Funisitis is associated with adverse neonatal outcome in low-risk unselected deliveries at or near term.

This study aimed to determine the incidence and clinical outcomes for varying patterns of placental histological inflammation (consistent with fetal or maternal inflammatory response) in an unselected population of >1000 women with a singleton pregnancy resulting in live birth delivering at or near term. One thousand one hundred nineteen cases were studied in a blind, prospective, unselected study with placentas categorized into five histological subgroups reflecting underlying maternal or fetal inflammatory response. Clinical outcomes studied included interventional delivery, an Apgar score <7 at 1 min, neonatal acidosis (pH < 7.2) and admission to neonatal special care. One hundred eighty-eight placentas (17%) showed histological evidence of acute inflammation: 64 with funisitis (with or without other inflammation; 6%); 16 with extensive acute inflammation across the chorionic plate, free membranes and subchorionic fibrin (1%); 28 with acute inflammation restricted to the chorionic plate (2%); 12 with acute inflammation restricted to the free membranes (1%) and 68 with acute inflammation restricted to the subchorionic fibrin (6%). Features of extensive acute inflammation were significantly associated with increased rate of interventional delivery (assisted vaginal delivery or emergency caesarean section; P < 0.01). The presence of funisitis was significantly associated with interventional delivery and other adverse outcomes including an Apgar score <7 at 1 min, clinical evidence of sepsis and admission to the neonatal intensive care unit (P < 0.05 for all). The data represent a quantitative rather than purely qualitative analysis of the contribution of histological lesions related to inflammation on short-term adverse neonatal outcomes and interventional delivery. Funisitis and extensive inflammation are associated with adverse clinical outcomes, but the precise mechanism underlying these remains to be elucidated.

Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin.

Cancer stem cells or tumour-propagating cells (TPCs) have been identified for a number of cancers, but data pertaining to their existence in lymphoma so far remain elusive. We show for the first time that a small subset of cells purified from human anaplastic lymphoma kinase (ALK)-positive and -negative, anaplastic large cell lymphoma cell lines and primary patient tumours using the side population (SP) technique have serial tumour-propagating capacity both in vitro and in vivo; they give rise to both themselves and the bulk tumour population as well as supporting growth of the latter through the production of soluble factors. In vivo serial dilution assays utilising a variety of model systems inclusive of human cell lines, primary human tumours and nucleophosmin (NPM)-ALK-induced murine tumours demonstrate the TPC frequency to vary from as many as 1/54 to 1/1336 tumour cells. In addition, the SP cells express higher levels of pluripotency-associated transcription factors and are enriched for a gene expression profile consistent with early thymic progenitors. Finally, our data show that the SP cells express higher levels of the NPM-ALK oncogene and are sensitive to an ALK inhibitor.

Umbilical cord coiling: clinical outcomes in an unselected population and systematic review.

This study was conducted to determine the frequency of pre-defined clinical outcomes in relation to umbilical cord coiling indices >90th percentile and <10th percentile in an unselected population of >1,000 women with a singleton pregnancy resulting in livebirth delivering at or near term and to report these findings in the context of a systematic review. Placentas of consecutive deliveries from an unselected low-risk population with >15 cm attached umbilical cords were included in the study. Clinical outcomes included interventional delivery, birthweight <10th percentile, Apgar score <7 at 1 min, neonatal acidosis (pH<7.2) and admission to neonatal special care. Standard MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines were observed for the systematic review. Umbilical coiling index was determined for 1,082 placentas. Mean maternal age was 30.7 years (standard deviation [SD] =5.7) and 519 women (48 %) were primiparous. Mean cord length was 43 cm (SD=13) and mean cord coiling index 0.20 (SD=0.09). A total of 866 cords were normally coiled, and 108 cases were hypercoiled (>90th centile) and 108 cases were undercoiled (<10th percentile). There were no differences between cases of overcoiled, normally coiled or undercoiled cords for any clinical outcome studied. The systematic review yielded a small number of clinical studies which were too statistically and clinically heterogenous to permit meta-analysis. There is insufficient evidence either from this unselected cohort study or from a systematic review to support the previous suggestion that cord coiling index >90th centile or <10th centile is associated with adverse clinical outcome in an unselected population. Previous studies that draw a link between abnormal cord coiling and clinical outcome are generally too small and/or selective to allow meaningful conclusions or applicability to low-risk populations.

Effects of Chlamydia trachomatis infection on the expression of natural killer (NK) cell ligands and susceptibility to NK cell lysis.

Natural killer (NK) cells are an important component of the immediate immune response to infections, including infection by intracellular bacteria. We have investigated recognition of Chlamydia trachomatis (CT) by NK cells and show that these cells are activated to produce interferon (IFN)-gamma when peripheral blood mononuclear cells (PBMC) are stimulated with CT organisms. Furthermore, infection of epithelial cell lines with CT renders them susceptible to lysis by human NK cells. Susceptibility was observed 18-24 h following infection and required protein synthesis by the infecting chlamydiae, but not by the host cell; heat or UV inactivated chlamydiae did not induce susceptibility to NK cell lysis. CT infection was also shown to decrease the expression of classical and non-classical major histocompatibility complex (MHC) molecules on infected cells, thus allowing recognition by NK cells when combined with an activating signal. A candidate activating signal is MICA/B, which was shown to be expressed constitutively on epithelial cells.