PubMed Health⌕ Search

Biomedical subjects

E Johannisson

Publications and source records attributed to E Johannisson.

At least 55 records · Page 3Linked to original sources
PubMed1988

The effect of RU486 administered during the proliferative and secretory phase of the cycle on the bleeding pattern, hormonal parameters and the endometrium.

Seventeen healthy women aged 24-45 years with regular menstrual periods, proven fertility and not using steroidal contraceptives or IUD were recruited for the study. The volunteers were followed during one control, one treatment and one follow-up cycle. Daily morning urine samples were obtained during the control and the treatment cycle. The samples were analysed with regard to pregnanediol glucuronide (P2-G), oestrone glucuronide (E1-G), oestradiol (E2), progesterone (P4), LH and creatinine. During the entire 3-month study the subjects kept a record of uterine bleeding and side effects. The subjects received 50 mg RU486 daily either on cycle days 7-10 (n = 7) or on cycle days 20-23 (n = 10). An endometrial biopsy was taken on cycle day 10 in the first group and on cycle days 21-28 in the second group of patients. Treatment during the proliferative phase caused significant prolongation of the cycle length due to a delay of the oestrogen and LH surge. However, once the oestrogen concentration started to increase, the remaining part of the cycle was normal. The length of the follow-up cycle was similar to that of the control cycle. The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle. All ovulating women (n = 9) treated in the mid-luteal phase started to bleed on the 3rd to 4th day of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Mechanism of action of intrauterine devices: biochemical changes.

The mechanism of action of intrauterine devices varies from one type of device to another, although the principle of action is the same, namely, to interfere with the physiology of reproduction at the endometrial level. The biochemical changes of the endometrial tissue and the composition of the uterine fluid have been reviewed in relation to the use of inert, copper-medicated and steroid-releasing IUDs. All IUDs, whether inert or medicated, provoke a significant increase in the number of neutrophils, mononuclear cells and plasma cells, the presence of which is unrelated to the tissue infiltration of inflammatory cells occurring pre-menstrually of the normal menstrual cycle. The increase of leucocytes in IUD-users is compatible with a foreign body reaction which may be related to the antifertility effect. The addition of copper to an inert IUD has been shown to significantly alter the metabolism of the endometrial cells, e.g. the enzymatic activity and the DOVA-synthesis. The steroid-medicated IUDs represent a new approach to intrauterine contraception where the morphology of the endometrium is considerably altered, showing massive decidual changes, atrophic glands and sometimes atrophy of the whole functional layer. In addition, there is an important foreign body reaction, similar to that of the inert IUDs. The enzymatic activity, as well as the proliferative activity was significantly altered in the endometrium of these IUD-users. Changes in the endometrial fibrinolytic activity in IUD-users have been demonstrated to be related to the presence of irregular bleeding. Micro-traumata of the endometrium and the increased fibrinolytic activity may also interfere with the protective processes present in the physiologically normal endometrium. Further studies on the factors influencing the fertilizing ability of the spermatozoa in the female genital tract, as well as on the conditions of the human endometrium required for the implantation of a blastocyst, may yield important information for the improvement of intrauterine contraception.

Endometrium↗
PubMed1987

Microfluorometric assessment of the DNA-DNP complex in human spermatozoa.

During spermiogenesis, the DNA-nucleoprotein complex undergoes alterations that are reflected in a decreasing capacity for binding DNA-specific dyes, such as ethidium bromide (EB). Human spermatozoa with a low or high capacity for EB binding were depleted of RNA and most nuclear proteins by exposure to RNAse, EDTA and trypsin, with and without additional high salt buffer (HSB) treatment. When treated with RNAse, EDTA and trypsin only, the haploid DNA fluorescence value (calculated from the diploid value of the standard cell population) was found at EB concentrations of 6.5 to 12.5 micrograms/mL. At these EB concentrations, a significantly lower fluorescence was found in the material also treated with HSB, probably reflecting an unwinding of the highly negatively supercoiled DNA loops that are induced by HSB treatment. Maximal fluorescence was not found until a concentration of 50 micrograms EB/mL. This may be due to an overwinding of the DNA by the positive supercoiling caused by EB. The significant difference in EB uptake initially found between the two groups whose spermatozoa showed low and high capacities for EB binding disappeared after removal of the nucleoproteins, suggesting that this compartment of the nucleoprotein-DNA complex is responsible for the different uptakes of EB.

Adult↗
PubMed1987

Endometrial morphology and peripheral hormone levels in women with regular menstrual cycles.

Endometrial biopsies from 90 women with regular menstrual cycles and a hormonal profile compatible with normal luteal function were morphometrically assessed using 11 different indices and the results were plotted in 48-hour periods around the day of the luteinizing hormone (LH) surge (LH +/- 0). The endometrial dating reached its highest significance from days LH -3/-2 to days LH +7/+8, when the changes occurred with a high degree of regularity regardless of the length of the preovulatory and postovulatory phases. It is proposed therefore that the dating of the endometrium should be related to the LH surge rather than to the "ideal" 28-day cycle. The results also seem to suggest the existence of a regulatory mechanism for the synchronization of follicular maturation and midcycle endometrial development. Further study of the factors involved in this mechanism may result in a better understanding of certain forms of unexplained infertility.

Adult↗
PubMed1986

Pituitary, ovarian and endometrial effects of graded doses of medroxyprogesterone acetate administered on cycle days 7 to 10.

Eighteen apparently healthy women with normal menstrual cycles were studied during a control cycle and then during a treatment cycle, in which graded doses (2.5, 5.0 and 10 mg/day) of medroxyprogesterone acetate (MPA) were administered orally on cycle days 7 to 10. In both the control and the treatment cycle peripheral blood was drawn daily for the assay of luteinizing hormone (LH), estradiol (E2) and progesterone (PROG) and an endometrial biopsy was taken on cycle day 11. The lowest dose of MPA (2.5 mg X 4) did not influence the various cycle characteristics. Administration of higher doses (5.0 or 10 mg X 4) resulted in a lengthening of the duration of E2-peak (P less than 0.05), an increase in the area under the E2-peak (P less than 0.05), a decrease in the area under the PROG-curve (P less than 0.05) and a reduction in the height of the LH-peak (P less than 0.05). Furthermore, in 5 of these 12 subjects there was no ovulatory-like PROG-pattern during the cycle in which MPA was administered for 4 days. Morphometric analysis of the endometrial biopsy specimens revealed that the administration of MPA increased the diameter of endometrial glands (P less than 0.01) and the number of vacuolated glandular cells (P less than 0.001), decreased the number of glandular (P less than 0.01) and stromal (P less than 0.05) mitoses and reduced pseudostratification (P less than 0.001). There was no change in the number of endometrial glands and in glandular epithelial height. No leukocytic infiltration was observed. Dating of the biopsies indicated that all control biopsies were proliferative and all, but one (a suppressed proliferation including predecidual reaction), biopsies obtained after MPA administration were early secretory. The most conspicuous effect of MPA administration was a marked increase in subnuclear vacuolation, which could be demonstrated even at the lowest dose (P less than 0.01).

Adult↗
PubMed1986

[Light and electron microscopy changes in the endometrium caused by the administration of a norgestimate-containing oral contraceptive (Cilest)].

Endometrium morphology has been analysed by means of light microscopy, scanning and transmission microscopy in patients before and during treatment with a norgestimate containing low dose combined pill (Cilest). Endometrium biopsies were taken after 1 (N = 3), 2 (N = 3), 3 (N = 7), 5 (N = 1) and 6 (N = 4) OC cycles. Light microscopy of the endometrium obtained during the OC-free pretreatment cycles shows a regular secretory transformed endometrium. During the first OC cycles of Cilest treatment slight growth retardation of endometrial glands was observed. Endometrium after 3 to 6 OC cycles showed an increasing delay of the growth of endometrial glands in terms of an abortive secretion. Morphometric studies revealed a retardation of the development of endometrial glands and an "arrest of secretion". The degree of proliferation varied slightly; a general delay between the date of the menstrual cycle and endometrial dating was evident. Using scanning electron microscopy the endometrium presented mostly a regular surface corresponding to the midcycle or a late proliferative phase up to the early secretory phase. Infiltrative dysplasia or inflammatory changes as well as local proliferations could not be detected. In transmission electron microscopy with semi-thin and ultrathin slices, stroma, structure of glands and surface appeared to be normal. Furthermore, no time delay between the endometrium and the day of menstrual cycle was observed. During treatment with a norgestimate containing low dose combined pill, only slight changes of the endometrium in terms of a growth retardation of endometrial glands were seen in the first 6 treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraceptives, Oral, Combined↗
PubMed1986

Effects of oestradiol and progesterone on the synthesis of DNA and the anti-haemophilic factor VIII antigen in human endometrial endothelial cells in vitro: a pilot study.

The effect of various concentrations of oestradiol and progesterone on DNA synthesis in endometrial endothelial cells derived from human decidua has been studied in vitro by means of a microfluorometric technique and [3H]thymidine incorporation. Oestradiol in concentrations of 10-40 ng/ml was found to significantly stimulate DNA synthesis in the cells whereas progesterone significantly decreased the incorporation of [3H]thymidine. A highly significant correlation (P less than 0.01) was found in the oestrogen-treated samples between the [3H]thymidine incorporation and the ethidium bromide fluorescence after the removal of RNA. No such correlation was found in the progesterone-treated samples. A microfluorometric assessment of the anti-haemophilic antigen Factor VIII following immunofluorescence labelling suggested an increase in the synthesis of this factor after oestradiol treatment whereas progesterone administration did not show any effect. Although no direct extrapolation can be made from the results of the in vitro studies to in vivo conditions the endothelial cell culture system provides a useful model for testing the effect of mitotic mediators and compounds interfering with intracellular protein synthesis. It may therefore contribute to a better understanding of the bleeding mechanism.

DNA↗
PubMed1985

The effect of a prostaglandin synthetase inhibitor on the hormonal profile and the endometrium in women.

A prostaglandin synthetase inhibitor, naproxen, was given continuously throughout the menstrual cycle at a dose of 250 mg twice daily to 10 healthy fertile women (group 1) and at a dose of 1000 mg per day to eight women in the secretory phase (group 2). Blood samples were withdrawn three times a week during a control cycle and during the treatment cycle. Luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol, and progesterone were analyzed. Endometrial biopsies were taken in the secretory phase of the control cycle and in the treatment cycle of group 1 and on the first day of menstruation of group 2. Naproxen treatment did not suppress ovulation in any cycle and did not affect the corpus luteum function either in group 1 or in group 2. In only one of the endometrial samples taken in the secretory phase (group 1) was the density of the lysosomes increased in the treatment cycle compared to the control cycle. The specimen taken during the early menstrual period (group 2) showed an increase in glandular epithelium and height following naproxen treatment. Furthermore, a significant increase in the number of plasmolemmal vesicles per square micrometer was observed in the capillary endothelial cells after the administration of 1000 mg of naproxen per day. This suggests that the transcellular exchange of water-soluble molecules in the endothelial cells was more active after the administration of a prostaglandin synthetase inhibitor than in the control group. In spite of the significant morphologic changes observed in the naproxen-treated material the onset of menstrual bleeding could not be prevented. The mechanism of the onset of menstruation needs to be further investigated.

Cyclooxygenase Inhibitors↗
PubMed1985

Pharmacokinetic and pharmacodynamic investigations with monthly injectable contraceptive preparations.

Eight normally menstruating women received Cycloprovera (25 mg medroxyprogesterone acetate with 5 mg estradiol cypionate) and seven other volunteers received HRP-102 (50 mg norethisterone enanthate with 5 mg estradiol valerate) injections at 30-day intervals for three consecutive months. The peripheral plasma levels of estradiol (E2), progesterone (PROG), medroxyprogesterone acetate (MPA) and norethisterone (NET) were measured in the luteal phase of a pretreatment cycle, during the third treatment month and during a subsequent recovery period of 60 days. Blood samples were drawn three times a week (Mondays, Wednesdays and Fridays) and endometrial biopsies were taken on day 20 to 26 of the pretreatment cycle, 20 to 24 days after the last injection and 20 to 24 days after the first normal menstrual-like bleeding during the recovery period. The (geometric) mean maximum level of MPA was 2.9 (2.4-3.7) nmol/1 and that of NET 10.1 (6.4-15.8) nmol/l. Thirty days after the last injection, the MPA level was 0.72 (0.46-1.1) nmol/l and that of NET 1.7 (1.2-2.3) nmol/l. The maximum level of exogenous E2 was 890 (700-1130) pmol/l after Cycloprovera and 1570 (870-2820) pmol/l after HRP-102 administration. Forty-nine and 41 days, respectively, after the last injection, a broad (endogenous) E2 peak was observed in all subjects, which was not followed by an ovulatory rise in PROG levels. The first ovulatory rise in PROG occurred between 71 and 90 days after the last Cycloprovera and 59 to 87 days after the last HRP-102 injection. One subject in each of the two groups failed to ovulate during the 90-day post injection period. Dating and morphometric analysis of the endometrial biopsy specimens obtained 20 to 24 days after the last injection revealed that the suppressive effect of Cycloprovera was stronger than that of HRP-102. Each injection of both formulations was followed by a bleeding-free period of approximately two weeks. The percentage of days with bleeding and spotting was 24% for Cycloprovera and 29% for HRP-102. It is concluded, that both monthly injectables inhibit follicle maturation for some 30 days and ovulation and corpus luteum formation for some 60 days, providing thus a considerable margin of safety in terms of the expected duration of contraceptive protection.

Adult↗
PubMed1985

A clinical pharmacological study of a new type of vaginal delivery system for levonorgestrel.

The pharmacokinetic and pharmacodynamic effects of a new type of levonorgestrel-releasing vaginal device (with an in vitro release rate of 25 micrograms/24 h) were studied in a group of 18 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were drawn three times weekly (Mondays, Wednesdays, Fridays) during a pretreatment (control) cycle and during the 90 days (3 segments) of exposure to levonorgestrel and the levels of levonorgestrel, progesterone and estradiol were analyzed. Blood samples were also drawn at frequent intervals during the first day and daily during the first week with the devices in situ. In addition, endometrial biopsy specimens were obtained during days 20-22 of the control cycle and then 6 and 10 weeks following the insertion of the devices for morphometric analysis and for the assay of progesterone and estradiol levels. Following insertion of the devices, plasma levels rapidly rose to 1 nmol/l in 12 hours; a plateau of approximately 1.6 nmol/l was reached in 3-4 days, after which the plasma levels declined in a linear fashion with a daily average rate of 7.4 pmol/l to 60% of the initial level in 90 days' time. Of the 54 treatment segments of 30 days, 68% were anovulatory and 24% showed normal, ovulatory-like estradiol and progesterone levels. A complete set of three biopsies were obtained from 15 of the 18 subjects. Of the biopsies obtained during exposure to levonorgestrel only one exhibited signs of atrophy, 80% showed suppressed or arrested proliferation, and 10% had a normal cyclic appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1985

Cyclic changes in human endometrial surface glycoproteins: a quantitative histochemical study.

We used histochemical methods specific for carbohydrates on accurately timed endometrial biopsies to examine changes in quantity or electronegativity of the endometrium's luminal glycocalyx through the menstrual cycle in normal fertile women. Electronegative glycocalyx was detectable light-microscopically throughout the menstrual cycle. On the third day after the luteinizing hormone peak, a significant increase (P = 0.005) in endometrial surface glycocalyx was evident along with the appearance, in endometrial glands, of material having the staining properties of acid mucus glycoprotein (MGP), which implies that after this material's production by the glands or by the surface epithelium, it becomes adsorbed onto the surface glycocalyx. This phenomenon was accompanied by an apparent decrease in glycocalyceal electronegativity as indicated by a shift from high iron diamine (pH 1.0) to alcian blue (pH 2.5) staining reactivity. Because the timing of the appearance of endometrial moderately acid MGP coincides with or precedes the time that the early fertilized embryo enters the endometrial cavity, a role for the MGP in embryo nutrition or in implantation is suggested.

Densitometry↗
PubMed1984

Return of ovulation following a single injection of depo-medroxyprogesterone acetate: a pharmacokinetic and pharmacodynamic study.

The effect of a single dose of 150 mg of depo-medroxyprogesterone acetate (DMPA) on pituitary, ovarian and endometrial function was assessed in relation to the peripheral levels of the compound in 8 women. The levels of medroxyprogesterone acetate (MPA), follitropin (FSH), lutropin (LH), prolactin, estradiol (E2) and progesterone ( Prog .) were measured 3 times a week during a pretreatment (control) cycle and then daily during postinjection weeks 14-17, 22-25 and 30-33. An endometrial biopsy specimen was obtained during postinjection weeks 17, 25 and 33. In three out of 8 subjects the daily hormone assays carried out during postinjection weeks 30-33 indicated anovulatory periods; in these subjects peripheral blood was drawn daily during postinjection weeks 46-49 and a fourth endometrial biopsy was taken during week 49.

Adult↗
PubMed1984

Pharmacokinetics, pharmacodynamic and endometrial effects of a single dose of 200 mg norethisterone enanthate.

Ovulation was confirmed by daily analyses of the peripheral plasma levels of estradiol (E2)4) and progesterone (P) in a pre-treatment cycle of 14 subjects. An endometrial biopsy was taken either in the proliferative or in the secretory phase of the cycle. On the 5th day of a subsequent cycle 200 mg norethisterone enanthate (NET-EN) was administered intramuscularly. The levels of E2, P and those of NET were analyzed during the next 19 days and again during 44-60 days following the injection. The endometrial biopsy was repeated on the 23rd and 59th day of the treated cycle. The levels of NET reached a peak of 34.3 nmol/1 on the sixth post-injection day and decreased to below detectable limits in 3 of 12 subjects by the end of the observation. Ovarian activity was completely suppressed in all women during the first period, but returned to different levels in 11 subjects during the second. Four of them exhibited ovulatory steroid pattern. The morphologic changes of the endometrium reflected the progestogen effect in the first post-injection period but were characteristic of the ovarian reaction in the second.

Adult↗
PubMed1984

Culture of human endothelial cells derived from capillaries of the decidual tissue.

Human endothelial cells derived from the capillary bed of endometrial decidua were studied in vitro using medium 199 supplemented with 20% fetal calf serum. Cells in primary and subcultures were identified in parallel by electron microscopy and indirect immunofluorescence microscopy. The abundance of microfilaments appearing in small bundles, the micropinocytotic vesicles in the cell periphery, the occurrence of characteristic Weibel-Palade bodies and the intense and specific fluorescence after decoration with antibodies to Factor VIII protein--all were criteria for a positive demonstration of the endothelial character in the cell cultures derived from the capillary bed of the human decidua. The proliferative activity of the in vitro system was studied by autoradiography of the endothelial cells after exposure to [3H]-thymidine at various periods of incubation. A statistically highly significant difference (p less than 0.001) was found between periods of 4-6 and 6-8 days of incubation and between 6-8 and 8-10 days of incubation (p less than 0.01). No such difference was found between 8-10 and 10-14 days of incubation. When the medium was switched to complete M 199 + 10% fetal calf serum and 10% human plasma containing 76 pg/ml of estradiol the thymidine index was 5 to 4 times as high as in the control medium after 5 to 6 days of incubation. The results indicate that the in vitro system developed on endometrial capillaries derived from human decidua provides a stable low background of DNA synthesis against which small amounts of possible mediators of endothelial mitoses, e.g. estradiol, progesterone and various synthetic progestogens, can be tested.

Autoradiography↗
PubMed1983

Pituitary, ovarian and endometrial effects of progesterone released prematurely during the proliferative phase.

The pituitary, ovarian and endometrial effects of premature exposure to progesterone during the proliferative phase were investigated in 18 normally menstruating women. Daily blood samples were drawn during a control cycle and an endometrial biopsy was obtained on cycle day 6 (in 9 subjects) and on cycle day 11 (in 9 subjects), respectively. Daily blood samples were drawn again throughout a treatment cycle, in which a vaginal delivery system releasing progesterone at a constant rate of 1.4 mg/24 h was inserted and left in situ for 96 hours during cycle days 2-6 (9 subjects) and cycle days 7-11 (9 subjects), respectively. On the 6th and 11th cycle day, respectively, the devices were removed and another biopsy specimen was obtained. In all blood samples the levels of immunoreactive lutropin (LH), estradiol (E2), 17-hydroxyprogesterone (17-HO-P), progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-HO-P) were estimated by radioimmunoassay. Insertion of the devices resulted in a rapid, approximately six-fold increase (from 0.5 to 3.0 nmol/l) in P levels and an approximately three-fold (from 0.5-0.6 to 1.5-2.0 nmol/l) increase in 20 alpha-HO-P levels. A high degree of correlation was found between P and 20 alpha-HO-P levels. No major changes were observed in the profiles and levels of the other hormonal indices studied. However, premature exposure to small amounts of P during cycle days 2-6 resulted in a significant decrease in the ratio of the E2 to LH peaks and exposure during cycle days 7-11 gave rise to a significant increase in the ratio of the length of follicular to luteal phases. Progesterone released during the early proliferative phase (days 2-6) exerted little, if any, effect on the appearance of the endometrium. However, the same dose of P released during the late proliferative phase (days 7-11) significantly diminished the number of glandular mitoses, the height of the glandular epithelium, reduced pseudostratification and the number of plasmolemmal vesicles, but did not induce any subnuclear vacuolation, predecidual reaction or leucocytic infiltration. It is suggested that systematic studies involving the exposure to progestogens in normally menstruating women during cycle days 7 to 11 will provide a reliable and practical method for the comparative assessment of the potency profile of individual progestogens in women.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Pharmacodynamic effects of ethinyl estradiol in women using vaginal devices releasing small doses of levonorgestrel at a constant rate.

Eight normally menstruating women were provided with vaginal devices releasing levonorgestrel (NOG)4) at a constant rate of 20 micrograms/24 h. On day 71 or 72 following the insertion of the device, oral doses of 50 micrograms of ethinyl estradiol (EE) were administered daily for one week. Peripheral blood samples were drawn three times weekly during a pretreatment (control) cycle and from day 29 of the treatment period. The levels of progesterone (P), estradiol (E2) and NOG were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by a steady state polyacrylamide gel electrophoresis and the percentage of binding of NOG, testosterone (T) and E2 by equilibrium dialysis of diluted plasma. An endometrial smear and a biopsy were taken from each subject on 3 occasions, viz. during the control cycle (cycle day 20-22), during the period with the NOG-releasing device in situ (44-50 days after the insertion of the device), and on the 7th day of concomitant EE administration.

Adult↗