Brain MRI in patients with past lupus-associated chorea.
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Adult↗
Biomedical subjects
D Dormont
Publications and source records attributed to D Dormont.
Prediction of malignant middle cerebral artery infarction by diffusion-weighted imaging.
BACKGROUND AND PURPOSE: This study was designed to analyze whether early diffusion-weighted imaging (DWI) provides reliable quantitative information for the prediction of stroke patients at risk of malignant brain infarct. METHODS: We selected 28 patients with a middle cerebral artery (MCA) infarct and proven MCA or carotid T occlusion on DWI and MRI angiography performed within 14 hours after onset (mean 6.5+/-3.5 hours, median 5.2 hours). Of these, 10 patients developed malignant MCA infarct, whereas 18 did not. For the 2 groups, we compared the National Institutes of Health Stroke Scale (NIHSS) score at admission, site of arterial occlusion, standardized visual analysis of DWI abnormalities, quantitative volume measurement of DWI abnormalities (volume(DWI)), and apparent diffusion coefficient values. Univariate and multivariate discriminant analysis was used to determine the most accurate predictors of malignant MCA infarct. RESULTS: Univariate analysis showed that an admission NIHSS score >20, total versus partial MCA infarct, and volume(DWI) >145 cm(3) were highly significant predictors of malignant infarct. The best predictor was volume(DWI) >145 cm(3), which achieved 100% sensitivity and 94% specificity. Prediction was further improved by bivariate models combining volume(DWI) and apparent diffusion coefficient measurements, which reached 100% sensitivity and specificity in this series of patients. CONCLUSIONS: Quantitative measurement of infarct volume on DWI is an accurate method for the prediction of malignant MCA infarct in patients with persistent arterial occlusion imaged within 14 hours of onset. This may be of importance for early management of severe stroke patients.
Adult↗
Prion protein is not detectable in dental pulp from patients with Creutzfeldt-Jakob disease.
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Blotting, Western↗
New variant of Creutzfeldt Jakob disease.
Work on experimental pathology carried out for over 10 years indicates that the biological properties of the BSE agent, responsible for the new variant of Creutzfeldt-Jakob disease (vCJD), are particular. In contrast to the situation observed in the other
Journal Article↗
Simian immunodeficiency virus mac251 infection of astrocytes.
Human immunodeficiency virus type 1 (HIV-1) infection of astrocytes has been demonstrated in the brains of patients with AIDS dementia complex (ADC) and may play an important role in neuropathological pathways of HIV-related encephalopathy. SIVmac-infected monkeys develop an acquired immunodeficiency syndrome (AIDS) with CNS involvement which is quite similar to that seen in human AIDS. We investigated the in vitro infection of primary astrocytes derived from adult macaques with SIVmac251 or an isogenic virus that expresses a non-functional Nef protein (SIVmac251-DeltaNef). In both cases we observed that viral expression was mostly limited to early regulatory genes after a transient phase of late viral gene expression (i.e. env and gag), as reported for HIV-1-infected astrocytes in vivo. Late viral gene expression could be reactivated by TNF-alpha, GM-CSF and IFN-gamma treatment of SIVmac251-infected astrocytes but not by similarly treated SIVmac251-DeltaNef-infected cells. Our findings suggest that Nef is not involved in the restricted expression of SIV in astrocytes, but may be important for astrocytes to function as a viral reservoir in the CNS. In additional experiments, we demonstrated Rev and Nef expression in 17 of 27 primary astrocyte cultures derived from macaques infected by SIVmac251. Nef was located in the cytoplasm of astrocytes infected by SIVmac251 in vivo, but displayed perinuclear localisation after infection in vitro. Attempts to activate late viral gene expression by astrocytes infected in vivo using cytokines or by coculture with human cord blood mononuclear cells were unsuccessful.
Animals↗
Bilateral subthalamic stimulation for Parkinson's disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance.
OBJECT: Several methods are used for stereotactically guided implantation of electrodes into the subthalamic nucleus (STN) for continuous high-frequency stimulation in the treatment of Parkinson's disease (PD). The authors present a stereotactic magnetic resonance (MR) method relying on three-dimensional (3D) T1-weighted images for surgical planning and multiplanar T2-weighted images for direct visualization of the STN, coupled with electrophysiological recording and stimulation guidance. METHODS: Twelve patients with advanced PD were enrolled in this study of bilateral STN implantation. Both STNs were visible as 3D ovoid biconvex hypointense structures located in the upper mesencephalon. The coordinates of the centers of the STNs were determined with reference to the patient's anterior commissure-posterior commissure line by using a new landmark, the anterior border of the red nucleus. Electrophysiological monitoring through five parallel tracks was performed simultaneously to define the functional target accurately. Microelectrode recording identified high-frequency, spontaneous, movement-related activity and tremor-related cells within the STNs. Acute STN macrostimulation improved contralateral rigidity and akinesia, suppressed tremor when present, and could induce dyskinesias. The central track, which was directed at the predetermined target by using MR imaging, was selected for implantation of 19 of 24 electrodes. No surgical complications were noted. CONCLUSIONS: At evaluation 6 months after surgery, continuous STN stimulation was shown to have improved parkinsonian motor disability by 64% and 78% in the "off' and "on" medication states, respectively. Antiparkinsonian drug treatment was reduced by 70% in 10 patients and withdrawn in two patients. The severity of levodopa-induced dyskinesias was reduced by 83% and motor fluctuations by 88%. Continuous high-frequency stimulation of the STN applied through electrodes implanted with the aid of 3D MR imaging and electrophysiological guidance is a safe and effective therapy for patients suffering from severe, advanced levodopa-responsive PD.
Aged↗
[The urgency of emergencies?].
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Emergency Treatment↗
[Secondary cytoreductions in the treatment of ovarian cancers].
UNLABELLED: The aim of this study was to investigate the potential benefit of secondary cytoreductive surgery for recurrent ovarian cancer. METHODS: Between 1980 and 1993, 85 patients (11 stage Ic, 4 stage IIc, 70 stage III) with an epithelial ovarian cancer were treated after initial surgery with an intraperitoneal and intravenous Cis Platin-based immunochemotherapy. Twenty patients of the 41 who relapsed underwent secondary cytoreductive surgery. RESULTS: Complete resection was achieved in 13 patients (65%) and was optimal with a < 0.5 cm residual disease left in one case. One patient died postoperatively. Surgery was suboptimal for six patients (30%). At a mean follow-up from recurrence of more than 54 months for the surviving patients, five of the 20 reoperated are still alive. All 21 patients who were not reoperated died with a median survival time from recurrence of eight months (10.5 months for the patients who refused to be reoperated and seven months for the patients rejected by the surgeons) against 29 for the 20 reoperated patients (P < 0.004). CONCLUSION: This series is too small to enable us to draw definitive conclusions. Nevertheless, our results seem to suggest the interest of secondary cytoreductive surgery. Indeed, only reoperated patients, above all if surgery was complete or at least optimal, have a chance of long survival. In our opinion, secondary surgical procedure should be proposed to relapsing patients to enhance efficacy of rescue chemotherapy, which is of limited value in bulky tumors.
Adult↗
Cerebral aneurysms treated by Guglielmi detachable coils: evaluation with diffusion-weighted MR imaging.
BACKGROUND AND PURPOSE: The most frequent and serious complications of endovascular treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs) are ischemic lesions caused by thromboembolic events. Diffusion-weighted MR imaging appears to be the most sensitive technique for detecting early ischemic phenomena. We evaluated this technique for the detection of brain changes in patients who underwent GDC treatment of aneurysms. METHODS: Twenty patients with a cerebral aneurysm were studied with diffusion-weighted imaging before and after endovascular treatment with GDCs. Aneurysms were located in the anterior (n = 16) or posterior (n = 4) circulation. Bleeding had occurred in 11 patients. MR studies, including fast fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted sequences, were scheduled before, 2 to 4 hours after, and 48 hours after treatment. MR images, including apparent diffusion coefficient (ADC) maps, were assessed for the presence of acute ischemic stroke lesions. RESULTS: In all patients, the aneurysm was excluded without neurologic worsening. In 18 patients, diffusion-weighted and FLAIR images showed no evidence of recent ischemic lesions after treatment. In one patient, an asymptomatic frontobasal hyperintense signal on diffusion-weighted images with a drop of ADC values corresponding to an acute ischemic lesion was observed. In another patient, multiple silent lesions were seen on diffusion-weighted images after embolization. These silent lesions were not all located in the vascular territory of the aneurysm's parent artery. CONCLUSION: This preliminary study suggests that diffusion-weighted MR imaging is a potentially useful tool for monitoring patients after endovascular treatment of a cerebral aneurysm. While small asymptomatic lesions can be observed on these images after embolization, their exact prevalence should be evaluated in a larger series.
Adult↗
Diffusion-weighted magnetic resonance imaging in a case of methanol intoxication.
BACKGROUND: Methanol intoxication is an uncommon clinical problem leading to profound metabolic acidosis with serious neurological deterioration. We describe methanol induced brain lesions on diffusion-weighted MR images and discuss the pathophysiology of these lesions in light of diffusion changes. CASE REPORT: Brain imaging was performed in a 32 year-old man in a coma with focal neurological signs. Bilateral putaminal [hyperintensity] was seen on fast spin echo T2-weighted sequences, on Fluid Attenuated Inversion Recovery (FLAIR) and on diffusion weighted images. Decreased ADC values were observed bilaterally in the putamina. In addition, FLAIR images showed diffuse hypersignal in the subarachnoidal space. The patient showed rapid neurological deterioration while blood chemical tests revealed a severe metabolic acidosis and plasma methanol levels of 21 mmol/L. The patient died from hepatic failure thirty six hours after admission. CONCLUSION: Although decreased ADC values on diffusion-weighted imaging are commonly associated with arterial ischemic stroke, this pattern can also be observed in the case of putaminal necrosis following methanol ingestion.
Adult↗
[Evaluation of the effect of early and massive tritherapy on the expression of cellular factors potentially implicated in antiretroviral therapy resistance].
Treatment of the human immunodeficiency virus (HIV) is restricted by therapeutic escape. The biological mechanisms of this chemoresistance rely notably on the modulation of cell kinase and P-glycoprotein (P-gp) expression. In this study, we investigated, in cynomolgus macaques, the roles of SHIV89.6P infection and of HAART in the mRNA expression of these cell factors. SHIV infection, or associated pathophysiological disorders, increase both thymidine kinase and thymidylate kinase mRNA expression and decrease those of P-gp. On the other hand, the expression of other cell kinases is not modulated. In parallel, HAART accentuates the decrease of P-gp expression and attenuates the increase of kinase expression. On the whole, such metabolic disorders, evidenced herein an animal model of HIV infection, could be involved in HIV-infected patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Antiretroviral ant anti-inflammatory properties of a novel platelet activation factor antagonist, PMS-601].
The platelet-activating factor (PAF) plays a major role in neuropathogenesis associated with human immunodeficiency virus (HIV) infection by enhancing the inflammatory syndrome and viral replication, particularly in cells of the macrophage lineage, and its neurotoxic properties. We therefore evaluated the ability of PAF-R antagonists to inhibit HIV-1 replication and down-modulate the synthesis of pro-inflammatory mediators in healthy or HIV-1-infected macrophages. PMS-601 demonstrated the highest anti-HIV activity. Considering its mode of action and anti-inflammatory properties, PMS-601 interferes with early and late steps of the HIV biological cycle and decreases the synthesis of PAF, TNF-alpha, MIP-1 alpha, MIP-1 beta and RANTES. Altogether, these results suggest that PAF-receptor antagonists, and particularly PMS-601, could be of potential value as treatment adjuvants in HIV infection.
Anti-HIV Agents↗
False-negative diffusion-weighted MR findings in acute ischemic stroke.
BACKGROUND AND PURPOSE: Lesions associated with acute stroke are often missed by diffusion-weighted imaging (DWI), suggesting that the sensitivity of this technique for detecting acute ischemic stroke may not be as high as initially thought. Our aim was to estimate the rate of false-negative DWI studies in patients with persistent neurologic deficit due to an ischemic stroke and to identify which stroke lesions are most likely to be missed by DWI. METHODS: We reviewed MR images obtained within 48 hours after stroke onset in 139 patients admitted for symptoms consistent with ischemic stroke in whom the deficit lasted more than 24 hours. Cases of negative initial DWI findings with an ischemic lesion visible on follow-up MR studies and a final diagnosis of arterial ischemic stroke were analyzed in terms of delay between onset of symptoms and initial DWI (MR latency), size and vascular distribution of the lesions, and relationship to findings in patients with positive initial DWI results. RESULTS: We found eight cases (5.8%) of false-negative initial DWI studies, of which four were positive on initial fluid-attenuated inversion recovery (FLAIR) imaging. Follow-up FLAIR/DWI showed a hyperintensity matching clinical presentation in all eight patients. The mean size of the lesion was 0.19 +/- 0.16 cm3. False-negative studies occurred more often in cases of stroke in the posterior (19%) than in the anterior (2%) circulation or when DWI was obtained within 24 hours after symptom onset. Of the six false-negative vertebrobasilar stroke lesions, five were located in the brain stem. In all, 31% of patients with vertebrobasilar ischemic stroke had a false-negative initial DWI study during the first 24 hours. CONCLUSION: A false-negative DWI study is not uncommon during the first 24 hours of ischemic stroke. Vertebrobasilar stroke should therefore not be ruled out on the basis of early negative DWI, especially when symptoms persist and are suggestive of this diagnosis.
Acute Disease↗
[Spinal cord involvement revealing systemic sarcoidosis].
Spinal neurosarcoidosis is rare (0.43 p. 100 of all sarcoidosis) and can be the initial manifestation of the disease. A 43-year-old right handed African man developed a progressive dorsal neck pain, slowly worsened paresthesia weakness in the legs and a gait disturbance. Magnetic resonance imaging (MRI) scan of the cervical and thoracic spinal cord (sagittal T(1)- weighted image) revealed diffuse enlargement of the cord from C2 to T7 with intense intramedullary enhancement from C2 to T3 after administration of contrast material on sagittal T(1)- weighted image. Cranial MRI scan was normal. Radiographs of the chest revealed bilateral symmetric hilar mediastinal lymphadenopathy with no pulmonary infiltrates. Bronchial biopsy demonstrated non caseating granulomas with langerhans giant cells. The serum angiotensin converting enzyme level was elevated. The patient received corticosteroid with good progressive response. His neurologic symptoms improved markedly and twenty months post-treatment MRI showed no abnormality on enhanced T(1)- weighted images. Two years later he had no relapse. Only 6 to 10 p. 100 of patients with neurosarcoidosis have spinal cord involvement, which may account for the first clinical manifestation of the disease. Most patients with neurosarcoidosis have associated extraneurologic abnormalities. The diagnosis is supported usually by extraneurologic biopsies. Spinal cord biopsy needs to be considered on case-by-case basis.
Adrenal Cortex Hormones↗
[MRI of drug-resistant epilepsies: contribution of FLAIR sequence in a series of 150 patients].
We studied the usefulness of the Fluid-Attenuated Inversion-Recovery (FLAIR) pulse sequence for patients with intractable seizures by reviewing the MR images of 150 consecutive patients including a standard imaging protocol and a FLAIR sequence. FLAIR images revealed a cortical lesion in 8 of the 81 patients with no lesion detected on the standard MR imaging protocol. In addition, FLAIR images provided additional informations for 13 patients of the 69 patients for whom a lesion was already detected on the standard MR imaging protocol. Therefore, our results indicated that FLAIR sequences were a useful imaging tool for patients with intractable seizures since it improved the MR diagnosis in 21 of 150 patients (14%).
Adolescent↗
New insight into abnormal prion protein using monoclonal antibodies.
Studies of abnormal prion protein (PrPres) are hindered by the lack of specific monoclonal antibodies (mAbs), and the relationships between PrPres, infectivity, and strain specificity in prion diseases are still subject to debate. We have studied PrPres with new mAbs produced against PrP in mice using various immunization strategies. PrPres was analyzed by Western blot with different prion strains in various hosts. Differences in the electrophoretic pattern of human PrPres revealed by these antibodies provide new insight into PrPres cleavage by proteases and interpretation of strain typing. This study confirms that the N-terminal extremity of PrPres is differentially sensitive to proteases. Conversely, the C-terminal extremity, which resists proteolysis, seems to be abnormally detectable by antibodies in ultrastructural studies. This work confirms the highly complex role of PrPres in prion diseases and provides new tools which will be made available to facilitate progress in qualitative and quantitative studies of PrP.
Amino Acid Sequence↗
An unusual HIV type 1 env sequence embedded in a mosaic virus from Cameroon: identification of a new env clade. European Network on the study of in utero transmission of HIV-1.
An atypical HIV-1 strain (CAM001) was identified in a pregnant Cameroonian woman in 1995. HMA subtyping of the env region was unsuccessful, and sequence analyses were performed. Unique sequence motifs were found at the V3 tip (GAGRALHA and GAGRAWIHA), and phylogenetic studies showed that the env C2-V5 sequence branched within group M but remained distinct from all known HIV-1 subtypes, while p17 gag branched with the subtype F sequences. Four other HIV group M viruses, undetermined by HMA, of African origin were found to cluster with CAM001 in the C2-V5 sequences. With the BLAST method, we found in databases three strains whose V3 sequences also clustered with CAM001. These unusual env sequences from eight HIV-1 strains derived from Cameroon formed a separate cluster in HIV-1 group M, which we designated k.
Amino Acid Sequence↗
Synthesis and in vitro anti-HIV activity in human monocyte-derived macrophages of 2-oxothiazolidine-4(R)-carboxylic acid derivatives.
Oxidative stress and glutathione (GSH) deficit may play an important role in HIV infection pathogenesis, and oral administration of GSH-replenishing drugs such as N-acetylcysteine (NAC) and 2-oxothiazolidine-4(R)-carboxylic acid (OTC) may be associated with an increased survival rate of HIV-infected patients. Nevertheless, beneficial effects of these molecules are restricted in vivo by the high concentrations that are necessary to obtain biological effects, rapid extracellular metabolization, and low availability and plasma concentrations. We synthesized OTC derivatives that are more lipophilic than OTC and theoretically able to overcome these limitations and to generate, in addition to cysteine, other substrates of the gamma-glutamyl cycle. Their antiviral effects were investigated in human HIV-1/Ba-L-infected monocyte-derived macrophages. In our experimental conditions, OTC exhibited anti-HIV-1 effects and little cytotoxicity at high doses. None of the nine tested derivatives showed higher cytotoxicity than OTC, nor anti-HIV-1/Ba-L activity.
Anti-HIV Agents↗