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Biomedical subjects

M P Slack

Publications and source records attributed to M P Slack.

At least 37 records · Page 2Linked to original sources
PubMed1993

Comparison of the epidemiology and cost of Haemophilus influenzae type b disease in five western countries.

To determine and compare the cost of Haemophilus influenzae type b (Hib) disease in Australia, Finland, Israel, Switzerland and the United Kingdom a collaborative study was undertaken. The incidence of Hib disease varies in these 5 countries from 34 to 58.5 cases per 100,000 children less than 5 years of age. Although the incidence of meningitis in this age group is similar (between 18 and 26/100,000) in these countries, the incidence of epiglottitis varies from 0 to 22.7/100,000. The cost of hospitalization and the frequency of sequelae are similar for 4 of the 5 countries; however, the break even cost of a vaccination program to prevent 90% of Hib disease is estimated to vary from $22 to $84 per child (US$). Because of a lower incidence of Hib disease and lower cost for hospitalization, these costs are considerably less than those for the United States ($301.64 using similar calculations).

Australia↗
PubMed1993

Polymerase chain reaction-based strain characterization of noncapsulate Haemophilus influenzae.

A polymerase chain reaction-based typing method for noncapsulate Haemophilus influenzae was developed. Randomly amplified polymorphic DNA fingerprints were generated from boiled supernatants prepared directly from bacterial colonies without the need for DNA extraction. The technique was applied to isolates obtained during putative outbreaks of chest infection and validated by comparison with sodium dodecyl sulfatepolyacrylamide gel electrophoresis analysis of outer membrane protein-enriched preparations and rRNA gene restriction analysis. There was complete concordance between the three techniques. The results show that randomly amplified polymorphic DNA analysis provides a highly discriminatory method of characterizing strains of noncapsulate H. influenzae which is eminently suitable as an epidemiological tool for the rapid investigation of outbreaks of infection.

Bacterial Typing Techniques↗
PubMed1993

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91).

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.

Age Factors↗
PubMed1992

A survey of invasive Haemophilus influenzae infections.

A survey of invasive H. influenzae infections has been underway in six regions of England and Wales since September 1990. In the first year, there were 433 cases of which 362 (84%) were due to H. influenzae type b (Hib). The majority of Hib infections were in children aged less than 5 years; there being an annual incidence of 26.4/100,000 in this age group. Meningitis occurred in 56% of cases of Hib infection. The results confirm previous evidence of the need to incorporate Hib vaccination into the childhood immunisation schedule. The ongoing survey data will provide useful information to assess the impact of an Hib immunisation programme.

Adolescent↗
PubMed1992

Molecular epidemiology of unrelated clusters of multiresistant strains of Haemophilus influenzae.

Three epidemiologically unrelated clusters of Haemophilus influenzae resistant to ampicillin, chloramphenicol, and tetracycline were studied. The biotypes and cell-envelope protein patterns were determined for 17 nonencapsulated strains, 6 from Dundee and 11 from Cheltenham, and for 6 type b encapsulated strains from Guildford. After mobilization by conjugation, large 32- to 36-MDa plasmids were purified from all the strains. The restriction fragment patterns of the plasmids were determined by ethidium bromide staining of digested purified plasmid or by Southern hybridization of digested total cellular DNA of the parent strains, probed with purified plasmid. Evidence is presented for a chromosomal location of the plasmids in the parent strains, the spread in nature of a plasmid between distinguishable strains of H. influenzae, the person-to-person spread of a strain within a cluster, and a high degree of sequence homology between distinguishable plasmids, implying their close relatedness.

Adult↗
PubMed1990

Cross-infection by non-encapsulated Haemophilus influenzae.

From October, 1988, to January, 1989, 18 patients admitted to an acute medical chest ward were infected with an ampicillin-resistant beta-lactamase-producing strain of Haemophilus influenzae. All 18 isolates were non-encapsulated strains of biotype III and showed identical cell envelope protein profiles, as judged by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The organism was not isolated from repeated environmental samples but there was strong circumstantial evidence that a spirometer was a common iatrogenic source of the cross-infection.

Bacterial Outer Membrane Proteins↗
PubMed1989

Permeability to cefsulodin of the outer membrane of Pseudomonas aeruginosa and discrimination between beta-lactamase-mediated trapping and hydrolysis as mechanisms of resistance.

A pair of strains of Pseudomonas aeruginosa (3-Pre: cefsulodin-sensitive, inducible beta-lactamase; and 3-Post: cefsulodin-resistant, elevated beta-lactamase, derived from 3-Pre by subculture in the presence of cefsulodin) were taken as representative of the class of bacteria resistant to third-generation cephalosporins due to elevated synthesis of the normally inducible, chromosomally encoded beta-lactamase. These two strains were used to differentiate between 'trapping' and 'hydrolytic' mechanisms of cefsulodin resistance by (a) measuring the outer-membrane permeabilities to cefsulodin, (b) measuring the kinetics of cefsulodin hydrolysis and the stoichiometry of cefsulodin trapping by the periplasmic beta-lactamase, and (c) comparing the predictions of the trapping and hydrolysis hypotheses with the minimum inhibitory concentrations (MIC) of cefsulodin. The MIC of cefsulodin for strains 3-Pre and 3-Post were 2.35 microM (1.25 micrograms ml-1) and 37.6 microM (20.0 micrograms ml-1) respectively. The permeability parameter for cefsulodin of the outer membrane of the resistant strain was 0.0034 cm3 min-1 mg dry mass-1, so the flux of cefsulodin across its outer membrane at the MIC was calculated to be 0.120 nmol min-1 mg dry mass-1. Hydrolysis of cefsulodin by the beta-lactamase in the periplasm occurred at a rate of 0.118 nmol min-1 mg dry mass-1 which can thus account for resistance by matching the above rate of inflow. Trapping by the beta-lactamase, even with a 1:1 stoichiometry, would require the enzyme to be synthesized at 5.0 micrograms protein min-1 mg dry mass-1 or about 40% of the dry mass/generation. We conclude that hydrolysis, but not trapping, adequately explains the resistance to cefsulodin in P. aeruginosa 3-Post. A similar calculation for latamoxef resistance, using data taken from the literature, led to the same conclusion.

Bacterial Outer Membrane Proteins↗
PubMed1989

The penetration of antibiotics into aggregates of mucoid and non-mucoid Pseudomonas aeruginosa.

Cells of mucoid and non-mucoid Pseudomonas aeruginosa in colonies were at least one-thousandfold less sensitive to the antibiotics tobramycin or cefsulodin than were cells of the same bacteria in dispersed suspension. We did not detect any difference between the mucoid form and the non-mucoid form in the antibiotic sensitivity of colonies, from which we infer that the exopolysaccharide of the mucoid form does not contribute to colony-resistance by forming a barrier to antibiotic diffusion. Mathematical models were constructed in order to estimate time-courses of penetration of tobramycin and cefsulodin into biofilms and microcolonies of mucoid and non-mucoid P. aeruginosa. For tobramycin penetration, adsorption of antibiotic to the exopolysaccharide of the glycocalyx and antibiotic uptake by cells were taken into account in the calculations. The longest time-period for the concentration of tobramycin at the base of a biofilm 100 micron deep to rise to 90% of the concentration outside the biofilm was predicted to be 2.4 h. For cefsulodin penetration, irreversible hydrolysis catalysed by beta-lactamase was taken into account, using beta-lactamase levels taken from the literature. The calculations predicted that the cefsulodin concentration at the base of a biofilm 100 micron deep would rise to 90% of the external concentration in 29 s when the beta-lactamase was synthesized at the basal level. For a similar biofilm of bacteria synthesizing enhanced levels of beta-lactamase ('derepressed'), the concentration of cefsulodin at the base was calculated to rise to 41% of the external concentration in about 50 s and then remain at that level. This was despite the fact that cefsulodin is a poor substrate for this beta-lactamase.

Anti-Bacterial Agents↗
PubMed1989

Haemophilus influenzae type b disease in the Oxford region.

A prospective survey of children in the Oxford region identified 200 cases of systemic Haemophilus influenzae type b disease in the first three and a half years of the study. The annual incidence in children less than 5 years of age was 33.4/100,000. This represents a cumulative incidence of one systemic infection in 600 children before their 5th birthday. The mortality was 5.0%. The risk of H influenzae type b meningitis was one in 850 with a mortality of 5.6%, and substantial morbidity among survivors. From the total live birth rate, about 1300 cases of systemic H influenzae type b disease, over 900 cases of H influenzae type b meningitis, and 65 deaths would be predicted annually in children in the United Kingdom.

Child↗
PubMed1988

Inhibition of tobramycin diffusion by binding to alginate.

[3H]tobramycin bound to sodium alginate and to exopolysaccharide prepared from two mucoid strains of Pseudomonas aeruginosa. Binding to sodium alginate was similar to binding to exopolysaccharide, both in the dependence on tobramycin concentration and in the maximum binding observed at saturation. Incorporation of sodium alginate into agar plates reduced the zone sizes of growth inhibition caused by tobramycin. The reductions in zone sizes were quantitatively accounted for by the binding of tobramycin to sodium alginate during diffusion of the antibiotic away from the well in which it had been placed at the start of the experiment. However, the binding of tobramycin to the exopolysaccharide of P. aeruginosa, and the resulting inhibition of diffusion of the antibiotic, did not significantly increase the penetration time of a spherical microcolony with a radius of 125 micron, such as might be found in the respiratory tract of a patient with cystic fibrosis (from a 90% penetration time of 12 s in the absence of exopolysaccharide to one of 35 s with an exopolysaccharide concentration of 1.0% [wt/vol]).

Alginates↗
PubMed1986

The permeability parameter of the outer membrane of Pseudomonas aeruginosa varies with the concentration of a test substrate, cephalosporin C.

The permeability parameter (C) for the movement of cephalosporin C across the outer membrane of Pseudomonas aeruginosa was measured using the widely accepted method of Zimmermann & Rosselet. In one experiment, the value of C varied continuously from 4.2 to 10.8 cm3 min-1 (mg dry wt cells)-1 over a range of concentrations of the test substrate, cephalosporin C, from 50 to 5 microM. Dependence of C on the concentration of test substrate was still observed when the effect of a possible electric potential difference across the outer membrane was corrected for. In quantitative studies of beta-lactam permeation the dependence of C on the concentration of beta-lactam should be taken into account.

Cell Membrane Permeability↗
PubMed1983

Synovial fluid lactate and the diagnosis of septic arthritis.

To assess the value of synovial fluid lactate estimation in the diagnosis of septic arthritis, 238 specimens received for routine culture and 75 reference samples were examined using a rapid enzyme technique. Samples were collected without special treatment and the effect of delay in transport to the laboratory investigated. Raised levels were found in all cases of untreated septic arthritis, in six out of ten partially treated patients and in 19 out of 219 non-septic fluids. Special treatment of the sample was unnecessary if it was examined within six hours of aspiration. The predictive value of a negative result was 98 per cent and the value of the test appeared to be in the rapid exclusion of sepsis in untreated patients.

Arthritis, Infectious↗