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Biomedical subjects

D Leys

Publications and source records attributed to D Leys.

At least 91 records · Page 5Linked to original sources
PubMed2000

Results in 95 hemorrhagic stroke patients included in CLASS, a controlled trial of clomethiazole versus placebo in acute stroke patients.

BACKGROUND AND PURPOSE: Clomethiazole is a neuroprotective drug that enhances gamma-aminobutyrate type A (GABA(A)) receptor activity. Its efficacy and safety were tested in the CLomethiazole Acute Stroke Study (CLASS). The protocol allowed a CT scan to be done after randomization but within 7 days of stroke onset to minimize delays before start of treatment. Ninety-five of the 1360 patients randomized were diagnosed as having intracranial hemorrhage rather than ischemic stroke. Safety results for clomethiazole compared with placebo in this group are reported. METHODS: The study included patients with a clinical diagnosis of acute hemispheric cerebral infarction. Treatment was a 24-hour intravenous infusion of 75 mg/kg clomethiazole or placebo. Patients with intracranial hemorrhage discovered on a postrandomization CT were withdrawn from study treatment if treatment was ongoing, and all patients were followed up to 90 days. RESULTS: Ninety-four patients received treatment, 47 in each group. The hemorrhage was classified as intracerebral in 89 patients (94%). Mortality at 90 days was 19.1% in the clomethiazole group and 23.4% in the placebo group. Sedation was the most common adverse event, occurring at a higher incidence in clomethiazole-treated patients (clomethiazole 53%, placebo 17%), followed by rhinitis and coughing. The incidence and pattern of serious adverse events was similar between the treatment groups. The percentage of patients reaching relative functional independence on the Barthel Index (score >/=60) at 90 days was 59.6% in the clomethiazole group and 53.2% in the placebo group. CONCLUSIONS: Clomethiazole appears safe to administer to hemorrhagic stroke patients compared with placebo. These results would obviate the need for a CT scan before therapy is initiated in acute stroke. The safety of clomethiazole in hemorrhagic stroke patients will be further evaluated in a prospective study that is under way in North America.

Acute Disease↗
PubMed2000

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.

Aged↗
PubMed2000

[Vertebral artery dissections: follow-up with magnetic resonance angiography and injection of gadolinium].

Vertebral artery dissection is a frequent cause of ischemic stroke in young adults but time course of VA dissections remains poorly documented. Angiography was considered as the gold standard for the diagnosis. Recently, non-invasive methods have been developed such as helical CT and magnetic resonance angiography. The purpose of the study was to assess the reliability of a gadolinium-enhanced fast three dimensional (3D) magnetic resonance (MR) angiographic sequence to image vertebral arteries and to assess the long-term follow-up of vertebral artery (VA) dissections. Sixteen consecutive patients with 18 angiographically documented VA dissections were followed-up by gadolinium-enhanced 3D MR angiography and cervical T1-weighted MR imaging at a median delay of 22 months. Ten patients had MR imaging scan at the acute stage as well and nine had early follow-up angiography at a median delay of 3 months. MR angiography was evaluated in a consensus manner including image quality, presence of residual stenosis, luminal irregularities and occlusion. All patients clinically improved. Ten of 11 stenotic dissections returned to normality whereas one stenotic dissection progressed to occlusion. Two pseudoaneurysms detected on the initial angiography resolved spontaneously, one appeared only on a delayed MR angiographic scan and one was detected on early MR angiograms and finally resolved on a late one. Of the seven initially occluded VAs, five reopened with a hairline residual lumen in three. Contrast MR angiography is an interesting tool to assess the late course of VA dissections. Most lesions resolved spontaneously but persisting occlusion or pseudoaneurysm may be found in long term follow-up.

Adult↗
PubMed2000

[Supra-aortic arteries angioplasty and stenting: an ultrasonographic follow up].

PURPOSE: Ultrasonographic follow up of patients with supra-aortic arteries angioplasty and stenting was performed to determine the normal characteristics and to detect restenosis or thrombosis at the repair site. MATERIAL AND METHODS: Twenty-eight patients were followed. The delay between the procedure and the ultrasonographic examination was 1 to 5 years. There were 32 procedures: 7 carotid angioplasties with stenting; 32 vertebral angioplasties (2 stentings), 2 brachiocephalic artery angioplasties (1 stenting); 1 subclavian artery angioplasty. The ultrasonographic examination included morphological and bilateral flow analysis. The usual criteria were measured. Special attention has been given to the morphological aspect of the stents. RESULTS: All of the carotid stents were patent. No restenosis appeared during the follow up. A parietal thickening was observed in one patient without significant reduction of the arterial lumen. There were one vertebral and one brachiocephalic stent thrombosis. The results of the ultrasonographic examinations correlated well with magnetic resonance imaging. CONCLUSION: The ultrasonographic follow up of supra aortic arteries angioplasty and stenting is feasible. An early examination is recommended after the vascular procedure to control the efficacy of the repair and to detect and quantify the residual lesions. This phase is compulsory for an optimal long term follow up.

Adult↗
PubMed1999

Structure and characterization of Ectothiorhodospira vacuolata cytochrome b(558), a prokaryotic homologue of cytochrome b(5).

A soluble cytochrome b(558) from the purple phototropic bacterium Ectothiorhodospira vacuolata was completely sequenced by a combination of automated Edman degradation and mass spectrometry. The protein, with a measured mass of 10,094.7 Da, contains 90 residues and binds a single protoheme. Unexpectedly, the sequence shows homology to eukaryotic cytochromes b(5). As no prokaryotic homologue had been reported so far, we developed a protocol for the expression, purification, and crystallization of recombinant cytochrome b(558). The structure was solved by molecular replacement to a resolution of 1.65 A. It shows that cytochrome b(558) is indeed the first bacterial cytochrome b(5) to be characterized and differs from its eukaryotic counterparts by the presence of a disulfide bridge and a four-residue insertion in front of the sixth ligand (histidine). Eukaryotes contain a variety of b(5) homologues, including soluble and membrane-bound multifunctional proteins as well as multidomain enzymes such as sulfite oxidase, fatty-acid desaturase, nitrate reductase, and lactate dehydrogenase. A search of the Mycobacterium tuberculosis genome showed that a previously unidentified gene encodes a fatty-acid desaturase with an N-terminal b(5) domain. Thus, it may provide another example of a bacterial b(5) homologue.

Amino Acid Sequence↗
PubMed1999

Cytochrome c" from the obligate methylotroph Methylophilus methylotrophus, an unexpected homolog of sphaeroides heme protein from the phototroph Rhodobacter sphaeroides.

The complete primary structure of an unusual soluble cytochrome c isolated from the obligate methylotrophic bacterium Methylophilus methylotrophus has been determined to contain 124 amino acids and to have an average molecular mass of 14293.0 Da. The sequence has two unusual features: firstly, the location of the heme-binding cysteines is far downstream from the N-terminus, namely at positions 49 and 52; secondly, an extra pair of cysteine residues is present near the C-terminus. In both respects, cytochrome c" is similar to the oxygen-binding heme protein SHP from the purple phototrophic bacterium Rhodobacter sphaeroides. In contrast to SHP, cytochrome c" changes from low-spin to high-spin upon reduction, due to dissociation of a sixth heme ligand histidine which is identified as His-95 by analogy to the class I cytochromes c. The distance of His-95 from the heme (41 residues) and the presence of certain consensus residues suggests that cytochrome c" is the second example of a variant class I cytochrome c.

Amino Acid Sequence↗
PubMed1999

[7 reasons for hospitalizing stroke patients in special treatment units].

THE HELSINGBORG DECLARATION: One of the primary objectives of the Helsingborg declaration was that all patients should have access to care in a neurovascular unit. However to date, only a few specialized facilities are available in Europe. SEVEN GOOD REASONS: There are seven good reasons why patients suffering cerebral vascular events should be hospitalized in specialized care units. 1. Improve chances of survival and recovery: mortality at 3 and 12 months is 25% lower in patients hospitalized in specialized units and the combined risk of death and institutionalization is reduced by one-third. The beneficial effect in terms of survival and function persists at 5 years. 2. Provide optimal management for emergency conditions which may be confounded with cerebral vascular events and which require emergency care. 3. Optimize health care organization. 4. Favor research and teaching. 5. Reduce health expenditures related to cerebral vascular events. 6. Inform health authorities of the needs of this population. 7. Prepare for the possible development of intravenous thrombolytic therapies. OUTDATED ATTITUDE: Fatalism and nihilism is no longer an acceptable attitude. Cerebral vascular events must be considered as an emergency condition and our health care system must change, adapting health care facilities to this new situation. Neurovascular units provide one of the most effective tools to meet this challenge.

Adult↗
PubMed1999

One-and-a-half syndrome in pontine infarcts: MRI correlates.

The one-and-a-half syndrome is characterised by a lateral gaze palsy in one direction and internuclear ophthalmoplegia in the other. It is due to a unilateral lesion of the dorsal pontine tegmentum, involving the ipsilateral paramedian pontine reticular formation, internuclear fibres of the ipsilateral medical longitudinal fasciculus and, usually, the abducens nucleus. The main causes of this rare syndrome are stroke and multiple sclerosis. Few cases have been reported since the introduction of MRI. Our aim was to examine clinicoradiological correlations in six patients with a one-and-a-half syndrome due to a stroke. Ophthalmological symptoms were diplopia, oscillopsia or blurred vision. Four patients had an associated facial nerve palsy, three a hemiparesis and one a unilateral hemihypoaesthesia. MRI revealed an infarct in the pons in all patients. The cause of the infarct was a basilar artery dissection in one patient, bilateral vertebral artery dissection in a second and unknown in the other four. All patients recovered within 2 days to 8 weeks. This study showed a good correlation between the site of the lesion (superior, inferior or extensive pontine ischaemia) and clinical deficits.

Adult↗
PubMed1999

Endovascular treatment of ruptured intracranial aneurysms.

The Guglielmi detachable coil (GDC) is an important tool for the treatment of ruptured intracranial aneuryms by an endovascular approach. This new device may be introduced under fluoroscopy into the aneurysmal sac through a microcatheter. When the coil is judged well positioned, it can be detached with accuracy by electrolytic breakdown. The procedure is completed when a dense coil packing is obtained. When vasospasm is present, papaverin infusion or angioplasty may be used by the endovascular approach as well. Best results are achieved in cases of small aneurysm with small neck. The morbidity and mortality rates in the first 200 patients treated by GDC for a ruptured intracranial aneurysm were 4% and 1.5%, respectively. Complications are generally related to rupture of the malformation by the endovascular device or to thromboembolic events. Despite these promising results, further studies using larger numbers of patients are required to determine the exact role of these procedures in patient care.

Aneurysm, Ruptured↗
PubMed1999

Structure and mechanism of the flavocytochrome c fumarate reductase of Shewanella putrefaciens MR-1.

Fumarate respiration is one of the most widespread types of anaerobic respiration. The soluble fumarate reductase of Shewanella putrefaciens MR-1 is a periplasmic tetraheme flavocytochrome c. The crystal structures of the enzyme were solved to 2.9 A for the uncomplexed form and to 2.8 A and 2.5 A for the fumarate and the succinate-bound protein, respectively. The structures reveal a flexible capping domain linked to the FAD-binding domain. A catalytic mechanism for fumarate reduction based on the structure of the complexed protein is proposed. The mechanism for the reverse reaction is a model for the homologous succinate dehydrogenase (complex II) of the respiratory chain. In flavocytochrome c fumarate reductase, all redox centers are in van der Waals contact with one another, thus providing an efficient conduit of electrons from the hemes via the FAD to fumarate.

Amino Acid Oxidoreductases↗
PubMed1999

Study on COgnition and Prognosis in the Elderly (SCOPE).

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by <10 mmHg since the randomization visit, or DBP is >85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged.

Aged↗
PubMed1999

Stroke and atrial fibrillation: is stroke prevention treatment appropriate beforehand? SAFE I Study Investigators.

OBJECTIVE: To undertake a pilot study before conducting a large European multicentre prospective study, to determine the proportion of patients with atrial fibrillation who were not receiving antithrombotic treatment before stroke onset, and their characteristics. DESIGN AND PATIENTS: The stroke in atrial fibrillation ensemble (SAFE) I study was an observational study conducted in 213 patients with atrial fibrillation consecutively admitted in 1997 to three European centres for an acute stroke or transient ischaemic attack (TIA). It was determined whether they were receiving prior antithrombotic treatment. RESULTS: Atrial fibrillation was known before stroke in 148 patients (69.5%). Of 213 patients, 34 (16.0%) were receiving anticoagulation treatment before stroke, but only six had an international normalised ratio between 2. 0 and 3.5; 65 (30.5%) were receiving antiplatelet treatment; and three (1.4%) were receiving both anticoagulation and antiplatelet treatment. Of 137 patients eligible for oral anticoagulation, 108 (78.8%) did not receive treatment. Of 142 patients eligible for any antithrombotic treatment, 62 (43.7%) were not treated. The logistic regression analysis, assuming anticoagulation treatment as a dependent variable, found digoxin treatment, absence of arterial hypertension, mitral stenosis, and cardioversion as independent factors. Assuming any antithrombotic treatment as a dependent variable, previously known atrial fibrillation, lower age, being a non-smoker, and absence of arterial hypertension were found to be independent factors. CONCLUSION: More than half of the patients with atrial fibrillation admitted for acute stroke or TIA were not receiving any antithrombotic treatment beforehand. New onset atrial fibrillation and contraindications account for a minority of non-prescriptions; thus, other reasons should be identified to improve stroke prevention in the community.

Adult↗
PubMed1999

Internal carotid arterial stenosis: CT angiography with volume rendering.

PURPOSE: To determine the reliability of helical computed tomography (CT) with volume rendering for evaluation of internal carotid arterial stenosis. MATERIALS AND METHODS: In 22 patients, 44 carotid arteries were evaluated with helical CT and selective conventional angiography. CT data were displayed on volume-rendered and maximum intensity projection (MIP) images. Stenoses were measured separately on axial, volume-rendered, and MIP images and on conventional angiograms. Each artery was then graded as having no stenosis, mild (< 30%) stenosis, moderate (30%-70%) stenosis, severe (> 70%) stenosis, near occlusion, or occlusion. RESULTS: One case of stenosis was not assessable at axial CT because of an inappropriate scanning plane; four cases were not assessable at MIP CT because of mural calcifications. All carotid arteries were assessable on volume-rendered images despite no depiction of the residual lumen at the site of narrowing in three cases of near occlusion. Correlations between angiography and helical CT were good. Axial, volume-rendered, and MIP images enabled correct classification of stenosis in 88%, 89%, and 90% of arteries, respectively. CT with volume rendering was slightly more sensitive for determining candidates for endarterectomy (i.e., those with > 70% stenosis and near occlusion); sensitivity was 100% and specificity, 92%. CONCLUSION: CT angiography with volume rendering enabled accurate evaluation of carotid disease, even when dense calcifications were present. However, no definite advantage over currently available techniques for CT measurement of stenosis severity was found.

Adult↗
PubMed1999

White matter changes in stroke patients. Relationship with stroke subtype and outcome.

White matter changes (WMC), detected by imaging techniques, are frequent in stroke patients. The aim of the study was to determine how WMC relate to stroke subtypes and to stroke outcome. We made a systematic Medline search for articles appearing with two of the following key words: either 'WMC or white matter lesions or leukoencephalopathy or leukoaraiosis' and 'stroke or cerebral infarct or cerebral hemorrhage or cerebrovascular disease or transient ischemic attack (TIA)'. WMC, as defined radiologically, are present in up to 44% of patients with stroke or TIA and in 50% of patients with vascular dementia. WMC are more frequent in patients with lacunar infarcts, deep intracerebral hemorrhages, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cerebral amyloid angiopathy. After an acute ischemic stroke, WMC are associated with a higher risk of death or dependency, recurrent stroke of any type, cerebral bleeding under anticoagulation, myocardial infarction, and poststroke dementia. WMC in stroke patients are often associated with small-vessel disease and lead to a higher risk of death, and poor cardiac and neurological outcome. However, several questions remain open and need further investigations.

Age Factors↗
PubMed1999

Confusional state in stroke: relation to preexisting dementia, patient characteristics, and outcome.

BACKGROUND AND PURPOSE: Acute confusional state (ACS) is frequent in hospitalized stroke patients. We previously showed that 16% of patients admitted for a stroke have preexisting dementia. The extent to which preexisting cognitive decline is associated with a risk of ACS at the acute stage of stroke remains to be systematically examined. The aim of this study was to evaluate the prevalence of ACS in acute stroke patients, to study the influence of preexisting cognitive decline and other patient characteristics, and to evaluate the influence of ACS on outcome. METHODS: We diagnosed ACS using DSM-IV criteria and the Delirium Rating Scale with a cutoff of 10 in 202 consecutive stroke patients aged 40 years or older (median age, 75 years; range, 42 to 101 years). Cognitive functioning before stroke was assessed with the Informant Questionnaire on Cognitive Decline in the Elderly. RESULTS: Forty-nine stroke patients (24.3%; 95% CI, 18.3% to 30.2%) had an ACS during hospitalization. Using logistic regression analysis, we found preexisting cognitive decline (P=0.006) and metabolic or infectious disorders (P=0.008) to be independent predictors of ACS. Functional, but not vital, prognosis was worse in patients with ACS at discharge and 6 months after stroke. CONCLUSIONS: ACS occurs in one fourth of stroke patients older than 40 years. Its occurrence requires inquiry for a preexisting cognitive decline, which usually remains unrecognized in the absence of a systematic evaluation.

Acute Disease↗