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Biomedical subjects

A J Moolenaar

Publications and source records attributed to A J Moolenaar.

At least 55 records · Page 3Linked to original sources

O,p'-DDD (mitotane) levels in plasma and tissues during chemotherapy and at autopsy.

The distribution of o,p'-DDD in various body compartments of patients being treated for metastatic adrenocortical carcinoma was studied. A highly significant semilogarithmic relationship was found between plasma and adipose tissue concentrations during therapy and between plasma and brain at autopsy. A linear relationship was found at autopsy between concentrations in adipose tissue and those in various other tissues, such as tumour and brain. The semilogarithmic relationship can be explained by the assumption of two plasma pools for o,p'-DDD, one with low affinity and high capacity and one with high affinity and low capacity. Plasma concentrations must be carefully monitored to obtain an impression of the tumour concentration and to detect impending central nervous system intoxication.

Adipose Tissue↗

Blood levels of o,p'-DDD following administration in various vehicles after a single dose and during long-term treatment.

Plasma levels of o,p'-DDD were measured after ingestion of a single oral dose. At the onset of therapy o,p'-DDD was administered as commercially available tablets and granules and in milk, chocolate, and an oil emulsion to 9, 12, 14, 10, and 6 patients, respectively. Following administration in chocolate, emulsion, and milk significantly higher mean plasma levels were recorded in the first 5- and 10-h periods than after tablets. Granules gave significantly lower plasma levels than all other forms. Plasma levels were also measured during maintenance therapy, when a total of 200 g o,p'-DDD was administered to 22 patients with adrenocortical carcinoma. The plasma disappearance rate after termination of long-term therapy was found to be between 18 and 159 days. The recovery of o,p'-DDD from faeces was about five times higher after ingestion of tablets than after administration in oil emulsion and milk. As far as the rapid increase in plasma levels and patient compliance are concerned, the best results were obtained with the milk powder mixture.

Administration, Oral↗

Adrenocortical tumour in untreated congenital adrenocortical hyperplasia associated with inadequate ACTH suppressibility.

Data are presented concerning a 60-year-old woman with untreated congenital adrenocortical hyperplasia due to 21-hydroxylase deficiency, who presented with a tumour of the left adrenal gland. Steroid excretion was partly suppressed with dexamethasone. After removal of the tumour, the excretion of several steroid fractions decreased substantially, but suppression by dexamethasone remained inadequate. Preoperatively, plasma ACTh was elevated in the afternoon and decreased only slightly after dexamethasone administration. After surgery, cortisol secretion decreased markedly, whereas ACTH dysregulation became more prominent. Negative feedback failure precluded the use of normal suppressive therapy with low doses of glucocorticosteroids and led to the therapeutic removal of the right adrenal gland, which showed histological signs of nodular hyperplasia.

Adenoma↗

The determination of cortisol in human plasma: evaluation and comparison of seven assays.

In a comparative study, seven different methods for the determination of cortisol in human plasma were evaluated, using routine patient samples. Four of these methods used radioactive steroids (125I- or 3H-labelled) and in three no radioactivity was needed. For the statistical evaluation a direct 3H-radioimmunoassay was arbitrarily taken as the independent variable. It was found that all other methods correlated well with this assay. However, the simplest method, the fluorimetric, cannot be recommended mainly because of its non-specific fluorescence and troublesome interference from some widely-used drugs. Of the methods evaluated a radioimmunoassay is recommended. For laboratories having no equipment for measurements of radioactivity, the more elaborate and time-consuming fluorometric method of Clark may represent a good alternative.

Binding, Competitive↗

The influence of bromocriptine on serum levels of growth hormone and other pituitary hormones and its metabolic effects in active acromegaly.

The effect of treatment with bromocriptine for 12--18 months on serum GH and metabolic responses was studied in sixteen patients with active acromegaly. Of this group ten patients showing a sustained GH reduction of more than 50% during an 8 h bromocriptine test, proved to be responsive to long-term therapy. In the responding patients GH levels decreased to 38% of the pretreatment level after 12 months of therapy. A dose higher than 10 mg did not produce a significantly greater effect. Prolactin and LH levels decreased in all patients, FSH levels showed a significant rise. Testosterone levels in the male patients increased significantly, indicating that the state of hypogonadism can at least be partially reversed. The GH levels became normal in only one patient. We conclude that the role of bromocriptine in acromagaly is limited and selective pituitary operation and/or irradiation is preferred as definitive treatment in most patients.

Acromegaly↗

A rapid semi-automated method of determining total estrogens in non-pregnancy urine.

A rapid routine method of determining estrogens in non-pregnancy urine is described. It involves the following steps: 1) Dilution of each urine sample with an equal volume of saturated ammonium sulfate solution; 2) Addition of Sephadex G-15 beads; 3) Filtration of the mixture; 4) Liberation of the estrogens from the Sephadex by washing the beads on the filter with 0.1N NaOH; 5) Automated fluorimetric analysis of the alkaline filtrate according to the procedure used for the determination of estrogen in pregnancy urine. A correction for non-specific fluorescence remains necessary and is achieved by measuring background fluorescence with a second fluorimeter.

Chromatography, Gel↗

Plasma levels of triamcinolone acetonide as determined by radioimmunoassay after topical application.

In this paper a method for the radioimmunological determination of triamcinolone acetonide (TAAc) in plasma is described. The antiserum used in the radioimmunological determinations showed high specifity for TAAc; the minimal detectable amount was 0.2 ng. The course of the plasma concentration-time curve of TAAc after intravenous injection into rats was analysed. The concentration of TAAc in the blood of the patients after topical application of the drug is very low. No detectable amount of TAAc was found in the blood of out-patients. Hospitalized patients treated with TAAc under plastic occlusion showed plasma levels ranging from 0.8 to 3.4 ng/ml. This level remained constant throughout the treatment.

Animals↗

Estimation of o,p'-DDD in plasma by gas-liquid chromatography.

A method is described for the estimation of o,p'-DDD in plasma. To 50 microl plasma, 0.2 ml acetone is added. The mixture is extracted with 2 ml n-heptane containing p,p'-DDD as an internal standard. Water is removed by adding desiccated sodium sulfate. The organic phase can be injected into a gas chromatograph equipped with an electron capture detector. The o,p'-DDD content of the sample can be read from a calibration curve. Recovery of o,p'-DDD added to plasma is over 93%. The same procedure can be used for the estimation of o,p'-DDE.

Chromatography, Gas↗

The influence of combined cyproterone acetate-ethinyl oestradiol therapy on serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women.

Serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women suffering from either idiopathic hirsutism or the polycystic ovary syndrome were determined before and during treatment with cyproterone acetate combined with ethinyl oestradiol. During this treatment the hirsutism decreased markedly. In untreated hirsute women serum dehydroepiandrosterone levels do not differ from those in normal women and do not change during therapy; androstenedione levels are higher than normal and decrease markedly during treatment, and the testosterone levels are elevated compared to normals, with a considerable overlap, and show only a tendency to decrease. There is no correlation between dehydroepiandrosterone and androstenedione levels or between androstenedione and testosterone levels in the serum of untreated hirsute women. After 12-14 months of cyproterone acetate-ethinyl oestradiol therapy a linear correlation is found between dehydroepiandrosterone and androstenedione levels. This can be explained by the relatively higher contribution of the peripheral conversion of dehydroepiandrosterone to androstenedione to the occurrence of lower androstenedione levels. The linear correlation between androstenedione and testosterone after treatment, also found in normal women, indicates the restoration of the role of androstenedione as the major peripheral precursor of testosterone.

Adolescent↗

Female phenotype in a male child due to 17-alpha-hydroxylase deficiency.

The discovery of testicles in a 3-year-old girl with XY karyotype led to a diagnosis of testicular feminization. Subsequently, however, hypokalaemia, hypertension, and severe prostration during a mild infection suggested adrenal involvement, and investigations showed a 17-alpha-hydroxylase deficiency. Diagnosis of testicular feminization should not be made without excluding a defect of testosterone synthesis.

Adrenocortical Hyperfunction↗