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Biomedical subjects

M Akerlund

Publications and source records attributed to M Akerlund.

At least 73 records · Page 4Linked to original sources

A solution to the problem of "missing" IUD threads.

A disposable, plastic, sterile instrument, RetrievetteR, for the retrieval of 'missing' threads of intrauterine contraceptive devices (IUD) at routine gynecological investigations was developed and tested in 80 patients. In 64 instances, the threads were found and easily drawn out through the cervical canal. In the remaining 16 cases, where the threads were not found, this was due to already expelled IUD in 6, too short threads in 5, inverted IUD in one, IUD which had partly perforated the uterine wall in one, unknown factors in 2 cases where the women chose to keep a correctly placed IUD in spite of missing threads and, finally, in only one case due to method failure. In the latter case, a correctly placed IUD with threads of normal length was later extracted under general anaesthesia. It is concluded that this instrument can help the physician avoid more complicated and unpleasant procedures with ultrasonic or X-ray localization and subsequent IUD extraction under local or general anesthesia in women with missing IUD threads.

Equipment Design↗

The effect on the human uterus of two newly developed competitive inhibitors of oxytocin and vasopressin.

In order to develop inhibitors of vasopressin (VP) and oxytocin (OXY) action on uterine activity, 1-deaminated vasotocin derivatives with modifications at positions 2, 4 and 8 were developed. Two of the most effective analogues in the rat, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-vasotocin (dE-VVT) and 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin (dE-TVT) were now tested on human nonpregnant myometrium obtained at hysterectomy in fertile age and on pregnant myometrial tissue obtained at elective cesarean section. The effect was compared with that of a previously synthesized analogue 1-deamino-Tyr(OEt)-oxytocin (dE-OXY) which has already been tested in nonpregnant and pregnant women in vivo. Both of the new analogues competitively inhibited the action of the posterior pituitary hormones. On the nonpregnant uterus dE-VVT was about five times and dE-TVT almost twenty-five times more potent than dE-OXY in inhibiting the effects of VP. On pregnant myometrium, dE-TVT inhibited oxytocin action about as effectively as a five-fold stronger concentration of dE-OXY, and dE-VVT slightly less. A moderate agonistic effect of dE-OXY on pregnant myometrium was found, whereas it was minimal with dE-VVT and not detectable at all with dE-TVT. It appears that these two analogues, particularly dE-TVT, would be interesting for clinical testing both in dysmenorrhea, where increased VP secretion could be of etiological importance, and in premature labor where an increased myometrial concentration of OXY receptors has been demonstrated.

Adult↗

Interaction of vasopressin and prostaglandins in the nonpregnant human uterus.

The interaction of vasopressin (VP) and prostaglandins (PG) on the nonpregnant human uterus was studied in vitro and in vivo. In organ baths arginine (A)- and lysine (L)-VP in concentrations of 0.6 to 100 ng/ml stimulated small human myometrial strips and uterine artery preparations to a similar degree. When these VPs were given in the presence of indomethacin or naproxen in concentrations of 1 microgram/ml and 5 micrograms/ml, respectively, the myometrial and arterial responses were not significantly influenced. PGF2 alpha in concentrations of 0.01-100 ng/ml stimulated the myometrial preparations but caused a slight relaxation of the arteries, with PGE2 the myometrial effects were insignificant and the relaxation of the arteries greater. When AVP was given together with either of the PGs to the bath the result was generally a summation of the individual effects of both types of substances.--In vivo during intrauterine pressure recordings in nonpregnant women 1-2 days before onset of menstruation LVP in single intravenous injection of 1.2 micrograms markedly stimulated uterine contractions. The response remained practically unaltered after pretreatment with 500 micrograms of naproxen given orally. The responses to LVP were also closely similar before, during and after intravenous infusion of PGF2 alpha at a rate of 5 micrograms/min.--It is concluded that the effect of VP on myometrium and uterine arteries is not to any great extent mediated by local synthesis of PG and that PGs do not cause potentiation or inhibition of the VP effects on the nonpregnant uterus.

Arginine Vasopressin↗

Vasopressin and prostaglandins in premenstrual pain and primary dysmenorrhea.

Both vasopressin and PGF2 alpha are effective uterine stimulants in the non-pregnant human uterus, especially around the onset of menstruation. In order to clarify the relationship of these hormones to menstrual pain, plasma concentrations of vasopressin and two prostaglandin metabolites (15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites) were measured in serial blood samples taken premenstrually and during menstruation. Five women with premenstrual pain gave 7-9 blood samples at intervals of 30 minutes on the day preceding the onset of menstruation. From 5 women with severe primary dysmenorrhea a corresponding series of blood samples were taken during the first day of menstruation. Two groups of 5 women with no symptoms served as controls, either premenstrually or during menstruation. In the women with premenstrual pain the vasopressin concentrations were significantly higher than in the corresponding control group. Even higher and markedly fluctuating vasopressin levels were found in the women with dysmenorrhea who, in general, had more intense pain than the women with premenstrual symptoms. In the group with dysmenorrhea there was also a significant rise in plasma concentration of the PG metabolites. No such increase was seen in the group with premenstrual pain. It is concluded that the pathophysiology of premenstrual pain could imply increased vasopressin secretion. The more severe pain in primary dysmenorrhea seems to be the result of a combined effect of vasopressin and PGF2 alpha.

Adolescent↗

Influence of danazol on uterine activity. A pilot study.

The influence of danazol treatment on uterine activity was studied by means of repeated intra-uterine pressure recordings in two women with laparoscopically diagnosed endometriosis. During a control cycle the women had normal plasma levels of FSH, LH, estradiol and progesterone and repeated recordings showed a varying uterine activity, with irregular small contractions in the follicular phase and regular ones with maximal amplitude and duration at the onset of menstruation. Treatment with danazol inhibited the fluctuations in circulating gonadotropins and invariably caused low levels of ovarian hormones. Between 2 and 3 weeks after starting treatment there was a period of increased myometrial activity and increased reactivity of the uterus, but thereafter a marked inhibition of the contractions was seen. It is suggested that danazol could be of value in the treatment of painful conditions with excessive uterine activity, such as primary--and to some extent also secondary--dysmenorrhea.

Adult↗

Inhibition of vasopressin effects on the uterus by a synthetic analogue.

A synthetic analogue, deamino-ethyl-oxytocin, which competitively inhibits vasopressin action on uterine activity both in vitro and in animal experiments was developed. The uterine effect of this analogue was studied during the recording of intrauterine pressure in 16 gynecologically healthy women. Increased uterine activity and dysmenorrhea-like pain was induced by infusing lysine vasopressin in a dose of 0.08 microgram/min. Deamino-ethyl-oxytocin inhibited vasopressin action, the threshold dose being approximately 200 micrograms given as a single intravenous injection for about 20 minutes. When given intranasally the drug was also shown to be effective in inhibiting vasopressin-induced uterine activity and symptoms. These results suggest that deamino-ethyl-oxytocin could be of therapeutic value in primary dysmenorrhea, a condition associated with increased vasopressin secretion.

Adult↗

Involvement of prostaglandins in vasopressin stimulation of the human uterus.

The involvement of prostaglandins (PG) in the vasopressin (VP) action on the human uterus was investigated in healthy women during three menstruations. Intrauterine pressure was recorded and total pressure area measured. Repeated plasma samples were taken for estimations of arginine(A)- and lysine(L)-VP, 15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites. During the first menstruation LVP was infused in a dose of 0.08 micrograms/min. During the second menstruation the infusion of LVP was repeated with the same dose, but 70 min before infusion the women received an oral dose of 500 mg of naproxen. During the third menstruation PGF2 alpha was administered intravenously in a dose of 25 micrograms/min. LVP infusion per se caused a significant increase in uterine activity and plasma levels of LVP and PG metabolites. When the women were pretreated with naproxen practically the same uterine activity was induced and closely similar plasma levels of LVP were obtained, but the levels of PG metabolites decreased significantly in comparison with the first series of experiments. Infusion of PGF2 alpha caused an increase in uterine activity but no change in the plasma levels of AVP. The results indicate that uterine stimulation with VP is possible without an obligatory last step of PG synthesis and release. The results also support the concept that an elevated VP level in primary dysmenorrhoea may be of aetiological importance and is not just released as a 'stress'-hormone because of the dysmenorrhoeic pain.

Adult↗

Vasopressin effects on isolated non-pregnant myometrium and uterine arteries and their inhibition by deamino-ethyl-lysine-vasopressin and deamino-ethyl-oxytocin.

The contractile effects of lysine- (L) and arginine- (A) vasopressin (VP) on isolated non-pregnant myometrium and uterine arteries and the inhibition of these actions by two analogues of posterior pituitary hormones, deamino-ethyl-LVP (dE-LVP) and deamino-ethyl-oxytocin (dE-OXY) were investigated. Both AVP and LVP effectively stimulated the smooth muscle preparations. The threshold dose for both agonists was about 2 ng/ml of bath fluid and a maximal response was obtained with approximately 75 ng/ml. No distinguishable effect was produced by dE-LVP and dE-OXY alone, but when given before the agonists in concentrations of 150 or 300 ng/ml, dose-dependent inhibition of the contractions was seen. The inhibition of the uterine artery responses was always greater than the inhibition of the effects on myometrial activity and dE-LVP appeared to have stronger antagonistic effects than de-OXY on the myometrial responses to the agonists. The inhibition of the myometrial and uterine artery responses to AVP could explain the therapeutic effect of dE-OXY recently found in primary dysmenorrhoea, where increased VP secretion seems to be of aetiological importance.

Arginine Vasopressin↗

Inhibition of lactation by cyclofenil and bromocriptine.

In a double blind controlled study of the inhibition of lactation 13 women received 300 mg of cyclofenil and 11 women 2.5 mg of bromocriptine twice daily for 14 days. Lactation was effectively inhibited by both drugs, but with bromocriptine there was a significantly higher frequency of relapse. The plasma concentration of prolactin, which decreased rapidly with bromocriptine, returned to the pretreatment level the day after drug treatment stopped, but with cyclofenil it remained low. Plasma oestradiol followed a similar pattern. Plasma FSH increased more rapidly with bromocriptine than with cyclofenil. There was no significant difference between the treatment groups at any stage for haematology, coagulation or liver function tests. The more sustained effect of cyclofenil on prolactin secretion with a reduced frequency of relapse, and the lower oestradiol level, which might indicate a reduced risk of thromboembolism, suggest that this drug has some advantage over bromocriptine in the inhibition of postpartum lactation.

Bromocriptine↗

Cerebrospinal fluid arginine vasopressin in degenerative disorders and other neurological diseases.

Arginine vasopressin (AVP) was determined in plasma and lumbar CSF from 46 patients with Parkinson's disease, dementia, cerebrovascular disease, multiple sclerosis and other, mostly peripheral neurological disorders. The mean plasma concentration of AVP was 1.62 microU/ml, the CSF concentration 1.14 microU/ml and the gradient CSF/plasma 0.72. There was a good correlation between the plasma and the CSF values in most patients. No sex difference could be found. A slight decrease of the CSF values could be found with increasing age. Significantly higher CSF-AVP values were found in patients with cerebrovascular disease, whereas lower CSF values were found in patients with dementia and Parkinson's disease. However there were decreased CSF/plasma gradients in patients with dementia and Parkinson's disease to about 0.30 compared to 0.98 in patients with peripheral neurological disorders. Patients with multiple sclerosis had an increased IgG index indicating an intrathecal IgG production but there was no obvious correlation between this and the AVP concentrations in plasma and CSF, nor with the total CSF protein content, nor with the albumin and IgG concentrations in plasma and CSF.

Adolescent↗

Fibromyomas and uterine activity.

Intra-uterine pressure was recorded with a triple-channelled microtransducer catheter in women with fibromyomas prior to hysterectomy or myomectomy and in women due to undergo hysterectomy because of other gynecological disorders. In most of the patients with myomas the uterine activity differed from that in the women without myomas and from findings in previous studies on uterine activity in healthy subjects. Thus, small and irregular contractions were frequently seen in the pressure recordings from the receptors placed in the vicinity of myomas. In women with dysmenorrhea secondary to the development of myomas, increased uterine activity was registered. It is concluded that myomas may have a clinically significant effect on uterine activity.

Adult↗

Dopamine influence on human uterine activity at term pregnancy.

The influence of dopamine on uterine activity was studied by external tocography in women at the end of a normal pregnancy. In those who were not in labour dopamine infusion (2 micrograms min-1 kg-1 body weight) induced regular uterine contractions and with higher doses the response increased. For women in spontaneous labour, dopamine at a dose of 4 micrograms min-1 kg-1 caused a significant increase in the frequency of contraction, but in women receiving an oxytocin infusion, no further stimulation was seen. Dopamine did not have any noticeable effect on fetal heart rate, maternal pulse rate or blood pressure and no other general effects were observed.

Dopamine↗

Effect of ovarian steroids on vasopressin secretion.

In normally menstruating women plasma vasopressin concentrations vary with the stage of the cycle and are highest at the time of ovulation and lowest at the onset of menstruation. To determine whether this is the result of changes in the circulating concentrations of ovarian steroids, vasopressin concentrations were determined in six postmenopausal women given oestrogen and progestogen. An increase in plasma oestradiol concentrations to 299 +/- 97.8 pmol/l augmented vasopressin release. Administration of medroxyprogesterone did not influence vasopressin concentrations but when given in combination with oestrogen a fall was observed. Thus it appears that ovarian steroids can modulate vasopressin release.

Animals↗

Comparison of plasma and myometrial tissue concentrations of estradiol-17 beta and progesterone in nonpregnant women.

Plasma and myometrial tissue concentrations of estradiol (E2) and progesterone (P) were measured by radioimmunoassay techniques in samples obtained from women with regular menstrual cycles and from women in pre- or postmenopausal age. In women with regular cycles, the tissue concentration of E2 ranged from 0.13 to 1.06 ng/g wet weight, with significantly higher levels around ovulation than in follicular or luteal phases of the cycle. The tissue concentration of P ranged from 2.06 to 14.85 ng/g wet weight with significantly higher level in luteal phase than in follicular phase. The tissue/plasma ratio of E2 ranged from 1.45 to 20.36 with very high values in early follicular phase and the lowest in mid-luteal phase. The ratio for P ranged from 0.54 to 23.7 and was significantly lower in the luteal phase than in other phases of the cycle. One woman in premenopausal age with an ovarian cyst was the only case with a tissue/plasma ratio of E2 Less Than 1, since her plasma E2 levels were exceptionally high. In postmenopausal women, the tissue concentration of E2 was not significantly lower than in menstruating women in follicular phase, and the tissue concentration of P was not significantly lower than in fertile women in any of the phases. Neither in these women nor in menstruating women was there a close correlation between tissue and plasma levels. The present data indicate that the myometrial uptake capacity for ovarian steroids may be saturated, and also that a certain amount of these steroids is bound to tissue even if plasma levels are low.

Adult↗

Influence of copper ions on uterine activity.

The influence of copper ions on myometrial activity was tested in nonpregnant rabbits in vitro and in vivo, and nonpregnant women in vivo. In an organ bath, CuCl2 in concentrations of 3 micro M and higher caused a dose-dependent increase in the contractile activity of isolated rabbit myometrium. In rabbits in vivo, intrauterine instillations of 0.2 to 2 mM of CuCl2 in 0.6 ml of saline solution caused a dose-dependent increase of myometrial activity in the uterine horn where it was injected, and the response lasted up to 30 minutes. The activity in the other horn remained unchanged and control injections with saline had no effect. Also, in nonpregnant women, a clear and dose-dependent effect of 1 ml of 0.3 to 3 mM of CuCl2 dissolved in saline was observed after intrauterine instillation. Saline itself in the same volume had no effect. It is estimated that the intrauterine doses of copper which were used in these experiments lead to Cu++ concentrations in the uterine tissues which were similar to those in women carrying a copper IUD, and it is suggested that the copper from such IUDs might have effects on myometrial activity contributing to the contraceptive action and to some of the side-effects of these devices.

Animals↗

Inhibitory effect of O-alkylated analogues of oxytocin and vasopressin on human and rat myometrial activity.

Analogues of oxytocin and vasopressin modified through O-alkylation (methyl, ethyl and butyl) at position 2 of the peptide chain were synthesized and tested for effects on the rat uterus in vivo and on isolated rat and human myometrial preparations. None of the analogues showed any appreciable oxytocic activity. When tested together with oxytocin or vasopressin the analogues inhibited the uterine response to the hormones in a dose-dependent and reversible way. Ethyl-analogues were more powerful antagonists than methyl-analogues but further prolongation of the alkyl-chain (butyl) diminished the antagonistic properties of the compounds. The effect of antagonistic potency of deamination at position 1 of the analogues varied among the analogues and depended on the test system used. The possible clinical value of the antagonists is discussed.

Animals↗

Variations in plasma concentrations of vasopressin during the menstrual cycle.

Plasma vasopressin concentrations, determined by radioimmunoassay, were followed throughout the menstrual cycle in eight healthy women. The concentrations were found to depend on the day of the menstrual cycle. The mean concentration on day 1 was 0.5 +/- 0.08 (S.E.M.) microunits/ml, while that on days 16-18 was 1.1 +/- 0.16 microunits/ml. These values were significantly (P less than 0.02) different. Vasopressin release in women may thus depend on the hormonal changes during the menstrual cycle.

Adult↗

Effects of prostaglandin inhibition on vasopressin levels in women with primary dysmenorrhea.

Arginine vasopressin (AVP) concentrations in plasma were studied in women with primary dysmenorrhea before and after treatment with naproxen, and in healthy control women on the first day of menstruation. In the treated group the AVP concentration was about 4 times higher than that in the controls, and the AVP level remained unchanged after almost complete pain relief had been obtained by treatment with the prostaglandin synthesis inhibitor. No significant differences were found between the 2 groups in plasma osmolality and sodium concentration on the first day of menstruation, or in the concentrations of progesterone and estradiol at this time or in the midluteal phase of the preceding menstrual cycle. These results indicate that increased secretion of AVP may play an etiologic role in dysmenorrhea, activating the uterus via a final step of prostaglandin synthesis an release.

Adult↗