Search PubMed⌕ Search

Biomedical subjects

D Dormont

Publications and source records attributed to D Dormont.

At least 217 records · Page 12Linked to original sources
PubMed1996

Cytokine mRNA levels in unmanipulated (ex vivo) and in vitro stimulated monkey PBMCs using a semi-quantitative RT-PCR and high sensitivity fluorescence-based detection strategy.

To investigate the spectrum of cytokines expressed by peripheral blood mononuclear cells (PBMC) from cynomolgus macaques (Macaca fascicularis), we used a semi-quantitative RT-PCR to determine levels of mRNA coding for IL-1 beta, IL-2, IL-4, IL-6, IL-10, IFN-gamma, and TNF-alpha. The PCR products were labelled and quantified using a new fluorescent tag TOTO-1 (thiazole orange dimer) and an automated fluorescence-based electrophoretic instrument. Using this assay, the base line levels of cytokine mRNA expression in unmanipulated PBMCs (ex vivo) from 10 healthy monkeys were compared with the mRNA levels for the same cytokines in PBMC samples from two pre-immunized monkeys following culture with previously defined optimal concentrations of purified protein derivative (PPD), tetanus toxoid (TT) and the mitogen concanavalin A (con-A). While transcripts or IL-2, IL-4 and IFN-gamma were either low or not detected in unmanipulated PBMCs, varying levels of IL-1 beta, IL-5, IL-10, and TNF-alpha were readily detected in the same samples. With the exception of IL-10, the mitogen con-A induced the highest levels of cytokine expression, followed by levels induced by culture with TT. The levels of cytokine expression induced by PPD however, were not significantly elevated, despite the fact that the cells showed marked proliferative responses. This assay is a simple and convenient method for evaluating the levels of cytokine expression in small PBMC samples and will allow for the concurrent evaluation of immune profiles with functional immune analyses.

Animals↗
PubMed1996

Long-term MR follow-up of cerebral lesions in neuro-Behçet's disease.

To study the long-term evolution of cerebral lesions in neuro-Behçet's disease, MRI was carried out on 12 patients, with follow-up from 1.5 to 6 years (mean 3.5 years). On the first MRI, 66 lesions in all were found; each patient had 1-10 lesions (mean 5.5). There were 30 (46%) lesions in the brain stem, 18 (27%) in the basal ganglia region and 18 (27%) in the periventricular white matter. Of these 22 (33%) were small, 31 (47%) medium-size and 13 (20%) large lesions. On the last MRI, 60 lesions were found: each patient had 1-10 lesions (mean 5). At this time 31 lesions (52%) were in the brain stem, 13 (22%) in the basal ganglia region and 16 (26%) in the periventricular white matter. There were 41 (68%) small, 13 (22%) medium-size and 6 (10%) large lesions. About 40% of the lesions disappeared, 35% reduced in size and 25% remained unchanged. No lesion had enlarged. Of the 60 final lesions 20 (34%) were not observed on the first study. Small new lesions were found in 5 of 12 patients (42%), and were asymptomatic. Medium-size or large new lesions were found in 2 patients (17%) who had stopped steroid treatment and had a neurological relapse. Enlargement of the ventricular system or worsening of initial cerebral atrophy was observed in 9 of 12 patients. Appearance of small lesions and worsening of cerebral atrophy on long-term follow-up suggest the possibility of subclinical progression of cerebral vasculitis and should be considered in the prognosis of neuro-Behçet's disease.

Adolescent↗
PubMed1996

First line immunochemotherapy with cisplatin-based protocol by intraperitoneal and intravenous routes in ovarian cancer: technique and results of 82 cases.

OBJECTIVES: The aim of this study, initiated in 1982, was to determine the feasibility and the interest of a first-line immunochemotherapy delivered by intraperitoneal (i.p.) and intravenous (i.v.) routes combined in ovarian cancer. STUDY DESIGN: Eighty-two naive patients with a common epithelial cancer entered the study from January 1982 to December 1990 (median follow up > 70 months). For i.p. infusion, we used a simple lumbar puncture needle left in situ for < 2 h. The first 18 patients received monthly by i.p. route: Adriamycin (DXR) 40 mg/m2, Fluorouracil 1000 mg/m2, Cisplatin (CDDP) 90 mg/m2, Bleomycin 30 mg -DGZ (extract of vibrio cholerae) 60 mg/m2. For the remaining 64 patients Aracytin 500 mg/m2 replaced DXR and the dose of CDDP was more than doubled (200 mg/m2) thanks to the use of sodium thiosulfate. All 82 patients received Ifosfamid 1300 mg/m2 intravenously. RESULTS: Local toxicity consisted in one subcutaneous abscess and one bacterial peritonitis out of 1508 abdominal punctures. Stage III turned out to be the most interesting group to evaluate the efficacy of a first-line protocol. In this group 34 out of 47 patients (72.3%) who underwent an initial incomplete surgery were in complete remission (CR) at second-look. Nevertheless, 21 out of the 34 patients in CR relapsed (61.7%) and 14 died (43.2%). CONCLUSION: These results show the efficacy of our regimen administered i.p., and the safety of the delivery by a simple needle which avoids the complications of the implantable systems. Nevertheless, the usefulness of a systematic second-line chemotherapy (Paclitaxel?), despite a prognosis situation as favourable as a CR at second-look, must be taken into consideration.

Adult↗
PubMed1996

[Evaluation of transmission of unconventional agents by human albumin].

Transmissible spongiform encephalopathy agents (TSA) or prions induce neurodegenerative diseases in humans and animals. Their nature is still unknown, even if the main component of infectivity is identified as an abnormal isoform of a host-encoded protein, the prion protein (PrP). Today, no diagnostic test is available routinely for the detection of infected patients. TSA are resistant to most of the physical and chemical procedures that are efficient against other micro-organisms. Iatrogenic transmissions of TSA have been reported in the past: they always involved either brain derivatives or instruments that have been in contact with infected central nervous system. In an infected individual, infectivity is mostly detectable in brain. However, a persistent low-level viremia can be demonstrated in association with the white blood cells; infectivity is never found in plasma, serum or in red blood cells. Epidemiological data do not evidence any relationship between spongiform encephalopathies and blood transfusion. Therefore, in 1995, TSA transmission trough albumin is only a theoretical risk.

Albumins↗
PubMed1996

The pattern of production of cytokine mRNAs is markedly altered at the onset of multiple sclerosis.

Using two independent PCR-based quantification techniques, we have determined the levels of IL1 beta, IL2, IL4, IL6, IL10, IFN gamma and TNF alpha mRNA in multiple sclerosis patients at the moment of diagnosis of the disease and prior to any immunosuppressive treatment. These patients exhibit markedly reduced IL2 and IL10 mRNA expression accompanied by decreased levels of TNF alpha mRNA. Our results add to the evidence that IL10 plays a role in multiple sclerosis and suggest that decreased production of this interleukin allows the proliferation of autoreactive T cells at the onset of the disease.

Acute Disease↗
PubMed1996

How to limit the spread of Creutzfeldt-Jakob disease.

Transmissible spongiform encephalopathies are rare lethal diseases induced in humans and animals by unconventional agents called transmissible spongiform encephalopathy agents (TSEAs), virions, or prions. Several cases of iatrogenic Creutzfeldt-Jakob disease (CJD) have been reported in the literature after neurosurgery, treatment with pituitary-derived hormones, corneal grafting, and use of dura mater lyophilisates. In a given infected individual, TSEA-associated infectiousness depends on the nature of the organ: the central nervous system has the highest infectiousness, spleen and lymph nodes a medium infectiousness, and organs such as bone, skin, or skeletal muscles do not harbor any detectable infectiousness in experimental models. Transmissible spongiform encephalopathy/prions have unconventional properties; in particular, they resist almost all the chemical and physical processes that inactivate conventional viruses. Therefore, prevention of CJD agent transmission must be taken into account in daily hospital practice. Efficient sterilization procedures should be determined. In tissue and blood donation, donors with a neurologic history must be excluded, and patients treated with pituitary-derived hormones should be considered potentially infected with TSEA and excluded.

Animals↗
PubMed1996

A clinical and neurophysiological study of a patient with an extensive transection of the spinal cord sparing only a part of one anterolateral quadrant.

In 1976, Noordenbos and Wall studied sensory functions in a woman with a surgically verified T3 spinal cord transection which spared only a part of the left anterolateral quadrant, We re-investigated this unique case 18 years after the lesion and included a comparable sensory examination, MRI of the spinal cord, somatosensory evoked potentials, PET-activation study during hand and foot vibration and analysis of flexion reflex modulation during the Jendrassik manoeuvre. Our results show that the residual anterolateral quadrant contains ascending pathways carrying a wide range of sensory information as well as descending pathways modulating flexion reflex activity at the spinal level. Moreover, the changes in sensory functions and the unique pattern of cortical activation suggest a functional reorganization of the connectivity between the periphery and the cerebral cortex. Changes of facilitation and/or of inhibition at different levels of the somatosensory system may account for these longterm plastic changes.

Evoked Potentials, Somatosensory↗
PubMed1996

Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy.

The development of transmissible spongiform encephalopathies in experimental models depends on two major factors: the intracerebral accumulation of an abnormal, protease-resistant isoform of PrP (PrPres), which is a host protein mainly expressed in neurons; and the existence of different strains of agent. In order to make a distinction between pathogenic mechanisms depending upon the accumulation of host-derived PrPres and the strain-specific effects, we quantified and compared the sequence of molecular [PrPres and glial fibrillary acidic protein (GFAP) accumulation] and pathological events in the brains of syngeneic mice throughout the course of infection with two different strains of agent. The bovine spongiform encephalopathy (BSE) agent exhibits properties different from any known scrapie source and has been studied in comparison with a classical scrapie strain. Convergent kinetic data in both models confirmed the cause-effect relationship between PrPres and pathological changes and showed that PrPres accumulation is directly responsible for astrocyte activation in vivo. Moreover, we observed a threshold level of PrPres for this effect on astroglial cells. However, despite similar infectivity titres, the BSE model produced less PrPres than scrapie, and the relative importance of gliosis was higher. The comparison of the molecular and pathological features after intracerebral or intraperitoneal inoculation also revealed differences between the models. Therefore, the mechanisms leading to the targeting and the fine regulation of the molecular events seem to be independent of the host PrP and to depend upon the agent. The possible involvement of a regulatory molecule accounting for these specificities has to be considered.

Animals↗
PubMed1996

Immune system-dependent and -independent replication of the scrapie agent.

Using the severe combined immunodeficiency (SCID) mouse model, we investigated the requirement of the immune system for the development of scrapie after peripheral inoculation. A total of 33% of SCID mice, all but one immunologically reconstituted SCID mice (93%), and all CB17 control mice developed the disease. PrPres was detectable in the brains of all diseased animals and in the spleens of reconstituted SCID and CB17 control mice but not of the diseased non-immunologically reconstituted SCID mice. The immune system appears to be a primary target in the pathogenesis of scrapie, but direct spread to the central nervous system from the peritoneum via visceral nerve fibers can probably also occur.

Animals↗
PubMed1996

Characterization of human immunodeficiency virus type 1 p17 matrix protein motifs associated with mother-to-child transmission.

In order to determine if viral selection occurs during mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), we used a direct solid-phase sequencing method to sequence the p17 matrix protein-encoding regions of viral isolates from 12 HIV-1-infected mother-and-child pairs, 4 infected infants, 4 transmitting mothers, and 22 nontransmitting mothers and compared the sequences. The blood samples were collected during the delivery period for the mothers and during the first month of life for most of the children. The p17 nucleic sequences were distributed among several clades corresponding to the HIV-1 A, B, and G subtypes. At the amino acid level, no significant differences within the known p17 functional regions were observed among the subtypes. Statistical analyses could be performed with the B subtype. Within the major p17 antibody binding site, a constant KIEEEQN motif (amino acids 103 to 109) was found in all mother-and-child isolates from the B subtype. On the other hand, 9 of 17 nontransmitting mother isolates were variable in this 103 to 109 region. Thus, this motif was significantly associated with the transmitting status (chi square, P = 0.0034). A valine residue at position 104 was significantly associated with the nontransmitting phenotype (chi square, P = 0.014), suggesting that it has a protective role during vertical transmission. The C-terminal end of p17 was globally conserved among nontransmitting mother isolates (chi square, P = 0.0037). These results might improve the understanding of the pathogenesis of HIV-1 vertical transmission and might allow the screening of seropositive mothers by a rapid molecular or peptide test.

Amino Acid Sequence↗
PubMed1996

Creutzfeldt-Jakob disease from contaminated growth hormone extracts in France.

We diagnosed Cruetzfeldt-Jakob disease in 34 patients (16 definite, 18 probable) who had received human growth hormone extract for various period of time (mean +/- SD, 2.9 years), but particularly during the period between January 1984 and July 1985, a potential high-risk factor. Disease duration for deceased patients (n = 30) was 17 +/- 9 months. The clinical picture was homogeneous, starting with cerebellar ataxia and ocular motor disorders in about 90% of the patients. Neurologic deterioration, including dementia and myoclonic jerks, occurred within months. The high number of cases (1.5% of those treated between 1959 and 1988, 3% of those treated during the putative high-risk period) is still unexplained. We discuss the possibility that new cases will be detected,the risk of contaminating the general public, and the sanitary measures undertaken to prevent this.

Adolescent↗
PubMed1996

[Iridium 192 brachytherapy of supra-tentorial high grade glioma recurring in irradiated areas: technique and preliminary results of the Pitié-Salpêtrière hospital group].

UNLABELLED: Our aim was to analyse feasibility and preliminary results obtained with iridium 192 re-irradiation of recurrent high grade gliomas. MATERIAL AND METHODS: a technique for implanting rigid plastic tubes afterloaded with iridium 192 wires was developed that utilised a stereotactic Leksell frame. Nineteen glioblastomas and one anaplastic glioma (12 males and 8 females: age: 20-69 years, median: 50) were implanted between January 1993 and December 1994. Previous treatments included surgery (18/20). 55-60 Gy external beam radiotherapy (20/20), and chemotherapy (16/20); interval between initial treatment and retreatment with iridium 192 was 6 to 39 months (median: 10). Maximum diameter of the tumour at the moment of implantation was 2.1-10.1 cm (median: 6.4 cm) and tumour volume 2.122 cm3 (median: 22 cm3). All tumours were supra-tentorial (right hemisphere: 9; left hemisphere: 11). Karnofsky index was 60-100 (median: 80). Implantation was carried out under local anaesthesia; tumour contours were visualised using either a CT-scan (16/20) or a MRI (4/20). Dosimetry was carried out using two orthogonal films and CT-scan images. Total dose on the reference isodose was 40-60 Gy (60 Gy: 9; 50 Gy: 7; 40 Gy: 4); dose-rate was 0.24-0.73 Gy/h (median: 0.38). RESULTS: probability of overall survival is 90% at 6 months, 55% at one year, and 26% at two years. Median survival is 56 weeks. Eleven patients died from local failure, and three from leptomeningeal metastasis. Six patients are alive, 15-30 months after the implantation. Two were reoperated for brain necrosis. Three patients showed evidence of bacterial meningitis, and three others of skin necrosis. CONCLUSION: according to this preliminary analysis, results obtained after reirradiation of high grade gliomas with iridium 192 are encouraging. More patients and longer follow-up are needed to draw definitive conclusions.

Adult↗
PubMed1996

[Magnetic resonance imaging of temporal lobe epilepsy].

MR has gained more and more importance in the evaluation of patients with temporal lobe epilepsy (TLE). Until recently, hippocampal sclerosis (which is the most frequent cause of temporal lobe epilepsy, accounting for 50-70% of the cases) could not be identified reliably. Using optimized magnetic resonance imaging techniques, hippocampal sclerosis can now be evidenced in a large proportion of patients with TLE. Tumors (10-15%), developmental abnormalities (5-7%), vascular malformations (mostly cavernous angiomas, 1-5%), and traumatic scars (5-10%) represent the other structural lesions associated with TLE. Studies of large series of patients with intractable epilepsy or with varying severity have shown that in only 8.5% and 20%, respectively, a specific imaging abnormality was not found. Specific MR sequences increase the diagnostic value of MR (coronal images perpendicular to the axis of the hippocampal formations, three-dimensional T1 weighted images, inversion recovery images, volumetry or more specific processes such as T1 and T2 relaxometry or spectroscopy). MR also helps guide placement of intra-cerebral and subdural electrodes in surgically relevant cases. All these results have given greater importance to MR in the definition of the epileptic syndrome of TLE and should probably be integrated in the criteria of international classifications.

Adult↗
PubMed1996

[Isolation, culture and characterization of astrocytes from adult monkey brains].

We have developed protocols for the isolation, the culture and the immunocytochemical characterization of astrocytes from simian adult brains. We have obtained pure astrocyte cultures without contamination with other cells present in brain. No microglial cells, oligodendrocytes, neurons or fibroblasts were detected by specific staining in immunocytochemistry.

Acquired Immunodeficiency Syndrome↗