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Biomedical subjects

U Ulmsten

Publications and source records attributed to U Ulmsten.

At least 181 records · Page 10Linked to original sources

Effects of calcium and nifedipine on noradrenaline- and PGF-2 alpha-induced activity of the ampullary-isthmic junction of the human oviduct in vitro.

From 22 women undergoing hysterectomy at various stages of the menstrual cycle, strip preparations were dissected from the outer, longitudinal and the inner, circular smooth muscle layers of the ampullary-isthmic junction (AIJ). The strips were mounted in organ baths, and isometric tension was recorded. Spontaneous contractions were recorded mainly in circular muscle strips. Contractions were elicited by 127 mM-K+, 10(-6) M-noradrenaline and 10(-6) M-PGF-2 alpha. Potassium induced biphasic responses that were slightly different in the two tissues. In circular muscle strips, noradrenaline and PGF-2 alpha induced phasic contractions superimposed on a rise in tone. In longitudinal muscle specimens, the two compounds produced tonic responses. All types of mechanical activity were inhibited by removal of extracellular calcium. K+-induced responses and phasic contractions produced by noradrenaline and PGF-2 alpha could be abolished by 10(-6) M-nifedipine whereas the tonic contractions in the circular and longitudinal muscle were more resistant to the calcium antagonist. The results suggest that K+-induced responses in circular and longitudinal muscle of the human AIJ, and the phasic contractions in circular muscle, depend on calcium influx via potential-sensitive membrane channels. Receptor-operated calcium channels seem to be involved in the tonic contractions observed mainly in the longitudinal smooth muscle.

Adult↗

A study of the in vitro release profile of a new prostaglandin E2 delivery system for local administration in obstetrics.

The in vitro release profile of prostaglandin E2 (PGE2) from a starch polymer hydrogel was studied. Using a diffusion cell apparatus the in vitro release was measured in a cumulative manner based on a steady-state diffusion concept. The results showed that PGE2 was slowly released for a total of 18 hours. The rate of release was constant for up to 2 hours before changing to a lower value for the remaining time period. The PGE2-hydrogel showed sustained release characteristics which could be of significance in the clinical situation in providing a delayed release mechanism.

Diffusion↗

Aspects of inhibition of myometrial hyperactivity in primary dysmenorrhea.

Uterine hypercontractility is considered to be an important factor in primary dysmenorrhea. A survey is given on possible mechanisms controlling the cytoplasmic concentration of free calcium and thereby contractile activity in the myometrial smooth muscle cell. Probably acting by different modes of action, inhibitors of prostaglandin synthesis, calcium antagonists and beta 2 stimulators have all been shown to reduce myometrial activity and relieve dysmenorrheic pain. The possibility of achieving further uterine relaxation after initial treatment with prostaglandin inhibitors by adding a calcium antagonist such as nifedipine is discussed. It is also suggested that when utilizing a reliable pressure recording technique in the evaluation of dysmenorrheic patients, the pronounced myometrial relaxation obtained by such combined therapy may be of diagnostic value.

Adrenergic beta-Agonists↗

Local application of prostaglandin E2 in gel. A new technique to ripen the cervix during pregnancy.

The methods used to date to ripen the unfavorable cervix during pregnancy have considerable disadvantages, chiefly from the practical point of view. Intracervical application of a small dose (0.5 mg) of prostaglandin E2 (PGE2) in viscous gel is a safe, easily performed and effective method to ripen the cervix in both early and late pregnancy. A new starch-based gel seems to have solved the pharmaceutical problems associated with gel preparations used hitherto. The histological and biochemical changes induced by local application of PGE2 are similar to those occurring spontaneously during late pregnancy.

Abortion, Induced↗

Human cervical connective tissue and its reaction to prostaglandin E2.

A survey of connective tissue in general and human cervical connective in particular is presented. It is concluded that about 90% of the human cervix consists of fibrous connective tissue which, according to the composition of the collagen and the proteoglycans, is very similar to that in skin and sclera. The high activity of collagenase probably gives the cervical connective tissue from pregnant women its potential to ripen following prostaglandin treatment. Electron microscopical examination has revealed an increased amount of amorphous substance after such treatment. This may be caused partly by degraded collagen fibers and partly by newly synthesized proteoglycans.

Animals↗

The impact on labor induction of intracervically applied PGE2-gel, related to gestational age in patients with an unripe cervix.

In 54 patients with an unripe cervix in late third trimester, in which gestational age had been properly determined by repeated ultrasound scannings, labor was induced by intracervical application of 0.5 mg PGE2 in viscous gel. It was found that the outcome of the induced labor was not related to the gestational duration, but to the pre-inductive cervical score. Thus, the number of successful inductions was smaller and induction-delivery time longer, the lower the cervical score. Moreover, instrumental deliveries occurred most frequently in nulliparous women, with a low pre-inductive cervical score. Taking into consideration the difficulties of labor induction in the present type of patient, the overall proportion of instrumental deliveries (17%, including 7% cesarean sections) was low. No maternal or fetal side effects were observed. It is concluded that intracervical application a small dose of PGE2 in gel can be recommended for cervical priming and labor induction in pre- and post-term pregnancy.

Adult↗

The effect of midodrine and its active metabolite ST 1059 on the human urethra in vitro and in vivo.

The directly acting alpha-receptor agonist midodrine is active through its metabolite ST 1059. The effects of ST 1059 were investigated in vitro on strips of human urethra and on small human omental arteries. ST 1059 was as potent as noradrenaline on the isolated urethra, but had only 40% of noradrenaline's maximum activity. In omental arteries noradrenaline was at least ten times more potent than ST 1059 which only had about one fourth of noradrenaline's maximum activity. Compared to its effect on the vessels ST 1059 was ten times more effective on the urethra, whereas noradrenaline was slightly more effective on the vessels than on the urethra. Thus, in vitro St 1059 exhibited some selectivity for urethral alpha-receptors. When midodrine was given to 13 female patients with stress incontinence in the doses 2.5 mg and 5 mg x 3 for two weeks, only two had a positive urethral closure pressure during treatment and were subjectively improved. There were no effects on blood pressure and heart rate; one patient complained of pilo-erection. Two further patients received 7.5 mg x 3 for two weeks; both were subjectively improved but complained of pronounced pilo-erection. Only one of them had a positive urethral closure pressure during treatment. Blood pressure or heart rate did not change. Although it cannot be excluded that midodrine can increase intraurethral pressure with minor effects on blood pressure, it seems as the doses needed cause pilo-erection to an extent that limits the clinical usefulness of the drug.

Adult↗

Low dose i.v. infusion of prostaglandin F2 alpha for induction of labor at term.

In 100 pregnant women at term, labor was induced for medical reasons by i.v. infusion of a low dose of prostaglandin F2 alpha (PGF2 alpha). With a dose not exceeding 6 micrograms PGF2 alpha/min, all patients were induced into labor. The mean induction-delivery time was 6.6 hours and the overall proportion of instrumental deliveries was 19%, including 6% cesarean sections. Very few side effects were observed. It is concluded that i.v. infusion of prostaglandin F2 alpha in a low dose regimen might be considered as an alternative to existing methods for the induction of labor at term.

Adolescent↗

Effects of nifedipine on oxytocin- and prostaglandin F2 alpha -induced activity in the postpartum uterus.

In order to get additional information on spontaneous and drug-induced uterine activity in the early postpartum period, intrauterine pressure was registered by the microtransducer technique in 19 patients. The effects of the calcium entry blocker nifedipine were also tested. Myometrial activity was induced by infusion of oxytocin (10 patients) or prostaglandin F 2 alpha (nine patients). Both hormones increased myometrial activity, with slightly different patterns of contractility. Nifedipine effectively reduced contractions induced by both drugs. The microtransducer technique seems to be a convenient and safe method for studying the effects of drugs and hormones on uterine activity post partum. Furthermore, nifedipine administered orally is a potent inhibitor of drug-induced myometrial activity in the early postpartum period.

Adult↗

Location of maximum intraurethral pressure related to urogenital diaphragm in the female subject as studied by simultaneous urethrocystometry and voiding urethrocystography.

The urethral pressure profiles were recorded by microtransducers in 25 continent female subjects. From the recordings, the urethral length and the site of maximum intraurethral pressure were determined with a high degree of precision. The urethral length and the distance from the external urethral meatus to the urogenital diaphragm were also assessed on 100 mm roentgenograms taken in the lateral projection. When the results from both recording techniques were compared, the urogenital diaphragm was found to be located, on average, 5.2 mm more distal in the urethra than the site of the maximum urethral pressure. Thus, the conclusion to be drawn is that the high-pressure zone of the urethra in continent women is located proximal to the urogenital diaphragm.

Adult↗

Effects of nifedipine on spontaneous and methylergometrine-induced activity post partum.

Intrauterine pressure changes were recorded by microtransducer catheter in 17 women immediately post partum. In all patients, spontaneous contractile activity was recorded, characterized by high contraction amplitudes (110 to 350 mm Hg). The calcium entry blocker nifedipine effectively inhibited these contractions. Both in vitro, in strips of pregnant myometrium, and in vivo, methylergometrine induced a contractile activity that could be blocked by nifedipine. The conclusion is that, for the testing of drugs that affect the contractile activity of pregnant myometrium, the use of intrauterine pressure recording by microtransducer catheters in the early postpartum period provides a suitable model.

Adult↗

The unstable female urethra.

Four hundred forty-seven patients with urinary incontinence were examined at the outpatient clinic and then referred to urodynamic investigation by urethral pressure profile measurement and simultaneous urethrocystometry. On urodynamic investigation, 55 patients showed signs of an unstable urethra (momentary variations in urethral pressure exceeding an amplitude of 15 cm of water by or without registration of bladder instability). Urethral instability was found in 15 patients with stress incontinence, in 23 patients with urge incontinence, and in 13 patients with combined stress and urge incontinence (i.e., signs and symptoms of both stress and urge incontinence). In four patients, urethral instability was the only pathologic finding when the recordings were made. From the pressure recordings, three types of urethral instability could be recognized: type 1, relatively small fluctuations in the urethral pressure at large bladder volumes; type 2, relatively large variations in urethral pressure with frequent decreases in the pressure, often combined with signs of unstable bladder; type 3, marked variations in the urethral pressure which appeared already at the start of urethrocystometry, i.e., at low bladder volumes. The variations in urethral pressure prevailed during the whole recording procedure, whereas bladder pressure was completely stable at all times.

Female↗

Evidence for a local effect of intracervical prostaglandin E2-gel.

Eight primigravid women with a mean gestational age of 9.4 weeks (9 to 10 weeks) who were admitted for first-trimester abortion by dilatation and evacuation were preoperatively treated for 6 hours with either intravenous infusion of oxytocin or a strictly intracervical application of prostaglandin E2 (PGE2) in viscous gel. Myometrial activity was monitored by intrauterine pressure recording throughout the treatment. Contractile activity was more pronounced in the oxytocin-treated group, whereas cervical priming occurred after the PGE2 treatment only. Intracervical PGE2-gel is suggested to have direct effects on the cervical tissues, independent of uterine contractile activity. Furthermore, myometrial stimulation induced by escape of gel into the extra-amniotic space can be avoided by adjusting the volume of gel and technique of application to the dimensions of the cervix.

Abortion, Induced↗

Pharmacokinetics of terodiline in human volunteers.

The pharmacokinetics of terodiline HCl was studied in nine healthy volunteers given 12.5 mg i.v. and p.o. or 20 mg i.v. and 25 mg p.o. on two different occasions. The serum concentrations were measured by gas chromatography--mas spectrometry, using deuterated terodiline HCl as the internal standard. After i.v. administration the kinetics could be described by a two-compartment model with a mean distribution half life of 0.3 h and a mean elimination half life of 63 h. The serum clearance and apparent volume of distribution varied about 4-fold with mean values of 4.8 1/h and 417 1, respectively. After oral administration, the mean half life of absorption was 0.7 h and that of elimination 65 h. The absolute bioavailability varied between 64% and 105% with a mean of 92%. The long serum half life of terodiline should permit its once daily administration.

Administration, Oral↗