Martin Stjernquist

A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy

OBJECTIVE Our purpose was to study the efficacy, safety, and acceptability of a new estradiol-releasing (6.5 to 9.5 micrograms per 24 hours) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries. STUDY DESIGN Gynecologic clinical status, vaginal pH, cytologic characteristics, and occurrence of bacteriuria were determined before starting and after 3 and 12 weeks of treatment in 146 postmenopausal women. RESULTS Both treatments alleviated the subjective and objective symptoms of estrogen deficiency excellently, and both were equally effective at restoring the vaginal pH to levels normally seen in fertile women (< 5.5). Vaginal cytologic studies showed a significant difference in maturation value in favor of the estradiol-releasing silicone rubber vaginal ring, as measured by the pathologists assessment of the proliferation of the vaginal mucosa. A total of 77% of users were classified as responders, compared with 39% in the pessary group. Both treatments were well accepted. The administration of the pessary was associated with a significantly higher (p < 0.001) incidence of discomfort than that of the ring, which was given better (p < 0.001) rating by the patients at the 12-week visit. A strong preference (p < 0.001) for the ring was shown by patients with previous experience with pessaries. CONCLUSION Treatment of urogenital symptoms in postmenopausal women with an estradiol-releasing vaginal ring is shown to be an effective and safe method, exhibiting advantages over treatment with estriol vaginal pessaries.

Existence and coexistence of peptides in nerves of the mammalian ovary and oviduct demonstrated by immunocytochemistry

SummaryThe immunocytochemical distribution of substance P (SP), gastrin releasing peptide (GRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), and neuropeptide Y (NPY) was studied in the ovary and the Fallopian tube (oviduct) of rats, guinea-pigs, cows, pigs and humans. Generally, the nerve supply was better developed in the oviduct than in the ovary. GRP fibers were most scarce in all tissues. Nerves containing SP were particularly numerous in the oviduct of rat and guinea-pig, supplying the muscular wall and blood vessels. VIP and PHI coexisted in dense plexuses of nerves, not only around blood vessels but also in the follicular wall and the interstitial gland of the ovary, as well as within the smooth muscle layers and subepithelially in the oviduct. The general distribution of NPY was similar, but these immunoreactive nerves were even more numerous. Sequential staining for dopamine-β-hydroxylase and NPY together with results of chemical sympathectomy with 6-hydroxydopamine suggested that NPY was stored in the noradrenergic sympathetic nerves.

Short term complications of the tension free vaginal tape operation for stress urinary incontinence in women.

Objective To assess the prevalence of intra‐ and post‐operative complications with the tension free vaginal tape operation for female urinary incontinence.

Immunocytochemical localization of galanin in the rat male and female genital tracts and motor effects in vitro

Galanin, a recently discovered neuropeptide, was studied in the rat male and female reproductive tracts by immunocytochemistry and in vitro pharmacology. Nerve fibers containing galanin immunoreactivity were most abundant in the female paracervical tissue, where they surrounded non-immunoreactive ganglion cells. Galanin nerves were also found in the uterus and Fallopian tubes, as well as in the vas deferens. When tested in vitro galanin contracted the smooth muscle of both the uterine horn and cervix. Galanin also slightly potentiated the response to electrical field stimulation in preparations from the uterine cervix and vas deferens, but it had no effect on the seminal vesicle. Galanin-(1-10), an N-terminal residue of galanin, also contracted the uterine horn, though higher concentrations were required. The neurally induced contractions were not influenced by galanin-(1-10) in any of the smooth muscle preparations tested. The muscle receptors mediating the direct contractile effects in the uterine horn seem to require the N-terminus of galanin, while the neuromodulatory effects on the electrically induced contractile activity seem to need the C-terminal part or the whole galanin molecule. Galanin may thus function as a neuromediator in the rat male and female genital organs.

Contractile effect of endothelin in the human uterine artery and autoradiographic localization of its binding sites

OBJECTIVE The aim was to study the effects, mode of action, and binding sites of endothelin-1 in the human uterine artery. STUDY DESIGN The contractile effect of endothelin-1 on the human uterine artery with and without endothelium and the effect of verapamil and nicardipine on the contraction was investigated in vitro. The Student t test was used. Iodine 125-endothelin-1 binding sites were localized with autoradiography. RESULTS Endothelin-1 induced a contraction that was unaffected by removal of the endothelium. Verapamil antagonized the contraction, whereas nicardipine showed no effect. Iodine 125-endothelin-1 binding sites were demonstrated in the smooth muscle layer. CONCLUSIONS These results show that endothelin-1 is a vasoconstrictor in the human uterine artery and suggest that the effect is mediated by receptors on the smooth muscle cells. The mode of action seems to involve Ca++ influx by other than dihydropyridine-sensitive Ca++ channels. Endothelin-1 does not seem to stimulate release of other endothelium-derived vasoactive agents.

Characterization of endothelin receptors and localization of 125I-endothelin-1 binding sites in human umbilical artery

The mechanisms of endothelin-1-induced contractile response in the human umbilical artery were investigated in vitro. Autoradiography revealed 125I-endothelin-1 binding sites in the smooth muscle layer of the vessel wall. Endothelin-1 and sarafotoxin S6b induced concentration-dependent contractions while endothelin-3 was virtually without contractile effect. The endothelin ETA receptor antagonist BQ 123 did not affect the contraction to endothelin-1 but antagonized the contraction to sarafotoxin S6b. The contraction to endothelin-1 and sarafotoxin S6b was diminished by both verapamil and nicardipine. It can be concluded that endothelin-1 is a vasoconstrictor in the human umbilical artery, probably acting via more than one contraction-mediating receptor. The 125I-endothelin-1 binding sites demonstrated in the smooth muscle layer of the vessel may correspond to receptors mediating the contractile effect. The mechanisms of action seems to involve activation of Ca2+ channels. The present study does not give any evidence for interaction of endothelin-1 with other endothelium-derived vasoactive agents in this vessel.

The Lactobacillus flora in vagina and rectum of fertile and postmenopausal healthy Swedish women

BackgroundLactobacillus species are the most often found inhabitants of vaginal ecosystem of fertile women. In postmenopausal women with low oestrogen levels, Lactobacillus flora is diminishing or absent. However, no studies have been performed to investigate the correlation between oestrogen levels and the lactobacilli in the gut. The aim of the present study was to investigate the relation in healthy women between vaginal and rectal microbial flora as well as possible variations with hormone levels.MethodsVaginal and rectal smears were taken from 20 healthy fertile women, average 40 years (range 28-49 years), in two different phases of the menstrual cycle, and from 20 postmenopausal women, average 60 years (range 52-85 years). Serum sex hormone levels were analyzed. Bacteria from the smears isolated on Rogosa Agar were grouped by Randomly Amplified Polymorphic DNA and identified by multiplex PCR and partial 16S rRNA gene sequencing.ResultsLactobacillus crispatus was more often found in the vaginal flora of fertile women than in that of postmenopausal (p = 0.036). Fifteen of 20 fertile women had lactobacilli in their rectal smears compared to 10 postmenopausal women (p = 0.071). There was no correlation between the number of bacteria in vagina and rectum, or between the number of bacteria and hormonal levels. Neither could any association between the presence of rectal lactobacilli and hormonal levels be found.ConclusionLactobacillus crispatus was more prevalent in the vaginal flora of fertile women, whereas the Lactobacillus flora of rectum did not correlate to the vaginal flora nor to hormonal levels.

Problem based learning and the case method--medical students change preferences during clerkship.

Background: The Case Method (Case) and Problem Based Learning (PBL) are two student active methods, increasingly used in medical education. Aim: The aim of this study was to compare medical student satisfaction with the two different active methods of learning and to see if there was any variation in preference between two stages in medical training. Methods: A short questionnaire was given out to 254 students during the eighth and eleventh term of medical training. Answers were obtained from 221 students. The results were computer analysed. Results: Students in the eighth term rated both methods high, while students in the eleventh term rated Case even higher while PBL decreased in popularity. Traditional lectures were given constant neutral rating. Case was rated better for problem solving. Conclusions: It seems that Case is more suitable than PBL for the later stages of medical training when clinical problem-solving skills need to be honed.

Neuronal localization and motor effects of gastrin-releasing peptide (GRP) in rat uterus

All parts of the internal female reproductive tract of the rat contained nerve fibers with immunocytochemically visible gastrin-releasing peptide (GRP)-like material. GRP-like immunoreactivity was also seen in nerve cell bodies of the paracervical ganglion formation, which in addition, harboured GRP nerve fibers. Pharmacological experiments were performed on isolated uterine and cervical smooth muscle tissue from two groups of spayed animals, one of which received estradiol. Both GRP and its non-mammalian counterpart, bombesin, evoked concentration-dependent clonic contractions in uterus and cervix, most pronounced in the estrogen-treated animals. Bombesin induced a stronger contractile force than GRP. The responses were not affected by tetrodotoxin. The observations suggest that GRP may be one of several neural messengers involved in the control of uterine motor activity.

Histochemical demonstration of a concomitant reduction in neural vasoactive intestinal polypeptide, acetylcholinesterase, and noradrenaline of cat uterus during pregnancy

Noradrenaline, acetylcholinesterase, and vasoactive intestinal polypeptide (VIP) were visualized in uterine nerves of cats by histochemical techniques. Alterations were followed in different regions of the organs at various stages of pregnancy and compared with the situation in non-pregnant controls. Positively stained nerve fibres, the adrenergic type being particularly well developed, were found along the muscle bundles and around blood vessels in the smooth muscle layers, as well as in the mucosa, of both uterine horns and cervix. The nerve supply was especially prominent in the upper part of the cervix. The distribution of VIP-immunoreactive and acetylcholinesterase-positive nerve fibres resembled each other, but they were less numerous than the adrenergic fibres. In the course of pregnancy there was a marked reduction in the number of all positively reacting nerves, so that almost no fibres were visible in the uterine horns near term. A small number of positive nerve fibres was found to remain, however, in the wall of the sterile (empty) horn during unilateral pregnancy. The reduction was less prominent in the cervix, particularly its lower part. Distinct changes were encountered already during early and mid pregnancy in those parts of the uterine wall distended by the growing conceptus, where almost no fibres were seen. The nerve supply was more intact in the non-distended portions located between the fetuses, and especially in the empty horn of unilateral pregnancy. No overt reduction in the number of positively stained nerve fibres was found in the cervix at these pregnancy stages. The results show that marked alterations take place in the uterine autonomic innervation during such an entirely physiological event as pregnancy. There is reason to assume that the histochemical observations reflect both structural and functional alterations in the innervation related both to the type of nerves involved and to the localization of the conceptus.