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Biomedical subjects

A G Jones

Publications and source records attributed to A G Jones.

At least 91 records · Page 5Linked to original sources

Single-photon emission computed tomography. A method of measuring cerebral blood flow in three dimensions (preliminary results of studies in patients with epilepsy and stroke).

The recent development of single-photon emitting radiopharmaceuticals that reflect cerebral blood flow has introduced a new era for the useful application of nuclear medicine to the investigation of neurological disease. Using 123I labelled N-isopropyl-p-iodoamphetamine, we have performed emission-computed tomographic scans of the brain in several clinical settings. These studies display cross-sectional maps of cerebral blood flow and promise significant clinical utility in a variety of brain diseases. In the eight patients with epilepsy, the scans showed good localization of the abnormal foci, and correlated well with the findings at operation in the five patients who were submitted to surgery. All 10 patients with stroke had abnormal scans, and the abnormalities in cerebral blood flow were frequently more extensive than the lesions seen on the transmission-computed tomographic scan. This initial experience leads us to anticipate an increasing role in clinical neurology for single-photon emission computed tomographic scans of cerebral blood flow.

Adolescent↗

A variant tandemly repeated nucleotide sequence in Balbiani ring 2 of Chironomus tentans.

pCtBR2-2 is a genomic clone from Chironomus tentans that hybridized in situ to Balbiani ring 2 (BR2) on salivary gland polytene chromosome IV. DNA sequencing indicated that the insert contained nearly four copies of a 180 bp tandemly repeated nucleotide sequence that was distinctly different from a previously reported BR2 repeat. Sequence titration experiments detected about 70 copies of the 180 bp repeat per haploid genome, which would correspond to approximately 34% of a 37 kb BR2 gene. Each 180 bp repeat included a conserved 90 bp segment whose sequence was internally nonrepeating (INR), and a variable 90 bp repeated (R) segment comprised of three 30 bp repeats that may have evolved from a 9 bp consensus sequence. Results presented here raise the distinct possibility that other BR genes may contain significantly different repeated sequences that have not been identified.

Amino Acid Sequence↗

Therapeutic benefits of 5-hydroxytryptamine inhibition following pulmonary embolism.

The smooth muscle-constricting, platelet amine, serotonin (5-hydroxytryptamine; 5-HT) is theorized to play an important role in the cardiopulmonary dysfunction that accompanies embolization. The present study was designed to examine this hypothesis. Autologous clot, 0.75 g/kg, was injected IV into 14 dogs. After 30 minutes, one half of the animals were randomly assigned to the treatment group and received a bolus infusion of 0.15 mg/kg ketanserin, a quinazoline derivative known to be a selective 5-HT receptor antagonist. Five minutes after embolization there were increases in mean pulmonary arterial pressure (MPAP) from 12 mm to 48 mmHg (p less than 0.001); pulmonary vascular resistance (PVR) from 2.2 mm to 12.2 mmHg X min/L (p less than 0.001); physiologic shunt (QS/QT) from 12% to 44% (p less than 0.01); and physiologic dead space (VD/VT), calculated from end tidal and arterial PCO2, from 8% to 39% (p less than 0.001). Within 15 minutes platelet counts decreased from 186,000/mm3 to 134,800/mm3 (p less than 0.05); 5-HT contained in circulating platelets fell from 1.71 micrograms/ to 1.44 micrograms/10(9) platelets (p less than 0.05). Five minutes after ketanserin, MPAP declined to 27 mmHg and was lower than the control value of 41 mmHg (p less than 0.05); PVR decreased to 6.2 mmHg X min/L, lower than 12 mmHg X min/L in controls (p less than 0.01); QS/QT fell to 26% in contrast to 47% in controls (p less than 0.05); and VD/VT declined moderately to 32% (p less than 0.05), although this value was not different from 38% in control animals. Cardiopulmonary function continued to improve in treated animals until termination of the experiment at four hours when pulmonary angiograms and perfusion scans demonstrated vascular recruitment compared with untreated embolized control dogs. These data demonstrate that the cardiopulmonary consequences of experimental embolization are primarily determined by the vasoconstrictive and bronchoconstrictive actions of 5-HT.

Animals↗

Biodistribution and dosimetry of N-isopropyl-p-[123I]iodoamphetamine in the primate.

The biodistribution of N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) in the Macaca fascicularis monkey was determined at 15 min and at 1, 4, 24, and 48 hr after intravenous injection. Brain uptake was 7.8% of the injected dose at 1 hr, with little change in concentration between 15 min and 1 hr, falling thereafter. Eye uptake reached a maximum of 0.23% of injected dose at 24 hr, with activity primarily in the pigmented layers. The human absorbed radiation dose was calculated on the basis of biodistribution data. The critical organ is the eye (0.407 rad/mCi of I-123 IMP). The eye dose increased to 1.11 rad/mCi with 4% contamination from I-124 IMP and to 0.535 rad/mCi with 0.4% contamination from I-125 IMP. The absorbed dose to the liver was 0.127 rad/mCi for pure I-123 IMP and the thyroid dose was 0.120 rad/mCi, both increasing with either I-124 or I-125 contamination. While delayed eye uptake has not yet been reported in the human, care should be exercised in limiting the amount of contaminating I-124 or I-125 to the lowest practical level.

Absorption↗

Leakage of radioactive particle systems from a synovial joint studied with a gamma camera. Its application to radiation synovectomy.

UNLABELLED: We have determined rates of leakage of radioactivity from a rabbit synovial pouch in vivo for a number of particle systems of varying sizes and differing resistance to degradation. The estimates were made using a gamma scintillation camera and without killing the test animals. The lowest leakage at twenty-four hours was seen with inert carbonized microspheres and the highest rates were seen with surface-labeled particles of biodegradable denatured human serum albumin and with erythrocytes. The carbonized microspheres had no adverse long-term effects on the health of the animals' articular cartilage. CLINICAL RELEVANCE: Results obtained with inert particles indicate that reducing the biodegradability of the particle or increasing its diameter, or both, reduces radioactivity losses from the knee joint. Large (twenty-five-micrometer-diameter) microspheres of human serum albumin incorporating the radioactivity and carbonized microspheres are suggested as potential carriers of isotopes for human radiation synovectomy.

Animals↗

The investigation of radiopharmaceutical components by fast atom bombardment mass spectrometry: the identification of Tc-HIDA and the epimers of Tc-CO2DADS.

The nature of two technetium-labeled radiopharmaceutical components has been established by means of fast-atom-bombardment mass spectrometry (FABMS) in combination with carrier-added (CA) and no-carrier-added (NCA) reversed-phase high-pressure liquid chromatography (HPLC). Negative-ion FABMS was used to determine that the epimers of Tc-CO2DADS are the oxo[N,N'-(1-carboxyethylene)-bis-(2-mercaptoacetimido)]technetate(V) ions; positive-ion FABMS showed that Tc-HIDA is bis[N-(2,6-dimethylphenyl-carbamoylmethyliminodiaceto]technetate(III).

Chromatography, High Pressure Liquid↗

External beam radiotherapy for palliation of pain from metastatic carcinoma of the prostate.

Radiotherapy often is used for palliation of bone pain from metastatic cancer of the prostate but an objective evaluation of its efficacy in a large series of patients is unavailable. We report the results of external beam irradiation in 62 patients who had bone pain secondary to stage D carcinoma of the prostate. The variables used to judge pain before and after radiotherapy included subjective evaluation of pain, status of activity and quantitation of analgesic use. Complete relief of pain was achieved in 26 patients (42 per cent), partial relief in 22 (35 per cent) and no relief in 14 (23 per cent). On the basis of our experience external beam irradiation is useful palliative therapy for pain from metastatic cancer of the prostate.

Aged↗

Chemical and in vivo studies of the anion oxo[N,N'-ethylenebis(2-mercaptoacetimido)]Technetate(V).

Studies of the anionic coordination complex 99Tc-oxo[N,N'-ethylene-bis(2-mercaptoacetimido)]technetate(V) ([TcO(ema)]-) are described. Syntheses performed both at carrier levels (10(-5)M) and with no carrier added (less than 10(-8)M) indicate that the complex is formed virtually quantitatively from pertechnetate ion over this range. Tissue distributions in normal rats are similar at both concentrations up to one hour after administration. It has been shown--using a combination of high-pressure liquid chromatography and field-desorption mass spectrometry--that the anion is excreted unchanged into both urine and bile. The effectiveness of this N2S2 donor set in sequestering Tc-99m, and the in vivo stability of the resulting complex, suggest that modified chelates of this structural class could provide a series of useful diagnostic agents.

Animals↗

Mediastinal lymphoscintigraphy in ovarian cancer using intraperitoneal autologous technetium-99m-labelled erythrocytes.

99Tcm-labelled autologous erythrocytes (approximately 2.0 ml and 2.0 mCi) were administered intraperitoneally (IP) to 15 patients with ovarian cancer. Anterior abdominal images were then collected for up to six hours to evaluate both the dynamics of intraperitoneal tracer distribution and the potential for visualizing internal mammary lymph nodes as correlated with the presence of diaphragmatic tumour. Results indicated that dispersion of red cells closely resembled that seen during IP contrast studies; the distribution patterns were heterogeneous, remained constant with time, and were intimately related to bowel peristalsis. Visualization of internal mammary lymph nodes indicated patency of diaphragmatic lymphatics; non-visualized nodes correlated with the presence of diaphragmatic tumour. The test had a sensitivity of 0.80 and a specificity of 0.90 for defining disease. Results of this study suggest use of 99Tcm-red blood cells as a diagnostic test for diaphragmatic involvement by ovarian cancer and as a method for monitoring the effects of therapy.

Diaphragm↗

Treatment of pain of diffuse metastatic cancer by stereotactic chemical hypophysectomy: long term results and observations on mechanism of action.

Stereotactic instillation of absolute alcohol into the sella turcica for pituitary destruction was carried out in 29 patients divided into two groups. Seventeen with prostatic carcinoma underwent a total of 19 injections with 94% good to excellent results that persisted throughout the remainder of the patient's life-span. The longest survival was 9 months. Brief relapses did occur, but spontaneous remissions were the rule. A second group of mixed cancers contained 12 patients who received a total of 13 injections. Eleven patients had good to excellent results that persisted in all but 1 patient. The longest survival was 7 months. Hormonal levels and prolactin stimulation tests failed to show any correlation between hormonal changes and pain relief. Naloxone reversal of analgesia did not occur. There was no loss of cognitive function shown on psychological testing. Pathological studies showed destruction of the pituitary gland, which was subtotal in some patients despite good pain relief. All examinations showed that the pituitary stalk was destroyed. Patients who survived longer also showed degeneration of the supraoptic and paraventricular nuclei of the hypothalamus and the median eminence. All but 1 patient with pain relief exhibited a lack of antidiuretic hormone (ADH) production. Interpretation of the data indicates that ADH or its associated neurophysins act as central pain transmitters. The production of these transmitters is decreased or abolished by chemical hypophysectomy through the destruction of hypothalamic nuclei.

Cognition↗

A survey of reducing agents for the synthesis of tetraphenylarsonium oxotechnetiumbis(ethanedithiolate) from [99Tc] pertechnetate in aqueous solution.

We have studied the effectiveness of various reducing agents in the production of the well-characterized complex [99TcO(SCH2CH2S)2]- from pertechnetate in aqueous solution. The reductants tested included sodium dithionite, hypophosphorous acid, formamidine sulfinic acid, dithiothreitol, hydrazine, and hydroxylamine. Of these, only sodium dithionite in the pH range 11--13 was found to give quantitative yields of the required technetium complex.

Arsenicals↗