Jan Roar Mellembakken - Academia.edu (original) (raw)

Papers by Jan Roar Mellembakken

Diabetes/Metabolism Research and Reviews, 2008

Recent studies on the pathogenesis of diabetic complications have demonstrated the important role... more Recent studies on the pathogenesis of diabetic complications have demonstrated the important role of a number of aberrantly expressed molecules acting together in the development of early diabetic microvascular complications. Soluble CD40 ligand (sCD40L) is supposed to be one of the most likely candidates for both retinopathy and nephropathy. In January 1989, sCD40L was measured in 340 normoalbuminuric diabetic adolescents and young adults. Participants were examined at baseline and biannually thereafter. sCD40L was measured every 2 years during a 16-year follow-up period. sCD40L was also measured in parents. Over 16 years, 32 out of 340 patients developed persistent microalbuminuria; no patient developed overt diabetic nephropathy. The risk of developing microalbuminuria was higher in children with increased sCD40L at the beginning of the study (using 6 ng/mL as the arbitrary cut-off value) (group A) compared with those with normal sCD40L (group B). Sex did not influence predictive value, sensitivity, or specificity. sCD40L was not significantly correlated with duration of diabetes. The percentage of offspring with both parents having sCD40L above the mean values was significantly higher in group A than in group B. The odds ratio (OR) for the occurrence of microalbuminuria after adjustment for confounding variables in patients with elevated baseline sCD40L was 4.2 (95% CI, 2.1-10.7). Persistently increased sCD40L levels from the onset of diabetes might help to identify those normotensive and normoalbuminuric young patients at increased risk of developing incipient nephropathy later in life.

Acta Obstetricia et Gynecologica Scandinavica, 2018

Pathology - Research and Practice, 2010

In this study, we distinguish two clinical and pathological entities that are similarly named: lu... more In this study, we distinguish two clinical and pathological entities that are similarly named: luteinized thecoma and luteinized thecoma associated with sclerosing peritonitis. Ovarian luteinized thecoma lacks definitive criteria for malignancy. Based on our case study of a mitotically active neoplasm without nuclear atypia in which the patient was living and well 19 years after operation and comparison with prior studies of luteinized thecoma and the closely related entity of cellular fibroma, we propose presumptive criteria for malignancy for this rare neoplasm. Increased mitotic activity in luteinized thecoma without significant nuclear atypia is not an indication of malignant behavior, and such cases should therefore be referred to as mitotically active cellular luteinized thecoma. We also contrast neoplasms in the luteinized thecoma category with the entity originally reported as luteinized thecoma associated with sclerosing peritonitis. In the latter, the ovarian stromal proliferations are typically bilateral, can have an exceedingly high mitotic rate as was seen in our illustrative case, often incorporate non-neoplastic ovarian structures at their periphery, and are responsive to medical therapy. In our patient with sclerosing peritonitis, both the ovarian masses and peritoneal sclerosis underwent complete regression following treatment with gonadotropin-releasing hormone agonist and high doses of steroids, and an ovarian biopsy taken 2 months after therapy showed a histologically normal ovary. The patient subsequently became pregnant and delivered a normal infant. This is, to our knowledge, the first case of successful medically conservative treatment of a young patient with this entity that led to complete relief of symptoms and allowed preservation of fertility. Because recent observations support the non-neoplastic nature of the ovarian stromal proliferations, we advocate use of the previously proposed term luteinized thecomatosis associated with sclerosing peritonitis for this entity.

The Journal of Heart and Lung Transplantation, 2004

342 days (range: 10 to 1270 days). SEMS removal was necessitated in 3 cases due to in-stent steno... more 342 days (range: 10 to 1270 days). SEMS removal was necessitated in 3 cases due to in-stent stenosis from excessive granulation tissue. The mean time to in-stent stenosis was 188 days. Stent migration into the mediastinum occurred in 1 patient, requiring replacement with a wider, longer stent. Two patients required repeat insertion of SEMS after removal, due to severe bronchomalacia. The mean time between stent replacements was 38 days. Conclusion: In patients with high-grade BD SEMS offers prospects for successful outcome. SEMS are known to be associated with significant granulation tissue formation. In our opinion this property of SEMS provides a platform for healing of dehiscence and in time, peribronchial soft-tissue support grows in to cover the defect allowing stent removal.

Hypertension, 2001

Preeclampsia is a potentially life-threatening disease for both mother and fetus. Endothelial dys... more Preeclampsia is a potentially life-threatening disease for both mother and fetus. Endothelial dysfunction is pivotal in the pathogenesis of this disorder, possibly reflecting a state of persistent inflammation. In the present study, we examined whether signs of inflammation with production of chemokines and leukocyte activation were present in the fetal circulation during preeclampsia. Venous cord blood was sampled during cesarean sections from 36 neonates born after uncomplicated pregnancies and from 35 born after severe preeclamptic pregnancies with premature newborns. The expression of adhesion molecules on neutrophils and monocytes was analyzed by flow cytometry, and plasma levels of chemokines and soluble adhesion molecules were analyzed by enzyme immunoassay. Newborns of preeclamptic mothers had increased expression of CD15s ( P =0.003), CD49d/CD29 ( P =0.01/0.005), and CD31 ( P =0.007) on neutrophils and CD15s ( P <0.001), CD11c ( P =0.009), and CD54 ( P =0.001) on monocyt...

Human Reproduction, 2011

background: Subfertility due to chronic anovulation is common in women with polycystic ovary synd... more background: Subfertility due to chronic anovulation is common in women with polycystic ovary syndrome (PCOS) and is often treated with IVF. Women with PCOS have an increased ovarian follicle and oocyte count, increased ovarian reserve and/or a slower rate of follicle atresia. If so, one would expect women with PCOS to display a delayed reduction in fertility with advancing age as compared with eumenorrheic women. methods: To test this hypothesis, we compared oocyte count and live birth rates among two groups undergoing IVF, 500 women with PCOS and 500 eumenorrheic women with infertility due to tubal factor only. results: Across the age range of 22-41 years, oocyte count and live birth rates remained stable in women with PCOS. In the eumenorrheic comparison group, these parameters decreased significantly with age. conclusions: Women with PCOS display sustained fertility with advancing age as compared with infertile eumenorrheic women.

Fertility and Sterility, 2012

Objective: To assess success rates of IVF and intracytoplasmic sperm injection in women with vari... more Objective: To assess success rates of IVF and intracytoplasmic sperm injection in women with various stages of endometriosis. Design: Retrospective cohort study. Setting: Reproductive medicine unit in a university hospital. Patient(s): Infertile women (n ¼ 2,245) with various stages of endometriosis or tubal factor infertility. Intervention(s): IVF or intracytoplasmic sperm injection. Main Outcome Measure(s): Dose of FSH, number of oocytes retrieved, fertilization rate, implantation rate, pregnancy rate (PR), live birth/ongoing PR. Result(s): Women with endometriosis had similar pregnancy and live birth/ongoing PR as did women with tubal factor infertility, but the American Society for Reproductive Medicine (ASRM) stage I and II endometriosis patients had a lower fertilization rate, and stage III and IV patients required more FSH and had fewer oocytes retrieved. Splitting the stage III and IV groups into patients with and without endometriomas showed that the endometrioma group required more FSH and had a significantly lower pregnancy and live birth/ongoing PR. Conclusion(s): With the exception of patients with endometrioma, infertile women with various stages of endometriosis have the same success rates with IVF and intracytoplasmic sperm injection as patients with tubal factor. This contrasts with the systematic review on which the European Society of Human Reproduction and Embryology bases its recommendations. (Fertil Steril Ò 2012;97:912-8. Ó2012 by American Society for Reproductive Medicine.

Endocrine connections, 2015

We aimed to examine whether a whole-grain crispbread (CB) low-fructose, low-calorie diet (LCD) mi... more We aimed to examine whether a whole-grain crispbread (CB) low-fructose, low-calorie diet (LCD) might be superior to a traditional LCD based on fructose-rich liquid meal replacements (LMRs) with respect to improvement of various cardiometabolic risk factors and reproductive hormones. Parallel-group randomised controlled clinical trial. Morbidly obese women with polycystic ovarian syndrome (PCOS) were randomised to either an 8-week CB-LCD or LMR-LCD (900-1100 kcal/day, fructose 17 g/day or 85 g/day). A total of 51 women completed the study. Body weight, fat mass and waist circumference reduced by mean (s.d.) 10.0 (4.8) kg, 7.4 (4.2) kg and 8.5 (4.4) cm, with no significant differences between groups. Total-cholesterol, HDL-cholesterol and Apo-A1 were significantly reduced within both groups (all P values <0.01), with no significant between-group differences. The triacylglycerol and LDL-cholesterol levels were reduced within the LMR group only, with no significant between-group diff...

Purpose: Our objective was to study the prevalence of metabolic syndrome in PCOS Norwegian women ... more Purpose: Our objective was to study the prevalence of metabolic syndrome in PCOS Norwegian women and South Asian immigrant women living in Norway. Methods: Our study included a total of 256 women with PCOS, 205 Caucasians (Norwegian women) and 51 Indian subcontinent women (IPW). These women were retrospectively identified in our clinical database with detailed records on hormone analysis in this cohort study. Results: 27.8% of Caucasians and 54.9% of IPW had MS, p=0.000. There was no difference in age, BMI, or waist-hip-ratio between the two groups. The IPW had significantly higher insulin levels during a 2 hour oral glucose tolerance test. Conclusion: MS and insulin resistance occurred significantly more often in IPW than in Caucasians. The higher occurrence cannot be explained by BMI or waist hip ratio as we did not find any significant differences in these parameters between the two groups. The difference in prevalence between the two groups may be explained by Yajniks “thin fat ...

Advanced Biomedical Bulletin, Apr 17, 2015

Objective To assess the possibility to diagnose placental insufficiency and metabolic acidosis by... more Objective To assess the possibility to diagnose placental insufficiency and metabolic acidosis by analysing the fetal heart rate (FHR) variability by using non-linear methods; symbolic dynamics or traditional linear stochastic theory. Study design The recorded FHR signal sets from the last hour of delivery in 21 live born fetuses were analysed. The complexity of the FHR variability was described by an entropy parameter using symbolic dynamics as well as by standard deviation of each FHR. Cases with placental insufficiency and metabolic acidosis were identified from cord artery blood gas analyses. Results No significant correlation was found between the entropy parameter and the arterial pH or between the standard deviation and the arterial pH. Results are improving when combining the two (entropy parameter and standard deviation) in a multiple regression analysis. Only one of the analysed cases was identified with metabolic acidosis (cord artery pH 12,0 mmol/L). Conclusion To know if it is possible to diagnose placental insufficiency and metabolic acidosis by analysing the FHR variability by using non-linear methods, symbolic dynamics or traditional linear stochastic theory, a study with FHR not influenced by uterine contractions during labour is needed to conclude if the lack of correlation is caused by uterine contractions or insufficient mathematical methodology.

Journal of Perinatology, 2011

Objective: The objective of this study is to determine the prevalence of placenta previa among di... more Objective: The objective of this study is to determine the prevalence of placenta previa among different racial and ethnic groups. Study Design: We conducted a retrospective cohort study to examine the prevalence of placenta previa among five major racial and ethnic groups: African American, Asian, Caucasian, Hispanic and Native American. We included all deliveries X20 weeks gestation from a large northern Californian Health Maintenance Organization from 1995-2006. A multivariable logistic regression model was used to control for potential confounders. Result: Of the 394 083 deliveries in our cohort, 1580 (0.40%) were complicated by placenta previa. The prevalence of placenta previa was: Asian 0.64%, Native American 0.60%, African American 0.44%, Caucasian 0.36%, Hispanic 0.34% and unknown 0.31% (P<0.001). In our multivariable logistic regression model, only Asians (odds ratio (OR) 1.73, 95% confidence intervals (CI) 1.53-1.95) and African Americans (OR 1.43, 95% CI 1.19-1.72) were at increased risk for having placenta previa, compared with Caucasians. Conclusion: Asian women have the highest prevalence of placenta previa.

Hypertension, 2002

Endothelial dysfunction and inflammation appear to play a major role in the pathogenesis of preec... more Endothelial dysfunction and inflammation appear to play a major role in the pathogenesis of preeclampsia. We hypothesize that a chronic inflammation in the decidua and placenta during preeclampsia may lead to a local leukocyte activation in this compartment. Venous blood was sampled simultaneously from antecubital and uterine veins during cesarean sections in 30 women with preeclampsia, 29 with uncomplicated pregnancies, and from 17 nonpregnant women. The expression of adhesion molecules and complement-related markers on neutrophils and monocytes was analyzed by flow cytometry. In patients with preeclampsia, neutrophil expression of the integrins CD11a, CD11b, and CD11c and of the complement related markers CD35 and CD59 was significantly higher in samples from uterine than from antecubital veins . No differences were found in nonpregnant women. On monocytes the expression of the Sialyl Lewis x antigen, the integrins CD11a, CD11c, and CD49d, and the complement-related markers CD46 a...

European Journal of Obstetrics & Gynecology and Reproductive Biology, 1993

There are a variety of effective treatment options to induce ovulation in women with polycystic o... more There are a variety of effective treatment options to induce ovulation in women with polycystic ovary syndrome (PCOS). The most effective treatments are primarily reproductive and target the hypothalamic-piuitary-ovarian (HPO) axis. Letrozole, an aromatase inhibitor, is headed towards replacing clomiphene, a selective estrogen receptor modulator, as the first choice option. Metabolic treatments likely work indirectly through the HPO axis. Many metabolic treatments have shown initial promise and later failed (troglitozone or d-chiro-inositol) or disappointed (metformin), further study is needed of newer agents to treat type 2 diabetes. Weight loss interventions, both lifestyle related, through obesity drugs, or through bariatric surgery have shown mixed results on pregnancy outcomes. With both reproductive and metabolic treatments, combination therapies (such as metformin and clomiphene together) may offer greater benefit to distinct subgroups of patients.

European Journal of Immunology, 2002

The contribution of peritoneal B cells to the intestinal lamina propria plasma cell population is... more The contribution of peritoneal B cells to the intestinal lamina propria plasma cell population is well documented in mice, but unknown in humans. We have analyzed immunoglobulin (Ig) genes of human peritoneal B cells, because such genes show distinctive characteristics in mucosal B cells, particularly highly mutated variable regions. Here, we report the characteristics of variable region genes used by IgM, IgA and IgG in peritoneal cells. We focused on the properties of IgV H 4-34 to allow comparisons of like-with-like between different isotypes and cells from different immune compartments. We observed that the IgM genes were mostly unmutated, and that the mutated subset had less mutations than would be expected in a mucosal B cell population. Likewise, the IgV H 4-34 genes used by IgA and IgG from peritoneal B cells had significantly lower numbers of mutations than observed in the mucosal counterparts. Other trends observed, while not reaching statistical significance, followed the trend of peripheral B cells. The peritoneal B cell population had more IgA1 than IgA2 sequences, and there was no dominance of J H 4 in the IgA from peritoneum or spleen, in contrast to the mucosal sequences. Overall, this study suggested that human peritoneal B cell are either peripheral or mixed in origin; they are unlikely to represent an inductive compartment for the mucosal B cell system.

Early Human Development, 1997

In most preparations of human cord arteries perfused in vitro, infusion of 10e7 M of serotonin le... more In most preparations of human cord arteries perfused in vitro, infusion of 10e7 M of serotonin leads to a biphasic pressure response starting with a transient minor vasodilatation followed by a dominant vasoconstriction. In some preparations, however, the vasoconstrictive part of the response with this dose of serotonin is less pronounced or completely absent, whereas the dilatation is stronger and more prominent. The present study deals exclusively with experiments on cord arteries displaying the latter type of serotonin reactivity, and was undertaken in order to characterize the relaxing effect of serotonin, and in particular, the role of the endotltelial layer. This was accomplished by studying the response pattern before and after treatment with different drugs or removal of the endothelium. The vasodilatatory action of serotonin was found to be abolished following treatment with methysergide, signiftcantly reduced after denudation (P <O.OS), slightly reduced after exposure to methylene blue or Nw-nitro-L-arginine methyl ester (L-NAME) (non-significantly), but not affected by indomethacin. The results suggest that the relaxing effect is mediated by specific serotonin receptors and that endothelium-derived substances, possibly including nitric oxide, are involved.

Endocrine Connections, 2021

Objective Obesity is considered to be the strongest predictive factor for cardio-metabolic risk i... more Objective Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) in normal weight women with PCOS and controls matched for age and BMI. Methods From a Nordic cross-sectional base of 2615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI < 25 kg/m2 (512 women with PCOS according to Rotterdam criteria and 281 age and BMI-matched controls). Participants underwent measurement of BP and body composition (BMI, waist-hip ratio), lipid status, and fasting BG. Data were presented as median (quartiles). Results The median age for women with PCOS were 28 (25, 32) years and median BMI was 22.2 (20.7, 23.4) kg/m2. Systolic BP was 118 (109, 128) mmHg in women with PCOS compared to 110 (105, 120) mmHg in controls and diastolic BP was 74 (67, 81) vs 70 (64, 75) mmHg, both P < 0.001. The prevalence of women with BP ≥ 1...

PLOS ONE, 2019

Objective To date, little is known about differences in the knowledge, diagnosis making and treat... more Objective To date, little is known about differences in the knowledge, diagnosis making and treatment strategies of health care providers regarding polycystic ovary syndrome (PCOS) across different disciplines in countries with similar health care systems. To inform guideline translation, we aimed to study physician reported awareness, diagnosis and management of PCOS and to explore differences between medical disciplines in the Nordic countries and Estonia. Methods This cross-sectional survey was conducted among 382 endocrinologists and obstetriciangynaecologists in the Nordic countries and Estonia in 2015-2016. Of the participating physicians, 43% resided in Finland,

Human Reproduction, 2017

Is oral glucose tolerance test (OGTT) needed in all women with polycystic ovary syndrome (PCOS)? ... more Is oral glucose tolerance test (OGTT) needed in all women with polycystic ovary syndrome (PCOS)? SUMMARY QNSWER: OGTT is not routinely needed in women with PCOS and BMI < 25 kg/m 2. WHAT IS KNOWN ALREADY: PCOS is associated with insulin resistance and increased prevalence of prediabetes and Type 2 diabetes (T2D) which is closely linked to obesity and possibly age, ethnicity and PCOS phenotype. Several guidelines recommend OGTT upon diagnosis of PCOS and during follow-up. STUDY DESIGN, SIZE, DURATION: A Nordic cross-sectional study including 876 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 876 Nordic women with PCOS, aged 14-57 years, were examined for T2D and prediabetes (impaired glucose tolerance [IGT] or impaired fasting glucose (IFG) by OGTT. MAIN RESULT AND THE ROLE OF CHANCE: Of all study subjects 3% (23/876) had T2D, 23% (204/876) prediabetes and 74% (649/876) had normal glucose tolerance (NGT). Increased BMI and waist circumference were significantly (P < 0.001) associated with prevalence of prediabetes and T2D. No normal-weight woman (BMI < 25 kg/m 2) was diagnosed with T 2 D. The prevalence of BMI ≥ 25 kg/m 2 was 66% (578/ 876). 91% of women (21/23) with T2D had BMI ≥ 30 kg/m 2. Testosterone levels and PCOS phenotype did not predict 2-h glucose levels during OGTT after adjustment for BMI and age. LIMITATIONS, REASONS FOR CAUTION: The present study included cross-sectional data and prospective studies are needed to confirm our results. These results may not apply to populations of other ethnic origin.

Fertility and Sterility, 2017

Context: Women with polycystic ovary syndrome (PCOS) exhibit various metabolic risks such as obes... more Context: Women with polycystic ovary syndrome (PCOS) exhibit various metabolic risks such as obesity, impaired glucose tolerance, insulin resistance, dyslipidemia and chronic inflammation, but studies regarding agerelated metabolic risk profiles of the syndrome are scarce. Objective: To compare the metabolic profiles of normo-and hyperandrogenic women with PCOS with those of control women throughout their reproductive life spans. Design: Case-control study. Setting: Eight study sites in Nordic countries. Patients: In all, 1526 women with PCOS (normoandrogenic, N=686 and hyperandrogenic, N=842) and 447 controls were divided into three age groups (< 30, 30-39 and > 39 years). Interventions: None. Main Outcome measures: Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Results: Both normo-and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, LDL, total cholesterol, blood pressure, and lower high-density lipoprotein levels (P < 0.001) independently of BMI when compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two-to fivefold higher in women with PCOS compared with controls, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusions: When evaluating metabolic risks in women with PCOS, androgenic status, and especially abdominal obesity and age should be taken into account, which would allow tailored management of the syndrome from early adulthood on.