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J Hildebrand

Publications and source records attributed to J Hildebrand.

At least 55 records · Page 3Linked to original sources
PubMed1997

Positron emission tomography and brain tumours.

The first applications of positron emission tomography (PET) for the study of brain tumours appeared early in the development of this technology. New trends in these particular PET applications tend to take into account the histological heterogeneity of these tumours and the necessity to integrate PET data in their surgical management. Better knowledge on PET tracers behavior in brain tumours should lead to new clinical uses, in particular in the promising field of cancer treatment evaluation.

Brain Neoplasms↗
PubMed1996

Regional glucose metabolism and histopathology of gliomas. A study based on positron emission tomography-guided stereotactic biopsy.

BACKGROUND: Positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) is widely applied to the study of gliomas. The histology of most gliomas is regionally heterogeneous. The relationship between histologic features and glucose metabolism evaluated by PET with FDG may therefore vary within the limits of the tumor. PET with FDG integrated in the planning of stereotactic brain biopsy allows precise comparison between local FDG uptake and histology. Using this approach, the authors investigated whether glucose metabolism of gliomas is related to anaplasia, and whether PET with FDG detects metabolic heterogeneity that parallels histologic heterogeneity of gliomas. METHODS: A total of 161 biopsy samples collected from 20 PET-guided procedures performed in patients with gliomas (8 low grade astrocytomas, 8 anaplastic astrocytomas, 1 anaplastic oligoastrocytoma, and 3 glioblastomas) were analyzed for the presence or absence of 8 histologic features. Stereotactic coordinates were used to calculate the metabolic rate of glucose (MRGlu) in the region of each biopsy sample. Gray and white matter MRGlu were used to define four metabolic grades that were compared with local histology. RESULTS: The difference in MRGlu expressed as micromoles per 100 g per minute was highly significant between anaplastic and nonanaplastic samples; the median +/- quartile deviation was 23 +/- 16 in anaplastic samples and 18 +/- 5 in nonanaplastic samples (P < 0.005). Even more significant differences were found when MRGlu was normalized to the cortex or to the white matter. Metabolic grades were different in anaplastic and nonanaplastic samples (P < 0.0001). Approximately 75% of samples metabolically graded 3 or 4 demonstrated signs of anaplasia, compared with 10% of samples graded 0 or 1. CONCLUSIONS: FDG uptake in gliomas is anatomically heterogeneous and is regionally related to the presence of anaplasia.

Adult↗
PubMed1996

Systemic and intrastriatal theophylline have opposite effects on dopamine and dopamine metabolites measured by intrastriatal microdialysis in the rat.

Using a model of intrastriatal microdialysis, we studied the effect of theophylline, an A1 and A2A adenosine receptor antagonist on striatal dopamine (DA) and DA metabolites. Systemic administration of theophylline (10 and 50 mg/kg) significantly reduced striatal extracellular (EC) levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxy-phenylacetic acid (HVA). Intrastriatal administration of theophylline (10(-2) M) significantly increased DA and its metabolites (DA1 + 120%; DOPAC, +28%; HVA, +30%). Contradictory effects of systemic and intrastriatal theophylline point to theophylline interactions with different receptors possibly at different locations.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Curative potential of herpes simplex virus thymidine kinase gene transfer in rats with 9L gliosarcoma.

The transfer of the gene coding for the thymidine kinase of the herpes simplex virus (HSV-tk), followed by ganciclovir (GCV) administration, has been described for the treatment of several types of cancer, especially brain tumors. We further studied the efficacy of this approach by using the 9L rat gliosarcoma model, and cells producing 5 x 10(3), 9 x 10(4), 3 x 10(5) HSV-tk retroviral particles per milliliter. Their stereotactic injection in 9L brain tumors and GCV treatment did not result in any increase of survival. To study a model of optimal in vivo transduction, we examined the survival of rats with tumors growing from 9L cells that had been previously transduced in vitro with the HSV-tk vectors (9LTk cells). We observed that GCV administration cured 26% (n = 42) of the animals with 9LTk brain tumors, with most of the relapsing tumors remaining HSV-tk positive. The increase of either the dose or the duration of GCV treatment did not improve the survival rate. But the cerebral localization of the tumor played an important role, because this survival rate reached 67% (n = 12) when similar tumors were growing subcutaneously. No or only marginal antitumoral responses were induced by the presence of a selectable marker gene in the HSV-tk vectors. These results demonstrate that in vitro HSV-tk gene transfer in 9L tumor cells, but not in vivo gene transfer, followed by GCV treatment, is able to cure rats at a rate that is higher for subcutaneous than for intracerebral tumors.

Animals↗
PubMed1996

Cerebellar hypermetria associated with a selective decrease in the rate of rise of antagonist activity.

Classically, cerebellar hypermetria observed during fast and accurate movements is ascribed to a delayed onset of the electromyographic activity of the antagonist muscle. We describe here 3 patients presenting a late-onset cerebellar degeneration and exhibiting a hypermetria during their fast and accurate movements in spite of a normal onset latency of the antagonist activity. Hypermetria was found to be due to a slower rate of rise of the antagonist activity.

Adult↗
PubMed1996

Slow increase of homovanillic acid in cerebrospinal fluid after levodopa administration.

Concentrations of major catabolites of dopamine were followed in the ventricular cerebrospinal fluid (CSF) in five patients undergoing intracranial pressure monitoring for chronic hydrocephalus. Determinations were made every 2 h following the administration of carbidopa/levodopa 25/250 mg (one Sinemet capsule) given 8 h apart. The rise of homovanillic acid (HVA) concentrations was slow and progressive, reaching the level of statistical significance (p < or = 0.01) only 8 h after the second administration of Sinemet. The rise in 3,4-dihydroxyphenylacetic acid (DOPAC) was faster than the rise in HVA, with the peak value detected 4 h after the first administration of Sinemet. These data are interpreted as a confirmation, in humans, of a slow pool of exogenous levodopa, previously demonstrated in animal studies.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Prognostic value positron emission tomography with [18F]fluoro-2-deoxy-D-glucose in the low-grade glioma.

OBJECTIVE: The natural history of the supratentorial low-grade glioma (LGG) of the adult is variable, and its malignant transformation is hardly predictable. Because positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG) has prognostic value in high-grade gliomas, this study was designed to search for a possible relationship between glucose metabolism and risk of malignant evolution in LGGs. METHODS: Positron emission tomography with FDG was performed in 28 patients with LGGs (22 at the time of diagnosis and 6 after the diagnosis). A metabolic grading system based on the visual inspection of the positron emission tomographic images was used. RESULTS: In 19 patients, no area of FDG uptake higher than in the white matter was detected (metabolic Grade 1). All of those patients were alive at the end of the follow-up period. Only one of the patients presented a histological modification 7 months after the diagnosis. Nine patients presented areas of increased FDG uptake (metabolic Grade 2 or 3). Those areas were found in the tumor area in eight patients and in an area of radionecrosis in one. Of the nine patients with FDG "hot spots," six died, two had recurrence but were alive at the end of the follow-up period, and the patient with radionecrosis had no signs of recurrence. CONCLUSIONS: The presence of areas of increased FDG uptake in a histologically proven LGG predicts, in most cases, a deleterious evolution. This metabolic feature, detectable with a noninvasive procedure, may provide a clue to cellular changes, announcing malignant transformation in a tumor that retains the histological features of an LGG. Protocols with aggressive therapeutic strategies in this situation should be considered for evaluation.

Adolescent↗
PubMed1996

Analysis of ballistic movements in ataxic hemiparesis following a pontine stroke.

Although cerebellar-like ataxia is a well known component of the ataxic hemiparesis (AH), the mechanism of hypermetria in AH has not been established. We describe a patient presenting a left AH following a right pontine infarction. We investigated the ballistic flexion movements of both wrists and the associated agonist and antagonist electromyographic (EMG) activities, before and after addition of inertial loads. At the time of motion analysis, neurological examination showed cerebellar-like dysmetria of the left side but the patient had recovered a normal strength. In the basal state (without addition of loads), movements of the left wrist were hypermetric. The duration of the agonist EMG activity was prolonged and the onset latency of the antagonist EMG activity was not delayed. Moreover, when a mass was added, the hypermetria was unchanged because the patient was unable to adapt appropriately neither the agonist, nor the antagonist EMG activity. We suggest that the hypermetria was due to an imbalance between the duration of the agonist EMG activity (the launching force) and the duration of the antagonist EMG activity (the braking force).

Aged↗
PubMed1996

Neuro-oncology.

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Astrocytoma↗
PubMed1996

[Mechanism of hypometria caused by pontocerebellar infarction].

By contrast to cerebellar hypermetria, the pathophysiology of cerebellar hypometria associated with a focal lesion is poorly understood. We describe a patient presenting an ischemic stroke involving the left lateral pons and middle cerebellar peduncle and exhibiting severely hypometric ballistic movements of the left wrist. Hypometria was associated with two distinct abnormalities of the triphasic electromyographic (EMG) pattern: a prolongation of the duration of the antagonist EMG activity and a reduced intensity of the agonist EMG activity. The first mechanism has been described previously in patients with a cerebellar disease and exhibiting hypometria, but not the second. The concomitant presence of these two elementary mechanisms contributed to the severity of hypometria in our patient. Moreover, this case illustrates that the integrity of the crossed pontocerebellar fibers passing through the middle cerebellar peduncle is necessary to generate an adequate agonist EMG activity.

Cerebellopontine Angle↗
PubMed1995

Recovery of hypermetria after a cerebellar stroke occurs as a multistage process.

In a prospective study, we repeatedly recorded fast goal-directed wrist movements of 8 patients who had experienced an acute cerebellar hypermetria due to a stroke and who had subsequently recovered clinically. Movements and the associated agonist and antagonist electromyographic (EMG) activities were recorded before and after addition of inertial loads. Four stages characterized the recovery process. At stage 1, hypermetria was present in the basal state and was not modified by the addition of inerital loads. At stage 2, hypermetria, which was present in the basal state, was enlarged by mass addition. At stage 3, hypermetria was absent in the basal state, but was revealed by an inertial load increase. At stage 4, as in healthy subjects, there was no hypermetria without or with addition of inertial loads. At stage 1, the patients presented several defects. (1) Facing an increased inertia, they could not increase their agonist EMG activity. (2) The onset latency of their antagonist EMG activity was delayed. (3) Facing an increased inertia, they could not increase their antagonist EMG activity. Among these three defects, the first disappeared at stage 2, the second at stage 3, and the third at stage 4.

Adult↗
PubMed1995

Peripheral and central pharmacokinetics of apomorphine and its effect on dopamine metabolism in humans.

Apomorphine is a dopamine receptor agonist increasingly used in the treatment of Parkinson's disease (PD). In the present study, we examined the plasma and ventricular cerebrospinal fluid (CSF) pharmacokinetics of apomorphine as well as its effects on dopamine metabolism in six patients (one woman and five men, mean age 79.5 years) without evidence of PD who underwent 48-h intracranial pressure monitoring for suspected normal pressure hydrocephalus. Maximal plasma apomorphine concentration (25.04 ng/ml) is found 20 min after subcutaneous injection (50 micrograms/kg), and the mean area under the curve is 1,439.37 ng/ml for 120 min. In contrast to plasma values, the maximal ventricular CSF apomorphine concentration (1.08 ng/ml) is found 30 min after injection and the mean area under that curve is 7% of that of plasma (96.69 ng/ml for 120 min). Apomorphine administration causes a significant reduction in ventricular CSF concentrations of dopamine and of its major metabolites sulfoconjugated dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). This effect starts 10 min after the injection of apomorphine, is maximal after 30 min (free dopamine, -30%; sulfoconjugated dopamine, -28%; HVA, -21%; DOPAC, -31%) and is still present, although to a lesser extent (-5 to -10%), 120 min after the injection of apomorphine. This study shows that in humans a dose of apomorphine commonly used in PD causes significant inhibition of dopamine metabolism lasting > 120 min. In addition to their symptomatic effects, dopamine agonists such as apomorphine may play a role in preventing or slowing the neurodegeneration in PD by autoreceptor-mediated inhibition of dopamine metabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effect of pergolide on endogenous and exogenous L-DOPA metabolism in the rat striatum: a microdialysis study.

We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergolide, a mixed D1/D2 dopamine (DA) receptor agonist with predominant D2 action in vivo, on the biotransformation of endogenous and exogenous L-DOPA. Levels of L-DOPA, DA, DOPAC, HVA and 5-HIAA were measured by high performance liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 47%, 65% and 70% decrease in basal striatal extracellular (EC) levels of DOPAC, HVA and DA, respectively. L-DOPA (100 mg/kg, i.p.), injected 2 hours after carbidopa, produced significant increase in EC levels of L-DOPA, DOPAC, HVA and DA in rats with and without local perfusion of 10(-4) M pergolide. The DOPAC peak value was lower and was reached 60 minutes later in the group with pergolide. This study demonstrated inhibitory effects of pergolide on endogenous DA release and influence of pergolide on exogenous L-DOPA biotransformation.

Animals↗
PubMed1995

PET findings in a brain abscess associated with a silent atrial septal defect.

Brain abscesses are classical complications of congenital heart disease (CHD) in children and adolescents. This association is rarely observed in adults. We report a 46-year-old man presenting a fronto-parietal abscess associated with an asymptomatic atrial septal defect. Positron emission tomography (PET) study revealed high uptake of L-[methyl-11C]methionine ([11C]methionine) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) around the brain abscess. We suggest (1) to exclude a silent cardiac malformation in the presence of a cerebral abscess of unknown source occurring in adults; (2) to consider the diagnosis of brain abscess in cases of high uptake of [11C]methionine and FDG in relation to a brain lesion.

Biopsy↗
PubMed1995

Basal ganglia and frontal lobe glucose metabolism. A reproducibility positron emission tomography study.

Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) is frequently used to study the metabolic correlates of movement and mental disorders. These studies generally focus on changes in the frontal cortex and the basal ganglia. The reproducibility of glucose metabolism estimates in these structures was tested in 13 normal subjects studied at rest using a standard and simple protocol. A reproducible dorsoventral metabolic gradient was demonstrated in the frontal cortex. Such a gradient was not present in the basal ganglia when the upper region of interest in the caudate nucleus, where the lower metabolic rate of glucose was probably attributable to partial volume effects, was not considered. Absolute values of glucose metabolic rates varied by 6.4 to 12.5% in the frontal cortex and by 6.8 to 14.7% in the basal ganglia. Variations in normalized values in the basal ganglia ranged from 4.0 to 8.6%. The number of subjects required to detect statistical differences in group comparison or in test-retest studies was calculated for different anticipated levels of change. With the variability detected in this experiment, less than 10 subjects were expected to be sufficient to detect a 15% change in most regions and in both types of studies.

Adult↗
PubMed1995

Alien hand syndrome without a corpus callosum lesion.

A 58 year old right handed woman developed a left alien hand syndrome after a right capsulothalamic haemorrhage with mesencephalic extension. No lesion was detected in the corpus callosum. Positron emission tomography suggested that right cortical dysfunction might account for the absence of recognition of the left hand whereas involuntary motor activity was attributed to the lesion itself. This case shows that the alien hand syndrome is not always the expression of a disconnection syndrome and may occur after a large, strategically located, posterior lesion.

Corpus Callosum↗