Biomedical subjects

S Warren

Publications and source records attributed to S Warren.

At least 19 recordsLinked to original sources

PubMed2026

First UK use of bacteriophage therapy with DAIR for chronic Staphylococcus aureus prosthetic joint infection.

BACKGROUND: Chronic Staphylococcus aureus prosthetic joint infection (PJI) remains difficult to manage when surgical revision and long-term antibiotics are not feasible. Bacteriophage therapy is emerging as a potential adjunct, though experience in orthopedic infections, particularly in the United Kingdom, is limited. CASE SUMMARY: We report the first UK case of intra-articular bacteriophage therapy administered alongside debridement, antibiotics, and implant retention (DAIR) for chronic methicillin-sensitive Staphylococcus aureus knee PJI. An 81-year-old man with multiple comorbidities developed persistent infection following revision knee arthroplasty, with recurrent sinus formation despite multiple surgical washouts and prolonged suppressive antibiotics. Major revision surgery and amputation were not viable options. Following a multidisciplinary review through the UK Clinical Phage Network, targeted phage therapy was pursued as salvage treatment. Phage susceptibility testing identified an active lytic phage (ISP). The patient underwent open DAIR with intra-articular phage administration, adjunctive local antibiotics, short-course intravenous antimicrobials, and subsequent oral suppressive therapy. Two further intra-articular phage doses were administered postoperatively. Initial sinus closure occurred, but recurrence developed within 4 weeks. At 18 months, symptoms were partially improved with better mobility and reduced inflammation, though one sinus tract persisted. No significant adverse effects were observed. Whole-genome sequencing of pretreatment isolates demonstrated a predominantly ST5 S. aureus genotype with conserved biofilm-associated virulence genes and limited antimicrobial resistance in addition to clonal diversification consistent with chronic biofilm infection. CONCLUSION: This case demonstrates the feasibility and safety of intra-articular phage therapy during DAIR in a UK setting but highlights biological, logistical, and pharmacological factors that may limit efficacy in advanced chronic PJI.

Staphylococcus aureus↗

PubMed2006

A tryptophan amphiphilic tetramerization domain-containing acetylcholinesterase from the bovine lungworm, Dictyocaulus viviparus.

Acetylcholine (ACh) is one of an array of neurotransmitters used by invertebrates and, analogous to vertebrate nervous systems, acetylcholinesterase (AChE) regulates synaptic levels of this transmitter. Similar to other invertebrates, nematodes possess several AChE genes. This is in contrast to vertebrates, which have a single AChE gene, transcripts of which are alternatively spliced to produce different types of the enzyme which vary at their C-termini. Parasitic nematodes have a repertoire of AChE genes which include those encoding neuromuscular AChEs and those genes which code for secreted AChEs. The latter proteins exist as soluble monomers released by the parasite during infection and these AChE are distinct from those enzymes which the nematodes use for synaptic transmission in their neuromuscular system. Thus far, Dictyocaulus viviparus is the only animal-parasitic nematode for which distinct genes that encode both neuromuscular and secreted AChEs have been defined. Here, we describe the isolation and characterization of a cDNA encoding a putative neuromuscular AChE from D. viviparus which contains a tryptophan amphiphilic tetramerization (WAT) domain at its C-terminus analogous to the common 'tailed' AChE form found in the neuromuscular systems of vertebrates and in the ACE-1 AChE from Caenorhabditis elegans. This enzyme differs from the previously isolated, D. viviparus neuromuscular AChE (Dv-ACE-2), which is a glycosylphosphatidylinositol-anchored variant analogous to vertebrate 'hydrophobic' AChE.

Acetylcholinesterase↗

PubMed2006

As a bacterial culture medium, citrated sheep blood agar is a practical alternative to citrated human blood agar in laboratories of developing countries.

Human blood agar (HuBA) is widely used in developing countries for the isolation of bacteria from clinical specimens. This study compared citrated sheep blood agar (CSBA) and HuBA with defibrinated horse blood agar and defibrinated sheep blood agar (DSBA) for the isolation and antibiotic susceptibility testing of reference and clinical strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Reference and clinical strains of all organisms were diluted in brain heart infusion and a clinical specimen of cerebrospinal fluid and cultured on all agars. Viable counts, colony morphology, and colony size were recorded. Susceptibility testing for S. pneumoniae and S. pyogenes was performed on defibrinated sheep blood Mueller-Hinton agar, citrated sheep blood Mueller-Hinton agar (CSB MHA), and human blood Mueller-Hinton agar plates. For all organisms, the colony numbers were similar on all agars. Substantially smaller colony sizes and absent or minimal hemolysis were noted on HuBA for all organisms. Antibiotic susceptibility results for S. pneumoniae were similar for the two sheep blood agars; however, larger zone sizes were displayed on HuBA, and quality control for the reference strain failed on HuBA. For S. pyogenes, larger zone sizes were demonstrated on HuBA and CSBA than on DSBA. Poor hemolysis made interpretation of the zone sizes difficult on HuBA. CSBA is an acceptable alternative for the isolation of these organisms. The characteristic morphology is not evident, and hemolysis is poor on HuBA; and so HuBA is not recommended for use for the isolation or the susceptibility testing of any of these organisms. CSB MHA may be suitable for use for the susceptibility testing of S. pneumoniae.

Agar↗

PubMed2005

Distinct phenotype associated with a cryptic subtelomeric deletion of 19p13.3-pter.

Telomeres are gene rich regions with a high recombination rate. Cryptic subtelomeric rearrangements are estimated to account for 5% of mental retardation/malformation syndromes. Here we present the first patient with a deletion of 19p13.3, identified by subtelomeric FISH analysis. His features included a distinctive facial appearance, cleft palate, hearing impairment, congenital heart malformation, keloid scarring, immune dysregulation, and mild learning difficulties. Subtelomeric FISH analysis identified a deletion of 19p13.3-pter. The deletion size was determined to be 1.2 Mb by FISH analysis. It extended from within the chromosomal region covered by BAC RP11-50C6 to 19pter. The deleted area encompassed approximately 60 genes. Fifteen possible candidate genes were considered with respect to the phenotype, including follistatin-related precursor 3 (FSTL3) and serine-threonine kinase 11 (STK-11).

Abnormalities, Multiple↗

PubMed2002

Measuring quality of life of persons with spinal cord injury: external and structural validity.

STUDY DESIGN: Measurement evaluation of the external and structural components of validity. OBJECTIVES: To examine the relationships between quality of life (QOL) as measured by the spinal cord injury (SCI) version of the Ferrans and Powers Quality of Life Index (QLI) and other constructs represented within the model of disablement; and to examine the domains and scoring model of the QLI by exploring item and overall score/section score relationships. SETTING: Community, Alberta, Canada. METHODS: A convenience sample of 98 individuals with SCI living in the community completed the QLI and measures representing the model of disablement including the ASIA motor index, Functional Independence Measure, Reintegration to Normal Living index, Rosenberg's Self-Esteem Scale and Rotter's Internal-External Locus of Control scale. RESULTS: Four of the five a priori hypotheses were supported. Locus of control was not significantly related to QOL as expected. Factor analysis resulted in a five-factor structure that differed from the four-domain model of the original QLI. Scoring relationships indicated that both the satisfaction and importance ratings contribute to the overall score, although not equally. CONCLUSION: There is support for the external component of validity although further examination regarding locus of control for persons with SCI is warranted. The structural component of validity requires further investigation to elucidate the domains of the SCI version of the QLI and the contribution of the importance scores.

Activities of Daily Living↗

PubMed2001

Tenascin-C aptamers are generated using tumor cells and purified protein.

Tenascin-C (TN-C) is an extracellular matrix protein that is overexpressed during tissue remodeling processes, including tumor growth. To identify an aptamer for testing as a tumor-selective ligand, SELEX (systematic evolution of ligands by exponential enrichment) procedures were performed using both TN-C and TN-C-expressing U251 glioblastoma cells. The different selection techniques yielded TN-C aptamers that are related in sequence. In addition, a crossover procedure that switched from tumor cell to purified protein selections was effective in isolating two high-affinity TN-C aptamers. When targeting tumor cells in vitro, the observed propensity of naive oligonucleotide pools to evolve TN-C aptamers may be due to the abundance of this protein. In vivo, TN-C abundance may also be well suited for aptamer accumulation in the tumor milieu. A size-minimized and nuclease-stabilized aptamer, TTA1, binds to the fibrinogen-like domain of TN-C with an equilibrium dissociation constant (K(d)) of 5 x 10(-9) m. At 13 kDa, this aptamer is intermediate in size between peptides and single chain antibody fragments, both of which are superior to antibodies for tumor targeting because of their smaller size. TTA1 defines a new class of ligands that are intended for targeted delivery of radioisotopes or chemical agents to diseased tissues.

Animals↗

PubMed2001

A comparative assessment of Boise, Idaho, ambient air fine particle samples using the plate and microsuspension Salmonella mutagenicity assays.

The primary objective of this study is to characterize the genotoxic potential of the ambient air aerosols collected within an air shed impacted primarily by wood smoke and automotive emissions. The study also examines the relative merits of a microsuspension assay and the standard plate assay for monitoring the presence of airborne particle-bound mutagens. Wintertime ambient air particulate samples collected from Boise, Idaho, USA, were shown to contain extractable organic matter that is mutagenic in the Salmonella typhimurium microsuspension and plate-incorporation assays. Differences in the results from the primary sites, auxiliary sites and the background site demonstrate that the particle-bound mutagens are not evenly distributed within the air shed and are more associated with the location of sampling than with the time of sampling or the type of bioassay used to evaluate the samples. This study also demonstrates that the bioassay protocol used in such studies should depend upon the characteristics of the air shed's mutagens and the purpose of the study. For example, the microsuspension assay gave somewhat more variable results between samples but was approximately threefold more sensitive than the plate assay. When strain TA98 was used in the microsuspension assay, the mutagenic response was greater without an exogenous activation system. The reverse was true for the plate assay in which the use of an exogenous activation system increased the mutagenicity response. TA100 in the microsuspension assay provided results comparable to those with TA98. This is important because TA100 can also be used to bioassay semivolatile and volatile organics associated with ambient air mutagenicity. This, in turn, allows a comparison of the mutagenicity of organics collected by differing methods due to their volatility. Future studies should be directed toward correlation of mutagenicity results with other analytical results in order to further develop methods for better characterization of the genotoxicity of ambient air.

Aerosols↗

PubMed2001

Genetic susceptibility to MS: a second stage analysis in Canadian MS families.

Four published genome screens have identified a number of markers with increased sharing in multiple sclerosis (MS) families, although none has reached statistical significance. One hundred and five markers previously identified as showing increased sharing in Canadian, British, Finnish, and American genome screens were genotyped in 219 sibling pairs ascertained from the database of the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No markers examined met criteria for significant linkage. Markers located at 5p14 and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS was confirmed (P<0.0001). Significant transmission disequilibrium was also observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of searching for genes with only mild-to-moderate effects on susceptibility, although large effects of specific loci may still be present in individual families. Future progress in the genetics of this complex trait may be helped by (1) focussing on more ethnically homogeneous samples, (2) using an increased number of MS families, and (3) using transmission disequilibrium analysis in candidate regions rather than the affected relative pair linkage analysis.

Canada↗

PubMed2001

Methods for the spiral Salmonella mutagenicity assay including specialized applications.

An automated approach to bacterial mutagenicity testing - the spiral Salmonella assay - was developed to simplify testing and to reduce the labor and materials required to generate dose-responsive mutagenicity information. This document provides the reader with an overview of the spiral assay and a discussion of its application for examining the mutagenic potential of pure compounds, complex environmental mixtures, and interactive effects. Guidelines for performing a routine spiral assay are presented, and alternative test methods intended to overcome a variety of technical difficulties (such as restricted sample availability, sample viscosity or volatility, etc.) are recommended. Methods for the computerized analysis of data and the interpretation of results are discussed.

Animals↗

PubMed2001

Measuring quality of life of persons with spinal cord injury: substantive and structural validation.

The purpose of this study was to evaluate the substantive and structural validity of an existing measure of quality of life (QOL), the spinal cord injury (SCI) version of the Ferrans and Powers quality of life index (QLI). To evaluate substantive validity, 11 individuals with a SCI participated in 'think aloud' interviews to determine meaningfulness of the QLI items and to identify areas requiring modification. Free sort and ranking exercises of the items were used to evaluate the structural validity of the domains and scoring rubric. Content analysis of the interview comments resulted in the addition of two items and wording revision to three items. The free sort exercise revealed that the domains as perceived by the participants differed somewhat from those of the test developer. The contribution of the satisfaction and importance sections proposed by the scoring model was not completely supported by the data from the ranking exercise. It is concluded that the modified version of the QLI reflects the perspectives of persons with SCI spinal cord injury as represented by the participants of this study. The structural validity evaluation has implications for the use of domain subscores and weighted vs. section scores. Further evaluation of the modified version is necessary before widespread use with this patient population.

Adult↗

PubMed2000

The effect of vitamin E exposure on cadmium toxicity in mouse embryo cells in vitro.

Heavy metals such as cadmium pose a number of environmental problems in addition to being detrimental to human health. Cadmium is known to be embryotoxic in animal models and to cause brain, limb and craniofacial malformations. Among numerous mechanisms proposed for cadmium toxicity are oxidative stress and lipid peroxidation. Vitamin E has been found to have antioxidant and cytoprotective properties in cultured cells but its effect on cadmium embryonic toxicity has not yet been determined. Epithelial-like cells derived from day-8 whole-mouse embryos were used as a model embryonic tissue. Cadmium toxicity in these cultured cells was found to be both time and concentration dependent. Prior exposure to 50 microM alpha-tocopherol or 25 or 50 microM alpha-tocopherol acetate resulted in a marked reduction in the toxicity of 5 microM CdCl2. The apparent cytoprotective effects may be partly non-specific, however, as a general growth enhancement was observed after vitamin E exposure in the absence of cadmium.

Animals↗

PubMed2000

Latent learning in medial temporal amnesia: evidence for disrupted representational but preserved attentional processes.

Damage to the hippocampus and medial temporal (MT) structures can lead to anterograde amnesia and may also impair latent learning, in which prior exposure to cues affects their subsequent associability. Normally, latent learning may reflect both representational and attentional mechanisms. Prior work has suggested that individuals with MT amnesia have specific deficits in representational processing; thus, latent learning that invokes primarily representational mechanisms might be especially impaired in MT amnesia. The current results provide preliminary confirmation of this prediction. In Experiment 1, a latent learning paradigm expected to invoke representational mechanisms was impaired in individuals with MT amnesia, whereas in Experiment 2, a paradigm expected to invoke other attentional mechanisms was spared in individuals with MT amnesia. This suggests the representational and attentional components of latent learning are dissociable and differentially affected in anterograde amnesia.

Adult↗

PubMed1999

Quality of life of stroke survivors.

Adaptation to stroke requires complex, long-term change in stroke survivors' lives. This study aimed at identifying those factors that influence quality of life (QOL) of geriatric stroke survivors 1-3 years post-discharge. The objectives were: to describe the overall quality of life of stroke survivors; to examine the relationships between sociodemographic variables, neurological variables, functional status, social support, perceived health status, depression, and overall QOL; and to determine the best predictors of QOL. Data were collected on 50 stroke survivors using a cross-sectional design and standardized questionnaires, including the Quality of Life Index, the Functional Independence Measure, the Social Support Inventory for Stroke Survivors and the Centre for Epidemiologic Studies Depression Scale. The overall quality of life of the study participants was low. The most important predictors of QOL were depression, marital status, quality of social support, and functional status. Depression was the strongest predictor of QOL. By employing a multi-dimensional perspective, this study confirmed that adaptation to stroke involves much more than physical function. Thus, rehabilitation programs for this group would be more effective if they are based upon a holistic approach.

Activities of Daily Living↗

PubMed1998

Deficient cancellation of the vestibular ocular reflex in schizophrenia.

Schizophrenia has long been associated with difficulties in visual tracking of a moving object. Deficits are most notable in tracking tasks that require inhibition of saccades during active smooth pursuit. In order to assess whether there is a more global problem in inhibition of other eye movement systems while the smooth pursuit system is active, this study examined cancellation of the vestibular ocular reflex (VOR). Cancellation of the VOR occurs in a task in which the subject is rotated while looking at a target that is also being rotated. This requires the subject to use the pursuit system to override the VOR, maintain the eye at a stable location within the orbit, and thus retain visual gaze upon the target. Thirteen individuals with schizophrenia and 15 normals were assessed during clockwise rotation at 60 degrees s-1. Schizophrenic subjects had a significant increase in counterclockwise slow velocity eye movements, suggesting an impaired ability to cancel the VOR. Cancellation of the VOR is thus another example of a breakthrough of an alternative eye movement system while the smooth pursuit system is active. Because of the simplicity of the VOR and its suitability for animal modeling, investigation of this phenomenon may delineate more precisely the mechanisms of visual tracking dysfunction in schizophrenia.

Adult↗

PubMed1998

Visual form of Alzheimer's disease and its response to anticholinesterase therapy.

In a 60-year-old woman with the visual variant of Alzheimer's disease, single photon emission computed tomography abnormalities were most marked in the parieto-occipital regions of the brain. After treatment with donepezil, improvement is noted on neuropsychological testing and on brain SPECT, including increased perfusion (metabolism) in the occipital lobes.

Alzheimer Disease↗

PubMed1998

Genotoxicity of bioremediated soils from the Reilly Tar site, St. Louis Park, Minnesota.

An in vitro approach was used to measure the genotoxicity of creosote-contaminated soil before and after four bioremediation processes. The soil was taken from the Reilly Tar site, a closed Superfund site in Saint Louis Park, Minnesota. The creosote soil was bioremediated in bioslurry, biopile, compost, and land treatment, which were optimized for effective treatment. Mutagenicity profiles of dichloromethane extracts of the five soils were determined in the Spiral technique of the Salmonella assay with seven tester strains. Quantitative mutagenic responses in the plate incorporation technique were then determined in the most sensitive strains, YG1041 and YG1042. Mutagenic potency (revertants per microgram extract) in YG1041 suggested that compost, land treatment, and untreated creosote soil extracts were moderately mutagenic with Arochlor-induced rat liver (S9) but were nonmutagenic without S9. However, the bioslurry extract was strongly mutagenic and the biopile extract was moderately mutagenic either with or without S9. A similar trend was obtained in strain YG1042. The strong mutagenic activity in the bioslurry extract was reduced by 50% in TA98NR, which suggested the presence of mutagenic nitrohydrocarbons. Variation in reproducibility was 15% or less for the bioassay and extraction procedures. Bioavailability of mutagens in the biopile soil was determined with six solvents; water-soluble mutagens accounted for 40% of the total mutagenic activity and they were stable at room temperature. The mutagenic activity in the bioslurry and biopsile samples was due to either the processes themselves or to the added sludge/manure amendments. The in vitro approach was effective in monitoring bioremediated soils for genotoxicity and will be useful in future laboratory and in situ studies.

Animals↗

PubMed1997

Propagation of fluorescent light.

BACKGROUND AND OBJECTIVE: In general, the remitted fluorescence spectrum is affected by the scattering and absorption properties of tissue. Other important factors are boundary conditions, geometry of the tissue sample, and the quantum yield of tissue fluorophores. Each of these factors is examined through a series of Monte Carlo simulations. STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo modeling is used to simulate the propagation of excitation light and the resulting fluorescence. Remitted fluorescence is determined for semi-infinite single and multiple layer geometries and for cubic geometries representing small tissue samples. Monte Carlo results are compared to approximations obtained with a heuristic model. RESULTS: Remitted fluorescence as a function of (1) the depth of fluorescence generation and (2) radial escape position is presented for semi-infinite single and multiple layer geometries. Fluorescence from a small tissue sample is simulated in terms of a cubic geometry, and losses from the sides and bottom are presented as a function of cube dimensions in terms of optical depth of the excitation wavelength. Monte Carlo results for a homogeneous semi-infinite layer are compared to a simple, fast heuristic model. CONCLUSION: Both Monte Carlo simulations and the heuristic model clearly detail the volume of tissue interrogated by fluorescence. Since approximately 35-40% of the remitted fluorescence is due to photons originally directed away from the surface, distal layers affect the remitted fluorescence. Fluorescence spectra from small biopsy samples may not produce the correct line shape owing to wavelength dependent losses.

Aorta↗

PubMed1997

Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus.

Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium-reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n = 6, albumin excretion rate (AER) mean (range) 4 (0-10) micrograms/min], and microalbuminuric [group B, n = 6, AER 88 (35-198) micrograms/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary beta 2-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2-15.1), 9.3 (5.9-15) and 4.1 (4.0-5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P < 0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with B 2-microglobulin in the diabetic subjects (r = 0.665, P < 0.05) and with the degree of microalbuminuria in group B patients (r = 1, P < 0.01). Urinary GH was also greater than 10 microU, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of 51Cr-ethylene diamine tetra-acetic acid (EDTA) and I125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbumiruric group compared with controls (P < 0.05) and group B (P < 0.05). Absolute proximal reabsorption of sodium and of water (APRNa and APRH2O) was significantly higher in group A patients (P < 0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may coexist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.

Absorption↗