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Biomedical subjects

H N Wagner

Publications and source records attributed to H N Wagner.

At least 163 records · Page 9Linked to original sources

In vivo binding of 3H-N-methylspiperone to dopamine and serotonin receptors.

3H-N-methylspiperone (3H-NMSP) was used to label dopamine-2 and serotonin-2 in vivo in the mouse. The striatum/cerebellum binding ratio reached a maximum of 80 eight hours after intravenous administration of 3H-NMSP. The frontal cortex/cerebellum ratio was 5 one hour after injection. The binding of 3H-NMSP was saturable in the frontal cortex and cerebellum between doses of 10 and 1,000 micrograms/kg. Between 0.01 and 10 micrograms/kg the ratio total/nonspecific binding increased from 14 to 21. Inhibition of 3H-NMSP binding in the frontal cortex and striatum by ketanserin, a selective serotonin-2 antagonist, demonstrated that 20% of the total binding in the striatum was to serotonin-2 receptors and 91% of the total binding in the frontal cortex was to serotonin-2 receptors. Compared to 3H-spiperone, 3H-NMSP results in a much higher specific/nonspecific binding ratio in the striatum and frontal cortex and displays more than a two-fold higher brain uptake.

Animals↗

On estimating the loss of quantification in PET due to finite detector resolution.

In positron emission computed tomography, images are reconstructed from projection data of the slice. Such projection data are inherently subject to bias owing to the detection of coincident annihilation photons with detectors of finite resolution. The influence of these unavoidable effects on reconstructed data is reviewed and a straight forward method is outlined for calculating the loss of quantification of small objects owing to finite detector resolution. A sample calculation using idealized point spread functions is presented.

Brain↗

Comparison of transaxial resolution in 180 degrees and 360 degrees SPECT with a rotating scintillation camera.

Using circular 180 degrees and 360 degrees SPECT acquisition modes the transaxial resolution of line sources in air and water were measured at different positions in the field of view. With the 180 degrees acquisition mode, all line sources in air located off the axis of camera rotation (AoR) showed an oval distortion. This distortion was systematically related to the starting point of the rotating detector. On axis line sources in air were undistorted, regardless of the 180 degrees acquisition starting angle. The 360 degrees acquisition images of the line sources in air showed a similar effect but in a very mild form. In water, transaxial reconstructions of line sources (off axis) showed an enhancement of the oval distortion for both the 180 degrees and 360 degrees acquisitions. Computer simulations of the line source measurements were performed and correlated well with the experimental data. The line source results are explainable by the inherent depth dependent response of the scintillation camera. In clinical SPECT studies, distortions of this nature will be most appreciable with 180 degrees imaging of small organs that are located off the AoR.

Air↗

Monitoring effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on left ventricular function in patients with essential hypertension with a cardiac probe.

The effects of alpha-hANP on left ventricular function were studied with a cardiac probe in ten patients with essential hypertension. Our data showed that intravenous administration of alpha-hANP significantly elevated left ventricular function. At 5 min, the elevation of EF, RCO, ER, RSV, PFR were 13.23% (P less than 0.02), 12.7 (P less than 0.02), 0.618 (P less than 0.02), 0.133 (P less than 0.05), 0.283 (P less than 0.01), respectively. At 10 min, the increase of EF, ER, were 11.07% (P less than 0.02) and 0.233 (P less than 0.01), respectively. Atriopeptin significantly reduced systolic and diastolic blood pressure from 2 min to 20 min (P less than 0.001-0.05).

Adult↗

Artifacts in camera based single photon emission tomography due to time activity variation.

Image quality in single photon emission computed tomography (SPECT) using a rotating gamma camera is dependent on the time course of the tracer in the field of view. If acquisition times are slow compared to the tracer turnover, artifacts may occur in the reconstructed images. The properties of such artifacts were studied by computer simulation. Experimental projection data of point sources, cylindrical phantoms, and an anatomically realistic brain phantom were altered by sequentially weighting the projections with a function that varied exponentially or linearly with time. The observed distortion in the reconstructed images could be related to the ratio between the object activity variation and the camera rotation time. If the tracer concentration changed less than a factor of two during one camera rotation then little image distortion was visible although quantitatively the resolution was degraded. If the object's activity variation with time is fast enough to produce noticeable distortion, the artifacts can be reduced by performing multiple, rapid, camera rotations, instead of one rotation, for the same total acquisition time. The proposed procedure is computer storage space intensive and takes longer to produce the transaxial images, but improves image quality.

Image Enhancement↗

Linear discriminant analysis of regional ejection fractions in the diagnosis of coronary artery disease.

We studied the application of linear discriminant analysis to the computer assisted interpretation of rest and exercise gated blood pool studies. Data were obtained in 45 patients in whom the presence or absence of coronary artery disease was determined by coronary angiography. Automated analysis of regional ejection fractions using a linear discriminant function (LDF) was compared to the fully automated calculation of global ejection fraction and to the subjective evaluation of wall motion. A LDF constructed from the data for the first 31 consecutive patients correctly classified 25/31 (81%). The change in global ejection fraction correctly classified 24/31 (77%) and wall motion analysis 25/31 (81%). In a distinct group of 14 patients the same LDF correctly classified 12/14 (86%), global ejection fraction 9/14 (64%) and wall motion analysis 10/14 (71%).

Coronary Disease↗

Radiosynthesis of a selective dopamine D-1 receptor antagonist: R(+)-7-chloro-8-hydroxy-3-[11C]methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3 -benzazepine ([11C]SCH 23390).

Carbon-11 labeled SCH 23390, a selective dopamine D-1 receptor antagonist (Fig. 1b), was prepared by N-alkylation of the nor-methyl precursor with [11C]iodomethane. The product was purified by semi-preparative HPLC and shown to be radiochemically pure at the end of synthesis. The synthesis was completed in approximately 22 min with an average radiochemical yield of 28% (based on [11C]iodomethane) and an average specific activity of approximately 1950 microCi/mumol calculated at the end of synthesis.

Benzazepines↗

Brain imaging agents: synthesis and characterization of (N-piperidinylethyl) hexamethyl diaminodithiolate oxo technetium(V) complexes.

Two 99mTc complexes of (N-piperidinylethyl) hexamethyl diaminodithiol (NEP-DADT) have shown high brain uptake in rodents and lower primates. One of these 99mTc complexes has given positive images of the brain in man which are qualitatively related to regional brain blood flow (rCBF). In order to determine the structure of these 99mTc products, the corresponding 99Tc(NEP-DADT) complexes were prepared and characterized by HPLC, TLC, fast-atom-bombardment mass spectrometry (FAB MS) and other analytical techniques. These results indicate that the two 99Tc (NEP-DADT) complexes are syn and anti isomers (i.e. one isomer has the N-piperdinylethyl side chain located syn to the technetium oxo core while the other has this side chain located anti to the technetium oxo core).

Brain↗

Radiometric studies on the oxidation of [1-14C]fatty acids and [U-14C]L-amino acids by mycobacteria.

A radiometric assay system has been used to study oxidation patterns of [1-14C]fatty acids and [U-14C]L-amino acids by drug-susceptible and drug-resistant organisms of the genus Mycobacterium. Two strains of M. tuberculosis susceptible to all drugs, H37Rv TMC 102 and Erdman, were used. Drug-resistant organisms included in this investigation were M. tuberculosis H37Rv TMC 303, M. bovis, M. avium, M. intracellulare, M. kansasii and M. chelonei. The organisms were inoculated into a sterile system containing liquid 7H9 medium along with one of the [1-14C]fatty acids or [U-14C]L-amino acids. Although each individual organism displayed a different pattern of fatty acid oxidation, these patterns were not distinctive enough for identification of the organism. Susceptible and resistant mycobacteria did not display any preferential oxidation of long chain or of short chain fatty acids that might help to distinguish these organisms. As with the fatty acid series, differential oxidation patterns for amino acids could be recognized, but again these patterns were not distinctive enough to identify each organism. Complex amino acids such as proline, phenylalanine and tyrosine were of no use in identification of mycobacteria, since virtually all organisms failed to oxidize them. Identification of each individual organism was feasible using a combination of fatty acids and amino acids which included butyric, octanoic, oleic, glycine and alanine. There was no combination of substrates able to separate susceptible and resistant organisms.

Amino Acids↗

Comparison of 99Tcm complexes (NEP-DADT, ME-NEP-DADT and HMPAO) with 123IAMP for brain SPECT imaging in dogs.

Several new lipophilic 99Tcm complexes have recently been described as alternatives to N-isopropyl (123I) iodoamphetamine (123IAMP) for measurement of regional cerebral blood flow (RCBF). In this study we have compared brain uptake and blood clearance of 99Tcm-N-ethylpiperidine-diamino dithiol (99Tcm-NEP DADT), its 4-methylated derivative (99Tcm-Me-NEP-DADT) and 99Tcm-hexamethyl-propylene-amine-oxime (99Tcm-HMPAO) with that of 123IAMP in two dogs. Single photon emission tomography (SPECT) was employed to measure brain accumulation and retention of the four radiopharmaceuticals. Cerebral uptake of the 99Tcm complexes (0.8-1.1%) was lower than that of 123IAMP (1.6% of the injected dose). There was considerable extracerebral activity in the dog's head, especially in the olfactory and snout regions. Because of slow blood clearance 99Tcm-HMPAO showed high uptake in these regions. Brain uptake of 99Tcm-HMPAO reached a plateau 5 to 10 min after intravenous injection and remained constant for the entire study period (1 h). 99Tcm-NEP-DADT, on the other hand, showed significant clearance from the brain after reaching maximal uptake at 10 to 15 min after injection. However, brain imaging with these agents was possible during the first 20 min. The mechanism of brain uptake, as well as the relationship between brain uptake and RCBF need to be evaluated for each of the four radiopharmaceuticals.

Amphetamines↗

Increased concentrations of 3-hydroxykynurenine in vitamin B6 deficient neonatal rat brain.

Increased concentrations of the endogenous tryptophan metabolite 3-hydroxykynurenine (3-HK) were measured in the brains of vitamin B6 deficient neonatal rats. Mean concentrations of 3-HK in B6 deficient cerebellum, corpus striatum, frontal cortex, and pons/medulla ranged from 9.7 to 18.6 and 102 to 142 nmol/g of wet tissue at 14 and 18 days of age, respectively. 3-HK was not significantly increased in control neonatal or adult rat brain, vitamin B6 deficient rat brain at 7 days of age, or in brains from adult rats deprived of vitamin B6 for 58 days. The administration of daily intraperitoneal injections of vitamin B6 from the 14th to the 18th day of age decreased the concentration of 3-HK to control levels. 3-HK has been shown by other investigators to produce seizures when injected into the cerebral ventricles of adult rodents. Thus, our studies show the accumulation in brain of a putative endogenous convulsant as the result of a nutritional deficiency.

Aging↗

Effects of perinatal vitamin B6 deficiency on dopaminergic neurochemistry.

Long-Evans dams were fed either a vitamin B6-deficient or a control diet from day 13-14 of gestation and throughout lactation. A control pair-fed group was also included because of differences in food intake between vitamin B6-deficient and control ad libitum dams. The progeny of vitamin B6-deficient dams had all the classic symptoms of B6 deficiency. These included weight loss, ataxia, tremor, and epileptic seizures. Concentrations of the neurotransmitter dopamine (DA), and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as D-2 dopamine receptor binding, 3,4-dihydroxyphenylalanine (DOPA) decarboxylase activity, and vitamin B6 levels were measured in the corpus striatum of progeny at 7, 14, and 18 days after birth. Striatal DA and HVA levels were significantly decreased in B6-deficient animals when compared to ad libitum or pair-fed controls. Daily injections of vitamin B6 to deprived animals from the 14th to 18th day after birth improved the abnormal movement and normalized the concentration of DA but not of HVA in corpus striatum. Striatal D-2 dopamine receptor binding using [3H]spiperone as ligand was significantly reduced in 18-day-old animals as compared to ad libitum and pair-fed controls. No significant differences were found at 14 days. The administration of vitamin B6 to deprived animals did not raise the level of D-2 receptor binding during the period of observation. Scatchard plots indicated that the differences in binding were due to changes in receptor number and not in KD. Corpus striatum DOPA decarboxylase activity with and without the addition of exogenous pyridoxal phosphate was significantly reduced in 14- and 18-day-old animals when compared to pair-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Immediate effect of expiratory loading on left ventricular stroke volume.

While the steady-state effects of positive pleural pressure on the circulation have been extensively studied, less is known about the immediate effects of positive intrathoracic pressure on cardiac dynamics. Therefore, we performed electrocardiographically gated radionuclide ventriculography with a respiratory gating technique in nine healthy subjects during quiet breathing and during expiration against a 24 cm H2O expiratory threshold load. During expiration, respiratory loading caused an increase in stroke counts by 29.4% (p less than .001) due to an increase in end-diastolic counts of 26.1% (p less than .001). End-systolic counts also rose 18.8% (p less than .05). The ejection fraction did not change significantly. These findings indicate that the increase in left ventricular stroke volume that occurs during the first 1 or 2 beats of a loaded expiration is due to an increase in left ventricular filling and not to augmentation of left ventricular ejection. This immediate increase in pulmonary venous return may reflect increased distensibility of the left ventricle due to decreased filling of the right ventricle.

Adolescent↗