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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 37 records · Page 2Linked to original sources

Saturation of postsynaptic receptors at central synapses?

A fundamental issue in synaptic physiology is whether the postsynaptic response to a quantum of transmitter is limited by the number of receptors available. Fierce debate over the past few years has yielded no consensus. The majority of evidence suggests that the degree of receptor occupancy is likely to be sensitive to a number of factors, including the detailed anatomy of the synaptic cleft and the time course of transmitter clearance, and is probably different from one synapse to the next.

Animals

State anxiety following 20 minutes of bicycle ergometer exercise at selected intensities.

An attempt was made to determine if state anxiety responses following acute exercise are influenced by the intensity of exercise. Fifteen adults (5 female, 10 male) completed 20 minute sessions of bicycle ergometer exercise on separate days at intensities equal to 40, 60, or 70% VO2peak. Expired gas spirometry was employed to determine peak oxygen consumption and to control the workload during the submaximal protocols. State anxiety (STAI-Y1) was assessed prior to and following each exercise session, and 5, 60 and 120 minutes post-exercise. Repeated measures ANOVA revealed that state anxiety decreased (p < 0.05) following each exercise condition. Post hoc analysis indicated that state anxiety was significantly (p < 0.05) reduced at all post-exercise assessments in the 40 and 60% VO2peak conditions. State anxiety was elevated by 3.4 units at 5 minutes following exercise at 70% VO2peak, but decreased (p < 0.05) below baseline at 60 and 120 minutes post-exercise to a degree not different from the other exercise conditions. Further analysis indicated the increase in anxiety 5 minutes following 70% VO2peak exercise was significant only in subjects with low baseline state anxiety values, whereas it was unchanged in subjects with higher baseline values. In conclusion, 20-minute sessions of cycle ergometer exercise at intensities ranging from light to heavy were equally effective in reducing state anxiety in young, healthy adults. However, this reduction is delayed somewhat following exercise at a high intensity (i.e., 70% VO2peak).

Adult

Killing of Streptococcus sanguis in biofilms using a light-activated antimicrobial agent.

The aim of this study was to determine whether Streptococcus sanguis, when in a biofilm, could be killed using a light-activated antimicrobial agent. Biofilms were grown on hydroxyapatite, irradiated with up to 12.2 J of light from a gallium aluminium arsenide laser in the presence of aluminium disulphonated phthalocyanine (AlPcS2) and survivors enumerated. No significant decrease in the viable count was found when either the AlPcS2 or the laser light was used alone. There was a light dose related decrease in the viable counts of irradiated AlPcS2-treated biofilms. No viable streptococci were detectable following irradiation with 12.2 J of laser light.

Aluminum

Pneumococcal keratitis, bacteremia, and septic arthritis in an asplenic patient.

We report the case of a 66-year-old black woman who presented with concomitant acute infectious keratitis, bacteremia, and septic arthritis caused by Streptococcus pneumonia. The septic arthritis resolved rapidly with surgical drainage and intravenous antibiotics, but despite aggressive topical and intravenous antibiotic therapy for the infectious keratitis, the cornea perforated, the patient developed endophthalmitis, and the eye eventually was eviscerated. To the best of our knowledge this is the first reported case of this nature. This patient had undergone splenectomy > 50 years prior to developing these infections. Although the risk of serious infection in clinically significant bacteremia is greatest in the perioperative period after splenectomy, these patients are at increased risk of such events for a lifetime. Because encapsulated bacteria, especially Pneumococcus, pose the greatest risk of sepsis and infection in asplenic patients, pneumococcal vaccination of penicillin prophylaxis must always be considered in these patients. A careful and complete medical history and systemic evaluation remain a crucial element of the evaluation and management of serious infectious keratitis.

Aged

Susceptibility of oral bacterial biofilms to antimicrobial agents.

There is great interest in the use of antimicrobial agents for the prevention and treatment of plaque-related oral diseases and many publications have reported the results of studies in which the minimum inhibitory concentrations of agents for cariogenic and periodontopathogenic bacteria have been determined. However, such data are relevant only to situations where the organisms of interest are in aqueous suspension, whereas in caries and the inflammatory periodontal diseases the target organisms are in the form of biofilms. On the basis of studies with medically important bacteria, it has been established that bacteria in biofilms are invariably less susceptible to antimicrobial agents than their planktonic counterparts. Therefore, in the laboratory assessment of agents which may be suitable for treating plaque-related diseases, the target organisms should be in the form of biofilms. While laboratory evaluation of chemical agents for the prevention of plaque formation has usually employed biofilm-based models, the search for antimicrobial agents effective in the treatment of plaque-related diseases has not. Therefore, there are few data available regarding those characteristics of antimicrobial agents (e.g., their biofilm eliminating concentrations or biofilm killing concentrations) that could be used to judge their suitability for treating plaque-related diseases. In this review the limited information available concerning the antimicrobial susceptibility of oral bacteria in biofilms is presented.

Anti-Bacterial Agents

The killing of Helicobacter pylori by low-power laser light in the presence of a photosensitiser.

Helicobacter pylori is associated with various gastrointestinal disorders. Lethal photosensitisation was investigated as a possible technique for killing H. pylori which might offer a better alternative to antibiotics. The susceptibility of H. pylori to lethal photosensitisation was determined by mixing suspensions of H. pylori with various photosensitisers and plating out on blood agar before irradiation with low-power laser light. Five sensitisers were studied further by mixing them with H. pylori in a tissue-culture plate and counting survivors after irradiation as a function of laser exposure time, dye concentration and pre-irradiation time. Crystal violet and thionine were ineffective as sensitisers, but zones of inhibition appeared with methylene blue (MB), protoporphyrin IX (PPIX), haematoporphyrin derivative (HPD), toluidine blue O (TBO) and disulphonated aluminium phthalocyanine (S2). Laser light or sensitiser alone did not affect bacterial viability. S2 (100 microg/ml) with a laser light energy density of 16 J/cm2, HPD (10O microg/ml) with 160 J/cm2, MB (100 microg/ml) with 21 J/cm2, PPIX (150 microg/ml) with 320 J/cm2 and TBO (50 microg/ml) with 160 J/cm2 all reduced bacterial viability by >99%. The killing of sensitised H. pylori by laser light offers a new approach to the treatment of localised infections when all colonised areas are accessible to light.

Coloring Agents

Susceptibility of biofilms of Streptococcus sanguis to chlorhexidine gluconate and cetylpyridinium chloride.

Biofilms of Streptococcus sanguis and planktonic cells of the organism were exposed to chlorhexidine gluconate and cetylpyridinium chloride, at concentrations used clinically, and survivors enumerated. S. sanguis exhibited a lower susceptibility to both antiseptics when it comprised a biofilm than when the organism was in the planktonic form. No viable bacteria were detectable after 5 min of exposure of planktonic cells to 0.2% (w/v) chlorhexidine gluconate or 0.05% (w/v) cetylpyridinium chloride, whereas viable bacterial survived in biofilms of S. sanguis even after exposure to these agents for 4 h. Older biofilms (7 days old) had similar susceptibilities to the antiseptics as younger biofilms (4 days old). Chlorhexidine achieved kills corresponding to approximately a 2 log10 reduction in the viable count of biofilms, containing approximately 10(7) colony-forming units after 5 min of incubation, whereas the corresponding kills achieved by cetylpyridinium chloride amounted to approximately a 1 log10 reduction. However, on a molar basis, cetylpyridinium chloride was the more effective of the two antiseptics. Minimum inhibitory concentration determinations showed chlorhexidine gluconate to be more effective against S. sanguis than cetylpyridinium chloride. The results of this study have revealed that the minimum inhibitory concentration is not a reliable predictor of the relative effectiveness of antimicrobial agents against S. sanguis biofilms.

Anti-Infective Agents, Local

The relationship between ethnicity and advance directives in a frail older population.

OBJECTIVE: To assess the relationship between ethnicity and Health Care wishes, including Advance Directives, in a group of frail older persons in PACE (Program For All Inclusive Care Of The Elderly). DESIGN: Retrospective chart review of 1193 participants in the PACE program. SETTING: Program of All Inclusive Care Of The Elderly (PACE), a comprehensive managed care demonstration program serving frail older participants at 10 sites across the nation. PARTICIPANTS: A total of 1193 older adults, all of whom met state criteria for nursing home level of care. There were 385 non-Hispanic whites, 364 blacks, 156 Hispanics, and 288 Asians. MEASUREMENTS: Presence or absence of advance directives, type of health care wishes selected including living will, durable power of attorney, and health care proxy. RESULTS: Frail older white, black, Hispanic and Asian Americans differ significantly in their health care wishes and how they choose to express them. Blacks were significantly more likely to select aggressive interventions and less likely than non-Hispanic whites and Hispanics to utilize a written instrument for expressing health care wishes. Whites were significantly more likely to utilize written documents for advance directives, whereas Asians were more likely to select less aggressive interventions but were unlikely to use written advance directives. CONCLUSIONS: In this population, we found significant ethnic variations in choice of health care wishes. Although health care wishes are an individual decision, an awareness of cross cultural patterns can assist practitioners in addressing the concerns of their patients, as well as assisting Health Care Policy Development.

Advance Directives

0.1%/0.2% commercial chlorhexidine solutions as subgingival irrigants in chronic periodontitis.

This study compared 2 proprietary chlorhexidine (CH) products, Corsodyl (CO-0.2% CH, then ICI, U.K.) and Eludril (EL-0.1% CH, Pierre Fabre, France) as subgingival irrigants adjunctive to Simplified Oral Hygiene. 19 subjects, 8M, 11F, aged 30-57 years, mean 44 years, took part. Probing pocket depth (PPD) ranged from 5-10 mm, mean 6.5 mm (CO and EL), with 60 CO and 65 EL sites. After oral hygiene instruction, without stress on interdental cleaning, patients received on visit supra- and subgingival debridement, and instruction in subgingival irrigation using the Max-I-Probe system (Smith & Nephew MPL, USA). For baseline, days 28 (end of irrigation), 56 and 84, data were respectively: GI (medians): 1.7, 1.2, 1.2, 1.0 (CO), 1.9, 1.5, 1.3, 1.0 EL); BOP (medians): 1.2, 0.4, 0.7, 0.4 (CO), 1.5, 0.6, 0.6, 0.25 (EL); PPD (mm) (means): 6.3, 4.8, 4.2, 4.5 (CO), 6.8, 5.2, 5.3, 4.7 (EL); PAL (mm) (means-change relative to day 0): 0.6, 0.5, 0.8 (CO), 0.8, 0.8, 1.5 (EL). By Wilcoxon for non-parametric and t-tests for parametric data, both groups showed significant improvement for all variables at all times relative to baseline, with only one significant difference between the groups, in favour of EL, for PAL at day 84 (p < 0.05). This pilot study indicates that both simplified oral hygiene regimes are effective in periodontitis, but that there was no difference between the 2 commercial irrigants as adjunctives.

Adult

Comparison of the pro-inflammatory cytokine-stimulating activity of the surface-associated proteins of periodontopathic bacteria.

Saline extraction of the periodontopathic bacterium, Actinobacillus actinomycetemcomitans, releases surface-associated material (SAM), a complex mixture of proteins and carbohydrates with potent biological actions on isolated bone and on various mammalian cell populations. In this study, the relative ability of the SAM from 5 organisms, implicated in the pathology of periodontal disease, to stimulate human mesenchymal and myelomonocytic cells to synthesize the proinflammatory cytokines - interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)alpha has been investigated. The bacteria investigated were Actinobacillus actinomycetemcomitans, Eikenella corrodens, Porphyromonas gingivalis, Prevotella intermedia and Campylobacter rectus. Human cells were exposed to a four log order range of concentrations of the SAM, or of Escherichia coli lipopolysaccharide, to provide full agonist dose responses in order to allow comparison of the potency and efficacy of each SAM. All SAMs demonstrated the capacity to stimulate human gingival fibroblasts (HGFs), human peripheral blood mononuclear cells (PBMCs) or the myelomonocytic cell line - Mono-Mac-6 to release one or all of the cytokines assayed. Activity was heat- and trypsin-sensitive suggesting that the active components were proteinaceous. However, there were substantial differences in the potency and efficacy of each SAM when compared on a concentration basis (w/v). The most active SAM was from A. actinomycetemcomitans with those from E. corrodens and P. gingivalis being slightly less active. The least active cytokine-stimulating SAMs were from C. rectus and Pr. intermedia. One major difference between the SAMs and E. coli LPS was the inability of the former to stimulate HGFs to release IL-1 beta or TNF alpha although they could stimulate PBMCs to release these cytokines. This may have relevance to the pathology of the periodontal diseases.

Aggregatibacter actinomycetemcomitans

Cytokine-inducing components of periodontopathogenic bacteria.

Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor (TNF) are believed to be the major pathological mediators of inflammatory diseases ranging from arthritis to the periodontal diseases. The stimuli inducing proinflammatory cytokine induction in the former disease is unclear but in the periodontal diseases it is obvious that the stimulus is the accumulation of bacteria in the subgingival region. As these bacteria do not invade the lesional tissues in large numbers, it is believed that their soluble components or products interact with host tissues to induce cytokine gene transcription. The paradigm is that lipopolysaccharide is the key bacterial component inducing pro-inflammatory cytokine gene expression. However, over the past decade a growing number of reports on non-oral bacteria have established that many other bacterial components, as well as secretory products, have the capacity to induce cytokine synthesis. Some of these, such as the protein pneumolysin from Streptococcus pneumoniae, are incredibly potent (in this case inducing cytokine synthesis at femtomolar concentrations). This review surveys the range of bacterial components and products which have been shown to stimulate cytokine synthesis with particular emphasis on the hypothesis that these components play a role in the pathology of the periodontal diseases.

Animals

Bacterially induced bone destruction: mechanisms and misconceptions.

Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities.

Alveolar Bone Loss

Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis.

Cytokines are a diverse group of proteins and glycoproteins which have potent and wide-ranging effects on eukaryotic cell function and are now recognized as important mediators of tissue pathology in infectious diseases. It is increasingly recognized that for many bacterial species, cytokine induction is a major virulence mechanism. Until recent years, the only bacterial component known to stimulate cytokine synthesis was lipopolysaccharide (LPS). It is only within the past decade that it has been clearly shown that many components associated with the bacterial cell wall, including proteins, glycoproteins, lipoproteins, carbohydrates, and lipids, have the capacity to stimulate mammalian cells to produce a diverse array of cytokines. It has been established that many of these cytokine-inducing molecules act by mechanisms distinct from that of LPS, and thus their activities are not due to LPS contamination. Bacteria produce a wide range of virulence factors which cause host tissue pathology, and these diverse factors have been grouped into four families: adhesins, aggressins, impedins, and invasins. We suggest that the array of bacterial cytokine-inducing molecules represents a new class of bacterial virulence factor, and, by analogy with the known virulence families, we suggest the term "modulin" to describe these molecules, because the action of cytokines is to modulate eukaryotic cell behavior. This review summarizes our current understanding of cytokine biology in relation to tissue homeostasis and disease and concisely reviews the current literature on the cytokine-inducing molecules produced by gram-negative and gram-positive bacteria, with an emphasis on the cellular mechanisms responsible for cytokine induction. We propose that modulins, by controlling the host immune and inflammatory responses, maintain the large commensal flora that all multicellular organisms support.

Animals

Infection control and urine drainage bag design.

Catheterisation carries a significant risk of infection. Catheter and drainage system design should reduce this risk. No one system will suit all users; new designs need extensive trials in use.

Cross Infection