Studies of coagulation and fibrinolysis in normal and pregnant subjects

In this thesis, the development, refinement and standardisation of a wide range of coagulation and fibrinolytic assay techniques are described. Particular attention was directed towards the assay of Factor VIII, cryofibrinogen and fibrin/fibrinogen degradation products (F.D.P.). A new type of coagulation end point recorder was investigated and the use of the Atlas computer in the analysis of results is outlined. In addition, a study was made of various standard plasma preparations for the control of coagulation factor assays. Using these laboratory techniques, the effect of severe and moderate exercise, adrenalin infusions and beta- adrenergic receptor blockage on selected parameters of the coagulation and fibrinolytic systems, in normal volunteers, were studied. No correlations were observed between parameter changes in either system, and contrary to some reports, Factor XII was not increased post exercise. Some subjects exhibited a low fibrinolytic response to the exercise procedures, confirming previous work from this laboratory, but the coagulation response in these individuals did not appear to differ in any constant manner from the normal pattern. The adrenalin induced changes in Factor VIII were completely blocked by Propranolol, but this drug only partially lowered the response to adrenalin of plasminogen activator. The new beta -adrenergic blocker drug, ICI 50172, was fouhd to have only minimal effects on the two systems. These results are fully discussed in the light of presently available concepts of the haemostatic mechanism. In the studies on pregnant subjects, parameters of coagulation and fibrinolysis throughout the gestational period were measured. One new finding was that of a significant increase of serum F.D.P. in late pregnancy. It was also found, in another study, that the reactivity of the fibrinolytic system to an exercise stress in the third trimester was greatly impaired in some subjects. Further coagulation and fibrinolytic studies in pregnant and non -pregnant patients undergoing intra- abdominal surgical operations, demonstrated that significant changes occurred in euglobulin lysis activity, fibrinogen and F.D.P. levels. The application of specific coagulation and fibrinolytic tests to clinical haemostatic emergencies of pregnancy is described in the final section. All these studies have provided a basis for a fuller discussion in each section, of concepts such as the Shwartzman reaction, disseminated intravascular coagulation, and haemorrhage and thromboembolism. It is concluded that although some of the physio-pathologidal interrelationships of coagulation and fibrinolysis are now becoming clarified, many problems still remain, and these may only be resolved when improved methodology becomes available. The extension of work reported in this thesis may aid in the elucidation of important aspects of haemorrhage and thrombosis

Participation and quality of life outcomes among individuals with earthquake-related physical disability: a systematic review

Objective: A literature review to evaluate quality of life and participation outcomes of individuals with earthquake-related physical injury. Data sources: A systematic review was performed using National Health Service (NHS) Centre for Reviews and Dissemination (CRD) guidelines. MEDLINE, Embase, PsychINFO, CINAHL and AMED electronic databases were searched from 1966 to January 2014. Study selection: Studies that measured quality of life or participation outcomes among individuals who acquired a physical disability as a result of an earthquake injury were included, with no limits on research design. Data extraction: The search yielded 961 potentially relevant articles after removal of duplicates. Of these, only 8 articles met the inclusion criteria. Studies were rated for quality using the Critical Appraisal Skills Programme (CASP) guidelines. Data synthesis: A narrative synthesis was performed due to the heterogeneity of the included studies. Results: Injured earthquake survivors in developing countries experience diminished participation and reduced quality of life. Small sample sizes and lack of uniformity in outcome measurement limit generalizability. No studies from developed countries were identified. Conclusion: To maximize our understanding of quality of life and participation in injured earthquake survivors, future research should consider both the functional consequences of the injury and the environmental impact of the earthquake. The research should be based on representative samples of the injured earthquake survivors and use validated condition-specific outcome measures that are clearly defined within the publications. In addition, research should include all countries that are affected by earthquakes

The Hunt for the “Holy Grail”: Condensed Tannins in Perennial Forage Legumes

A recent advance using molecular biology has identified a transcription factor or master switch that can ‘turn on’ the condensed tannin pathway present in white clover, and with the appropriate promoters allows biologically significant levels of condensed tannin expression in leaf tissue. In vitro tests have demonstrated that the condensed tannins produced in white clover leaves can bind protein at a pH 6.5, as found in the rumen, and then release them at pH 2.5, the pH in the abomasum, before entering the small intestine for amino acid absorption. Additional tests have demonstrated that these condensed tannins can reduce methane production by up to 25% in the first 6 hours of incubation. The journey to this point and the challenges ahead to deliver white clover cultivars with condensed tannin expression will be described

Condensed Tannin Concentration and Herbage Accumulation of a White Clover Bred for Increased Floral Condensed Tannin

White clover is a high quality feed for ruminants, however, its high protein content results in excessive urea excretion in urine and can cause bloat, reducing its potential value for animal production. The condensed tannins (CT) in some forages can reduce these problems, but plants may have poor agronomic performance. White clover produces CT in its flower heads, but herbage CT concentrations are normally too low to benefit animals. This paper reports CT concentrations and herbage accumulation over 2 years of an experimental line of white clover (HT) selected for increased flowering and floral CT concentrations

High Floral Tannin White Clover Reduces Rumen Ammonia Concentrations in Dairy Cows

White clover produces high quality forage for ruminant production, but it results in high rumen ammonia concentrations, indicating extensive protein degradation. The excess ammonia is absorbed through the rumen and excreted as urea in urine, at a cost to the animal and the environment. Condensed tannins (CT) contained in some forages reduce proteolysis in the rumen, which can lead to increased amino acid absorption and therefore improved animal performance. White clover produces CT in its flower heads, but concentrations are normally too low to benefit animals. This paper reports on comparisons of rumen ammonia concentrations in dairy cows grazing HT (high tannin) white clover (an experimental line of white clover with increased flowering) or Grasslands Huia white clover

Orbital dynamics: The origin of the anomalous optical spectra in ferromagnetic manganites

We discuss the role of orbital degeneracy in the transport properties of perovskite manganites, focusing in particular on the optical conductivity in the metallic ferromagnetic phase at low temperatures. Orbital degeneracy and strong correlations are described by an orbital t-J model which we treat in a slave-boson approach. Employing the memory-function formalism we calculate the optical conductivity, which is found to exhibit a broad incoherent component extending up to bare bandwidth accompanied by a strong suppression of the Drude weight. Further, we calculate the constant of T-linear specific heat. Our results are in overall agreement with experiment and suggest low-energy orbital fluctuations as the origin of the strongly correlated nature of the metallic phase of manganites.Comment: To appear in: Phys. Rev. B 58 (Rapid Communications), 1 November 199

Anomalous magnetic field dependence of the thermodynamic transition line in the isotropic superconductor (K,Ba)Bi03

Thermodynamic (specific heat, reversible magnetization, tunneling spectroscopy) and transport measurements have been performed on high quality (K,Ba)BiO$_3$ single crystals. The temperature dependence of the magnetic field $H_{Cp}$ corresponding to the onset of the specific heat anomaly presents a clear positive curvature. $H_{Cp}$ is significantly smaller than the field $H_\Delta$ for which the superconducting gap vanishes but is closely related to the irreversibility line deduced from transport data. Moreover, the temperature dependence of the reversible magnetization present a strong deviation from the Ginzburg--Landau theory emphasazing the peculiar nature of the superconducting transition in this material.Comment: 4 pages, 4 figures, 28 reference

Engineering of a complex bone tissue model with endothelialised channels and capillary-like networks

In engineering of tissue analogues, upscaling to clinically-relevant sized constructs remains a significant challenge. The successful integration of a vascular network throughout the engineered tissue is anticipated to overcome the lack of nutrient and oxygen supply to residing cells. This work aimed at developing a multiscale bone-tissue-specific vascularisation strategy. Engineering pre-vascularised bone leads to biological and fabrication dilemmas. To fabricate channels endowed with an endothelium and suitable for osteogenesis, rather stiff materials are preferable, while capillarisation requires soft matrices. To overcome this challenge, gelatine-methacryloyl hydrogels were tailored by changing the degree of functionalisation to allow for cell spreading within the hydrogel, while still enabling endothelialisation on the hydrogel surface. An additional challenge was the combination of the multiple required cell-types within one biomaterial, sharing the same culture medium. Consequently, a new medium composition was investigated that simultaneously allowed for endothelialisation, capillarisation and osteogenesis. Integrated multipotent mesenchymal stromal cells, which give rise to pericyte-like and osteogenic cells, and endothelial-colony-forming cells (ECFCs) which form capillaries and endothelium, were used. Based on the aforementioned optimisation, a construct of 8 × 8 × 3 mm, with a central channel of 600 µm in diameter, was engineered. In this construct, ECFCs covered the channel with endothelium and osteogenic cells resided in the hydrogel, adjacent to self-assembled capillary-like networks. This study showed the promise of engineering complex tissue constructs by means of human primary cells, paving the way for scaling-up and finally overcoming the challenge of engineering vascularised tissues