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Biomedical subjects

A Jouvet

Publications and source records attributed to A Jouvet.

At least 37 records · Page 2Linked to original sources
PubMed2002

Sudden death caused by parasites: postmortem cerebral malaria discoveries in the african endemic zone.

This survey presents several cases of sudden deaths in Africa, specifically in Cote d'Ivoire, where the postmortem diagnosis of human cerebral malaria was determined after autopsy followed by pathologic examination of the brain. It is thought that cerebral malaria may be the primary cause of sudden death in nonimmunized persons during or after traveling in such endemic areas of Africa. The target population is composed of tourists, business travelers, and sailors. Because death caused by cerebral malaria occurs so suddenly, it can lead to forensic issues. Therefore, in any cases involving sudden death, it is very important for the forensic scientist to do a systematic evaluation, including pathologic examination of brain tissue, to rule in or exclude cerebral malaria. This practice will reinforce and aid research in progress directed at developing a vaccine and elucidating the role of tumor necrosis factor in this disease. Furthermore, this study will alert the physician to the importance of an effective and well-followed prophylaxis.

Adult↗
PubMed2002

Establishment of human tumoral ependymal cell lines and coculture with tubular-like human endothelial cells.

Ependymomas, rare neoplasms of the central nervous system, occur predominantly in children. They are highly vascularized, and histological findings show many perivascular rosettes of tumoral cells radially organized around capillaries. Treatment of ependymomas relies on surgery combined with radio- or chemotherapy, but the efficiency of chemotherapy is limited, probably because of their multidrug resistance (MDR) phenotype. Progress in the therapy of these neoplasms is dramatically limited by the absence of cell line models. We established conditions for the long-term culture of human tumoral ependymocytes and their 3D coculture in Matrigel with endothelial cells. Histological, immunological, and ultrastructural studies showed that the morphological features (microvilli, cilia, and caveolae) of these cultured cells were similar to those of the tumor in vivo. The cells expressed potential oncological markers related to the immature state of tumoral cells (nestin and Notch-1), their tumorigenicity [caveolae and epidermal growth factor-receptor (EGF-R)], or the MDR phenotype [P-glycoprotein (P-gp)]. The expression of P-gp, EGF-R, and caveolin-1 by these tumoral ependymocytes could be useful in studies on new drugs. This coculture model might represent a new powerful tool to study new therapeutic delivery strategies in tumoral cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Germline SDHD mutation in paraganglioma of the spinal cord.

Hereditary paraganglioma of the head and neck is associated with germline mutations in the SDHD gene, which encodes a mitochondrial respiratory chain protein. Paragangliomas of the central nervous system are very rare, occur almost exclusively in the cauda equina of the spinal cord and are considered non-familial. In the present study, we screened 22 apparently sporadic paragangliomas of the cauda equina for SDHD mutations. One spinal paraganglioma and similar cerebellar tumours that developed 22 years later in the same patient contained a missense mutation at codon 12 (GGT-->AGT, Gly-->Ser) and a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). There was no family history of paragangliomas but DNA from white blood cells of this patient showed the same sequence alterations, indicating the presence of a germline mutation. All other cases of spinal paraganglioma had the wild-type SDHD sequence, except one case with a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). This is the first observation indicating that inherited SDHD mutations may occasionally cause the development of paragangliomas in the central nervous system.

Cauda Equina↗
PubMed2001

Differential expression of somatostatin receptors in ependymoma: implications for diagnosis.

Somatostatin receptors (SSts) have been found in a variety of brain tumors, e.g., meningiomas, medulloblastomas and astrocytomas. Our aim was to investigate their expression in ependymomas. Using RT-PCR, expression of mRNA for the different SSt subtypes was analyzed and quantified in 28 ependymomas and correlated with different variables (age, tumor location, histological grade, recurrence and survival). In addition, in 8 cases, protein expression was studied in vitro, using immunohistochemistry, and in vivo, by somatostatin scintigraphy. mRNAs for all 5 subtypes were variably expressed in each ependymoma. The Southern blotting signal obtained after SSt(1) and SSt(2) amplification was higher than that for the other receptor subtypes. No significant correlation was seen between the level of SSt(1) and SSt(2) mRNA expression and age, location, histological grading, recurrence or survival. In the 8 cases, SSt(1) staining was negative in 3 and low in 5. Staining for SSt(2A) was positive but low in every specimen analyzed. SSt(1) and SSt(2) immunoreactivity was seen only in the cytoplasm of tumoral cells. Somatostatin scintigraphy showed clear uptake, which agreed with MRI data in the majority of cases. However, no correlation was seen between tracer uptake intensity and histological grade, SSt(1) and SSt(2) mRNA expression or immunostaining intensity. This evidence for the expression of SSt(2) receptors in ependymomas opens interesting prospects for their follow-up.

Adolescent↗
PubMed2001

Central nervous system cavernomas in the pediatric age group.

Pediatric CNS cavernomas still are diagnostically and therapeutically challenging lesions. With the help of magnetic resonance imaging, the natural history of cavernomas now guiding therapeutic strategies is well documented in adults but remains poorly known in the pediatric age group, since most previous studies dealt with adult and pediatric patients together. This paper focuses on clinical, imaging, and therapeutic features and differential diagnosis of CNS cavernomas with an emphasis on their specificities in the pediatric age group. It is based upon a critical review of the literature and our single-center experience with 36 children (35 with cerebral cavernomas and one with spinal cord cavernoma) operated on during the period of 1985-1999 as well as with seven additional unoperated pediatric cases. Our experience resembles that of other authors regarding the high hemorrhagic risk in children compared to adults. These angiographically occult vascular malformations are often revealed by the sudden onset of intracerebral hematoma with acute focal neurologic deficits, concomitant manifestations, and/or signs of raised intracranial pressure. True epilepsy is less common and may be related to chronic or recurrent microbleeding. Evocative imaging findings are also somewhat different in the two age groups, and we propose here an imaging classification of cerebral cavernomas based on both morphological and signal characteristics that is applicable to the pediatric age group. A sharply demarcated spherical intracerebral hematoma or heterogeneous lesion should always make one consider the hypothesis of a cavernoma. For symptomatic lesions and most rapidly growing asymptomatic lesions, the treatment of choice is complete microsurgical excision preceded by careful anatomical and functional evaluation. Improvements in surgical techniques and anesthesiology over recent years have brought good results in most operated children. The limited role of radiosurgery in the management of pediatric cerebral cavernomas is discussed. There is still a need for well-conducted specific evaluation of the natural history of these lesions in the pediatric age group to aid in systematic research, follow-up, and therapeutic strategies for asymptomatic cavernomas.

Central Nervous System Neoplasms↗
PubMed2001

Visceral cancer metastasis to pituitary adenoma: report of two cases.

BACKGROUND: We report two cases of metastases from visceral cancers to pituitary adenomas, and review the literature. CASE DESCRIPTION: Two female patients, aged 75 and 87 years, underwent transesophageal surgery for presumably benign pituitary adenomas. Using extensive immunostaining studies, histopathological examination showed that the surgical specimens from both patients were composed of metastatic deposits within gonadotropin adenomas. Fourteen cases of metastases to pituitary adenomas have been mentioned in 11 reports in the literature. In all cases, the correct diagnosis was made after autopsy or histopathological studies, even in patients known to suffer from visceral malignancies. In our cases, immunohistochemical studies were conclusive in characterizing the two distinct tumor components. The pathogenetic mechanisms favoring the development of metastases in pituitary adenomas are discussed, especially those altering the normal hypophyseal circulation. CONCLUSION: Neurosurgeons performing pituitary surgery should be aware of the possibility of metastases in pituitary adenomas.

Adenoma↗
PubMed2001

Redifferentiation therapy in brain tumors: long-lasting complete regression of glioblastomas and an anaplastic astrocytoma under long term 1-alpha-hydroxycholecalciferol.

PURPOSE: Classical and new therapies in anaplastic astrocytomas and glioblastomas do not yield sufficient results. Agents able to redifferentiate neoplastic cells in vitro are known. We proposed alfacalcidol, a vitamin D analog able to bind to nuclear receptors regulating mitotic activity, in the treatment of malignant gliomas. PATIENTS AND METHODS: Patients with glioblastomas and anaplastic astrocytomas were enrolled in a phase II trial involving surgery or biopsy, radiotherapy (64 Gy), chemotherapy with VM26-CCNU or fotemustine, and alfacalcidol at the daily dose of 0.04 microg/kg. MRI took place every 6 months. RESULTS: Eleven patients were included and completed the study. The series involved 10 glioblastomas and 1 anaplastic astrocytoma. Three patients out of 11 patients (27%), 2 glioblastomas and 1 astrocytoma grade III, exhibited a particular response, consisting in the progressive regression of the radiological lesion, with a decrease of the gadolinium-enhanced area. Simultaneously, the patients showed a complete clinical remission, observed respectively for 7, 5 and 4 years. In the series of 10 patients with glioblastomas, 2 cases showed this response; after 4 years, 2 of 10 patients with glioblastomas (20%) were alive; the median survival time is 21 months. Normal or subnormal calcemia was observed, at the dose proposed, so that no interruption of the drug was necessary. CONCLUSIONS: Alfacalcidol, an in vitro agent of redifferentiation, is safe and seems able to induce in some patients, in synergy with classical surgery-radiotherapy-chemotherapy treatments, a particular progressive and durable regression of the tumor. The responders might represent about 20% of malignant gliomas.

Adjuvants, Immunologic↗
PubMed2001

Lack of evidence of osteo-medullary metastases at diagnosis in patients with high grade gliomas.

High grade gliomas usually show a transient response to standard therapy by radiation. A local evolution leads to patient death in most of the cases. Necropsic series suggest that metastatic evolution is rather frequent in lungs, lymph nodes, bones or bone marrow. Are these metastatic deposits present initially? The authors retrospectively reviewed the bone marrow smears performed in 20 patients and the bone scans in 10 patients with high grade gliomas at time of diagnosis. None of these investigations showed metastatic deposits. It is thus suggested that metastatic deposits are probably a late event in the natural history of high grade gliomas. However, if local treatment could reach local control, metastases would probably become a major problem. Thus definitive cure of high grade glioma may require multidisciplinary approach.

Astrocytoma↗
PubMed2001

Differential expression of somatostatin receptors in medulloblastoma.

OBJECT: Somatostatin receptors have been found on a variety of tumours like neuroendocrine breast or brain tumours. Their detection opens new diagnostic and therapeutic paths. The aim of this work was to investigate their expression in medulloblastomas. METHODS: Using both techniques, reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analysed mRNA of different subtypes of somatostatin receptors in 15 medulloblastomas and the localisation of the subtype SSTR2 receptor at the cellular level in 13 medulloblastomas. All five subtypes mRNA were variably expressed in each medulloblastoma. The signal obtained after Southern blotting for SSTR2 receptor amplification was the highest as compared to the signal obtained for the other receptor subtypes. Immunostaining for SSTR2A receptor was present in every tumour specimen and was specifically located to the cellular membrane of neoplastic cells. No staining was identified at the level of peritumoral veins. CONCLUSION: The evidence of predominant expression of SSTR2 receptors in medulloblastomas opens interesting prospects for their diagnosis and therapy.

Cerebellar Neoplasms↗
PubMed2000

Parenchymal pineal tumors: a clinicopathological study of 76 cases.

PURPOSE: The aim of this study was to identify factors that could lead to optimization of the management of pineal parenchymal tumors (PPT) which remains equivocal and controversial. METHODS AND MATERIALS: In order to determine factors that influence PPT prognosis, a series of 76 consecutive patients from 12 European centers with histologically proven tumors was retrospectively reviewed. The clinical records and material for histologic review were available in all cases. Follow-up was achieved in 90% of cases. RESULTS: According to WHO classification, there were 19 pineocytomas, 28 intermediate and mixed PPT, and 29 pineoblastomas. According to a four-grade institutional classification, there were 11 Grade 1, 27 Grade 2, 20 Grade 3, and 18 Grade 4. Surgical resection was attempted in 44 patients, whereas 30 had biopsy only. In one case, diagnosis was made at autopsy and in another on spinal deposits. Forty-four patients were irradiated following surgery, 15 patients received chemotherapy. Forty-one patients were alive (median follow-up: 85 months); 9 patients died perioperatively; 26 patients relapsed. Univariate analysis showed a good outcome correlated with age above 20 years, tumor diameter less than 25 mm, and low-grade histology. Multivariate analysis confirmed histology and tumor volume to be significant independent prognostic factors. The extent of surgery and radiotherapy had no clear influence on survival. CONCLUSIONS: This review highlights the prognostic features of PPT and may help to determine treatment strategies based on radiologic and pathologic characteristics.

Adolescent↗
PubMed2000

Radiologic anatomy of the spinal dorsal horn at the cervical level (anatomic-MRI correlations).

The spinal dorsal horn is known for its important functional role in the field of transmission and modulation of sensory afferents. Because of this, the dorsal horn represents a target for numerous analgesic and antispastic procedures. Thus, it would be interesting to develop imaging dedicated to this spinal structure. The purpose of this study was to investigate the radiologic anatomy of the cervical dorsal horn by magnetic resonance imaging (MRI) (1.5T). The first step consisted in the validation of the anatomic information provided by MRI on 5 human cadavers. A spin-echo sequence (T2, 2000/45) enabled the demonstration of good correlations between histologic sections and axial MRI slices performed at the corresponding cervical levels. The second step was the < > exploration of 20 subjects, aiming at the development of a gradient echo sequence (T2*) with a conventional MRI unit, compatible with a routine clinical examination. The dorsal horn was clearly identified in 77% of the axial slices performed (n = 300). The angle between the dorsal horn axis and the sagittal plane was measured as from 25.5 degrees at C2 to 40 degrees at C8 segments. The results of this anatomico-radiologic study of the cervical dorsal horn suggest that preoperative MRI could be useful to design the surgical approach to this structure, as performed during cervical microsurgical drezotomy (DREZ = dorsal root entry zone) for the treatment of selected cases of chronic pain or disabling spasticity in the upper limbs.

Aged↗
PubMed2000

Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases.

The WHO classification of CNS tumors divides pineal parenchymal tumors (PPT) into pineocytoma (PC), pineoblastoma (PB) and mixed pineocytoma-pineoblastoma or PPT with intermediate differentiation. The reported incidence of mixed/intermediate PPT varies and this may reflect the difficulty in classifying tumors of this type. In an attempt to overcome the problem of the classification of PPT with intermediate differentiation, we describe the relationship between histological features and patient survival in a large cooperative series of 66 PPT from 12 neurosurgical centres. All tumors were studied with both light microscopy and immunohistochemically using antibodies against glial markers or neural/neuroendocrine markers. Our series included 11 PC, 39 mixed/intermediate PPT and 16 PB. A number of mitoses greater than 6 and the presence of necrosis were associated with a poorer outcome, while positive immunostaining for neurofilaments was associated with a better survival. We propose a new prognostic grading of 4 grades, grade I for PC, grade II for PPT with fewer than 6 mitoses and positive immunolabelling for neurofilaments, grade III for PPT with either 6 or more than 6 mitoses or fewer than 6 mitoses but without immunostaining for neurofilaments and grade IV for PB.

Adolescent↗
PubMed2000

[Practical recommendations for management of the biopsy in an expansive intra-cerebral process].

Diagnosis of an intracerebral mass requires a good collaboration between clinicians and pathologists. Different techniques may be necessary. The interest of cytological preparations and immunohistochemistry is reported. The main characteristic features of cerebral tumors are described and the differential diagnosis with reactive and inflammatory masses simulating neoplasia is discussed.

Biopsy↗
PubMed1999

Tyrosine hydroxylase and aromatic L-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex.

Immunoreactivity for aromatic L-amino acid decarboxylase (AADC), the second step dopamine-synthesizing enzyme, was found immunohistochemically in neurons of the human anterior cingulate cortex (ACC). Most of these neurons were located in layers V and VI and subcortical white matter; a small number were occasionally found in layer III. Double immunohistochemistry for tyrosine hydroxylase (TH: the first step dopamine-synthesizing enzyme) and AADC revealed that no neuronal cell bodies in the ACC were doubly immunostained for TH and AADC, suggesting that these TH-only- or AADC-only-immunoreactive neurons were not dopaminergic. AADC neurons in the human ACC might transform L-DOPA to dopamine, droxidopa to noradrenaline, and/or 5-hydroxytryptophan to serotonin.

Adult↗
PubMed1999

Molecular analysis of glioma and skin-tumour alterations in a xeroderma-pigmentosum child.

Xeroderma pigmentosum (XP) is a rare hereditary disease characterized by a very high frequency of skin tumours due to a defect in the nucleotide-excision-repair process. Some of these patients have also been reported to develop internal tumours with higher frequency than the normal population. Reported here are the clinical features and molecular analysis of an XP patient who developed multiple skin cancers as well as a thalamic glioma. Complementation analysis with recombinant retrovirus, cloning efficiency and unscheduled DNA synthesis after UV-C indicate that the patient belongs to the C group. Characterization of the p53 mutations in the 2 tumours of the patient leads to speculation on the aetiological agents involved in tumour initiation. The skin tumour is clearly induced by the presence of unrepaired UVB-induced DNA damage on the non-transcribed strand of the p53 gene, while the glioma may be induced by unrepaired DNA lesions produced by free radicals.

Brain Neoplasms↗
PubMed1999

Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations.

The hSNF5/INI1 gene which encodes a member of the SWI/SNF chromatin ATP-dependent remodeling complex, is a new tumor suppressor gene localized on chromosome 22q11.2 and recently shown to be mutated in malignant rhabdoid tumors. We have searched for hSNF5/INI1 mutations in 229 tumors of various origins using a screening method based on denaturing high-performance liquid chromatography. A total of 31 homozygous deletions and 36 point alterations were identified. Point mutations were scattered along the coding sequence and included 15 nonsense, 15 frameshift, three splice site, two missense and one editing mutations. Mutations were retrieved in most rhabdoid tumors, whatever their sites of occurrence, indicating the common pathogenetic origin of these tumors. Recurrent hSNF5/INI1 alterations were also observed in choroid plexus carcinomas and in a subset of central primitive neuroectodermal tumors (cPNETs) and medulloblastomas. In contrast, hSNF5/INI1 point mutations were not detected in breast cancers, Wilms' tumors, gliomas, ependymomas, sarcomas and other tumor types, even though most analyzed cases harbored loss of heterozygosity at 22q11.2 loci. These results suggest that rhabdoid tumors, choroid plexus carcinomas and a subset of medulloblastomas and cPNETs share common pathways of oncogenesis related to hSNF5/INI1 alteration and that hSNF5/INI1 mutations define a genetically homogeneous family of highly aggressive cancers mainly occurring in young children and frequently, but not always, exhibiting a rhabdoid phenotype.

Chromatography, High Pressure Liquid↗