The anatomy and physiology of the human body : containing The anatomy of the bones, muscles, and joints, and the heart and arteries /

Earlier eds. have title: The anatomy of the human body.

Doxorubicin pharmacokinetics following a single-dose infusion to sulphur-crested cockatoos (Cacatua galerita)

Objective To determine the pharmacokinetics of doxorubicin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. Design A pharmacokinetic study of doxorubicin, following a single intravenous (IV) infusion over 20 min, was performed in four healthy sulphur-crested cockatoos (Cacatua galerita). Procedure Birds were anaesthetised and both jugular veins were cannulated, one for doxorubicin infusion and the other for blood collection. Doxorubicin hydrochloride (2 mg/kg) in normal saline was infused IV over 20 min at a constant rate. Serial blood samples were collected for 96 h after initiation of the infusion. Plasma doxorubicin concentrations were assayed using an HPLC method involving ethyl acetate extraction, reverse-phase chromatography and fluorescence detection. The limit of quantification was 20 ng/mL. Established non-parametric methods were used for the analysis of plasma doxorubicin data. Results During the infusion the mean +/- SD for the C-max of doxorubicin was 4037 +/- 2577 ng/mL. Plasma concentrations declined biexponentially immediately after the infusion was ceased. There was considerable intersubject variability in all pharmacokinetic variables. The terminal (beta-phase) half-life was 41.4 +/- 18.5 min, the systemic clearance (Cl) was 45.7 +/- 18.0 mL/min/kg, the mean residence time (MRT) was 4.8 +/- 1.4 min, and the volume of distribution at steady state (V-SS) was 238 131 mL/kg. The extrapolated area under the curve (AUC(0-infinity)) was 950 +/- 677 ng/mL.h. The reduced metabolite, doxorubicinol, was detected in the plasma of all four parrots but could be quantified in only one bird with the profile suggesting formation rate-limited pharmacokinetics of doxorubicinol. Conclusions and clinical relevance Doxorubicin infusion in sulphur-crested cockatoos produced mild, transient inappetence. The volume of distribution per kilogram and terminal half-life were considerably smaller, but the clearance per kilogram was similar to or larger than reported in the dog, rat and humans. Traces of doxorubicinol, a metabolite of doxorubicin, were detected in the plasma.

A model to study intestinal and hepatic metabolism of propranolol in the dog

A model to investigate hepatic drug uptake and metabolism in the dog was developed for this study. Catheters were placed in the portal and hepatic veins during exploratory laparotomy to collect pre- and posthepatic blood samples at defined intervals. Drug concentrations in the portal vein were taken to reflect intestinal uptake and metabolism of an p.o. administered drug (propranolol), while differences in drug and metabolite concentrations between portal and hepatic veins reflected hepatic uptake and metabolism. A significant difference in propranolol concentration between hepatic and portal veins confirmed a high hepatic extraction of this therapeutic agent in the dog. This technically uncomplicated model may be used experimentally or clinically to determine hepatic function and metabolism of drugs that may be administered during anaesthesia and surgery.

Penetration of a topically applied nonsteroidal anti-inflammatory drug into local tissues and synovial fluid of dogs

Objective-To investigate penetration of a topically applied nonsteroidal anti-inflammatory drug (NSAID) into tissues and synovial fluid. Animals-5 Greyhounds. Procedure-Dogs were anesthetized and microdialysis probes placed in the dermis and gluteal muscle over each coxofemoral (hip) joint. Methylsalicylate (MeSA) was applied topically over the left hip joint. Dialysate and plasma (blood samples from the cephalic and femoral veins) were obtained during the subsequent 5 hours. Dogs were euthanatized, and tissue samples and synovial fluid were collected and analyzed for salicylic acid (SA) and MeSA by use of high-pressure liquid chromatography. Results-SA and MeSA concentrations increased rapidly (< 30 minutes after application) in dialysate obtained from treated dermis. Salicylic acid also appeared in plasma within 30 minutes and reached a plateau concentration after 2 hours, although combined drug concentrations (SA plus MeSA) in plasma obtained from femoral vein samples were twice those measured in plasma obtained from the cephalic vein (SA only). Treated muscle had a progressive decrease in NSAID concentration with increasing depth (SA and MeSA), but it was significantly higher than the concentration in untreated muscle. Substantial amounts of SA and MeSA were also measured in synovial fluid of treated joints. Conclusions and Clinical Relevance-Topically applied NSAIDs can penetrate deeply into tissues and synovial fluid. Local concentrations higher than circulating systemic concentrations are suggestive that direct diffusion and local blood redistribution are contributing to this effect. Systemic blood concentrations may be inadequate to describe regional kinetics of topically applied drugs.

Microchemistry and microstructures of hydrothermally altered shock-metamorphosed basement gneiss, Woodleigh impact structure, Southern Carnarvon Basin, Western Australia

Hydrothermally altered shock-metamorphosed gneisses consisting of relic igneous biotite-K-feldspor-Na-rich alkali feldspar - plagioclase - quartz assemblages ( accessory garnet, corundum, titanite, monazite, zircon), and showing extensive replacement by montmorillonite, illite, sericite, and to a lesser extent chlorite, calcite, epidote, zoisite and pyrite, occur in the basement core uplift of the Woodleigh impact structure, Western Australia. The rocks display extensive hydrothermal clay alteration, complicating identification of pre-hydrothermal and pre-impact textures and compositions. Analysis of quartz-hosted planar deformation features (PDFs) indicates a majority of indexed sets parallel to omega{10 (1) over bar3}, a lesser abundance of sets parallel to pi{10 (1) over bar2}, and some sets parallel to the basal plane (0001) and r,z {10 (1) over bar1}, consistent with pressures about or over 20 GPa. Feldspar-hosted FDFs form reticulate vein networks displaying checkerboard-like to irregular and serrated patterns attributable to preferential replacement of shock-damaged PDFs and/or perthitic twin lamella by clay minerals. The gneisses are pervaded by clay-dominated intergranular and intragranular veins of cryptocrystalline material that display marked departures from bulk-rock chemistry and from mineral compositions. XRD analysis identifies the cryptocrystalline components as illite - montmorillonite, illite and chlorite, while laser Raman analysis identifies high-fluorescence sub-micrometre clay assemblage, feldspar, quartz and minor mica. SEM/EDS-probe and laser-ICPMS analysis indicate low-K high-Mg clay mineral compositions consistent with montmorillonite. Quartz PDF-hosted cryptocrystalline laminae display distinct enrichments in Al, Mg, Ca and K. Altered intergranular veins and feldspar-hosted cryptocrystalline components show consistent enrichment in the relatively refractory elements (Al, Cc, Mg, Fe) and depletion in relatively volatile elements (Si, K, Na). The clay alteration retards determination whether clay-dominated vein networks represent altered shock-induced pseudotachylite veins, diaplectic zones and/or shock-damaged twin lamella, and/or result from purely mineralogical and chemical differentiation affected by hydrothermal fluids, Overall enrichment of the shocked gneiss and of the cryptocrystalline components in Mg and trace ferromagnesian elements (Ni, Cc, Cr) may be attributed alternatively to introduction of siderophile element-rich fluid from the projectile, or/and contamination of hydrothermal fluids by MgO from dolomites surrounding the basement uplift. High Ni/Co and Ni/Cr and anomalous DGE (platinum group elements) may support the former model.

Trends in morphine prescriptions, illicit morphine use and associated harms among regular injecting drug users in Australia

This paper examines population trends in morphine prescriptions in Australia, and contrasts them with findings from annual surveys with regular injecting drug users (IDU). Data on morphine prescriptions from 1995 to 2003 were obtained from the Drug Monitoring System (DRUMS) run by the Australian Government Department of Health and Ageing. Data collected from regular IDU as part of the Australian Illicit Drug Reporting System (IDRS) were analysed (2001-2004). The rate of morphine prescription per person aged 15-54 years increased by 89% across Australia between 1995 and 2003 (from 46.3 to 85.9 mg per person). Almost half (46%) of IDU surveyed in 2004 reported illicit morphine use, with the highest rates in jurisdictions where heroin was less available. Recent morphine injectors were significantly more likely to be male, unemployed, out of treatment and homeless in comparison to IDU who had not injected morphine. They were also more likely to have injected other pharmaceutical drugs and to report injection related problems. Among those who had injected morphine recently, the most commonly reported injecting harms were morphine dependence (38%), difficulty finding veins into which to inject (36%) and scarring or bruising (27%). Morphine use and injection is a common practice among regular IDU in Australia. In some cases, morphine may be a substitute for illicit heroin; in others, it may be being used to treat heroin dependence where other pharmacotherapies, such as methadone and buprenorphine, are perceived as being unavailable or undesirable by IDU. Morphine injection appears to be associated with polydrug use, and with it, a range of problems related to drug injection. Further research is required to monitor and reduce morphine diversion and related harms by such polydrug injectors.

Zinc deposits and related mineralization of the Burketown mineral field, including the world-class Century Deposit, Northern Australia: Fluid inclusion and stable isotope evidence for basin fluid sources

The stratiform Century Zn-Pb deposit and the discordant Zn-Pb lode deposits of the Burketown mineral field, northern Australia, host ore and gangue minerals with primary fluid inclusions that have not been affected by the Isan orogeny, thus providing a unique opportunity to investigate the nature of the ore-forming brines. All of the deposits are hosted in shales and siltstones belonging to the Isa superbasin and comprise sphalerite, pyrite, carbonate, quartz, galena, minor chalcopyrite, and minor illite. According to Pb model ages, the main ore stage of mineralization at Century formed at I575 Ma, some 20 m.y. after deposition of the host shale sequence. Microthermometry on undeformed, primary fluid inclusions hosted in porous sphalerite shows that the Zn at Century was transported to the deposit by a homogeneous, Ca2+- and Na+-bearing brine with a salinity of 21.6 wt percent NaCl equiv. delta D-fluid of the fluid inclusion water ranges from -89 to -83 per mil, consistent with a basinal brine that evolved from meteoric water. Fluid inclusion homogenization temperatures range between 74 degrees and 125 degrees C, which are lower than the 120 degrees to 160 degrees C range calculated from vitrinite reflectance and illite crystallinity data from the deposit. This discrepancy indicates that mineralization likely formed at 50 to 85 Mpa, corresponding to a depth of 1,900 to 3,100 m. Transgressive galena-sphalerite veins that cut stratiform mineralization at Century and breccia-filled quartz-dolomite-sphalerite-galena veins in the discordant Zn-Pb lodes have Pb model ages between 1575 and 1485 Ma. Raman spectroscopy and microthermometry reveal that the primary fluid inclusions in these veins contain Ca2+, Na+. but they have lower salinities between 23 and 10 wt percent NaCl equiv and higher delta D-fluid values ranging from -89 to -61 per mil than fluid inclusions in porous sphalerite from Century. Fluid inclusion water from sphalerite in one of the lode deposits has delta O-18(fluid) values of 1.6 and 2.4 per mil, indistinguishable from delta O-18(fluid) values between -0.3 to +7.4 per mil calculated from the isotopic composition of coexisting quartz, dolomite, and illite. The trend toward lower salinities and higher delta D-fluid values relative to the earlier mineralizing fluids is attributed to mixing between the fluid that formed Century and a seawater-derived fluid from a different source. Based on seismic data from the Lawn Hill platform and paragenetic and geochemical results from the Leichhardt River fault trough to the south, diagenetic aquifers in the Underlying Calvert superbasin appear to have been the most likely sources for the fluids that formed Century and the discordant lode deposits. Paragenetically late sphalerite and calcite cut sphalerite, quartz, and dolomite in the lode deposits and contain Na+-dominated fluid inclusions with much lower salinities than their older counterparts. The isotopic composition of calcite also indicates delta O-18(fluid) from 3.3 to 10.7 per mil, which is larger than the range obtained from synmineralization minerals, supporting the idea that a unique fluid source was involved. The absolute timing of this event is unclear, but a plethora of Pb model, K-Ar, and Ar-40/Ar-39 ages between 1440 and 1300 Ma indicate that a significant volume of fluid was mobilized at this time. The deposition of the Roper superbasin from ca. 1492 +/- 4 Ma suggests that these late veins formed from fluids that may have been derived from aquifers in overlying sediments of the Roper superbasin. Clear, buck, and drusy quartz in veins unrelated to any form of Pb-Zn mineralization record the last major fluid event in the Burketown mineral field and form distinct outcrops and ridges in the district. Fluid inclusions in these veins indicate formation from a low-salinity, 300 degrees +/- 80 degrees C fluid. Temperatures approaching 300 degrees C recorded in organic matter adjacent to faults and at sequence boundaries correspond to K-Ar ages spanning 1300 to 1100 Ma, which coincides with regional hydrothermal activity in the northern Lawn Hill platform and the emplacement of the Lakeview Dolerite at the time of assemblage of the Rodinia supercontinent.

The fountain amacrine cells of the rabbit retina

We have characterized a distinctive type of bistratified amacrine cell in the rabbit retina at both the single cell and population levels. These cells correspond to the fountain amacrine cells recently identified by MacNeil and Masland (1998). The fountain cells can be distinguished in superfused retinal wholemounts labeled with nuclear dyes, thus enabling them to be targeted for intracellular injection with Neurobiotin. This revealed that the primary dendrites ascend steeply to sublamina b of the inner plexiform layer, where they form an irregular arbor at the border of strata 4 and 5. These dendrites then give rise to multiple varicose processes that descend obliquely to sublamina a, where they form a more extensive arbor in stratum 1. The fountain amacrine cells show strong homologous tracer coupling when injected with Neurobiotin, and this has enabled us to map their density distribution across the retina and to examine the dendritic relationships between neighboring cells. The fountain amacrine cells range in density from 90 to 360 cells/mm(2) and they account for 1.5% of the amacrine cells in the rabbit retina. The thick tapering dendrites in sublamina b form highly territorial arbors that tile the retina with minimal overlap, whereas the thin varicose processes intermingle in sublamina a. The fountain cells are immunopositive for gamma-aminobutyric acid and immunonegative for glycine. We further propose that these cells are homologous to the substance P-immunoreactive (SP-IR) amacrine cells in the cat retina and that they may account for a subset of the SP-IR amacrine cells in the rabbit retina.

Free radical reactions in atherosclerosis; An EPR spectrometry study

The copper catalysed oxidation of homocysteine has been studied by electron paramagnetic resonance (EPR) spectroscopy and spin trapping techniques to determine the nature of free radical species formed under varying experimental conditions. Three radicals; thiyl, alkyl and hydroxyl were detected with hydroxyl being predominant. A reaction mechanism is proposed involving Fenton chemistry. Inclusion of catalase to test for intermediate generation of hydrogen peroxide showed a marked reduction in amount of hydroxyl radical generated. In contrast, the addition of superoxide dismutase showed no significant effect on the level of hydroxyl radical formed. Enhanced radical formation was observed at higher levels of oxygen, an effect which has consequences for differential oxygen levels in arterial and venous systems. Implications are drawn for a higher incidence of atherosclerotic plaque formation in arteries versus veins. © 2006 - IOS Press and the authors. All rights reserved.

The geochemistry of the sedimentary rocks of the Harlech Dome, North Wales

Bedrock geochemical analysis, coupled with detailed data analysis, was carried out on some 260 samples taken from two areas of 'the Harlech Dome, near Dolgellau, North Wales. This was done to determine if rocks from mineralised and non-mineralised areas could be distinguished, and to determine mineralisation types and wall rock alterations. The Northern Area, near Talsarnau, has no recorded mineralisation, while the Southern Area, near Bontddu, has been exploited for gold. The rocks sampled, in both areas, were from the Cambrian Gamlan Flags, Clogau Shales, Vigra Flags, later vein materials, and igneous intrusions. All samples were analysed, using a new rapid, atomic absorption spectrophotometric technique, for Si, AI, Fe, Cu, Ni, Zn, Pb, Sr, Hg, and Ba. In addition 60 samples were analysed by X-ray fluorescence for Mn, Ti, Ca, K, Na, P, Cr, Ce, La, S, Y , Rh, and Th. Total CO2 was determined, on selected samples, using a combustion technique. Elemental distributions, for each rock type, in each area, were· plotted, and means, standard deviations, and enrichment indices were calculated. Multivariate statistical analysis on the results distinguished a Cu-type mineralisation in the Northern area, and both Cu and Pb/Zn types in the Southern Area. It also showed the Northern Area to be less strongly mineralised than the Southern one in which both mineralisation types are associated with wall rock alteration. Elemental associations and trends due to sedimentary processes were distinguished from those related to mineralisation. Hg is related to mineralisation, and plots of factor scores, on the sampling grid, produced clusters of mineralisation related factors in areas of known mineralisation. A double Fourier Trend Analysis program, with a wavelength search routine, was developed and used to recognise sedimentary trends for Sr. Y., Rb, and Th. These trends were interpreted to represent areas of low pH and reducing conditions. They also indicate that the supply of sediment remained constant over Gamlan, Clogau, and Vigra times. The trend surface of Hg showed no association with rock type. It is shown that analysis of a small number of samples, for a carefully selected number of elements, with detailed data analysis, can provide more useful information than analysis of a large number of samples for many elements. The mineralisation is suggested to have been the result of water solutions leaching ore metals from the sedimentary rocks and redepositing them in veins.

The relationship of mineralization to petrology at Parys Mountain, Anglesey

The Lower Palaeozoic succession at Parys Mountain overlies a Precambrian basement (the Iona Series). This succession consists of Ordovician slates, overlain by, and in part interbedded with, Ordovician dacitic and rhyolitic volcanics, which in turn are unconformably overlain by Silurian slates. Both basement and Palaeozoic rocks have been deformed during Caledonian and Variscan orogenies. The resultant structure of Parys Mountain is interpreted as an east-north-easterly trending, single syncline overturned to the north. Many primary extrusive characters are retained by the volcanic rocks, despite the high degree of deformation. The lithologies and textures allow subdivision and interpretation of these rocks as dacite, lithic tuff, siliceous sinter, rhyolitic tuff, rhyolitic ignimbrite, rhyolitic tuff-lava, and rhyolitic lava. The results of 61 bulk chemical analyses are interpreted to show that the volcanism was of the orogenic calc-alkaline type from a continental margin/island arc environment. The magmas probably result from either partial melting of the crustal part of the oceanic lithosphere on a Benioff zone, or partial melting of the mantle, above a Benioff zone, under high load pressures and high water pressures. The mineral deposits are largely confined within the volcanic succession though some occur in the Ordovician and Silurian slates near to their contacts with the volcanics. The majority of the deposits form conformable lenses and tabular bodies, with subordinate deposits as veins and stockworks. The ore mineral assemblages are of chalcopyrite, galena, sphalerite, and pyrite. The general paragenetic sequence (73 sections) is pyrite--chalcopyrite--galena-sphalerite. The main mineralization episode is interpreted to be syngenetic, genetically related to the volcanism. The veins and stockworks probably result from Caledonian and Variscan remobilization of the primary mineralization. Trace element analyses (Cu, Zn, Pb, Ni, Co, Cd, Cr, Hg, Ba, Sr), on 350 specimens, detected anomalous concentrations of these elements around the mineralized zones, though some occur where no mineralization was found. The analyses also indicate a close relationship between the mineralization and the volcanic horizons, especially the siliceous sinter.

Diagenetic processes in ore formation with special reference to the Zambian copperbelt and permian marl slate.

This thesis is concerned with the role of diagenesis in forming ore deposits. Two sedimentary 'ore-types' have been examined; the Proterozoic copper-cobalt orebodies of the Konkola Basin on the Zambian Copperbelt, and the Permian Marl Slate of North East England. Facies analysis of the Konkola Basin shows the Ore-Shale to have formed in a subtidal to intertidal environment. A sequence of diagenetic events is outlined from which it is concluded that the sulphide ores are an integral part of the diagenetic process. Sulphur isotope data establish that the sulphides formed as a consequence of the bacterial reduction of sulphate, while the isotopic and geochemical composition of carbonates is shown to reflect changes in the compositions of diagenetic pore fluids. Geochemical studies indicate that the copper and cobalt bearing mineralising fluids probably had different sources. Veins which crosscut the orebodies contain hydrocarbon inclusions, and are shown to be of late diagenetic lateral secretion origin. RbiSr dating indicates that the Ore-Shale was subject to metamorphism at 529 A- 20 myrs. The sedimentology and petrology of the Marl Slate are described. Textural and geochemical studies suggest that much of the pyrite (framboidal) in the Marl Slate formed in an anoxic water column, while euhedral pyrite and base metal sulphides formed within the sediment during early diagenesis. Sulphur isotope data confirm that conditions were almost "ideal" for sulphide formation during Marl Slate deposition, the limiting factors in ore formation being the restricted supply of chalcophile elements. Carbon and oxygen isotope data, along with petrographic observations, indicate that much of the calcite and dolomite occurring in the Marl Slate is primary, and probably formed in isotopic equilibrium. A depositional model is proposed which explains all of the data presented and links the lithological variations with fluctuations in the anoxicioxic boundary layer of the water column.

Localisation of members of the vascular endothelial growth factor (VEGF) family and their receptors in human atherosclerotic arteries

Background: Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. The existence of single or multiple VEGF isoforms and receptors suggests that these proteins may have overlapping but distinct functions, which may be reflected in their cell expression and distribution. Methods: The localisation of VEGFs A–C and their receptors (VEGFRs 1–3, respectively) in 30 fresh human atherosclerotic arteries, 15 normal uterine arteries, and 15 saphenous veins using immunohistochemistry and western blotting. Results: Saphenous veins showed no staining for VEGF-B or VEGFR-2. Smooth muscle cells (SMCs) showed the strongest staining for VEGF-A, VEGF-B, VEGFR-1, and VEGFR-2 in all specimens. Conversely, VEGFR-3 and VEGF-C were predominately localised to the endothelial vasa vasorum in normal arteries, whereas medial SMCs showed the strongest staining in atherosclerotic arteries. Western blotting showed variations in VEGF protein localisation, with lower amounts of VEGF-B and VEGF-C in saphenous veins, compared with arterial tissue. Amounts of VEGF-C were lower than those of VEGF-A and VEGF-B in all specimens. Conclusion: This study provides direct evidence of the presence of VEGF proteins and receptors in human physiology and pathology, with variations in both the amounts of VEGF proteins expressed and their cellular distribution in normal arteries compared with atherosclerotic arteries. The presence of VEGFs A–C and their receptors in normal arterial tissue implies that VEGF functions may extend beyond endothelial cell proliferation. Reduced VEGFR-2 staining in atherosclerotic arteries may have implications for the atherosclerosis process and the development of vascular disease and its complications.

Ageing effect on flicker-induced diameter changes in retinal microvessels of healthy individuals

Purpose: To compare flicker-induced retinal vessel diameter changes in varying age groups with low cardiovascular risk. Methods: Retinal vascular reactivity to flicker light was assessed by means of dynamic retinal vessel analysis in 57 participants aged 19-30 years, 75 participants aged 31-50 years and 62 participants aged 51-70 years participants. Other assessments included carotid intima-media thickness (c-IMT), augmentation index (AIx), blood pressure profiles, blood lipid metabolism markers and Framingham risk scores (FRS). Results: Retinal arterial dilation amplitude (DA) and postflicker percentage constriction (MC%) were significantly decreased in the oldest group compared to the middle-aged (p = 0.028; p = 0.021) and youngest group (p = 0.003; p = 0.026). The arterial constriction slope (SlopeAC) was also decreased in the oldest group compared to the youngest group (p = 0.027). On the venous side, MC% was decreased in the middle-aged and oldest groups in comparison with the youngest group (p = 0.015; p = 0.010, respectively). Additionally, men exhibited increased arterial DA (p = 0.007), and percentage dilation (MD%, p < 0.001) in comparison with women, but only in the youngest age group. Both AIx and c-IMT scores increased with age (both p < 0.001); however, no correlations were found between the observed differences in the measured retinal vascular function and systemic parameters. Conclusion: In individuals with low cardiovascular risk, there are age-related differences in flicker-induced retinal vessel diameter changes throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the arterial dilatory phase and are only present in young individuals.

Retinal vascular function and cardiovascular risk factors

The current platform of conventional cardiovascular risk assessments tends to forsake the importance of endothelial function - a key biological mechanism by which cardiovascular risk factors exert their propensity for adverse vascular events. Moreover, the presence and severity of endothelial dysfunction in ‘low-risk’ individuals suggests considerable variability in pre-clinical risk that could potentially be detected well before the onset of disease. The aim of the present thesis was to investigate the presence and impact of retinal vascular dysfunction, as a barometer of endothelial function, in otherwise healthy individuals with one or more cardiovascular risk factors, but low to moderate cardiovascular risk. Systemic circulatory influences on retinal vascular function were also evaluated. The principle sections and findings of this work are: 1. Ageing effect on retinal vascular function • In low-risk individuals, there are age differences in retinal vascular function throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the dilatory phase and are only present in young individuals. 2. Retinal vascular function in healthy individuals with a family history of cardiovascular disease • In low-risk individuals with a family history of cardiovascular disease, impairments in microvascular function at the retinal level correlate with established plasma markers for cardiovascular risk. 3. Ethnic differences in retinal vascular function • When compared to age-matched White Europeans, in low-risk middle-aged South Asians, there are impairments in retinal vascular function that correlate with established cardiovascular risk indicators. 4. Systemic circulatory influences on retinalµvascular function • Systemic antioxidant capacity (redox index) and plasma markers for cardiovascular risk (lipids) influence retinal microvascular function at both arterial and venous levels. 5. Retinal vascular function in individuals with obstructive sleep apnoea: a preliminarystudy • Patients with moderate to severe sleep apnoea exhibit attenuated retinal vascular function.