PubMed Health⌕ Search

Biomedical subjects

D Kingston

Publications and source records attributed to D Kingston.

At least 19 recordsLinked to original sources

Experimental pathology of intravenous polyurethane cannulae containing disinfectant.

Cannula tubing (1.6 mm external, 1 mm internal diameter) manufactured from medical grade polyurethane containing 2%, 2,4,4'-tri-chloro-2'-hydroxydiphenylether ('Irgasan', Ciba-Geigy) was found to have no effect other than that seen with control ('Irgasan'-free) tubing in the following test systems: (i) haemolysis, (ii) endothelial cell cultures, (iii) paravertebral muscle of rabbits, (iv) jugular vein of rabbits, (v) cannulation of baboons and (vi) clotting times of human platelet-rich plasma. However, the results from (iv) showed a significant amount of damage from both inpregnated and control cannulae and (v) showed that all detectable 'Irgasan' had been eluted from the portions of tubing retained within the animal before the end of the experiment, more rapidly than predicted from in-vitro studies. The rate of elution of 'Irgasan' in vivo needs to be further investigated, and consideration should be given to developing a plastic-disinfectant combination with a slower rate of loss of disinfectant.

Animals↗

Current hypotheses on synergistic microbial gangrene.

We have reviewed spreading infections of the dermis, with special reference to the importance of synergy in their causation. Evidence for this is accumulating from both clinical studies and from studies in laboratory animals. Necrotizing fasciitis (rapid spread over 24 h) can be caused by beta-haemolytic streptococci, sometimes with Staphylococcus aureus, or by mixed infections of aerobes and anaerobes, often of gut origin. Animal studies provide good evidence that S. aureus can potentiate the beta-haemolytic streptococcal infection in necrotizing fasciitis. There is also evidence that mixtures of aerobes and anaerobes can act synergistically, but animal models for necrotizing fasciitis have not been developed. Anaerobic cellulitis (variable rate of spread from hours to days) can be caused by mixed aerobes and anaerobes or by mixed clostridia. Animal studies provide good evidence for synergy in the former. Meleney's synergistic postoperative gangrene (slow spread over weeks) may be cutaneous amoebiasis: the animal model of Brewer and Meleney relates to the more rapid infections of anaerobic cellulitis.

Animals↗

Elution of disinfectant from polyurethane cannula tubing.

Cannula tubing (1.6 mm external, 1 mm internal diameter) was fabricated from medical grade polyurethane containing 2% 2,4,4'-trichloro-2'-hydroxydiphenyl ether ('Irgasan', Ciba-Geigy). When shaken with 10 ml of phosphate-buffered saline an equilibrium was set up with only traces of 'Irgasan' in the aqueous phase. When phosphate-buffered saline flowed through the tubing, 0.26 mg of 'Irgasan' per g of tubing per day was eluted, and this was not detectably increased by buffers of pH 3 or pH 8.5. However, a 20% lipid emulsion eluted 6 mg per g of tubing per day with a flow rate of 250 ml per day and 11 mg with a flow rate of 11 per day. These results scaled up show that a 7.11 g Hickman catheter would lose 78 mg of Irgasan in the first day with Intralipid, compared to 1.8 mg with PBS. If elution by tissue fluids (including blood) does not exceed that by Intralipid then comparison with available toxicological data suggests an adequate margin of safety for adults, but not for premature babies.

Anti-Infective Agents, Local↗

Memorandum on the infections hazards of the common communion cup with especial reference to AIDS.

Bacteriological studies on the communion cup have shown that there is a low level of contamination with mouth organisms on the rim. The death rate of bacteria on the cup surface would not be significant, but the wine had a bactericidal effect on most but not all organisms tested. However droplets of saliva did not readily mix with the wine. In considering the spread of AIDS, extensive studies of people infected with human immunodeficiency virus (HIV) in hospital or at home have shown that the established routes of spread are the injection of blood or blood products, sexual intercourse or at birth. There are only very rare examples of spread by other means. The virus is rarely isolated from the saliva and a study of homosexuals indulging in oral sexual intercourse suggests that it is very poorly infectious when taken into the mouth or swallowed. It is concluded that the risk of transmission of HIV by the common communion cup can be neglected under ordinary circumstances. Suggestions are made for improving the hygiene of the communion service which may be useful under special circumstances: there is no evidence that disease is spread in this way under normal conditions.

Acquired Immunodeficiency Syndrome↗

Streptococcal necrotizing fasciitis: development of an animal model to study its pathogenesis.

Necrotizing fasciitis is a serious and increasingly common human disease which can be caused by an infection with beta-haemolytic streptococci (BHS) of Lancefield groups A, C or G, spreading rapidly in the loose connective tissue over the muscle fascia. To facilitate study of its pathogenesis, we have developed an animal model for the production of a spreading infection with BHS in the loose connective tissue over the muscle layer in the skin of New Zealand White rabbits. Intradermal injection of group A BHS alone into the flank was unsatisfactory in that a spreading lesion occurred on only 12% of occasions. When the group A BHS were co-injected with cultures of Staphylococcus aureus, the results depended on the strain of S. aureus used: an abscess-producing strain isolated from pigs gave rise to a spreading lesion on 50% of occasions. When BHS were injected with the alpha-lysin of S. aureus at a titre which produced inflammation without necrosis, spreading lesions occurred on 75% of occasions. However, both inoculated and uninoculated broth acted synergistically with the alpha-lysin in potentiating the spread of the streptococci. This demonstration of synergy between BHS and alpha-lysin of S. aureus may reflect the clinical situation in the human, as both organisms have been found to occur together at sites where spreading streptococcal infections have originated.

Animals↗

Self-disinfecting plastics for intravenous catheters and prosthetic inserts.

A disinfectant (2,4,4'-trichloro-2'-hydroxydiphenyl ether: Irgasan, Ciba-Geigy) was incorporated into plastic washers fabricated from ethylvinyl acetate (EVA), polyethylene, polypropylene or TPX. Plastics containing 0.2 and 2% Irgasan gave zones of inhibition on nutrient and blood agar plates seeded with micro-organisms (Staphylococcus aureus, Staph. epidermidis, Escherichia coli, Proteus mirabilis or Candida albicans) even after thorough washing. Exceptionally, C. albicans was inhibited only by 2% Irgasan, and EVA gave good inhibition only against the staphylococci. Similar washers of each plastic were implanted subcutaneously into the flanks of rabbits; before insertion each was washed, had thread woven into it and was surrounded by a plasma clot containing 2 X 10(8) Staph. aureus. All the plastics without Irgasan gave rise to abscesses, none of the plastics impregnated with 2% Irgasan did, though from 2 out of 12 sites small numbers of Staph. aureus were isolated at post mortem. Using either clinical or bacteriological criteria, the results were highly significant (P less than 0.00001 and P less than 0.001 respectively), demonstrating the effectiveness of this technique in preventing plastic-associated infection.

Animals↗

Antibody production to milk proteins in the jejunal mucosa of children with Cow's milk protein intolerance.

A direct immunofluorescent technique with fluorescein-labeled antigens was used to examine the jejunal mucosa for specific antibody reduction in 23 children aged 2--25 months referred for diagnostic biopsy. Plasma cells containing antibodies to beta-lactoglobulin (beta LG) or bovine serum albumin (BSA) were present in 11 of 16 biopsies from patients with cow's milk protein intolerance (CMPI) but only one of eight controls, all on a diet containing cow's milk. Antibody-containing cells (ACC) constituted approximately 0.5--5% of the total (IgA + IgM) plasma cell population. Their presence did not correlate with either histologic abnormality or IgA plasma cell count. Double immunofluorescence with rhodamine-labeled antigens and fluorescein-labeled class-specific anti-human immunoglobulin sera showed the ACC to be approximately 70% IgA cells and 30% IgE cells.

Animals↗

Eczema and atopy in early childhood: low IgA plasma cell counts in the jejunal mucosa.

Twenty-one children aged between 2 and 54 months, 14 with eczema and 7 with allergies in first-degree relatives, were referred for diagnostic jejunal mucosal biopsy for a variety of symptoms. A partial villous atrophy was found in 19 of the 21 biopsies obtained; the other 2 were normal. We report a highly significant (P less than 0.0001) lower IgA cell count in biopsies with partial villous atrophy compared with the results of our previous study of IgA and IgM plasma cells in the mucosal biopsies in children without eczema or a history of atopy matched for age and histological appearances. The IgM cell count was also lower.

Atrophy↗

Plasma cell counts on human jejunal biopsy specimens examined by immunofluorescence and immunoperoxidase techniques: a comparative study.

Ten human jejunal biopsy specimens were examined by both immunofluorescence (IF) and immunoperoxidase (IP) methods to compare both plasma cell counts and the distribution of extracellular immunoglobulins. Each specimen was cut into at least two portions, one fixed in 5% formaldehyde in phosphate-buffered saline before being snap-frozen and sectioned on a cryostat for IF, the other being fixed in half-strength Zenker and embedded in paraffin wax by standard methods for IP. Plasma cell counts were comparable in the eight biopsy specimens for which they could be estimated, geometric mean values being IgA 22.9 (IF), 19.3 (IP) and IgM 9.5 (IF), 10.6 (IP). Two specimens showing subtotal villous atrophy had too much extracellular IgA for plasma cell counts to be feasible. For these the IF methods had the advantage that the extracellular immunoglobulin was more readily distinguishable from background staining.

Cell Count↗

Jejunal mucosal morphometry in children with and without gut symptoms and in normal adults.

Nineteen diagnostic peroral biopsy specimens from 18 children without diarrhoea, vomiting, or abdominal pain ('control' children) were compared with those taken from 23 children with diarrhoea of varying aetiology to establish the morphometric characteristics of jejunal mucosa in childhood. Comparison was also made with normal jejunal mucosa from adults. Statistical analysis of each characteristic individually showed no significant difference between the 'control' children and those with diarrhoea, but there were significant differences between the mucosae of 'control' children and those of adults; the villi tended to be shorter and the crypts longer in children. Thirty-seven per cent of specimens from the 'control' children showed a partial villous atrophy, that is, they were abnormal by adult criteria. Discriminant analysis of the features measured showed effective separation of the following groups: normal histology from partial villous atrophy in children, healthy adults from 'control' children, and normal histology in adults from normal histology in children.

Adult↗

Protein A-like activity and streptococcal cross-reactions.

Recognition of the protein A-like activity of some strains of group A streptococci has thrown doubt on much previous work suggesting antigenic cross-reactions between these streptococci and mammalian tissues. The strains used in our previous studies have now been examined by the mixed reverse passive antiglobulin reaction (MRPAH) for the 'non-specific' absorption of purified Fc portion of human IgG. They were found to have only traces of activity. The strain of Staphylococcus aureus used to control 'non-specific' absorption by bacterial cell walls was strongly positive. Protein A-like material as detected in this way was not therefore responsible for our earlier results.

Cross Reactions↗

Tetrabenazine for involuntary movement disorders.

The use of tetrabenazine to treat the movement disorder of Huntington's chorea and other dyskinesias is described. Tetrabenazine produced moderate to marked improvement in the movement disorder in 79% of a series of 40 Australian patients. The most commonly reported side effects were depression, drowsiness and Parkinsonism.

Humans↗

Histopathologic changes and the immune response within the jejunal mucosa in infants and children.

Jejunal biopsies obtained from 45 children referred for a variety of clinical conditions were examined histologically and by standard immunofluorescence methods. The number of plasma cells was recorded per "mucosal tissue unit". The results showed that most of the immunoglobulin A (IgA) counts in infants under 3 yr with normal mucosa were low and that there was a rise in the number of IgA plasma cells starting after this age. Despite this, under pathologic conditions (partial villous atrophy with increased inflammatory cell infiltration--PVA) a significant rise in IgA plasma cells occurred in all age groups. Patients with coeliac disease tended to show the highest IgA as well as IgM plasma cell counts. In all other patients, IgM counts did not change significantly with age or histologic abnormalities.

Adolescent↗

Streptococcal cross-reacting antigen and the bundle of His.

Five sera raised in rabbits against three strains of Streptococcus pyogenes (grown in semi-synthetic media) were shown by immunofluorescence to have antibodies reacting with both myocardial and conducting fibres. The pattern of staining on the conducting fibres was different to that on myocardial fibres and suggested the presence of larger amounts of cross-reacting antigen. Most work was done on ox heart, but the results were confirmed on human heart and rabbit heart. Absorption studies, carried out with three sera on ox heart only, showed that absorption with the homologous organism abolished in parallel the staining of both types of fibre. Absorption with heterologous organisms was less effective indicating the existence of more than one cardiac cross-reacting antigen. Absorption with myocardium, suggested that the conducting fibres contained streptococcal cross-reacting antigens additional to those found in the contractile fibres.

Animals↗