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Biomedical subjects

R A Cooper

Publications and source records attributed to R A Cooper.

At least 19 recordsLinked to original sources

An evaluation of different methods for the recovery of meticillin-resistant Staphylococcus aureus from environmental surfaces.

Although the association between environmental surfaces contaminated with meticillin-resistant Staphylococcus aureus (MRSA) and hospital infection rates is not fully understood, monitoring programmes can provide an objective starting point for the development and assessment of infection control strategies incorporating improved cleaning. There is, however, no universally accepted method for the recovery of MRSA from environmental surfaces, and the aim of this study was to evaluate a selection of currently available methods. Using five clinical isolates of MRSA and seven protocols, known numbers of bacteria were inoculated on to a stainless steel surface and either recovered immediately (without drying or adsorption) or recovered after 30min (with drying at room temperature and adsorption of cells to the surface). Surfaces were either swabbed or sampled directly by contact methods, and four nutritive media (blood, tryptone soya, oxacillin and meticillin-resistant agars) were tested. Relative sampling efficiencies were determined and the sensitivity of each method per 100cm(2) was calculated. Wide variation in the ability to recover MRSA was found between the different protocols. In the recovery of dried (adsorbed) cells, direct contact methods demonstrated higher sampling efficiency than swabs. The sensitivity of all methods was lower in recovering adsorbed cells from surfaces than unadsorbed cells. Sampling methods consistently proved to be more important than the choice of medium. Dipslides coated with selective agar are recommended for recovering MRSA from flat environmental surfaces.

Bacteriological Techniques↗

The antibacterial activity of honey against coagulase-negative staphylococci.

OBJECTIVES: Development of antibiotic-resistant strains of coagulase-negative staphylococci has complicated the management of infections associated with the use of invasive medical devices, and innovative treatment and prophylactic options are needed. Honey is increasingly being used to treat infected wounds, but little is known about its effectiveness against coagulase-negative staphylococci. The aim of this study was to determine the minimum active dilution of two standardized, representative honeys for 18 clinical isolates of coagulase-negative staphylococci. METHODS: An agar incorporation technique was used to determine the minimum active dilution, with dilution steps of 1% (v/v) honey [or steps of 5% (v/v) of a sugar syrup matching the osmotic effect of honey]. The plates were inoculated with 10 microL spots of cultures of the isolates. RESULTS: The honeys were inhibitory at dilutions down to 3.6 +/- 0.7% (v/v) for the pasture honey, 3.4 +/- 0.5% (v/v) for the manuka honey and 29.9 +/- 1.9% (v/v) for the sugar syrup. CONCLUSIONS: Typical honeys are about eight times more potent against coagulase-negative staphylococci than if bacterial inhibition were due to their osmolarity alone. Therefore, honey applied to skin at the insertion points of medical devices may have a role in the treatment or prevention of infections by coagulase-negative staphylococci.

Anti-Bacterial Agents↗

Effective treatment of anal cancer in the elderly with low-dose chemoradiotherapy.

Chemoradiotherapy (CRT) is accepted as the standard initial treatment for squamous cell anal cancer. However, frail elderly patients cannot always tolerate full-dose CRT. This paper reports the results of a modified regimen for this group of patients. In all, 16 patients with biopsy-proven squamous cell carcinoma of the anal canal or margin and performance status or co-morbidity precluding the use of full-dose CRT were included in this protocol. The median age was 81 (range 77-91). Patients received a dose of 30 Gy to the gross tumour volume plus 3 cm margin in all directions. Concurrent chemotherapy comprised 5-fluorouracil 600 mg m(-2) given over 24 h on days 1-4 of radiotherapy. The treatment was well tolerated. All 16 patients completed treatment as planned. Only one patient experienced any grade 3 toxicity (skin). The local control at a median follow-up of 16 months was 73% (13 out of 16). The overall survival was 69% and disease-specific survival 86%. This is a well-tolerated regimen for elderly/poor performance patients with anal cancer, which can achieve high rates of local control and survival. Longer follow-up will determine whether these encouraging results are maintained.

Age Factors↗

Accuracy and feasibility of dynamic contrast-enhanced 3D MR imaging in the assessment of lung perfusion: comparison with Tc-99 MAA perfusion scintigraphy.

AIM: The aim of this study was to correlate findings of perfusion magnetic resonance imaging (MRI) and perfusion scintigraphy in cases where there was a suspicion of abnormal pulmonary vasculature, and to evaluate the usefulness of MRI in the detection of perfusion deficits of the lung. METHODS: In all, 17 patients with suspected abnormality of the pulmonary vasculature underwent dynamic contrast-enhanced MRI. T1-weighted 3D fast-field echo pulse sequences were obtained (TR/TE 3.3/1.58 ms; flip angle 30 degrees; slice thickness 12 to 15 mm). The dynamic study was acquired in the coronal plane following administration of 0.1 mmol/kg gadopentetate dimeglumine. A total of 8 to 10 sections repeated 20 to 25 times at intervals of 1s were performed. Perfusion lung scintigraphy was carried out a maximum of 48 h before the MR examination in all cases. Two radiologists, who were blinded to the clinical data and results of other imaging methods, reviewed all coronal sections. MR perfusion images were independently assessed in terms of segmental or lobar perfusion defects in the 85 lobes of the 17 individuals, and the findings were compared with the results of scintigraphy. RESULTS: Of the 17 patients, 8 were found to have pulmonary emboli, 2 chronic obstructive pulmonary disease with emphysema, 2 bullous emphysema, 2 Takayasu arteritis and 1 had a hypoplastic pulmonary artery. Pulmonary perfusion was completely normal in 2 cases. In 35 lobes, perfusion defects were detected using both methods, in 4 with MR alone and in 9 only with scintigraphy. There was good agreement between MRI and scintigraphy findings (kappa=0.695). CONCLUSION: Pulmonary perfusion MRI is a new alternative to scintigraphy in the evaluation of pulmonary perfusion for various lung disorders. In addition, this technique allows measurement and quantification of pulmonary perfusion abnormalities.

Adult↗

Indication of a Lombard vocal response in the St. Lawrence River Beluga.

Noise pollution is recognized as a potential danger to marine mammals in general, and to the St. Lawrence beluga in particular. One method of determining the impacts of noise on an animal's communication is to observe a natural and repeatable response of the vocal system to variations in noise level. This is accomplished by observing intensity changes in animal vocalizations in response to environmental noise. One such response observed in humans, songbirds, and some primates is the Lombard vocal response. This response represents a vocal system reaction manifested by changes in vocalization level in direct response to changes in the noise field. In this research, a population of belugas in the St. Lawrence River Estuary was tested to determine whether a Lombard response existed by using hidden Markhov-classified vocalizations as targets for acoustical analyses. Correlation and regression analyses of signals and noise indicated that the phenomenon does exist. Further, results of human subjects experiments [Egan, J. J. (1966), Ph.D. dissertation; Scheifele, P. M. (2003), Ph.D. dissertation], along with previously reported data from other animal species, are similar to those exhibited by the belugas. Overall, findings suggest that typical noise levels in the St. Lawrence River Estuary have a detectable effect on the communication of the beluga.

Animal Communication↗

Small-cell carcinoma of the urinary bladder: 10-year experience.

AIMS: Small-cell carcinoma of the urinary bladder is rarely encountered in clinical practice. We report on our clinical experience with affected patients presenting to our institution from 1986 to 1996. MATERIALS AND METHODS: We retrospectively analysed 14 pathologically confirmed cases, specifically looking at stage, presenting features, treatment and overall survival. The median age at presentation was 74 years (range 54-91 years). RESULTS: Ten patients presented with stage III disease, and four patients with stage IV disease (1 = nodal, 3 = distant metastases). Four patients were treated with radical radiotherapy (one patient receiving neoadjuvant chemotherapy) and two underwent a radical cystoprostatectomy. Five patients received palliative bladder radiotherapy and three were too frail for treatment at presentation. The overall median survival was 5 months. Patients receiving radical treatment had a median overall survival of 21 months, with only one long-term survivor. CONCLUSION: This highly aggressive tumour tends to affect an elderly population who are generally frail and have significant comorbidity. Many are unfit for radical treatment. In patients with disease confined to the pelvis who are able to tolerate radical intervention, the results of local therapy alone are poor. It therefore remains incumbent on treating clinicians to explore means of improving these results. Initial chemotherapy analogous to small-cell lung cancer may offer a durable response with a better chance for long-term survival.

Aged↗

Proteomic approaches to studying drug targets and resistance in Plasmodium.

Ever increasing drug resistance by Plasmodium falciparum, the most virulent of human malaria parasites, is creating new challenges in malaria chemotherapy. The entire genome sequences of P. falciparum and the rodent malaria parasite, P. yoelii yoelii are now available. Extensive genome sequence data from other Plasmodium species including another important human malaria parasite, P. vivax are also available. Powerful research techniques coupled to genomic resources are needed to help identify new drug and vaccine targets against malaria. Applied to Plasmodium, proteomics combines high-resolution protein or peptide separation with mass spectrometry and computer software to rapidly identify large numbers of proteins expressed from various stages of parasite development. Proteomic methods can be applied to study sub-cellular localization, cell function, organelle composition, changes in protein expression patterns in response to drug exposure, drug-protein binding and validation of data from genomic annotation and transcript expression studies. Recent high-throughput proteomic approaches have provided a wealth of protein expression data on P. falciparum, while smaller-scale studies examining specific drug-related hypotheses are also appearing. Of particular interest is the study of mechanisms of action and resistance of drugs such as the quinolines, whose targets currently may not be predictable from genomic data. Coupling the Plasmodium sequence data with bioinformatics, proteomics and RNA transcript expression profiling opens unprecedented opportunities for exploring new malaria control strategies. This review will focus on pharmacological research in malaria and other intracellular parasites using proteomic techniques, emphasizing resources and strategies available for Plasmodium.

Animals↗

Honey stimulates inflammatory cytokine production from monocytes.

Clinical observations indicate that honey may initiate or accelerate the healing of chronic wounds and has, therefore, been claimed to have anti-inflammatory properties. The aim of this study was to investigate the effects of honey on the activation state of immunocompetent cells, using the monocytic cell line, MonoMac-6 (MM6), as a model. We investigated the effect of each of the three honeys (manuka, pasture and jelly bush) on the release of important inflammatory cytokines from MM6 cells. These honeys, together with a sugar syrup control (artificial honey), were incubated with MM6 cells at a concentration of 1% (w/v) for 0-24h. Cell culture supernatants were tested using specific ELISA assays for tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta and IL-6. All honeys significantly increased the TNF-alpha, IL-1beta and IL-6 release from MM6 cells (and human monocytes) when compared with untreated and artificial-honey-treated cells (P<0.001). Jelly bush honey significantly induced the maximal release of each cytokine compared with manuka, pasture or artificial honeys (P<0.001). These results suggest that the effect of honey on wound healing may in part be related to the stimulation of inflammatory cytokines from monocytic cells. Such cell types are known to play an important role in healing and tissue repair.

Cell Line↗

The sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds.

AIMS: To determine the sensitivity to honey of Gram-positive cocci of clinical significance in wounds and demonstrate that inhibition is not exclusively due to osmotic effects. METHODS AND RESULTS: Eighteen strains of methicillin-resistant Staphylococcus aureus and seven strains of vancomycin-sensitive enterococci were isolated from infected wounds and 20 strains of vancomycin-resistant enterococci were isolated from hospital environmental surfaces. Using an agar incorporation technique to determine the minimum inhibitory concentration (MIC), their sensitivity to two natural honeys of median levels of antibacterial activity was established and compared with an artificial honey solution. For all of the strains tested, the MIC values against manuka and pasture honey were below 10% (v/v), but concentrations of artificial honey at least three times higher were required to achieve equivalent inhibition in vitro. Comparison of the MIC values of antibiotic-sensitive strains with their respective antibiotic-resistant strains demonstrated no marked differences in their susceptibilities to honey. CONCLUSIONS: The inhibition of bacteria by honey is not exclusively due to osmolarity. For the Gram-positive cocci tested, antibiotic-sensitive and -resistant strains showed similar sensitivity to honey. SIGNIFICANCE AND IMPACT OF THE STUDY: A possible role for honey in the treatment of wounds colonized by antibiotic-resistant bacteria is indicated.

Drug Resistance, Bacterial↗

Stimulation of TNF-alpha release in monocytes by honey.

Although evidence exists for the antibacterial effects of honey there is limited objective evidence for direct promotion of healing. We investigated the effect of manuka, pasture and an artificial honey on macrophage function. Reactive oxygen intermediate (ROI) production was assessed by luminol enhanced chemoluminescence and tumour necrosis factor-alpha (TNF-alpha) release was determined by immunoassay. ROI production was significantly (P<0.001) decreased by pasture honey and manuka honey. TNF-alpha release was significantly enhanced (P<0.001) in unprimed MM6 cells by manuka and pasture honey but was not altered in primed cells. These results could explain the suggested therapeutic properties of honey in promoting wound healing.

Cell Line↗

Tumor vascularity: a histological measure of angiogenesis and hypoxia.

In this study we sought to clarify the relationship between tumor vascularity, hypoxia, and angiogenesis in human cervix tumors. Two hypotheses were established: first, that measurement of tumor vascularity can provide a histological assessment of both hypoxia and angiogenesis; and second, that expression of angiogenesis-related proteins will provide a surrogate measure of tumor hypoxia. To test the first hypothesis, we studied the prognostic significance of tumor vascularity measured as both intercapillary distance (ICD; thought to reflect tumor oxygenation) and microvessel density (MVD; the hotspot method that provides a histological assessment of tumor angiogenesis). The relationship was also examined of tumor hypoxia, measured using an Eppendorf needle electrode [percentage of values less than 5 mm Hg (HP5)], with ICD and MVD. To test the second hypothesis we examined the relationship between HP5 and the expression of angiogenesis-associated proteins [vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)]. All of the biological measurements were made on pretreatment tumors. Analysis of data was carried out using log-rank statistics, Cox multivariate analysis, and Spearman's rank correlation. Both ICD and MVD were significant independent prognostic factors for local control. Patients with poorly vascularized tumors (long ICD) had poor local control (P = 0.042). However, patients with poorly vascularized tumors, measured as low MVD, had good local control (P = 0.036). For 107 patients in whom both of the measurements were obtained on the same tumor sections, ICD and MVD provided independent prognostic information in multivariate analysis. There was a significant correlation between tumor hypoxia and ICD (P < 0.005) but not MVD (P = 0.41). There was no relationship between hypoxia and the expression of angiogenic factors (VEGF, PD-ECGF). These analyses show that measurement of tumor vascularity can provide different biological information that is dependent on the method used. It is, therefore, important that studies measuring vascularity should include an appropriate definition. There is no relationship between hypoxia and angiogenesis in advanced carcinoma of the cervix and examining the levels of angiogenic proteins may not have a role in assessing hypoxia in cervix cancer.

Cell Hypoxia↗

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Chromosomes, Human, Pair 1↗

An autoregressive modeling approach to analyzing wheelchair propulsion forces.

Biomechanical signals collected during wheelchair propulsion are often analyzed by computing averages and/or peak values over several strokes. Due to the complex nature of the signals, this type of analysis may not be specific to identifying factors that may predispose a wheelchair user to joint pain/injury. Hence, a new technique is introduced that uses a system identification approach, autoregressive (AR) modeling, to analyze wheelchair propulsion force waveforms. In this application an AR method was used to create a model force waveform based on current and past values of digital pushrim force data. The feasibility of the AR modeling method over point-wise methods to detect asymmetry among force waveforms was tested with a group of 20 wheelchair users. Subjects propelled at a constant 0.9 m/s on a roller system during which 20 s of force data were collected from the SMART(Wheel)s, force and torque sensing pushrims. Both methods showed that the wheelchair users as a group propelled evenly, however, individual analysis using the AR model error estimates indicated that twenty-five percent demonstrated significant asymmetry in their force waveforms. If only point-wise means and variances of the applied bilateral forces were considered, most subjects would have appeared symmetrical. Thus, the AR modeling approach is more sensitive to detecting anomalies in propulsion technique.

Adult↗

Kinematic comparison of Hybrid II test dummy to wheelchair user.

Hybrid test dummies provide a safe alternative to human subjects when investigating mechanisms of wheelchair tips and falls. The data that researchers acquire from these test dummies are more useful if the test dummy represents the population being studied. The goal of this study was to measure the validity of a 50th percentile Hybrid II test dummy (HTD) as an accurate representation of a wheelchair user. A test pilot with T8 paraplegia due to traumatic spinal cord injury served as a basis for validation. Simple modifications were made to the HTD to approximate the trunk stability characteristics of a person with a spinal cord injury. An HTD, a modified HTD, and a human test pilot were seated in an electric-powered wheelchair and several braking tests performed. The standard HTD underestimated the kinematics when compared to the test pilot. The modified HTD had less trunk stability than the standard HTD during all braking methods. The modified HTD and wheelchair test pilot had similar trunk stability characteristics during kill switch and joystick full-reverse braking conditions. The modified HTD is a satisfactory representation of a wheelchair user with a spinal cord injury; however, the modified test dummy underestimates the trunk dynamics during the less extreme joystick release braking. Work should continue on the development of a low-speed, low-impact test dummy that emulates the wheelchair user population.

Biomechanical Phenomena↗

Does computer game play aid in motivation of exercise and increase metabolic activity during wheelchair ergometry?

GAME(Wheels) is an interface between a portable roller system and a computer that enables a wheelchair user to play commercially available computer video games. The subject controls the game play with the propulsion of their wheelchair's wheels on the rollers. The purpose of this study was to investigate whether using the GAME(Wheels) System during wheelchair propulsion exercise can help increase the individual's physiological response and aid in the motivation to exercise. Fifteen subjects participated in this study. The subjects propelled their wheelchairs on a portable roller that was equipped with the GAME(Wheels) System. There were two exercise trials consisting of 2 min of warm-up, 16 min of exercise and 2 min of cool-down. Physiological data (ventilation rate, oxygen consumption, heart rate) were collected. A significant difference (P<0.05) was found between exercise with GAME(Wheels) versus without GAME(Wheels) for average ventilation rate and average oxygen consumption. The differences were found during time periods of transition from warm-up to exercise, and before and after the midpoint of exercise. Written questionnaires showed that 87% of the individuals tested reported the system would help them work out on a regular basis. Playing the video game helped these individuals to reach their exercise training zone faster and maintain it for the entire exercise trial.

Adult↗

Mechanical efficiency and user power requirement with a pushrim activated power assisted wheelchair.

The objective of this study was to quantify the difference in mechanical efficiency and user power generation between traditional manual wheelchairs and a pushrim activated power assisted wheelchair (PAPAW). Ten manual wheelchair users were evaluated in a repeated measures design trial with and without the PAPAW for propulsion efficiency. Subjects propelled a Quickie GP equipped with the PAPAW and their own chair on a computer controlled wheelchair dynamometer at five different resistance levels. Power output, user power with the PAPAW hubs, subjects' oxygen consumption per minute and mechanical efficiency were analyzed. Metabolic energy and user power were significantly lower (p<0.05), and mechanical efficiency significantly higher with the PAPAW than with subjects' own chairs. Subjects needed to generate on average 3.65 times more power when propelling their own wheelchairs as compared to PAPAW. Mean mechanical efficiency over all trials was 80.33% higher with the power assisted hubs. PAPAW provides on average 73% of the total power when subjects propel with power assistance. Significantly increased efficiency and reduced requirement of user power is achieved using the PAPAW. With use, the PAPAW may contribute to delaying secondary injuries of manual wheelchair users. In addition, it may be suitable for people who have (or at risk for) upper extremity joint degeneration, reduced exercise capacity, low strength or endurance who currently use electric powered wheelchairs.

Adult↗