Biomedical subjects
Publications and source records attributed to E Diczfalusy.
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Ten patients with previously untreated prostatic carcinoma were studied to evaluate the hormonal effects of different doses of estramustine phosphate (Estracyt). The drug was given by mouth in increasing doses; during the first month 70 mg daily, during the second 140 mg, during the third 280 mg and during the fourth and following months 560 mg. The following hormonal parameters were studied before the treatment and then once weekly during a period of four months: testosterone, dihydrotestosterone, androstenedione, cortisol, FSH and LH. The levels of the steroids were also re-assessed one to two years later. The patients were also followed clinically at regular intervals. Initial testosterone levels of approximately 20 nmol/l plasma were reduced to approximately 0.6 nmol/l already by the lowest Estracyt dose of 70 mg/day. No further decrease was obtained by a stepwise increase of doses up to 560 mg/day. The plasma levels of dihydrotestosterone, androstenedione, FSH and LH were also reduced significantly following the administration of the lowest daily Estracyt dose and then remained at that low level. Cortisol levels increased steadily during the four months of the study. After longterm treatment the hormonal indices were by and large the same as during the last initial treatment period. Initially, the clinical effect of the treatment was excellent. In 4 patients, however, the therapy had to be discontinued after some time, because of complicating oedema (2 patients) or refractoriness to therapy (2 patients). Three years after initiating the therapy 6 patients still were on Estracyt treatment. All of them were doing well subjectively. In 5 patients the prostatic cancer was in remission or at least stable. In one patient, however, skeletal metastases were progressing. In conclusion, Estracyt was found to possess a maximal hormonal (oestrogenic) effect already in doses far below those usually recommended.
Since many contraceptives appropriate for use in developing countries are not of major interest to the pharmaceutical companies in developed countries, the World Health Organization has sponsored a program whereby contraceptives are developed outside the traditional pharmaceutical industry channels. This program might serve as a model for the develoment of other drugs or even pesticides.
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In order to assess the pharmacokinetics properties of estradiol cypionate, valerate and benzoate, the daily plasma levels of estradiol and estrone were analysed in groups of 10, 9 and 10 subjects, respectively, before and during 3 weeks after the intramuscular administration of a single dose of 5.0 mg in 1.0 ml arachis oil. In order to minimize the contribution of endogenous estrogens to the plasma levels, all subjects were receiving a combined oral contraceptive consisting of levonorgestrel (150 micrograms) and ethinyl estradiol (30 micrograms) for three months prior to the study and during the study period. The administration of estradiol cypionate gave significantly lower peak levels of estradiol and estrone than that of the valerate and benzoate. Peak plasma levels of estradiol and estrone were reached in approximately 4 days following the administration of estradiol cypionate and in a significantly shorter time (approximately 2 days) following the administration of both the valerate and benzoate. One hour after the injection of the esters, the average percentage increases in plasma estradiol and estrone levels were significantly higher in the valerate and benzoate groups compared to the subjects receiving estradiol cypionate. The average duration of elevated estrogen levels was shortest in the benzoate group (4-5 days) followed by the valerate (7-8 days) and cypionate (approximately 11 days). In none of the subjects studied were elevated estradiol and/or estrone levels encountered 2 weeks after the injection of the various esters. The data suggests that among the three esters studied, the valerate provides the most predictable pharmacokinetic behaviour.
Fifteen patients underwent first-trimester abortion by one of two techniques. In group P, seven patients received prostaglandin vaginal suppositories during the 12 hours prior to vacuum aspiration, whereas eight patients in group V were aborted by aspiration alone. During the first postabortion menstrual cycle, daily peripheral blood levels of several hormones, including follicle-stimulating hormone (FSH), luteinizing hormone, human chorionic gonadotropin, estradiol, and progesterone, were determined. Patients in group P demonstrated a more rapid fall in progesterone levels following pregnancy termination (P less than 0.01). They also experienced a more physiologic first postabortion cycle as evidenced by a larger preovulatory estradiol peak (P less than 0.05) and a more normal luteal phase as judged by both the duration and elevation of progesterone levels. Certain endocrine changes common to both groups but different from those of normally menstruating women were also observed. These consisted of short-term spurts of progesterone secretion in many patients (10 of 15) prior to ovulation and exaggerated levels of FSH during the early follicular phase.
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Freshly prepared aqueous decocts of the Mexican plant Montanoa tomentosa (Zoapatle) were administered orally to six women in the early stages of pregnancy for two days prior to the interruption of gestation by vacuum aspiration. The daily dose administered varied between 1.0 and 1.4 gm-equivalent of dry leaves per kilogram of body weight. A comparable control group of six pregnant women received the same volume of commercial tea according to the same schedule before vacuum aspiration. Administration of Zoapatle extracts resulted in a menstrual-like cramp and a significant dilatation of the cervix in all subjects studied. In four of the six subjects the menstrual-like pains were associated with bleeding. No comparable effects were observed in the control group. Peroral administration of Zoapatle decocts did not produce any cardiovascular changes, and it did not influence the hematologic status, liver, kidney, and thyroid function, blood lipids, proteins, and electrolyte status. Under the experimental conditions used, Zoapatle extracts did not induce a luteolytic effect judged from the plasma progesterone (and estradiol) levels. It is concluded that peroral administration of freshly prepared decocts of Zoapatle in early pregnancy exerts a distinct uterotonic effect and induces cervical dilatation and uterine bleeding. These changes are not associated with any effect on the plasma levels of progesterone and estradiol or with any untoward side effects.
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