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Biomedical subjects

R Slack

Publications and source records attributed to R Slack.

At least 19 recordsLinked to original sources

Escherichia coli O157 infection associated with a farm visitor centre.

During the summer of 1994, four cases of bloody diarrhoea and/or haemolytic uraemic syndrome were reported to the consultants in communicable disease control in Nottingham and Leicester. One case was an adult, and there were three children aged 2 to 4 years. The initial investigation failed to reveal any common foodstuff as the cause of the outbreak, but all four cases had attended a farm visitor centre in Leicestershire in the three weeks before they became ill. A further three cases were found who had visited the same farm. A joint investigation took place with environmental health officers and the local veterinary investigation centre of the Ministry of Agriculture, Fisheries and Food. A questionnaire designed to ascertain possible sources of infection was sent to all cases. Several of the animals on the farm were sampled for Escherichia coli O157 and the farm's facilities for food preparation and hygiene were assessed. The pattern of infection did not suggest a point source for the outbreak. Analysis of responses to the questionnaires failed to reveal any common factor other than the visit to the farm, and all but one case remembered stroking and feeding the animals. Food preparation in the farm restaurant appeared to be satisfactory and there was no evidence of contamination of food with pathogenic bacteria. E. coli O157: H7, PT2, VT2 was isolated from four of the seven human cases and also from four cattle and six goats. Further analysis using restriction fragment length polymorphism (RFLP) showed that the four human strains were indistinguishable from nine of the 10 animal strains. It was concluded that the most likely cause of this outbreak was direct contact with the animals. This was further supported by poor handwashing facilities and lack of information for the visitors on the importance of personal hygiene.

Adolescent

Effect of retinoic acid on Nm/23 nucleoside diphosphate kinase and components of cyclic adenosine monophosphate-dependent signalling in human neuroblastoma cell lines.

The effects of retinoic acid on components of the cAMP-dependent signalling system were examined in two related human neuroblastoma cell lines SK-N-SH-F (SHF) and SK-N-SH-N (SHN). Retinoid treatment for a week significantly increased the concentration of intracellular cAMP and the levels of activity of protein kinase A and adenylate cyclase in both cell lines. Retinoic acid treatment also caused a very marked translocation of nucleoside diphosphate kinase from the cytosol to the membrane fraction. The increases in cyclic nucleotide and protein kinase A activity were observed to occur as early as within 1 and 2 days respectively and preceded or were concurrent with the onset of observable morphological differentiation. Results also indicated that agents which elevated intracellular cAMP caused neuronal differentiation and blunted retinoic acid-induced melanocytic differentiation in SHF cells. However, increases in cAMP brought about by treatment of SHF cells with retinoic acid alone were several-fold smaller and thus insufficient to induce neuritogenesis in these cells. The results as a whole indicate that one overall effect of retinoic acid treatment is to upgrade the activity of components of the cAMP-dependent signalling system in both neuroblastoma cell lines. However, retinoic acid causes the SH-F and SH-N cell lines to differentiate along different routes which means that the upgrading responses may be related to more general aspects of differentiation rather than to specific phenotype expression.

Adenylyl Cyclases

The silver nail.

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Bandages

Transfer of arachidonyl groups within the lipids of two human neuroblastoma cell lines.

The incorporation and mobilization of [3H]arachidonic acid in lipids of human neuroblastoma cell lines, SK-N-SHF and LA-N-5, was studied. Essentially similar results were obtained with these two cell lines. Except for phosphatidylinositol which displayed the highest specific activity, the incorporation patterns within phospholipid classes tended to reflect phospholipid composition initially. However at later stages, counts in the acid-stable phosphatidylcholine plateaued and/or decreased while those of plasmenylethaniolamine and acid-stable phosphatidylethanolamine increased steadily. When cells were pulse-labelled with [3H]arachidonic acid and chased with fresh medium, there was a movement of label from diacyl (acid-stable) phosphatidylcholine to plasmenylethanolamine and diacyl (acid-stable) phosphatidylethanolamine. Plasmenylcholine did not appear to be involved in the arachidonyl group transfer. Under these chase conditions there was extensive turnover in the 32P-labelled polar headgroup of phosphatidylinositol but not in that of the other phospholipids. In both incorporation and chase studies involving [3H]arachidonic acid, a movement of arachidonyl groups from triacylglycerol to phospholipid could be observed. The results indicated that the patterns of incorporation and redistribution of arachidonic acid in human neuroblastoma cells were effectively regulated to favor lipids such as phosphatidylinositol and the subclasses of phosphatidylethanolamine. Possible mechanisms involved in these enrichment processes are discussed.

Arachidonic Acid

The prevention of infection in open fractures: an experimental study of the effect of fracture stability.

An experimental model of a contaminated open fracture has been developed. This model has been used to test the hypothesis that stable fixation of a contaminated open fracture will reduce its susceptibility to infection. The tibiae of male New Zealand white rabbits were fractured and then fixed with either a dynamic compression plate (stable group) or a loose-fitting intramedullary rod (unstable group). The fracture site was then inoculated with a standard inoculum of Staphylococcus aureus. There were 20 rabbits in the stable group and osteomyelitis developed in seven (35 per cent); in the unstable group 15 (71 per cent) out of 21 animals developed osteomyelitis. This difference in infection rates was statistically significant (P < 0.02). This experimental study supports the concept of stabilization of open fractures in man.

Animals

Retinoic acid- and staurosporine-induced bidirectional differentiation of human neuroblastoma cell lines.

The differentiation pattern of two related human neuroblastoma cell lines, SK-N-SHF and SK-N-SHN, induced by retinoic acid and staurosporine was studied. Immunohistochemical and electron microscopic examination of the cells indicated that the SHF variant could undergo differentiation along a melanocytic route when treated with retinoic acid and to neuronal cells when treated with retionic acid and staurosporine together. Treatment of SHN cells with either or both these agents caused neuronal differentiation. The melanocytic pathway was characterized in part by the flattening of the cells, the appearance of melanocytic antigens and various forms of melanosomes, an increase in tyrosinase activity, and the absence of neuronal marker proteins. The neuronal route was typified by the development of long neuritic processes containing microtubules and numerous neurosecretory granules as well as by immunohistochemical reactions for neural cell adhesion molecule, synaptophysin, and neurofilament proteins. The significance of these results is discussed in terms of the differentiation responses of neuroblastoma cells to chemical agents as well as some of the factors involved in the regulation of phenotype expressions of these cells.

Alkaloids

A comparison of aztreonam/metronidazole and cefotaxime/metronidazole in elective colorectal surgery: antimicrobial prophylaxis must include gram-positive cover.

Aztreonam/metronidazole and cefotaxime/metronidazole were compared in a prospective trial in 154 patients undergoing elective colorectal surgery. Three antibiotic doses were given over 16 hours. A significant excess of wound sepsis in the aztreonam group was seen (23/71 vs 9/70 chi 2 6.60; P less than 0.01). Sepsis was almost invariably due to Gram-positive organisms and, in particular, Staphylococcus aureus.

Aztreonam

Morbidity variation and RAWP.

STUDY OBJECTIVE: Resource allocations from the central government to the English health regions are determined by population levels adjusted by relative standardised mortality ratios (SMRs). The White Paper Working for Patients proposes that allocations should in future be based on capitation adjusted by some other measures of health. The aim of this paper was to investigate the effect of using morbidity data in the weighting algorithm instead of relative SMRs. DESIGN: Morbidity data were obtained from the Health and Lifestyle Survey, 1986. Three different measures of self reported morbidity were used (Long Standing Illness, Any Declared Condition, Any Handicap). Population weightings were calculated by national average bed use for these conditions and again for SMRs. SETTING: This was a national survey using data from all the English health regions. MAIN RESULTS: All three measures of morbidity showed a wider variation between regions than SMRs, and the weighted populations showed a correspondingly wide variation (approximately double that obtained when using SMRs). CONCLUSION: The weighting of populations will be crucial in determining resource allocations to budget holders, whether in the hospital or primary care sector. However without a prior agreement on what counts as "need", the choice of these alternative measures will be arbitrary.

Health Care Rationing

A prospective study of urinary tract infection during pelvic radiotherapy.

The frequency of urinary tract infection before and during pelvic radiotherapy was studied prospectively in 172 patients who were not catheterised and had not had instrumentation for at least 4 weeks prior to radiotherapy. The incidence of urinary tract infection prior to radiotherapy was 17% and a further 17% of patients developed a urinary tract infection during radiotherapy. Mid-stream specimens of urine (MSU) should be examined for infection on a weekly basis during pelvic radiotherapy not only to identify this additional 17% of patients but also to detect those patients who have persistent urinary tract infection in spite of treatment with appropriate antibiotics.

Adult

Studies on the effects of vitamin E on neuroblastoma N1E 115.

The effects of DL-alpha-tocopherol and DL-alpha-tocopherol succinate on neuroblastoma N1E 115 cells were studied. Tocopherol had no growth-arresting properties, whereas its succinate ester derivative inhibited growth at concentrations greater than or equal to 20 microM. The succinate derivative was taken up somewhat more readily than free tocopherol; however, for any equal uptake of both forms of vitamin E, only the succinate derivative could affect growth. Tocopherol succinate was taken up without marked conversion to tocopherol. Following uptake, plasma membrane and organelle fractions contained most of the vitamin E derivatives; however, the particulate and membrane fractions were about twice as enriched in the succinate derivative as in free tocopherol. On the other hand, a proportionally higher amount of unconjugated vitamin E was recovered in the cytosol fraction. Fluorescence polarization studies indicated no differences in the overall fluidity of the plasma membranes treated or not treated with either form of vitamin E. The data point to the functionality of the free carboxyl group of the succinate derivative as a basis for the difference in potency of the two forms of vitamin E.

Animals

Sub-inhibitory and post-antibiotic effects of spiramycin and erythromycin on Staphylococcus aureus.

The antibacterial responses of clinical isolates of Staphylococcus aureus to spiramycin and erythromycin were compared. Conventional MICs showed erythromycin-sensitive strains to be 16-32 times less sensitive to spiramycin. MBCs were only four to eight times higher for spiramycin. Erythromycin resistant S. aureus were more frequently encountered. Concentrations of both macrolides at 1/4 MIC produced antibacterial effects. Post-antibiotic effects were more marked with spiramycin. After 3 h exposure to 4 x MIC of antibiotic the delay in regrowth of S. aureus was 5 h for erythromycin and 9 h for spiramycin. In a continuous cultivation model, spiramycin produced an inhibitory effect on S. aureus for 12 h whereas the effect of erythromycin was only apparent for 6 h. In conclusion, spiramycin is more active against staphylococci in vitro than would be expected by its modest MICs.

Drug Resistance, Microbial