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Biomedical subjects

J Sunderland

Publications and source records attributed to J Sunderland.

At least 19 recordsLinked to original sources
PubMed2005

Ventriculitis due to a hetero strain of vancomycin intermediate Staphylococcus aureus (hVISA): successful treatment with linezolid in combination with intraventricular vancomycin.

A 67-year male presented with relapse 14 days after treatment with vancomycin for a MRSA ventriculitis. CSF samples taken at the time of relapse grew MRSA with a MIC for vancomycin of 4 mg/L by E-test and therapy with linezolid (600 mg bd) and intraventricular vancomycin (20 mg od) was initiated. Using the macrodilution E-test, the isolate was found to have sub-populations with a MIC for vancomycin of 8 mg/L and teicoplanin of 12 mg/L and a population analysis profile almost identical to the hVISA strain MU3, indicative of a hVISA strain. Concentrations of vancomycin in the CSF over the period of therapy ranged from 25.6-192.5 mg/L after intraventricular administration and those of linezolid ranged from 3.4-6.7 mg/L after intravenous administration, exceeding the MICs for this isolate. The patient made a successful recovery, with no further episodes of ventriculitis at 1-year follow-up. We report the first case of ventriculitis due to hVISA. It was successfully treated with intrathecal vancomycin and intravenous linezolid. We also believe this to be the first documented case of clinical infection due to hVISA in South Africa.

Acetamides↗
PubMed2005

Effect of the growth promoter avilamycin on emergence and persistence of antimicrobial resistance in enteric bacteria in the pig.

AIM: To assess the effect of the growth promoter avilamycin on emergence and persistence of resistance in enteric bacteria in the pig. METHODS AND RESULTS: Pigs (treated with avilamycin for 3 months and controls) were challenged with multi-resistant Salmonella Typhimurium DT104 and faecal counts were performed for enterococci, Escherichia coli, S. Typhimurium and Campylobacter (before, during and 5 weeks post-treatment). Representative isolates were tested for antibiotic resistance and for the presence of resistance genes. Avilamycin-resistant Enterococci faecalis (speciated by PCR) were isolated from the treated pigs and continued to be detected for the first week after treatment had ceased. The avilamycin-resistance gene was characterized by PCR as the emtA gene and speciation by PCR. MIC profiling confirmed that more than one strain of Ent. faecalis carried this gene. There was no evidence of increased antimicrobial resistance in the E. coli, Salmonella and Campylobacter populations, although there was a higher incidence of tetB positive E. coli in the treated pigs than the controls. CONCLUSION: Although avilamycin selects for resistance in the native enterococci population of the pig, no resistant isolates were detected beyond 1 week post-treatment. This suggests that resistant isolates were unable to persist once selective pressure was removed and were out-competed by the sensitive microflora. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data suggest the risk of resistant isolates becoming carcass contaminants and infecting humans could be minimized by introducing a withdrawal period after using avilamycin and prior to slaughter.

Animal Husbandry↗
PubMed2003

The effect of chlortetracycline treatment and its subsequent withdrawal on multi-resistant Salmonella enterica serovar Typhimurium DT104 and commensal Escherichia coli in the pig.

AIMS: To investigate the effect of a therapeutic and sub-therapeutic chlortetracycline treatment on tetracycline-resistant Salmonella enterica serovar Typhimurium DT104 and on the commensal Escherichia coli in pig. METHODS AND RESULTS: Salmonella Typhimurium DT104 was orally administered in all pigs prior to antibiotic treatment, and monitored with the native E. coli. Higher numbers of S. Typhimurium DT104 were shed from treated pigs than untreated pigs. This lasted up to 6 weeks post-treatment in the high-dose group. In this group, there was a 30% increase in E. coli with a chlortetracycline minimal inhibitory concentration (MIC) > 16 mg l-1 and a 10% increase in E. coli with an MIC > 50 mg l-1 during and 2 weeks post-treatment. This effect was less-pronounced in the low-dose group. PCR identified the predominant tetracycline resistance genes in the E. coli as tetA, tetB and tetC. The concentration of chlortetracycline in the pig faeces was measured by HPLC and levels reached 80 microg g-1 faeces during treatment. CONCLUSION: Chlortetracycline treatment increases the proportion of resistant enteric bacteria beyond the current withdrawal time. SIGNIFICANCE AND IMPACT OF THE STUDY: Treated pigs are more likely to enter abattoirs with higher levels of resistant bacteria than untreated pigs promoting the risk of these moving up the food chain and infecting man.

Animals↗
PubMed2001

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.

AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.

Adult↗
PubMed2001

Food allergy--towards predictive testing for novel foods.

The risks associated with IgE-mediated food allergy highlight the need for methods to screen for potential food allergens. Clinical and immunological tests are available for the diagnosis of food allergy to known food allergens, but this does not extend to the evaluation, or prediction of allergenicity in novel foods. This category, includes foods produced using novel processes genetically modified (GM) foods, and foods that might be used as alternatives to traditional foods. Through the collation and analysis of the protein sequences of known allergens and their epitopes, it is possible to identify related groups which correlate with observed clinical cross-reactivities. 3-D modelling extends the use of sequence data and can be used to display eptiopes on the surface of a molecule. Experimental models support sequence analysis and 3-D modelling. Observed cross-reactivities can be examined by Western blots prepared from native 2-D gels of a whole food preparation (e.g. hazelnut, peanut), and common proteins identified. IgEs to novel proteins can be raised in Brown Norway rat (a high IgE responder strain) and the proteins tested in simulated digest to determine epitope stability. Using the CSL serum bank, epitope binding can be examined through the ability of an allergen to cross-link the high affinity IgE receptor and thereby release mediators using in vitro cell-based models. This range of methods, in combination with data mining, provides a variety of screening options for testing the potential of a novel food to be allergenic, which does not involve prior exposure to the consumer.

Allergens↗
PubMed2001

Antimicrobial activity of fluoroquinolone photodegradation products determined by parallel-line bioassay and high performance liquid chromatography.

The fluoroquinolones produce multiple photodegradation products. Little is known about these products, particularly whether any possess antimicrobial activity. To investigate this, we used the parallel-line bioassay to investigate discrepancies in zone of inhibition size in conjunction with high performance liquid chromatography (HPLC) analysis. A continuous flow photochemical reaction unit ('Beam-Boost') was used to partially photodegrade the fluoroquinolones ofloxacin, levofloxacin, ciprofloxacin and moxifloxacin (0.02 mM) by between 15 and 89%, as confirmed by HPLC. The concentration of residual parent fluoroquinolone in each irradiated sample was measured by HPLC and a non-irradiated control solution was prepared at the same concentration. These were compared by parallel-line bioassays using Escherichia coli, Enterobacter cloacae and Klebsiella oxytoca. With ofloxacin and levofloxacin, the zone size for the control solution was significantly less than that of the irradiated solutions, with >15% photodegradation in at least two of the indicator organisms, indicating that the photodegradation products possess antimicrobial activity. No difference was seen with ciprofloxacin at any level of photodegradation with any of the indicator organisms, nor with moxifloxacin at 30 and 54% photodegradation. A significant difference was observed with E. cloacae only, at 83% photodegradation.

Anti-Infective Agents↗
PubMed2001

A simple, isocratic high-performance liquid chromatography assay for linezolid in human serum.

A rapid high-performance liquid chromatography (HPLC) assay for the detection of linezolid in human serum was developed. The method used a Hypersil 5ODS stationary phase. The mobile phase was 1% ortho-phosphoric acid, 30% methanol, 2 g/L heptane sulphonic acid, pH 5. UV absorbance detection was used (lambda(max) 254 nm). Samples were prepared by mixing with acetonitrile and an injection volume of 20 microL was used. The inter- and intra-day assay reproducibility were assessed. Assay linearity, specificity and accuracy were investigated. The detection limit and recovery of linezolid from serum were determined. In addition, the stability of linezolid, stored under a variety of conditions, was assessed. The retention time of linezolid was c. 6.5 min. The intra- and inter-day reproducibility was good and the assay was linear across the therapeutic range. Serum recovery was c. 100% at all concentrations tested. The detection limit was 0.1 mg/L and the assay was accurate. The assay was specific as there was no significant interference with the linezolid peak. Linezolid was demonstrated to be stable. This rapid assay is ideal for busy clinical laboratories with basic HPLC equipment.

Acetamides↗
PubMed2001

Analysis of repertory grids in clinical practice.

OBJECTIVES: This paper illustrates the use of several different forms of analysis of repertory grid data, using a case study of a client who completed repertory grids at various stages of therapy. METHOD: Participants in a survivors' group completed grids before and after therapy and at 3- and 6-month follow-up. Grids from one of the participants, who had been sexually abused as a child, are presented using different levels of analysis: visual inspection of the raw grid; analysis of dissimilarities between pairs of elements or constructs; hierarchical cluster analysis of elements and constructs both separately and combined; principal components analysis; biplot representation of elements and constructs combined; multidimensional scaling analysis and unfolding analysis. The latter two methods also provide ways of presenting a combined analysis of a number of grids. Computer packages are reviewed, and SYSTAT commands are presented to perform the analyses. RESULTS: The review of methods illustrates how different levels of analysis can usefully back up clients' own accounts of progress through therapy, from detailed analysis of individual ratings in the raw grid, through analyses that pull out structural patterns at the expense of detail, to the broad sweep provided by methods that combine data from a number of grids. CONCLUSIONS: Analysis of repertory grids completed at various stages of therapy can provide useful qualitative information on progress, but can also provide some simple quantitative measures (such as Self-Ideal Self discrepancy as a measure of self esteem) to track progress. Different forms of analysis can be informative, highlighting different aspects of progress, but also allowing checks on adequacy and goodness-of-fit of particular analyses.

Adult↗
PubMed2000

Identification of peanut and hazelnut allergens by native two-dimensional gel electrophoresis.

A procedure for the native two-dimensional electrophoresis of peanut and hazelnut proteins is described. Proteins were solubilised after acetone treatment using a combination of 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and tetramethylene sulphone. These extracts were analysed by a combination of isoelectric focusing in the presence of lactose in immobilized pH gradients followed by charge shift electrophoresis. Immunoblot analysis, using sera from nut allergic patients, allowed the identification of a peanut and hazelnut allergen with identical isoelectric point and apparent molecular mass. These proteins were recovered from duplicate gels using a mixture of formic acid, acetonitrile (ACN) and isopropanol. The molecular masses for both proteins, determined by matrix assisted laser desorption/ionisation-mass spectrometry (MALDI-MS), were 4826 Da.

2-Propanol↗
PubMed1998

Comparison of the modified Stokes' method of susceptibility testing with results obtained using MIC methods and British Society of Antimicrobial Chemotherapy breakpoints.

The majority of clinical microbiology laboratories in the UK use comparative disc diffusion methods based on the Stokes' method to determine antibiotic susceptibility. The technical validity of the results obtained from the modified Stokes' method of disc testing and how they relate to MIC data are not known. We studied susceptibility testing using a modified Stokes' disc diffusion method for a wide range of clinical isolates against which MICs had been determined by collaborators not involved with the disc testing evaluation. Results indicated that for 1301 organism-antibiotic combinations the number of major errors (where resistant strains were reported as sensitive) was 21/468 (4.4%) and the number of minor errors (where sensitive strains were reported as resistant) was 14/713 (1.9%) using ciprofloxacin breakpoints of 0.5 and 2 mg/L. There was good correlation between the disc susceptibility test and the MIC for 119 isolates of Enterobacteriaceae tested with the exception of Serratia spp. Excluding Serratia spp. the number of major errors for Enterobacteriaceae was 1/200 (0.5%). Data revealed 2/25 (8%) major errors for Pseudomonas aeruginosa and 1/45 (2.2%) for Acinetobacter spp. Haemophilus influenzae showed a number of unexpected categorization errors. The modified Stokes' method performed accurately for Staphylococcus aureus and coagulase-negative staphylococci when tested for susceptibility to gentamicin, erythromycin, teicoplanin and vancomycin. No major errors were reported for Streptococcus pneumoniae and beta-haemolytic streptococci. Problems occurred with the detection of antibiotic resistance in Enterococcus spp. Major errors were seen for ampicillin (2/12 strains), teicoplanin (5/6 strains) and vancomycin (5/13 strains) using a 30 microg disc but only 1/13 strains using a 5 microg disc. Overall, from our data, the modified Stokes' disc diffusion antibiotic susceptibility test showed an unacceptable number of major errors but an acceptable number of minor errors.

Anti-Bacterial Agents↗
PubMed1997

Time-kill kinetics of quinupristin/dalfopristin on Staphylococcus aureus with and without a raised MBC evaluated by two methods.

Some strains of staphylococci have raised MBCs of quinupristin/dalfopristin compared with their MICs. In this study, the time-kill kinetics of quinupristin/dalfopristin at 2 mg/L on two strains of Staphylococcus aureus were determined by viable count and intracellular ATP measurement. After 24 h exposure to quinupristin/dalfopristin, the percentage survival of the strain with a raised MBC was 5.9 and that of the strain with a normal MBC was 0.04. The time-kill kinetics of the strain with a raised MBC were analogous to those associated with phenotypic tolerance.

Anti-Bacterial Agents↗
PubMed1996

A search for immunoglobulins inhibiting gonadal cell steroidogenesis in premature ovarian failure.

Premature ovarian failure (POF) may be caused by the action of circulating gonadotrophin receptor-blocking antibodies. Luteinizing hormone (LH)-stimulated testosterone production from mouse Leydig cells and follicle stimulating hormone (FSH)-stimulated oestradiol production from immature rat Sertoli cells were therefore studied in the presence of protein-G purified immunoglobulin G (IgG) samples from control subjects (n = 9), infertile women with elevated early follicular phase FSH levels but otherwise normal menstrual cycles (n = 10), and patients with POF (n = 10) or Graves' disease (n = 10). A saturating and subsaturating (78% for LH; 60% for FSH) dose of each hormone was chosen for study. A commercial preparation of human IgG (Sigma IgG, 0.75 mg/ml) employed as negative control had no effect on basal or gonadotrophin-stimulated steroidogenesis. In its presence, saturating doses of LH (2 IU/l) and FSH (20 IU/l) gave rise to 11.2 +/- 0.8 (n = 7) and 25.1 +/- 5.8 (n = 8) fold increases in steroid secretion. IgG (0.75 mg/ml) had no effect in the four groups on LH-stimulated testosterone outputs using a saturating (2 IU/l) or subsaturating (1 IU/l) dose of hormone. For example, LH (2 IU/l)-stimulated testosterone production was 94% (83-96 median; interquartile range) and 88% (81-99) of the Sigma IgG control for control and POF groups respectively. However, four out of nine IgG samples from the normal subjects (mean +/- SEM = 86 +/- 6%), two out of 10 of the high FSH group (77 +/- 4%), five out of 10 with Graves' disease (86 +/- 3%) and six out of 10 with POF (76 +/- 6%) gave rise to LH (2 IU/l)-stimulated testosterone outputs which were lower (P < 0.05) than that of Sigma IgG control. Using the identical set of patients and an IgG concentration of 0.25 mg/ml, the FSH-stimulated oestradiol outputs of the four groups were similar when using either the saturating (20 IU/l) or subsaturating (5 IU/l) dose of the hormone. Thus, the percentage of FSH (20 IU/l)-stimulated oestradiol production of the Sigma IgG control was 81 (66-89 median, interquartile range) and 50 (38-84) for control and POF groups respectively. However, once again individual patients had inhibitory IgGs such that four out of nine (controls), three out of 10 (high FSH group), four out of 10 (Graves' disease) and six out of 10 (POF patients) inhibited (P < 0.05) FSH (20 IU/l)-stimulated oestradiol secretion by 52 +/- 9 (mean +/- SEM), 44 +/- 7, 52 +/- 6 and 41 +/- 6% respectively. Of the patients with inhibitory IgGs the extent of inhibition of gonadotrophin-stimulated steroid secretion was similar between the groups. In conclusion, there is little evidence to suggest that immunoglobulins blocking gonadotrophin receptors are a mechanism for POF in a large proportion of women suffering from this condition.

Adult↗