Chapter 1. Introduction, Background and Literature review.... Chapter 2. Study aims, Objectives and Research Questions.. . Chapter 3. UK ED survey 44 Chapter 4. Pilot and Main Study Methodology Chapter 5. Results: Derivation of the Clinical Decision Rule. .. Chapter 6. Results: The ROSE Rule Chapter 7. Results: Validation of the Clinical Decision Rule. .. Chapter 8. Results: Performance of the ROSE rule and comparison to existing guidelines Chapter 9. The role of Troponin 1 Chapter 10. The role of D-Dimer Chapter 11. Final discussion, suggestions for further work and conclusions References Appendices Total thesis word count = 29418 words (excluding references and appendices) Et al. has been used when there are more than three authors. If an author has more than one citation in any one year, the year has been referenced in the text. If there are many citations in any one year, each is referenced with the year followed by a, b, c, etc.

SUMMARY Ovulation has been induced in the cyclic guinea-pig at a time when the ovaries contain mature follicles, by a single injection of purified luteinizing hormone (LH), follicle-stimulating hormone or guinea-pig gonadotrophins from homogenates of female guinea-pig anterior pituitaries. An injection of any one of the substances given too early only caused follicular luteinization and the ova were retained, even with increased dosage. A single injection of LH in mid-dioestrus caused 'LH effects' on the follicles (destruction of the growing follicles), giving a histological picture similar to that which obtains at the time of ovulation in the untreated animal. Homogenates of anterior pituitaries taken from donor guinea-pigs 1–2 days before ovulation was due (but not at any other time in the cycle) when injected into recipients at middioestrus had similar effects on the follicles. Donor anterior pituitaries taken from guinea-pigs in which ovulation had been inhibited by daily injections of progesterone, caused ovulation in recipients with mature ovarian follicles or 'LH effects' in those in mid-dioestrus. It is suggested that in the guinea-pig there is a basal secretion of gonadotrophins during most of the cycle. A day or two before ovulation occurs and when the ovaries already contain ripe follicles, there is a marked increase in the synthesis of LH which is then released from the anterior pituitary gland and rupture of the follicles occurs.

Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.

SUMMARY The metabolism of 17α-ethynyloestradiol was studied in one man and 16 women. After intravenous or oral administration, 22·6–46·9% of the dose was excreted in the urine over a 5-day period. Up to 36% of the urinary radioactivity may be present in the unconjugated form with a further 64% being extractable after enzymic hydrolysis. Sulphate conjugates formed only 11·4% of the urinary radioactivity. Semi-quantitation of these extracts showed ethynyloestradiol itself to be the major metabolite, accounting for 3·2–8·4% of the administered dose in the unconjugated fraction with a further 2·4–16·5% in the enzyme hydrolysed fraction. Up to 16·5% of the dose was therefore excreted unchanged, and metabolites less and more polar than ethynyloestradiol were also found. Excretion via the faeces accounted for up to 30% of the administered dose, with most of the extractable radioactivity being in the unconjugated form. Ethynyloestradiol accounted for up to 29·6% of faecal radioactivity. No significant amounts of radioactivity were detected in sweat collected from one subject 2 or 24 h after administration of the dose. Plasma levels of 3·32% and 1·72% of the administered dose per litre were found 1 and 24 h after administration. Metabolites in plasma were present mainly as sulphate conjugates.

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A comprehensive model of the dynamic, three-dimensional physical fates of contaminants in the marine environment has been developed. For oil spills, dissolution of aromatics from surface slicks and entrained oil droplets are the source of potential effects for biota in the water column. Oil on the surface and along shorelines provides the basis for evaluation of impacts on birds, marine mammals, and recreational activities. A graphical user interface couples the model to a variety of environmental databases and tools to facilitate specific applications and viewing of simulation results.

The immature female guinea-pig approaching first oestrus and ovulation has been studied. A clear relationship between the rate of growth of the animal and the age at puberty has been found. The 'crucial period', a time just before first oestrus, when external signs of endogenous hormonal activity give an indication of the presence of ripening follicles in the ovary, has been defined. At this time premature ovulation can be regularly induced by a single injection of gonadotrophin (guinea-pig anterior pituitary homogenate, purified luteinizing hormone or follicle-stimulating hormone). Injection of oestrogen advanced vaginal opening but, in contrast to the rat, did not cause premature ovulation.

4-14C]Ethynyloestradiol was administered to women at varying times before hysterectomy. At operation, samples of blood, adipose tissue and tissue from the reproductive tract were obtained. All tissues examined took up radioactivity, the concentration at 1 h varying from 0\m=.\22 to 0\m=.\4% of the dose per 100 g of tissue except for stroma and endometrium which showed high levels (0\m=.\68% and 0\m=.\60%,respectively). By 24 h the amount of radioactivity in the tissues had decreased markedly. Mean values for the amount of radioactivity present in total tissues at 1 h were: uterus, 0\m=.\9%; adipose tissue, 28\m=.\2%;blood, 8\m=.\8%.By 24 h these values had declined to 0\m=.\2%,6\m=.\8% and 1\m=.\6%,respectively. In adipose tissue almost all the radioactivity was present in a freely extractable state whereas in myometrium and cervix about 20 % of the radioactivity was in a conjugated form. In plasma, more than 80% of the metabolites were conjugated, mainly as sulphates. The major metabolite detected in the uterus was ethynyloestradiol itself and most of the radioactivity in the myometrium was associated with the nuclear fraction. In one pregnant subject studied, radioactivity crossed the placenta and small amounts of the dose were found in the foetus.