Biomedical subjects
P Hodgson
Publications and source records attributed to P Hodgson.
Entropy-driven hydrogen bonding: stereodynamics of a protonated, N,N-chiral "proton sponge".
The C2-symmetric ("[DL]") and achiral ("[meso]") diastereoisomers of the hydrogen iodide salt of 1,8-bis-(N-benzyl-N-methylamino)naphthalene ([2H]-[I] ) interconvert in solution. Direct interconversion of the diastereoisomers of [2H]+ must involve hydrogen bond fission (to give "[nonHB-2H+]") and rotation-inversion of the non-protonated nitrogen centre. The global activation parameters (deltaH++ and deltaS++) for diastereoisomer interconversion in [D7]DMF have been determined from rate data obtained by temperature-drop and magnetisation-transfer 13C NMR spectroscopy over a temperature range of 170 degrees C. The process is found to have a high entropy of activation in both directions (deltaS++=163(+/-4) and 169(+/-4) JK(-1)mol(-1)) and this is suggested to arise through hydrogen bonding of the ammonium centre in [nonHB-2H+] with the solvent ([D7]DMF). Comparison of the enthalpy of activation (deltaH++) with that earlier found for diastereoisomer interconversion of the free-base form 2 suggests that the intramolecular hydrogen bond in [2H]+ is roughly equal in enthalpic strength (deltaH) with that made with the solvent ([D7]DMF) in the non-hydrogen-bonded intermediate [nonHB-2H+]. As such, the hydrogen bonding in [2H]+ may be considered as predominantly an entropically driven process, without any unusual enthalpic strength.
Hepatic fibrosis and cytochrome P450: experimental models of fibrosis compared to AHR knockout mice.
Hepatic fibrosis is characterized by abnormal collagen deposition resulting from increased collagen synthesis and decreased collagen degradation. Cytochrome P450 mediates major drug metabolizing enzyme activity in the liver and this activity is reduced in hepatic fibrosis. In this study we assess cytochrome P450 and CYP 1A mRNA in livers of animals that have been induced to hepatic fibrosis using the heterologous serum induced model of fibrosis in rats compared to controls. Fibrosis was confirmed by assessing the collagen in liver sections as quantified by Sirius red/Fast green staining, a quantitative measure of fibrosis as well as by visualization of the hepatic fibrosis. Collagen levels in the liver sections of heterologous serum induced fibrotic rats was increased by 33% compared to controls and a typical fibrotic pattern was seen. Messenger RNA was prepared from heterologous serum induced fibrotic rats and compared to controls. CYP 1A2 was assessed using a specific probe and the CYP 1A2 level was significantly reduced in the heterologous serum induced fibrotic rats compared to controls. These results further suggest that cytochrome P450 is reduced in the presence of hepatic fibrosis. Thus, in three well established experimental models of hepatic fibrosis which had clearly developed hepatic fibrosis (as shown by Sirius red/Fast green staining), cytochrome P450 mediated enzyme activity, or specifically, CYP 1A messenger RNA is decreased. We then investigated a transgenic mouse, deficient in the arylhydrocarbon hydroxylase receptor (AHR), which has undetectable levels of CYP 1A messenger RNA. We quantitated the collagen in liver sections obtained from AHR knockout mice compared to controls, as an indication of the presence of hepatic fibrosis. Collagen concentration was significantly increased by 53% (P<0.0005) in sections from Ahr-/- (knockout) mice compared to wild-type controls. Collagen in livers of the Ahr+/- heterozygous mice was not different from wild-type controls. The increase in collagen concentration in liver sections is an indication of fibrosis in Ahr-/- mice. Collagen protein deposition was also elevated in liver sections from bile duct ligated rats (by 44%) compared to sham operated controls, was elevated in liver sections from heterologous serum induced fibrosis in rats (33%) compared to controls, and was elevated in liver sections from yellow phosphorous induced hepatic fibrosis (74%) compared to vehicle treated controls. In conclusion, these results indicate that cytochrome P450 and specific subtypes of P450, the CYP 1A subgroup, are significantly reduced in three experimental models of hepatic fibrosis when there is evidence of increased collagen deposition in the livers. These results also indicate that mice that are deficient in CYP 1A have elevated levels of hepatic collagen protein, an indication of hepatic fibrosis.
An action plan for tobacco control at regional level.
Smoking is the single biggest preventable cause of death in the UK; killing over 120 000 people each year, contributing to inequalities in health, exacerbating and causing poverty. Smoking has increased steadily among children since 1988 and more recently, among young adults. The current context in the UK is highly favourable for introducing comprehensive tobacco control measures. This paper summarises a regional action plan for tobacco control. Actions at district and regional levels are outlined to establish a comprehensive local tobacco control framework and complement national tobacco control measures. Measures include: a 'SWOT' analysis of current activity; systematic monitoring of smoking prevalence, attitudes to smoking, and the impact of tobacco control interventions; provision of effective smoking cessation support to a minimum standard throughout the health service; increased coverage of smoke-free public places and workplaces; enforcement of legislation on illegal sales to children and against smuggling and selling illegally imported tobacco; paid and unpaid mass media campaigns; and systematic lobbying for fiscal and legislative measures. One of the key components of the plan is the introduction of evidence-based tobacco control strategies at district levels. These should include a performance framework with clear organisational and managerial accountability and employ a co-ordinated, multiagency, partnership approach. Priority groups should be identified. Strategies should seek to engage the public to build support for tobacco control measures. Sufficient time, staff, resources and training must be allocated to tobacco control work and progress towards objectives monitored.
Position of the internal jugular vein in children. A study of the anatomy using ultrasonography.
The relative anatomy of the internal jugular vein (IJV) was studied in 25 patients undergoing cardiac catheterization under general anaesthesia, with the use of a portable ultrasound probe. In 14 of cases the IJV was anterior, 1 anterolateral and in 10 lateral to the carotid artery between the two heads of the sternocleidomastoid muscle. At the level of the cricoid cartilage, in six cases the IJV was anterior, three anterolateral and in 16 of children the IJV was lateral to the carotid artery. When attempting to cannulate the IJV, because of the variability in relationship of the IJV to CA the technique used should be modified depending upon the level at which cannulation is attempted. The position of the IJV in the child appears to be so variable extra care should be taken when cannulating the IJV and it should not be assumed that the techniques used in adults are directly transferable.
Dental office urgencies and emergencies--how we would manage them.
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A probe-signal study of auditory discrimination of complex tones.
The present experiments used an analogue of the probe-signal method of Greenberg and Larkin [J. Acoust. Soc. Am. 44, 1513-1523 (1968)] to investigate the extent to which listeners direct attention to a particular spectral region when discriminating complex tones. The listeners' task was to discriminate between two seven-component complex tones on the basis of an increment in the level of a single component. On two-thirds of trials the increment was achieved by adding a fixed primary signal to one component of the complex. The primary-signal trials were relatively easy and were intended to cue listeners to attend to the component to which the primary was added. On the remaining trials a smaller probe signal was added either to the cued component, or to one of three other components. The results of the first experiment, in which the complex tones had a flat spectrum, showed significantly better performance for probe signals applied to the cued component compared to the other three components. To control for the possibility that the observed pattern of results was due to the use of timbral cues, a second experiment was conducted in which the spectral profile of the tones was randomized between trials. The results for the second experiment were similar to those of the first experiment and are consistent with the idea that listeners were focusing attention on the spectral region defined by the primary signal.
Glucose determination by a pulsed photoacoustic technique: an experimental study using a gelatin-based tissue phantom.
A preliminary study of using a gelatin-based in vivo tissue model to investigate some of the near infrared photoacoustic characteristics that may influence the sensitivity of non-invasive photoacoustic detection of blood glucose in human tissue is described. It is shown that the optical absorption change due to glucose in the near infrared region is small and that the pulsed photoacoustic technique may offer a better detection sensitivity than other conventional optical transmission measurement systems being developed for blood glucose monitoring.
A comparison of the laryngeal mask airway and Guedel airway, bag and facemask for manual ventilation following formal training.
Ten volunteers, with no previous experience of resuscitation, were formally trained in the use of the laryngeal mask airway and the oropharyngeal airway (Guedel), bag and facemask for manual ventilation of the lungs in 104 fit, anaesthetised adults. They then used both airways in turn. The order of insertion was randomly allocated, and the times taken for insertion were also recorded. Ventilation for each airway was deemed to be successful if an increase in end-tidal carbon dioxide partial pressure did not occur and arterial oxygen saturation remained greater than 90%. Success rates for the laryngeal mask airway and the Guedel airway, bag and facemask were 87% and 43% respectively (p < 0.001) and the average insertion times were 27.4 s (SEM 1.5) and 15.8 s (SEM 0.50) (no significant difference), respectively. The laryngeal mask airway proved to be easier to use for manual ventilation than the Guedel airway, bag and mask for inexperienced personnel who had received a period of formal training in both techniques.
Epidural infusion and neuropraxia.
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Arthrogryposis multiplex congenita of the temporomandibular joint.
A case of arthrogryposis multiplex congenita involving the temporomandibular joint is reported. This is only the second reported case in which surgery was used in an attempt to alleviate the limited mandibular opening that may be associated with this uncommon condition. The clinical findings at the time of surgery differed significantly from those classically associated with other joints afflicted with this condition, suggesting that a different pathophysiologic mechanism may be involved.
Incidence and prevalence of preclinical carcinoma of cervix in a British population.
Quantitative knowledge of the natural history of cancer of the cervix is essential to the design of optimal screening programmes. We have estimated the incidence and prevalence of cervical intraepithelial neoplasia in a population of women receiving cytological examinations, and compared the results with those from other series. Relative risk of disease is reported in relation to easily identified variables (marital status, parity, contraceptive use, symptoms) which are likely to be of practical value in defining selective screening policies.
Objective treatment planning.
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