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S P Barrett

Publications and source records attributed to S P Barrett.

At least 19 recordsLinked to original sources
PubMed1999

Molecular epidemiology of multi-resistant Escherichia coli.

In this case-control study multi-resistant Escherichia coli isolates were characterized on a molecular level and risk factors for their development were identified. Thirty-two multi-resistant E. coli strains were isolated from the urine of 13 patients attending a renal clinic for chronic urinary tract infection (UTI) and from different sites of 11 terminally ill patients with nosocomial infections hospitalized on five different wards. All 32 isolates were resistant to ciprofloxacin, cotrimoxazole and produced beta-lactamase. All strains contained plasmids of 2-110 MDa of which a 50 MDa and a 100 MDa plasmid were present in 81% of the strains. Pulse-field gel electrophoresis (PFGE) analysis demonstrated 17 genotypes among 32 strains which indicates a polyclonal outbreak with some geographic clustering. Monitoring of patients over the study period showed that either the resident genotype remained the same and that these retained strains underwent changes in their plasmid contents, or that they were replaced by a different genotype after several months of therapy for chronic UTI. Univariate analysis indicated that multi-resistant E. coli develop in the presence of long-term selective ciprofloxacin pressure at a dosing regimen of 250 mg bid for more than 20 days and that treatment with a broad spectrum antimicrobial for more than three days favours the selection of multi-resistant E. coli in the flora of terminally ill patients with multiple disorders.

Aged↗
PubMed1999

Antibiotic sensitivity of bacteria associated with community-acquired urinary tract infection in Britain.

Twelve laboratories in different parts of Britain each supplied approximately 80 consecutive urinary bacterial isolates from community patients. All strains were identified by a central laboratory, where sensitivity to a variety of orally administered antimicrobials was determined by microtitre broth dilution. 65.1% of isolates were Escherichia coli, 23.4% 'coliforms' other than E. coli, 4.6% Proteus and Morganella spp., 1.8% Pseudomonas spp., 2.4% enterococci, 0.7% group B streptococci, 1.5% coagulase-negative staphylococci and 0.5% Staphylococcus aureus. Using previously published breakpoint sensitivity values, 98.9% of all isolates were found to be sensitive to norfloxacin and to ciprofloxacin, 95.7% to co-amoxiclav, 86.8% to nitrofurantoin, 77.4% to cephalexin, 75.6% to trimethoprim, 75.0% to cephradine and 51.7% to amoxycillin. There were some differences in sensitivities between centres, particularly those of the cephalosporins. Using standard breakpoints, submitting laboratories were found to overestimate sensitivity to nitrofurantoin and to underestimate sensitivity to the quinolones and to co-amoxiclav; there was considerable overestimation of sensitivity to cephalosporins.

Anti-Bacterial Agents↗
PubMed1999

DNA banding pattern polymorphism in vancomycin-resistant Enterococcus faecium and criteria for defining strains.

The degree of DNA banding pattern polymorphism exhibited by vancomycin-resistant Enterococcus faecium (VREM) strains isolated on a renal unit over an 11-month period was investigated. Thirty VREM strains from different patients were analyzed by pulsed-field gel electrophoresis (PFGE; with extended run and optimal pulse times), ribotyping, plasmid profile analysis, biotyping, pyrolysis mass spectrometry, and antibiogram analysis. PFGE resolved 17 banding patterns which formed four distinct clusters at the 82% similarity level. Intercluster band differences ranged from 14 to 31 bands. The strains in one cluster, which contained seven patterns that differed from each other by one to seven bands and from the common pattern by five bands, were confirmed to be a single strain by four of the five other typing methods. The strains in a second cluster with eight patterns, which differed from each other by 1 to 12 bands, contained two subclusters. This subdivision was supported by ribotyping and biotyping. However, it was unclear whether these subclusters represented distinct strains. In one strain, marked polymorphism (patterns that differed from each other by up to four bands) was observed in the ribotype pattern. This study demonstrates the high degree of DNA banding pattern polymorphism found for some strains of VREM and illustrates the complexity involved in defining such strains.

Anti-Bacterial Agents↗
PubMed1998

Trying to control MRSA causes more problems than it solves.

Despite occasional reports of local success, the steadily increasing prevalence of strains of Staphylococcus aureus resistant to methicillin (MRSA) shows that attempts to limit their spread do not work. In this commentary we suggest that efforts to control the spread of methicillin-resistance are counterproductive, and that energies should instead be directed towards the control of outbreaks of disease and preventing the emergence of antibiotic resistance.

Cross Infection↗
PubMed1998

Variation amongst human isolates of Brachyspira (Serpulina) pilosicoli based on biochemical characterization and 16S rRNA gene sequencing.

Brachyspira pilosicoli (formerly Serpulina pilosicoli) causes swine spirochaetosis and can also be isolated fro human faeces, although its role in human disease remains unclear. The genetic and biochemical variations amongst 19 isolates of human spirochaetes from five different countries were evaluated and compared to those found amongst swine isolates of B. pilosicoli. All isolates were negative for beta-glucosidase and all but one were positive for hippurate hydrolysis, which are characteristics typical of B. pilosicoli. The isolates showed variation in indole production and alpha-galactosidase and alpha-glucosidase activity, other characteristics which can be used to identify B. pilosicoli. The DNA sequences of part of the 16S rRNA gene differed from each other and from that of B. pilosicoli by 0-3 bp out of 283 bp. It is concluded that there is considerable variation amongst human intestinal spirochaetes. Since few of the isolates reported here match the current criteria for B. pilosicoli, it is concluded that this species is more heterogeneous than previously appreciated. However, it cannot be excluded that some isolates may belong to uncharacterized related Brachyspira/Serpulina species.

Animals↗
PubMed1998

Human enteric pathogens identified in a London teaching hospital and a rural public health laboratory: 1994.

Two microbiology laboratories, one serving an inner city hospital and one a rural public health laboratory, collected data on the outcome of examining faecal specimens in 1994. Overall, 6.7% of the investigations were positive, but the rates were lower for hospital inpatients, for recently described pathogens, and in the absence of relevant clinical details; rates were higher for patients with a history of foreign travel. No benefit was gained by examining more than two specimens from any patient. Clostridium difficile was the only investigation frequently positive among patients already in hospital, and virological tests were often positive in patients investigated by general practitioners.

Communicable Diseases↗
PubMed1997

Infection control and the Internet.

The Internet can be enormously valuable for infection control workers. It provides access to policy documents and discussion groups debating everyday problems, and is a comprehensive source of information on infection-related topics. Here we discuss some of the more useful Internet connections.

Computer Communication Networks↗
PubMed1996

Interferon-gamma is required during the initiation of an organ-specific autoimmune disease.

Autoimmune gastritis induced by neonatal thymectomy of mice is a CD4+ T cell-mediated organ-specific autoimmune disease. The characteristic features of autoimmune gastritis, which include a mononuclear infiltrate within the gastric mucosa, loss of parietal and chief cells and circulating autoantibodies to the gastric H+/K+ ATPase, appear 6-10 weeks after thymectomy. Here we have assessed the role of interferon-gamma (IFN-gamma) in the pathogenesis of the gastric lesion. Splenic T cells derived from mice with gastritis produced three- to tenfold more IFN-gamma than T cells from normal animals after stimulation with anti-CD3 antibodies. Treatment of neonatally thymectomized mice at weekly intervals for 6 or 12 weeks with a neutralizing rat monoclonal antibody to mouse IFN-gamma abolished the production of anti-gastric autoantibodies and decreased the incidence of gastric mononuclear infiltrates from the 69% observed in normal rat immunoglobulin (Ig)-injected mice to 16%. Further, in mice treated with only a single dose of anti-IFN-gamma immediately after thymectomy at 3 days after birth, the incidence of autoimmune gastritis was 1/19 compared to 8/19 in normal rat Ig-injected mice. Prevention of autoimmunity by neutralization of IFN-gamma several weeks prior to the detection of a pathological lesion strongly suggests that IFN-gamma plays an essential role in the initiation of the gastric autoimmune response.

Animals↗
PubMed1996

Heterogeneity of human intestinal spirochaetes demonstrated by one-dimensional polyacrylamide gel electrophoresis of proteins visualised by (35)S-methionine labelling and Coomassie blue staining.

The relatedness of strains of a human intestinal spirochaete was investigated by comparison of electrophoretic protein profiles produced by Coomassie Blue staining of proteins separated by polyacrylamide gel electrophoresis (PAGE) of lysed organisms and by examination of autoradiographs following PAGE of lysed (35)S-methionine-labelled organisms. A wide diversity of strains was revealed by both techniques but clustering of strains was different by the two methods. These findings support the view that the human intestinal spirochaetes comprise a group of bacteria of considerable heterogeneity.

Autoradiography↗
PubMed1995

Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia.

Autoimmune gastritis, a CD4+ T cell-mediated organ-specific autoimmune disease, can be induced by thymectomy of neonatal, but not of older, BALB/c mice. Here we have shown that autoimmune gastritis can also be induced in 6-8-week-old BALB/c mice by thymectomy combined with a single dose of cyclophosphamide (300 mg/kg). This treatment reduced the numbers of splenic T and B cells approximately 25-fold. However, by 8 days after treatment, the number of splenic lymphocytes had returned to normal adult levels. Approximately 50% of treated mice developed autoimmune gastritis after 10-12 weeks. These mice had mononuclear cellular infiltrates within the gastric mucosa and serum autoantibodies to the alpha and beta subunits of the gastric H+/K+ ATPase. Transgenic mice, expressing the gastric H+/K+ ATPase beta-subunit in the thymus (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419), did not develop autoimmune gastritis after the adult thymectomy/cyclophosphamide treatment. Thus a T cell response to the H+/K+ ATPase beta-subunit is likely to be required for the onset of gastritis. These observations suggest that pathogenic autoreactive T cells exist in the periphery of normal adult mice and that autoimmunity can be induced by the activation of these autoreactive T cells following transient lymphopenia. Cyclophosphamide-treatment of adult mice without thymectomy did not induce autoimmune gastritis, suggesting thymic regulation of these pathogenic T cells.

Aging↗
PubMed1995

Expression of a gastric autoantigen in pancreatic islets results in non-destructive insulitis after neonatal thymectomy.

Autoimmune gastritis, induced by day-3 thymectomy of BALB/c mice, is a destructive CD4+ T cell-mediated disease characterized by leukocyte infiltrates in the gastric mucosa, loss of parietal and chief cells and anti-gastric H/K ATPase autoantibodies. Our previous studies have indicated that a T cell response to the H/K ATPase beta subunit is required for the onset of autoimmune gastritis (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419). To determine whether a response to the beta subunit autoantigen is alone sufficient to induce autoimmunity, or whether other tissue-specific factors are required, we have generated transgenic mice expressing the gastric H/K ATPase beta subunit in beta islet cells of the pancreas (RIP-H/K beta). RIP-H/K beta mice developed autoimmune gastritis and insulitis after day-3 thymectomy. Significantly, insulitis, observed as a peri-islet infiltrate, was only detected in thymectomized mice with autoimmune gastritis. There was no apparent immune destruction of the pancreas as insulitis did not progress to invasion of the islets or diabetes. Double transgenic mice, expressing the gastric H/K ATPase beta subunit in the thymus and in the pancreas, were protected from both gastritis and insulitis after day-3 thymectomy. Therefore, insulitis in the RIP-H/K beta mice appears to be dependent on a T cell response to the H/K ATPase beta subunit. This is the first example where an organ-specific initiating autoantigen has been expressed in another peripheral tissue. Autoimmune destruction in the stomach, but not the pancreas, indicates that tissue-specific factors play a fundamental role in the development of organ-specific autoimmunity.

Animals↗
PubMed1995

Control of infection with multiple antibiotic resistant bacteria in a hospital renal unit: the value of plasmid characterization.

An outbreak of infections due to multiple antibiotic-resistant bacteria took place over a period of approximately 18 months in a renal unit. Strains of Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Citrobacter spp. and Pseudomonas spp. were involved, and a variety of antibiotic resistances was encountered. Closely related plasmids encoding resistance to aztreonam, ceftazidime and piperacillin, possibly derived from an archetypal plasmid of 105 kb were found in the majority of isolates examined. After limiting the use of aztreonam the incidence of new patient isolates of multiple-resistant organisms was greatly reduced. This study demonstrated how molecular studies can contribute to the control of an outbreak situation in a hospital unit by providing an impetus to reduce the use of specific antibiotics.

Cross Infection↗
PubMed1995

Detection of mycobacteria in bone marrow biopsy specimens taken to investigate pyrexia of unknown origin.

AIMS: To investigate the value of bone marrow biopsy in the diagnosis of mycobacterial infection. METHODS: The culture results of 433 bone marrow samples taken between 1983 and 1992 were reviewed. The histopathology reports on bone marrow trephine specimens of culture positive samples and all those on HIV positive patients sent in 1992 were also reviewed. RESULTS: Fifty one specimens yielded Mycobacterium spp, 47 were obtained from HIV positive patients. Of the isolates, 42 were Mycobacterium avium-intracellulare (MAI), five were M tuberculosis (MTB), and the remaining four comprised a variety of atypical mycobacteria. All MAI positive samples were obtained from HIV positive patients, with the bone marrow being the only culture positive specimen in one third. Bone marrow yielded MTB only in patients from whom it was also isolated in other specimens. Eleven of 47 trephine specimens from positive bone marrow showed granulomata and nine showed acid-fast bacilli. No acid-fast bacilli were seen in the absence of granulomata. CONCLUSION: Bone marrow biopsy for mycobacterial culture should be reserved for severely immunosuppressed patients and should not be advocated for immunocompetent patients with suspected tuberculosis. Bone marrow biopsy still has a role in the investigation of pyrexia of unknown origin in HIV positive patients, despite the advent of mycobacterial blood culture techniques, particularly if these can be processed safely in automated systems.

Bone Marrow↗
PubMed1995

Fast freeze-fixation/freeze-substitution reveals the secretory membranes of the gastric parietal cell as a network of helically coiled tubule. A new model for parietal cell transformation.

The parietal cell of the gastric mucosa undergoes rapid morphological transformation when it is stimulated to produce hydrochloric acid. In chemically fixed cells, this process is seen as a reduction in number of cytoplasmic 'tubulovesicles' as the apical surface of the cell progressively invaginates to increase the secretory surface area. It is widely believed that the tubulovesicles represent stored secretory membrane in the cytoplasm of the unstimulated cell, which is incorporated into the apical membrane upon stimulation, because they share H+,K+-ATPase activity with the apical membrane. However, fusion of tubulovesicles with the apical membrane concomitant with parietal cell activation has never been convincingly demonstrated. We have used fast freeze-fixation and freeze-substitution to study stages of morphological transformation in these cells. Tubulovesicles were not seen in the cytoplasm of any of our cryoprepared cells. Instead, the cytoplasm of the unstimulated cell contained numerous and densely packed helical coils of tubule, each having an axial core of cytoplasm. The helical coils were linked together by connecting tubules, lengths of relatively straight tubule. Lengths of straight connecting tubule also extended from coils lying adjacent to the apical and canalicular surfaces and ended at the apical and canaliculus membranes. Immunogold labelling with alpha- and beta-subunit-specific antibodies showed that the gastric H+,K+-ATPase was localized to the membranes of this tubular system, which therefore represented the configuration of the secretory membrane in the cytoplasm of the unstimulated parietal cell. Stimulation of the cells with histamine and isobutylmethylxanthine lead to modification of the tubular membrane system, correlated with progressive invagination of the apical membrane. The volume of the tubule lumen increased and, as this occurred, the tight spiral twist of the helical coils was lost, indicating that tubule distension was accounted for by partial unwinding. This exposed the cores of cytoplasm in the axes of the coils as rod-shaped elements of a three-dimensional reticulum, resembling a series of microvilli in random thin sections. Conversely, treatment with the H2 antagonist cimetidine caused severe contraction of the tubular membrane system and intracellular canaliculi. Our results indicate that tubulovesicles are an artifact of chemical fixation; consequently, they cannot have a role in parietal cell transformation. From our findings we propose an alternative model for morphological transformation in the parietal cell. This model predicts cytoskeleton-mediated control over expansion and contraction of the tubular membrane network revealed by cryopreparation. The model is compatible with the localization of cytoskeletal components in these cells.

Animals↗