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Biomedical subjects

L Abrahamsson

Publications and source records attributed to L Abrahamsson.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics of triazolam in geriatric patients.

Serum triazolam levels were determined in eight geriatric patients (average age 80 years) on Days 1 and 7 of administration of triazolam 0.25 mg once daily, 1 h after a standard breakfast. Triazolam was rapidly absorbed reaching average peak concentrations of 2.0 and 2.04 ng/ml, 1.5 and 1.38 h after administration on Days 1 and 7, respectively. The mean apparent elimination half-life was 1.41 h (range 0.73-4.13 h) on Day 1 and 1.37 h (range 0.69-3.36 h) on Day 7. There was no significant difference between mean serum triazolam concentrations or pharmacokinetic parameters on Days 1 and 7 of the treatment. Serum samples were also assayed for alpha-hydroxytriazolam, an active metabolite of triazolam, but none could be detected in any of the samples from Days 1 or 7, assay sensitivity 0.09 ng/2 ml serum. The range of half-lives of triazolam in the patients in the present study is in close agreement with that previously reported in elderly subjects. The study provides further evidence of the lack of change in pharmacokinetic parameters on multiple dosing and that drug accumulation did not occur.

Aged↗

Effects of a continuous estrogen-progestogen therapy for climacteric symptoms on circulating sex steroids and gonadotrophins.

Twenty-six peri- and postmenopausal women with climacteric symptoms were given each day for 1 year a tablet containing 2 mg 17-beta-estradiol, 1 mg estriol and 1 mg norethisterone acetate. Blood samples were collected before, after 3 months and after 12 months of treatment and were analysed for their gonadotrophins, estradiol, estrone, testosterone, androstenedione content and for their SHBG binding capacity. Serum levels of estrone and androstenedione before treatment were found to be higher in the perimenopausal than in the postmenopausal group. An increase of serum estrogens concomitant with a decrease of gonadotrophins was noted. The estrone/estradiol ratios after 3 and 12 months of treatment were 5.3 and 4.7, respectively. A decrease in the serum concentration of testosterone and androstenedione was recorded during treatment. The reduction of gonadotrophins, especially LH, might have been responsible for the reduction in circulating androgens. The reduction of serum levels of androgens during the present long-term replacement therapy could be of metabolic importance.

Adult↗

Kinetics and concentration effects of TPA-induced differentiation of cultured human neuroblastoma cells.

SH-SY5Y human neuroblastoma cells differentiate morphologically and biochemically in the presence of 12-0-tetradecanoylphorbol-13-acetate (TPA). The degree of differentiation, as demonstrated by the appearance of cell surface projections, growth inhibition and increase in noradrenalin concentration, was dependent on the TPA concentration and had an optimum at 1.6 X 10(-8) M of TPA. At that concentration neuron specific enolase (NSE) increased to a maximum level after 10 days of culture with no further changes in the NSE level during additional culture for 10 days. In contrast, the noradrenalin concentration reached a maximum after 4 days of TPA treatment and decreased during longer exposures to TPA. Based on the facts that the phorbolester induced differentiation shows stereo specificity and was optimal at the same concentration range as common polypeptide hormones, a putative TPA-hormone receptor interaction is discussed. An opposite effect of TPA on the SH-SY5Y cells, antagonizing the differentiation effect, is further suggested to explain the decrease in differentiation observed at TPA concentrations higher than 1.6 X 10(-8) M.

Caenorhabditis elegans Proteins↗

Quantitative analysis of plasma nicotine using selected ion monitoring at high resolution.

A highly sensitive and specific method for the quantitative determination of nicotine in plasma is described. Using simple one-step work-up technique and (5',5'-2H2) nicotine as internal standard, the analytical procedure is based on combined capillary column gas chromatography and high resolution selected ion monitoring. Incorporation of a specially designed gas chromatograph/mass spectrometer interface allowing introduction of the eluent by a fused silica capillary via the direct inlet port into the ion source brings the detection level for nicotine in an alcoholic solution down to below 100 fg. The discriminatory nature of the method also makes it well suited for studying ambiguities of instrumental nicotine assay and some of these are discussed.

Gas Chromatography-Mass Spectrometry↗

[Long-term treatment of virilized women with cyproterone acetate (author's transl)].

76 women with virilizing features (68 women suffering from hirsutism and 8 from acne) were treated on average for 25 months according to different models of Androcur medication. Success of treatment was clinically assessed as good in 3/4 of the cases and slight in the remaining 1/4. However, treatment is more successful in cases of adrenal hirsutism than in idiopathic hirsutism. Moreover, success of treatment seems to be better in women below 35 than over 35 years of age. Side effects, mostly bleeding anomalies and fatigue, were found in 31 women; these must be attributed to the gestagenic component of cyproterone acetate. By contrast, 12 women showed positive side effects such as weight reduction, improvement in depression states and reversal of hair loss, which must be attributed to the antiandrogenic component. The selected continuation rate in all subjects was 86% and the unselected 72%, over a treatment period of 4.5 years. Furthermore, hormonal controls were carried out under treatment. These showed, on average, a depression of plasma androstendione of 17%, of total plasma testosterone of 47%, as well as an inhibition of the testosterone/sex hormone-binding globulin quotient of 58%. These inhibition effects speak in favour of alterations taking place in steroid metabolism. However, by inhibition of androgenic serum levels, the mechanism of cyproterone acetate is only assisted, while the main mechanism is based on peripheral receptor inhibition. Furthermore, as additional component in this action a slight increase in plasma binding capacity was found during combined cyproterone-oestrogen treatment.

Acne Vulgaris↗

Catabolic effects and the influence on hormonal variables under treatment with Gynodian-Depot or dehydroepiandrosterone (DHEA) oenanthate.

53 patients from a mainly climacteric population were treated monthly with 200 mg dehydroepiandrosterone (DHEA) oenanthate or with 1 ampoule Gynodian-Depot. Pronounced adiposity was present in 15 of these cases. Hormonal variables were determined before the treatment and during the depot effect of the preparations in order to study the principle which supports the oestrogenic influence and any weight-reducing influence under administration of DHEA. The elimination of low-polar oestrogens increased considerably in 4 out of 13 post-menopausal cases treated with DHEA. This effect is probably indirect and presupposes intact ovaries. The incorporation of exogenous DHEA into the excretion of 17-ketosteroids and of 17-ketogenic steroids, such as those of androsterone + aethio-cholanolone, depends on the size of the initial pool inasmuch as it is higher in small initial pools than in saturated pools- the size of the pool being age-dependent. An average weight loss of greater than 1 kg/mth was observed under DHEA treatment in 7 out of 15 adipose cases. In comparison to the other 8 adipose cases, these 7 were younger and therefore also displayed higher values for 17-ketosteroids and their individual fractions. These circumstances appeared to explain why the administration of DHEA resulted in higher levels of free plasma DHEA which, in contrast to the cases without loss of weight, also resulted in an increase of renal DHEA-sulphate clearance. It was concluded from the findings that this is the explanation for the catabolic effect of exogenous DHEA. Post-menopausally increased FSH and LH fractions were markedly suppressed in about half of the determinations after Gynodian-Depot administration, the findings indicating that DHEA is probably involved in suppression of the LH fraction.

17-Hydroxycorticosteroids↗

[Clinical results and hormonal aspects of the treatment of virilizing symptoms in women with cyproterone acetate (author's transl)].

28 cases of moderate to severe hirsutism, two cases of acne and one case of axilary hidrosadenitis were tested continuously on average over 6 months by the daily administration of 100 mg cyproterone acetate. This drug was then given together with 1-2 mg oestradiol valerate over a further 6 month period by reversed sequential therapy. The effect of treatment was judged as being moderate only in 7 cases of idiopathic and one case of adrenal hirsutism and good in the remaining cases. However, this regimen caused a marked lowering of the urinary dehydroepiandrosterone sulphate and low polar oestrogen levels and also the plasma testosterone level. At the same time, according to preliminary results, the fraction of sex hormone binding globulin was raised. The plasma hydrocortisone level was depressed by about 20%. The fractions of 17-KS and 17-KGS decreased slightly at first, but then returned to normal. The side effects of continuous treatment were mainly gestagenic and of reversed sequential therapy mainly oestrogenic in nature. The continuation rate was 81% during a treatment period of two years.

17-Ketosteroids↗

Hormone profile in premenstrual tension: effects of bromocriptine and diuretics.

Plasma levels of prolactin, FSH, LH, progesterone and 17-beta-oestradiol in twenty women with premenstrual tension were compared with those in twenty controls. The former group was studied also during treatment with bromocriptine. The mean prolactin level in the PMT group was lower in the follicular phase than in the luteal phase (P less than 0.01), but there was no difference between the PMT and control group in the luteal phase. No differences were found between the controls and the PMT group in FSH,LH, 17-beta-oestradiol and progesterone levels in the luteal phase. Bromocriptine suppressed prolactin concentrations (P less than 0.01), but had no effect on the FSH, LH, 17-B-oestradiol or progesterone levels.

Adult↗

[Clinical screening of sterility cases for the possible presence of luteal phase defect (author's transl)].

Eighty consecutive cases of sterility was screened for suspected insufficiency of luteal function. The parameters used in the assessment were one value each for pregnandiol and oestrogen excretion, the basal temperature, the histological picture of secretory endometrium, as well as the activity of endometrial malate dehydrogenase and carbonanhydrase, or malate dehydrogenase and succinic dehydrogenase. Histological irregularities, a short luteal phase as indicated by the basal temperature, early abortion and a pregnandiol excretion of less than 1.9 mg were usually accompanied by low endometrial enzymatic acitvity. A comparison of pregnandiol excretion levels with the other four investigated parameters indicated that the number of negative findings increased with decreasing pregnandiol values. In this way, low oestrogen excretion values occurred more frequently with low pregnandiol values. However, when taken in conjunction with other findings, a low oestrogen value does not seem to be characteristic of luteal insufficiency. In certain cases the suspicion of luteal insufficiency increases with decreasing pregnandiol values and with the number of negative findings concerning basal temperature, endometrial histology and enzymatic activity, as well as oestrogen excretion. According to this point of view the incidence of a presumptive luteal phase defect was 33% in the present investigation.

Corpus Luteum↗