A national survey of obstetric early warning systems in the United Kingdom

BackgroundDespite recommendations in the two most recent Confidential Enquiries into Maternal and Child Health (CEMACH) reports, and improvements in patient care using early warning scoring systems (EWS) in the general adult population, no validated system currently exists for the obstetric population.MethodsWe performed an Obstetric Anaesthetists’ Association (OAA) approved postal survey of all UK consultant-led obstetric anaesthetic units in November 2007 to assess opinions on the value and of such a system and how it could be implemented, and invited comments and samples of systems already in use.ResultsThe response rate was 71%. Of those who replied a median usefulness score of 80% for a standardised national obstetric EWS was demonstrated. Eighty-nine percent of units thought it would be possible to implement a system, and although 96% of UK hospitals already use a non-obstetric EWS, only 23% of respondents thought this to be relevant to obstetric physiology and disease. Nine units returned copies of their obstetric EWS. Using extracts from some of the submitted versions we have designed and implemented a system locally and submitted it to the OAA for consideration.ConclusionsThe survey results support CEMACH recommendations for a nationally agreed obstetric EWS.     

Cancer heterogeneity and “The Struggle for Existence”: Diagnostic and analytical challenges

The notions of inter- and intra-tumour heterogeneity (ITH) have been recognised for many years but recent advances in sequencing technology are allowing the true extent of both forms of heterogeneity to be revealed in detail for the first time. In this review we examine the current evidence for ITH, the possibility of cancers following a branched rather than linear evolutionary path and the potential implications both of these may have for the mechanisms of drug resistance acquisition. We also note that although clearly present in many cases, heterogeneity and branched evolution are not universal, with cases of tumour homogeneity and linear evolution still detected relatively frequently.     

Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts

Apoptosis is accompanied by the activation of a number of apoptotic proteases (caspases) which selectively cleave specific cellular substrates. Caspases themselves are zymogens which are activated by proteolysis. It is widely believed that 'initiator' caspases are recruited to and activated within apoptotic signalling complexes, and then cleave and activate downstream 'effector' caspases. While activation of the effector caspase, caspase-3, has indeed been observed as distal to activation of several different initiator caspases, evidence for a further downstream proteolytic cascade is limited. In particular, there is little evidence that cellular levels of caspase-3 that are activated via one pathway are sufficient to cleave and activate other initiator caspases. To address this issue, the ability of caspase-3, activated upon addition to cytosolic extracts of cytochrome c, to cause cleavage of caspase-2 was investigated. It was demonstrated that cleavage of caspase-2 follows, and is dependent upon, activation of caspase-3. Moreover, the activation of both caspases was inhibited by Bcl-2. Together, these data indicate that Bcl-2 can protect cells from apoptosis by acting at a point downstream from release of mitochondrial cytochrome c, thereby preventing a caspase-3 dependent proteolytic cascade.     

Isolation of antibodies which neutralise the activity of early pregnancy factor

Early pregnancy factor (EPF) is a secreted protein with growth regulatory and immunomodulatory properties. It functions as an autocrine growth factor for tumour cells and as an autocrine or paracrine growth factor for regenerating normal cells. Anti-EPF antibodies have demonstrable anti-tumour activity and, as a result, hybridomas which produce such antibodies are unstable. In this study, the phage display antibody techniques have been investigated as a means of producing recombinant anti-EPF antibodies. Mice were immunised with synthetic peptides which correspond to the N or C terminal regions of EPF, and their splenic tissue was used to make combinatorial antibody libraries. The Fab repertoire was displayed on the surface of phage and panned over recombinant EPF. Reactive Fabs were identified by ELISA and their binding was characterised by BIAcore analysis and functional studies. Three libraries with a size of greater than 5x10(7)cfu were constructed and a total of 26 unique Fabs with specific reactivity against EPF were identified. Three Fabs were purified and of these one demonstrated strong EPF neutralising activity, one had intermediate activity and the other was not neutralising. Phage display has provided the means of circumventing the problems of anti-EPF hybridoma development and has resulted in the production of antibodies with potential applications in the diagnosis of pregnancy and the diagnosis and therapy of cancer.     

Cyclosporin A and erythromycin: A study of a drug interaction in the in situ perfused rat liver model

Using the in situ perfused rat liver model, the effect of erythromycin (Ery) on the disposition of cyclosporin A (CyA) and the major human metabolite, AMl, was investigated. Prior to perfusion experiments, oral dosing was carried out for three days on three groups of male Sprague—Dawley rats (300–350 g), involving pretreatment with water (control and H₂O/Ery groups) or erythromycin (Ery oral group). On the fourth day, perfusion experiments took place using standard techniques, with the addition of 20 mg Ery to the H₂O/Ery and Ery oral groups, and 2.5 mg CyA to all groups. Perfusate and bile samples were collected and assayed for CyA and AMl by HPLC. Results indicated that inhibition of CyA metabolism had occurred as the CyA concentration in perfusate was significantly higher in both Ery groups at all times compared to the control group, and the levels of AMl in both perfusate and bile were significantly lower than in the control group. There was also a marked reduction in the apparent metabolic clearance of CyA in the Ery groups. It was concluded that AMl production had been inhibited by Ery, the most likely mechanism being inhibition of the isoenzyme CYP3A with which Ery forms a stable complex.     

Dipyridamole magnetic resonance imaging: a comparison with thallium-201 emission tomography.

Limitation of space and motion artefact make magnetic resonance imaging during dynamic exercise difficult. Pharmacological stress with dipyridamole can be used as an alternative to exercise for thallium scanning. Forty patients with a history of angina and an abnormal exercise electrocardiogram were studied by dipyridamole thallium myocardial perfusion tomography and dipyridamole magnetic resonance wall motion imaging with a cine gradient refocused sequence. Images for both scans were obtained in the oblique horizontal and vertical long axis and short axis planes before and after pharmacological stress with dipyridamole. The myocardium was divided into nine segments for direct comparison of perfusion with wall motion. Segments were assessed visually into grades--normal, hypokinesis or reduced perfusion, and akinesis or very reduced perfusion. After dipyridamole there were reversible wall motion abnormalities in 24 (62%) of 39 patients with coronary artery disease and 24 (67%) of 36 patients with reversible thallium defects. The site of wall motion deterioration was always the site of a reversible thallium defect. Thallium defects affecting more than two segments were always associated with wall motion deterioration but most single segment thallium defects were undetected by magnetic resonance imaging. There was a significant correlation between detection of wall motion abnormality, the angiographic severity of coronary artery disease, and the induction of chest pain by dipyridamole. There were no significant differences in ventricular volume or ejection fraction changes after dipyridamole between the groups with and without detectable reversible wall motion changes but the normalised magnetic resonance signal intensity of the abnormally moving segments was significantly less than the signal intensity of the normal segments. In nine patients the change was apparent visually and it was maximal in the subendocardial region. Magnetic resonance imaging of reversible wall motion abnormalities in patients with coronary artery disease is feasible during pharmacological stress with dipyridamole and may be associated with a reduced magnetic resonance signal. The failure to show wall motion abnormalities in all cases of reversible thallium defects may be because the defect was small or because dipyridamole caused perfusion defects in the absence of myocardial ischaemia.     

Gated blood-pool emission tomography: a new technique for the investigation of cardiac structure and function

ECG-gated single-photon emission-computed tomography of the intracardiac blood pool is a new technique that has not previously been widely applied. It involves the acquisition of ECG-gated images of the intracardiac blood pools labelled with sodium pertechnetate Tc 99m in 32 projections around the left-anterior hemithorax using a rotating gamma camera. From these images, tomographic sections are reconstructed orthogonal to the long axis of the left ventricle. The heart is therefore imaged three dimensionally, and more extensive information is obtained than in planar radionuclide ventriculography where imaging is usually restricted to only a single projection. Both structure and function can be studied, and the left-ventricular volume and ejection fraction, and wall motion are obtained. Of 50 patients studied, 7 cases are illustrated in order to show normal findings, examples of wall motion that were not shown by planar-contrast and radionuclide ventriculography, examples of the localisation of ventricular hypertrophy, and a comparison between blood-pool and 201TI myocardial tomography.     

Gynaecological surgery in the older population: a comparative study between two 3-year samples over a decade.

This study aimed to assess the increase, if any, of the number of operations being performed in older women and try to determine the reasons behind any such increase.