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Biomedical subjects

A L Benabid

Publications and source records attributed to A L Benabid.

At least 19 recordsLinked to original sources
PubMed1992

Potential use of robots in endoscopic neurosurgery.

A 6-axis stereotactic robot has been designed and linked to a stereotactic frame for routine use. Robot software allows the positioning of a probe holder in order to reach a given target. A calibration step enables the robot to compute the position of the x-ray beam and correct its final position to avoid parallax errors. The co-ordinates of the target are presently taken from anteroposterior and lateral X-rays using a digitizing table. Connection with a digitized angiography system is in progress and will allow direct sampling of numerical data from the x-ray data. Further steps will include connections with a 3D-reconstructed image from MRI and CAT as well as with a resident computerized atlas. Present experience after 14 months of daily practice represents 140 stereotactic procedures which can be extended to any special use, including endoscopic approaches.

Brain Diseases↗
PubMed1992

Stereotactic approach to intracranial lesions.

The diagnostic and therapeutic approach to intracranial lesions must be different considering the different possibilities offered by the various methods. The diagnostic reliability and safety of stereotactic biopsy are often indispensable in order to optimize the subsequent therapy. The results obtained in selected pathologies allow us to propose the stereotactic approach to treat: -various kind of cysts by aspiration and/or Beta endocavitary radiation therapy; -blood or abscessual collections that can be aspirated in a similar way; -arterio venous malformations or tumours by radiosurgery; -tumours by brachicurietherapy or by computer assisted stereotactic surgery. We present some cases treated at the C.H.S.A. of Paris and at the C.H.R.U. of Grenoble utilizing Talairach methodology.

Adolescent↗
PubMed1992

EGF receptor amplification and expression in human brain tumours.

Human epidermal growth factor receptor (EGFr) gene amplification, rearrangements and expression were studied in tumours of the human nervous system. EGFr gene amplification was studied in 46 brain tumours. Gene expression was analysed by northern blot in 37 tumours and binding of its protein to EGF in 27 tumours. The EGFr gene was simultaneously amplified (with arrangements in 12.5% of gliomas) and overexpressed in 53% (9/17) of malignant gliomas, but never in meningiomas. In five high grade gliomas, amplification was always associated with a high level of receptors. However, since high amounts of EGF receptors found in one glioma were not the result of gene amplification, several systems of deregulation in EGFr production may exist and could be located at translational and/or post-translational levels.

Adolescent↗
PubMed1992

[The EGF receptor pathway in human cerebral tumors].

The epidermal growth factor receptor gene is the most frequently involved proto-oncogene in human glial brain tumors, in the present series in agreement with previous reports in literature. It is therefore important to study this gene from DNA to the protein product. The vicinity of cystic fluid (C.F.) to tumor cells of the cystic wall has suggested investigation of possible "E.G.F.-like" autocrine activities in C.F. In 40% of gliomas, E.G.F.-R. gene is amplified and overexpressed. This is never observed in low grade astrocytomas. In 12% of the cases, mutations of the E.G.F.-R. gene are observed. In correlation with genomic abnormalities, E.G.F.-R. is immunoprecipitated in 40% gliomas. The basal phosphorylation of the receptor is increased in 50% gliomas. In C.F., unexpectedly, E.G.F.-R. phosphorylation inhibitory effect is observed. Its biochemical analysis suggests an anti-tyrosine kinase activity. The observation of anti-tyrosine kinase activity in C.Fs suggests the presence of negative modulatory factors of the proto-oncogene activation in tumor tissues. This could have therapeutical interest.

Blotting, Northern↗
PubMed1992

Metabolism and aerobic capacity of skeletal muscle in chronic respiratory failure related to chronic obstructive pulmonary disease.

The calf muscle energy metabolism of 8 stable chronic obstructive pulmonary disease (COPD) patients with chronic respiratory failure (arterial oxygen tension (Pao2) 7.7 +/- 0.4 kPa or 58 +/- 3 mmHg) was studied, using 31-phosphorus magnetic resonance spectroscopy (31P MRS). MRS spectra were acquired at rest and during the course of 360 pedal movements at 20, 35 and 50% of the maximal voluntary contraction (MVC) and during recovery. Eight healthy age-matched subjects served as the control group. No significant differences between groups were observed in resting muscle, as regards intracellular pH, Pi/PCr ratio (Pi: inorganic phosphate; PCr: phosphocreatine) and the relative ATP expressed as the ratio beta ATP/PCr + Pi + PME (PME: phosphomonoester). Although effective power outputs were similar for both groups at each work level, COPD patients exhibited a higher Pi/PCr ratio than health controls (3.34 +/- 0.89 vs 0.49 +/- 0.05 at 50% MVC; p less than 0.01) and a lower pHi (6.65 +/- 0.11 vs 7.06 +/- 0.02 at 50% MVC; p less than 0.01). PCr resynthesis during recovery was slower in patients than in control subjects (t1/2 PCr 1.27 +/- 0.26 min vs 0.47 +/- 0.05 min; p less than 0.05). These results suggest impairment of aerobic capacity in a non-ventilatory working muscle, which may be due to hypoxaemia in patients with chronic respiratory failure.

Aged↗
PubMed1991

Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.

Clone pTB16 has been isolated by differential screening of a human glioma cDNA library. Northern blot analysis has shown that pTB16 expression is several times (greater than 11-fold) higher in gliomas than in a primitive neuroectodermal tumor. This observation was supported by in situ hybridization and extended to nine other gliomas. Expression was virtually absent in adenocarcinoma cells metastasized to brain. Malignant gliomas showed stronger hybridization than benign gliomas, while blood capillaries did not show hybridization. pTB16 mRNA was also shown to be expressed in established glioma cell lines and at high levels in epileptic foci, indicating that expression of the gene may be limited to certain cell types and that its upregulation is not merely a consequence of cellular proliferation. Nucleotide sequence analysis identified pTB16 as the human counterpart for rat testicular sulfated glycoprotein 2 (SGP-2), whose function in the reproductive system remains unknown. Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death.

Blotting, Northern↗
PubMed1991

Activation of myc gene family in human lung carcinomas and during heterotransplantation into nude mice.

myc gene family activation (c-myc, L-myc, and N-myc) was examined in 26 human lung carcinomas and in their corresponding xenografts in nude mice. Of the 16 neuroendocrine (NE) carcinomas studied, amplification was observed in 4 with a c-myc probe and in 1 with both L- and N-myc probes. Overexpression was found in 1 of 7 cases studied for c-myc mRNA, in 1 of 7 cases for N-myc, and in 2 of 7 cases for L-myc. Of the 10 non-small cell lung carcinomas studied, only c-myc was amplified in 1 case and overexpressed in 5 of 7 cases. These results suggest that L- and N-myc gene activation are restricted to NE carcinomas. Over-expression of the myc gene without amplification was detected in 36% of cases. During heterotransplantation, there was a 27% change in myc gene abnormality and a 57% increase in myc expression levels, mostly in NE carcinomas (5 of 7; 71%). In a total of 42 xenografted lung carcinomas studied, 45% amplification and 77% overexpression of one of the myc genes were detected with a high prevalence of L-myc overexpression in NE carcinomas (50%) and of c-myc overexpression in non-small cell lung carcinomas (66%). Finally, 19 of 26 (73%) tumors are growing in nude mice with no myc gene amplification and 43% with no myc mRNA overexpression. Thus myc gene activation is not strictly required for heterotransplantation but seems to be a favorable factor in the maintenance and progression of lung carcinomas in vivo.

Animals↗
PubMed1991

Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.

The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.

Aged↗
PubMed1991

Proton spectroscopic imaging: a tool for studying intracerebral tumor models in rat.

Water-suppressed 2D 1H spectroscopic imaging was used with surface coils to study in vivo the cerebral metabolism changes in rat brain induced by a glial tumor growing in situ. To achieve slice selection without a chemical-shift artifact, we exploited the depth pulse properties of a spin-echo sequence. In order to give a spectral response which is independent of the position, the water suppression was achieved by using a spin-locking excitation and a binomial refocusing pulse. Spectroscopic images were obtained with an in-plane resolution of 1.1 X 1.1 mm and a slice thickness of roughly 3 mm. The growing of the tumor induced dramatic modifications in the proton spectra, including a nearly complete loss of N-acetyl aspartate, an increase of the 1.3-ppm peak, an increase in choline, and a decrease in creatine. The results demonstrate the potential of spectroscopic imaging in the study of intracranial tumor models in rats.

Animals↗
PubMed1991

Impairment of muscular metabolism in chronic respiratory failure. A human 31P MRS study.

The calf muscle metabolism of 7 patients with stable chronic respiratory failure (PaO2 below 65 Torr) was studied using 31P NMR spectroscopy. NMR spectra were acquired at rest, during the course of 360 pedal movements at 20, 35 and 50% of the maximal voluntary contraction (MVC) and during recovery. Eight normal aged-matched subjects served as a control group. In resting muscle, no significant differences were observed between both groups as regards intracellular pH, inorganic phosphate/phosphocreatine (Pi/PCr) and beta-ATP/PCr + Pi + phosphomonoester (PME) ratios. Although effective power outputs were similar for both groups at each work level, patients exhibited a higher Pi/PCr ratio than healthy controls (3.19 +/- 1.01 vs 0.49 +/- 0.05 at 50% MVC; p less than 0.01) and a lower pHi (6.65 +/- 0.11 vs 7.06 +/- 0.02 at 50% MVC; p less than 0.01). Moreover, PCr resynthesis during recovery was slower in patients than in control subjects (t1/2 PCr = 1.26 +/- 0.30 vs 0.47 +/- 0.05 min; p = 0.01). These results suggest impairment of aerobic capacity in a non-ventilatory working muscle, probably due to hypoxemia in patients with chronic respiratory failure.

Adenosine Triphosphate↗
PubMed1991

Aphemia after a penetrating brain wound: a case study.

The speech of a patient with aphemia (pure anarthria) resulting from a penetrating brain wound was studied using linguistic and acoustic observations as well as electromyographic recordings from four labial muscles. The results are discussed in relation to phonetic disintegration's syndrome and apraxia of speech which, respectively, enhance linguistic disorders and motor programming disturbance.

Aphasia↗
PubMed1990

Intensity-dependent nociceptive responses from presumed dopaminergic neurons of the substantia nigra, pars compacta in the rat and their modification by lateral habenula inputs.

The characteristics of nociceptive responses from presumed dopaminergic (DAergic) neurons in the SN were investigated in the anesthetized rat with extracellular recordings. 194 presumed DAergic neurons were recorded. A majority of these neurons (78%) were inhibited by intensive electrical stimulation performed at the tail (PNS) and 15% were excited. Both inhibitory and excitatory responses were intensity-dependent. Single shock stimulation of the lateral habenula (LHb) inhibited 89% of the tested DAergic neurons, most of which (83.8%) were also inhibited by PNS. LHb stimulation increased PNS-induced inhibition of DAergic neurons and electrical destruction of ipsilateral LHb depressed their nociceptive responses. Our results strongly suggest that DAergic neurons encode the nociceptive stimulation intensity and that the LHb shares a step in nociceptive projection to the SN.

Animals↗
PubMed1990

Analysis of the activation of the myc family oncogene and of its stability over time in xenografted human lung carcinomas.

In order to validate the use of the nude mouse as a model for studying lung cancers, 21 different lung cancers were xenografted onto nude mice and the tumoral DNA and RNA were analyzed for abnormality in the myc family genes (c-myc, L-myc, and N-myc). Six of 14 small cell lung cancers (SCLC) showed a 4-35-fold amplification for L-myc, 5 of 7 non-SCLC a 3-5-fold amplification for c-myc, and 1 of 14 SCLC an 80-fold amplification for N-myc. Of the 7 SCLC with amplified L- or N-myc oncogenes, 4 were of the small and large histological type, while only 5 of the 21 cases studied were of the small and large type. All xenografted tumors with amplification of one of the myc genes showed overexpression of the related mRNA. Overexpression without amplification of the myc genes was observed for 3 SCLC and 2 non-SCLC. These results indicate that the L-myc gene seems to be associated with the small and large phenotype in SCLC, whereas c-myc seems to be implicated in non-SCLC. Of the 21 lung cancers studied 14 were analyzed for myc family gene activation for serial passages into nude mice. No variation of DNA amplification was observed during long-term growth in nude mice for any of the myc oncogenes. Changes in the level of mRNA expression were observed only for c-myc; a beginning of expression in one SCLC and an increase in expression in one non-SCLC were noted in late passages when compared with early ones. The nude mouse is therefore a valuable model for the study of lung cancers "over a 4-year period at least."

Animals↗
PubMed1990

Failure to detect viral genomic sequences of three viruses (herpes simplex, simian virus 40 and adenovirus) in human and rat brain tumors.

Little is known about oncogenesis in brain tumors. Viruses are thought to be involved in some neurological diseases, the presence of subfractions of viral DNA has been reported in various circumstances and the oncogenicity of some viruses has been demonstrated in animal experiments. The discovery of homologies between retroviral oncogenes and normal cellular genes (proto-oncogenes) has stimulated once again the search for viral responsibility in oncogenesis. Having a large bank of tumor material available, we systematically examined 39 brain tumors using Southern blot hybridization with DNAs of three viruses, known to be involved in neurological diseases: herpes simplex virus (HSV), simian virus 40 (SV40) and adenovirus type 2 (Ad2). We detected no homology between the DNAs of the examined material and the viral DNA probes. We compare these negative results with those of other published studies and discuss the experimental conditions, with special reference to the possibility of non-specific hybridization, which could account for the positive results reported. The present negative results could be interpreted either as absence of involvement of the three investigated viruses in brain tumor oncogenesis, or an indirect involvement through a hit-and-run mechanism or a highly dispersed state of the viral sequences among the host genome, which would prevent hybridization with the probe, as it has been supposed to be the case during the latency phase of herpes virus.

Adenoviridae↗
PubMed1990

[Subcutaneous administration of apomorphine in motor fluctuations in Parkinson's disease].

Apomorphine, a dopaminergic agonist was given over a period of 12 months to 14 parkinsonian patients suffering from severe L-dopa induced on-off effects. Nine patients (mean age: 52 years; mean age at onset of the disease: 37 years), were treated by continuous infusion with a portable minipump, and 5 others by multiple injections with a penject. The mean duration of daily off periods was reduced by two thirds in all patients. The motor fluctuation intensity was only diminished in the 9 patients treated by continuous infusion. These patients received a mean apomorphine daily dose of 93 mg and L-dopa dosage was reduced by 53 p. 100. Red fibrous subcutaneous nodules occurred at the injection sites in all patients treated by infusion. This study confirms the effectiveness of subcutaneous apomorphine administration in the treatment of severe motor fluctuations.

Adult↗
PubMed1989

Cells of the rat lateral habenula respond to high-threshold somatosensory inputs.

Extracellular electrical recordings of single units in the anaesthetized rat demonstrate that about two thirds of the neurons in the lateral habenula respond to peripheral noxious stimuli in a way similar to that of the cells in the centrum-medianum complex which can be activated (with several peaks of various latencies) or inhibited. The firing pattern of these lateral habenula cells is either excitatory (75%) or inhibitory (24%) and is related to the intensity of the stimulus; their receptive field is large and bilateral. Most of these cells also respond to other kinds of noxious but not to non-noxious stimuli. The present study strongly suggests that the lateral habenula is a central target at the upper brainstem level for nociceptive inputs. This original finding is consistent with our previous observation of naloxone reversible analgesia induced by stimulation of the habenula and suggests an involvement of this structure in the processing of noxious inputs.

Action Potentials↗