Spreading endothelial cell dysfunction in response to necrotic trophoblasts. Soluble factors released from endothelial cells that have phagocytosed necrotic shed trophoblasts reduce the proliferation of additional endothelial cells

The pathogenesis of preeclampsia is not clear but the disease is characterised by systemic endothelial cell dysfunction that is considered to be triggered by a placental factor. Necrotic trophoblastic debris that is deported in the maternal blood is one possible placental trigger for preeclampsia. Syncytial knots were first associated with preeclampsia over 100 years ago. However, syncytial knots are very large and most are trapped in the pulmonary capillaries making it difficult to envisage how they could lead to widespread systemic endothelial cell dysfunction. This study was undertaken to examine whether conditioned medium from endothelial cells that have phagocytosed necrotic trophoblastic debris could adversely affect the proliferation or survival of fresh endothelial cells. Trophoblastic cellular debris, harvested from placental explants was added to endothelial cell monolayers directly or after induction of necrosis by freeze-thawing. Conditioned medium from the endothelial cell cultures was exposed to fresh endothelial cells and their proliferation measured by Alamar Blue, and CyQUANTNF cell proliferation assays. Endothelial cell death was examined by a fluorogenic caspase-3 activity assay and LDH release. Conditioned medium from endothelial cells that had phagocytosed necrotic but not apoptotic trophoblastic debris significantly inhibited the proliferation of fresh endothelial cells but did not induce their death. The conditioned medium also reduced cell-surface endoglin expression by fresh endothelial cells. These results confirm that phagocytosis of necrotic trophoblastic debris by endothelial cells results in the secretion of soluble factors that might explain how necrotic trophoblastic debris trapped in the pulmonary capillaries could induce systemic endothelial cell dysfunction.     

IFPA Meeting 2008 Workshops Report

Workshops are an important part of the IFPA annual meeting. At the IFPA meeting 2008 diverse topics were discussed in 12 themed workshops. Topics covered included: immunology of placentation; galectins and trophoblast invasion; signaling in implantation and invasion; markers to identify trophoblast subpopulations; placental pathology; placental toxicology; stereology; placental transport of fatty acids; placental mesenchymal stem cells; comparative placentation; trophoblast and neoplasia; trophoblast differentiation. This report is a summary of the various topics covered.     

Accidental Cs-137 contamination

Widespread use of radionuclides in medicine and industry poses the possibility of radiation accidents. We describe such an occurrence involving three industrial workers. The accident resulted from careless handling of a Cs-137 source. Evaluation of the Cs-137 whole body burden was carried out using stationary and scanning whole body counters. In addition, regional and whole body activity from contamination was assessed using an uncollimated gamma camera. This report emphasizes the value of the gamma camera for detection of radionuclide contamination in radiation accidents.     

Clinical and experimental vasogenic edema: in vivo sodium MR imaging. Work in progress

To investigate the sodium magnetic resonance (MR) imaging characteristics of acute vasogenic edema, an experimental canine model was developed. Vasogenic edema was produced in the hemisphere of the dogs by the intraarterial infusion of hypertonic mannitol (25%). This solution opens the blood-brain barrier, allowing the influx of water, electrolytes, and proteins into the brain. The main advantage of this model over the established "cold injury" model is the lack of associated brain necrosis. Two patients with chronic vasogenic edema secondary to well-circumscribed meningiomas also underwent MR imaging. The sodium signal was markedly elevated in both clinical and experimental studies of vasogenic edema fluid compared with signal in healthy brain tissue. Extracellular sodium associated with vasogenic edema displayed MR imaging characteristics similar to that of sodium in serum. There was a trend toward a shortened T2 in edema fluid secondary to the presence of serum macromolecules.     

Value of CT in the preoperative assessment of lung cancer: a survey of thoracic surgeons

Practicing thoracic surgeons were randomly surveyed to evaluate how computed tomography (CT) has influenced the preoperative evaluation of bronchogenic carcinoma. Thirty-six percent of the 529 respondents routinely requested CT and 62% did so selectively. Approximately 40% indicated that CT provided useful information in most cases. Nearly all surgeons (98.7%) do not rely on the identification of enlarged lymph nodes with CT to spare the patient surgical staging; however, 77.5% are influenced by CT results in their staging procedures. Fifty-seven percent reported that a negative CT study eliminates surgical staging entirely unless the patient has a "coin lesion," in which case 75% are willing to proceed directly to thoracotomy. For surgeons who use CT selectively, an abnormal mediastinal contour on the radiograph was the most frequent radiologic abnormality to prompt CT (85%). Thirty-seven percent are influenced by tumor histology in their decision to request CT. There was little difference in the pattern of CT use between university and community hospital surgeons.     

Malignant hyperthermia in infancy and identification of novel RYR1 mutation

Malignant hyperthermia (MH) has been reported as non-existent in children less than 1 yr old, although several unconfirmed reports have been published. A case report of MH in a 6-month-old child is presented, with confirmation of MH susceptibility by in vitro contracture testing of quadriceps muscle at 13 yr old. Genetic analysis revealed a novel RYR1 mutation that substitutes arginine 2452 for tryptophan in a region of the calcium channel mutated in several other MH pedigrees.      

Exploring healthcare professionals' perspectives of barriers and facilitators to supporting people with severe mental illness and Type 2 diabetes mellitus

Individuals with comorbid severe mental illness (SMI) and diabetes experience an average mortality gap of 20 years compared to individuals without these conditions. There has been some recognition by policies that there is a gap between mental healthcare and physical healthcare for SMI patients. Despite this, there are still no defined care pathways for individuals with SMI and diabetes. The aim of this study was to explore healthcare professionals' (HCPs) perspectives of barriers and solutions to supporting people with SMI and diabetes. HCPs in areas of South London were invited to attend a workshop event to discuss their views of SMI and diabetes pathways. Fifty participants were recruited using the Local Care Network. HCPs included GPs, mental health nurses, psychiatrists, diabetologists and care co‐ordinators. The main themes were as follows: (a) poor coordination of care and care planning between services; (b) key techniques to improve integrated care; (c) perceived difficulties achieving better care and (d) supporting patient empowerment. The findings and recommendations from this workshop may provide some insight into key factors in providing and improving integrated SMI and diabetes care for patients in South East London and further afield.