Preben Kjølhede

Factors associated with pelvic floor dysfunction with emphasis on urinary and fecal incontinence and genital prolapse: an epidemiological study

Objective.  To describe a general population of women with regard to factors associated with urinary and fecal incontinence and genital prolapse symptoms.

Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes.

Type 2 diabetes (T2D) is strongly linked to obesity and an adipose tissue unresponsive to insulin. The insulin resistance is due to defective insulin signaling, but details remain largely unknown. We examined insulin signaling in adipocytes from T2D patients, and contrary to findings in animal studies, we observed attenuation of insulin activation of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). As a consequence, mTORC1 downstream effects were also affected in T2D: feedback signaling by insulin to signal-mediator insulin receptor substrate-1 (IRS1) was attenuated, mitochondria were impaired and autophagy was strongly upregulated. There was concomitant autophagic destruction of mitochondria and lipofuscin particles, and a dependence on autophagy for ATP production. Conversely, mitochondrial dysfunction attenuated insulin activation of mTORC1, enhanced autophagy and attenuated feedback to IRS1. The overactive autophagy was associated with large numbers of cytosolic lipid droplets, a subset with colocalization of perlipin and the autophagy protein LC3/atg8, which can contribute to excessive fatty acid release. Patients with diagnoses of T2D and overweight were consecutively recruited from elective surgery, whereas controls did not have T2D. Results were validated in a cohort of patients without diabetes who exhibited a wide range of insulin sensitivities. Because mitochondrial dysfunction, inflammation, endoplasmic-reticulum stress and hypoxia all inactivate mTORC1, our results may suggest a unifying mechanism for the pathogenesis of insulin resistance in T2D, although the underlying causes might differ.0

Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes

Insulin resistance is a cardinal feature of type 2 diabetes and also a consequence of trauma such as surgery. Directly after surgery and cell isolation, adipocytes were insulin resistant, but this was reversed after overnight incubation in 10% CO2 at 37 °C. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)1 was insulin sensitive, but protein kinase B (PKB) and downstream metabolic effects exhibited insulin resistance that was reversed by overnight incubation. MAP‐kinases ERK1/2 and p38 were strongly phosphorylated after surgery, but was dephosphorylated during reversal of insulin resistance. Phosphorylation of MAP‐kinase was not caused by collagenase treatment during cell isolation and was present also in tissue pieces that were not subjected to cell isolation procedures. The insulin resistance directly after surgery and cell isolation was different from insulin resistance of type 2 diabetes; adipocytes from patients with type 2 diabetes remained insulin resistant after overnight incubation. IRS1, PKB, and downstream metabolic effects, but not insulin‐stimulated tyrosine phosphorylation of insulin receptor, exhibited insulin resistance. These findings suggest a new approach in the study of surgery‐induced insulin resistance and indicate that human adipocytes should recover after surgical procedures for analysis of insulin signalling. Moreover, we pinpoint the signalling dysregulation in type 2 diabetes to be the insulin‐stimulated phosphorylation of IRS1 in human adipocytes.

Prognostic factors and long-term results of the Burch colposuspension: A retrospective study

The purpose of this retrospective study was to evaluate the importance of different preoperative estimates and postoperative complications on the outcome of the Burch colposuspension with respect to urinary continence.

Long-term efficacy of Burch colposuspension: a 14-year follow-up study.

Background.  The aim of this study is to investigate the long‐term efficacy of the Burch colposuspension and to analyze the risk factors for an unsuccessful outcome at the long‐term follow‐up of more than 10 years.

Prediction of genital prolapse after Burch colposuspension

Objective. The aim of this prospective observational study was to investigate the gynecological and defecographic features in women with stress urinary incontinence operated with Burch colposuspension in order to analyze if the findings could predict subsequent development of genital prolapse.

Psychological wellbeing after laparoscopic and abdominal hysterectomy- : a randomised controlled multicentre study

Objective  To compare laparoscopic hysterectomy and abdominal total hysterectomy regarding influence on postoperative psychological wellbeing and surgical measures.

Obstetric anal sphincter rupture in older primiparous women: a case–control study

Objective. To determine if maternal age (35 years of age or older) in primiparous women is a risk factor for the development of obstetric anal sphincter rupture (OASR) and to identify obstetric factors associated with it. Material and methods. This is a retrospective case–control study. The study population was made up of the 5,345 primiparous women aged 24–45 years who delivered vaginally with singleton live‐born neonates during 1990–99 at the Department of Obstetrics and Gynecology, Linköping University Hospital, Sweden. As cases the 327 primiparous women aged 35–45 years at delivery were selected. For each case two primiparous controls ten years younger were selected, matched for gestational age and year of delivery, in all 654 controls. Maternal, obstetrical, and neonatal data were obtained from the delivery records. Obstetric factors for the development of OASR were assessed with multivariate logistic regression analysis. Results. No significant association was found between the primiparous age category and OASR. Vacuum extraction, forceps delivery, and the head circumference of the neonate were found to be independent risk factors for OASR, while the use of mediolateral episiotomy or epidural analgesia were independent protective factors for developing OASR. Conclusions. Primiparous women, 35 years of age or older, do not seem to have a greater risk of OASR than younger primiparous women. Risk factors for OASR are instrumental vaginal delivery and the size of the neonate. Mediolateral episiotomy and epidural analgesia seem to reduce the risk for OASR.

Short-term overeating induces insulin resistance in fat cells in lean human subjects.

Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity. Numerous prospective studies have reported on weight gain, insulin resistance, and insulin signaling in experimental animals, but not in humans. We examined insulin signaling in adipocytes from lean volunteers, before and at the end of a 4-wk period of consuming a fast-food, high-calorie diet that led to weight gain. We also examined adipocytes from patients with T2D. During the high-calorie diet, subjects gained 10% body weight and 19% total body fat, but stayed lean (body mass index = 24.3 kg/m2) and developed moderate systemic insulin resistance. Similarly to the situation in T2D subjects, in subjects on the high-calorie diet, the amount of insulin receptors was reduced and phosphorylation of IRS1 at tyrosine and at serine-307 (human sequence, corresponding to murine serine-302) were impaired. The amount of insulin receptor substrate protein-1 (IRS1) and the phosphorylation of IRS1 at serine-312 (human sequence, corresponding to murine serine-307) were unaffected by the diet. Unlike the T2D subjects, in subjects on the high-calorie diet, likely owing to the ongoing weight-gain, phosphorylation of MAP-kinases ERK1/2 became hyperresponsive to insulin. To our knowledge this study is the first to investigate insulin signaling during overeating in humans, and it demonstrates that T2D effects on intracellular insulin signaling already occur after 4 wks of a high-calorie diet and that the effects in humans differ from those in laboratory animals.

Impact of maternal age on obstetric and neonatal outcome with emphasis on primiparous adolescents and older women: a Swedish Medical Birth Register Study

Objectives To evaluate the associations between maternal age and obstetric and neonatal outcomes in primiparous women with emphasis on teenagers and older women. Design A population-based cohort study. Setting The Swedish Medical Birth Register. Participants Primiparous women with singleton births from 1992 through 2010 (N=798 674) were divided into seven age groups: <17 years, 17–19 years and an additional five 5-year classes. The reference group consisted of the women aged 25–29 years. Primary outcome Obstetric and neonatal outcome. Results The teenager groups had significantly more vaginal births (adjusted OR (aOR) 2.04 (1.79 to 2.32) and 1.95 (1.88 to 2.02) for age <17 years and 17–19 years, respectively); fewer caesarean sections (aOR 0.57 (0.48 to 0.67) and 0.55 (0.53 to 0.58)), and instrumental vaginal births (aOR 0.43 (0.36 to 0.52) and 0.50 (0.48 to 0.53)) compared with the reference group. The opposite was found among older women reaching a fourfold increased OR for caesarean section. The teenagers showed no increased risk of adverse neonatal outcome but presented an increased risk of prematurity <32 weeks (aOR 1.66 (1.10 to 2.51) and 1.20 (1.04 to 1.38)). Women with advancing age (≥30 years) revealed significantly increased risk of prematurity, perineal lacerations, preeclampsia, abruption, placenta previa, postpartum haemorrhage and unfavourable neonatal outcomes compared with the reference group. Conclusions For clinicians counselling young women it is of importance to highlight the obstetrically positive consequences that fewer maternal complications and favourable neonatal outcomes are expected. The results imply that there is a need for individualising antenatal surveillance programmes and obstetric care based on age grouping in order to attempt to improve the outcomes in the age groups with less favourable obstetric and neonatal outcomes. Such changes in surveillance programmes and obstetric interventions need to be evaluated in further studies.