Three coronary arteries arising from the right coronary cusp with a malignant sub-pulmonary course of the left anterior descending artery

AbstractWe describe a case of a 45-year-old man presenting with acute myocardial infarction investigated by computed tomography coronary angiography. Interestingly all three coronary arteries arose from the right coronary cusp. The left anterior descending artery (LAD) subtended an acute angle from the aortic root, associated with significant kinking and stenosis at the ostium, before passing anteriorly, taking a sub-pulmonic course and descending in the anterior interventricular groove. The distal vessel was small with an atrophic appearance. The circumflex artery followed a retro-aortic route, before trifurcating to supply the lateral and posterior walls of the left ventricle. The right coronary artery was normal. Given his unstable presentation and the potentially lethal course of the LAD, he was referred for grafting of the LAD vessel which successfully ameliorated his symptoms and has thus far prevented recurrent myocardial infarction.<Learning objective: Computed tomography coronary angiography is becoming increasingly accessible to physicians for the investigation of patients with suspected coronary disease and the planning of surgery. As such, coronary anomalies are likely to be encountered more frequently, and it is important to appreciate their clinical significance.

Long term improvements in activities of daily living in patients with hemispatial neglect

No abstract available

Novel approaches to the development and assessment of an ovine model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive, endocrine and metabolic disorder present in women of reproductive age. Despite the widespread prevalence and heritability of PCOS, the heterogeneous and polygenic traits have made the successful identification of candidate genes difficult. Animal models have been developed on the premise that early exposure to sex steroids can programme epigenetic changes that predispose the fetus to the adult features of PCOS. Past research has modelled ovarian dysfunction, endocrine abnormalities and metabolic perturbances in rodent, non-human primate and sheep PCOS models, through the enhanced neonatal or prenatal exposure to the male sex hormone, testosterone. The modelling of PCOS in a large domestic species such as the sheep is advantageous due to similar biological reproductive function as the human. In this regard the sheep has been extensively used to model PCOS by the treatment of pregnant ewes from early to midgestation with androgens such as testosterone propionate (TP). These experiments have demonstrated the fetal programming effects of androgens on offspring that go on to develop PCOS-like characteristics in adulthood. One of the caveats of assessing steroid effects in this way is the effect of the placenta in mediating the transfer of these hormones. TP is an aromatisable androgen and thus some of its effects in the fetus may be attributable to placental by-products such as estrogens. This thesis describes the development and assessment of a novel model of prenatal androgenisation. Two models were compared: the indirect maternal exposure to TP (the current model) and the direct fetal injection of TP. In directly treating the fetus this allowed control over the dose of TP administered and avoidance of secondary effects that androgens may exert in the mother that could be transferred to the fetus. For the maternal model, pregnant Scottish Greyface ewes were administered TP twice weekly from day (d)62-102 of a 147 day gestation. For the fetal model, fetuses were injected twice while the ewe was anaesthetised with graded doses of TP during the same period of treatment as the maternal model. The effects of prenatal androgenisation were assessed in the female fetus shortly after treatment and also in young adult sheep. Fetal ovarian and adrenal steroidogenic gene expression was monitored and found to be altered in response to elevated levels of sex steroids. At d90 the morphology of the developing ovary was not changed by prenatal androgens. In the adult a detailed ovarian and endocrine assessment was undertaken, by examination of ovarian morphology, hormone levels, ovulatory cycles, hypothalamic pituitary ovarian function and follicle steroidogenesis, during the first breeding season. In addition, the metabolic effects of prenatal androgens were monitored by measuring body fat, insulin and glucose homeostasis and liver function. Neither maternal nor fetal prenatal androgenisation during mid-gestation resulted in a perturbed hormonal milieu or polycystic ovaries in young adults. These treatments did however programme a clear ovarian phenotype demonstrated by the increased capacity of follicles to secrete androgens, independently of an abnormal endocrine environment and disordered folliculogenesis. Furthermore, animals that were exposed maternally to TP developed fatty liver and had increased insulin secretion in response to glucose load. A major outcome of this study was the finding that the fetally injected control animals were phenotypically different than the maternal control animals. In fact, some of the reproductive and metabolic features of maternal TP exposure were found in the fetal control group. This unexpected finding has raised the possibility that it is the fetal exposure to stress, that is secondary to elevated maternal androgens, rather than androgens per se that is responsible for at least some of the multitude of anomalies encountered in PCOS

Patients’ preferences for nutrition-related health outcomes in liver disease : a preliminary study using an electronic questionnaire

Background: Patients with liver disease frequently have nutritional problems but intervening to improve these is challenging. Healthcare interventions that respond to patients’ needs are associated with better health outcomes but no studies investigating patients’ preferences for nutrition-related outcomes in liver disease have been published. The aim of this study was to identify nutrition-related health outcomes that are important to patients with liver disease. Methodology: An electronic questionnaire was devised and reviewed by patients and dietitians with relevant experience. It comprised Likert scale and open questions focussing on six domains considered pertinent to patients with liver disease. An invitation to participate was posted on the website of a national liver charity and sent to liver patient support groups. Results: Fifty-one patients participated (22 men / 29 women). Responses indicated a wide range of preferred nutrition-related outcomes with those identified as very important most frequently focussing on gaining knowledge about which foods to eat more or less of, and on understanding why nutrition is important in liver disease. Women tended to score outcomes as more important than men. Participants who considered themselves overweight scored outcomes on body size and shape as more important than those with other nutritional problems. Additional outcomes were identified and included increased knowledge of healthy eating, interactions between medication and food, and supplementation. Conclusions: The study identified a wide range of nutrition-related outcomes that were important to this small sample of patients with liver disease and these may be useful to guide the direction of future nutrition-related management.Peer reviewedFinal Accepted Versio

Inhibitor of Differentiation (Id) Genes Are Expressed in the Steroidogenic Cells of the Ovine Ovary and Are Differentially Regulated by Members of the Transforming Growth Factor-beta Family

Inhibitor of Differentiation (Id) proteins act during embryogenesis and development to repress gene transcription required for lineage commitment, whilst promoting cell growth. Growth factors belonging to the transforming growth factor beta (TGFβ) superfamily of signaling molecules, notably the bone morphogenetic proteins (BMPs) and activin, can regulate Id expression in these tissues. Id expression and function in adult physiology is less well determined and we hypothesized a role for Id proteins in the adult mammalian ovary. Immunohistochemistry for Id1, Id2, Id3 and Id4 in the sheep ovary revealed consistent expression in granulosa and thecal cells of ovarian follicles throughout development. In atretic follicles Id proteins were selectively down-regulated in thecal cells (P<0.0001). Additionally Id1 was universally up-regulated in the cumulus cells adjacent to the oocyte. Immunohistochemistry for phospho (p)-smad 1/5/8 signalling components (stimulated by BMPs) showed a punctate pattern of expression whereas p-smad 2/3 (stimulated by activin) was ubiquitously expressed in follicles. Neither pathway however displayed differential staining in line with Id1 cumulus specific expression, suggesting a more complex relationship between Id1 expression and TGFβ signaling in these cells. Nevertheless, in vitro, stimulation of ovine granulosa cells with BMP6 or activin A led to a respective increase and decrease in Id1 (P<0.0001), Id2 (P<0.0001), Id3 (P<0.0001) and Id4 (P<0.05) transcripts and Id1 gene expression was further manipulated by the oocyte-secreted factors BMP15 and GDF9 (P<0.001). These data confirm that TGFβ signaling can regulate Id gene expression in the sheep ovarian follicle and suggest a functional role for the Id family in the mammalian ovary

Subcontractors' liability for project delays

The paper addresses the contractual problem of how main contractors pass on liability for project delays to their subcontractors; a topic that is difficult and has not been grasped properly in the previous literature. The survey reveals that the ‘normal’ approach is illogical and that the issue is misunderstood by a significant proportion of practitioners in the UK

Low-mass members of the young cluster IC 4665 and pre-main-sequence lithium depletion

We have used fibre spectroscopy to establish cluster membership and examine pre-main-sequence (PMS) lithium depletion for low-mass stars (spectral types F to M) in the sparse young (~30 Myr) cluster IC 4665. We present a filtered candidate list of 40 stars that should contain 75 per cent of single cluster members with V of 11.5 to 18 in the central square degree of the cluster. Whilst F- and G-type stars in IC 4665 have depleted little or no lithium, the K- and early M-type stars have depleted more Li than expected when compared with similar stars in other clusters of known age. An empirical age estimate based on Li-depletion among the late-type stars of IC 4665 would suggest it is older than 100 Myr. This disagrees entirely with ages determined either from the nuclear turn-off, from isochronal matches to low-mass stars or from the re-appearance of lithium previously found in much lower mass stars (the ``lithium depletion boundary''). We suggest that other parameters besides age, perhaps composition or rotation, are very influential in determining the degree of PMS Li-depletion in stars with M greater than 0.5 Msun. Further work is required to identify and assess the effects of these additional parameters, particularly to probe conditions at the interface between the sub-photospheric convection zone and developing radiative core. Until then, PMS Li depletion in F- to early M-type stars cannot be confidently used as a precise age indicator in young clusters, kinematic groups or individual field stars.Comment: Accepted for publication in MNRA