Anders Norström

Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality

Diagnostic curettage has for many years been the method of choice to diagnose endometrial cancer in women with postmenopausal bleeding. The costs for curettage performed today are huge, and approximately only 10% in this group of women will be diagnosed with endometrial cancer. Thus less expansive techniques to obtain endometrial samples have been evaluated, but all of them are invasive. The value of endovaginal ultrasonography for identifying endometrial abnormality in this group of women has not been evaluated until now. This study used endometrial thickness as measured by endovaginal ultrasonography as an indicator of endometrial abnormality. It was demonstrated in 205 women with postmenopausal bleeding that if the endometrium was less than 9 mm thick, no endometrial cancer was found at curettage. The mean endometrial thickness in those women with endometrial cancer was 18.2 +/- 6.2 mm as compared with 3.4 +/- 1.2 mm in those women with atrophic endometrium. If the cutoff limit for endometrial abnormality was 5 mm, the positive predictive value for identifying endometrial abnormality was 87.3%. If this limit had been used in this study, 70% of the curettage procedures could have been avoided.

Molecular and Pharmacological Properties of Human Embryonic Stem Cell–Derived Cardiomyocytes

Human embryonic stem cells (hESCs) can be coaxed to differentiate Into specific cell types, including cardiomyocyte-like cells. These cells express cardiac-specific markers and display functional similarities to their adult counterparts. Based on these properties, hESC-derived cardiomyocytes have the potential to be extremely useful in various in vitro applications and to provide the opportunity for cardiac cell replacement therapies. However, before this can become a reality, the molecular and functional characteristics of these cells need to be Investigated in more detail. In the present study we differentiate hESCs into cardiomyocyte-like cells via embryoid bodies (EBs). The fraction of spontaneously beating clusters obtained from the EBs averaged approximately 30% of the total number of EBs used. These cell clusters were isolated, dissociated into single-cell suspensions, and frozen for long-term storage. The cryopreserved cells could be successfully thawed and subcultured. Using electron microscopy, we observed Z discs and tight Junctions in the hESC-derived cardiomyocytes, and by Immunohistochemical analysis we detected expression of cardiac-specific markers (cTnl and cMHC). Notably, using BrdU labeling we also could demonstrate that some of the hESC-derived cardiomyocytes retain a proliferative capacity. Furthermore, pharmacological stimulation of the cells resulted in responses Indicative of functional adrenergic and muscarinic receptor coupling systems. Taken together, these results lend support to the notion that hESCs can be used as a source for the procurement of cardiomyocytes for in vitro and in vivo applications.

Vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening at term: a randomized controlled study☆

OBJECTIVE Our aim was to examine the effect of the nitric oxide donor isosorbide mononitrate on the uterine cervix at term and to evaluate possible adverse effects of this treatment. STUDY DESIGN Term pregnant women were randomly selected to receive either 40 mg vaginally administered isosorbide mononitrate or placebo 4 hours before elective cesarean section. Cervical status, maternal blood pressure, maternal pulse rate, fetal heart rate, umbilical arterial Doppler indices, and various side effects were examined. RESULTS Isosorbide mononitrate induced a significant increase in cervical distensibility. It also caused a significant change in maternal blood pressure and maternal pulse rate. In addition, the frequency of maternal headache and palpitations was significantly higher in the isosorbide mononitrate group versus the placebo group. However, the intensity of these symptoms was moderate. CONCLUSION Vaginal administration of 40 mg of isosorbide mononitrate induces cervical ripening at term. Although the majority of women experienced side effects, no serious clinical maternal or fetal adverse effects, resulting in specific medication or emergency cesarean section, were diagnosed.

Carcinoma of the uterine cervix in pregnancy: A study of the incidence and treatment in the Western region of Sweden 1973 to 1992

Objective. To review the incidence, treatment and outcome of cervical cancer during pregnancy in the Western region of Sweden.

Distinct Expression Pattern of Dicer1 Correlates with Ovarian-Derived Steroid Hormone Receptor Expression in Human Fallopian Tubes during Ovulation and the Midsecretory Phase

CONTEXT Tissue-specific dicer1 knockout mice display severe, irreversible Fallopian tube damage and disrupted tubal transport. It is not known how Dicer1 affects human Fallopian tube function. OBJECTIVE The aim of the study was to investigate the regulation of tubal Dicer1 expression during ovulation and the midsecretory phase and to assess Dicer1-associated alterations in estrogen receptor (ER) subtype and progesterone receptor (PR) expression. DESIGN Fallopian tissue was obtained from patients at early (n = 4), late (n = 4), and postovulatory (n = 5) phases and the midsecretory phase (n = 4). Serum was obtained immediately before surgery (sterilization or hysterectomy) to confirm the phases. The localization and regulation of Dicer1, ER subtypes, and PR isoforms were determined by immunofluorescence, confocal microscopy, and quantitative RT-PCR. RESULTS Dicer1 protein was expressed most abundantly in Fallopian epithelial cells; mRNA and protein levels peaked in the late ovulatory phase. ER subtype and PR isoform mRNA levels were not related to ovulatory stages; however, ERβ1 and ERβ2 mRNA/protein levels were highest and PRA/B and PRB mRNA/protein levels were lowest in the midsecretory phase. Dicer1 mRNA expression correlated positively with ERα mRNA expression in the late ovulatory phase and negatively with ERβ2 mRNA expression in the midsecretory phase and PRB mRNA in the early ovulatory phase. CONCLUSION Dicer1 expression is up-regulated in cell-specific fashion in human Fallopian tubes during ovulation. The stage-dependent expression of Dicer1 and its correlation with ERα, ERβ2, and PRB mRNA suggests that tubal Dicer1 helps regulate tubal expression of steroid hormone receptors in a cycle-dependent manner and may contribute to tubal transport in humans.

Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights

Human ectopic pregnancy (EP) remains a common cause of pregnancy-related first trimester death. Nitric oxide (NO) is synthesized from L-arginine by three NO synthases (NOS) in different tissues, including the Fallopian tube. Studies of knockout mouse models have improved our understanding of the function of NOS isoforms in reproduction, but their roles and specific mechanisms in infection-induced tubal dysfunction have not been fully elucidated. Here, we provide an overview of the expression, regulation and possible function of NOS isoforms in the Fallopian tube, highlighting the effects of infection-induced changes in the tubal cellular microenvironment (imbalance of NO production) on tubal dysfunction and the potential involvement of NOS isoforms in tubal EP after Chlamydia trachomatis genital infection. The non-equivalent regulation of tubal NOS isoforms during the menstrual cycle suggests that endogenous ovarian steroid hormones regulate NOS in an isoform-specific manner. The current literature suggests that infection with C. trachomatis induces an inflammatory response that eventually leads to tubal epithelial destruction and functional impairment, caused by a high NO output mediated by inducible NOS (iNOS). Therefore, tissue-specific therapeutic approaches to suppress iNOS expression may help to prevent ectopic implantation in patients with prior C. trachomatis infection of the Fallopian tube.

Nitric oxide–mediated effects on myometrial contractility at term during prelabor and labor

OBJECTIVE To assess the existence of a nitric oxide (NO) system in the human myometrium and the effects of mediators of this system on contractile activity in vitro. METHODS Myometrial tissue was obtained before the onset of labor and during labor at term. Production of NO was assessed by the use of nicotinamide dinucleotide phosphate diaphorase staining and by immunoblots for NO. Effects of NO were examined by adding L-arginine (the substrate for NO synthesis); N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase); two NO donors, sodium nitroprusside and spermine NONOate; as well as 8-bromo cyclic guanosine monophosphate (8-bromo cGMP) (a second messenger analogue) to organ baths. RESULTS Myometrial NO production was indicated by positive nicotinamide adenine dinucleotide phosphate diaphorase staining. Immunoblots detected endothelial NO synthase, whereas only a weak signal for inducible NO synthase was seen. The addition of L-arginine (10(-4)-10(-3) mol/L) did not result in any change of contractility. N(G)-nitro-L-arginine methyl ester (10(-3) mol/L) caused a minor increase of contractility in half of the specimens. Sodium nitroprusside, spermine NONOate, and 8-bromo cGMP resulted in a concentration-dependent inhibition of contractility (10(-7)-10(-6) mol/L for sodium nitroprusside, 10(-6)-10(-5) mol/L for spermine NONOate, and 10(-5)-10(-3) mol/L for 8-bromo cGMP). However, at 10(-5)-10(-4) mol/L, sodium nitroprusside exhibited a dose-dependent increase in the frequency of contractions. Women in prelabor did not differ from those in active labor. CONCLUSION The myometrium produces NO at term. Nitric oxide inhibits myometrial contractile activity. The responsiveness to NO is similar in nonlaboring and laboring women.

Induction of Labor by Intra-Cervical Pge2 in Viscous Gel: Mechanism of Action and Clinical Treatment Routines

Induction of labor in women with immature cervix was accomplished by four different treatment schedules. the case material included a total of 100 subjects, each treatment group having 25 cases:

Reduced Incidence of Postoperative Endometritis by the use of Laminaria Tents in Connection with First Trimester Abortion

A Laminaria tent was inserted in the cervical canal of 115 primigravidae prior to vacuum aspiration in the first trimester. A mean dilatation of 9.7 mm was thereby achieved. Only 2 of these patients were treated by antibiotics due to ‘mild’ endometritis, as compared with 10 of 130 control patients due to endometritis and 7 patients due to ‘mild’ endometritis. Three non‐treated control patients had to undergo laparoscopy due to perforation of the uterus during dilatation of the cervical canal. It is concluded that pre‐treatment with the Laminaria tent prior to vacuum aspiration reduces the incidence of per‐ and post‐operative complications.

Coordinate regulation of heterogeneous nuclear ribonucleoprotein dynamics by steroid hormones in the human fallopian tube and endometrium in vivo and in vitro

Heterogeneous nuclear ribonucleoproteins (hnRNPs), which are chromatin-associated RNA-binding proteins, participate in mRNA stability, transport, intracellular localization, and translation by acting as transacting factors. Several studies have shown that steroid hormones can regulate hnRNP expression. However, to date, the regulation of hnRNPs and their interactions with steroid hormone signaling in fallopian tubes and endometrium are not fully elucidated. In the present study, we determined whether hnRNP expression is regulated during the menstrual cycle and correlates with estrogen receptor (ER) and progesterone receptor (PR) levels in human fallopian tubes in vivo. Because of the limited availability of human tubal tissues for the research, we also explored the mechanisms of hnRNP regulation in human endometrium in vitro. Fallopian tissue was obtained from patients in the early, late, and postovulatory phases and the midsecretory phase and endometrial tissue from premenopausal and postmenopausal women undergoing hysterectomy. We measured expression of hnRNPs and assessed their intracellular localization and interactions with ERs and PRs. We also determined the effects of human chorionic gonadotropin, 17β-estradiol (E(2)), and progesterone (P(4)) on hnRNP expression. In fallopian tubes, mRNA and protein levels of hnRNP A1, AB, D, G, H, and U changed dynamically during ovulation and in the midsecretory phase. In coimmunolocation and coimmunoprecipitation experiments, hnRNPs interacted with each other and with ERs and PRs in fallopian tubes. After treatment with E(2) and/or P(4) to activate ERs and PRs, hnRNP A1, AB, D, G, and U proteins displayed overlapping but distinct patterns of regulation in the endometrium in vitro. Our findings expand the physiological repertoire of hnRNPs in human fallopian tubes and endometrium and suggest that steroid hormones regulate different hnRNPs directly by interacting with ERs and/or PRs or indirectly by binding other hnRNPs. Both actions may contribute to regulation of gene transcription.