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Biomedical subjects

M Chatel

Publications and source records attributed to M Chatel.

At least 37 records · Page 2Linked to original sources

Expression of vascular endothelial growth factor-b in human astrocytoma.

Growth of human malignant gliomas is stringently dependent on an angiogenic process that probably involves vascular endothelial growth factor (VEGF). Expressions of mRNA coding for the different forms of VEGF were analyzed in surgical specimens from human astrocytomas. Low levels of placental growth factor (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in Northern blot experiments. VEGF mRNA was found in some but not all grade and grade IV astrocytomas. VEGFB mRNA was observed in all tissue samples analyzed irrespective of the tumor grade. A new splice variant of VEGFB (VEGFB155) that lacks exons 5 and 6 is described. Expressions of VEGF mRNA in cultured glioblastomas cells were upregulated by hypoxia, but the sensitivity of the cells to hypoxia was reduced as compared with normal rat astrocytes. VEGF expression was depressed by dexamethasone. Expressions of VEGFB mRNA were affected neither by hypoxia nor by dexamethasone. The results indicate a coexpression of VEGF mRNA and VEGFB mRNA in human astrocytomas. Expression of VEGFB is markedly different from that of VEGF. Possible roles of VEGFB as a cofactor for hypoxia-induced angiogenesis in human astrocytomas are discussed.

Alternative Splicing↗

Fasting, postprandial, and post-methionine-load homocysteinaemia and methylenetetrahydrofolate reductase polymorphism in vascular disease.

Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) is a common genetic cause of increased homocysteine (HCY) levels. Post-methionine-load HCY concentrations allow identification of certain cases of hyperhomocysteinaemia not demonstrated by fasting levels. This study investigated the relationship between MTHFR polymorphism and (1) fasting HCY levels (77 patients); (2) post-methionine HCY levels (54 patients); and (3) postprandial HCY concentrations (36 patients) in cardiovascular disease. As expected, mean fasting HCY value was higher in the +/+ patients. Moreover, patients who were homozygous for the mutation exhibited significantly increased mean post-methionine-load HCY; in contrast, literature results are conflicting. Mean postprandial HCY, which is not known to be increased in controls, was also increased in the (+/+) patients, although the difference did not reach statistical significance, probably owing to the small size of the sample. MTFHR polymorphism is known to be aggravated by a drop in circulating folate. Additional risk factors may be more prevalent in patients with cardiovascular disease.

Adolescent↗

Boron neutron capture enhancement (BNCE) of fast neutron irradiation for glioblastoma: increase of thermal neutron flux with heavy material collimation, a theoretical evaluation.

Despite the fact that fast neutron irradiation of glioblastoma has shown on autopsies an ability to sterilize tumors, no therapeutic windows have been found for these particles due to their toxicity toward normal brain. Therefore, the Boron Neutron Capture Enhancement (BNCE) of fast neutron beam has been suggested. This paper addresses the problem of fast neutron beam collimation, which induces a dramatic decrease of the thermal neutron flux in the depth of the tissues when smaller irradiation fields are used. Thermoluminescent dosimeter TLD-600 and TLD-700 were used to determine the thermal neutron flux within a Plexiglas phantom irradiated under the Nice Biomedical Cyclotron p(60)+Be(32) fast neutron beam. A BNCE of 4.6% in physical dose was determined for a 10 x 10 cm2 field, and of 10.4% for a 20 x 20 cm2 one. A Dose Modification Factor of 1.19 was calculated for CAL 58 glioblastoma cells irradiated thanks to the larger field. In order to increase the thermal flux in depth while shaping the beam, heavy material collimation was studied with Monte Carlo simulations using coupled FLUKA and MCNP-4A codes. The use of 20 cm width lead blocks allowed a 2 fold thermal neutron flux increase in the depth of the phantom, while shielding the fast neutron beam with a fast neutron dose transmission of 23%. Using the DMF of 1.19, a BNCE of 40% was calculated in the beam axis. This enhancement might be sufficient to open, at least theoretically, a therapeutic window.

Beryllium↗

Leukoencephalopathy in multiple myeloma: two case reports.

BACKGROUND: No case of leukoencephalopathy has been reported associated with multiple myeloma. PATIENTS: We report on two patients with a very rare association of leukoencephalopathy and multiple myeloma revealed by cognitive impairment. RESULTS: Chemotherapy has improved neurological and biological signs. Radiological abnormalities have been stabilized. CONCLUSION: The authors suggest that leukoencephalopathy is probably a direct cerebral expression of malignant gammopathy.

Aged↗

Ictal asomatognosia with hemiparesis.

A 69-year-old woman presented with an ictal Anton-Babinski syndrome (asomatognosia with hemiparesis). Except for head and eye deviation to the side of the paralyzed limb, epileptic nystagmus, brief episodes of impaired consciousness, and automatisms, clinical symptomatology was identical to Anton-Babinski syndrome of vascular origin. Results of MRI imaging were normal. EEG showed a simple partial nonconvulsive status epilepticus of right parieto-temporal origin. Anton-Babinski syndrome may thus be a functional expression of focal status epilepticus.

Aged↗

[Autosomal dominant nocturnal frontal lobe epilepsy].

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a recently identified seizure disorder. The disease maps to the long arm of chromosome 20 and may be related in some families to a missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit. We describe one of the first European family with ADNFLE, including five affected individuals spanning four generations. In the most severely affected subject, the onset was during the second month of life and persisted through adult life. Seizures were very frequent during infancy, although long-term evolution was relatively benign. Ictal video-EEG studies showed that attacks occurred in clusters during sleep and were partial seizures that were consistent with a frontal origin. Neuro-imaging was normal. Carbamazepine had a dramatic effectiveness. Although recognition of this syndrome is important for appropriate therapy and genetic counselling, underestimation of cases is likely: the disease was in our family perceived like a hereditary curse, and subsequently concealed, including to medical attention. Relationships with other partial familial epilepsies and with idiopathic benign partial epilepsies of childhood are discussed.

Adult↗

[Germinal tumor metastases. Case report].

Germinoma is the most frequent type of intracranial germ-cell tumor initial presentation is usually acute intracranial hypertension. MRI investigations are non-specific. Most of the time, only stereotactic surgery is performed before treatment. Metastases are rare but germ cells can disseminate both by infiltration and via ventricular and subarachnoid pathways. Abdominal and pelvic metastases occur in 10 p. 100 of patients who have received ventriculosomatic shunting. Since germinoma is well known to be a very radiosensitive tumor, patients are usually given radiation therapy. Chemotherapy seems to be an interesting alternative treatment.

Adult↗

[Orthostatic hypotension revealing vitamin B12 deficiency].

Neurological manifestations of cobalamin deficiency are well known and various. We describe an uncommon clinical setting where major orthostatic hypotension was the primary symptom. Recovery was rapidly and completely stabilized with parenteral cobalamin substitution. There was no clinical or electrophysiological signs of neuropathic disorder. This entity is rare but few cases are described in literature. All of them were reversible with vitamin substitution treatment.

Aged↗

Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome.

The aim of this study was to perform a multivariate analysis including clinical and biological prognostic factors on glial tumor outcome. Seventy-nine patients were analyzed (48 men and 31 women; mean age = 56 years, range = 16-77 years): 7 had a benign glial tumor (grades 1 and 2), 21 had an anaplastic glial tumor (grade 3), and 51 had a glioblastoma (grade 4). Median follow-up was 17.9 months for patients who survived (50 patients died). Biopsies were obtained at time of diagnosis (complete tumor resection in 62 patients and stereotaxic biopsies in 17 patients). Epidermal growth factor receptor (EGFR) was measured by a binding assay, and labeling index (LI) was measured by tritiated thymidine incorporation. EGFR varied from 4 to 73,110 fmol/mg protein (mean = 3912 fmol/mg protein; median = 374 fmol/mg protein; n = 79). LI varied between 0.1 and 16.5% (mean = 6.2%; median = 5.2%; n = 40). Log10 EGFR was significantly and positively correlated with patient age. LI was significantly different according to tumor histology. Univariate Cox analysis (end point was cancer death) showed that age (P = 0.027), log10 EGFR (P = 0.025), and LI (P = 0.0019) were significant continuous variables, the survival being shortened when the covariable increased; tumor resection (P = 0.015, relative risk = 0.45) and histology (P = 0.0009) were significant categorical factors. A multivariate Cox analysis (forward selection) including age, histology, tumor resection, log10 EGFR, and LI revealed that log10 EGFR, LI, and tumor resection were the only independent significant predictors of survival. This multivariate approach reveals that the clinical prognostic factors of glial tumors, namely age and tumor histology, disappear, to the benefit of intrinsic characteristics of the tumor, i.e., EGFR expression and LI, suggesting that coupled EGFR and LI determination could be a useful tool for better evaluation of glial tumor outcome.

Adolescent↗

[Cerebral vascular complication of hyperhomocysteinemia. Controlling thromboembolic complications with folates].

BACKGROUND: Young patients who experience cardiovascular events may have raised levels of homocysteine. There may be several causes for this hyperhomocysteinemia. CASE REPORT: Cerebrovascular disease occurred in a 40-year-old female smoker with hyperhomocysteinemia. This patient subsequently had several episodes of thromboembolism involving the brain and lower limb arteries. Prothrombin concentration was difficult to control with antivitamin K anticoagulants. Investigations to identify a genetic cause of hyperhomocysteinemia revealed that she was homozygous for the C677T mutation on the methylenetetrahydrofolate reductase gene. There was no G1691A mutation of the factor V gene, a risk factor for familial thrombosis. Supplementation with folic acid successfully halted episodes of thromboembolism (follow-up 2 years) and prothrombin levels stabilized under treatment. DISCUSSION: The C677T mutation, which is common in the general population (15.7%), cannot explain the effect of folate supplementation alone. Other mutations affecting homocysteine metabolism could have a potentializing effect on vascular events.

Adult↗

Total plasma homocysteine determination by liquid chromatography before and after methionine loading. Results in cerebrovascular disease.

Elevated homocysteine (HCY) levels in tissues and blood are associated with premature occlusive diseases. A number of techniques have been developed to assay HCY, including high-performance liquid chromatography (HPLC) with fluorimetric or electrochemical detection, and radioenzymatic methods. The present study evaluated the adaptation of a liquid chromatographic, ion-exchange technique with postcolumn derivatization using ninhydrin. Fasting and moreover post-methionine load total plasma HCY were assayed in 50 patients three months after a stroke and in 20 age-matched controls. Ion-exchange liquid chromatography was performed on an amino acid analyzer using a modified procedure to improve methionine and HCY separation. HCY values in the fasting state were moderately but significantly increased (P<0.05) in the patients compared to the controls: 10.5+/-3.4 versus 9.3+/-2.3 micromol/l. The difference between the two groups was amplified in post-load HCY results, which were significantly increased (P<0.05) in the patients: 41.6+/-17.8 versus 29.2+/-5.5 micromol/l in controls. The relationship between cerebrovascular disease and impaired HCY metabolism has previously been emphasized by other investigators. Our findings suggest that certain inherited and/or acquired HCY disorders observed in the fasting state (14%) and especially in post-methionine load conditions (32%) may occur during acute disease, and that total plasma HCY can be determined by ion-exchange chromatography even after oral methionine loading.

Adult↗

Solitary meningeal plasmacytomas.

BACKGROUND: Solitary extramedullary plasmacytoma (SEP) represents a rare separate clinical pathological entity; it is radiosensitive, curable, and unrelated to myeloma. Only 15 cases have been reported. PATIENTS AND METHODS: Authors report two well documented cases of dural plasmocytomas mimicking meningiomas. This paper points out differences between plasmacytomas, with very different initial presentation, and other meningeal tumors including extensive radiological investigations. Diagnostic options and outcomes are discussed. CONCLUSION: With solitary plasmacytomas, radiological diagnosis is difficult to assess. Serum is generally free of monoclonal protein. The importance of the most recent techniques in ruling out other pathological entities is stressed. Histopathological examination is required to document a monoclonal type of plasma cell tumor. Treatment includes surgery and radiotherapy. Differential radiological diagnosis will be discussed.

Adult↗

Boron neutron capture irradiation: setting up a clinical programme in Nice.

Neutron capture irradiation aims to selectively destroy tumor cells using 10B(n,alpha)7Li nuclear reactions produced within themselves. Following the capture reaction, an alpha particle and a, 7Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 microns. These captures, used exclusively with a 'slow' neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an 'epithermal' neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.

Boron Neutron Capture Therapy↗

Ehlers-Danlos syndrome with subependymal periventricular heterotopias.

A 24-year-old woman with Ehlers-Danlos syndrome had complex partial and right sensory motor seizures. MRI showed periventricular subependymal heterotopias, agenesis of the posterior part of the corpus callosum, mega cisterna magna, and aneurysms of the sinuses of Valsalva. This may constitute a new subtype of type 1 Ehlers-Danlos syndrome characterized by X-linked periventricular subependymal heterotopias and epilepsy.

Adult↗

Cytogenetics of malignant gliomas: I. The autosomes with reference to rearrangements.

Autosomal chromosome abnormalities are far from always detectable and, when detected, far from fully consistent in malignant gliomas. In 15 of 41 malignant gliomas, we found autosomal chromosome aberrations ranging from solitary trisomy to a wildly abnormal polyploid complement. The sequence of chromosome events appears to proceed from the normal to the near-diploid state (via structural and numerical changes) to near-tetraploidy (via polyploidization), and finally toward near-triploidy (via chromosome loss and additional rearrangements). Characteristic chromosome changes of trisomy 7 and monosomy 10 were repeatedly found, usually together in the same cell clones. In only one case was trisomy 7 an isolated change. We observed structural rearrangements of chromosomes 7 and 10 which may be of some use in mapping specific genes duplicated or deleted by the whole-chromosome changes of chromosomes 7 and 10. Nonrandom structural changes of other autosomes, including chromosomes 1, 5, and 11, fit with the model of malignant glioma as a process involving multiple genes. An unusual concentration of breakpoints in 12q13, juxtaposing it to at least five other regions, reflects the presence of genetic information in 12q13 important to the development of malignant gliomas.

Adult↗