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Biomedical subjects

H E Larson

Publications and source records attributed to H E Larson.

At least 37 records · Page 2Linked to original sources

Epidemiology of experimental enterocecitis due to Clostridium difficile.

Hamsters can survive a course of clindamycin if they are held in a protected environment. Inoculation of Clostridium difficile regularly results in fatal enterocecitis in such animals but is without effect in untreated animals. These findings suggest that in the development of enterocecitis, clindamycin treatment and infection with C. difficile are separate events, and they imply that hamsters usually acquire C. difficile from environmental sources. Environments appear to differ in the risk of exposure to C. difficile, high-, medium-, and low-risk areas being recognizable. Once introduced, C. difficile may spread from animal to animal. Parallel with the incidence and epidemiology of human antibiotic-associated pseudomembranous colitis are discussed.

Animals↗

The experimental pathogenesis of antibiotic related colitis.

Findings from several countries now closely associate Clostridium difficile and its toxin with PMC. In fact, testing for the toxin by means of tissue culture assay is being used more and more to define the proportion of patients with clinically significant antibiotic associated colitis. Reproduction of a similar entity in hamsters appears to fulfil the Koch-Henle postulates, establishing C. difficile as the cause of the syndrome. Antibiotic treatment creates susceptibility to infection rather than being directly responsible for the lesions. The manner in which this occurs is not clear. Animal experiments show that C. difficile is present in some environments and that it may spread through the air and be ingested to cause infection.

Animals↗

Impaired polymorphonuclear leucocyte chemotaxis after influenza virus infection.

Polymorphonuclear leucocyte function was assessed in 13 patients with influenza by measuring phagocytosis of staphylococci and chemotaxis. Significant impairment of chemotaxis was shown. Subsequeuntly polymorph chemotaxis was found to be impaired in a group of volunteers infected with virus recombinants of A/New Jersey/8/76 but not in volunteers infected with a virus recombinant of A/Victoria/3/75. These results accord well with the in vitro effects of certain influenza viruses on polymorph function and suggest that interference with polymorph function may predispose to bacterial pneumonia after clinical influenza.

Chemotaxis, Leukocyte↗

Morphology of experimental antibiotic-associated enterocolitis in the hamster: a model for human pseudomembranous colitis and antibiotic-associated diarrhoea.

The morphology of antibiotic-associated enterocolitis in the hamster is described and compared with human antibiotic-associated pseudomembranous colitis. It is shown to be a caecal disease with proliferative mucosal changes and in this respect unlike the human counterpart. The bacteriology and toxicology, however, are identical. In addition, mucosal changes are described in animals on antibiotics but without established enterocolitis. As a result we suggest that there may be a spectrum of human disease ranging from mild antibiotic-associated diarrhoea to established pseudomembranous colitis. Therefore, despite the morphological variation, the hamster remains a good model for investigating the pathogenesis of pseudomembranous colitis and antibiotic-associated enteropathy in general.

Animals↗

Clostridium difficile and the aetiology of pseudomembranous colitis.

Bacterial isolates from 5 patients with pseudomembranous colitis (P.M.C.) were screened for toxin production. Strains of Clostridium from 4 patients produced in vitro a toxin similar to that found in P.M.C. faecal suspension. These were identified as C. difficile. Use of the strains from 2 patients induced a fatal enterocolitis when inoculated orally into hamsters pretreated with vancomycin. The C. difficile that produced the toxin in vitro was then re-isolated from hamster caecal contents. These findings suggest that P.M.C. results from infection with C. difficile and that previous antibiotic therapy produces susceptibility to infection.

Adult↗

Immunity to challenge in volunteers vaccinated with an inactivated current or earlier strain of influenza A(H3N2).

Volunteers were inoculated with vaccine made from the 30c mutant, A/Port Chalmers/73 or B/Hong Kong/8/73. Preliminary experiments showed that the 30 c strain was antigenically quite close to A/HK/8/68. Volunteers given 30c developed haemagglutination inhibiting antibodies against the 'current' 1973 serotypes (as well as to the vaccine virus) but the titres were less than those after the A/PC/73 vaccine. Volunteers were then challenged with a live attenuated virus, WRL 105, with A/Finland/4/74 antigens, by intranasal inoculation. The rates of infection were 43% after B/Hong Kong/8/73, 20% after 30c and 5% after A/PC/73. This indicated that the 30c gave some protection but that the vaccine prepared from the current strain gave more.

Antibodies, Viral↗

An isolation unit in a district general hospital.

The working of a 19-bed isolation unit in a general hospital was studied from August 1975 to July 1976. A few patients received the highest degree of isolation, but infections in all categories were contained and patients at risk in the same unit were protected from infection.

Cross Infection↗

Undescribed toxin in pseudomembranous colitis.

A girl aged 12 developed pseudomembranous colitis after a short course of oral penicillin. She had no history of adverse reaction to penicillin before or after the illness. No pathogenic bacteria, mycoplasmas, or viruses were found in her faeces, but they did contain a toxin. Toxin was also found in four of five other patients with pseudomembranous colitis but not in six specimens obtained from patients with diarrhoea caused by other disorders. Further studies may show that pseudomembranous colitis is caused by a bacterial toxin.

Bacterial Toxins↗

Influenza viruses and staphylococci in vitro: some interactions with polymorphonuclear leucocytes and epithelial cells.

Bacterial infection contributes substantially to the morbidity and mortality of human influenza. In vitro experiments were performed to test two hypotheses regarding a possible relationship between the virus and bacterial infection. Firstly, maintenance media from tissue and organ cultures infected with influenza virus were tested for the presence of staphylococcal growth-promoting factors; no evidence for these was found. Secondly, we looked for a virus effect on polymorphonuclear leucocyte function. We found that human leucocytes purified from venous blood and exposed to influenza virus responded normally to stimulation of hexose monophosphate shunt activity and chemiluminescence. However, their responses in tests of phagocytic function and of chemotaxis were inhibited. By various criteria this effect was specific to the virus and could be obtained even when only a few virus particles were present per leucocyte. We propose that this is a mechanism by which influenza virus could enhance susceptibility to bacterial infection in the lung.

Animals↗

Impairment of human polymorphonuclear leucocyte function by influenza virus.

The effects of an influenza virus on polymorphonuclear leucocyte function were examined in vitro with a view to explaining why bacterial pneumonia often accompanies influenza in man. The ability of human polymorphonuclear leucocytes to show chemotaxis and to phagocytose staphylococci was inhibited when they were incubated with influenza viruses. Hexose-monophosphate-shunt activation was unaffected. The inhibitory effects were apparently specific to the virus.

Cell Migration Inhibition↗