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ObjectiveTo estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP).Materials and MethodsWe present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy.ResultsDuring the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500.ConclusionsUsing first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.

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The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and fibroids from women with and without preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, from post-menopausal women, from pregnant women and in myometrium from women without fibroid disease. Women with menstrual periods were classified according to the phase of the cycle. In tissues from non-treated premenopausal women, IGF-I mRNA expression was significantly higher in fibroids than in myometrium, with no differences related to phase of the menstrual cycle. In post-menopausal women and in GnRH agonist-treated women responding to treatment, similar mRNA expression was seen in myometrium and fibroids but the concentrations were lower than in untreated premenopausal women. The IGF-I mRNA value in fibroids from pregnant women was higher than in any other group and myometrium from pregnant women exhibited higher mRNA expression than myometrium from non-treated premenopausal women. The IGF-I protein was more abundant in fibroids than in myometrium of non-treated premenopausal and of pregnant women and in both tissues the concentration was significantly higher in the group of pregnant women. The IGF-I protein concentrations in fibroids and myometrium from GnRH agonist-treated and post-menopausal women were similar to those from premenopausal non-treated women. High sex steroid concentrations in pregnant and non-pregnant women of fertile age seem to be associated with a higher expression of IGF-I in fibroids than in myometrium, suggesting that IGF-I contributes to the selective growth advantage of these tumours.

Immunoblot experiments and reverse-phase h.p.l.c. were used to study the levels of glutathione transferase subunits 1, 2, 3, 4, 6, 7 and 8 in the liver and adrenal of intact and hypophysectomized male and female Sprague-Dawley rats. A sexual dimorphism in the levels of several of these isoenzymes and in their responses to hypophysectomy was demonstrated. In the liver of sham-operated females and males there are differences in glutathione transferase activities and isoenzyme pattern. H.p.l.c. analysis showed higher levels of subunits 1, 3 and 4 in male rats compared with females. In contrast with the pronounced sex differences in sham-operated rats, the isoenzyme patterns of hypophysectomized males and females were very similar. In the adrenal glands, however, a sexual dimorphism became apparent only after hypophysectomy, when the level of subunit 4 was increased 14-fold in the female, whereas the corresponding increase in the male rat was only 2.7-fold. The hepatic pattern of glutathione transferase subunits could be altered by continuous infusion of growth hormone to both sham-operated and hypophysectomized rats of both sexes. This treatment feminized the isoenzyme pattern in sham-operated males and a similar effect was obtained upon treating hypophysectomized rats with thyroxine, cortisone acetate and a continuous infusion of growth hormone.

Background and aims The present randomized open label parallel group study was conducted to evaluate if an oral oxycodone (OXY) regimen can be at least equally effective and as safe for postoperative analgesia after caesarean section (CS) as a standard of care program using nurse-administered intravenous morphine (IVM), followed by oral codeine. Methods Eighty women (40 + 40) were scheduled for elective CS under spinal anaesthesia. All patients received postoperative multimodal analgesic therapy, including ibuprofen and paracetamol. The OXY group got standardized extended release and short acting oral treatment (and in a few cases intravenous OXY) as needed and the other group received current standard of care, IVM as needed for 24 h, followed by codeine. Opioid treatment lasted maximum five days. Outcome measures were pain intensity (numerical rating scale, NRS), opioid requirements, duration of administering opioids and safety for mother and newborn. All opioids in the study were expressed in OXY equivalents, using a conversion table. As the bioavailability of each opioid has a certain extent of interindividual bioavailability this conversion represents an approximation. The possible influence of opioids on the newborns was evaluated by the Neurological Adaptive Capacity Score at birth and at 24 and 48 h. Results During the first 24 h, there were no differences between treatments in opioid requirements or mean pain intensity at rest but pain intensity when asking for rescue medication was lower in the OXY than in the IVM group (mean ± SD; 5.41 ± 6.42 vs. 6.42 ± 1.61; p = 0.027). Provoked pain (uterus palpation) during the first 6h was also less in the OXY group (3.26 ± 2.13 vs. 4.60 ± 2.10; p = 0.007). During the 25-48 h period postoperatively, patients on OXY reported significantly lower pain intensity at rest (2.9 ± 1.9 vs. 3.8 ± 1.8; p = 0.039) and consumed less opioids (OXY equivalents; mg) (31.5 ± 9.6 vs. 38.2 ± 38.2; p = 0.001) than those on IVM/codeine. The total amount of opioids 0-5 days postoperatively was significantly lower in the OXY than in the IVM/codeine group (108.7 ± 37.6 vs. 138.2 ± 45.1; p = 0.002). Duration of administering opioids was significantly shorter in the OXY group. Time to first spontaneous bowel movement was shorter in the OXY group compared with the IVM/codeine group. No serious adverse events were recorded in the mothers but the total number of common opioid adverse effects was higher among women on IVM/codeine than among those receiving OXY (15 vs. 3; p = 0.007). No adverse outcomes in the newborns related to treatment were observed in either group. Conclusions In a multimodal protocol for postoperative analgesia after CS better pain control and lower opioid intake was observed in patients receiving oral OXY as compared to those on IVM/codeine. No safety risks for mother and child were identified with either protocol. Implications Our findings support the view that use of oral OXY is a simple, effective and time saving treatment for postoperative pain after CS.

The expression patterns of the liver-enriched transcription factors CCAAT/enhancer-binding protein (C/EBP) alpha and beta and hepatocyte nuclear factor (HNF)-1 and HNF-4 were studied in liver nodules and hepatocellular carcinomas from male rats treated according to the resistant hepatocyte (RH) model. C/EBP alpha expression was lower at the transcriptional, mRNA, and protein levels in persistent nodules than in the respective surrounding livers. Expression was further decreased in the tumors. Transcriptional downregulation of C/EBP alpha gene expression was observed already in very early nodules, isolated 3 wk after partial hepatectomy in the RH model. However, no detectable changes were observed in preneoplastic nodules in the transcription or in steady-state mRNA levels of C/EBP beta, HNF-1, and HNF-4. A slight decrease in C/EBP beta protein and a more pronounced attenuation of HNF-1 and HNF-4 levels was observed in nodules, being 67%, 37%, and 46% of the levels in the corresponding surrounding livers, respectively. In conclusion, differential regulation of several transcription factors that are associated with the maintenance of the differentiated state of the hepatocytes was observed in preneoplastic and neoplastic liver lesions. This could have an impact on the regulation of a wide array of genes during liver carcinogenesis. Furthermore, the attenuation of C/EBP alpha expression, regarded as a negative growth regulator, could contribute to the proliferative advantage of nodules during liver carcinogenesis.

PostprintThis is the accepted version of a paper published in Acta Obstetricia et Gynecologica Scandinavica. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Citation for the original published paper (version of record):Niklasson, B., Georgsson Öhman, S., Segerdahl, M., Blanck, A. (2015) Risk factors for persistent pain and its influence on maternal wellbeing after cesarean section. Acta Obstetricia et Gynecologica Conflicts of InterestThe authors have no conflict of interest.Persistent pain and Cesarean section 3 AbstractObjectives. To investigate the overall incidence and risk factors for persistent pain and its interference with daily life after cesarean section (CS).Design. Prospective long-term follow up study. Setting. Karolinska University Hospital, Stockholm, Sweden. Population. 260 healthy women who underwent elective CS. Methods: Key message boxSevere postoperative pain, a first time CS and if the operation was performed for psychological reasons were risk factors for developing persistent pain. Parameters related to quality of life were significantly impaired in women with long-term pain.Persistent pain and Cesarean section 5