[3-Methylglutaconic aciduria].
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Acidosis↗
Biomedical subjects
A Ruokonen
Publications and source records attributed to A Ruokonen.
Alpha-thiolproteinase inhibitor, alpha 1-antitrypsin and serum proteins in suction blister fluid; effect of local glucocorticosteroid treatment.
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Adult↗
Regulation of serum testosterone in men with steroid sulfatase deficiency: response to human chorionic gonadotropin.
Human chorionic gonadotropin (hCG; 5000 IU) was administered to 6 control men and 6 patients with recessive x-linked ichthyosis (RXLI) with verified 3 beta-hydroxysteroid sulfate sulfatase (3 beta-HSS) deficiency in their skin biopsy samples. Concentrations of steroids and their sulfate conjugates were determined in peripheral serum specimens collected a day before and 4 days after hCG administration. Testosterone concentrations were identical in patients and controls. Baseline serum LH concentrations were also identical in the 2 groups showing that there were no major differences in the regulation of the hypothalamic-pituitary-gonadal axis. The significantly increased (31-82%) serum concentrations of sulfated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol in patients compared with controls indicated that their circulating concentrations were regulated by 3 beta-HSS. This is in line with the fact that the baseline concentrations of the same unconjugated steroids were significantly lower (32-90%) in patients with RXLI, suggesting that a proportion of these circulating steroids were derived from the corresponding sulfated precursors. The response patterns and actual concentrations of testosterone, 17-hydroxyprogesterone and estradiol were similar in the patients and the controls after hCG. The decreased concentrations of testosterone sulfated at carbon 17 under baseline conditions and after hCG in patients with RXLI remains enigmatic. In conclusion, testosterone production and the response to hCG seem to be identical in patients with RXLI and controls despite the fact that significant differences were observed in the circulating concentrations of several unconjugated and sulfated testosterone precursors.
Adult↗
Comparison of the effects of follicle-stimulating hormone and human menopausal gonadotropin on peripheral serum and follicular fluid hormones during ovarian stimulation.
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Adult↗
[An internal quality control system for the detection of clinically significant analytical errors].
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Clinical Laboratory Techniques↗
Hormonal parameters and conception rate during five different types of treatment of polycystic ovarian syndrome.
Hormonal parameters and conception rate of 66 women with polycystic ovarian syndrome (PCO) were studied in a prospective way. Main therapy was clomiphene citrate (N 25) for 6 cycles. Previous clomiphene failures (N 23) underwent ovarian wedge resection, and they who did not menstruate after wedge resection (N 9) received further clomiphene as above. Patients, who did not want to conceive, were treated with dydrogesterone (N 11) or with an estrogen-progestin combination pill (N 7). Clomiphene citrate and ovarian wedge resection decreased luteal phase FSH and LH levels, increased serum estradiol and resulted in frequent ovulations (clomiphene 80%, wedge resection 45%, wedge resection + clomiphene 67%) and pregnancies (clomiphene 60%, wedge resection 36%, wedge resection + 67%), whereas cyclic progestin and estrogen-progestin treatment lowered elevated serum testosterone concentrations without influencing on FSH or luteinizing hormone (LH) levels. Thus clomiphene citrate seems to be the therapy of choice in infertile PCO patients, whereas progestin or estrogen-progestin lower the elevated testosterone concentrations in serum.
Adult↗
Testicular responsiveness to hCG before and after long-term antiestrogen treatment in oligozoospermic men.
In order to further investigate the role of endogenous estradiol in the regulation of testicular steroidogenesis an hCG-stimulation test (a single dose of 5000 i.u. i.m.) was performed in 5 normogonadotropic oligozoospermic men before and after 3 months of antiestrogen (clomiphene citrate = CC) treatment (50 mg p.o. daily). Peripheral blood samples were collected immediately before hCG administration and thereafter at 1, 4 and 7 days, and were analyzed for testosterone (T), estradiol (E2), 17-hydroxyprogesterone (17-OHP4), 17-hydroxypregnenolone (17-OHP5), 11 other free and sulfate-conjugated steroids, and for sex hormone-binding globulin (SHBG). The results demonstrated that CC-treatment caused a significant rise in peripheral serum concentrations of SHBG, T, 5 alpha-dihydrotestosterone (DHT), E2 and the sulfate conjugates of pregnenolone, 17-OHP5, 5-androstene-3 beta, 17 beta-diol and T. In the basal state, before the CC-treatment, apparently normal responses to hCG were seen in unconjugated steroids: 17-OHP4 and E2 concentrations were significantly elevated at 1 day, and those of T at 4 days. After CC, only the concentrations of 17-OHP4 rose significantly following hCG administration. The peripheral serum concentrations of the 5-ene- and sulfate-conjugated precursors of T were not influenced by hCG in the basal state or after CC. These results suggest that the apparently E2-mediated inhibition of 17,20-lyase activity in the 4-ene-pathway of T synthesis could not be totally prevented by long-term antiestrogen treatment, and that in the 5-ene-pathway no sign of 17,20-lyase inhibition was demonstrated either before or following CC-treatment. The significant rise in the circulating concentrations of sulfate-conjugated steroids following long-term CC administration, apparently due to increased synthesis of T and its precursors in the 5-ene-pathway, strengthens the concept of their importance in testicular steroidogenesis.
Adult↗
Relationships between unconjugated and sulphated steroids in porcine primary Leydig cell culture.
Steroidogenesis in immature porcine Leydig cells was investigated in primary culture at 48-84 h under basal conditions and in the presence of hCG. The basal accumulation of unconjugated steroids was close to linear only during the first 4 h of study, whereas the sulphate-conjugated steroids accumulated essentially linearly over the 36 h experimental period. At the last time point, 95% of the steroids measured were sulphated. Stimulation with hCG (1 ng/ml) led to a still more pronounced sulphate conjugation, and approx 99% of the steroids measured were sulphated at 36 h. Under maximal stimulation with hCG (100 ng/ml) the sulphates accounted for 74% of the total steroids measured at 36 h. Testosterone, androstenedione, dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol and estrone were usually quantitatively the most important unconjugated steroids, and sulphated dehydroepiandrosterone, estrone, testosterone and 5-androstene-3 beta, 17 beta-diol were the most important steroid sulphates, especially following maximal stimulation of the cultures. These data emphasize the importance of steroid sulphates in porcine testicular steroid metabolism. Under stimulation with hCG, there was a rapid response in testicular steroidogenesis, initially seen as a rapid increase in the secretion of unconjugated and sulphated steroids. At approx 4-12 h, the rate of sulphate conjugation appeared to reach or even to exceed that of steroid biosynthesis, which lead to stabilisation or a decrease in the concentrations of unconjugated steroids. Only high doses of hCG, 10-100 ng/ml, were then able to lead to a net accumulation of unconjugated steroids, at 24-36 h of incubation with hCG.
Animals↗
Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man.
The influence of high doses of testosterone and anabolic steroids on testicular endocrine function and on circulating steroid binding proteins, sex hormone binding globulin (SHBG) and cortisol binding globulin (CBG), were investigated in power athletes for 26 weeks of steroid self-administration and for the following 16 weeks after drug withdrawal. Serum testosterone and androstenedione concentrations increased (P less than 0.05) but pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol, progesterone and 17-hydroxyprogesterone concentrations strongly decreased (P less than 0.001) during steroid administration. Serum pregnenolone, 17-hydroxypregnenolone and dehydroepiandrosterone sulphate concentrations followed the changes of the corresponding unconjugated steroids but 5-androstene-3 beta, 17 beta-diol and testosterone sulphate concentrations remained unchanged during the follow-up time. During drug administration SHBG concentrations decreased by about 80 to 90% and remained low even for the 16 weeks following steroid withdrawal. Steroid administration had no influence on serum CBG concentrations. In conclusion, self-administration of testosterone and anabolic steroids soon led to impairment of testicular endocrine function which was characterized by low concentrations of testosterone precursors, high ratios of testosterone to its precursor steroids and low SHBG concentrations. Decreased concentrations of SHBG and testicular steroids were still partly evident during the 16 weeks after drug withdrawal. The depressed circulating levels of dehydroepiandrosterone and its sulphate may indicate that the androgenic-anabolic steroids also suppress adrenal androgen production.
17-alpha-Hydroxypregnenolone↗
Effects of desogestrel, levonorgestrel and lynestrenol on serum sex hormone binding globulin, cortisol binding globulin, ceruloplasmin and HDL-cholesterol.
The effects of 0.125 mg daily doses of the new progestagen, desogestrel, 0.125 mg of levonorgestrel or 5 mg of lynestrenol on serum sex hormone binding globulin (SHBG), cortisol binding globulin (CBG), ceruloplasmin and HDL-cholesterol were studied in 30 healthy female volunteers to compare the possible androgenic and oestrogenic effects of these contraceptive steroids in vivo. All the progestagens in the applied dosages decreased SHBG and HDL-cholesterol concentrations, suggesting some androgenicity. Lynestrenol increased ceruloplasmin and CBG concentrations, indicating weak oestrogenic effects of the steroid. During desogestrel treatments, CBG and ceruloplasmin concentrations remained unchanged. After 30 days treatment with levonorgestrel there was a slight decrease (P less than 0.05) in ceruloplasmin concentrations. Thirty days after finishing the progestagen treatments serum protein concentrations were normal. In conclusion, at the doses used and under the present test conditions the progestagens studied had a weak androgen-like effect and lynestrenol also showed weak oestrogenic activity, as determined by their effects on serum proteins.
Adolescent↗
Metoclopramide and breast feeding: efficacy and anterior pituitary responses of the mother and the child.
The purpose of this randomized, double-blind clinical study was to evaluate the efficacy of the antidopaminergic agent metoclopramide (MC) in the treatment of puerperal lactational insufficiency, and prolactin, TSH and free thyroxine responses of the mother and the child to this therapy. Therefore, 11 women received MC (10 mg 3 times daily orally) and 14 a placebo for 3 wk. MC increased the serum concentration of PRL from 57.5 + 45.5 U/l to 315.0 + 300.0 U/l (P less than 0.001), and the amount of daily milk yield in 8 women with established lactational deficiency rose from 285 + 75 ml to 530 + 162 ml (P less than 0.01) while the placebo was ineffective. Serum concentrations of TSH and free thyroxine did not change during either of the treatments. Serum concentrations of PRL, TSH and free thyroxine in the infants were similar in both groups and remained unchanged throughout the study. Our results suggest that MC is useful in the treatment of deficient puerperal lactation, and it does not stimulate the pituitary lactotropes or thyrotropes of the nursing infants.
Adult↗
Short-term effects of testolactone on human testicular steroid production and on the response to human chorionic gonadotropin.
Testicular responsiveness to a single dose of human chorionic gonadotropin was studied in five normal men before and during short-term treatment with an aromatization inhibitor, testolactone (TL). TL alone resulted in significant increases in the serum concentrations of progesterone, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione, and the sulfate conjugates of pregnenolone, 17-hydroxypregnenolone and testosterone (T). Concentrations of 5-androstene-3 beta, 17 beta-diol and T remained unchanged, and those of estradiol (E2) decreased. TL had no major influence on serum luteinizing hormone, follicle-stimulating hormone, prolactin, or sex-hormone-binding globulin concentrations. During TL administration, human chorionic gonadotropin stimulation led to a significantly decreased E2 response, but the T response was unchanged. Alleviation of an inhibitory influence of E2 on the steroidogenic enzymes, especially 17,20-desmolase, was probably the reason behind the increased synthesis of several T precursors. In addition, TL appeared to have an inhibitory influence on the 17 beta-reduction of T precursors. TL resulted in increased serum concentrations of some steroid sulfates, but the mechanism of this effect remains unclear.
Adult↗
Finnish type of sialic acid storage disease with sialuria (Salla disease): the occurrence and diagnostic significance of cytoplasmic vacuoles in blood lymphocytes.
In this study peripheral blood smears from 29 patients (17 males and 12 females; mean age 28 years, range 3-65 years) with a confirmed diagnosis of the Finnish type of sialic acid storage disease (FSASD) and 200 controls with mental retardation without any evidence of metabolic disease were examined for the presence of vacuolated lymphocytes. Urine samples were analysed by thin-layer chromatography for free sialic acid. Only 62% of the patients with FSASD had a clearly increased percentage of vacuolated lymphocytes (greater than normal mean + 2 s.d.). In thin-layer chromatography all the FSASD patients gave a positive test result. No false positive or negative results were obtained. Electronmicroscopical examination of peripheral blood lymphocytes demonstrated only non-specific changes in a few cells. Examination of peripheral lymphocytes for vacuoles is not a reliable screening test for FSASD. The screening method of choice is the analysis of free sialic acid by thin-layer chromatography.
Adolescent↗
Ichthyosis hystrix (Curth-Macklin). Light and electron microscopic studies performed before and after etretinate treatment.
Clinical and light and electron microscopic observations of a 16-year-old male patient suffering from ichthyosis hystrix (Curth-Macklin) are presented. The patient had no family history for this disease. The diagnosis was based on the distinct electron microscopic finding of continuous perinuclear tonofibril shells in the keratinocytes. About 10% of the keratinocytes were binucleate and one third contained conspicuous vacuoles. The steroid sulphatase activity in a skin biopsy was normal. Etretinate treatment proved beneficial during the first year of therapy. Later the treatment was less effective. The basic genetic defect persisted in the phenotype of the keratinocytes during etretinate therapy, but the exceedingly thick horny layer was considerably thinned.
Adolescent↗
Gallium67 citrate scanning in patients with lacrimal gland and conjunctival sarcoidosis. A report on three cases.
Gallium citrate Ga67 scanning of the head and thorax of 3 patients with sarcoidosis is presented. Two patients had a progressive pulmonary sarcoidosis of recent onset and in one patient, with a chronic course of the disease, the lung changes had resolved. All 3 patients had a conjunctival sarcoid change confirmed by biopsy and a lacrimal gland affection suggested by clinical examination. A highly increased Ga67 uptake in the lacrimal and parotid glands as well as in the nasopharynx was found in all patients, and an increased lung uptake was found in the newly detected cases. It is concluded that gallium scanning is a sensitive method for detecting minute ophthalmic changes in sarcoidosis. It also reveals chronic localized ocular affection in cases in which the lung changes are no longer detectable. The mechanism and specificity of gallium uptake in sarcoidosis is also discussed.
Adult↗
External quality assessment of serum hormone determinations in the Nordic countries.
Since 1979 the Nordic Clinical Chemistry Project (NORDKEM) has organized four external quality assessment surveys of serum hormone determinations in the five Nordic countries. Charcoal-stripped control sera with weighed additions of the following hormones have been used: thyrotropin, human placental lactogen, prolactin, estriol, estradiol, testosterone, cortisol, triiodothyronine, thyroxine, and, in the fourth survey, progesterone. Human serum was usually used but in the first survey the serum matrix for the protein hormones was calf serum. In three years no systematic improvement in the coefficients of variation of the results has occurred. The change from calf serum to human serum also had no major effects on the results. Percentage coefficients of bias usually varied on both sides of the true value, but at low hormone concentrations the results were almost always positively biased. It is therefore useful to know the true hormone concentrations of the control samples because all-laboratory means are relatively often biased from these. Variation produced by different methods of calculation of the radioimmunoassay results and the influence of outlying standard points on these data processing routines were studied in the third survey. It is possible that sometimes the variation produced by different methods of calculation is one of the main components of the total variation in external quality assessment of RIA. There were no major differences between the performance of computerized or manual calculation methods. The influence of different calibration standards on serum thyroxine determination was studied in the fourth survey. Of the total coefficient of variation (10.8% to 17.0%) the component of variation produced by different thyroxine calibration standards was 0.8% to 4.6%. In conclusion, standardization of the data processing methods and further standardization of assay reagents are urgently needed to give possibilities to identify more subtle differences in the analytical performance of the laboratories. External quality assessment of hormone determinations needs improvement of the quality of reference materials.
Chemistry, Clinical↗
Internal quality control of hormone determinations by RIA. Detection of clinically significant analytical errors of serum thyroxine determination.
An internal quality control system by which clinically significant analytical errors can be detected with high probability was developed for serum thyroxine (T4) determination by RIA. The mean concentration of the quality control samples (C1, C2, and C3) were 40.0, 101.8, and 156.7 nmol/l, and their total standard deviations (st) 2.5, 4.1, and 7.1 nmol/l, respectively, in stable analytical performance of the T4 assay. From the clinical point of view it was accepted that the results of C1 varied from 30 to 50 nmol/l at the most. When expressed in standard deviations, the same size of error was accepted for C2 and C3. It followed that the quality control system had to detect a systematic shift of 2.43st (delta SEc) and a 2.08 times increase in random error (delta REc) in order that the quality goals could be reached. With three control samples the combination of rules, 1: 3s/CS1: (1.0s; 2.7s), which was chosen for manual quality control, detected the delta SEc with about an 80% probability and the delta REc with about a 30% probability. The probability of false rejections was less than 1%. The probability of detecting the delta SEc was considered acceptable, but to detect the delta REc with a higher probability, the within-assay variation of each run was calculated from the results of duplicate patient samples. Although the whole run was not rejected because of systematic and/or random errors, individual samples were reanalysed if the results of their duplicate determinations differed from the criteria stated.(ABSTRACT TRUNCATED AT 250 WORDS)
False Negative Reactions↗
Problems of prenatal diagnosis of non-ketotic hyperglycinaemia.
Non-ketotic hyperglycinaemia (NKH) is a rare disorder of amino acid metabolism, causing severe, frequently lethal neurological symptoms in the neonatal period. There is no curative therapy, and attempts at prenatal diagnosis have been unsuccessful. In the present study the usefulness of the determination of the glycine/serine ratio in the prenatal diagnosis of NKH was studied. The glycine/serine ratio of the amniotic fluid of the last trimester of pregnancies with a fetus affected with NKH was higher (8.5 +/- 3.3; mean +/- SD) than in pregnancies of NKH-heterozygote mothers with a healthy fetus (4.1 +/- 1.7) or than in pregnancies of healthy mothers (4.3 +/- 1.5). There is, however, overlapping of individual values, which limits the usefulness of this test for prenatal diagnosis of NKH.
Amino Acid Metabolism, Inborn Errors↗