Browsing by Author "Van Jaarsveld, P. P."
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- ItemEndogenous immunoreactive digitalis-like substance in neonatal serum and placental extracts(Health & Medical Publishing Group, 1984) Beyers, A. D.; Spruyt, L. L.; Seifart, H. I.; Kriegler, A.; Parkin, D. P.; Van Jaarsveld, P. P.Therapeutic levels of digoxin in the serum of untreated neonates delivered to mothers who had not received the drug prenatally were detected by radio-immunoassay. Digoxin levels in neonates should be interpreted with care because of the unknown contribution by the endogenous digitalis-like substance (DLS) to the level of the drug. Three commercially available radio-immunoassay kits were compared with regard to their sensitivity and reproducibility in detecting the endogenous DLS. The kit from Clinical Assays (Cambridge, Mass., USA) was selected for further investigations. In a series of 35 paired samples of maternal and cord blood the average DLS values in terms of digoxin were 0.52 ± 0.07 and 0.81 ± 0.27 ng/ml respectively. This difference is statistically highly significant. In the case of infants with DLS values of 1-1.5 ng/ml in terms of digoxin, approximately 1 week was required to reach non-therapeutic digoxin levels, i.e. below 0.5 ng/ml. Gel chromatography showed that the DLS in neonatal serum was more closely associated with protein than is authentic digoxin. In placental extracts it followed the elution profile of the protein completely, but it shifted to fractions with a lower molecular weight than haemoglobin after trypsinization. The level of DLS in neonatal serum was also increased by more than half its original value by trypsinization. Proteolysis therefore seems to have a releasing effect on DLS. The molecular size of this substance is probably in the same range as that of polypeptides, since it was not dialysable from trypsinized and untreated samples through a membrane with a 22,000 dalton molecular weight cut-off point.
- ItemImmunoreactive digitalis-like substance in pre-eclampsia(Health & Medical Publishing Group, 1986) Odendaal, H. J.; Beyers, A. D.; Van Heyningen, C. F.; Spruyt, L. L.; Kotze, T. J. van W.; Van Jaarsveld, P. P.An endogenous digitalis-like substance (DLS) may be involved in the pathogenesis of essential hypertension and pre-eclampsia. The digoxin levels in maternal and cord blood of 504 randomly selected patients were determined. Since none of the patients received digoxin, these levels indicated a cross-reacting substance (immunoreactive DLS). DLS levels were significantly higher in the cord blood of pre-eclamptic patients than in the cord blood of controls. DLS levels in cord blood increased with the severity of pre-eclampsia, and levels were higher in primigravidas than in multigravidas. The structure and biological activity of DLS must be determined before definite conclusions about its role in the pathogenesis of pre-eclampsia can be made.
- ItemIntra-ocular concentration-time relationships of subconjunctivally administered gentamicin(Health & Medical Publishing Group, 1991) Van Rooyen, M. M. B.; Coetzee, J. F.; Du Toit, D. F.; Van Jaarsveld, P. P.Eighty-nine patients scheduled for cataract removal or lens implantation were divided randomly into three groups. Each received 5, 10 or 20 mg gentamicin subconjunctivally at times varying between 0,2 and 19 hours pre-operatively. At surgery a sample of aqueous humour was obtained and analysed for gentamicin concentration. The data for each group were subjected to non-linear regression analysis to fit an open one-compartment pharmacokinetic model with first-order kinetics. A statistically acceptable fit was obtained. The average values of the pharmacokinetic parameters obtained from the single doses were used to simulate multiple-dose kinetics. The average target intra-ocular gentamicin concentrations and dosage interval were specified in the computer program, which subsequently allowed calculation of the dose required. This allowed the construction of a simple linear nomogram that can be used to read off the dose needed for handling specific clinical situations.
- ItemA phase I trial of hypoxoside as an oral prodrug for cancer therapy : absence of toxicity(Health & Medical Publishing Group, 1995) Smit, B. J.; Albrecht, C. F.; Liebenberg, R. W.; Kruger, P. B.; Freestone, M.; Gouws, L.; Theron, E.; Bouic, P. J. D.; Etsebeth, S.; Van Jaarsveld, P. P.Objective. To assess the toxicity of hypoxoside taken orally by 24 patients with lung cancer. Design. Open study with patients taking 1 200 - 3 200 mg standardised Hypoxis plant extract (200 mg capsules) per day divided in 3 doses in order to maintain metabolite blood levels near 100 μg/ml. Participants and setting. Patients with histologically proven squamous, large-cell or adenocarcinoma were hospitalised initially at the radiation oncology ward, Karl Bremer Hospital, Bellville, W. Cape. Thereafter they returned every 2 weeks for full clinical examinations. Methods. Routine biochemical and haematological measurements were done. Patients underwent regular full clinical examinations including radiographs and computed tomography scanning according to the discretion of the principal investigator. Results. Nineteen patients on hypoxoside therapy survived for an average of 4 months with progression of their primary tumours and metastases, while 5 survived for more than a year. One of them survived for 5 years and histological examination of the primary lesion showed absence of cancer. No toxic effects, in clinical examinations or biochemical or haematological measurements, were found that could be ascribed to the ingestion of hypoxoside. Only one occasion of possible drug intolerance, with anxiety, nausea, vomiting and diarrhoea, was noted. Conclusion. The absence of toxicity warrants further investigation of hypoxoside as an oral prodrug, especially in patients with slow-growing necrotising tumours that are inoperable and have high concentrations of β-glucuronidase and sulphatase as high sensitivity for rooperol.