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Biomedical subjects

B J Smit

Publications and source records attributed to B J Smit.

At least 37 records · Page 2Linked to original sources
PubMed1995

The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung cancer in a phase I trial.

OBJECTIVE: To study the pharmacokinetic behaviour of hypoxoside taken orally by 24 patients with lung cancer. DESIGN: Randomised open study with three single doses of 1,600, 2,400 and 3,200 mg standardised Hypoxis plant extract (200 mg capsules) and a multiple-dose study on the first 6 patients taking 4 capsules 3 times daily for 11 days. PARTICIPANTS AND SETTING: Patients with histologically proven squamous, large-cell or adenocarcinoma were hospitalised at the Radiation Oncology Ward, Karl Bremer Hospital, Bellville, W. Cape. METHODS: Blood was drawn at regular intervals up to 75 hours after single doses and the concentrations of metabolites of the aglucone of hypoxoside, rooperol, were measured with a high-performance liquid chromatography method. For the multiple-dose study blood was drawn before the first dose each day. Concentration-time relationships were analysed according to a conventional single open-compartment model and also by using the NONMEM digital computer programme. RESULTS: Neither hypoxoside nor rooperol appear in circulation. This is due to complete phase II biotransformation to diglucuronide, disulphate and mixed glucuronide-sulphate metabolites, of which the latter is the major component. Considerable interpatient variation in concentration-time relationships was found in the single-dose studies. It was due to an active enterohepatic recirculation in some patients and a distinct lag phase in others together with zero-order rate of formation of rooperol in the colon. Computer modelling indicated a single open-compartment model in which the mass of the patient did not influence volume of distribution and clearance because formation of the metabolites is dependent on the metabolising capacity of the patient. However, the elimination of the metabolites follows first-order kinetics with half-lives ranging from 50 hours for the major metabolite to 20 hours for the two minor metabolites. Multiple-dose studies also showed large interpatient variation. CONCLUSION: In order to reach metabolite levels near 100 micrograms/ml, which have been shown to be tumouricidal after enzymatic deconjugation to rooperol, maintenance doses need to be individualised for each patient. For most patients, however, a daily dose of 2,400 mg was sufficient.

Adult↗
PubMed1995

A phase I trial of hypoxoside as an oral prodrug for cancer therapy--absence of toxicity.

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 micrograms/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 beta-glucuronidase and sulphatase as well as a high sensitivity for rooperol.

Adenocarcinoma↗
PubMed1994

Cocaine use in pregnancy in Amsterdam.

To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine-using pregnant women (n = 21) and their offspring (n = 23) were obtained retrospectively (1987-1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks and a median birth weight of 3090 g. There were six preterm infants, two small-for-gestational-age infants and five infants with a small head circumference. Three infants had a congenital malformation. One infant (Potter's syndrome) died shortly before birth. One infant had congenital syphilis, four had intracerebral abnormalities on ultrasound and four had abnormal neurologic symptoms in the neonatal period. One infant died after 21 days of life. At follow-up four infants showed abnormal development. In 12 of the 23 infants (52%), one or more possible effects of cocaine were found.

Child of Impaired Parents↗
PubMed1994

Substance use in pregnancy: do we care?

Two cohorts of substance-using women were compared retrospectively. From 1969 to 1979 a very high perinatal mortality rate (PMR 9.8%) was found among 92 polydrug-using women (1 twin excluded). Preterm delivery occurred in 25% of all pregnancies and in 30% of the children birth weight was below the 10th percentile. Nineteen women using heroin only had a worse fetal outcome (PMR 32%, preterm delivery in 47%, birth weight < 10th percentile in 42%). These results led to a strict surveillance system. In the period 1980-1989, 240 women (4 twins excluded) delivered after 16 weeks. Total fetal loss decreased to 2.1% and PMR to 0.4%, which was similar to results in controls. However, 22% of the women still delivered before 37 weeks and 27% delivered a child < 10th percentile. Methadone-using women were able to halve their dosage during pregnancy and 16 were detoxified. Multivariate analysis within the substance users of the second cohort showed that the neonatal abstinence syndrome, but not the (registered) amount of opiates used, was related to a lower birth weight. Not coping with prenatal care was related to a shorter pregnancy length. Multivariate analysis, including the controls, showed a significant relation of birth weight (345 g lower) with substance use. Also, head circumference was 0.8 cm smaller. Length of pregnancy however was related to smoking. This study shows that it is difficult to make substance users attend prenatal care, but also that women coping with prenatal care reduce substance intake. Opiate use might be responsible for lower birth weight, although not in a clear dose-response relationship, whereas lifestyle, as represented by not coping with prenatal care and the quantity of cigarette smoking, shortens the length of pregnancy.

Adult↗
PubMed1994

Lethal exposure.

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Environmental Monitoring↗
PubMed1993

[Pain, pain assessment and analgesia in newborn infants].

Although during the past few years more knowledge on pain and analgesia in the neonate has been acquired, adequate treatment is not always given. To achieve better understanding and treatment of pain in newborn infants, a review of pain perception and pain assessment is given as well as guidelines regarding its prevention and treatment. A proper assessment and an adequate relief of pain contributes to the quality of care for the newborn infant.

Analgesia↗
PubMed1992

Radiotherapy of aggressive fibromatosis.

The long term results of 24 patients treated with postoperative irradiation for aggressive fibromatosis are presented. Tumour sites were the pelvis (8), chest wall (5), shoulder (5), extremities (4) and head and neck (2). Macroscopic complete resection (R1) was performed in 3 cases. 17 patients presented postoperatively with gross disease (R2), 8 of which were recurrent tumours. 4 patients with inoperable disease had biopsies only. Radiation doses ranged from 28 to 64 Gy at a fractionation of 5 x 2 or 4 x 2.5 Gy/week. 4 patients had external irradiation in combination with 192Ir implants, 2 were irradiated with implants alone. In the combined treatment group, external doses ranged from 28 to 52 Gy and additional interstitial doses from 35 to 50 Gy. 192Ir treatment alone was given with 45 and 57 Gy to the contour of the target volume. The 10 year recurrence free survival rate is 75%. A dose response relationship has been established in the dose range of 30-60 Gy revealing an expected 80% persistent tumour control rate at 60 Gy. A dose volume relationship however, could not be derived from our data. Moderate fibrosis without functional impairment developed in 5 patients (21%). These data support a policy of postoperative radiotherapy with 60 Gy in patients with incompletely excised or gross residual tumour following surgery.

Adolescent↗