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Biomedical subjects

L Stuart

Publications and source records attributed to L Stuart.

15 recordsLinked to original sources
PubMed2005

Interclinician variation in diabetes foot assessment--a national lottery?

AIM: The aim was to evaluate variation among clinicians in the outcome of assessments of foot health status and risk status in patients with diabetes. METHODS: Seventeen clinicians assessed three patients with diabetes using a standardized assessment form and risk classification system. RESULTS: There was variation among clinicians in all aspects of the assessment; recording basic demographic information; taking a medical history; vascular and neurological assessments. Variation was also evident in the risk categories allocated to each of the three patients. CONCLUSIONS: As a consequence of the variation among clinicians in the foot assessment the same patient would have received different care pathways to monitor and manage their foot health depending upon which clinician undertook their initial assessment. We therefore recommend that more attention is placed on training for objective clinical testing, at both pre- and postgraduate levels.

Aged↗
PubMed2001

Nonphlogistic clearance of late apoptotic neutrophils by macrophages: efficient phagocytosis independent of beta 2 integrins.

Neutrophils undergo constitutive death by apoptosis, leading to safe nonphlogistic phagocytosis and clearance by macrophages. Recent work has shown that before secondary necrosis, neutrophils exhibiting classical features of apoptosis can progress to a morphologically defined late apoptotic state. However, whether such neutrophils could be safely cleared was unknown. We now report that human late apoptotic neutrophils could be purified from cultured neutrophil populations undergoing constitutive death and were subsequently ingested by human monocyte-derived macrophages by serum-independent mechanisms that did not trigger the release of IL-8 or TNF-alpha. Such ingestion was specifically inhibited by Abs to thrombospondin-1 and the alpha(v)beta(3) vitronectin receptor. Murine bone marrow-derived macrophage phagocytosis of late and early apoptotic neutrophils occurred by similar mechanisms, proceeding with the same efficiency as that observed for wild-type controls when macrophages from [alpha(m)](-/-) or [beta(2)](-/-) mice were used. We conclude that specific nonphlogistic, beta(2) integrin-independent mechanisms involving thrombospondin-1 and alpha(v)beta(3) allow macrophages to ingest late apoptotic neutrophils without eliciting inflammatory cytokine secretion.

Animals↗
PubMed2001

Role for cysteine residues in the in vivo folding and assembly of the phage P22 tailspike.

The predominantly beta-sheet phage P22 tailspike adhesin contains eight reduced cysteines per 666 residue chain, which are buried and unreactive in the native trimer. In the pathway to the native trimer, both in vivo and in vitro transient interchain disulfide bonds are formed and reduced. This occurs in the protrimer, an intermediate in the formation of the interdigitated beta-sheets of the trimeric tailspike. Each of the eight cysteines was replaced with serine by site-specific mutagenesis of the cloned P22 tailspike gene and the mutant genes expressed in Escherichia coli. Although the yields of native-like Cys>Ser proteins varied, sufficient soluble trimeric forms of each of the eight mutants accumulated to permit purification. All eight single Cys>Ser mature proteins maintained the high thermostability of the wild type, as well as the wild-type biological activity in forming infectious virions. Thus, these cysteine thiols are not required for the stability or activity of the native state. When their in vivo folding and assembly kinetics were examined, six of the mutant substitutions--C267S, C287S, C458S, C613S, and C635S--were significantly impaired at higher temperatures. Four--C290S, C496, C613S, and C635--showed significantly impaired kinetics even at lower temperatures. The in vivo folding of the C613S/C635S double mutant was severely defective independent of temperature. Since the trimeric states of the single Cys>Ser substituted chains were as stable and active as wild type, the impairment of tailspike maturation presumably reflects problems in the in vivo folding or assembly pathways. The formation or reduction of the transient interchain disulfide bonds in the protrimer may be the locus of these kinetic functions.

Adhesins, Bacterial↗
PubMed2000

Diminished epidermal growth factor levels in infants with necrotizing enterocolitis.

BACKGROUND/PURPOSE: Because epidermal growth factor (EGF) is trophic to the intestinal mucosa, and neonatal necrotizing enterocolitis (NEC) is associated with a disrupted intestinal mucosal barrier, the authors sought to determine whether diminished levels of EGF were present in infants with NEC. METHODS: Saliva, serum, and urine specimens were obtained from infants with NEC during a 3-year period (February 1995 to May 1998). Control patients without NEC were chosen based on similar postnatal age and birthweight. EGF levels were determined by enzyme-linked immunosorbent assay (ELISA). Differences between groups were compared using Mann-Whitney Rank sum test with P less than .05 considered significant. Results are presented as mean values +/-SEM. RESULTS: Twenty-five infants with NEC were compared with 19 control patients. Birth weight (1,616+/-238 g control v. 1,271+/-124 g NEC) and postnatal age (23+/-6 days control v. 22+/-3 days NEC) were similar. Infants with NEC had significantly lower levels of EGF in both saliva (590+/-80 pg/mL control v. 239+/-41 pg/mL NEC; P<.001) and serum (35+/-8 pg/mL control v. 5.6+/-1.9 pg/mL NEC; P<.001). Urinary EGF was also lower in the NEC group, but was not statistically significant. CONCLUSIONS: Premature infants with NEC have significantly diminished levels of salivary and serum EGF. Reduced levels of this growth factor may distinguish infants at risk for NEC and play a pivotal role in the pathogenesis of the perturbed intestinal mucosal barrier that is central to this condition.

Enterocolitis, Necrotizing↗
PubMed2000

Tornado disaster in rural Georgia: triage response, injury patterns, lessons learned.

Our objective was to characterize the medical response and injury patterns from a recent tornado disaster in rural southeastern Georgia. We conducted a retrospective review of 11 patients treated at a Level I trauma center after sustaining injuries due to an April 9, 1998 F3 tornado. Data were obtained from trauma registry and medical records. Of 11 victims, 8 (73%) were male. Ages ranged from 5 to 54 years. Two patients were triaged directly by military helicopter, six arrived as secondary triage from local rural hospitals (2 by air, 4 by ground), and three arrived by delayed secondary transfer. Six patients were thrown by the tornado, and five were struck by flying debris. All victims were either in exposed areas or mobile homes. Injuries by anatomic region included the chest (45%), abdomen (27%), extremity (91%), and head (45%). Nine (82%) of the patients required surgical intervention. These included three laparotomies, one thoracotomy, six orthopedic procedures, and one neurosurgical procedure. The average Injury Severity Score (ISS) was 23. Among patients who were thrown mean ISS was 31; among those struck by debris, mean ISS was 12. Hemodynamically significant pelvic fractures occurred in three patients (27%). The major complication, sepsis due to Serratia marcescens was seen in three patients, all of whom had been thrown and had clinically significant wound contamination. Both patients who died had Serratia sepsis and multiorgan system failure. The injuries and inclement weather characteristic of tornado disasters stress regional trauma triage responses, cause significant injury, and disrupt communities. Injury patterns involve multiple systems and require coordinated efforts among caretakers. Infectious complications are common and frequently involve Gram-negative bacilli and are associated with soil-contaminated wounds. Trauma severity increases if the victim is thrown rather than struck by flying debris.

Adolescent↗
PubMed1998

Reversible snaring for proper prosthetic seating during valve replacement.

A method of reversible suture snaring is described for evaluating the final valve seating and positioning before knot tying of valve sutures. This allows for alteration of the operative plan before investing substantial ischemic time in a nonfunctional result. The procedure has been used in 577 consecutive prosthetic valve replacements in the past 5 years. The technique maintains proper seating while the valve is permanently anchored in place.

Heart Valve Diseases↗
PubMed1997

A comparison of qualitative and quantitative research methods used to assess knowledge of foot care among people with diabetes.

Many diabetes-related pathologies, especially among neuropathic patients, are potentially avoidable. Prevention, however, requires appropriate knowledge and understanding. To assess our ability to effect change in behaviour we need adequate tools to measure not only knowledge but also understanding and change of behaviour. To assess individuals' knowledge and beliefs towards diabetic footcare, we used both quantitative and qualitative methods: a structured questionnaire composed of 20 questions was completed by the respondent, followed by a semi-structured interview conducted by the chiropodist. Results from the structured questionnaire were inconsistent with those from the interviews (Wilcoxon test, p < 0.008). The former demonstrated an average knowledge score of 45% while performance during the interview generated data which suggested poorer knowledge levels. Respondents who correctly identified a series of statements regarding diabetic footcare within the questionnaire could not then apply this knowledge meaningfully when interviewed. A structured questionnaire may not be the best means of assessing patients' knowledge and understanding. We need not only to improve patient education regarding footcare, but also to improve our means of measuring patient knowledge and understanding, more accurately to assess the success or otherwise of our interventions.

Aged↗
PubMed1996

Redox regulation of manganese superoxide dismutase.

The importance of reactive oxygen species (ROS) or changes in cellular redox state in signal transduction and gene regulation is becoming increasingly evident. In this study, we tested the hypothesis that ROS are directly involved in the induction of the mitochondrial antioxidant manganese superoxide dismutase (MnSOD) and mediate the induction of MnSOD by tumor necrosis factor-alpha (TNF-alpha). Pretreatment of human pulmonary adenocarcinoma cells H441 with the antioxidants N-acetyl-L-cysteine (NAC) and nordihydroguaiaretic acid (NDGA) blocked MnSOD induction by TNF-alpha, implicating ROS as a signaling agent in this pathway. Treatment of H441 cells with the exogenous oxidants hydrogen peroxide (H2O2) and diamide increased MnSOD mRNA, supporting the hypothesis that ROS directly affect expression of MnSOD. The temporal pattern of MnSOD induction differed for TNF-alpha and H2O2, suggesting distinct signaling pathways. DNA binding of two redox-sensitive transcription factors, NF-kappa B and activator protein (AP)-1, was evaluated. TNF-alpha increased nuclear factor (NF)-kappa B-DNA binding, an effect blocked by pretreatment with NAC. H2O2 did not alter NF-kappa B-DNA binding. There was no evidence of AP-1 binding in cells treated with either TNF-alpha or H2O2. We conclude that ROS directly alter MnSOD expression and are involved in the induction of MnSOD by TNF-alpha.

Antioxidants↗
PubMed1991

Antinuclear antibodies using HEp-2 cells in normal children and in children with common infections.

Antinuclear antibody (ANA) immunofluorescence tests, using HEp-2 cells, were performed on 100 children without a history of connective tissue disease. Eighteen (18%) were positive at titres greater than or equal to 1:40, nine (9%) being greater than 1:160. Interlaboratory variability was demonstrated with some specimens. No association with possible intercurrent infection was found to account for positive results. Of 44 children with proven infections five (11%) were positive. Antinuclear antibody may be found in some normal children when using the sensitive HEp-2 cell substrate, and in the absence of clinical features should not necessarily suggest the presence of a connective tissue disease.

Adolescent↗
PubMed1976

Transplantation in miniature swine. I. Fixation of the major histocompatibility complex.

Three strains of miniature swine, each homozygous for a different allele of the major histocompatibility locus (MHC), have been developed by a selective breeding scheme based on tissue typing of the offspring of each generation. Prior to breeding, the original parents were reciprocally immunized by skin grafts and lymphocyte injections to produce lymphocytotoxic antisera. These antisera were then used to assess the MHC genotype of the offspring by an analysis based on selective absorption of cytotoxicity. Offspring inheriting the same serologically determined genotype were then bred sequentially. Subsequent mixed lymphocyte cultures showed a pattern of reactivity consistent with the serological genotyping, further confirming the homology between the MHC of these miniature swine and those of man and mouse. In addition to their usefulness as a model for large animal surgical transplantation, these animals provide an abundant homozygous source of histocompatibility antigens and of antihistocompatibility antisera for use in chemical characterization of products of the MHC.

Animals↗
PubMedDate not supplied

The correlation grid: analysis of synchronous spiking in multi-dimensional spike train data and identification of feasible connection architectures.

This paper presents a visualization technique specifically designed to support the analysis of synchronous firings in multiple, simultaneously recorded, spike trains. This technique, called the correlation grid, enables investigators to identify groups of spike trains, where each pair of spike trains has a high probability of generating spikes approximately simultaneously or within a constant time shift. Moreover, the correlation grid was developed to help solve the following reverse problem: identification of the connection architecture between spike train generating units, which may produce a spike train dataset similar to the one under analysis. To demonstrate the efficacy of this approach, results are presented from a study of three simulated, noisy, spike train datasets. The parameters of the simulated neurons were chosen to reflect the typical characteristics of cortical pyramidal neurons. The schemes of neuronal connections were not known to the analysts. Nevertheless, the correlation grid enabled the analysts to find the correct connection architecture for each of these three data sets.

Action Potentials↗
PubMedDate not supplied

Visualisation of synchronous firing in multi-dimensional spike trains.

The gravity transform algorithm is used to study the dependencies in firing of multi-dimensional spike trains. The pros and cons of this algorithm are discussed and the necessity for improved representation of output data is demonstrated. Parallel coordinates are introduced to visualise the results of the gravity transform and principal component analysis (PCA) is used to reduce the quantity of data represented whilst minimising loss of information.

Action Potentials↗