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Biomedical subjects

A Kauppila

Publications and source records attributed to A Kauppila.

At least 145 records · Page 8Linked to original sources

Steroidal regulation of endometriosis tissue: lack of induction of 17 beta-hydroxysteroid dehydrogenase activity by progesterone, medroxyprogesterone acetate, or danazol.

Cytosol and nuclear estrogen receptors were detected in 73% and 89% of untreated endometriosis specimens, respectively. The corresponding figures for cytosol and nuclear progestin receptors were 94% and 100%, respectively. Compared with the endometrium, the concentrations in endometriosis tissue were low. The anatomic site, the severity of the disease, and the phase of the menstrual cycle had no significant influence on receptor concentrations in endometriosis tissue. The activities of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not increase during the luteal phase. Danazol for 1, 3, 7 to 11, and 18 to 30 days, or medroxyprogesterone acetate for 5 days, had no effect on receptor concentrations or 17 beta-HSD activity in endometriosis tissue. The frequent presence of the receptors suggests that endometriosis lesions are under the control of steroid hormones. The lack of effect by progesterone and progestins on 17 beta-HSD shows that this regulation is different in endometriosis tissue and in the endometrium.

17-Hydroxysteroid Dehydrogenases↗

Short-term effects of tamoxifen, medroxyprogesterone acetate, and their combination on receptor kinetics and 17 beta-hydroxysteroid dehydrogenase in human endometrium.

The interactions of an antiestrogen (tamoxifen) and a progestin (medroxyprogesterone acetate) on endometrial 17 beta-hydroxysteroid dehydrogenase activities were studied in short-term experiments (four to 96 hours) in normally menstruating women at the follicular phase and were related to simultaneously measured concentrations of cytosol and nuclear estrogen and progestin receptors. Tamoxifen effected a decrease in the activity of 17 beta-hydroxysteroid dehydrogenase. This was associated with an apparent translocation to and retention of estrogen receptor in the nucleus without any significant changes in cellular progestin receptor. Medroxyprogesterone acetate administration led to a rapid increase in endometrial 17 beta-hydroxysteroid dehydrogenase activity, and depletion of cytosol and total cellular progestin receptor. Combination of the drugs led to effects that could be addressed to the individual drugs separately, and under the experimental conditions the effects of medroxyprogesterone acetate were uninfluenced by simultaneous tamoxifen administration. Put together with the authors' previous findings on the same parameters during long-term (three-week) medroxyprogesterone acetate administration, it seems possible that potentiation of progestin effects on endometrial carcinoma is not to be expected during long-term simultaneous antiestrogen-progestin treatment. It is therefore likely that the favorable effects of combining these two drugs in long-term treatment are due to their different endocrine action mechanisms.

17-Hydroxysteroid Dehydrogenases↗

Naproxen sodium in dysmenorrhea secondary to endometriosis.

Twenty patients with moderate to very severe painful menstrual periods secondary to endometriosis were treated in a double-blind, four-period, crossover clinical trial with naproxen sodium and placebo. Complete or substantial pain relief was obtained in 83% of the cases of painful menstruation with naproxen sodium and in 41% with placebo (P = .008). Only 5% of the naproxen sodium-treated women needed supplemental analgesics compared with 36% of the placebo-treated women (P = .002). There was a trend towards diminished interference of dysmenorrhea with normal patient activities during naproxen sodium treatment compared with placebo (P = .069). No significant side effects occurred with either treatment. These results indicated that naproxen sodium is efficacious and safe for the treatment of menstrual distress in patients with endometriosis.

Adult↗

Peripheral blood concentrations of progesterone and oestradiol during human pregnancy and delivery.

To evaluate the significance of progesterone and estradiol in human uterine activity during pregnancy and delivery the blood concentrations of these hormones were monitored weekly during the last trimester of pregnancy and at the onset of labour in 15 women, and before and 3 hours after the induction of term delivery in 83 parturients. Neither plasma concentrations of progesterone or estradiol nor the ratio of progesterone to estradiol changed significantly during the last trimester of pregnancy or at the onset of delivery. After the induction of delivery parturients with initial progesterone dominance (ratio of progesterone to estradiol higher than 5 before induction) demonstrated a significant fall in serum concentration of progesterone and in the ratio of progesterone to estradiol while estradiol concentration rose significantly. In estrogen dominant women (progesterone to estradiol ratio equal to or lower than 5) the serum concentration of progesterone and the ratio of progesterone to estradiol rose significantly during the 3 hours after the induction of delivery. Our results suggest that the peripheral blood levels of progesterone and estradiol do not correlate with the tissue biochemical changes which prepare the uterine cervix and myometrium for delivery. The observation that the ratio of progesterone to estradiol decreased in progesterone-dominant and increased in estrogen-dominant women stresses the importance of a well balanced equilibrium of these hormones for prostaglandin metabolism during human delivery.

Estradiol↗

Low serum selenium concentration in patients with cervical or endometrial cancer.

Serum concentrations of selenium were determined in 37 patients with cervical and 64 patients with endometrial cancer. The patients had lower (P less than 0.001) serum concentrations of selenium than the age-, weight- and place of residence-matched paired control women. There was no difference in the selenium concentration between various age groups or different clinical stages of cervical or endometrial cancer. A low serum concentration of selenium might be a contributing factor in uterine carcinogenesis.

Adult↗

A prospective, randomized, national trial for treatment of ovarian cancer: the role of chemotherapy and external irradiation.

A prospective, randomized, national trial for comparing the effects of cytotoxic agents and radiotherapy on survival in primary epithelial ovarian cancer stages I-IV was carried out in 363 patients. After laparotomy, the patients were staged according to disease spread and randomized into treatment groups within each stage. The single or combined cytotoxic agents used were: cyclophosphamide (C) and vincristine (V); 5-fluorouracil (F) and dactinomycin (D) and V; treosulfan (T); and CF. In stages I, II and III there was one treatment group receiving external irradiation; in stage IV only different cytostatics were used. It was found that, in stage I, surgery alone was superior to surgery +CV or surgery + irradiation. In stage II disease, no differences in survival between treatment groups receiving pelvic irradiation or FDV, and in stage III between whole abdomen + pelvic irradiation or CV or FDV were found. In stage IV, FDV, T and CF were of similar, poor efficacy. The authors conclude that in stage I pelvic irradiation or combined chemotherapy do not improve survival. In advanced disease, chemotherapy may be better tolerated and thus preferable to whole abdomen irradiation; the combination of more modern cancer drugs with the ones used in this study is probably likely to improve the treatment results.

Abdomen↗

Serum selenium and glutathione peroxidase, and plasma lipid peroxides in uterine, ovarian or vulvar cancer, and their responses to antioxidants in patients with ovarian cancer.

The concentrations of serum selenium and plasma lipid peroxides, and the activity of serum glutathione peroxidase (GSH-Px) were measured before any therapy in patients suffering from uterine, ovarian or vulvar cancer, and in association with 1-day combination cytotoxic chemotherapy of ovarian cancer following 1-week supplementation with selenium (96 micrograms/day), vitamin E (300 mg/day), selenium and vitamin E, or placebo. Patients with gynaecological cancer (N = 44) had lower serum concentration of selenium (1.15 +/- 0.04 S.E. mumol/l; P less than 0.05) and serum activity of GSH-Px (404 +/- 13 units/l, P less than 0.01) than the control subjects (N = 56; 1.25 +/- 0.03 mumol/l and 444 +/- 8 units/l, respectively). In association with cytotoxic chemotherapy selenium alone (P less than 0.05), vitamin E alone (P less than 0.05) and both of them together (P less than 0.001) decreased the plasma concentration of lipid peroxides, and the combination of selenium and vitamin E also increased the activity of serum GSH-Px (P less than 0.01). During placebo, cytotoxic chemotherapy did not affect plasma lipid peroxides but it decreased (P less than 0.001) the activity of GSH-Px. Selenium inhibited this effect. Our data suggest that antioxidative mechanisms of patients with gynaecological cancer may be defective and that treatment with selenium and vitamin E results in changes of biochemical factors related to lipid peroxidation.

Adult↗

Luteinizing hormone receptor disorder in endometriosis.

Luteinizing hormone (LH) receptor concentrations in ovarian follicles and corpora lutea were measured in 51 patients with histologically proven endometriosis and in 41 control patients. The LH receptor concentrations in cases of endometriosis were lower during the early (0.43 +/- 0.11 [mean +/- standard error] versus 1.31 +/- 0.27 fmol/mg protein; P less than 0.001) and late (0.48 +/- 0.10 versus 1.59 +/- 0.22 fmol/mg protein; P less than 0.001) follicular phase, and during the late luteal phase (2.62 +/- 0.55 versus 4.62 +/- 0.65 fmol/mg protein; P less than 0.05) of the cycle than in control patients. In contrast to the control patients, the LH receptor concentration during the follicular phase remained constant in endometriosis, being lower in patients with extensive or severe disease than in patients with moderate or mild disease (0.28 +/- 0.07 versus 0.61 +/- 0.21 fmol/mg protein; P less than 0.05). Endometriosis-associated infertility might be a consequence of a defect in the mechanism mediating LH action in the ovaries.

Adult↗

Maternal and umbilical cord plasma noradrenaline concentrations during labour with and without segmental extradural analgesia, and during caesarean section.

Serial measurements of maternal and umbilical cord plasma noradrenaline concentrations were obtained in 10 patients undergoing normal vaginal delivery with segmental extradural analgesia, in 10 patients undergoing normal vaginal delivery without extradural analgesia, and in 12 patients undergoing elective Caesarean section under general anaesthesia. Maternal noradrenaline concentrations increased significantly during delivery in all three groups, the peak concentrations occurring at delivery. However, the increase in the maternal noradrenaline concentration during delivery in the extradural group was lower than in the non-extradural group (P less than 0.05). Umbilical venous and arterial concentrations of noradrenaline were lower after Caesarean section than after vaginal delivery. However, extradural analgesia did not affect the fetal noradrenaline concentrations. Since noradrenaline is probably required for the adaptation of the newborn to extrauterine life, the unaltered fetal response may be beneficial.

Anesthesia, Epidural↗

Serum selenium in patients with ovarian cancer during and after therapy.

Serum concentrations of selenium were determined by atomic absorption spectrophotometry in 40 patients with ovarian cancer in association with and after surgical and cytostatic therapy. Patients with ovarian cancer had significantly (p less than 0.001) lower serum concentrations (mean +/- SE) of selenium (0.93 +/- 0.04 mumol/l) than age-, weight- and place of residence-matched control subjects (1.22 +/- 0.03 mumol/l). In clinical stage IV disease there was a lower serum level of selenium (0.82 +/- 0.07 mumol/l) than in clinical stages I and II combined (1.00 +/- 0.04 mumol/l). Serum selenium concentrations also showed a tendency to follow the outcome of the disease; an increase in patients with remission and a decrease in patients with progressive disease, probably because of nutritional reasons.

Adult↗

Human chorionic gonadotrophin and pregnancy-specific beta-1-glycoprotein in predicting pregnancy outcome and in association with early pregnancy vomiting.

Serum concentrations of human chorionic gonadotrophin (HCG) and pregnancy-specific beta 1-glycoprotein (SP1) were measured in 99 women between the 6th and 10th gestational week, before the onset of pregnancy-threatening complications. The markers failed to predict threatening abortion appearing 9-112 days after sampling (n = 11), regardless of whether the pregnancy continued (n = 2) or ended with abortion (n = 9). Normal HCG and SP1 values were observed in 4 women who subsequently had preterm delivery. 14 women with daily vomiting had higher mean serum concentrations of HCG (p less than 0.01) and SP1 (p less than 0.05) than 12 women of the same gestational duration without nausea or vomiting. Our results thus show that random single HCG or SP1 determinations have minimal clinical value in predicting the failure of pregnancy and that early pregnancy vomiting seems to be associated with raised serum HCG and SP1 concentrations.

Abortion, Spontaneous↗

Degree of female stress urinary incontinence: an objective classification by simultaneous urethrocystometry.

Urodynamic examinations carried out on 45 patients with stress urinary incontinence (SUI) and 17 women without a history of incontinence using simultaneous microtransducer urethrocystometry were examined in order to develop an objective indicator of the severity of the condition. Five urethral pressure profiles (UPP) with stress were recorded, maintaining a constant coughing strength as seen in the bladder pressure rises. The coughing strength was increased stepwise for successive profiles. Zero urethral closure pressure, indicating genuine SUI, appeared with bladder pressure rises of less than 50, 75 and 100 mm Hg and of 100 mm Hg or more in 7, 27, 45 and 67% of the 45 symptomatic patients, respectively. 33% had a positive closure pressure in every UPP. 2 women without symptomatic incontinence had negative urethral closure pressures. The lowest bladder pressure rise needed for zero urethral closure pressure showed a significant negative correlation with the clinical grade of SUI and the degrees of social restriction experienced. We suggest that SUI can be classified urodynamically into minimal (lowest bladder pressure rise producing zero urethral closure pressure 100 mm Hg or more), mild (75-99 mm Hg), moderate (50-74 mm Hg) and severe forms (less than 50 mm Hg).

Adult↗

Pubertal and menstrual disorders of female runners, skiers and volleyball players.

In order to evaluate the onset of puberty and the presence of menstrual disorders in Finnish sportswomen with different training programs, 53 long-distance runners, 39 skiers and their 93 controls, and 63 volleyball players with 64 controls were interviewed. All the sportswomen had trained intensively for several years and were in the top category of their sport in Finland. Menarche and thelarche in all the sportswomen and also pubarche in the volleyball players developed significantly later than in their controls. The runners and skiers (43%) suffered significantly more often from menstrual irregularities than their controls (27%), whereas volleyball players (19%) did not differ from their controls (13%) in this respect. Among runners and skiers, but not among volleyball players, premenarchal start of sports activity had an aggravating effect on these endocrine disorders. Dysmenorrhea was found to occur more seldom in sportswomen than in the control subjects, and physical exercise often alleviated menstrual distress. Because the runners and skiers trained as often and used as much time for their sport as the volleyball players, the more common occurrence of their menstrual disorders may be due to the nature of training and competition activity which is characterized by endurance physical exercise.

Adolescent↗

Amniotic fluid norepinephrine concentration as an indicator of fetal sympathetic nervous activity. Effect of pregnancy complications.

The concentrations of norepinephrine in amniotic fluid and maternal plasma were measured in 71 third trimester pregnancies, 31 of which were uncomplicated and 40 complicated. The amniotic fluid norepinephrine concentration (mean +/- SD) in cases of hypertension treated with clonidine (0.4 +/- 0.1 ng/ml, n = 12) and in insulin-dependent diabetes (0.5 +/- 0.2 ng/ml, n = 7) was lower, and in renal insufficiency (1.7 +/- 0.8 ng/ml, n = 8) higher than in control subjects (0.7 +/- 0.4 ng/ml, n = 31). In fetal-growth retardation (0.6 +/- 0.2 ng/ml, n = 8) and in latent diabetes (0.7 +/- 0.2 ng/ml, n = 5) the values were similar to those in the control subjects. There was a significant positive correlation between mature lecithin-sphingomyelin (L/S) ratio and norepinephrine concentration. Clonidine-treated hypertension was associated with decreased (0.2 +/- 0.1 ng/ml) and renal insufficiency with increased (0.9 +/- 0.7 ng/ml) maternal plasma norepinephrine concentrations (control group, 0.3 +/- 0.1 ng/ml). The present results indicate that measurement of catecholamines in amniotic fluid can be useful in the evaluation of fetal sympathoadrenal function.

Amniotic Fluid↗

Effects of metoclopramide-induced hyperprolactinemia during early follicular development on human ovarian function.

Nine healthy women, aged 25 to 36 yr, were treated with metoclopramide (MC) (10 mg orally three times daily) from the first to the sixth day of their cycle (treatment A) for two successive cycles (n = 18) and six of these women later received MC from -3 to the fifth day of the menstrual cycle (treatment B) during one or two cycles (n = 10), to investigate the effects of hyperprolactinemia during the early phase of ovarian follicular growth. Comparisons were performed with control cycles in the same women. The treatment cycles were characterized by low serum concentrations of LH during the early follicular phase and at midcycle, low early follicular phase serum testosterone (T) levels and high luteal phase T and free T index values, with no significant differences between A and B treatment modalities. We classified the treatment cycles into two categories, seriously disturbed and normal or only slightly disturbed, on the basis of ultrasonographic findings and midcycle estradiol (E2) and luteal phase progesterone (P) concentrations. Folliculogenesis was seriously disturbed in 11 of the 28 treatment cycles (39%). During these cycles, midcycle serum LH and the LH to FSH ratio were lowered, luteal phase LH and FSH increased, midcycle E2 and luteal phase P and the P to E2 ratio decreased, luteal phase T and the free T index and androstenedione increased, and luteal phase 5 alpha-dihydrotestosterone decreased. During the early follicular phase and at midcycle the ratios of T to E2 and androstenedione to E2 were increased, and at midcycle and during the luteal phase of the cycle the ratio of T to 5 alpha-dihydrotestosterone was increased. These changes in steroid hormones were probably of ovarian origin since the serum concentrations of dehydroepiandrosterone sulfate and sex hormone-binding globulin were similar in seriously disturbed and control cycles. Four of the nine study subjects were hyperprolactinemia sensitive (disturbed folliculogenesis) and five hyperprolactinemia resistant (no disturbance in folliculogenesis). During the control cycles the hyperprolactinemia-sensitive women had significantly higher serum concentrations of T than the other women. The present observations indicate that hyperprolactinemia may impair the development of the ovarian follicles during their recruitment period, especially in women with relatively high serum T levels.

Adult↗

Progestin therapy of endometrial, breast and ovarian carcinoma. A review of clinical observations.

A survey of the literature shows that in studies employing standardized criteria to define the response to progestin therapy, an objective remission is achieved in about one-third of patients with endometrial and breast cancer, and it is much less frequent in ovarian malignancy. The response is seldom complete and it is mostly of a short duration. There is a tendency towards an increased response-rate with increased dosage of progestin, in both endometrial and breast carcinoma, while the route of administration appears to be of minor importance. The clinical benefit of adjuvant progestin therapy in endometrial cancer is unproven. Simultaneous therapy with progestin and cytotoxic drugs seems not to increase the survival figures obtainable by cytotoxic therapy alone. The antiestrogen tamoxifen has an established efficacy in all these malignancies. The spectra of tumors sensitive to tamoxifen and to progestin are not completely identical. The optimal combination of these drugs awaits results from prospective studies. Selection of patients for progestin therapy with a sufficient degree of accuracy is not feasible by use of clinical or histological parameters. On the other hand, estrogen receptor determination already has an established position in the clinical evaluation of the sensitivity of breast cancer to endocrine therapy. The assay of progestin receptors from endometrial carcinoma tissue also seems to give reliable information; correct prediction was observed in 86% when the receptor data from five studies with 105 progestin therapies were correlated with the treatment results.

Aminoglutethimide↗

Cytosol estrogen and progestin receptor concentrations and 17 beta-hydroxysteroid dehydrogenase activities in the endometrium and endometriotic tissue. Effects of hormonal treatment.

Concentrations of cytosol estrogen (ERc) and progestin (PRc) receptors and the activities of 17 beta-hydroxysteroid dehydrogenase (17-HSD) were measured in 80 untreated and 23 danazol-treated endometriotic tissue specimens. The results were compared with those obtained from endometrium specimens prior to or following danazol or medroxyprogesterone acetate (MPA) treatment. The concentrations of ERc and PRc in the endometriotic tissue were lower than corresponding values in the endometrium. Cytosol female sex steroid receptors were always present in the normal endometrium, whereas only 70% of the endometriotic lesions were simultaneously ERc- PRc-positive (receptor concentration greater than or equal to 3 and greater than or equal to 6 fmol/mg cytosol protein respectively), 24% PRc-positive, and 6% receptor-negative. In the endometriotic tissue, the mean concentrations of PRc during the luteal phase of the cycle (90 +/- 23, SE, fmol/mg protein) were lower (p less than 0.05) than during the follicular phase (177 +/- 32 fmol/mg protein), while the ERc concentrations and 17-HSD activities did not show any cyclic variations. Danazol and MPA had similar effects on the endometrium, both inducing a decrease in concentration of the female sex steroid receptors and an increase in activity of 17-HSD during short-term treatment (one week), and a decrease in activity of the enzyme during long-term treatment (3 weeks). The effect of danazol on the endometriotic tissue differed from that found in the endometrium. Danazol did not alter the activity of 17-HSD or the concentration of PRc but tended to increase the concentration of ERc in endometriotic tissue when given for 7-30 days.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗