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Biomedical subjects

R Paton

Publications and source records attributed to R Paton.

At least 19 recordsLinked to original sources

Linkage of ciprofloxacin resistance with a single genotypic cluster of Klebsiella pneumoniae.

The objective of this study was to examine the epidemiology of ciprofloxacin-resistant, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strains. Sixty-nine unique patient isolates of K. pneumoniae isolated from a variety of clinical specimens submitted to the clinical bacteriology laboratories of The Royal Infirmary of Edinburgh and associated General Practices were identified and susceptibility testing was performed with the Vitek system. Strains flagged as ESBL-positive by the Vitek system were subjected to isoelectric focusing. The results suggested that all 69 isolates harboured at least one ESBL, which was later confirmed by polymerase chain reaction (PCR) with bla(TEM) and/or bla(SHV) primers. The purified PCR product was subjected to automated sequencing and the results were compared with the BLAST online search engine. Of the 69 isolates, 32 (46.4%) were found to be resistant to ciprofloxacin, 11 (15.9%) were intermediate and 26 (37.7%) were sensitive. To investigate the epidemiological relationship between the ciprofloxacin-resistant ESBL-positive strains, pulsed-field gel electrophoresis (PFGE) was performed. Rapidest software was used to calculate the genetic distance by the Nei distance method. PFGE analysis indicated that the clinical isolates belonged to four distinct genotype clusters (Groups A, B, C and D); each group or cluster was homogeneous or compact with respect to certain characteristics. Group A consisted of 25 isolates, group B of 3 isolates and Groups C and D of 2 isolates each. These results indicate that the spread of resistance is largely as a result of the dissemination of a single clonal strain. PCR was used to amplify the gyrA and parC genes from genomic DNA of the ciprofloxacin-resistant isolates. The amplified product was sent for analysis by automated DNA sequencing and the resulting DNA sequences were compared with the gyrA gene of K. pneumoniae. The sequencing results demonstrated that alteration of the GyrA subunit of DNA gyrase at amino acid 83 and/or amino acid 87 plays a central role in conferring high-level quinolone resistance in K. pneumoniae possessing ESBLs.

Anti-Infective Agents↗

Characterization of extended-spectrum beta-lactamase (ESBL)-producing Kuwait and UK strains identified by the Vitek system, and subsequent comparison of the Vitek system with other commercial ESBL-testing systems using these strains.

Two hundred and fifty-one unique patient isolates of Klebsiella pneumoniae (123), Escherichia coli (114), Klebsiella oxytoca (7), Enterobacter cloacae (5) and Citrobacter freundii (2), flagged as extended-spectrum beta-lactamase (ESBL) positive by the Vitek system (GNS-526 card), were collected. These strains were isolated from a variety of clinical specimens submitted to the clinical bacteriology laboratories of the Royal Infirmary of Edinburgh (RIE), Edinburgh, UK (and associated GP practices), Hairmyers Hospital, Glasgow, UK, and the Amiri and Farwania Hospitals, Kuwait. Of the 101 RIE strains tested, 15 E. coli strains were found to be ESBL negative by Etest ESBL strips. On retesting the 15 E. coli strains with the Vitek GNS-532 card, 14 were found to be ESBL negative, despite being originally flagged as ESBL positive. The remaining 236 ESBL-producing strains were also subjected to the double disc-diffusion (DDD) technique for the detection of ESBLs. Of these, two were false negatives by Etest ESBL test strips (using both cefotaxime and ceftazidime strips), and 38 were false negatives by the DDD method. The Etest false-negative ESBL-producing strains of K. pneumoniae were positive by DDD. Technically, the Vitek method was the least demanding method to perform, as it was an integral part of the routine susceptibility test card. Etest strips were reliable, but were the most expensive of all the techniques used. The DDD test, while relatively inexpensive, was technically subjective, and in our hands, seven of the ESBL-positive strains that were confirmed by the other two techniques were not detected. Despite the false-positive ESBL-producing E. coli strains, the Vitek susceptibility card with its integral ESBL test offers the clinical laboratory a valuable and quick option to screen for ESBL-producing Klebsiella spp. and E. coli as part of the routine laboratory methodology.

Anti-Bacterial Agents↗

Long-term continuous positive airway pressure (CPAP) outcomes from a sleep service using limited sleep studies and daycase CPAP titration in the management of obstructive sleep apnoea/hypopnoea syndrome.

BACKGROUND: Detailed polysomnography (PSG) and overnight continuous positive airway pressure (CPAP) titration as the basis for investigation and treatment of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) incurs high costs from inpatient stays and technician attendance, even when split night studies are employed. Responding to rapidly increasing demand, from 1996 the sleep service at Glasgow Royal Infirmary adopted limited sleep studies and daycase CPAP titration as first line management. Here we describe the outcomes of this service between 1996 and 1999. METHODS: Data were collected from prospective records made at follow up by sleep technicians and by casenote review. RESULTS: Results were available for 158 subjects (97.5%) of 162 commenced on CPAP during this period. One hundred and forty-eight (91%) were diagnosed by limited sleep studies and 80 (50%) were diagnosed at home. The median follow up was 23 months (interquartile range (IQR), 13-35). Median use of CPAP in those continuing therapy was 5.3 hours/night (IQR, 3.1 to 6.5) and 77% were still using CPAP at three years. Only initial low CPAP compliance (< 2 hours/night) significantly predicted early CPAP cessation. In those still on CPAP in 1999, the mean drop in Epworth Sleepiness Scale score was 4.6 points (95% confidence intervals, 3.2 to 6.0). CONCLUSION: These data from the CPAP population at Glasgow Royal Infirmary provide information on longterm outcomes using a diagnostic protocol based on limited sleep studies and daycase CPAP titration.

Adult↗

Thunderstorm-associated asthma in an inland town in south-eastern Australia. Who is at risk?

The aim of the study was to characterize patients at risk of asthma exacerbation during spring thunderstorms and identify potential measures to ameliorate the impact of those events. A case-control study was conducted among patients aged 7-60 yrs, who attended Wagga Hospital (NSW, Australia) for asthma during the period of 1 June 1997 to 31 October 1997. One hundred and eighty-three patients who attended on 30 and 31 October 1997 were the cases and the remaining 121 patients were the controls. Questionnaire data were obtained from 148 (81%) cases and 91 (75%) controls. One hundred and thirty-eight (95%) cases who attended during the thunderstorm gave a history of hayfever prior to the event compared to 66 (74%) controls who attended at other times (odds ratio (OR) 6.01, 95% confidence interval (CI) 2.55-14.15); 111 (96%) cases were allergic to rye grass pollen compared to 47 (64%) controls (OR 23.6, 95% CI 6.6-84.3). Among subjects with a prior diagnosis of asthma (64% cases and 82% controls), controls (56%) were more likely to be taking inhaled steroids at time of the thunderstorm than cases (27%, OR 0.3, 95% CI 0.16-0.57). History of hayfever and allergy to rye grass are strong predictors for asthma exacerbation during thunderstorms in spring. The lower rate of inhaled steroid use in thunderstorm cases suggests that this treatment may be effective in preventing severe attacks during thunderstorms.

Adolescent↗

Susceptibility testing of Haemophilus influenzae to clarithromycin.

Susceptibility testing of Haemophilus influenzae to the macrolide compounds has often been problematic. This is as a result of the inability of many isolates of H. influenzae to grow without the addition of 5% CO2 to the incubation atmosphere and the subsequent detrimental effect that CO2 has on the activity of the macrolide group of compounds. This report describes refinements and recommendations for susceptibility testing of H. influenzae to the macrolide clarithromycin.

Anti-Bacterial Agents↗

The persistence and clonal spread of a single strain of Acinetobacter 13TU in a large Scottish teaching hospital.

This study describes the persistence and spread of a single strain of Acinetobacter 13TU in a large Scottish teaching hospital. Acinetobacter spp. are reported with increasing frequency as a cause of nosocomial infection. The species most implicated in these infections is Acinetobacter baumannii. Following an outbreak of infection with Acinetobacter 13TU within the intensive therapy unit (ITU) of Edinburgh Royal Infirmary (ERI) during 1994-1995, the current epidemiological Acinetobacter situation within the hospital was monitored to determine whether or not control of infection procedures instigated at that time had been successful in controlling the outbreak. Sixty-eight strains of Acinetobacter spp were isolated from clinical specimens received from various wards in the ERI and other associated hospitals over a 7-month period. Each isolate was typed phenotypically by the API20NE system and genotypically by pulsed field gel electrophoresis (PFGE) in order to compare them with the previous outbreak strain. Fifty-three percent of the isolates collected were originally identified as A. junii by API 20 NE, of which 83% (mainly from ITU) were shown to be genotypically related to the previous outbreak strain. Subsequent tDNA fingerprinting of one of the original outbreak strains showed it to be a member of the genospecies 13TU and not A. junii as originally thought.

Acinetobacter↗

Epidemiology and control of vancomycin-resistant enterococci (VRE) in a renal unit.

This study reports an outbreak of infection and colonization caused by vancomycin-resistant enterococci (VRE) in the renal service of a large teaching hospital. The polymerase chain reaction and pulsed-field gel electrophoresis were used to study the epidemiology of 26/34 strains of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium from the outbreak in comparison with five strains from other hospitals in Edinburgh and the Borders, and three from other wards in the Royal Infirmary. The study revealed a heterogeneous population of vancomycin-resistant E. faecalis. Over 60% of E. faecium isolates had matching pulsed-field gel electrophoresis patterns and all of these were of VanA phenotype. These results suggest that clonal spread of VanA phenotype E. faecium within and possibly between hospitals is the major vancomycin-resistant enterococcal problem in Edinburgh. Screening of patients and isolation of colonized and infected patients appear to have been successful in controlling the spread of VRE.

Anti-Bacterial Agents↗

The organisations of hereditary information.

The meaning of hereditary information is not simple. It includes not only what a system receives and transmits but particularly what it makes. The syntactic basis to hereditary information is also not straightforward. For example, is DNA instructions, or data, or both? The answer to this question requires an appreciation of the meaning of the information yet there are a number of possible semantic systems for describing hereditary information including proteins and development. The descriptive boundaries of hereditary information are examined by locating some general organising themes including hierarchy, ecology, regulation, epigenetic systems and talkback. Though metaphors have limits in terms of their explanatory power a number have influenced the development of biological thinking and biosystems have variously been represented as chemical laboratories, computers, electromechanical machines and societies. In this article a further metaphor is discussed, that of life-as-a-play or dance in which the trio of script (genome), cast (metabolism) and stage (cellular structure) co-exist and pre-exist the phenotypic life history which inherits them. A fuller examination of this trio provides an important perspective on the study of the organisations of information processing in hereditary systems.

Genetic Code↗

Metaphors, models and bioinformation.

The notion of bioinformation is central to the biosciences. This short paper examines a number of metaphors which are intimately related to this idea. These include metaphors about 'system' as well as metaphors associated with biosystem as 'text'. A framework its presented which allows ideas about biosystems and computer systems to be displaced and a number of specific topics are then discussed. Firstly, information processing in non-neural tissues is given as an example of parallel distributed processing. This is followed with a number of metaphors associated with 'text', including 'glue', 'verbs' and 'interpretation'. The paper concludes with a proposal on how to integrate general ideas of bioinformation using the idea of the 'ecology of domains'.

Information Theory↗

An object-oriented approach to knowledge representation in a biomedical domain.

An object-oriented approach has been applied to the different stages involved in developing a knowledge base about insulin metabolism. At an early stage the separation of terminological and assertional knowledge was made. The terminological component was developed by medical experts and represented in CORE. An object-oriented knowledge acquisition process was applied to the assertional knowledge. A frame description is proposed which includes features like states and events, inheritance and collaboration. States and events are formalized with qualitative calculus. The terminological knowledge was very useful in the development of the assertional component. It assisted in understanding the problem domain, and in the implementation stage, it assisted in building good inheritance hierarchies.

Algorithms↗

Biochemical properties of inducible beta-lactamases produced from Xanthomonas maltophilia.

Four different beta-lactamases have been found in several strains of Xanthomonas maltophilia isolated from blood cultures during 1984 to 1991 at the Edinburgh Royal Infirmary. One was a metallo-beta-lactamase with predominantly penicillinase activity and an isoelectric point of 6.8. Its molecular size as determined by gel filtration was 96 kDa but was only 26 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), suggesting a tetramer of four equal subunits. The enzyme hydrolyzed all classes of beta-lactams except the monobactam aztreonam. This enzyme was not inhibited by potassium clavulanate or BRL 42715 but was inhibited by p-chloromercuribenzoate, mercuric chloride, and EDTA. The beta-lactamase was unstable in 50 mM sodium phosphate buffer (pH 8.0) but stable in 50 mM Tris HCl (pH 8.0). The other beta-lactamases focused as a series of different isoelectric points, ranging from pI 5.2 to 6.6. Together, these enzymes exhibited a broad spectrum of activity, hydrolyzing most classes of beta-lactams but not imipenem or aztreonam. Their molecular size was 48 kDa by Sephadex gel filtration and 24 kDa by SDS-PAGE, indicating that they were enzymes consisting of two equal subunits. They were inhibited by p-chloromercuribenzoate, mercuric chloride, potassium clavulanate, and BRL 42715 but not EDTA. This study demonstrated that X. maltophilia produces more than just the L1 and L2 beta-lactamases.

Anti-Bacterial Agents↗

Activity of clindamycin against Staphylococcus aureus and Staphylococcus epidermidis from four UK centres.

MICs of penicillin, methicillin, clindamycin, erythromycin, sodium fusidate and gentamicin were determined by an agar dilution method for 300 current isolates of Staphylococcus aureus and 100 of S. epidermidis, collected from four centres, and 38 stock strains of methicillin-resistant S. aureus (MRSA). All but one of the 300 current isolates of S. aureus were sensitive to clindamycin (MIC less than 0.5 mg/l), with an MIC90 of 0.12 mg/l. Of a total of 39 MRSA strains, 11 (28.2%) were resistant to clindamycin (MIC greater than 32 mg/l); all of these strains were also resistant to erythromycin. Ten of the 100 strains of S. epidermidis were resistant to clindamycin; they came from a reasonably equal geographical distribution and were also resistant to erythromycin. The results suggest that clindamycin might still be useful as a second-line agent for infections caused by S. aureus and S. epidermidis, although its activity against MRSA was limited to approximately two-thirds of the MRSA strains tested in this study.

Clindamycin↗

Who pays for PREPP?

Although it is now known that PREPP is to be implemented, there is still much uncertainty as to how it will be funded. Will nurses receive funding for their continuing education needs from health trusts, be expected to self-fund or seek sponsorship from drug companies?

Education, Nursing, Continuing↗