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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 307 records · Page 17Linked to original sources

Antibiotic policy.

Antibiotics are often effective in curing a patient of his infection even when used in a suboptimal manner. In this situation it is often difficult for the prescriber to accept that he/she is using antibiotics "badly" when he can point to the majority of his infections responding well--either to the antibiotic or the patient's own immune response. Many attempts have been made to limit antibiotic use by selective laboratory reporting, by restricting the antibiotics available, by producing guidelines for initial therapy of infection or prophylaxis, by involvement of infectious disease specialists in all antibiotic use and by several other systems. It appears, however, that antibiotic use is still heavily criticised and is a continuing source of conflict in medicine. Consensus on antibiotic indications is still difficult to obtain and is likely to be achieved very slowly. It is clear that polemic is not sufficient and that consensus practices can only be based upon firm scientifically acquired data and detailed discussion of the options by those most intimately involved.

Anti-Bacterial Agents↗

Activation of human polymorphonuclear leucocytes by particulate zymosan is related to both its major carbohydrate components: glucan and mannan.

Unopsonized particulate zymosan and its major carbohydrate component glucan were phagocytosed under serum-free conditions by adherent polymorphonuclear leucocytes (PMN) in a dose- and time-dependent manner. Preincubation of PMN monolayers with mannan did not cause a reduction in the phagocytosis of either particle. The phagocytic response was inhibited by preincubation of the cells with trypsin at a concentration that did not inhibit the phagocytosis of sheep erythrocytes coated with IgG or of latex particles. Homology of the recognition mechanisms for glucan and zymosan was confirmed when cells cultured on fixed glucan or on fixed zymosan failed to ingest either particle to more than 40% of control phagocytosis. Similarly, zymosan and glucan activated PMN in suspension, in a dose- and time-dependent manner, to generate reactive oxygen species which were measured as luminol-dependent chemiluminescence (CL). There was, however, a four-fold greater CL response to zymosan. Preincubation of PMN with mannan resulted in a significantly decreased CL response to zymosan, while the response to glucan was unaffected. The CL response was also sensitive to a range of concentrations of trypsin. In contrast, two other complex polysaccharide particles (barley-derived beta-glucan and algae-derived laminarin) were not phagocytosed by PMN, nor did they cause the generation of CL, despite the fact that they possessed the capacity, in common with zymosan and glucan, to activate the alternative pathway of complement. The identification of a trypsin-sensitive recognition mechanism on the surface of human PMN for unopsonized zymosan and glucan represents a response not hitherto characterized. Furthermore, our data indicate that the phagocytosis of unopsonized zymosan by human PMN is dependent primarily on its glucan content, but that its capacity to activate the respiratory burst may involve mannan and the recruitment of a second cell surface recognition mechanism.

Complement Activation↗

Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function.

The effects of dietary fish-oil fatty acids on the function of the 5-lipoxygenase pathway of peripheral-blood polymorphonuclear leukocytes and monocytes were determined in seven normal subjects who supplemented their usual diet for six weeks with daily doses of triglycerides containing 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid. The diet increased the eicosapentaenoic acid content in neutrophils and monocytes more than sevenfold, without changing the quantities of arachidonic acid and docosahexaenoic acid. When the neutrophils were activated, the release of [3H]arachidonic acid and its labeled metabolites was reduced by a mean of 37 per cent, and the maximum generation of three products of the 5-lipoxygenase pathway was reduced by more than 48 per cent. The ionophore-induced release of [3H]arachidonic acid and its labeled metabolites from monocytes in monolayers was reduced by a mean of 39 per cent, and the generation of leukotriene B4 by 58 per cent. The adherence of neutrophils to bovine endothelial-cell monolayers pretreated with leukotriene B4 was inhibited completely, and their average chemotactic response to leukotriene B4 was inhibited by 70 per cent, as compared with values determined before the diet was begun and six weeks after its discontinuation. We conclude that diets enriched with fish-oil-derived fatty acids may have antiinflammatory effects by inhibiting the 5-lipoxygenase pathway in neutrophils and monocytes and inhibiting the leukotriene B4-mediated functions of neutrophils.

Adult↗

Outbreak of systemic Candida albicans in intensive care unit caused by cross infection.

The first documented outbreak of systemic candidosis shown to be due to cross infection with a particular strain of Candida albicans is reported. Over nine months in an intensive care unit 13 patients developed definite and one probable systemic candidosis. Twenty five further patients had superficial candidal infections. The strain that caused the outbreak (serotype A, morphotype A1, biotype 0/(1)5 5/7) was responsible for all the cases of systemic candidosis acquired in the intensive care unit, 11 (44%) of the superficial candidal infections in the unit, and 17% of candidal infections outside the unit but in the same hospital. The strain was also isolated from oral swabs taken from four nurses working in the unit and the hands of one of these nurses. Two out of 17 nurses were shown to have acquired the strain on their hands when examined immediately after nursing systemically infected patients. No environmental source could be identified. The strain also showed enhanced survival in handwashing experiments and was relatively resistant to Hibiscrub. Management of patients with systemic candidosis might include measures to prevent cross infection and handwashing with disinfectants that are active against candida.

Adult↗

Evaluation of the Ramco latex agglutination test in the early diagnosis of systemic candidiasis.

The value of the Ramco latex agglutination test in the diagnosis of systemic candidiasis was determined using 225 serum samples from 30 patients with systemic candidiasis, 81 serum samples from patients colonized with Candida albicans and 400 control serum samples from hospital patients with no evidence of Candida albicans infection. Results were positive (titres greater than or equal to 1:4) in 20 of the patients with systemic candidiasis; ten had titres of 1:8. Only one of the 81 sera from colonized patients was positive (titre greater than 1:4); this serum came from a patient with colonization of the intravenous catheter. No positive results (titres greater than 1:2) were obtained in the control sera once rheumatoid factor was excluded. The test reliably differentiated between colonization and systemic infection but failed to detect some cases of systemic infection. A poor detection rate was seen in cases where only one serum sample was taken. The importance of taking daily serum samples for continuous monitoring is emphasised. Rheumatoid factor positivity and intravenous line colonization should be excluded when interpreting a result.

Candidiasis↗

Radiation exposure rates near brachytherapy patients containing 137Cs sources.

For 30 brachytherapy patients, whose lateral pelvic diameters, 2r, ranged from 28 to 47 cm, and who contained activities Ac of 137Cs expressed in equivalent milligrams of 226Ra, the normalized exposure rates, X(r)/Ac, in mR h-1 (mg Ra eq)-1 at 1 m lateral from the midline of the pelvis, can be expressed by X(r)/Ac = (1.3 +/- 0.5)e-(0.07 +/- 0.02)r. Patient and applicator effects that contribute to the large uncertainties in the model coefficients are identified.

Brachytherapy↗

Transferable resistance and aminoglycoside-modifying enzymes in enterococci.

Ten isolates of Streptococcus faecalis and two isolates of S. faecium were studied together with an NCTC strain of each species. Antibiotic susceptibility tests showed different patterns of high-level resistance to aminoglycosides. Three S. faecalis strains were highly resistant to gentamicin and other aminoglycosides. By means of a filter membrane technique, transfer of high-level resistance to aminoglycosides was demonstrated from S. faecalis to S. faecalis, from S. faecium to S. faecalis and from S. faecalis to S. faecium, the last of which has not previously been described. Aminoglycoside-modifying enzymes were assayed with radiolabelled cofactors. High-level resistance to gentamicin and other aminoglycosides could be attributed to the production of 2''-O-phosphotransferases, 3'-O-phosphotransferases, 6-O-adenylyltransferases and 6'-N-acetyltransferases. Other resistance mechanisms accounted for resistance in two strains of S. faecalis and one strain of S. faecium that were highly resistant only to streptomycin and one S. faecalis strain that was moderately resistant to all aminoglycosides. A low level of 6'-N-acetyltransferases was detected in the three strains of S. faecium but this did not confer high-level resistance to aminoglycosides and this trait could not be transferred.

Acetyltransferases↗

The occurrence of the snail Lymnaea columella on grazing areas in New South Wales and studies on its susceptibility to Fasciola hepatica.

Field surveys were carried out in the Lismore and Casino area for the presence of fresh water snails potentially responsible for the transmission of trematodes in ruminants. Although the North American snail, Lymnaea columella has previously only been reported from metropolitan areas, large populations of the snail were found east of Lismore. Natural infection with F. hepatica was detected in some of the snails and laboratory studies showed that this snail species was highly susceptible to infection with miracidia of F. hepatica and produced viable metacercariae. Three species of planorbid snails, Helicorbis australiensis, Pygmanisus pelorius and Gyraulus gilberti were also found. The first 2 planorbid species were infected with paramphistomid cercariae.

Animals↗

The southward spread of buffalo fly (Haematobia irritans exigua) in eastern Australia and its survival through a severe winter.

The southward spread of buffalo fly (Haematobia irritans exigua) in coastal eastern Australia from Bororen, Queensland in 1974 to Coffs Harbour, New South Wales in 1982 is documented. Surveys after a cold, dry winter in 1982 recorded overwintering sites and subsequent spread of flies in southern Queensland and northern New South Wales. Buffalo fly overwintered at several places in the Maryborough-Bauple districts and further north. Overwintering also occurred in the Currumbin Valley-Mudgeeraba area on the Queensland-New South Wales border. Other infestations detected early in the season and believed to have arisen from local overwintering populations were observed at Kin Kin, Mount Tamborine and Flinders Peak. By May 1983 flies had recolonised much of coastal south eastern Queensland, and as far south as Ballina and west to the Richmond Range in New South Wales. Implications of these findings for control are discussed.

Animals↗

The activity of temocillin against Enterobacteriaceae, Pseudomonas and Haemophilus influenzae.

The in vitro antimicrobial activity of temocillin against 130 strains of Enterobacteriaceae and 27 strains of Pseudomonas and other related Gram-negative organisms was compared with carbenicillin, mezlocillin and piperacillin. Temocillin was compared with ampicillin against 76 strains of Haemophilus influenzae. More than 90% of Enterobacteriaceae including 65 carbenicillin-resistant strains were inhibited by 8 mg/L of temocillin. Pseudomonas spp. were less susceptible to temocillin than to the other 3 penicillins. 35 out of 38 strains of beta-lactamase-producing H. influenzae were inhibited by 2 mg/L of temocillin. But with 38 ampicillin-sensitive and non-beta-lactamase-producing ampicillin-resistant strains, temocillin was slightly less active than ampicillin. There was no significant enhancement of temocillin activity by clavulanic acid against 20 strains of Gram-negative rods producing characterised beta-lactamases. The resistance to plasmid-mediated and chromosomal beta-lactamase extracts was also studied by bioassay method. No enzyme extracts tested could hydrolyse temocillin except that from one Flavobacterium strain.

Clavulanic Acid↗

The place of temocillin in the treatment of hospital infections.

Infection due to Gram-negative bacteria continues to be a common problem in the hospital environment, for which a wide variety of antibiotics is available. Among Enterobacteria, resistance is expressed most commonly via beta-lactamases. Temocillin is the first penicillin to show stability to beta-lactamases of Gram-negative bacteria, therefore it is in this type of infection that the initial assessments of temocillin should be made.

Carbenicillin↗

Intracellular retention of the 5-lipoxygenase pathway product, leukotriene B4, by human neutrophils activated with unopsonized zymosan.

The cellular and extracellular distribution of leukotriene B4 (LTB4) generated in human neutrophilic polymorphonuclear leukocytes (PMN) stimulated with unopsonized zymosan has been compared with that generated in PMN activated by the calcium ionophore. The amounts of extracellular and intracellular LTB4 were quantitated by radioimmunoassay. The authenticity of the immunoreactive LTB4 was confirmed by the elution of a single immunoreactive peak after reverse phase-high performance liquid chromatography (RP-HPLC) at the retention time of synthetic LTB4, by the identical elution time of a peak of radiolabeled product derived from [3H]arachidonic acid-labeled PMN with the immunoreactive product, and by the comparable chemotactic activity on a weight basis of immunoreactive LTB4 and synthetic LTB4 standard. Under optimal conditions of stimulation by unopsonized zymosan, more than 78% of the generated immunoreactive LTB4 remained intracellular, whereas with optimal activation by the ionophore, less than 8.6% of immunoreactive LTB4 was retained. Resolution by RP-HPLC of the products from the supernatants and cell extracts of [3H]arachidonic acid-labeled PMN stimulated with unopsonized zymosan and those stimulated with calcium ionophore allowed identification and measurement of 5-hydroxyeicosatetraenoic acid (5-HETE), 6-trans-LTB4, LTB4, and omega oxidation products of LTB4 by radioactivity. With zymosan stimulation of PMN, 5-HETE and the 6-trans-LTB4 diastereoisomers were not released, LTB4 was partially released, and the omega oxidation products of LTB4 were preferentially extracellular in distribution. In contrast, with ionophore stimulation, only 5-HETE had any duration of intracellular residence being equally distributed intra- and extracellularly throughout the 30-min period of observation; 6-trans-LTB4, LTB4, and the omega oxidation products of LTB4 were retained at less than 19%. The respective distributions of 5-HETE after zymosan and ionophore stimulation were not altered by the introduction of albumin to the reaction mixtures to prevent reacylation, or by hydrolysis of the cell extract to uncover any product that had been reacylated. The finding that stimulation of PMN with unopsonized zymosan results in the cellular retention of 5-lipoxygenase products suggests that release of these metabolites may be an event that is regulated separately from their generation.

Arachidonate Lipoxygenases↗

Cephalosporin resistance in Pseudomonas aeruginosa, with special reference to the proposed trapping of antibiotics by beta-lactamase.

Resistance of Pseudomonas aeruginosa strains to newer cephalosporins is often associated with stable derepression of synthesis of the chromosomal beta-lactamase. Similar resistance is developed by enzyme inducible (i.e. normal) strains in response to beta-lactamase inducers. By comparing the responses of otherwise isogenic P. aeruginosa beta-lactamase inducibility mutants to antipseudomonal cephalosporins alone or in combination with potent beta-lactamase inducers we confirmed that resistance to cefotaxime, ceftriaxone, cefoperazone, and ceftazidime and latamoxef was caused by beta-lactamase action. The low-level resistance to carbenicillin and cefsulodin which was exhibited by some fully beta-lactamase derepressed strains was not confirmed to be beta-lactamase determined and may have reflected concurrent target or permeability changes. The mechanism whereby the enzyme protected the cell against cefotaxime and ceftriaxone was also investigated. These agents are reportedly stable to the enzyme and some workers have suggested that resistance entails their being trapped rather than hydrolysed. However, the use of a novel model of cellular beta-lactamase function indicated that a hydrolytic resistance mechanism remained likely.

Cefotaxime↗