Subclavian catheterisation is frequently used for acute vascular access for haemodialysis and is thought to rarely result in long-term clinical problems. Venography in 36 cases, however, revealed subclavian stenosis in 18 (50%), of whom five developed clinical problems. The incidence of subclavian-vein stenosis was related to the duration of catheterisation (P less than 0.05). It may also be more common in black patients. Subclavian catheterisation is therefore not necessarily an ideal form of acute vascular access.

Twenty eight patients who had received haemodialysis for more than 10 years were reviewed to establish the incidence of joint problems. Only six patients had no joint symptoms, one had avascular necrosis, one had had recent septic arthritis, and four had hyperparathyroidism. The remaining 16 patients had no evidence of hyperparathyroidism yet had an arthropathy causing pain and stiffness in many joints, particularly the shoulders. Ten of these 16 patients had a recurrent carpal tunnel syndrome requiring repeated surgical decompressions, which resulted in only partial improvement. Of the eight patients who had received dialysis for more than 15 years, seven had this "dialysis arthropathy" and six had recurrent carpal tunnel syndrome.Dialysis arthropathy is a common and often severe and disabling complication of long term treatment with haemodialysis. The cause is not known, but amyloid was found in a synovial biopsy specimen from one patient.

1 SK&F 93944 (temelastine), a novel histamine HI-receptor antagonist, has been studied in a variety of in vitro and in vivo test systems. 2 SK&F 93944 was a competitive antagonist of histamine-induced contractions of guinea-pig ileum with a pA2 of 9.55 and a weak, non-competitive, inhibitor of the effects of histamine on guinea-pig atrium. 3 In anaesthetized guinea-pigs SK&F 93944 displaced histamine bronchoconstriction dose-response curves at doses which had negligible effects on histamine tachycardia. 4 In anaesthetized cats SK&F 93944 antagonized depressor responses to the histamine HI-receptor agonists, 2-(2-aminoethyl)pyridine and betahistine, at doses which had no effects on responses to the histamine H2-receptor agonist, dimaprit. described HI-receptor antagonists in that it lacks a tertiary amino group and is largely unprotonated at physiological pH. This paper describes the pharmacology of SK&F 93944 in a range of in vitro and in vivo models designed to evaluate both its potency and selectivity. In addition, studies are described which show that the compound has negligible ability to cross the bloodbrain barrier in rats, and is consequently highly unlikely to elicit CNS side-effects. A Animals were artificially ventilated through a tracheal cannula using the volume of air just required to fill the lungs at an airway pressure of 12 cmH2O. A pressure transducer was inserted into the outflow limb of the system to measure airway inflation pressure as an index of resistance. Blood pressure, heart rate and airway pressure were registered continuously on an electronic recorder (Lectromed, Ml 9). Dose-response curves for histamine-induced bronchoconstriction and tachycardia were constructed in each animal prior to and following intravenous injection of a histamine HI-receptor antagonist at a series of doses. In a further series ofexperiments with SK&F 93944, carbachol was used as the agonist to elicit bronchoconstriction.Studies in anaesthetized cats Studies were carried out in cats of either sex, body weight 1.65-3.15 kg. Following induction of anaesthesia the trachea was cannulated. Systemic blood pressure was measured from a catheter in one carotid or femoral artery and monitored on a Lectromed M19 recorder. Heart rate was measured with an instantaneous rate meter triggered by the blood pressure pulse. Injections of drugs and supplementary doses ofanaesthetic were made via cannulae inserted into the femoral and/or brachial veins.Studies with selective histamine receptor agonists Cats were anaesthetized with sodium pentobarbitone, 60 mg kg-' i.p. Responses to 2-(2-aminoethyl) pyridine (2-PEA), betahistine and dimaprit were obtained in separate groups of cats, using procedures described by Owen (1975 Vascular permeability changes were measured 15 min after injection of histamine since preliminary experiments indicated this time to be optimal in the rat. At this time the rats were again anaesthetized, the abdomen opened and a I ml sample of blood taken from the vena cava. The animals were then killed and th...

To cite this article: Freeman DJ, Tham K, Brown EA, Rumley A, Lowe GD, Greer IA. Fetal corticotrophin-releasing hormone mRNA, but not phosphatidylserine-exposing microparticles, in maternal plasma are associated with factor VII activity in pre-eclampsia. J Thromb Haemost 2008; 6: 421-7Summary. Background: Pre-eclampsia is associated with increased placental debris circulating in maternal plasma. Objectives: This study related placental debris to maternal markers of coagulation and endothelial activation in pre-eclampsia. Patients/methods: Circulating fetal corticotrophin-releasing hormone (CRH) mRNA and phosphatidylserine (PS)-exposing microparticles were assayed in third trimester plasma from women with pre-eclampsia (n = 32) and controls (n = 32) matched for age, body mass index, parity, and gestational age at sampling. Markers of maternal hemostasis and endothelial function were assessed. Results: Fetal CRH mRNA levels were higher in pre-eclampsia [mean 0.75 (SD 2.77) CRH/glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) mRNA ratio] than in control pregnancies [0.20 (0.74), P = 0.014]. PS-exposing microparticle levels were not different between the groups. Women with pre-eclampsia had higher levels of tissue factor pathway inhibitor (TFPI), prothrombin F 1+2 fragment (F 1+2 ), factor XIIa, soluble vascular cell adhesion molecule 1, von Willebrand factor and plasminogen activator inhibitor 1 than controls. Fetal CRH mRNA correlated with TFPI in pre-eclampsia and control groups (r = 0.38, P = 0.031, and r = 0.37, P = 0.039, respectively). Fetal CRH mRNA correlated with FVII activity (r = 0.43, P = 0.017) and PS-exposing microparticles correlated inversely with F 1+2 (r = )0.64, P < 0.001) in preeclampsia. Conclusions: Placental debris, assessed by fetal CRH mRNA levels in maternal blood, is related to coagulation potential, i.e. FVII activity, but not to markers of coagulation or endothelial activation in pre-eclampsia.

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