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Biomedical subjects

P Honour

Publications and source records attributed to P Honour.

17 recordsLinked to original sources

Antibiotics attenuate experimental hypertension in rats.

Hypertension was produced in Sprague-Dawley rats by intramuscular injections of either corticosterone or ACTH. Lower increases in blood pressure to these challenges were observed in Sprague-Dawley rats pretreated with neomycin or vancomycin which alone had no effect on blood pressure or growth. The development of high blood pressure in spontaneously hypertensive rats of a stroke-prone substrain was also attenuated by oral administration of neomycin. These results suggest that experimental hypertension can be modulated by the administration of antibiotics.

Adrenocorticotropic Hormone↗

Concomitance of cytotoxigenic and non-cytotoxigenic Clostridium difficile in stool specimens.

Six patients with antibiotic-associated diarrhea and one patient with diarrhea unrelated to antibiotic use yielded both cytotoxigenic and non-cytotoxigenic isolates of Clostridium difficile from the same stool specimens. In addition, these isolates were shown to be pathogenic and nonpathogenic, respectively, in the hamster model of antibiotic-associated colitis. These data imply that more than one toxin type of C. difficile may be harbored simultaneously. If toxin testing is used to identify C. difficile, more than one colony must be tested.

Adolescent↗

Household pets as a potential reservoir for Clostridium difficile infection.

The purpose of this study was to assess the carriage of Clostridium difficile by household pets to determine their potential as a reservoir of infection. The selective cycloserine-cefoxitin medium was used for C difficile isolation, and tissue culture used for detection of cytotoxin. Carriage of C difficile by household pets was found to be common (23%). The carriage tends to be transient and does not appear to be associated with gastrointestinal disease. Although carriage was higher in animals who had antecedent antibiotic treatment (31%) compared to those which had not (19%), the differences were not statistically significant. In most cases non-cytotoxigenic strains were isolated. Of the cytotoxigenic strains isolated at least one strain was pathogenic in a well documented animal model of human disease. Both cytotoxigenic and non-cytotoxigenic strains of C difficile could be isolated from the environment of the animals studied.

Animals↗

Epidemiology of Clostridium difficile in infants.

The epidemiology of Clostridium difficile was studied prospectively in 451 newborn infants by daily screening of fecal samples. Colonization rates in three postnatal wards ranged from 2% to 52%. Many colonizations were sporadic, but on two wards there was evidence of clustering. On one of these occasions prospective environmental sampling yielded C. difficile organisms from a potential common source. Mothers were shown not to be the sources of their infants' organisms. Both toxin-producing and non-toxigenic strains were common; differentiation according to toxin type was epidemiologically useful. Cross contamination is the most likely explanation of the spread of C. difficile among hospitalized infants; the organism could spread among adults who are at risk of developing antibiotic-associated colitis in a similar manner.

Bacterial Toxins↗

Simplified procedure for the routine isolation of Clostridium difficile from faeces.

The use of alcohol, at a final concentration of 50%, as a selective procedure for the isolation of Clostridium difficile was compared to a selective medium containing 250 microgram /ml of cycloserine and 10 microgram /ml of cefoxitin. Of 266 faecal samples 82 were shown to be positive by one or other method. Seventy-seven (94%) of these were detected by the selective agar (SA) and 72 (88%) by the alcohol procedure (AP). Ten samples (12%) were positive only by SA and five samples (6%) by AP only. The AP was further modified so that all manipulations prior to incubation were performed on the open bench. Of 18 positive samples, 18 (100%) were detected by SA and 16 (89%) by AP.

Agar↗

Bacteriostasis of Escherichia coli by milk. V. The bacteriostatic properties of milk of West African mothers in the Gambia: in-vitro studies.

Bacteriostatic activity was measured in 244 specimens of milk collected during 1977 throughout lactation of up to one year from 78 mothers; the activity varied from very good to fair and only seven were inactive. There was a wider range of activity than was found previously in milk from English mothers. Activity usually fell slowly during lactation but some of the Gambian mothers produced milk of very high activity, like that of colostrum into the second week of lactation, and two mothers did so at six and nine months; other mothers produced good-activity milk throughout lactation. The bacteriostatic activity varied little with the season but slight decreases from that expected were found after the high incidence of infant diarrhoea towards the end of the rainy season. The bacteriostatic activity of most of the milk tested could be prevented by iron salts but that of colostrum and some of the milks with high activity could not. Only these highly active colostra and milks were inhibitory in vitro when the inoculum was increased from 10(4) to 10(6) organisms per ml. These and less active milks were able to inhibit the smaller, standard inoculum for longer than 3 h with the addition of bicarbonate and extra iron-binding protein at the concentrations likely to be present in vivo. Both commensal and pathogenic E. coli were inhibited to a similar degree by these milks and there was no evidence of serotype specificity.

Colostrum↗

Bacteriostasis of Escherichia coli by milk. VI. The in-vitro bacteriostatic property of Gambian mothers' breast milk in relation to the in-vivo protection of their infants against diarrhoeal disease.

A one-year field-study has been carried out in a diarrhoea-endemic area in West Africa to determine the relationship between the bacteriostatic activity of fresh human milk for Escherichia coli in vitro and freedom from diarrhoea of the infant recipients of the milk. The specific contribution of E. coli gastroenteritis to gastrointestinal diseases of infants in general is not known, nor is its particular role in the Gambian infants studied. During the study period, however, both enteropathogenic and toxigenic strains of E. coli were isolated. The incidence of diarrhoea in Gambian infants of seven age-groups from 2 days to 12 months was not significantly correlated with the bacteriostatic activity of milk. This was due rather to absence of diarrhoea in babies fed on low-activity milk than illness in those receiving highly bacteriostatic milk. Indeed, very active milk appeared to protect recipients almost completely, including seven babies of over 3 months of age, five of them during the rainy season, when the risk was high. Babies receiving lower-activity milk experienced more diarrhoea. In a situation where diarrhoeal disease is multifactorial, field evaluation of the protective action by one antibacterial property of milk is difficult. A better understanding of in vivo protection is important, and the factors which have to be taken into account are discussed.

Diarrhea↗

Bacteriostasis of Escherichia coli by milk. III. The activity and stability of early, transitional and mature human milk collected locally.

Milk from 150 local mothers has been assayed for bacteriostatic activity for milk-sensitive and milk-resistant indicator strains of Escherichia coli. Activity is greatest in colostrum which is active directly against all strains of E. coli. One week after delivery of the baby, milk is active against the milk-sensitive strain and becomes active against the milk-resistant strain in the presence of physiological amounts of bicarbonate and iron-binding protein. This activity decreases within 2--4 days on keeping milk unheated at 4 degrees C but is preserved for at least 4 months and often up to 2 years in milk heated to 56 degrees C then stored at 4 degrees C or in milk frozen, unheated, at -28 degrees C provided it is not repeatedly thawed and frozen. Later lactation milks are usually indistinguishable in activity from 1-week post-partum milk but may be less stable on storage particularly if frozen. Lyophyilization in vacuo preserves activity of early-lactation milk for at least 6 months. Heating milk to above 65 degrees C causes a progressive loss of activity which can be partially restored by adding bicarbonate and iron-binding protein. Iron abolishes the activity of milk and reduces that of colostrum.

Bicarbonates↗

Bacteriostasis of Escherichia coli by milk. IV. The bacteriostatic antibody of human milk.

Bacteriostatic activity for milk-sensitive and milk-resistant strains of Escherichia coli is reduced when IgA is removed from milk by precipitation. Lysozyme is not involved in bacteriostasis and can be removed without loss of activity; heavy bentonite absorption however removes some lactoferrin causing partial loss of activity. The heat-labile antigen eliciting bacteriostatic antibody for E. coli is present in milk-sensitive and milk-resistant strains and in some other Enterobacteriaceae, e.g. salmonella; it cross reacts with the antigen in others, e.g. proteus and enterobacter. The antibody is therefore likely to be present in all human milk as a result of the normal commensal gut flora and with widespread activity.

Antibody Specificity↗

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↗

Bacteriostasis of Escherichia coli by milk. I. Colonization of breast-fed infants by milk resistant organisms.

Human milk has a bacteriostatic effect on Escherichia coli in vitro. The milks of 40 mothers were tested for this effect against E. coli isolated from their stools, from those of their own babies, and from those of babies not breast-fed. The milks had a direct bacteriostatic effect, not dependent on complement, on some but not all the strains of E. coli. Breast-fed babies receiving supplementary bottle feeds were colonized with milk-resistant strains, whereas bottle-fed babies and, surprisingly, babies completely breast-fed were colonized equally with milk-sensitive and milk-resistant strains, as were the mothers. These results suggest that the bacteriostatic effect of human milk, demonstrable in vitro does sometimes operate in vivo. The antibacterial activity of human milk is not infleunced by the O, H, or K antigens of E. coli and is effective against other Gram-negative organisms, e.g. Salmonella, Klebsiella, Proteus.

Actinomycetaceae↗

Bacteriostasis of Escherichia coli by milk. II. Effect of bicarbonate and transferrin on the activity of infant feeds.

Fresh human and bovine milk are bacteriostatic in vitro for only some (milk-sensitive) strains of E. coli. The addition of bicarbonate to the test system potentiates the bacteriostasis so that otherwise milk-resistant strains are inhibited. By titration of the bicarbonate in the milk, it is possible to determine the minimum concentration that will activate milk aganinst a milk resistant strain but be ineffective in boiled milk, i.e. it potentiates a heat-labile system in milk and does not merely exert a direct toxic effect. This concentration is lower for human milk than for cow's milk and can be reduced even further by the addition of more iron-binding protein. Lactoferrin and bicarbonate may be present in the gut of the newborn. In an attempt to imitate conditions in the infant gut, we therefore reinvestigated, in vitro and in the presence of added bicarbonate and transferrin, the bacteriostatic activity against E. coli of fresh breast-milk, commercial bottle-milk, and mixtures of these as fed to infants in the study. The results, and information about events in vivo deduced from the ratio of milk-sensitive to milk-resistant strains of E. coli isolated from babies' stool suggest that neonatal intestinal secretions may contribute to the bacteriostatic activity of their feeds so that (1) in fully breastfed babies all strains of E. coli are inhibited to the same extent; there is no selection on the basis of milk sensitivity and equal numbers of strains resistant and sensitive to milk are found in the stools; (2) in fully bottle-fed babies E. coli is not inhibited since the milk is non-bacteriostatic and again there is no selection; (3) in babies fed at the breast but bottle-milk supplemented, only milk-sensitive strains are inhibited; milk-resistant strains are not, and preferentially colonize the large intestines.

Animals↗

Duodenal bacterial flora in early stages of transient monosaccharide intolerance in infants.

The aerobic and anaerobic bacterial flora of the duodenum were studied in 10 infants with transient monosaccharide intolerance. 5 infants had protracted diarrhoea after an episode of acute gastroenteritis and 5 had acute gastroenteritis. The duration of monosaccharide intolerance ranged from 1 to 20 days. Serial intubations were performed on 8 infants. In 5 of 8 cases the bacterial flora were of a normal type at the first intubation at 0--4 days after the onset of monosaccharide intolerance. In 4 of those 5 patients there was an increase in bacterial count a few days later and anaerobes appeared. These findings are not consistent with the suggestion that monosaccharide intolerance is caused by abnormal bacteria in the upper small bowel.

Bacteria↗