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Biomedical subjects

A Veyre

Publications and source records attributed to A Veyre.

At least 55 records · Page 3Linked to original sources
PubMed1992

Synthesis of potential 99mTc nitrido tumor imaging disposition in mice.

Several cationic or neutral technetium-nitrido complexes of Schiff bases [for which 5-methyl 3-(2-hydroxyphenyl methylene) dithiocarbazate (L1) was a prototype], bis-aminoethanethiol (BAT-TM) and macrocyclic amines were prepared. We report here, the synthesis and isolation of these TcNLn complexes from reaction mixtures by high pressure liquid chromatography or sephadex G25 column. In vivo tissue distribution studies were performed on tumor bearing mice (B16, EMT6, 3LL) after i.v. injection of 10-20 microCi of TcNLn. Although pharmacokinetic differences appeared between the three studied ranges, we did not obtain proof of any particular specificity to tumor tissues. Nevertheless, the complexes were very stable and some of the ligands could be used as chelators after linking side chains or groups inducing specific tumor localization.

Animals↗
PubMed1991

The lymphatic drainage of the human ovary in vivo investigated by isotopic lymphography before and after the menopause.

The authors report 14 lymphoscintigraphies of the ovary, 8 before and 6 after the menopause. Injection of colloid labeled with technetium 99 m with elective lymphatic absorption was made into the mesovarium under laparoscopic control. Frontal and lateral images of the lymphatic drainage were made with a gamma camera 4-6 h after injection. Even in this short preliminary series, the premenopausal women showed major local and regional lymphatic circulation with drainage to the lumbo-aortic and pelvic nodes. After the menopause the lymphatic flow decreased and drainage was essentially by the aorto-lumbar nodes.

Adult↗
PubMed1991

Comparison of the myocardial distributions of 201Tl and 99Tcm-MIBI on SPECT images.

The distributions of 201Tl and 99Tcm-MIBI on stress images were quantitatively measured in a series of 15 patients presenting with documented coronary artery disease. Following two sequential, one-week apart, peak-exercise injections of either 74 MBq of 201Tl or 370 MBq of 99Tcm-MIBI, tomographic views of the myocardium were reconstructed and two thick, central short-axis sections were divided into nine sectors. A sector was considered as showing a defect if its relative activity was lower than 30, 40, 50 or 60% of the highest level of activity in the 18 sectors. Results demonstrate that there were more defects with 201Tl than with 99Tcm-MIBI. However, the difference disappeared if the inferior wall was not included. These results suggest that depth attenuation could be, at least partly, responsible for the higher rate of positive results observed in single photon emission computed tomography with 201Tl than with 99Tcm-MIBI.

Adult↗
PubMed1991

Disposition and metabolism of acetylcholinesterase reactivators 2PAM-I, TMB4 and R665 in rats submitted to organophosphate poisoning.

1. The dispositions of the acetylcholinesterase reactivators: 2PAM-I, TMB4 and R665, labelled with 14C on the oxime group, have been studied in normal rats and rats poisoned by the organophosphates Soman and A4. 2. For all three compounds, radioactivity was eliminated mostly in the urine (60-90% dose in 24 h). Faecal elimination was low (5.8-17.2% in 72 h). 3. All three compounds concentrated in kidney, but only 2PAM-I and R665 concentrated in liver. TMB4 and R665 concentrated in mucopolysaccharide-containing tissues such as cartilage and intervertebral disc. Other tissues were weakly and uniformly labelled. Soman poisoning does not modify the kinetic parameters of both compounds, but A4 poisoning increases 2PAM-I tissue concentration. 4. Chromatography of urine and plasma showed only unchanged 2PAM-I, TMB4 and R665 in both healthy and poisoned animals. Despite the high concentration of 2PAM-I and R665 in liver, these oximes are not metabolized.

Acetylcholinesterase↗
PubMed1991

Reorientation of the left ventricular long-axis on myocardial transaxial tomograms by a linear fitting method.

A method is described for reorientating the left ventricular (LV) long-axis from myocardial transaxial tomographic data. On a midventricular transverse slice and on a midventricular sagittal slice, the apical and basal limits are selected successively by the operator. The linear activity profiles between these two limits are plotted line by line. In each profile, the two points with the maximum counts in the septal and lateral walls on the transverse slice, or in the anterior and inferior walls on the sagittal slice, are detected. The intermediate point with the minimum counts is then determined. The set of points with minimum counts are fitted by a straight line using the least squares method. This line is taken as the LV long-axis. In a series of 15 cases with stress-delayed 201Tl SPECT, the reproducibility of the reorientation with this semi-automatic method was compared with manual selection of the LV long-axis. In all patients, a successful reorientation was obtained with the present method. The reproducibility was significantly better with the semi-automatic method than with the manual selection of the LV long-axis.

Adult↗
PubMed1991

[Validation of an ultrasonographic method of gastric emptying measurement in men].

Our purpose was to validate an ultrasonographic technique based on the assessment of the gastric antrum. Sixteen patients presenting with various functional disorders were studied by ultrasound on two occasions. Ten healthy volunteers were simultaneously studied by scinti- and ultrasonic scans. After an overnight fast, the healthy subjects ingested a 2,000 kJ test meal containing 150 microCi of 111In DTPA in 250 ml orange juice and 3 mCi of 99m Tc sulfur colloid in chicken liver. Using an ultrasound scanner fitted with a 3.5 MHz transducer, the area of the gastric antrum section was always measured in the same plane. Ultrasonographic measurement of gastric emptying rate was feasible in all of the 10 healthy subjects and in 14 of 16 selected patients. The ultrasonographic method was reproducible, and repeated t 1/2 measurements in 14 patients correlated well (95.3 +/- 27.9 vs 99.2 +/- 20.6 min; r = 0.70, P less than 0.001). The t 1/2 measurement was 39.4 +/- 7.7 min with the ultrasonographic method, and correlated well with 36.4 +/- 4.3 min for the t 1/2 measurement of the liquid phase with the scintigraphic method. We conclude that the ultrasonic method was reproducible and could be used for assessment of gastric emptying rate when repeated measurements are necessary, especially in pharmacologic studies.

Adult↗
PubMed1990

DNA damage induced by a new 2-chloroethyl nitrosourea on malignant melanoma cells.

Different biological aspects of a novel 2-chloroethyl nitrosourea derived from cysteamine, N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]-N'- nitrosourea (CMSOEN2), were studied. Drug-induced cytotoxic effects, uptake kinetics, DNA damage, and O6-alkylguanine-DNA alkyltransferase activity were determined in 3 melanoma cell lines: the murine B16 and 2 human metastatic-derived cell lines (M4 Beu and M3 Dau). We found that radioactivity uptake and incorporation in acido-precipitable material was inversely proportional to cell drug viability. The highly CMSOEN2-sensitive B16 line showed the lowest total radioactivity uptake. In fact, among the melanoma cell parameters studied, 3 of them were well correlated: (a) cytotoxicity as reflected by the colony-forming assay; (b) DNA cross-link frequency estimated by the alkaline elution technique; and (c) O6-alkylguanine-DNA alkyltransferase activity (Mer phenotype), defined as the ability of cell extracts to remove O6-methylguanine from N-methyl-N-nitrosourea-alkylated DNA. The 2 human cell lines (M4 Beu and M3 Dau), the most resistant to the cytostatic drug effects, showed little or no ability to form DNA lethal cross-links. These results correspond to the higher O6-alkylguanine-DNA alkyltransferase activity found in human-derived cell lines compared with that present in murine B16 cell lines. This study confirms that the cell content in this repair DNA protein is certainly one of the important factors implicated in the variability of response to 2-chloroethyl nitrosourea treatment observed in a number of established malignant cell lines. It has been shown that pretreatment of derived cell lines with methylating agents (N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine) or O6-methylguanine used as a free base, increased cytotoxic effects of this class of anticancer agents, likely by saturating receptor sites (sulfhydryl groups) of this specific DNA repair enzyme. Nevertheless, in preliminary Phase I and II clinical trials, 2 patients who had been treated with multiple chemotherapies including alkylating agents [1-(2-chloroethyl)-3- cyclohexyl-1-nitrosourea, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide, platinum derivatives], presented complete or partial remission after CMSOEN2 treatment. Our results raise the question of the exact relation between the Mer phenotype determined in derived murine or human cultured cells and that directly observed on surgically excised tumors in cancer patients. The original Mer phenotype could be modified by cell culture conditions since it has been shown that O6-alkylguanine-DNA alkyltransferase activity is widely distributed between normal and tumoral tissues without any real difference.

Antineoplastic Agents↗
PubMed1990

Disposition and metabolism of two acetylcholinesterase reactivators, pyrimidoxime and HI6, in rats submitted to organophosphate poisoning.

1. The dispositions of two acetylcholinesterase reactivators, pyrimidoxime and HI6, labelled with 14C on the oxime group, have been studied in normal rats and rats poisoned by the organophosphates Soman and A4. 2. For both compounds, and for healthy and poisoned rats, radioactivity was eliminated essentially in the urine (85% dose in 24 h). Faecal elimination was low (4% in 72 h). 3. Both compounds were concentrated in kidney and mucopolysaccharide-containing tissues such as cartilage and intervertebral disc. Soman and A4 poisoning do not modify the kinetic parameters of pyrimidoxime, but A4 poisoning increases HI6 tissue concentration. 4. Chromatography of urine and plasma showed only unchanged pyrimidoxime in both healthy and poisoned animals. In contrast, HI6 in plasma and urine was strongly degraded by scission of the quaternary ammonium bond, and formation of 2-pyridine aldoxime.

Acetylcholinesterase↗
PubMed1990

[Adaptation of the left ventricle function to exercise in aortic stenosis. Study with cavitary angioscintigraphy].

Eighteen patients with pure aortic stenosis without coronary artery disease underwent equilibrium radionuclide angiography to evaluate the adaptation of their left ventricular function to exercise. The left ventricular ejection fraction, peak left ventricular ejection, and fillings, and their timing were calculated from time-activity curves and their first derivatives at rest and at the maximum of exercise. There were no clinical complications. The ST segment and T wave changes of 14 patients were accentuated and 3 patients developed anginal pain. The ejection fraction was normal at rest and did not change significantly during exercise. The peak ejection did not vary but peak left ventricular filling was prolonged by exercise. There was a correlation between peak ventricular ejection at rest and the aortic valve surface area at catheterisation. This isotopic parameter was inversely correlated with LVEDP. There was a close correlation between age and peak ventricular filling on exercise. The variation between resting and exercise values of this parameter was inversely correlated with age. This study shows that exercise stress testing can be undertaken without risk in patients with aortic stenosis. The results of radionuclide angiography show that peak left ventricular ejection is a valuable parameter. The interpretation of the diastolic parameters is however more difficult because they are age-related.

Adult↗
PubMed1990

[Perspectives of scintigraphic diagnosis of malignant lymphoma using a new radiopharmaceutical].

In the sequence of our studies on radiopharmaceuticals for malignant melanoma detection the results were most promising for the possible use of 125I or 123I-N-(2-diethyl amino ethyl)4-iodobenzamide. The biodistribution in mice bearing melanoma either human or animal from 4 to 24 hrs. post i.v. injection showed high uptake in tumor tissue together with relatively low uptake in muscle, brain, lung and liver. Scintigraphic images of the tumor obtained at the same times confirmed that melanoma detection was very promising.

Animals↗
PubMed1990

Unusual features of neonatal thyroid function in small-for-gestational-age lambs. Origin of plasma T4 and T3 deficiencies.

Thyroid function was studied in small for gestational age (SGA) or control newborn lambs. Neonatal changes in plasma concentrations of TSH, T3, rT3, total and free T4 were monitored, and thyroid scintigraphs were performed. Responsiveness of the hypothalamic-pituitary-thyroid axis to cold exposure and TRH or TSH administration was assessed. In addition, T4 and T3 kinetic studies were performed. In agreement with results obtained in babies, plasma T3, total T4 and free T4 concentrations were depressed in low birth weight animals, whereas TSH and rT3 levels were not affected. Thyroid size expressed relatively to the body weight was higher in SGA animals, thus suggesting that a partial compensation for low thyroid hormone levels had occurred during the fetal life. Plasma TSH and T4 concentrations increased by a same extent after exposure to cold and TRH or TSH administration in SGA and control lambs; however, the rise in T3 levels was depressed in the former in all stimulation tests. T3 and T4 production rates were similar in the two experimental groups. In SGA lambs, the metabolic clearance rate and the total distribution space of these two hormones were significantly increased; the fast T3 pool was higher, and the slow T3 pool lower than in control animals. All these results demonstrate that, despite low circulating thyroid hormone concentrations, SGA lambs are not hypothyroid. An increased T4 and T3 storage in the extravascular compartment is probably the major factor involved in the occurrence of this plasma deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Gastrointestinal scintigraphy with 99mTc-DTPA labeled tablets in fed and fasting subjects.

The in vitro and in vivo dissolution of a sustained release theophylline formulation labeled with 99mTc-diethyltriaminepentaacetic acid (DTPA) has been monitored in six subjects with a scintillation camera. The study was performed in fasting conditions and was repeated after ingestion of a standardized meal. Results showed that the presence of food in the stomach dramatically increased the oesoduodenal transit time of the tablet (74 +/- 27 min vs 352 +/- 77 min, P less than 0.001) but did not modify the biodisponibility of theophylline. This study is another example when scintigraphy can be of definite value in pharmacokinetics.

Adult↗
PubMed1989

Metabolism of a new radioprotector; S-acetyl-N-glycyl cysteamine. II. Main tissue metabolites in mice bearing EMT6 tumours.

1. The major tissue metabolites of the radioprotector S-acetyl-N-glycl cysteamine (I) labelled with 14C on the cysteamine group, were quantified and identified in normal tissues and EMT6 tumours implanted in mice, by chromatographic comparison with authentic reference compounds. 2. In all tissues the radioprotector undergoes rapid deacetylation and hydrolysis leading to the formation of cysteamine, which is the main metabolite involved in radioprotection. A major part of this metabolite is reversibly inactivated by binding to endogenous SH. 3. The differential radioprotection of healthy tissues versus EMT6 tumour is explained both by a lower uptake of radioprotector, and a weaker deacetylation and hydrolysis rate, in the tumour cells.

Animals↗
PubMed1989

Comparison between 180 degrees and 360 degrees data collection in technetium-99m MIBI SPECT of the myocardium.

In a series of 12 patients presenting with a single-vessel coronary artery disease and who were injected with 370 MBq of 99mTc-2-methoxyisobutylisonitrile at peak exercise, two consecutive single photon emission computed tomography (SPECT) data collections, i.e., 32 views of 30 sec during a 180 degrees rotation and 64 views of 15 sec during a 360 degrees rotation, were performed 1 hr later. In both cases, transverse sections were reconstructed using (a) a backprojection method with a ramp filter, (b) a correction for downscatter, (c) a correction for depth attenuation by the Chang method, or (d) both corrections. Each reconstructed myocardium was then divided into four short-axis sections which were radially divided into nine sectors. Sectors with an activity below 80% of the maximum were considered as abnormal. Sensitivity and specificity were calculated relative to a sector-by-sector theoretical anatomic distribution of the perfusion abnormalities. Results demonstrate that, of all situations, the best balance between sensitivity and specificity was achieved with the 180 degrees data collection and no correction at reconstruction. Using the 360 degrees data sampling technique mainly lowered the sensitivity in the patients with a circumflex or right coronary artery disease. It is concluded that there does not seem to be any definite advantage in performing a 360 degrees rather than a 180 degrees data collection in 99mTc myocardial SPECT.

Adult↗
PubMed1988

Metabolism of a new radioprotector; S-acetyl-N-glycyl cysteamine. I. Absorption, distribution and excretion metabolites in mice bearing EMT6 tumours.

1. The disposition of S-acetyl-N-glycyl cysteamine (I) labelled with 14C on the cysteamine group (label 1), the glycyl group (label 2) and the acetyl group (label 3) has been studied in mice bearing EMT6 tumours. 2. Label 1 was mainly excreted in urine (63.1% dose in 24 h). Label 2 elimination was both in urine (36.0% dose in 24 h) and in expired air as 14CO2 (12.1% dose in 24 h). Label 3 was essentially eliminated in expired air as 14CO2 (55.4% dose in 24 h). 3. Tissue distribution studies of label 1 and label 2 showed that concentrations in tissues were higher than blood concentration as early as 10 min after administration. Whichever label was used, only little radio-activity was found in EMT6 tumour and brain. 4. Analysis of the urinary elimination products showed the presence of unchanged I and of cystamine, N-acetylcystamine, N-acetyl-S-methyl cysteamine sulphoxide and taurine. I is a prodrug of cysteamine which is released after deacetylation and hydrolysis of the amide bond. A metabolic pathway is proposed for this new radioprotective agent.

Animals↗