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Biomedical subjects

J L Baulieu

Publications and source records attributed to J L Baulieu.

At least 19 recordsLinked to original sources

Cortical perfusion response to an electrical stimulation of the auditory nerve in profoundly deaf patients: study with technetium-99m hexamethylpropylene amine oxime single photon emission tomography.

Brain activation procedures associated with single photon emission tomography (SPET) have recently been developed in healthy controls and diseased patients in order to help in their diagnosis and treatment. We investigated the effects of a promontory test (PT) on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) in 7 profoundly deaf patients, 6 PT+ and one PT-. The count variation in the temporal lobe was calculated on 6 coronal slices using the ratio (Rstimulation-Rdeprivation)/Rdeprivation where R = counts in the temporal lobe/whole-brain count. A count increase in the temporal lobe was observed in all patients and was higher in all patients with PT+ than in the patient with PT-. The problems of head positioning and resolution of the system were taken into account, and we considered that the maximal count increment was related to the auditory cortex response to the stimulus. Further clinical investigations with high-resolution systems have to be performed in order to validate this presurgery test in cochlear implant assessment.

Adult

Estrogen receptor imaging with 17 alpha-[123I]iodovinyl-11 beta-methoxyestradiol (MIVE2)--Part I. Radiotracer preparation and characterization.

It is important to know the estrogen receptor rate in breast carcinoma management. Thus, an in vivo and atraumatic method would be very useful. Different ligands have been proposed for this. We present here the specific synthesis of 20E- and 20Z-17 alpha-iodovinyl-11 beta-methoxyestradiols and their biological characterization as estrogen receptor ligands. The two isomers were analysed by current chemical methods (NMR) and purified by HPLC. We carried out an in vivo study with 21-day-old Swiss mice to compare properties of the two ligands. The 20E-MIVE2 showed the best affinity for estrogen receptors, the uterus-to-blood ratio was 15-fold higher for the trans derivative. We enhanced the in vivo and in vitro properties of the 20E-MIVE2: the affinity constant was determined by Scatchard analysis, Kd = 16 x 10(-10) M, and biodistributions were performed with unlabelled estradiol pre-injection. We concluded that 20E-MIVE2 can be used for a feasibility study in patients with breast carcinoma.

Animals

Estrogen receptor imaging with 17 alpha-[123I]iodovinyl-11 beta-methoxyestradiol (MIVE2)--Part II. Preliminary results in patients with breast carcinoma.

17 alpha-[123I]Iodovinyl-11 beta-methoxyestradiol was injected into 19 women: group 1 (n = 8), initial evaluation of breast cancer; group 2, (n = 11) postoperative follow-up including 9 patients with bone metastases. The primary tumor (size: 8-10 mm) was visualized by breast tomoscintigraphy in 2/4 patients of group 1 with high estrogen receptor concentration (162-445 fmol/mg) and was not detectable in 4 patients with low estrogen receptor concentration (6-32 fmol/mg). Axillary lymph node metastases were detected in 1 patient of group 1 and in 1 patient of group 2. In 4 patients of group 2 with previous primary tumor containing estrogen receptors, MIVE2 uptake in bone metastases was demonstrated. MIVE2 scintigraphy is an original, specific and non-invasive method for breast cancer estrogen receptor imaging in primary and in metastatic tumors.

Adult

Synthesis and in vitro binding properties of halogenated analogues of GBR as new dopamine uptake carrier ligands.

We present the original synthesis of two halogenated analogues of the diphenyl piperazine GBR, bromo-GBR and iodo-GBR, as new dopamine uptake carrier ligands. The derivatives were purified by HPLC and chemically characterized. Bromo-GBR and iodo-GBR and iodo-GBR are potent inhibitors of [3H]GBR 12935 binding to rat striatal membrane, with Ki values of 116 and 113 nM, respectively. We prepared iodo-GBR labeled with iodide-125 from the brominated derivative and concluded that [123I]iodo-GBR could be a potential tool to explore the in vivo dopamine uptake carrier.

Animals

Scintigraphy with J001 macrophage targeting glycolipopeptide. A new approach for sarcoidosis imaging.

Scintigraphy with radiolabeled J001 as a ligand for macrophage targeting is a new approach for sarcoidosis imaging. J001 is a fully characterized acylated peptido-poly (1,3) galactoside isolated from Klebsiella membrane proteoglycans and able to bind electively recruited macrophages. Its physiochemical properties allow rapid absorption by the respiratory tract when this agent, labeled by 99m technetium, is administered as an aerosol. Images are obtained within 3 to 5 h after inhalation. In the present study, we determined the ability of J001 scintigraphy to localize areas of sarcoidosis involvement in 22 patients compared with gallium scanning in ten of them. Nineteen patients underwent bronchoalveolar lavage (BAL) and serum angiotensin-converting enzyme (ACE) assay. J001 scintigraphy was also performed on a control group of six patients with extrathoracic melanoma, in whom J001 scintigraphy was used to evaluate the cutaneous extent of the tumor and the lymph node involvement. In this control group, no fixation appeared in the thoracic area. In the sarcoidosis group, 18 positive results were observed. One stage 0 patient had a mediastinal fixation. Five of the six stage 1 patients had a fixation located in the mediastinum, the lungs, and the wrists. Five of the six stage 2 patients had positive foci located in the mediastinum or the lung areas and in the myocardium in one of them. Six of the nine stage 3 patients had positive J001 scintigraphy occurring in the lungs and/or the mediastinum. One patient had a fixation on the main bronchi. J001 scintigraphy and gallium scanning, performed in ten patients, were positive in seven of them. There were discrepancies between the BAL results and J001 scintigraphy, as well as between the ACE results and J001 scintigraphy. In conclusion, 99mTc-J001 scintigraphy appears to be a sensitive and rapid technique for the imaging of thoracic sarcoidosis at the three stages of the disease.

Adult

[Scintigraphic detection of gastrointestinal hemorrhage. Value and limitations].

A technetium-99m labelled red blood cell scintigraphy was performed in 51 patients with an unexplained gastro intestinal bleeding. Static images were acquired on the injection day then at 24 hours. Forty one patients had a positive scintigraphy. In 13 patients with a positive scintigraphy, on the injection day (5 cases) and later (8 cases), no intestinal bleeding was identified in spite of further investigations guided by scintigraphy. In 24 patients, with a positive scintigraphy on the injection day (20 cases) and later (4 cases), an intestinal lesion was identified and treated; data were confirmed in 19 cases: there were 15 colon lesions, localized on caecum in 10 cases and 4 small bowel lesions. Clinical value and limitations of the investigation are discussed. The scintigraphic localization is usually accurate if the abnormal focus activity is noticed on the injection day. It helps to guide further investigations of the bleeding site. This non invasive method should be performed more quickly to help to localize intestinal bleeding which poses a diagnostic problem.

Adolescent

Increment of brain temporal perfusion during auditory stimulation. Preliminary study with technetium-99m HMPAO SPET.

A study on the dynamic exploration of the auditory pathway is presented, in which technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPET) was used in volunteers with normal hearing. Changes in 99mTc-HMPAO distribution were calculated using a region of interest/whole-brain count ratio. The results showed a temporal perfusion increment of 17% (right) and 19% (left) during tonal supraliminar stimulation, which was significantly different from the control ROI. Sensitivity tests for the method were requested before any clinical application.

Acoustic Stimulation

[HMPAO radionuclide of temporal cortex in the study of deafness].

A new method of dynamic exploration of central auditory pathway is presented, using measurement of cortical temporal perfusion variations, during auditory stimulation (tonal stimulation in normal hearing patients, electrical stimulation with promontory test in profoundly deaf patients). This study shows a perfusion increment in normal hearing and deaf patients with positive promontory test, which doesn't exist in a patient with negative promontory test. Further development of this study could help for optimization of post implantation auditory results.

Acoustic Stimulation

Iodobenzamide for in vivo exploration of central dopamine receptors: evaluation in animal models of supersensitivity.

Iodobenzamide is a promising agent to investigate D2 receptors by SPECT in living human brain. In this work, we have evaluated this radiolabeled compound in two animal models of D2 receptors supersensitivity. In the first model, rats were treated chronically with haloperidol during three weeks (S.C. injection of 0.5 mg/kg/day). One week after the last day of treatment, they were I.V. injected with 125I-IBZM. In vivo specific binding study showed a 45 percent increase of 125I-IBZM fixation in the striatum of treated rats. In a second step of experiments, animals were unilaterally lesioned by a stereotaxic injection of 6-OHDA in the substantia nigra, 23 days before receiving 125I-IBZM. Autoradiographic analysis of coronal brain sections showed a 38 percent enhancement of 125I-IBZM in vivo binding in the striatum on the lesioned side as compared to the contralateral intact side; this increase occurred in striatal lateral area. These data demonstrate that 125I-IBZM is convenient to detect alterations of dopamine D2 receptors in vivo in the rat. Thus IBZM labelled with 123I can be a very useful imaging agent for the exploration of D2 receptors in pathological situations.

Animals

Iodoethylspiperone, a new potential agent for exploration of central dopamine D2 receptors: synthesis and preliminary in vivo study.

We synthesized a new spiperone derivative: iodoethylspiperone (IES) to perform dopamine D2 receptor exploration by SPECT. IES was prepared from a precursor: tosylethylspiperone, and characterized by i.r. and 1H-NMR analyses. [125I]IES was obtained with 80% yield. In vivo biodistribution in rats showed a high and specific uptake in the striatum. The uptake ratio between the striatum and the cerebellum reached a maximum value 4 h after injection (10.05 +/- 2.81). IES labeled with 123I should be a promising new agent to investigate D2 receptors in the living human brain.

Animals

[125I]MIBG uptake and release in different regions of the rat brain.

Radioiodinated m-iodobenzylguanidine [( 125I]MIBG) and tritiated norepinephrine [( 3H]NE]) uptake and release were compared, in different regions of the brain of the rat. The classification of the regions according to uptake was the same for both tracers:striatum greater than hypothalamus greater than hippocampus greater than cortex greater than brainstem. Tetrabenazine (TBZ), a granular monoamine uptake inhibitor reduced the uptake in the different regions. The inhibition rate was higher for [3H]NE uptake than for [125I]MIBG. The spontaneous release was the same for [125I]MIBG and [3H]NE and was the lowest in the striatum. The K+ stimulated release of [3H]NE was more complete than the release of [125I]MIBG and was the most important in the striatum. From these results, it is inferred that MIBG enters the brain tissue via NE uptake mechanisms. It appears that MIBG is stored in the chromaffin granules, as NE, but also in the cytoplasm. A modified molecule derived from MIBG which would cross the blood-brain barrier, would then appear as a potential scintigraphic marker of monoamine uptake, storage and release.

3-Iodobenzylguanidine

Diagnosis of medullary carcinoma of the thyroid (MCT) by calcitonin assay using monoclonal antibodies: criteria for the pentagastrin stimulation test in hereditary MCT.

A new calcitonin (CT) immunoradiometric assay, using anti-11-7 and anti-24-32 CT fragment monoclonal antibodies was evaluated and compared to classical RIA. The sensitivity was 2.5 ng/L, the normal basal level (n = 83) was lower than 10 ng/L, the response to pentagastrin stimulation in control subjects was absent in nine and between 10-30 ng/L in nine others. (mean, 15.4). In patients with renal failure the basal level was increased between 10-52 ng/L. In patients with medullary thyroid carcinoma (MTC; n = 28), the basal level was between 189-28,900 ng/L. A pentagastrin test was performed as screening for familial MTC in eight patients with confirmed MTC at subsequent surgery; the calcitonin peak was equal or greater than 38 ng/L. Large differences exist between CT levels measured by RIA and immunoradiometric assay. The latter method provides a greater sensitivity to pentagastrin test and allows a better identification of microcarcinoma in hereditary cases of MTC.

Adolescent

[The current role of lymphoscintigraphy in the study of lymphedema of the limbs].

After a brief review of the classical methodology and results of lymphoscintigraphy, the technique is considered in terms of an original kinetic study approach. Immediately after distal subcutaneous injection of a technetium colloid (rhenium sulfocolloid), 40 1-min serial images of the limbs are recorded followed 4 h after injection by recording of static images. The main abnormalities detected by scintigraphy concern the lymphatic vessels, nodes and interstitium. They reveal the presence of lymphedema and provide information about its mechanism, indicating, particularly in the case of primary lymphedema, whether there is predominant hyperplasia or hypoplasia in vessels or nodes. Synoptic study of the initial dynamic recording based on simple examination of serial images is difficult. Complementary data provided by activity curves determined from manually selected regions of interest (ROI'S) are of limited value since the ROI'S correspond to superimposed spatial structures. Two data-processing techniques--the condensed image (CI) and factorial analysis (FA)--were therefore applied to dynamic scintigraphic recordings in order to study lymphatic progress of the radiotracer in the legs. A complete dynamic series is described in two IC, one for each leg. The CI, obtained by mounting the 40 serial images in vertical strips 1 pixel in width, describes the spatial distribution of radioactivity along the leg during recording. Factorial analysis provides automatic extraction of pure kinetic components or factors from the dynamic series despite their spatial superposition. The factors are described by factorial curves and factorial images representing the spatial identity of the factor. Three-factor FA was applied successively to each leg.(ABSTRACT TRUNCATED AT 250 WORDS)

Arm

[Scintigraphic assessment of pulmonary deposition of pentamidine administered by aerosol].

Isotopic techniques enable to determine the best conditions to aerosolize pentamidine as a preventive treatment of pneumocystis. An original labelling technique of pentamidine isethionate has led into a feasibility study of pentamidine scintigraphy in the monkey, and then to a clinical study. A tracer dose of 2 mg of pentamidine isethionate was diluted into 200 mg of pentamidine mesylate. An ultrasonic nebulizer (TV 6000) and a jet nebulizer (Venticis II) were first compared in four baboons. With the two nebulisers the curves of pulmonary kinetic activity showed a peak 10-15 minutes after the beginning of inhalation and then a plateau. With the ultrasonic TV6000 the pulmonary dose was on average 0.8 mg or 0.4% of the pentamidine aerosolized and the gastric contamination 3.1%. With the Venticis II compressed air apparatus the amount of pentamidine delivered to the deep lung was a mean of 4.2 mg or 2.1% of the aerosolized dose whereas the gastric contamination was only 0.5%. The delivery of the aerosol by the ultrasonic inhaler TV 6000 was then compared with two compressed air inhalers Venticis II and Respirgard II in four patients infected with HIV virus who were submitted to a preventative therapy against pneumocystis. With the ultrasonic TV 6000 the pulmonary dose was 0.8 mg or 0.3%-0.5% of the dose of pentamidine aerosolized and the digestive contamination was 3.1%. The performance of the two compressed air nebulizers Venticis II and Respirgard II were similar. The amount of pentamidine delivered to the deep lung was respectively 12 and 14 mg or 6 and 8% of the dose of pentamidine aerosolized and the digestive activity was 0.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

The potential usefulness of condensed image processing of sequential lymphoscintigrams in patients with lymphedema.

Condensed image processing (CIP), a computerized technique of scintiscans that generates a vertical distribution of activity as a function of time in a single image, was applied to isotopic lymphoscintigrams of four patients with leg lymphedema. By "condensing" information gained from multiple images into a single image, CIP better evaluates ascending progression of radiolabeled colloid in peripheral lymph and better localizes stagnant areas. In "high lymph flow failure," CIP also depicts radioactive "bursts" suggestive of increased lymphatic truncal contractility. This data processing method improves interpretation of dynamic scintiscan recordings and seems ideally suited for evaluation of peripheral lymph kinetics.

Adolescent

Linkage analysis of hereditary thyroid carcinoma with and without pheochromocytoma.

The use of polymorphic DNA segments as markers for the gene for the multiple endocrine neoplasia (MEN) syndrome, type 2a, allows the identification of family members at high risk for developing medullary carcinoma of the thyroid and other tumors, especially pheochromocytoma. Several families have also been identified in which medullary thyroid carcinoma is inherited, but pheochromocytoma is not seen. We have analysed 18 families, 9 with MEN 2A and 9 with medullary carcinoma of the thyroid without pheochromocytoma, with probes specific for the pericentromeric region of chromosome 10 and conclude that the mutations for the two presentations are closely situated. Genetic heterogeneity of the susceptibility locus was not seen among this sample of 18 families. The genetic mutation for medullary carcinoma was in disequilibrium with the marker alleles of the two closely linked probes, IRBPH4 and MCK2. These data suggest that different mutant alleles of the same gene or closely linked mutations account for the variation in penetrance of pheochromocytoma in families with hereditary medullary thyroid carcinoma.

Adolescent