Acta Obstetricia et Gynecologica Scandinavica, Apr 1, 2003
Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manag... more Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manage menopausal symptoms. It is clear that it has many other effects and here we review its impact on the risk of breast cancer. A clear risk is seen for current uses of combined oestrogen/progestagen pills, but this returns to normal shortly after treatment cessation. The role of oestrogen only replacement therapy is less clear, but most studies find a weaker, but still positive, association in current users. Recent sharp reductions in HRT use have been correlated with declines in breast cancer incidence in the USA, but not so clearly elsewhere.
Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isola... more Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isolated Synaptosomes from Rat Cerebral Cortex. Heterogeneity of Binding and Desensitization of Receptors "Pod Staun-Olsen ...
European Journal of Clinical Investigation, Aug 1, 1983
The human vagina and uterus are heavily innervated by VIP-containing nerve fibres. In the present... more The human vagina and uterus are heavily innervated by VIP-containing nerve fibres. In the present study, we have measured vaginal blood flow, transmucosal oxygen tension and uterine smooth muscle activity during stepwise intravenous infusion of vasoactive intestinal polypeptide (VIP) (0, 100, 300, 900 pmol kg-' h-I) in non-pregnant women. Vaginal blood flow was measured by the heat clearance technique, transmucosal oxygen tension by an 02-electrode and uterine activity by a micro-tip pressure catheter in the uterine cavity. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral venous blood were monitored. VIP induced a concentration-dependent increase in vaginal blood flow. The transmucosal oxygen tension was not significantly changed by VIP. The maximum dose of VIP decreased systolic as well as diastolic blood pressure and increased pulse frequency. VIP inhibited uterine activity. These findings suggest that VIP participates as a neurotransmitter in the control of genital physiological responses.
The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal grow... more The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. We developed a semiautomated, time-resolved, immunofluorometric assay for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range of 78 -1248 g/L. Serum samples derived from women in the first trimester of a normal pregnancy (n ϭ 324) and from women who later developed preeclampsia during pregnancy (n ϭ 160) were obtained from the First Trimester Copenhagen Study. ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were converted to multiples of the median (MoM) after log-linear regression of concentration versus gestational age. Results: Serum ADAM12 levels in women who developed preeclampsia during pregnancy had a mean log MoM of -0.066, which was significantly lower than the mean log MoM of -0.001 for ADAM12 levels observed in serum samples from women with normal pregnancy (P ϭ .008). The mean log MoM was even lower in serum derived from preeclamptic women whose infant's weight at birth was less than 2,500 g (n ϭ 27, mean log MoM of -0.120, P ϭ .053). The maternal serum levels of ADAM12 are significantly lower during the first trimester in women who later develop preeclampsia during pregnancy when compared with levels in women with normal pregnancies. Because the secreted form of ADAM12 cleaves insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5, the IGF axis may play a role in preeclampsia. ADAM12 may be a useful early marker for preeclampsia.
: Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the... more : Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the brain cortex. VIP receptors were studied in subcellular fractions isolated from rat cerebral cortex. The receptor binding of 125I‐VIP was greatest in the synaptosomal fraction at membrane protein concentrations of 50–100 μg/ml, a temperature of 37°C, and a pH from 7.4 to 7.7. Under these conditions the concomitant proteolytic degradation of 125I‐VIP was approximately 10% after 60 min of incubation. The binding of 60 pmoI/L 125I‐VIP reached steady‐state after 60 min and was maintained up to 240 min. At steady‐state, the receptor‐bound 125I‐VIP was displaced by unlabelled VIP with half‐maximal inhibition (IC50) at a concentration of approximately 3 nmol/L. The binding of 125I‐VIP in the concentration range of 10 pmol/L to 6 nmol/L was superimposable on the VIP displacement curve. The Scatchard plot was curvilinear with upward concavity, which can be interpreted to represent two classes of receptors with KD of 2.5 and 125 nmol/L, one class of receptors with negative cooperative interactions, or heterogeneity of the 125I‐ VIP preparation. The total amount of receptors was 9.5 pmol/mg of membrane protein. Secretin displaced receptor‐bound 125I‐VIP with an IC50 of 0.3 μmol/L, whereas glucagon snowed no inhibition up to 1 μmol/L. The dissociation of receptor‐bound 125I‐VIP was biexponential with rate constants (k2) of 4.1 – 10−3 and 0.18 min−1 corresponding to half‐times of approximately 170 and 4 min, respectively. The size of the two components was dependent on the duration of the 125I‐VIP association period. Initially, both components increased; at steady‐state, the rapid component declined, whereas the slow component increased to approximately 70% after 120 min. The association rate constants (k1) were estimated from the initial velocities as 106 and 4. 106 L. mol−1. min−1, and a calculation of the KD as k2/k1 gave values of 4.1 and 45 nmol/L, respectively. In conclusion, the presence of receptors for VIP on synaptosomes from the cerebral cortex supports the role of VIP as a neurotransmitter in the brain. The receptor binding was heterogeneous, suggesting the presence of two classes of receptors. The binding kinetics showed a time‐dependent transition of VIP receptors from a low‐ to a high‐affinity state, which may be interpreted as desensitisation of synapses to the action of VIP.
The feline myometrium is heavily innervated by VIP-containing nerve fibres. Transmural electrical... more The feline myometrium is heavily innervated by VIP-containing nerve fibres. Transmural electrical stimulation (10 Hz, 2 msec, 150 mA) of muscle strips from feline myometrium in the presence of adrenoreceptor blocking agents caused a muscle relaxation. The smooth muscle relaxation was accompanied by a significant increase in immunoreactive VIP in the superfusate. Both the VIP release and the relaxation were completely annulled by tetrodotoxin, a selective blocker of axonal conduction. Furthermore, passive immunoneutralization with antiserum against VIP markedly reduced the smooth muscle relaxation induced by electrical stimulation. In the light of the previously demonstrated smooth muscle relaxant effect of VIP, the present findings indicate that the peptides may participate as neurotransmitter in non-adrenergic relaxation of the feline myometrium. Vasoactive intestinal polypeptide Neuropeptides Female genital tract Labour Uterus
Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are... more Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are performed by laparotomy, although the use of laparoscopically assisted techniques is increasing. Laparoscopic surgery seems to lead to a reduction in the need for postoperative hospitalization and convalescence, which is confirmed in the few available randomised and to our knowledge all retrospective studies. The length of stay seems to be reduced from four to two days if the patient is hysterectomised by the laparoscopically assisted or vaginal techniques. The introduction of endoscopic techniques has caused a change in routines and recommendations, but not for women operated by the classical open procedures. In this article we question the relevance of comparing different types of operations given the fact that the routines and recommendations are different.
Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and femal... more Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and female genitourinary tract, appearing to innervate vascular and nonvascular smooth and epithelial cells. In the present study the concentration of VIP in tissue extracts of different parts of the male genitourinary tract from cat and man was determined by radioimmunoassay. In addition, the effect of VIP on the contractility of the smooth muscle from the cat genitourinary tract was investigated in vitro. The tissue concentrations of VIP were generally higher in cat than in man. In both species high concentrations were found in the vas deferens, bladder, urethra and prostate, In concentration from 3 x 10(-8) to 6 x 10(-7) mol x 1-1, VIP inhibited in a concentration-dependent manner the muscle contractions in specimens from all regions examined, i.e., the vas deferens, ureter, corpus of the bladder, and urethra. The data indicate that VIP might play a physiologic role in the local nervous control of the smooth muscle activity in the male genitourinary tract.
Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in diseas... more Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in disease activity during pregnancy, and a predictable flare in the months after they give birth. The cause of these changes is unknown. We hypothesized that understanding biological changes (through gene expression) that occur from pre-pregnancy through the pregnancy and post-partum periods will contribute important evidence to our knowledge of the drivers of disease activity in RA during and after pregnancy. Methods: We have established a prospective RA pregnancy cohort, with clinical data and blood samples collected at pre-pregnancy (T0), each trimester of pregnancy and every 3 months up to a year post-partum (up to 8 time points). Disease activity at each time point was assessed using disease activity scores (DAS28CRP4); women who showed an improvement during pregnancy were selected for analysis (n=9). Global gene expression profiles for each sample were generated using RNA-sequencing (RNA-seq). Raw reads were pseudo-aligned and quantified using kallisto. Random effects regression models were used to estimate the effects of changes in gene expression on disease activity (a) from T0 through the pregnancy period (P1), and (b) in the post-partum period (P2). The models were adjusted for age, medication status at baseline and batch effects. Significance was assessed using a threshold of q<0.05 (FDR-adjusted). Functional enrichment analysis was performed using WebGestalt. Results: During pregnancy, 1,174 genes had expression patterns significantly associated with disease activity. While these were not significantly enriched in specific pathways, the genes whose increased expression was associated with the largest decrease (improvement) in disease activity during pregnancy were immune-related, and included ERAP1, CSNK2A1 and FAM175B. ERAP1 is involved in trimming peptides for presentation on MHC class I molecules; CSNK2A1 regulates cellular processes including cellular response to viral infection; FAM175B is involved in interferon-signaling. In the post-partum period, 4,693 genes had expression patterns significantly associated with disease activity. These were enriched (p<1x10^(-6)) in numerous immune-related pathways including MAPK signaling, T cell receptor signaling, osteoclast differentiation, hematopoietic cell lineage, B cell receptor signaling, Toll-like receptor signaling and leukocyte trans-endothelial migration, in addition to several pathways related to cancer. The genes whose increased expression were associated with larger increases in disease activity included EI24, CMTM7, PPP2CB and BFAR which are related to tumor suppression and/or regulation of apoptosis. Conclusion: In this pilot RA pregnancy cohort study with longitudinal RNA-seq data, several candidate genes were identified as significantly associated with improvement in disease activity during pregnancy, and others were associated with post-partum flares. These results warrant further investigations into possible roles of these genes in modulating RA disease activity in a larger cohort.
Acta Obstetricia et Gynecologica Scandinavica, Jul 1, 2003
Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manag... more Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manage menopausal symptoms. It is clear that it has many other effects and here we review its impact on the risk of breast cancer. A clear risk is seen for current uses of combined oestrogen/progestagen pills, but this returns to normal shortly after treatment cessation. The role of oestrogen only replacement therapy is less clear, but most studies find a weaker, but still positive, association in current users. Recent sharp reductions in HRT use have been correlated with declines in breast cancer incidence in the USA, but not so clearly elsewhere.
Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memoria... more Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memorial lecture. The role of obstetricians and gynecologists in primary healthcare for women. Frontline lectures: Fetal cells or genetic diagnosis. Genetics of gynecological cancer. Fetal therapy. Reproductive impact of sexually transmitted infections. Updates: Environment and reproductive health. Obstetric imaging. Screening for gynecological cancer. Minimally invasive surgery. Electronic fetal monitoring. Plenary sessions: Advances in prenatal diagnosis. Women's right and women's health. Changing concepts in antenatal care. Ovarian cancer. Optimizing the infertility evaluation. Advances in perinatal medicine. Evidence-based practice in gynecology. Induced abortion. Violence against women. Emergency contraception: the casualty department of family planning. Debates: Is there a normal Cesarean rate and can it be achieved? Hormone replacement therapy for all? Can cervical cancer screening b e cost-effective? There is no place for electronic fetal monitoring in the low-risk patient. Does continuing medical education improve professional performance? New technology: Human genome project. Three-dimensional ultrasound. Microfertilization procedures. Gynecological endoscopy. Electronic journalism. New developments: Cloning perspectives in veterinarian and human medicine. Telemedicine. Are some diseases in adult life caused by factors before birth? Index.
Introduction and hypothesis The aim of this study was to describe the incidence of pelvic organ p... more Introduction and hypothesis The aim of this study was to describe the incidence of pelvic organ prolapse (POP) surgery after hysterectomy from 1977 to 2009, the time interval from hysterectomy to POP surgery, and age characteristics of women undergoing POP surgery after hysterectomy and to estimate the risk of undergoing POP surgery after hysterectomy. Methods The study was a population-based registry study. Patient data from 154,882 women hysterectomized for benign conditions in the period from 1977 to 2009 were extracted from the Danish National Patient Registry. Patients were followed up from hysterectomy to POP surgery, death/emigration, or end of study period. An estimate of the hazard of undergoing POP surgery following hysterectomy was calculated. Survival analysis was performed using the Kaplan-Meier product limit method. Results The frequency of POP surgery on hysterectomized women was high the first 2 years of the follow-up period with almost 800 women operated yearly. More than one third (n= 2,872) of all women operated for POP were operated less than 5 years after the hysterectomy with a median of 8.6 years. The cumulated incidence of POP surgery after hysterectomy with follow-up of up to 32 years was 12 %; 50 % (n=5,451) of all POP surgeries were in the posterior compartment. The mean age of women undergoing a first POP surgery after hysterectomy was 60 years. Conclusions POP after hysterectomy occurs as a long-term complication of hysterectomy; 12 % of hysterectomized women were operated for POP. They were operated at younger age than non-hysterectomized women and half the POP operations were performed in the posterior compartment.
The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mec... more The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mechanical activity in non‐pregnant estradiol‐treated rabbits was investigated using in vivo and in vitro methods. The studies were performed on spontaneous, oxytocin‐, car‐bachol‐, and prostaglandin‐F2α‐induced activity. VIP had a dose‐related inhbitory effect on both myoelectrical and mechanical activity. The concentration needed for 50% inhibition (ID50) was 2xl0−10mol VIP 1−1(in vivo), and 6xl0−8mol VIP‐ l−1(in vitro). This inhibition was unaffected by the presence of atropine (10−5mol‐ I−1), propranolol (10−5), phentolamine (10−5), naloxone (10−5), apamin (10−4), and tetrodotoxin (10−5). These findings indicate that VIP may act via a specific receptor on the smooth muscle and supports the hypothesis that VIP may be a neurotransmitter involved in the local nervous control of uterine smooth muscle activity.
Acta Obstetricia et Gynecologica Scandinavica, Apr 1, 2003
Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manag... more Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manage menopausal symptoms. It is clear that it has many other effects and here we review its impact on the risk of breast cancer. A clear risk is seen for current uses of combined oestrogen/progestagen pills, but this returns to normal shortly after treatment cessation. The role of oestrogen only replacement therapy is less clear, but most studies find a weaker, but still positive, association in current users. Recent sharp reductions in HRT use have been correlated with declines in breast cancer incidence in the USA, but not so clearly elsewhere.
Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isola... more Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isolated Synaptosomes from Rat Cerebral Cortex. Heterogeneity of Binding and Desensitization of Receptors &quot;Pod Staun-Olsen ...
European Journal of Clinical Investigation, Aug 1, 1983
The human vagina and uterus are heavily innervated by VIP-containing nerve fibres. In the present... more The human vagina and uterus are heavily innervated by VIP-containing nerve fibres. In the present study, we have measured vaginal blood flow, transmucosal oxygen tension and uterine smooth muscle activity during stepwise intravenous infusion of vasoactive intestinal polypeptide (VIP) (0, 100, 300, 900 pmol kg-' h-I) in non-pregnant women. Vaginal blood flow was measured by the heat clearance technique, transmucosal oxygen tension by an 02-electrode and uterine activity by a micro-tip pressure catheter in the uterine cavity. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral venous blood were monitored. VIP induced a concentration-dependent increase in vaginal blood flow. The transmucosal oxygen tension was not significantly changed by VIP. The maximum dose of VIP decreased systolic as well as diastolic blood pressure and increased pulse frequency. VIP inhibited uterine activity. These findings suggest that VIP participates as a neurotransmitter in the control of genital physiological responses.
The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal grow... more The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. We developed a semiautomated, time-resolved, immunofluorometric assay for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range of 78 -1248 g/L. Serum samples derived from women in the first trimester of a normal pregnancy (n ϭ 324) and from women who later developed preeclampsia during pregnancy (n ϭ 160) were obtained from the First Trimester Copenhagen Study. ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were converted to multiples of the median (MoM) after log-linear regression of concentration versus gestational age. Results: Serum ADAM12 levels in women who developed preeclampsia during pregnancy had a mean log MoM of -0.066, which was significantly lower than the mean log MoM of -0.001 for ADAM12 levels observed in serum samples from women with normal pregnancy (P ϭ .008). The mean log MoM was even lower in serum derived from preeclamptic women whose infant's weight at birth was less than 2,500 g (n ϭ 27, mean log MoM of -0.120, P ϭ .053). The maternal serum levels of ADAM12 are significantly lower during the first trimester in women who later develop preeclampsia during pregnancy when compared with levels in women with normal pregnancies. Because the secreted form of ADAM12 cleaves insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5, the IGF axis may play a role in preeclampsia. ADAM12 may be a useful early marker for preeclampsia.
: Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the... more : Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the brain cortex. VIP receptors were studied in subcellular fractions isolated from rat cerebral cortex. The receptor binding of 125I‐VIP was greatest in the synaptosomal fraction at membrane protein concentrations of 50–100 μg/ml, a temperature of 37°C, and a pH from 7.4 to 7.7. Under these conditions the concomitant proteolytic degradation of 125I‐VIP was approximately 10% after 60 min of incubation. The binding of 60 pmoI/L 125I‐VIP reached steady‐state after 60 min and was maintained up to 240 min. At steady‐state, the receptor‐bound 125I‐VIP was displaced by unlabelled VIP with half‐maximal inhibition (IC50) at a concentration of approximately 3 nmol/L. The binding of 125I‐VIP in the concentration range of 10 pmol/L to 6 nmol/L was superimposable on the VIP displacement curve. The Scatchard plot was curvilinear with upward concavity, which can be interpreted to represent two classes of receptors with KD of 2.5 and 125 nmol/L, one class of receptors with negative cooperative interactions, or heterogeneity of the 125I‐ VIP preparation. The total amount of receptors was 9.5 pmol/mg of membrane protein. Secretin displaced receptor‐bound 125I‐VIP with an IC50 of 0.3 μmol/L, whereas glucagon snowed no inhibition up to 1 μmol/L. The dissociation of receptor‐bound 125I‐VIP was biexponential with rate constants (k2) of 4.1 – 10−3 and 0.18 min−1 corresponding to half‐times of approximately 170 and 4 min, respectively. The size of the two components was dependent on the duration of the 125I‐VIP association period. Initially, both components increased; at steady‐state, the rapid component declined, whereas the slow component increased to approximately 70% after 120 min. The association rate constants (k1) were estimated from the initial velocities as 106 and 4. 106 L. mol−1. min−1, and a calculation of the KD as k2/k1 gave values of 4.1 and 45 nmol/L, respectively. In conclusion, the presence of receptors for VIP on synaptosomes from the cerebral cortex supports the role of VIP as a neurotransmitter in the brain. The receptor binding was heterogeneous, suggesting the presence of two classes of receptors. The binding kinetics showed a time‐dependent transition of VIP receptors from a low‐ to a high‐affinity state, which may be interpreted as desensitisation of synapses to the action of VIP.
The feline myometrium is heavily innervated by VIP-containing nerve fibres. Transmural electrical... more The feline myometrium is heavily innervated by VIP-containing nerve fibres. Transmural electrical stimulation (10 Hz, 2 msec, 150 mA) of muscle strips from feline myometrium in the presence of adrenoreceptor blocking agents caused a muscle relaxation. The smooth muscle relaxation was accompanied by a significant increase in immunoreactive VIP in the superfusate. Both the VIP release and the relaxation were completely annulled by tetrodotoxin, a selective blocker of axonal conduction. Furthermore, passive immunoneutralization with antiserum against VIP markedly reduced the smooth muscle relaxation induced by electrical stimulation. In the light of the previously demonstrated smooth muscle relaxant effect of VIP, the present findings indicate that the peptides may participate as neurotransmitter in non-adrenergic relaxation of the feline myometrium. Vasoactive intestinal polypeptide Neuropeptides Female genital tract Labour Uterus
Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are... more Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are performed by laparotomy, although the use of laparoscopically assisted techniques is increasing. Laparoscopic surgery seems to lead to a reduction in the need for postoperative hospitalization and convalescence, which is confirmed in the few available randomised and to our knowledge all retrospective studies. The length of stay seems to be reduced from four to two days if the patient is hysterectomised by the laparoscopically assisted or vaginal techniques. The introduction of endoscopic techniques has caused a change in routines and recommendations, but not for women operated by the classical open procedures. In this article we question the relevance of comparing different types of operations given the fact that the routines and recommendations are different.
Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and femal... more Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and female genitourinary tract, appearing to innervate vascular and nonvascular smooth and epithelial cells. In the present study the concentration of VIP in tissue extracts of different parts of the male genitourinary tract from cat and man was determined by radioimmunoassay. In addition, the effect of VIP on the contractility of the smooth muscle from the cat genitourinary tract was investigated in vitro. The tissue concentrations of VIP were generally higher in cat than in man. In both species high concentrations were found in the vas deferens, bladder, urethra and prostate, In concentration from 3 x 10(-8) to 6 x 10(-7) mol x 1-1, VIP inhibited in a concentration-dependent manner the muscle contractions in specimens from all regions examined, i.e., the vas deferens, ureter, corpus of the bladder, and urethra. The data indicate that VIP might play a physiologic role in the local nervous control of the smooth muscle activity in the male genitourinary tract.
Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in diseas... more Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in disease activity during pregnancy, and a predictable flare in the months after they give birth. The cause of these changes is unknown. We hypothesized that understanding biological changes (through gene expression) that occur from pre-pregnancy through the pregnancy and post-partum periods will contribute important evidence to our knowledge of the drivers of disease activity in RA during and after pregnancy. Methods: We have established a prospective RA pregnancy cohort, with clinical data and blood samples collected at pre-pregnancy (T0), each trimester of pregnancy and every 3 months up to a year post-partum (up to 8 time points). Disease activity at each time point was assessed using disease activity scores (DAS28CRP4); women who showed an improvement during pregnancy were selected for analysis (n=9). Global gene expression profiles for each sample were generated using RNA-sequencing (RNA-seq). Raw reads were pseudo-aligned and quantified using kallisto. Random effects regression models were used to estimate the effects of changes in gene expression on disease activity (a) from T0 through the pregnancy period (P1), and (b) in the post-partum period (P2). The models were adjusted for age, medication status at baseline and batch effects. Significance was assessed using a threshold of q<0.05 (FDR-adjusted). Functional enrichment analysis was performed using WebGestalt. Results: During pregnancy, 1,174 genes had expression patterns significantly associated with disease activity. While these were not significantly enriched in specific pathways, the genes whose increased expression was associated with the largest decrease (improvement) in disease activity during pregnancy were immune-related, and included ERAP1, CSNK2A1 and FAM175B. ERAP1 is involved in trimming peptides for presentation on MHC class I molecules; CSNK2A1 regulates cellular processes including cellular response to viral infection; FAM175B is involved in interferon-signaling. In the post-partum period, 4,693 genes had expression patterns significantly associated with disease activity. These were enriched (p<1x10^(-6)) in numerous immune-related pathways including MAPK signaling, T cell receptor signaling, osteoclast differentiation, hematopoietic cell lineage, B cell receptor signaling, Toll-like receptor signaling and leukocyte trans-endothelial migration, in addition to several pathways related to cancer. The genes whose increased expression were associated with larger increases in disease activity included EI24, CMTM7, PPP2CB and BFAR which are related to tumor suppression and/or regulation of apoptosis. Conclusion: In this pilot RA pregnancy cohort study with longitudinal RNA-seq data, several candidate genes were identified as significantly associated with improvement in disease activity during pregnancy, and others were associated with post-partum flares. These results warrant further investigations into possible roles of these genes in modulating RA disease activity in a larger cohort.
Acta Obstetricia et Gynecologica Scandinavica, Jul 1, 2003
Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manag... more Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manage menopausal symptoms. It is clear that it has many other effects and here we review its impact on the risk of breast cancer. A clear risk is seen for current uses of combined oestrogen/progestagen pills, but this returns to normal shortly after treatment cessation. The role of oestrogen only replacement therapy is less clear, but most studies find a weaker, but still positive, association in current users. Recent sharp reductions in HRT use have been correlated with declines in breast cancer incidence in the USA, but not so clearly elsewhere.
Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memoria... more Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memorial lecture. The role of obstetricians and gynecologists in primary healthcare for women. Frontline lectures: Fetal cells or genetic diagnosis. Genetics of gynecological cancer. Fetal therapy. Reproductive impact of sexually transmitted infections. Updates: Environment and reproductive health. Obstetric imaging. Screening for gynecological cancer. Minimally invasive surgery. Electronic fetal monitoring. Plenary sessions: Advances in prenatal diagnosis. Women's right and women's health. Changing concepts in antenatal care. Ovarian cancer. Optimizing the infertility evaluation. Advances in perinatal medicine. Evidence-based practice in gynecology. Induced abortion. Violence against women. Emergency contraception: the casualty department of family planning. Debates: Is there a normal Cesarean rate and can it be achieved? Hormone replacement therapy for all? Can cervical cancer screening b e cost-effective? There is no place for electronic fetal monitoring in the low-risk patient. Does continuing medical education improve professional performance? New technology: Human genome project. Three-dimensional ultrasound. Microfertilization procedures. Gynecological endoscopy. Electronic journalism. New developments: Cloning perspectives in veterinarian and human medicine. Telemedicine. Are some diseases in adult life caused by factors before birth? Index.
Introduction and hypothesis The aim of this study was to describe the incidence of pelvic organ p... more Introduction and hypothesis The aim of this study was to describe the incidence of pelvic organ prolapse (POP) surgery after hysterectomy from 1977 to 2009, the time interval from hysterectomy to POP surgery, and age characteristics of women undergoing POP surgery after hysterectomy and to estimate the risk of undergoing POP surgery after hysterectomy. Methods The study was a population-based registry study. Patient data from 154,882 women hysterectomized for benign conditions in the period from 1977 to 2009 were extracted from the Danish National Patient Registry. Patients were followed up from hysterectomy to POP surgery, death/emigration, or end of study period. An estimate of the hazard of undergoing POP surgery following hysterectomy was calculated. Survival analysis was performed using the Kaplan-Meier product limit method. Results The frequency of POP surgery on hysterectomized women was high the first 2 years of the follow-up period with almost 800 women operated yearly. More than one third (n= 2,872) of all women operated for POP were operated less than 5 years after the hysterectomy with a median of 8.6 years. The cumulated incidence of POP surgery after hysterectomy with follow-up of up to 32 years was 12 %; 50 % (n=5,451) of all POP surgeries were in the posterior compartment. The mean age of women undergoing a first POP surgery after hysterectomy was 60 years. Conclusions POP after hysterectomy occurs as a long-term complication of hysterectomy; 12 % of hysterectomized women were operated for POP. They were operated at younger age than non-hysterectomized women and half the POP operations were performed in the posterior compartment.
The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mec... more The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mechanical activity in non‐pregnant estradiol‐treated rabbits was investigated using in vivo and in vitro methods. The studies were performed on spontaneous, oxytocin‐, car‐bachol‐, and prostaglandin‐F2α‐induced activity. VIP had a dose‐related inhbitory effect on both myoelectrical and mechanical activity. The concentration needed for 50% inhibition (ID50) was 2xl0−10mol VIP 1−1(in vivo), and 6xl0−8mol VIP‐ l−1(in vitro). This inhibition was unaffected by the presence of atropine (10−5mol‐ I−1), propranolol (10−5), phentolamine (10−5), naloxone (10−5), apamin (10−4), and tetrodotoxin (10−5). These findings indicate that VIP may act via a specific receptor on the smooth muscle and supports the hypothesis that VIP may be a neurotransmitter involved in the local nervous control of uterine smooth muscle activity.
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