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Biomedical subjects

M Haukkamaa

Publications and source records attributed to M Haukkamaa.

At least 37 records · Page 2Linked to original sources
PubMed1989

Distribution of RU 486 and its demethylated metabolites in humans.

The concentrations of RU 486 and its demethylated metabolites were determined by RIA in samples of myometrium, abdominal adipose tissue, and serum, which were collected at hysterectomies performed 12-15 h after oral administration of 200 mg RU 486. The RU 486 concentrations in myometrium were similar in the five women studied, with a mean of 148 +/- 58 (+/- SD) ng/g (344 +/- 135 pmol/g). The adipose tissue RU 486 levels varied more, the mean concentration being 447 +/- 191 ng/g (1041 +/- 445 pmol/g). The serum RU 486 concentrations ranged from 175-899 ng/ml [mean, 396 +/- 259 ng/mL (922 +/- 603 nmol/L)]. In these women the nonprotein-bound fraction of [6,7-3H]RU 486 varied from 1.4-3.1% (mean, 2.3%). The approximate concentrations of the combined mono- and didemethylated metabolites of RU 486 were 1.4, 3.1, and 5.2 times higher in adipose tissue, myometrial tissue, and serum, respectively, than those of the parent RU 486. In vitro, rapid and nonsaturable accumulation of [6,7-3H]RU 486 from phosphate buffer into adipose tissue was inhibited by the addition of alpha 1-acid glycoprotein, the specific serum transport protein for RU 486, to the buffer medium. Accumulation of [6,7-3H]RU 486 in myometrial specimens was poor. The enterohepatic cycling of RU 486 was assessed in four normal subjects by repetitive intake of charcoal subsequent to ingestion of 200 mg RU 486. Compared to other normal subjects, the serum levels and areas under the concentration curves were lower and t1/2 values shorter in the group given charcoal, suggesting that in vivo RU 486 may be partly pooled in the enterohepatic cycle. Our studies suggest that despite the low volume of distribution and the effective serum binding of RU 486, the myometrial and adipose tissue concentrations of RU 486 and its metabolites were similar (approximately 10(-9)-10(-10) mol/g) after oral intake of RU 486.

Adipose Tissue↗
PubMed1988

Inhibition of folliculogenesis and ovulation by the antiprogesterone RU 486.

Healthy, regularly menstruating women were treated with the antiprogesterone RU 486, Mifepristone (Roussel-Uclaf, Romainville, France) during the follicular phase of the cycle. Three women were given 25 mg of RU 486 on days 1 to 14 of the cycle and five received 25 mg on days 1 to 21 of the cycle. Venous blood samples were collected three times per week during a control cycle and during one treatment cycle in each subject. Serum concentrations of estradiol (E2), progesterone (P), and RU 486 were determined by radioimmunoassays. No drug-related side effects and no spotting or bleeding during RU 486 treatment were observed. Menstrual bleeding was delayed by 8.7 +/- 3.8 days (mean +/- SD) after treatment over days 1 to 14 and by 12.6 +/- 3.2 days after treatment over days 1 to 21. During the treatment with RU 486, the serum concentrations of E2 remained low, indicating effective inhibition of folliculogenesis. After cessation of RU 486 treatment, serum E2 levels rose to similar values as in the control cycle, and subsequently serum P concentrations also reached ovulatory levels in six out of the eight volunteers. The results showed that the antiprogesterone RU 486 delayed folliculogenesis and luteinization even at low doses when given during the follicular phase of the menstrual cycle. It is speculated that this property of RU 486 could be utilized in the design of an estrogen-free combined oral contraceptives.

Adult↗
PubMed1987

Bacterial flora of the cervix in women using an intrauterine device.

The cervical bacterial flora of 18 healthy, parous, sexually active women was analysed before, and 3-5 months after insertion of a copper-releasing intrauterine device (IUD) and after long-term use of an IUD for 3-5.5 years in another nine women. No significant differences were found in the number of aerobic bacteria isolated before or after IUD insertion or after long-term use of an IUD. In contrast to aerobic bacteria, significantly more anaerobes were isolated in the cervix of women having used an IUD for several years when compared to those using barrier contraception with a condom. None of the women had clinical signs of pelvic infection and a cervical bacterial flora rich in anaerobes can be regarded as a normal finding in healthy sexually active women using an IUD for contraception.

Adult↗
PubMed1987

Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study.

The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levonorgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized, comparative multicenter trial. The Lng-IUD was inserted in 1821, and the Nova T in 937 women. The 12-month net pregnancy rate with the Lng-IUD (0.1 per hundred women) was significantly lower than that with the Nova T (0.9 per hundred). Removal rates for menstrual problems and/or pain were similar for the two methods (net rates 7.5 and 8.7, respectively). The 12-month continuation rates were 82.2 for the Nova T and 79.7 for the Lng-IUD. The reduction of the bleeding led to oligomenorrhea and amenorrhea in users of the Lng-IUD; the removal rate for these reasons was 1.4. The removal rate for hormonal side effects with the Lng-IUD was 2.4. Blood hemoglobin concentrations increased among users of the Lng-IUD and decreased among users of the Nova T. The results show that the Lng-IUD was a highly effective contraceptive method which reduced menstrual bleeding. It is a promising alternative for women desiring a highly effective method for long-term use.

Adult↗
PubMed1986

Bacterial flora of the cervix in women using different methods of contraception.

Bacteriologic culture samples were taken from the cervix in three groups of 10 healthy, sexually active women using barrier contraception, oral contraceptives, or a levonorgestrel-releasing intrauterine contraceptive device. Culture samples for Candida albicans and Trichomonas vaginalis were taken, a cytologic vaginal smear was obtained, and an amine sniff test was performed; these were in addition to a routine gynecologic examination. Multiple bacteria were isolated from the cervix in women using oral contraceptives or an intrauterine contraceptive device, whereas lactobacilli alone dominated the flora of women using barrier contraception. Significantly more anaerobic bacteria were isolated from the cervix in oral contraceptive and intrauterine contraceptive device users when compared with the barrier method users. Symptoms and findings evident of anaerobic vaginosis were associated with the occurrence of anaerobic bacteria in the cervix of three patients using the intrauterine contraceptive device. The results showed that the cervical bacterial flora in sexually active healthy women is rich in anaerobes that can be regarded as a normal finding in women using oral contraceptives or intrauterine contraceptive devices. Barrier contraception with a condom prevents this anaerobic shift and maintains a lactobacilli-dominated flora in the cervix.

Adolescent↗
PubMed1986

Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment.

The contraceptive efficacy of progestin-only contraception was studied in epileptic patients using NORPLANT subdermal capsules. The effect of anticonvulsants on levonorgestrel plasma levels was determined. NORPLANT subdermal capsules were inserted into nine epileptic women, and ten control women using no medication. Venous blood samples were taken at 0, 1, 3, 6, 9 and 12 months after insertion and the concentration of levonorgestrel was determined by radioimmunoassay. At 3 to 12 months, the overall mean concentration of plasma levonorgestrel was significantly lower in the six epileptics taking phenytoin alone or in combination with other anticonvulsants (203 +/- 128 pg/ml, mean +/- SD) than in the controls (325 +/- 135 pg/ml, p less than 0.01). After one year, nine of the control patients continued the use of NORPLANT and no pregnancies occurred. Two of the nine epileptics became pregnant during contraception by NORPLANT. They both used phenytoin and their plasma concentrations of levonorgestrel were low near the time of conception. Levonorgestrel released from the capsules had no apparent harmful effects on epilepsy and none of the patients reported an increase in seizure frequency. The results show that contraception by the progestin levonorgestrel is not reliable in epileptic patients using anticonvulsants known to induce metabolizing enzymes of the liver.

Adult↗
PubMed1986

Five years' experience with levonorgestrel-releasing IUDs.

Two levonorgestrel-releasing IUDs and a copper-releasing IUD of the same shape were studied in a randomized comparative study over five years. The levonorgestrel-releasing IUDs released 20 micrograms or 30 micrograms per day. The Pearl index during the 10,600 woman-months of LNG-IUD use was 0.11. The control device releasing copper had a Pearl index of 1.6. The amount and duration of menstrual bleeding was greatly reduced, leading to a high incidence of oligo- or amenorrhea. The continuation rate in this pioneer trial was 53 per 100 users for the levonorgestrel-releasing IUD (LNG-IUDs) and 50 per 100 users for the copper-releasing IUD (Nova T). The removal rates for reasons other than amenorrhea were not significantly different. Discontinuation because of amenorrhea occurred during the first two years, the cumulative termination rate for this reason was 11.6 per 100 users at five years. The LNG-IUDs removed for investigation after five years of use revealed that the devices contained about 40 percent of the original load. The effective lifespan of the device has been demonstrated by this study to be five years; the residual steroid gives an additional safety period of two more years. The LNG-IUD is a highly effective reversible contraceptive method, which strongly reduced the amount and duration of bleeding. During the first two months there is scanty but frequent spotting which, like the high incidence of oligo- and/or amenorrhea, requires counselling of health personnel and women using LNG-IUDs.

Adult↗
PubMed1986

Endometrial morphology during long-term use of levonorgestrel-releasing intrauterine devices.

Levonorgestrel-releasing intrauterine devices (IUD) were inserted in 92 women. Endometrial biopsies were taken between 3 months and 7 years after these insertions. Intrauterine release of levonorgestrel resulted in endometrial glandular atrophy and decidualized stroma. Inflammation and necrosis were also seen as local signs of IUD use. The biopsies were similar regardless of the duration of IUD use. Endometrial morphology returned to normal in biopsy specimens taken 1-3 months after IUD removal.

Adolescent↗
PubMed1985

Serum salbutamol concentrations during oral and intravenous treatment in pregnant women.

The serum concentration of salbutamol was determined in 29 pregnant women during oral treatment (4 mg five times per day) and in seven during intravenous infusion (6-30 micrograms/min) because of premature labour. The concentration of salbutamol was determined by combined gas-liquid chromatography mass spectrometry. The mean concentration of serum salbutamol was twice as high during intravenous treatment (24; SD 9 ng/ml), than during oral treatment (12; SD 3 mg/ml). During oral treatment, the salbutamol levels were not correlated to maternal height, weight or the incidence or severity of side-effects. The serum concentrations of salbutamol in patients with twin pregnancies did not differ from those with singleton pregnancies. After stopping intravenous treatment, serum salbutamol levels remained high for several hours and oral treatment can be started 4-6 h after stopping intravenous infusion.

Administration, Oral↗
PubMed1984

High affinity progesterone binding sites of human uterine microsomal membranes.

Microsomal membranes sedimented at 40 000 g were prepared from human myometrium samples. The progesterone binding properties of microsomal suspensions were determined by incubating microsomes and [3H]progesterone at 4 degrees C. Dextran-coated charcoal was used for the separation of bound and free steroids. Membrane-associated progesterone binding sites of high affinity were identified in microsomes prepared from pregnant and nonpregnant uteri. The binding was saturable (Kd approximately 4 X 10(-9) M, concentration of binding sites 400-900 fmol/mg microsomal protein) and specific for natural progesterone. Of 21 steroids tested only 21-hydroxy-4-pregnene-3,20-dione, 17 alpha-hydroxyprogesterone and testosterone showed moderate competition against progesterone with relative affinities between 7.0-20.0% (R.A. of progesterone 100%). 5 alpha-Dihydroprogesterone and 5 alpha-dihydrotestosterone showed weak cross reaction (relative affinities 2.5 and 2.0%, respectively). Corticosteroids, estrogens and the 5 synthetic progestins tested showed only weak competition with relative affinities lower than 1.0%. These microsomal progesterone binding sites of high affinity and limited capacity resemble steroid hormone receptors but they are different from the soluble cytosolic progesterone receptor of human uterus in terms of steroid specificity. The physiological function of this microsomal progesterone receptor is unknown.

Binding, Competitive↗
PubMed1983

Vaginal contraception with gossypol: a clinical study.

A clinical study concerning the vaginal contraceptive efficacy of gossypol acetic acid was performed. Fifteen women who had undergone tubal sterilization volunteered for the study. The effect of vaginal gossypol-containing gel on spermatozoa was determined by postcoital tests performed in subjects without and after using gossypol gel. After gossypol application, the number of spermatozoa found in cervical mucus was greatly decreased and, in eleven of the fifteen women, all spermatozoa seen were immobilized. In four cases a few poorly motile spermatozoa were seen but they showed no forward progression. We have previously reported that gossypol has an inhibitory effect on herpes simplex virus type 2 in vitro. This anti-viral property of gossypol makes it particularly attractive as a topical barrier contraceptive. The present study shows that gossypol is also promising as a vaginal contraceptive agent in human in vivo experiments.

Adult↗
PubMed1983

Serum histidine-rich glycoprotein during pregnancy and hormone treatment.

The concentration of serum histidine-rich glycoprotein (HRG) was determined by radial immunodiffusion during weeks 27-42 of pregnancy in 110 pregnant women. HRG was also measured in serum from 11 lactating women 6 weeks post partum, from 11 women taking oral contraceptives, and from four women having progestin-releasing subcutaneous capsules used for contraception. The concentration of serum HRG decreased during the last trimester of pregnancy reaching a nadir at the 36-37th week (HRG 49 +/- 14 g/l, mean +/- SD). Thereafter serum HRG increased slightly towards term. In pregnancies complicated by hypertension the concentration of HRG was lower than in normal pregnancies at 32 weeks of pregnancy, but in other pathological pregnancies the values fell within the normal range. By 6 weeks postpartum normal non-pregnant HRG levels had been reached (107 +/- 13 g/l). The concentration of serum HRG was significantly lower in oral contraceptive users (74 +/- 22 g/l) than in controls (109 +/- 25 g/l, P less than 0.005). Low dose progestin treatment had no effect on serum HRG. The results show that serum HRG decreases during pregnancy and with oral contraceptive treatment and suggest that oestrogens are responsible for this increase.

Blood Proteins↗
PubMed1982

Levonorgestrel in milk and plasma of breast-feeding women with a levonorgestrel-releasing IUD.

A levonorgestrel-releasing intrauterine contraceptive device was used by 10 breast-feeding women beginning 6 weeks after delivery. Two models of IUD were used. One released 10 microgram (5 patients), the other 30 microgram (5 patients) of levonorgestrel per day. Plasma and milk samples were collected 8 times over a 3-month period and the concentrations of levonorgestrel determined by radioimmunoassay. An improved and sensitive method for the determination of levonorgestrel in milk was developed. A column chromatographic purification of a milk extract before radioimmunoassay made possible the use of large milk samples in order to improve the sensitivity. The plasma concentrations during the follow-up period were 207 +/- 64 pg/ml (mean + SD) in the 10 microgram and 235 +/- 87 pg/ml in the 30 microgram/day releasing IUD groups. The milk levonorgestrel concentrations were 56 +/- 35 and 57 +/- 34 pg/ml, respectively. The plasma to milk ratio of levonorgestrel was initially 100:15 and at the end of the 3-month follow-up period 100:25. There were no significant differences in the milk and plasma concentrations between the study groups. The total amount of levonorgestrel excreted per day in 600 ml breast milk is approximately 0.1 per cent of a daily dose of 30 microgram.

Breast Feeding↗
PubMed1982

Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD.

Thirteen women who were scheduled for hysterectomy volunteered for the study. Nine women had a levonorgestrel-releasing intrauterine contraceptive device inserted between 36 and 49 days prior to surgery and four women were on oral levonorgestrel treatment for 7 days prior to surgery. After the surgical removal of the uterus, samples of endometrial, myometrial, fallopian tube and fat tissue were obtained. Methods for measuring tissue concentrations of levonorgestrel were developed and the uptake of levonorgestrel by fat tissue in vitro was studied. The concentrations of levonorgestrel in myometrial, fallopian tube and fat tissue were all of the same order, of between 1 and 5 ng/g of wet weight of tissue, in both the intrauterine device group and the orally treated group. In the endometrium the levonorgestrel concentrations were many-fold higher in the intrauterine device group. The in vitro experiments showed a rapid uptake of levonorgestrel and an unsaturability of the fat tissue by the steroid at the concentrations used. The fat tissue concentrations of levonorgestrel correlated with the plasma concentrations.

Adipose Tissue↗
PubMed1982

Decrease of serum oestriol during intravenous hexoprenaline or salbutamol treatment.

Patients with premature labour were treated with intravenous hexoprenaline (18 patients) or salbutamol (10 patients) infusion between 26 and 36 weeks gestation. After at least 12 h infusion, oral therapy was started. Serum total oestriol was determined by radioimmunoassay every 6 h during intravenous beta-mimetic infusion (p less than 0.005). One day after stopping intravenous treatment, and then every day after stopping the infusion, for 4 days. The mean serum total oestriol concentration decreased significantly during the intravenous treatment, serum oestriol returned to pretreatment levels. The results show that fetal monitoring by maternal oestriol determinations is not reliable during intravenous beta-adrenoceptor agonist therapy.

Adult↗
PubMed1982

The monitoring of labor by telemetry.

Telemetry and conventional cardiotocography were compared by monitoring the labor of 60 patients with an uneventful pregnancy and delivery in the 38th-42nd week of pregnancy. 31 patients were monitored by telemetry and 29 by cardiotocography. The patients were matched for age (+/- 5 years), duration of pregnancy (+/- 7 days) and parity (I or II). The husband attended labor and delivery in 42% of the cases in the telemetry group and in 59% of the cases in the control group. Induction of labor by amniotomy was performed in 32% of the cases in the telemetry group and in 24% of the cases in the cardiotocography group. The patients monitored subjective pain every half hour during the opening phase. The telemetric patients were encouraged to sit or walk during the first stage. No maternal or fetal complications occurred. All infants were born in good condition with APGAR scores greater than or equal to 7 recorded at one and five minutes. There were 4 operative deliveries in the telemetry group and 5 in the control group. Indications for these were maternal or uterine exhaustion with the exception of two control patients where fetal asphyxia was suspected. The duration of the first stage of labor did not differ significantly between the telemetry and the cardiotocography groups. The telemetric patients received less analgesics than the controls but this difference was not significant. In spite of less analgesia in the telemetry group, the secondparas of the telemetry group experienced significantly less (p less than 0.01) labor pain than the controls. In addition, the secondparas of the telemetry group considered the present labor less painful than the previous one significantly more often than the controls. Among the primiparous patients there was no difference in the amount of pain experienced by the patients.

Adult↗
PubMed1982

Diagnostic value of a rapid HCG-beta-subunit radioimmunoassay in cases of suspected ectopic pregnancies.

A rapid and sensitive RIA specific for the beta-subunit of HCG was developed. This RIA gives the results in less than 3 hours, and is able to detect the pregnancy 12 days after the midcycle LH-peak. The clinical reliability was evaluated by assaying plasma samples from 128 patients with acute gynecologic symptoms and suspicion of ectopic pregnancy. Other diagnostic methods including urinary pregnancy test (117 patients), culdocentesis (57 patients), and endometrial curettage (66 patients) were also performed. The final clinical diagnosis was ectopic pregnancy in 45 cases, intrauterine pregnancy in 31 cases, and no pregnancy in 52 cases. The rapid HGC-RIA gave a positive result in 93%, 97%, and 6% of these patient groups, respectively. The conventional diagnostic methods were less reliable and gave a positive result in only 52-59% of the ectopic pregnancies. Three false negative results (7%) in the HCG-RIA were obtained in cases of ectopic pregnancy. Three false positive results (6%) were obtained in patients not pregnant. The results show the superiority of the HCG beta-subunit RIA compared to the conventional diagnostic methods in the diagnosis of ectopic pregnancy.

Animals↗