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Biomedical subjects

F A de Wolff

Publications and source records attributed to F A de Wolff.

At least 73 records · Page 4Linked to original sources

Aluminum affects interconnections between aggregates of cultured hippocampal neurons. Neurotoxicity of aluminum in vitro.

The effect of aluminum (Al) was studied in an in vitro system of cultured hippocampal neurons from fetal rats in a chemically defined medium. Neuronal aggregates interconnected by neurites were detected light and electron microscopically in control and Al-treated cultures. In the Al-treated cultures disruptions of the fibers were observed proximal to the aggregates; the number of disruptions increased with The Al concentration applied. It is concluded that interference of intracellular Al with the neuronal skeleton occurs, leading to an enhanced fragility of the interconnecting neurites. The concentration-dependent Al-induced disruption of interconnecting neurites may serve as an in vitro model for further research in Al neurotoxicity.

Aluminum↗

[Canthaxanthin retinopathy without intake of canthaxanthin].

Seven patients are described who presented with the typical fundus finding of gold-colored crystals in the superficial layers of retina in the macular area (characteristic of canthaxanthin retinopathy) without having taken canthaxanthin-containing drugs. Canthaxanthin used as a food additive is discussed as a possible cause of the crystal deposition. There may be a rather high individual tendency to develop crystal deposition, possibly related to a metabolic defect affecting canthaxanthin kinetics or to pre-existing changes in the retinal pigment epithelium. In one patient a slight decrease in crystalline deposition was observed in the course of four years.

Adult↗

Elevation of serum aluminium concentrations in patients with rheumatoid arthritis treated with drugs containing aluminium.

In a group of 19 rheumatoid arthritis (RA) patients with normal renal function, serum levels of aluminium (AlS) were monitored during treatment with drugs containing this metal (Al). The AlS levels during treatment were significantly higher (0.005 less than p less than 0.01) than those before treatment, i.e. 19.4 (SEM 2.3) micrograms/l and 12.3 (1.7), respectively. This increase in AlS was significantly (0.025 less than p less than 0.05) correlated with the pretreatment serum creatinine level (mean value for the whole group 80.5 (SEM 4.7) mumol/l) but showed no correlation with the predicted creatinine clearance. Although the increase in AlS during therapy with A1 containing drugs is not dramatic in RA patients with normal renal function, the rheumatologist should be aware of the risk of increased AlS concentration in RA patients, especially those with impaired renal function.

Adult↗

Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family.

The mode of inheritance of insufficient phenytoin p-hydroxylation was studied in the family of a patient who had previously suffered from a phenytoin intoxication caused by insufficient metabolism of this drug. This family was compared with a control group. The rate of phenytoin metabolism was derived from the phenytoin/metabolite ratio in serum 6 hours after an oral test dose of 300 mg phenytoin. The propositus, a brother and a sister, were very slow metabolizers of phenytoin, with a metabolic ratio of approximately 20. In the other individuals, 22 family members of the second generation and 37 control subjects, a metabolic ratio of 4.7 +/- 2.2 (mean +/- SD; n = 59) was found. When comparing the members of the second generation (F2) with the control group, two statistically significantly different groups appear to exist: F2, with a metabolic ratio of 6.6 +/- 1.7 (mean +/- SD; n = 22), and the control group, with a metabolic ratio of 3.7 +/- 1.8 (mean +/- SD; n = 37) (p less than 0.001). Based on these results the mode of inheritance of this defect seems to be autosomal recessive.

Adult↗

Nutritional toxicology: the significance of natural toxins.

1. The human diet may act as a carrier for substances which have a deleterious effect on human health either acutely or after chronic intake. 2. These substances can be divided into nutrients, contaminants, food additives and natural toxicants. 3. Recent research has mainly focused upon the contaminants and additives. This has led to regulatory measures which aim to prevent disease from exposure to such chemicals. 4. The natural toxicants have not been as widely studied as the other classes of dietary toxins. Their possible impact on human health, however, justifies stimulation of research into this important branch of toxicology.

Diet↗

Therapeutic drug monitoring of amitriptyline: impact of age, smoking and contraceptives on drug and metabolite levels in bulimic women.

Concentrations of amitriptyline (AT), nortriptyline (NT) and E-10-hydroxynortriptyline (E-10-OH-NT) were measured in 18 women with bulimia receiving 100 mg AT/day for at least 6 wk. After onset of treatment between days 36 and 57 there is a decrease in AT and an increase in E-10-OH-NT concentrations, probably due to an autoinductive effect on hydroxylation. The estimated mean (+/- SD; range; n) elimination half-life time of AT was 14.0 (+/- 7.8 h; 7.5-38.5 h; 14). On day 36, AT concentrations in females using oral contraceptives (OC) were higher than in non-users of OC, which indicates inhibition of AT metabolism by OC. In all smokers the E-10-OH-NT concentrations on day 36 were lower than in non-smokers. Our findings suggest induction of N-demethylation and glucuronidation by smoke components.

Adolescent↗

Idiopathic oedema and diuretics.

Diuretic abuse has been invoked as the cause of idiopathic oedema. In this study, eight patients with idiopathic oedema were studied. Symptoms and weight variation continued despite the proven absence of diuretics in seven of them as determined by urinary chromatograms. Idiopathic oedema cannot therefore be attributed to diuretic use alone.

Adult↗

Serum aluminium concentrations in patients with rheumatoid arthritis.

Aluminium (AlS) and zinc (ZnS) concentrations in serum were measured in patients with rheumatoid arthritis (RA) with and without Al-containing drugs and compared with levels in healthy controls. In RA patients without Al-containing antacids, the AlS levels did not differ from those of the healthy controls (mean 9.9, SEM 0.9 microgram/l and mean 8.6, SEM 0.5 microgram/l). However, the AlS levels in RA patients treated with Al-containing drugs were significantly (p less than 0.05) higher than in the other two groups (mean 14.1, SEM 1.1 microgram/l). Serum zinc (ZnS) levels in both RA groups were significantly (0.01 less than p less than 0.025) lower than in the healthy controls (mean 10.5, SEM 0.4 mumol/l and mean 10.2, SEM 0.4 mumol/l for the RA groups with and without Al-containing drugs, and in healthy volunteers mean 14.4, SEM 0.6 mumol/l). The difference in AlS levels might be due not only to the intestinal absorption of Al from Al-containing drugs, but also to a slightly impaired renal function, serum creatinine being slightly but significantly higher (p less than 0.05) in the Al-treated RA group than in non-Al-treated one. This difference in serum creatinine between the two RA groups might be explained by the more frequent use of cimetidine in the Al-treated RA group.

Aluminum↗

Biological monitoring of aluminium in renal patients.

During the past decade, aluminium (Al) has been shown to possess a potential for systemic toxicity. Renal patients form a high-risk group for Al poisoning, and biological monitoring is indicated to diagnose and prevent toxicity. Electrothermal atomic absorption spectrometry is the analytical method of choice for measuring Al levels. Special precautions have to be taken to prevent contamination with environmental Al or adsorption of Al to glassware during analysis. Since this metal is almost evenly distributed between plasma and erythrocytes, either plasma or whole blood may be used to estimate exposure to Al. Measurement in dialysis fluid is suitable to assess parenteral uptake. Hair analysis is of no value. The normal value in plasma is 7.3 +/- 2.0 micrograms/l (mean +/- SD, n = 10); toxic symptoms are mainly associated with levels above 100 micrograms/l. A dialysate level not exceeding 5 micrograms/l may be considered safe; intestinal absorption is then the only remaining, highly variable source of Al uptake.

Aluminum↗

Zinc in hair and urine of paediatric patients.

Zinc concentrations in hair and urine were measured in groups of children varying in one condition - short stature, or after prolonged upper respiratory infection, or during non-infectious diarrhea, or while on chemotherapy for acute lymphatic leukaemia and in healthy controls. As compared with controls, hair zinc was significantly low after respiratory infection (p less than 0.0001) and high in short stature (p less than 0.01). Urinary zinc was increased during initial chemotherapy (p less than 0.001) and diarrhea (p less than 0.02). It is shown that zinc deficiency occurs in one of the common symptoms in paediatric medicine, namely upper respiratory tract infection. The high overlap (34-88%) proves hair and urine zinc to be of no use for reliable individual diagnostic statements.

Child↗

Intestinal absorption of aluminum in rats: effect of intraluminal pH and aluminum concentration.

The intestinal absorption of aluminum (Al) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The jejunum-ileum was perfused with media containing 4.63, 9.25 and 18.50 mmol l-1 Al chloride at pH 4.0 and 7.0. Both mucosal retention was not affected by pH but at lower pH more Al was released into the blood. The amount of Al which appeared in the blood was linearly related to the mucosal retention. The Al release into the blood was much less (mumol l-1) than the mucosal retention (mmol l-1). It is concluded that the intestinal absorption of Al is pH- and concentration-dependent.

Aluminum↗

Pharmacokinetics of tiapride in patients with tardive dyskinesia and Huntington's disease.

The pharmacokinetics of tiapride were determined at steady-state in 5 patients with tardive dyskinesia and 2 patients with Huntington's disease given tiapride 100 mg t.i.d. for 7 days. The maximum serum concentration of tiapride of 1.47 +/- 0.35 micrograms/ml was reached after 1.4 +/- 0.67 h. The half-life time of elimination was 229 +/- 41 min. About 50% of the dose of tiapride was excreted unchanged by the kidney. Neither protein binding nor glucuronide, sulphate or acetyl conjugation was observed. Renal clearance in the patients appeared to be lower but the other pharmacokinetic parameters did not differ from previous findings in healthy young volunteers.

Aged↗

Analgesic and antidepressive effects of low-dose amitriptyline in relation to its metabolism in patients with chronic pain.

The analgesic and antidepressive effects of amitriptyline (AT) in relation to its kinetics and metabolism were studied in 19 outpatients with chronic pain who received a daily dose of 75 mg AT for at least 6 weeks. Riboflavin was added to the medication to check compliance. On days 0, 4, and 8 and weeks 3, 6, 9, and 12 after the start of dosing, blood samples were drawn from the patients 10 +/- 1 hours after the first morning dose and a sample of the first morning urine was taken to check riboflavin. Serum levels of AT and its metabolites, especially nortriptyline (NT) and E-10-hydroxy-nortriptyline (E-10-OH-NT), were measured by HPLC. On day 0 and at 3, 6, and 12 weeks the severity of depression was scored by means of a self-rating depression scale and pain intensity scores were measured. In addition, after 6 weeks of dosing patients estimated their percentage of pain in comparison with baseline. Mean (+/- SD) steady-state concentrations of AT, NT, and E-10-OH-NT were 36 +/- 23.5, 28 +/- 14.9, and 52 +/- 23.7 micrograms/L, respectively, in male patients (n = 8; age 45 +/- 7.4 years) and 34 +/- 14.6, 45 +/- 25.1, and 40 +/- 15.6 micrograms/L, respectively, in female patients (n = 11; age 46 +/- 6.8 years). There was a significant sex-related difference in the NT/AT ratio, which was higher in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗