exists no relationship between the distribution pattern of imidazoline receptors and alpha 2 adrenoceptors, indicating that these binding sites are independent from each other.

Aged↗

Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study.

In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with 6 mg sumatriptan sc using an autoinjector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated "adequately" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an autoinjector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist.

Acute Disease↗

Bromocriptine therapy in multiple sclerosis: an open label pilot study.

Bromocriptine suppresses the duration and severity of clinical signs of experimental allergic encephalitis, which is considered as an animal model for multiple sclerosis (MS). We conducted an open pilot study with 2.5 mg of bromocriptine two times a day on 18 patients with clinically or laboratory-supported definite MS (10 with the relapsing-remitting form and eight with the chronic progressive form). After 1 year of treatment, 14 of the 15 patients who completed the study showed disease progression as evidenced by one or more of the following parameters: worsening of the EDSS score, clinical relapses, appearance of new lesions on MRI of the brain and brainstem, or increased latencies of visual or auditory evoked responses. These findings indicate that bromocriptine does not completely suppresses ongoing disease activity in patients with multiple sclerosis.

Adult↗

The European Stroke Scale.

BACKGROUND AND PURPOSE: For detecting therapeutic effect and matching of treatment groups in stroke trials, a scale that meets the clinimetric criteria is of the utmost importance. METHODS: The European Stroke Scale consists of 14 items selected for their specificity and their prognostic value. It is designed for patients with middle cerebral artery stroke. Interrater reliability, internal consistency, and time for completion were investigated in 74 patients. Intrarater reliability was studied in 38 patients. To establish concurrent validity, two trials were performed in 20 and 44 patients. The scale was correlated with the MCA Neurological Scale, the Canadian Stroke Scale, the Scandinavian Stroke Scale, the Barthel Index, and the Rankin Scale. Correlations were calculated by means of Spearman's correlation coefficient. The trial in 44 patients also investigated the prognostic validity of the scale for 1-month and 8-month neurological, functional, and handicap status. These data were analyzed by linear regression. RESULTS: Interrater (kappa value range, 0.62 to 0.85) and intrarater (kappa value range, 0.65 to 1.00) reliability for each item was good, and internal consistency was excellent (Cronbach's alpha coefficient, 0.92). Mean time for completion was 8.2 minutes (range, 4 to 14 minutes). Correlations of the European Stroke Scale with other neurological scales ranged from 0.93 to 0.95. The correlation with the Barthel Index and the Rankin Scale was 0.84 and -0.86. The R2 values for prognostic validity ranged from 0.45 to 0.81 (P < or = .0001). CONCLUSIONS: The European Stroke Scale has been developed according to the clinimetric criteria.

Adult↗

What intracranial tissues in humans contain sumatriptan-sensitive serotonin 5-HT1-type receptors?

We investigated the presence of sumatriptan-sensitive serotonin (5-HT)1 receptors in different human tissues by using a radioligand-binding technique with [3H]5-HT. Sumatriptan displaced [3H]5-HT from frontal cortical and striatal membranes in a biphasic manner, with a high-affinity site corresponding to binding to the 5-HT1D receptor. In blood platelet membranes, sumatriptan displaced [3H]5-HT with a 100-fold lower affinity. Sumatriptan failed to displace [3H]5-HT in membranes from large cerebral arteries, pial vessels, coronary arteries and dura mater. These findings suggest that either there are no sumatriptan-sensitive 5-HT1 receptors on intracranial blood vessels or they are so small in number that they cannot be detected by the radioligand-binding technique. Other mechanisms, possibly centrally mediated, may be responsible for the antimigraine action of sumatriptan.

Adult↗