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Biomedical subjects

B Brochet

Publications and source records attributed to B Brochet.

50 records · Page 3Linked to original sources

Double blind placebo controlled multicentre study of ginkgolide B in treatment of acute exacerbations of multiple sclerosis. The Ginkgolide Study Group in multiple sclerosis.

After an open labelled pilot study of ginkgolide B, a potent inhibitor of platelet activating factor, in the treatment of acute exacerbations of multiple sclerosis, a randomised double blind placebo controlled study was undertaken. One hundred and four patients were enrolled in the study: for seven days 43 received placebo, 29 received 240 mg/day ginkgolide B and 32 received 360 mg/day ginkgolide B. There was no statistical difference between the three groups for changes in Rankin, Kurtzke expanded disability status scale (EDSS), and Hauser ambulation index (AI) scores. Although there was a trend in favour of groups treated with ginkgolide for a change of Rankin and AI scores, it is concluded that ginkgolide B is not an effective treatment of exacerbations of multiple sclerosis.

Activities of Daily Living↗

Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR and magnetization transfer.

PURPOSE: To study bystander demyelination in multiple sclerosis with an experimental in vivo model of toxic demyelination. METHODS: Toxic demyelinating lesions were created in two monkeys by injection of lysophosphatidylcholine in the centrum semiovale. Follow-up was done clinically and with serial MR studies, including T2-weighted and gadolinium-enhanced T1-weighted images and measurement of magnetization transfer ratio, until the animals were killed at days 14 and 34, respectively. Light and electron microscopy analysis was compared with MR data. RESULTS: Interval measurement of magnetization transfer ratio during the course of the experiment revealed a maximum decrease at day 7 to day 8, associated with the greatest clinical manifestations. The lowest values of magnetization transfer ratio correlated with histopathologic findings of myelin and axon destruction. Magnetization transfer ratio measurements appear to be sensitive to macromolecular destruction and specifically to membrane disorganization. At no time was gadolinium enhancement observed in this model of toxic demyelination. CONCLUSION: Preliminary results of this study indicated that magnetization transfer is a good technique to follow in vivo matrix destruction in brain parenchyma lesions. The results suggest also that phases of toxic demyelination in multiple sclerosis might not show gadolinium enhancement. Differentiation between demyelinating activity and associated inflammation in multiple sclerosis lesions should be considered in further in vivo work.

Animals↗

Spontaneous and 5HT-induced cyclic contractions in superficial temporal arteries from chronic and episodic cluster headache patients.

Superficial temporal arteries (STAs) are abnormally dilated in the painful side during cluster headache (CH) attacks. We have assessed the possible dysfunction of these arteries by comparing in vitro the reactivity of STAs removed from the painful side of CH patients during a cluster of attacks with that of STAs from patients free of CH. The responses to KCl and norepinephrine (NE) of both types of arteries were similar. Serotonin (5HT) induced a classical dose-dependent constriction in arteries from non-CH patients, but systematically triggered rhythmic contractions in arteries from episodic CH patients. Arteries from chronic CH patients also showed spontaneous rhythmic contractions. In both cases, this activity was stopped by calcitonin gene-related peptide (CGRP) but, even in the presence of CGRP, it could be restored by low concentrations of 5HT. Thus, 5HT, unlike NA, can trigger rythmic activity in STAs of CH patients and may play a major role in CH through abnormal smooth muscle cell reactivity.

Adult↗

Seric immune complexes in multiple sclerosis do not contain MBP epitopes.

Immune complexes from sera of MS patients, other neurological diseases, and healthy donors were precipitated using polyethyleneglycol and analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Silver staining evidenced additional protein bands whose molecular weights were 14-16, 38, and 43 kDa. These IC proteins were present in most MS patients studied. To identify their nature, immunoblotting was performed with antihuman immunoglobulins A, M, G antibodies. No immunoreactivity was found below a molecular weight of 66 kDa on a nitrocellulose sheet having the transferred protein pattern of MS IC. Using purified human myelin, MS IC transferred to an immobilon sheet and antihuman myelin basic protein antibodies, an immunoreactivity was seen only on purified human MBP. The small proteins of 14-16 kDa and the others of 38, 43 kDa were not immunoreactive. Identification of the nature of these additional proteins in MS IC is in progress.

Antigen-Antibody Complex↗

Validity of the International Headache Society criteria for migraine. GRIM. Groupe de Recherche Interdisciplinaire sur la Migraine.

For general practitioners and in epidemiological studies, migraine poses diagnostic problems. It is a polymorphous disease, with diagnosis based on a subjective description of symptoms. The International Headache Society (IHS) proposed a set of rigorous criteria for the diagnosis of migraine. We studied its validity on 171 outpatients of headache clinics and on 96 headache sufferers detected during an annual checkup for workers. The criteria showed an excellent specificity, however sensitivity in both samples was < 50%. This lack of validity could be due to IHS criteria being too restrictive. We therefore elaborated and validated our own diagnostic tool, based on the IHS criteria, to a sensitivity of 95% and a specificity of 78%. We propose our tool for epidemiological studies.

Adolescent↗

A nationwide survey of migraine in France: prevalence and clinical features in adults. GRIM.

In November 1990 a nationwide survey of migraine was conducted in France on a representative sample of residents aged 15 years and older. The diagnosis of migraine was based on the International Headache Society (IHS) classification. In a previous study, we validated a diagnostic algorithm which classifies headache sufferers as IHS migraine, "borderline" migraine, possible migraine and non-migrainous headache. The overall prevalence of migraine patients with the IHS criteria in the present study was 8.1%; another 4% were classified as "borderline" migraine, which we in fact considered as definite migraine. Age, gender and occupation were found to be risk factors for migraine. Neither frequency and duration of attacks nor length of time of disease differed with gender. Expressed intensity of attacks, however, was greater in females.

Adolescent↗

[Pilot study of Ginkgolide B, a PAF-acether specific inhibitor in the treatment of acute outbreaks of multiple sclerosis].

Ten patients with relapsing-remitting multiple sclerosis in acute relapse were treated with a five-day course of intravenous ginkgolide B, a specific inhibitor of PAF-acether. Eight patients had improvement of their neurological score, beginning 2 to 6 days after the initiation of therapy. This improvement was sustained in 5 patients and only transient in 3. Two out of these 3 patients with secondary failure and the other 2 who did not respond to ginkgolide therapy, received i.v. methylprednisolone. Three patients experienced mild side effects under ginkgolide therapy but none of the patients had any serious adverse effect. A controlled randomized study is underway, in order to confirm these results and test higher dosages and more prolonged administration.

Adult↗

Cluster headache: ultrastructural evidence for mast cell degranulation and interaction with nerve fibres in the human temporal artery.

It has been suggested that histamine plays an important role in the pathogenesis of cluster headache. In addition, both neurogenic and vascular components have been described during cluster headache attacks without an obvious anatomical link between them. Our ultrastructural observations of human temporal arteries from cluster headache patients and their comparison to those from a control group strongly suggest that mast cells may be this link. Mast cells in both groups show a very close apposition with nerve fibres, suggesting a functional interaction between them. Moreover, in the cluster headache group exclusively, adventitial mast cells show profound morphological modifications suggesting progressive degranulation. These data strongly suggest that mast cells could be directly or indirectly involved in the pathophysiology of cluster headaches.

Adult↗

Monoclonal anti-conjugated azelaic acid antibody production: application to multiple sclerosis.

We have previously reported the existence of anti-conjugated azelaic acid (Aze A) antibodies in the serum of patients with multiple sclerosis (MS). In order to demonstrate the specificity of these antibodies, we have produced a monoclonal antibody directed against Aze A conjugated by an acylation reaction to a protein. In competition experiments, with ELISA method, we demonstrated that a part of the antibodies, raised in rabbit after immunization by human immunoglobulins (Ig) of MS patients, recognized the antigen-combining site of our monoclonal anti-conjugated Aze A antibody. These results clearly demonstrate that a part of human Ig obtained from sera of MS patients shared common idiotopes with mouse monoclonal antibody raised against conjugated Aze A.

Acylation↗

[Recurrent herpetic encephalitis].

A 64 year-old woman experienced, at 6 weeks' interval, two episodes of encephalitis with left hemiparesis, coma and signs of meningitis. Paraclinical examinations showed lymphocytic meningitis, right temporal hypodensity at CT and high titers for herpes simplex at blood serology. The spontaneous course was favourable with almost complete recovery. A third recurrence took place 2 months later with left hemiplegia, confusion and meningism. A tentative diagnosis of herpes simplex encephalitis was confirmed by major intrathecal synthesis of herpes virus specific antibodies and by highly suggestive MRI images. Treatment with acyclovir resulted in rapid regression of motor deficit and meningism, but neuropsychological disorders regressed more slowly with persistent visuo-constructive and memory disorders. During a fourth and milder recurrence, a stereotactic temporal brain biopsy was performed, which showed lesions of encephalitis and elevated titers for HSV1 in the temporal fluid. Another course of acyclovir followed by vidarabine produced complete remission. The possibility of recurrent types of herpes simplex encephalitis is discussed.

Acyclovir↗

[Peripheral neuropathies disclosing sarcoidosis].

A 54 year-old woman presented with an asymmetrical polyneuropathy, with in addition signs of hepatitis and hypercalcemia. The diagnosis of sarcoidosis was made by hepatic and neuromuscular biopsies. Electrophysiological studies showed an asymmetrical clear neurogenic involvement with an axonal pattern. Ultrastructural study of the nerve showed sarcoid granulomas in epineurium, perineurium and endoneurium, with images of Wallerian degeneration. No features of primary demyelination were found. Granulomas were also present in muscle and liver. Possible etiological mechanisms are discussed: compression of nerve or vessels, or immune angiitis.

Electrophysiology↗

[Polyneuropathies during prolonged stays in resuscitation].

Extensive multiple neuropathies were observed in four patients after prolonged stay in intensive care units. Date of onset of the multiple disorders was difficult to determine due to disturbed consciousness of all patients during the first few weeks of intensive care: it was probably between the 10th and 30th days. Electrophysiological examinations in the 4 patients, and ultrastructural study of musculocutaneous nerve of leg in 2 cases, suggested an acute axonal lesion. All patients survived the causal affection which had justified prolonged intensive care, 3 recovering from the multiple neuropathy within 3 to 4 months, the last patient having marked neuromuscular sequelae. Several factors can be incriminated at the origin of this multiple neuropathy. Whereas retrospective studies allowed exclusion of a toxic, infectious or drug-related cause, severe nutritional deficiencies existed; proteins in all cases and vitamins in one patient despite enteral re-nutrition judged as satisfactory. Additionally, a role for a previous lesion of peripheral nerves from chronic hypoxia was possible in 2 cases as well as for a non-insulin dependent diabetes in one of these two patients. A rarely reported but probably not exceptional complication, diagnosis is assisted by early electrophysiologic exploration. Correction of nutritional disorders may require parenteral feeding exclusively, this possibly accelerating neurologic recovery, as proposed in the several rare studies reported in the literature.

Aged↗