Pregnancies in women with Turner syndrome: a retrospective multicentre UK study.

OBJECTIVE: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome. DESIGN: Retrospective 20-year cohort study (2000-20). SETTING: Sixteen tertiary referral maternity units in the UK. POPULATION OR SAMPLE: A total of 81 women with Turner syndrome who became pregnant. METHODS: Retrospective chart analysis. MAIN OUTCOME MEASURES: Mode of conception, pregnancy outcomes. RESULTS: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving. CONCLUSIONS: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team. TWEETABLE ABSTRACT: Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection.

Variation in outcome reporting in randomized controlled trials of interventions for prevention and treatment of fetal growth restriction.

OBJECTIVE: Although fetal growth restriction (FGR) is well known to be associated with adverse outcomes for the mother and offspring, effective interventions for the management of FGR are yet to be established. Trials reporting interventions for the prevention and treatment of FGR may be limited by heterogeneity in the underlying pathophysiology. The aim of this study was to conduct a systematic review of outcomes reported in randomized controlled trials (RCTs) assessing interventions for the prevention or treatment of FGR, in order to identify and categorize the variation in outcome reporting. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched from inception until August 2018 for RCTs investigating therapies for the prevention and treatment of FGR. Studies were assessed systematically and data on outcomes that were reported in the included studies were extracted and categorized. The methodological quality of the included studies was assessed using the Jadad score. RESULTS: The search identified 2609 citations, of which 153 were selected for full-text review and 72 studies (68 trials) were included in the final analysis. There were 44 trials relating to the prevention of FGR and 24 trials investigating interventions for the treatment of FGR. The mean Jadad score of all studies was 3.07, and only nine of them received a score of 5. We identified 238 outcomes across the included studies. The most commonly reported were birth weight (88.2%), gestational age at birth (72.1%) and small-for-gestational age (67.6%). Few studies reported on any measure of neonatal morbidity (27.9%), while adverse effects of the interventions were reported in only 17.6% of trials. CONCLUSIONS: There is significant variation in outcome reporting across RCTs of therapies for the prevention and treatment of FGR. The clinical applicability of future research would be enhanced by the development of a core outcome set for use in future trials. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Expression of neuronal markers in the endometrium of women with and those without endometriosis.

STUDY QUESTION: How do the expression patterns of neuronal markers differ in the endometrium of women with and without endometriosis? SUMMARY ANSWER: The neuronal markers, PGP9.5, NGFp75 and VR1, are expressed in the endometrium at levels that do not differ between women with and without endometriosis. WHAT IS KNOWN ALREADY: Aberrant neuronal growth within the uterus may contribute to abnormal fertility and uterine dysfunction. However, controversy still exists as to whether aberrant innervation in the endometrium is associated with gynaecological pathology such as endometriosis. This may reflect the use of subjective methods such as histology to assess the innervation of the endometrium. We, therefore, employed a quantitative method, western blotting, to study markers of endometrial innervation in the presence and absence of endometriosis. STUDY DESIGN, SIZE, DURATION: This study included 45 women undergoing laparoscopic examination for the diagnosis of endometriosis. Endometrial samples were analysed by western blot for the expression of neuronal and neurotrophic markers, PGP9.5, VR1 and NGFp75. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Endometrial pipelle biopsies were obtained from patients with (n = 20, study group) and without (n = 25, control group) endometriosis. Tissue was analysed by immunohistochemistry and western blot analysis for the expression of pan-neuronal marker, PGP9.5, sensory nociceptive marker, TPVR1, and low-affinity neurotrophic growth factor receptor, NGFRp75. MAIN RESULTS AND THE ROLE OF CHANCE: PGP9.5, NGFp75 and VR1 were expressed in the endometrium of women, independent of the presence of endometriosis. Furthermore, the expression level of PGP9.5, VR1 and NGFp75 did not alter between the two cohorts of women. LIMITATIONS, REASONS FOR CAUTION: Studies of this nature are subject to the heterogeneous nature of patient population and tissue samples despite attempts to standardize these parameters. Hence, further studies using similar methodology will be required to confirm our results. WIDER IMPLICATIONS OF THE FINDINGS: Our results highlight that sensory neuronal markers are present in women with and without endometriosis. Future work will assess what the targets of the endometrial nerves are and investigate their function, their impact on endometrial biology and, in particular, whether aberrant neuronal function, rather than the mere presence of neuronal function, could be the root cause of subfertility and/or pain affecting many endometriosis sufferers. Our results do not, however, confirm the previous paradigm of increased innervation in the endometrium of women with endometriosis, nor the use of nerve cell detection from pipelle biopsies to diagnose endometriosis.

Paralysis in hedgehogs (Erinaceus europaeus) associated with demyelination.

Paraplegia affected 14 hedgehogs (Erinaceus europaeus) in a wildlife rescue hospital over a period of six months. Postmortem examination revealed demyelination in the brain and spinal cord and an inflammatory response in the meninges, choroid plexus and CNS. The peripheral nervous system was not affected. In the spleen, lungs and liver there was an accumulation of megakaryocytes and other evidence of extramedullary haemopoiesis, but there was no haematological evidence of anaemia. The pattern of disease incidence and the nature of the changes in the CNS suggest they were of viral origin, but no causal agent was isolated and the possibility of a neurotoxin cause cannot be ruled out.

Infectious canine hepatitis in red foxes (Vulpes vulpes) in the United Kingdom.

The pathological findings are described in three cases of infectious canine hepatitis in free-ranging red foxes (Vulpes vulpes) in England. The foxes died after short periods of clinical illness. Mild jaundice and hepatic congestion were evident grossly. On histopathological examination, intranuclear inclusion bodies were visible in hepatocytes, in association with hepatocyte dissociation and necrosis, as well as in renal glomeruli, renal tubular epithelial cells and vascular endothelial cells. Canine adenovirus type 1 (CAV-1) was isolated from all three foxes. In a serological study, antibodies to CAV-1 were detected in tissue fluid extracts taken from 11 of 58 (19 per cent) frozen red fox carcases from England and Scotland.

Polymorphism in the epidermal growth factor gene is associated with birthweight in Sinhalese and white Western Europeans.

Birthweight predicts health later in life and is influenced by inherited factors. We investigated the association of the c.61G > A, and c.2566G > A polymorphisms in the epidermal growth factor (EGF) gene [GenBank NM_001963] with birthweight in three groups of healthy pregnant women, and in women with pregnancies affected by fetal growth restriction (FGR). Subjects comprised 171 Sinhalese women with normal pregnancies (Group A), 64 white Western European women with normal pregnancies (Group B), 101 white Western European women with normal pregnancies and their babies (Group C) and 107 women with pregnancies affected by FGR, their partners and their babies (Group D). Maternal EGF genotypes were associated with birthweight of healthy babies of women in Groups A (P = 0.03), B (P = 0.001) and C (P = 0.01). The association persisted following adjustment for confounding by gestational age, sex, maternal weight, parity and smoking habit. The trend from heaviest to lightest birthweights in all these groups was c.61AA > c.61GA > c.61GG and c.2566GG > c.2566GA > c.2566AA. The EGF haplotype associated with lower birthweight (c.61G, c.2566A) was transmitted at increased frequency from heterozygous parents to babies affected by FGR in Group D (P = 0.02). These findings support the hypothesis that growth factors expressed by the feto-maternal unit affect birthweight, and implicates polymorphism in the EGF gene in the aetiology of birthweight variability.

[Met-Hb formation and local anesthesia using bupivacaine, carticaine and etidocaine (author's transl)]. / Haemiglobinspiegel unter Lokalanaesthesie mit Bupivacain, Carticain und Etidocain.

Hemoglobin-(= Met-Hb)formation by local anaesthesia and local anaesthetics is still a point for discussion. Until now met-hb-aemia only was proven to develop under local anaesthetics with relationship to aniline (Benzocaine, Citanest). Since aniline does not possess any oxidative properties, met-hb-formation only can occur after metabolism (phenylhydroxylamine or para-aminophenol), first of all amino- and nitro-groups [6, 14] will be made responsible for oxidation. Because of the fact that neither the relationship to aniline nor the benzol-structure is the pre-supposition for met-hb-formation, possibly other substances with amino- or nitro-groups may induce it. In consequence of incidental cyanosis under intra and extradural analgesia we studied the met-hb-behaviour after the use of different local anaesthetics. The aniline-related bupivacaine and etidocaine were opposed to the thiophene-related carticaine. In this examination we found neither an elevation of hemoglobin by the aniline-related nor by the thiophene-related substances.

[Methaemoglobin-behaviour due to carticaine (= Ultracain) (author's transl)]. / Methaemoglobinverhalten unter Anwendung von Carticain (= Ultracain).

The influence of carticaine on the formation of methaemoglobin was investigated in 22 patients undergoind spinal (n = 10) or epidural (n = 12) anaesthesia. Carticaine in a dose of 1,35 mg/kg, as used for spinal anaesthesia, did not influence the concentration of methaemoglobin. Carticaine in a dose of 5 mg/kg however, as used for epidural anaesthesia, increased the formation of methaemoglobin slightly at 30 min after injection. This increase is of little clinical importance since the upper limits of the normal range were not reached.

[A fatal bleeding complication following central venous catheterization in end-stage pancytopenia. Medical and legal consequences]. / Tödliche Blutungskomplikation nach zentralem Venenkatheterismus bei behandelter Panzytopenie im Finalstadium. Medizinische und strafrechtliche Konsequenzen.

An attempt to insert a central venous catheter into the internal jugular vein of a patient suffering from pancytopenia failed and due to massive bleeding into the cervical tissue the patient developed severe dyspnoea and died during unsuccessful endotracheal intubation. A five-year judicial inquiry finally discharged the anaesthesiologist revealing that forensic aspects like a valid patient's consent, exact documentation of operations and therapies, clear arrangement with patient's relatives as well as an early detailed written epicrisis play a major role. This may be the only way to early counteract medically inane causal relationship being presented by the relative's advocate. Especially in the patient at high risk central venous catheterisation requires strict checking the indication, the corresponding choice of the correct technique during venipuncture, and a sufficient haemostatic pretreatment and care after catheterisation.

[Diagnosis and therapy of disseminated intravascular coagulation]. / Diagnose und Therapie pathologischer Gerinnungsaktivierungen.

Consumptive coagulation disorders are frequently observed in critically ill patients secondary to other underlying diseases. Initial hypercoagulability leads to subsequent hypocoagulability due to consumption of procoagulant proteins, inhibitors, and platelets. This process evolves in three distinct phases: an initial increase in coagulation activity is characterised by the activation of coagulation factors and platelets without any clinical symptoms of a haemorrhagic diathesis. The ongoing process of activation and accelerated consumption of coagulation factors and inhibitors causes a critical reduction in the haemostatic potential. The time of onset of the clinical symptoms of bleeding depends on the patient's underlying disease and its pharmacological management. Coagulation processes that are restricted locally under normal conditions become disseminated when the inhibitory potential--mainly represented by antithrombin III (AT III)--is exhausted. Therefore, thrombin formation occurs, especially in the microcirculation, where fibrin clot deposition begins to cause inhomogeneities of blood flow and thus to reduce oxygen delivery to the tissues. Hypocoagulability, reactive hyperfibrinolysis, and diffuse bleeding lead to an irreversible systemic breakdown of haemostatic mechanisms (disseminated intravascular coagulation, DIC). The laboratory diagnosis of accelerated consumption is based on the course of global coagulation tests (e.g., prothrombin time, activated partial thromboplastin time, platelet count) and more sensitive ("dynamic") activation parameters such as prothrombin fragment F1 + 2, thrombin-AT III complex, fibrin monomers, or d-dimer. Measurements of plasminogen, tissue plasminogen activator, plasminogen activator inhibitor 1, and alpha 2-antiplasmin-plasmin complex provide information on fibrinolytic turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

[Urine pseudocyst following multiple injury with closed subpelvic ureteral rupture in childhood]. / Urinpseudozyste nach Mehrfachverletzung mit geschlossenem subpelvinen Harnleiterabriss im Kindesalter.

The authors discuss special aspects concerning children and traffic accidents, prompted by the frequency of such accidents. They present a model of the pathogenesis of closed injuries of the ureter. On the basis of the mechanics of accidents and clinical experience, closed subpelvic rupture of the ureter is to be seen as the result of a deceleration trauma. Problems of the treatment of patients with multiple injuries and the diagnosis and therapy of closed injuries of the ureter are presented on the basis of a clinical observation.

[The special aspects in the planning and use of an electron linear accelerator facility for intraoperative radiotherapy (IORT)]. / Besondere Aspekte bei Planung und Nutzung einer Elektronenlinearbeschleuniger-Anlage für intraoperative Strahlentherapie (IORT).

Limiting conditions for the planning of the installation of an electron linear accelerator in an operating theatre are described taking into account the radiotherapeutical and surgical requirements based on the example of the Essen facility for intraoperative radiotherapy (IORT) with electrons. Special features of the facility like a non-contact electron applicator system with television monitoring, table-top trolley, which is used also during irradiation, are explained in detail. Measured isodose curves for all tubes and all electron energies serve for the radiotherapist as criteria for decision on tube size and electron energy selection during surgical operation. The influence of misalignments of the tube on dose distributions is investigated. Limit values of alignment tolerances are deduced. Daily constancy tests for monitor calibration, electron energy, and tube alignment system are to be performed for quality assurance. Tables of the planned and realized treatments and of a representative time schedule of an IORT give a survey on the indications and the necessary time effort and staff. Completion of the set of tubes as well as optimization of the tube fixation accessory and of the table-top trolley are main subjects for future developments.