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Biomedical subjects

J Rousseau

Publications and source records attributed to J Rousseau.

At least 55 records · Page 3Linked to original sources

[Intraoperative radioisotope detection: review of the acquired experience and perspectives].

Intraoperative radio-isotope detection is an old idea which has been recently revived following the development of new detectors. The authors describe two points of view concerning this technique: external detection or surface detection. Based on the experience of more than 250 cases, they review the current status of the indications for ttris technique in endocrine surgery. They discuss the prospects of this technique in the light of the development of nuclear medicine and the basic requirements of surgery: new tracers and intraoperative scintigraphy.

Adrenal Gland Neoplasms↗

[Parental communication and support perceived in families of suicidal and non-suicidal adolescents].

This study focuses on two family-related variables linked to the issue of teenage suicide, namely communication and parental support. The purpose of the study is to compare the perceptions of suicidal and non-suicidal teenagers with those of their parents in order to better understand the relation between these variables and the issue of teenage suicide. Results confirm that communication and parental support represents a problem in families with suicidal teenagers. These dimensions are perceived more negatively by the latter subjects in comparison to the control group. In addition, the variations in perception between the adolescent and his or her parents are much greater in families with suicidal teens. This data supports the usefulness of family interventions when family problems are identified during detection measures or when counseling is requited by a suicidal teenager.

Adolescent↗

A miniature cesium iodide-photodiode detector for ambulatory monitoring of left ventricular function.

The physical characteristics of a portable nonimaging scintillation probe system for continuous ambulatory monitoring of the left ventricular function are described. The detector of the equilibrium radionuclide labeled blood pool is a single cesium iodide (CsI) crystal coupled to a silicium photodiode and interfaced to a microcomputer. The spatial properties of this small CsI crystal (1 x 1 x 1 cm3) were evaluated with various single-hole collimators. Linearity was studied in nonattenuating medium. Saturation began at 3000 cps, count loss was 10% at 4000 cps, maximal count rate was 24,000 cps. In attenuating medium, isocount curve of 5% of the maximal count rate was 100 mm deep and 160 mm wide. The most appropriate tested lead collimator to record the global ejection fraction of the left ventricle was a disc-shaped (thickness 5 mm, diameter 41 mm) single-hole (proximal aperture 8 mm, distal aperture 18 mm) collimator. Sensitivity was similar to the sensitivity of a sodium iodide nuclear probe. The detection performance appeared comparable to other available detector systems. Our results indicate that such a CsI-photodiode probe is a promising candidate for left ventricular function monitoring. The application to an ambulatory multicrystal detector system is presented and discussed.

Biophysical Phenomena↗

Technical note: magnetic resonance imaging of agarose gel phantom for assessment of three-dimensional dose distribution in linac radiosurgery.

An agarose gel phantom is used to evaluate the spatial distribution of the dose delivered by a linac radiosurgery device. Dependence of the absorbed dose on the T1 relaxation time is checked. T1 magnetic resonance images show the close correspondence between the actual absorbed dose distribution and the dose distribution expected by the treatment planning.

Gels↗

Evaluation of a 99mTc-antimyosin kit for myocardial infarct imaging.

The Fab fragment of a mouse monoclonal antibody AM(3-48) that recognizes alpha and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain of human slow skeletal muscle myosin [CardioVisionTM] was labeled with 99mTc using stannous reductant in a simple, instant kit method. The infarcted heart uptake in dogs of 99mTc-AM(3-48)Fab' was compared with that of established radiopharmaceuticals routinely used for cardiac imaging in humans. The dog infarct was induced by bringing a catheter from the femoral artery to the coronary artery where an artificial blood clot was generated. The 99mTc-AM(3-48)Fab' preparation was selectively taken up by infarcted myocardium, resulting in diagnostic quality images of the infarcted area as early as 6 hour post-injection, rendering CardioVisionTM particularly useful for SPECT imaging. Good agreement was found between the images obtained with 99mTc-Pyrophosphate and those obtained with 99mTc-AM(3-48)Fab', while the infarcted area was clearly delineated as a cold spot with 99mTc-MIBI or 201 Tl-thallous chloride. The biodistribution of 99mTc-AM(3-48)Fab' was also studied in healthy and isoproterenol-infarcted rats, from which dosimetry values in man were extrapolated. The data indicate that the kidneys will receive the highest radiation dose and that they will be the main contributors to the total radiation burden, which was estimated at 0.005 rad/mCi.

Animals↗

High-resolution PET imaging and quantitation of pharmaceutical biodistributions in a small animal using avalanche photodiode detectors.

UNLABELLED: The feasibility of high-resolution PET using BGO-avalanche photodiode detectors for in vivo imaging and quantitation of the biodistribution of radiopharmaceuticals in small animals is demonstrated. A prototype PET camera consisting of two scanning arrays of eight EG&G C30994 solid-state scintillation detectors was used to simulate a 310-mm diameter dual-ring animal tomograph having a 130-mm port and three imaging slices, each about 3.5 mm thick. The spatial resolution (FWHM) is 3 mm or less, isotropic and uniform throughout the 120-mm diameter field of view. METHODS: Female Fischer 344/CRBL rats implanted with subcutaneous mammary adenocarcinoma tumors were injected with copper-tetrasulfophthalocyanine (CuPcS4), a potential sensitizer for the photodynamic therapy of cancer, labeled with 64Cu (T1/2 = 12.7 hr, beta +:19%). RESULTS: In spite of the low specific radioactivity of 64Cu and other inherent limitations, organs such as the liver, kidneys and the tumor could be resolved with sufficient detail for their separation and quantitation. Apart from the tumor, agreement was obtained between the biodistributions measured by PET and by scintillation counting. The discrepancy for the tumor measurement results from averaging the radioactivity over the entire tumor volume when, in fact, CuPcS4 does not completely penetrate the tumor. This incomplete penetration is noted on the PET images. CONCLUSIONS: PET based on avalanche photodiode detectors provides an accurate measurement of target organ and tumor tissue concentrations. These preliminary results demonstrate the potential of very high resolution PET for biodistribution studies in small animals.

Animals↗

2- and 4-fluorinated 16 alpha(-)[125I]iodoestradiol derivatives: synthesis and effect on estrogen receptor binding and receptor-mediated target tissue uptake.

The effect of 2- and 4-fluoro substitution on the estrogen receptor-mediated tissue localization of radioiodinated 16 alpha-iodoestradiol (16 alpha-IE2) and its 11 beta-methoxy analogue (11 beta-OMe-16 alpha-IE2) was evaluated. Electrophilic substitution of estrone or 11 beta-methoxyestrone with N-fluoropyridinium salt gave the 2- and 4-fluoro derivatives which were subsequently converted to the 3,17 beta-enol diacetate and brominated to yield exclusively the 16 alpha-bromo analogues. Epimerization gave the corresponding 16 beta-bromoestrones which were reduced to the 17 beta-hydroxy derivatives. Halogen exchange with NaI or Na[125I]I provided the A-ring fluorinated 16 alpha-iodoestradiols. The 4-F analogue exhibited higher affinity for estrogen receptors than the corresponding 2-F analogue, and these differences were more pronounced at higher incubation temperatures. Biodistribution studies in immature female rats showed that 4-fluoro substitution had only a moderate effect on receptor-mediated tissue uptake of the parent molecules whereas 2-fluoro substitution resulted in strongly diminished tissue specificity. The lower target selectivity of the 2-F, compared to the 4-F, analogue correlates to some extent with their different receptor binding properties; however, the rate of catabolism may also be involved. Differences in blood clearance further accentuated the localization properties to yield particularly high uterus to blood ratios in the case of the 4-F-11 beta-OMe-16 alpha-IE2, suggesting the potential of the analog labeled with 123I as a radiopharmaceutical for receptor imaging in nuclear medicine. The isopotential maps of the fluorinated steroids, obtained via semiempirical computer modeling on the molecular structures, show striking differences between the 4-F and 2-F derivatives reflecting their varying biological properties.

Animals↗

Synthesis of A-ring fluorinated derivatives of (17 alpha,20E/Z)-[125I]iodovinylestradiols: effect on receptor binding and receptor-mediated target tissue uptake.

We have prepared a series of 2- and 4-fluoro derivatives of the isomeric (17 alpha,20E)- and (17 alpha, 20Z)iodovinylestradiols (IVE2) and also the analogs substituted with either a 7 alpha-methyl (7 alpha-Me-IVE2) or 11 beta-methoxy group (11 beta-OMe-IVE2) and evaluated their in vitro and in vivo properties. Electrophilic substitution of the estrone derivatives with N-fluoropyridinium salt gave the 2- and 4-fluoro analogs which were subsequently converted to the 17 alpha-ethynyl derivatives. The tributylstannyl intermediates were obtained from the corresponding 17 alpha-ethynyl analogs using azobisisobutyronitrile or triethylborane as catalyst. All 12 products were also prepared as their no-carrier-added [125I]iodovinyl analogs via destannylation of the tributylstannyl precursors. Binding affinity for the estrogen receptor (ER) was in general higher for the 4-F derivatives as compared to the 2-F derivatives, while the 20Z isomers of the same compounds showed somewhat higher ER binding affinity as compared to the 20E isomers. The combination of an A-ring fluoro and 7 alpha- or 11 beta-substituent decreased ER binding affinity. Substitution of a fluoro atom at C-4 on either the 17 alpha-ethynylestradiol or isomeric 17 alpha-IVE2 enhanced the affinity of the parent molecule for the ER. A-ring fluorination of all other analogues tested had no effect or depressed ER binding affinity. Varying incubation conditions showed substantial differences in ER binding kinetics between the 20E and 20Z isomers. Tissue distribution in immature female rats showed that the highest uterus uptake and uterus to blood/nontarget ratios in the IVE2 series were obtained with the 4-F-(17 alpha,20Z)IVE2 isomer. The combination of A-ring fluoro and 7 alpha- or 11 beta-substitution decreased uterus uptake but had little or no effect on uterus to blood/nontarget ratios. The highest uterus to blood ratios were observed for the 4-F-(17 alpha,20E)11 beta-OMe-IVE2 (75 at 6 h and 125 at 12 h pi) reflecting rapid blood clearance and in vivo stability, as confirmed by the low levels of thyroid radioactivity. The lack of correlation between ER binding affinities and uterus uptake, and/or uptake ratios, suggests that other factors, including nonspecific binding and metabolic processes, also are involved in the tissue localization process. Our data suggest that 4-F substitution onto (17 alpha,20Z)IVE2 and (17 alpha,20E)11 beta-OMe-IVE2 enhances the potential of these compounds to function as SPECT imaging agents of ER-rich tissues.

Animals↗

7 alpha-Methyl- and 11 beta-ethoxy-substitution of [125I]-16 alpha-iodoestradiol: effect on estrogen receptor-mediated target tissue uptake.

The 7 alpha-methyl and 11 beta-ethoxy derivatives of 16 alpha-[125I]iodoestradiol were prepared via halogen exchange with 125I of the corresponding 16 beta-bromoestradiol precursors. The 16 alpha-bromo derivatives were obtained via halogenation of the analogous 17-enol acetate, epimerization to the 16 beta-isomer, and hydride reduction. Stereochemical assignments were based on high resolution 1H NMR. To evaluate the effect of the nature and stereochemistry of the 16-halo substituent on the relative binding affinity for the estrogen receptor, the analogous 16-chloro derivatives were also prepared. The highest binding affinities were observed with the 7 alpha-methyl-16 alpha-haloestradiols, particularly the bromo and chloro derivatives while the 16 alpha-iodo derivatives gave somewhat lower values. Both the 11 beta-ethoxy and 7 alpha-methyl-16 alpha-[125I]iodoestradiols localize in the uteri of immature female rats via a receptor-mediated process. Rapid blood clearance of the 125I-labeled 7 alpha-methyl derivative results in lower 125I uptake by the uterus as well as nontarget organs as compared to the 11 beta-substituted estradiol analogs. However, uterus to blood and nontarget ratios are more favorable for the 7 alpha-methyl-16 alpha-[125I]iodoestradiol as compared to the analogous 11 beta-ethoxy derivatives suggesting that this compound substituted with 123I may be useful for the in vivo imaging of estrogen receptor-rich breast tumors by single photon emission computerized tomography.

Animals↗

Bone mineral and fat measurement with a novel dual photon absorptiometer.

The authors have produced an original dual-photon absorptiometer, with specific algorithms, permitting real-time automatic bone recognition, to reduce examination time (to 5 min). It permits the simultaneous measurement of the mineral density of an area of bone (BMD), the fat percentage of the soft tissues (PFST) that surround it, and the variation in this percentage. It visually represents, on one and the same picture, freely defined in terms of dimension and definition, bone mineral distribution and fat mass distribution. The performances are analysed, using phantoms and taking ten control subjects, in the region of the femoral neck. The variations in PFST in the control subjects are compared with the measurements carried out in MRI in the same region. In all these control subjects, there is a regular decrease in PFST in this region along an upper external/lower internal axis. This decrease has been likened to a regression line, the slope of which, representing between -0.16 per cent of fat per cm and -1.7 per cent per cm, has a mean value of -0.81 per cent per cm. The BMD is thus reduced by 0-2.5 per cent, depending on the subjects.

Absorptiometry, Photon↗

Synthesis, receptor binding and biodistribution of the gem-21-chloro-21-iodovinylestradiol derivatives.

Radioiodinated 11 beta-methoxy-(17 alpha,20E)iodovinylestradiol (11 beta-OMe-IVE2) shows high estrogen receptor (ER)-mediated uterus uptake and good potential as an ER-imaging agent. In order to examine the tolerance of the ER for modification about the iodovinyl substituent, we prepared the (17 alpha,20Z-chloro)21-chloro-21-iodovinylestradiol (4a) and several derivatives featuring 11 beta-methoxy (4b), 11 beta-ethoxy (4c) or 7 alpha-methyl (4d) substituents. All gem-dihalogen derivatives 4a-d were prepared from the 17 alpha-chloroethynyl precursors. The intermediate chlorostannylvinyl derivatives were obtained using tri-n-butyltin hydride and palladium acetate catalyst. Compounds 4a and 4b were labeled with 125I via their corresponding tin intermediates and their tissue distribution was studied in immature female rats. Addition of a 21-Cl to the 17 alpha-ethynylestradiols reduced ER binding affinity, except for the 11 beta-substituted analogs which showed a pronounced increase. Surprisingly, addition of a 21-Cl to the (17 alpha,20E)IVE2 resulted in increased ER binding affinities and augmented ER-mediated uterus uptake, which may result from the pronounced increase in the dipole moment of the molecule. Thus, further modifications at the C-21 position of IVE2 are well tolerated by the ER. However, addition of the 21-Cl also resulted in increased radioiodine uptake by the thyroid, much slower blood clearance and lower uterus to blood/nontarget ratios, suggesting increased in vivo instability of the C--I bond of the gem-chlorine-iodine atoms which may reflect the increase in steric and electronic interference.

Animals↗

The value of variable number of tandem-repeat polymorphisms in cases of disputed paternity not resolved by conventional markers: two case reports.

Disputed paternity cases are routinely tested in the authors' laboratory for red cell antigen, plasma protein, red cell enzyme, and HLA polymorphisms. This report concerns two cases in which the above test results made exclusion of paternity doubtful. In one case, exclusion of paternity was based on one discrepancy in the Duffy blood group system only, a unique situation in the investigators' experience of more than 2500 cases; the investigators were, therefore, reluctant to use this as the only evidence of exclusion. In the other case, it was necessary to postulate the presence of a rare haplotype, MSu, in the MNS blood group system to explain paternity. It was therefore decided to investigate allelic variable number of tandem-repeat (VNTR) DNA polymorphisms in these disputed paternity trios. VNTR DNA typing convincingly excluded these accused men from paternity.

Blood Group Antigens↗

Frameless method of stereotaxic localization with DSA.

PURPOSE: To improve a method of stereotaxic localization with digital subtraction angiography that does not require use of a localization frame fixed to the patient's skull during examination. MATERIALS AND METHODS: An independent, low-cost, stereotaxic computing system was devised. Software programs used magnetic resonance images, computed tomographic scans, and digitized radiographs of plastic bone implants with head landmarks to establish reference trihedrons in each imaging system, transpose target coordinates from one system to another, adjust surgical instruments, help plan radiation surgery, and compute and display isodose curves. RESULTS: The geometric distortions of the image intensifier were corrected. Distortion problems of the conic projection were solved, and three-dimensional localization was achieved with only two associated front and lateral views. Accuracy to within 1 mm was achieved for the three coordinates. CONCLUSION: This frameless stereotaxic localization technique is highly accurate and reliable. The system allows maximum automation of examination procedures.

Angiography, Digital Subtraction↗

Approach, avoidance, and contact behavior of individually recognized animals automatically quantified with an imaging technique.

A low-cost system was developed that allows the assessment of the location and the direction of movements of two individually recognized animals in a social interaction. The program was validated by (i) assessing deliberately induced approach and avoidance movements of artificial objects, (ii) the effects of known differences in social behavior between differently treated rats, and (iii) repeatedly testing social behavior under similar circumstances to assess enhanced social contact due to being familiar with the arena. Movements toward and away from each other of individually housed versus group-housed animals, and of young versus aged animals, were analyzed by the system. The results obtained, demonstrated that in the case of randomly moving artificial objects specific approachers or avoiders could not be identified, whereas isolated and young rats showed more approach behavior than their respective controls. In addition, the algorithm applied for calculating relative approach and avoidance movements elucidated differences between groups that were not noticed by human observers. Social contact behavior of rats was assessed automatically. Habituation to the testing situation in repeated testing increased social contact behavior.

Aging↗

Synthesis, receptor binding and target-tissue uptake of carbon-11-labeled carbamate derivatives of estradiol and hexestrol.

Carbon-11-labeled estradiol and hexestrol derivatives were prepared via the reaction of [11C]ethylchloroformate with the 2- and 4-amino derivatives of estradiol, the 3'-amino derivatives of hexestrol, and the 1-aminophenoxy derivatives of hexestrol and 1-norhexestrol. The corresponding nonradioactive carbamates were prepared for chemical characterization and in vitro receptor binding assays. The positions of the substituents on the parent molecules were selected with a view to minimize interference with the receptor binding process. In spite of this, affinity for the estrogen receptor was strongly impaired for all carbamate derivatives. Likewise, in vivo, the [11C]carbamate analogs failed to localize in receptor rich tissue via an estrogen receptor mediated process.

Amines↗

[Role of echoencephalography in myelomeningocele].

Infants with myelomeningocele very often present cranio-cerebral anomalies such as Arnold Chiari malformation. Cranial ultrasonography allows early evaluation of these malformations and helps to detect complications in surgically treated children.

Arnold-Chiari Malformation↗