Production of high purity fission molybdenum-99 in South Africa.
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Biomedical subjects
Publications and source records attributed to P J Fourie.
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N-(4-(n-butyl)-acetanilide)iminodiacetic acid (BIDA), N-(2,6-diisopropylacetanilide)iminodiacetic acid (DISIDA), diethylenetriaminepentaacetic acid (DTPA) and methylene diphosphonic acid (MDP) are used in labelling kits. The contents of BIDA, DISIDA or MDP of the 99mTc-labelled compounds can be determined (indirectly) spectrophotometrically with copper, eriochrome cyaanine R (ECC) and dodecylethyldimethylammonium bromide (DEDA) in a sodium barbital buffered system at pH 8.5. The calibration curves obey Beer's Law from 0 to 40 micrograms/25 mL for BIDA and DISIDA, 0 to 60 micrograms/25 mL for DTPA and 0 to 100 micrograms/10 mL for MDP.
The high incidence of hepatocellular carcinoma amongst certain population groups of Southern Africa made feasible the investigation of a radiolabelled monoclonal anti-alpha-foetoprotein as a radioimmunodiagnostic agent for this disease. This paper reports the preclinical trials with monoclonal anti-alpha-foetoprotein E.9 (anti-AFP) and its F(ab')2 fragment after radiolabelling with 131I. Various radioiodinations were tried. The best results were obtained with the lodogen and Bolton-Hunter methods. 131I from only one of the sources tested gave an 131I-labelled anti-AFP with meaningful immunoreactivity. It was shown by means of gamma-camera scans and monitoring of radioactivity in individual organs that 131I-anti-AFP and the 131I-anti-AFP F(ab')2 fragments did not accumulate abnormally in any organ(s) in healthy animals. The correlation in healthy mice of the biodistribution of 125I human IgG to 131I-anti-AFP, and 125I human IgG to 131I-F(ab')2 was good. Human hepatoma xenografts in athymic mice showed uptake of 131I-anti-AFP and the 131I-F(ab')2 fragment. The uptake of 131I-F(ab')2 was improved by liver background subtraction. There was correlation between circulatory alpha-foetoprotein concentrations and tumour uptake of 131I-F(ab')2 in tumour-bearing athymic mice and a definite relationship was found between tumour size and radiolabelled antibody and the F(ab')2 fragment. After the biological action of the 131I-anti-AFP and the 131I-F(ab')2 fragment was known, sterile pyrogen-free consignments were supplied for clinical trials in humans on a regular basis.
A continuous infusion technique for atracurium was investigated. It provided a stable neuromuscular block, with a mean infusion rate of 0.008 mg/kg/min after an initial bolus of 0.5 mg/kg. A wide individual response was found and an arbitrary infusion rate based on mass alone is therefore not possible. The above rate is thus a starting point and should be adjusted according to individual requirements, preferably by using a peripheral nerve stimulator. The technique obviates the need for repeated increments of atracurium during lengthy surgical procedures.
Atracurium 0.3 mg/kg was compared with alcuronium 0.25 mg/kg as the sole muscle relaxant for tracheal intubation and abdominal relaxation for gynaecological laparoscopy in 46 patients during nitrous oxide, oxygen and halothane anaesthesia. Speed of onset, intubation conditions, effect on blood pressure and pulse rate, and ease of reversal were compared. Alcuronium had a significantly faster onset of action than atracurium; intubation conditions were adequate and abdominal relaxation was satisfactory for both drugs. The effect of atracurium was readily reversible within 10 minutes; in contrast alcuronium was significantly more resistant and mean recovery time was 28.03 minutes. Although alcuronium provided good muscle relaxation, it is not suitable for short procedures because of difficulty in reversing its action. Atracurium allowed earlier and more complete reversal of neuromuscular block.
(o)-[77Br]bromohippuran (BHIP) was developed as renal tubular function agent due to its favourable chemical and physical properties and compared to (o)-[131I]iodohippuran (IHIP). Renograms obtained from baboons were compared and absorbed radiation dose calculations performed. Although BHIP showed a delayed kidney uptake and washout pattern, good kidney clearance of the radionuclide was obtained after 30 min. Radiation dose values for BHIP were markedly lower than for IHIP indicating that larger activities of BHIP could be administered to increase counting statistics. BHIP imaging in normal volunteers did however not substantiate the favourable behaviour obtained in the primate.
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Five new HIDA-compounds were synthesized, labelled with 99mTc and compared with 99mTc-(2,6-dimethyl)HIDA viz. (N-2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid by means of TLC and biodistribution studies on rabbits. The computerized method used by Britton and Brown during renal studies was successfully adapted to study the biodistribution of these agents.
Radiolabeling procedures may modify the structure of the Fc portion of the immunoglobulin molecule in such a way that its in vivo immunological behavior may be altered and its efficacy as radiopharmaceutical for inflammatory lesions impaired. This study tested the efficacy of thiol reduction-mediated 99mTc human IgG for scintigraphy of focal inflammatory lesions, either bacterially or chemically induced and located either in the abdominal/thoracical region or in the thigh of baboons. Positive images were obtained in the thigh lesions between 4 and 7 hr after i.v. administration of the labeled IgG. The abdominal/thoracic lesions were never very clear, mostly because of very hot kidneys. Late visualization (20 hr) of all lesions was poor and a high background was present. Bacterially induced lesions were better visible, although no neutrophil nor monocyte activity could be established in the mechanism of the IgG localization.