An Investigation of the Kinetics of Co-trifamole, Co-trimoxazole, Trimethoprim Alone and Clavulanate Potentiated Ticarcillin with Consideration of the Prediction of Plasma Drug Concentration

This thesis has examined aspects of the pharmcokinetics and assay of some antimicrobial chemotherapeutic agents with particular reference to the kinetics of fixed dose combinations and methods of predicting plasma concentration. An extracted diazotisation procedure for the assay of sulphonamides was evaluated and found to be satisfactory for estimation of both serum and urine concentrations. An analytical procedure was devised for the liquid chromatographic determination of trimethoprim and was used to conduct pharmacokinetic studies of trimethoprim in serum, urine, saliva and sputum. The disposition of trimethoprim and sulphonamide following the use of the fixed dose trimethoprim / sulphonamide combinations co-trimoxazole and co-trifamole were determined; the kinetics of sulphamethoxazole and sulphamoxole, the constituent sulphonamides, and trimethoprim were compared; for sulphamoxole this was the first full charaterisation of its kinetics. From the ratios of trimethoprim to either of the sulphomamides it was evident that the ratios achieved in urine were notably inferior to those found in vitro to have synergistic effect. Interpolation of these results with the clinical, bacteriological and pharmacokinetic findings of other workers strongly suggested that trimethoprim alone should be an effective treatment in uncomplicated urinary tract infection. A comparison of two trimethoprim formulations with different dosing schedules showed equivalent bioavailability and urine trimethoprim levels likely to be effective against susceptible organisms. A relationship between urinary trimethoprim concentrations and urine pH was noted. However serum concentrations were found to fall below the minimum inhibitory concentrations when the dosage schedule for 300 mg trimethoprim once daily was used; the 200 mg twice daily regimen was found to give rise to more acceptable plasma concentrations. Saliva concentrations of trimethoprim were obtained simultaneously with serum concentrations to allow consideration of the relationship between drug concentrations in these fluids for a drug which is highly ionized at physiological serum and saliva pH. Trimethoprim was an ideal probe for such an investigation, association between saliva and serum concentrations was established and there was a non-linear correlation between saliva flow rate and hydrogen-ion concentration. The prediction of serum trimethoprim concentrations from saliva concentration read from the regression line with observed serum concentration, was compared with a predictive equation based upon the Henderson-Hasselbalch equation and was found to be superior. In a double blind trial of trimethoprim and ampicillin in a general practice study of treatment of exacerbations of chronic bronchitis, the levels of trimethoprim in sputum were compared with clinical and bacteriological cure. There was no clear relationship but sputum trimethoprim levels well in excess of the minimum inhibitory concentration of sensitive organisms were shown to be acheived. The study demonstrated that trimethoprim was as effective as ampicillin in the treatment of exacerbations of chronic bronchitis. A further examination of prediction of serum trimethoprim concentration, using the data from the bioequivalence study was undertaken, using a computer programme, OPT. The programme uses Bayesian forecasting with estimates of maximum likelihood. The precision and bias of forecasts of future serum concentration were acceptable provided care was exercised in interpretation this would require a user having an appreciation of kinetic principles. Liquid chromatographic assays were developed for the determination of clavulanic acid and the isomers of ticarcillin in serum and urine. These assays were applied to the investigation of the kinetics of the combination of these drugs in subjects with various degrees of renal failure and undergiong dialysis. Both drugs showed notable renal clearance and their serum clearances decreased with increasing renal impairment, however the clearance of clavulanic acid in anephric subjects was greater than anticipated and it is postulated that this may be due to induction of metabolism. Haemodialysis cleared both drugs more efficiently than continuous ambulatory peritoneal dialysis, the former was associated with significant rebound levels of ticarcillin on cessation of dialysis. From the observed kinetics a dosing scheme for the administration of the ticarcillin/clavulanic acid combination was proposed. The limitations of current pharmacokinetic models and investigations are discussed and the relationship between antimicrobial and antineoplastic chemotherapy considered. It is anticipated that intracellular aspects of chemotherapy may be usefully examined

Determining Hybridization in Jack Pine and Lodgepole Pine from British Columbia

This study was conducted to find wood quality evidence of hybridization between jack pine (Pinus banksiana) and lodgepole pine (Pinus contorta var. latifolia) in northeast British Columbia (BC). To determine if wood and fiber traits could be used as distinguishing features among jack pine, lodgepole pine, and their hybrids, differences in morphology and wood and fiber traits were related to the genetic identity of each sample. Thirty samples each of pure lodgepole pine, pure jack pine, and potential hybrids were collected from the Prince George area of BC, the Smoky Lake area of Alberta, and the Fort Nelson region of BC, respectively. Two 10-mm cores (bark to bark) were taken from each tree and analyzed for fiber length and coarseness, microfibril angle (MFA), basic density, earlywood:latewood ratios, and cell dimensions. Needle and cone morphology was used to distinguish among species groups in the field. Based on genetically identified samples, the fiber traits that best differentiated among pure jack pine, lodgepole pine, and hybrids were MFA and cell area

Economic Review of Pasture Development Options for North Australian Beef Enterprises

Beef cattle grazing (~14 million head) native pastures is the dominant economic use of northern grazing lands (2.3 million km2). Few enterprises make positive economic returns in most years or achieve the necessary productivity gains (~2% per annum) to offset an ongoing cost-price squeeze (McCosker et al., 2010). A significant contributor to poor performance is low reproductive performance, management of first calving heifers, calf growth and weaning rates and liveweight gain - linked to nutrition and the low quality of pastures. Pasture development technologies (Gramshaw and Walker, 1988) are available but uptake has been poor. Three pasture development options offering technical promise include (a) mosaic irrigation - small-scale schemes utilising favourable soils and access to water, (b) broad-scale over-sowing of native pastures with improved grasses and legumes, (c) high intensity-short duration (cell) grazing and (c) increasing stock access to underutilised pasture resources by expanding water and fencing infrastructure. How these options might alter the economic performance of enterprises has received limited attention. A formal review employed simulation models and regional case studies to explore the scope for mosaic irrigation to change the production and marketing orientation of northern beef enterprises and deliver economic benefits (MacLeod et al., 2013). Consideration was also given to alternative development options viz. broad-scale pasture sowing, high intensity-short duration (cell) grazing, and additional water and fencing infrastructure. The economic results of these options for three of the regional case studies are summarised in this paper

GaN directional couplers for integrated quantum photonics

Large cross-section GaN waveguides are proposed as a suitable architecture to achieve integrated quantum photonic circuits. Directional couplers with this geometry have been designed with aid of the beam propagation method and fabricated using inductively coupled plasma etching. Scanning electron microscopy inspection shows high quality facets for end coupling and a well defined gap between rib pairs in the coupling region. Optical characterization at 800 nm shows single-mode operation and coupling-length-dependent splitting ratios. Two photon interference of degenerate photon pairs has been observed in the directional coupler by measurement of the Hong-Ou-Mandel dip with 96% visibility.Comment: 4 pages, 5 figure

Temperature-dependent efficiency droop of blue InGaN micro-light emitting diodes

Temperature-dependent trends in radiative and Auger recombination coefficients have been determined at different injection carrier concentrations using InGaN micro-light emitting diodes 40 μm in diameter. The differential lifetime was obtained first from the measured modulation bandwidth and was then employed to calculate the carrier concentration in the quantum well active region. When the temperature increases, the carrier concentration increases, but both the radiative and Auger recombination coefficients decrease. In addition, the temperature dependence of radiative and Auger recombination coefficients is weaker at a higher injection carrier concentration, which is strongly related to phase space filling

Aging characteristics of blue InGaN micro-light emitting diodes at an extremely high current density of 3.5kAcm−2

The aging characteristics of blue InGaN micro-light emitting diodes (micro-LEDs) with different sizes have been studied at an extremely high current density 3.5 kA cm−2 for emerging microLED applications including visible light communication (VLC), micro-LED pumped organic lasers and optogenetics. The light output power of micro-LEDs first increases and then decreases due to the competition of Mg activation in p-GaN layer and defect generation in the active region. The smaller micro-LEDs show less light output power degradation compared with larger micro-LEDs, which is attributed to the lower junction temperature of smaller micro-LEDs. It is found that the high current density without additional junction temperature cannot induce significant micro-LED degradation at room temperature but the combination of the high current density and high junction temperature leads to strong degradation. Furthermore, the cluster LEDs, composed of a micro-LED array, have been developed with both high light output power and less light output degradation for micro-LED applications in solid state lighting and VLC

Incomplete renal tubular acidosis as a predisposing factor for calcium phosphate stones in neuropathic bladder: a case report

We present a male tetraplegic patient, who developed stones in neuropathic bladder six times within a span of three years. Unusual features of this case are: (1) This patient started developing stones in urinary bladder thirteen years after sustaining spinal cord injury. (2) He was performing intermittent catheterisation and did not have an indwelling catheter. (3) The presenting symptom of vesical lithiasis was abdominal spasms and not urine infection. (4) The major component of the stones was calcium phosphate; magnesium ammonium phosphate was completely absent in the calculus on four occasions. (5) Proteus species were not grown from urine at any time. (6) This patient failed to acidify urine below a pH of 5.3 after taking simultaneously furosemide (40 mg) and fludrocortrisone (1 mg), which suggested incomplete renal tubular acidosis type 1

Active-matrix GaN micro light-emitting diode display with unprecedented brightness

Displays based on microsized gallium nitride light-emitting diodes possess extraordinary brightness. It is demonstrated here both theoretically and experimentally that the layout of the n-contact in these devices is important for the best device performance. We highlight, in particular, the significance of a nonthermal increase of differential resistance upon multipixel operation. These findings underpin the realization of a blue microdisplay with a luminance of 10⁶ cd/m²

High speed spatial encoding enabled by CMOS-controlled micro-LED arrays

Arrays of GaN light-emitting diodes can be used for rapid display of pattern sequences or high speed parallel data transmission using different sites of the array. These operation modes can be combined with each other and are useful for light- fidelity networks with Gb/s capacity

Clone stories: ‘shallow are the souls that have forgotten how to shudder’

This article explores literary interrogations of the bioethical implications of cloning. It does so by outlining the basic science of cloning before going on to question the dominance of the Freudian notion of the ‘uncanny’ in the critical theoretical responses to cloning by figures such as Jean Baudrillard and Slavoj Žižek. The second half of the article turns to two recent novels exploring the theme of cloning: Eva Hoffman's The Secret, and Kazuo Ishiguro's Never Let Me Go. It is argued that the former rehearses familiar themes of revulsion connected to the figure of the clone, yet resolves the struggle for identity in a ‘human’ conclusion; whereas the latter maintains the uncanny in-human difference of the clone even as it highlights the dangers of the biopolitical instrumentalization of life itself. The article therefore argues that fictional treatments of cloning can provide an important alternative to simplified debates on the subject in the mass media