Biomedical subjects

Mark Saunders

Publications and source records attributed to Mark Saunders.

6 recordsLinked to original sources

PubMed2006

The reaction products of the 193 nm photolysis of vinyl bromide and vinyl chloride studied by time-resolved Fourier transform infrared emission spectroscopy.

Time-resolved Fourier transform infrared (TRFTIR) emission spectroscopy has been used to study the 193 nm photolysis of vinyl bromide (C(2)H(3)Br) and vinyl chloride (C(2)H(3)Cl). Time-resolved IR emission was analysed to obtain nascent vibrational state populations of two primary photolysis products: HBr (v = 1-7) and HCl (v = 1-6). In both cases the nascent vibrational state populations monotonically decrease with increasing v and are in excellent agreement with previously published data. Time-resolved populations were analysed to yield rate constants for vibrational relaxation of HBr (v = 1-3) and HCl (v = 1-4) by parent vinyl bromide and vinyl chloride, respectively. In both cases the rate constants were found to increase with increasing vibrational quantum number, in agreement with a single quantum de-excitation via vibrational to vibrational energy transfer. Butadiene (C(4)H(6)) was identified as a secondary product of the photolysis of both vinyl halides, and shown to be formed from the reaction of parent vinyl halide with the vinyl radical. The presence of a buffer gas was found to produce a strong emission feature centred at 2,200 cm(-1), the intensity of which was dependent on the pressure of the buffer gas used, and whose kinetics are indicative of a secondary reaction product. We propose that this emission is from the vibrational progression of the electronic transition A(0, v, 1) --> X(0, v, 2) in the secondary reaction product C(2)H, whose formation route is favoured by the presence of buffer gas.

Journal Article↗

PubMed2006

Vaccination of colorectal cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) induces immune responses which correlate with disease control: a phase I/II trial.

PURPOSE: The highly attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA), encoding the tumor antigen 5T4 (termed TroVax), has been evaluated in an open-label phase I/II study in colorectal cancer patients. The primary objectives were to assess the safety and immunogenicity of ascending doses of TroVax and to determine the biodistribution of the vector. EXPERIMENTAL DESIGN: TroVax was given to 22 patients with metastatic colorectal cancer. Seventeen patients received doses of TroVax ranging from 5 x 10(7) up to 5 x 10(8) plaque-forming units at 0, 4, and 8 weeks and were considered to be evaluable for assessment of immunologic responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector were monitored throughout the study. RESULTS: TroVax was well tolerated in all patients with no serious adverse events attributed to vaccination. Of 17 evaluable patients, 16 showed 5T4-specific cellular responses whereas 14 had detectable antibody levels following vaccination. TroVax was able to boost 5T4-specific immune responses in the presence of MVA neutralizing antibodies. Periods of disease stabilization ranging from 3 to 18 months were observed in five patients, all of whom mounted 5T4-specific immune responses. Furthermore, statistical analysis showed a positive association between the development of a 5T4 (but not MVA) antibody response and patient survival or time to disease progression. CONCLUSION: These data indicate that vaccination with TroVax is safe and well tolerated and that immune responses to 5T4 can be induced without any evidence of autoimmune toxicity. Furthermore, 5T4-specific antibody responses correlate with evidence of disease control.

Adjuvants, Immunologic↗

PubMed2006

HyperDSC studies of amorphous polyvinylpyrrolidone in a model wet granulation system.

Measurements of the properties of amorphous materials are very important to help in the understanding of how materials behave during manufacture, storage and use of medicines. However, there are few methods that are suited to the study of amorphous materials, especially if in multi-component systems or model formulations. The goal here was to explore the potential for the use of HyperDSC to study a model granulation system. It was found that the sensitivity of HyperDSC was such that the glass transition (Tg) of polyvinylpyrrolidone (PVP) could be detected in granules made with realistic levels of this binder. The measured Tg in the granules, even after drying, was very different to that of PVP alone and to PVP in physical mixtures with lactose. It is argued that the granulation process has resulted in the dissolution of some lactose and that the amorphous binder holding the granules together is in fact a solid dispersion of PVP and lactose. Based on the standard Gordon-Taylor equation it was estimated that the solid dispersion contained 50% of PVP and lactose. Given that solid dispersions have a tendency to crystallise on storage, it could be expected that changes in the binder properties will occur with time after granulation. We believe that this is the first measurement of in situ properties of a binder in this way and opens the possibility of studies on formulated systems.

Calorimetry, Differential Scanning↗

PubMed2006

Decoupling the direct and indirect effects of nitrogen deposition on ecosystem function.

Elevated nitrogen (N) inputs into terrestrial ecosystems are causing major changes to the composition and functioning of ecosystems. Understanding these changes is challenging because there are complex interactions between 'direct' effects of N on plant physiology and soil biogeochemistry, and 'indirect' effects caused by changes in plant species composition. By planting high N and low N plant community compositions into high and low N deposition model terrestrial ecosystems we experimentally decoupled direct and indirect effects and quantified their contribution to changes in carbon, N and water cycling. Our results show that direct effects on plant growth dominate ecosystem response to N deposition, although long-term carbon storage is reduced under high N plant-species composition. These findings suggest that direct effects of N deposition on ecosystem function could be relatively strong in comparison with the indirect effects of plant community change.

Ecosystem↗

PubMed2004

The potential of high speed DSC (hyper-DSC) for the detection and quantification of small amounts of amorphous content in predominantly crystalline samples.

The purpose of this study was to explore whether it is possible to use hyper differential scanning calorimetry (HDSC) to detect and quantify low levels of amorphous content in samples that are mostly crystalline. HDSC uses scan rates that are much faster than conventional DSC, and consequently results in greater sensitivity. It was found that with every increase in scan rate it became easier to detect the glass transition (Tg) response. Scanning at 500 degrees C/min was possible and this gave such great sensitivity that very low sample mass (ca. 1 mg) could be used without any loss in detection of Tg. Mixtures of crystalline and amorphous (spray dried) lactose were prepared and scanned at 500 degrees C/min. It was observed that the Tg response was easily detected even for samples that contained 1.5% amorphous content when using very low samples mass. The view held at present is that DSC is not well suited to studies of amorphous content if the sample contains 10% or less of the amorphous material. The data generated here show that much better detection sensitivity is possible when using the rapid scan rates. As well as being able to detect the presence of very low amorphous contents it was also possible to obtain a quantification, as a linear response was obtained for the step height change in heat flow as a function of amorphous content. It was concluded that HDSC provides a method of obtaining a very fast assessment of the presence of amorphous form, the possibility to quantify this and the need to use a very low sample mass. The combination of speed, low sample mass and sensitivity makes this a very valuable technique for studies on partially amorphous samples.

Calorimetry, Differential Scanning↗

PubMedDate not supplied

A diplopia dilemma.

A 38-year-old man experienced double vision with pupillary abnormalities and convergence retraction nystagmus. A mass, which responded to radiation therapy, was seen as the cause of his dorsal midbrain syndrome. The neural control of vertical eye movements is reviewed and the management of a third ventricular-pineal region mass discussed.

Adult↗