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Biomedical subjects

D Wilson

Publications and source records attributed to D Wilson.

At least 37 records · Page 2Linked to original sources

The use of CT-MR image registration to define target volumes in pelvic radiotherapy in the presence of bilateral hip replacements.

Increasing numbers of patients with hip replacements are presenting for pelvic radiotherapy, which is usually planned using CT images. Image artefacts caused by the presence of metallic implants tend not to be severe for single hip replacements and allow for adequate definition of target volumes. When bilateral hip replacements are present, the image artefacts can render CT images useless for target definition, particularly for tumours of the prostate and bladder. MR images are not susceptible to such severe artefacts. This note describes a small series of patients with bilateral hip replacements on whom CT-MR image registration has been used to successfully define adequate target volumes.

Aged↗

Diagnostic yield of peripheral lymph node needle-core biopsies in HIV-infected adults with suspected smear-negative tuberculosis.

Significant lymphadenopathy in human immunodeficiency virus (HIV) infected adults in developing countries is usually caused by tuberculosis. We studied the safety and diagnostic yield of needle-core biopsies, under local anaesthetic, of enlarged lymph nodes in 26 HIV-infected adults presenting with suspected tuberculosis who were sputum smear-negative. Biopsy samples were sent for histology and mycobacterial culture. Induced sputum, urine and blood were also sent for mycobacterial culture. The procedure was well tolerated. A definitive diagnosis was made on initial needle-core biopsy in 22 subjects (85%) and in two of three subjects who underwent a second needle-core biopsy. Tuberculosis was the final diagnosis in 24 subjects (92%).

AIDS-Related Opportunistic Infections↗

Philosophy, policy and procedures of the World Organisation for Animal Health for the development of standards in animal welfare.

Animal welfare was identified as a priority for the World Organisation for Animal Health (OIE) in the 2001-2005 OIE Strategic Plan. Member Countries recognised that, as animal protection is a complex, multi-faceted public policy issue which includes important scientific, ethical, economic and political dimensions, the OIE needed to develop a detailed vision and strategy incorporating and balancing these dimensions. A permanent working group on animal welfare was established in order to provide guidance to the OIE in its work on the development of science-based standards and guidelines. The Working Group decided to give priority to the welfare of animals used in agriculture and aquaculture, and that, within those groups, the topics of transportation, slaughter for human consumption and killing for disease control purposes would be addressed first. Some guiding principles were approved by the International Committee of OIE Member Countries during the 72nd General Session in May 2004, and these have been followed by four specific guidelines on the priority topics listed above.

Abattoirs↗

Dynamic neuromagnetic responses to auditory motion: a novel index for evaluation of attention.

Our previous studies have demonstrated that there is a motion-related magnetic response evoked by moving sound but not stationary sound. The motion-related response reflects the dynamic activities of brain processing of auditory motion. This study focuses on the effect of attention on the response. Six normal hearing subjects were studied using a 151-channel whole-cortex magnetoencephalography (MEG) system. Four sound stimuli were designed: two sounds moved from left to right (rightward) and the other two sounds moved from right to left (leftward). Two sounds moving in the same direction were separated with an attention task. The attention task was a mathematical calculation. The results showed that when subjects listened to the moving sound, there was a clearly auditory motion related response at a latency of 649 +/- 14.2 ms. However, when subjects were doing the calculation while listening to the moving sounds, the motion related response completely disappeared. Strikingly, there was a dent at a latency of 600 ms. To our knowledge, this is probably the first study showing a neuromagnetic response which can be clearly elicited or inhibited by an attention task. We consider that the motion related response has the potential to be an objective index for the study of attention.

Acoustic Stimulation↗

Automatic localization of epileptic zones using magnetoencephalography.

Conventional visual identification of epileptic spike is a challenging problem in the clinical application of magnetoencephalography (MEG). More importantly, the conventional method has problems of detecting other abnormalities such as high frequency oscillation in the human epileptic brain. The objective of this study was to develop a new approach using magnetic spectral analysis and spatial filtering. Twelve patients with seizure have been studied with a whole cortex MEG system. Fifteen epochs were recorded for each patient; each epoch was 120 seconds. Neuromagnetic spectrum was analyzed using a new method called accumulated spectrogram. Focal increases of spectral power were localized using synthetic aperture magnetometry (SAM). The MEG results were then compared with clinical findings. Focal increases of spectral power have been identified in all patients (12/12, 100%). The locations of the focal increases of spectral power were in agreement with dipole locations of spikes in 9 patients (9/12, 75%). A comparison between MEG results and clinical findings indicated that SAM revealed focal epileptic activities in two patients when dipole fitting failed. The results suggest that epileptic regions could be quantitatively identified and accurately localized using accumulated spectrogram and SAM. In comparison to visual identification of spike, the new approach is objective and sensitive, and provides the possibility of analyzing much wider frequency bands.

Adolescent↗

Developing complex interventions for rigorous evaluation--a case study from rural Zimbabwe.

Much attention has been placed on the need to develop and evaluate complex interventions targeting public health issues, such as reproductive health. However, and as has been the case in the recent past, even well-designed trials will be flawed unless meticulous attention is paid to ensuring the most appropriate intervention is designed and developed. This requires a well-resourced and carefully planned feasibility study, incorporating both formative and process evaluation, with particular attention being paid to the context of the proposed intervention. In this paper, we describe the way in which a feasibility study helped redesign and shape a complex intervention targeting adolescent sexual health in rural Zimbabwe. By using a mixture of in-depth interviews, focus groups and participant observation with pupils, parents, teachers and education officers, we were able to show that the intervention as originally conceived was unlikely to be deliverable. Process evaluation findings from the feasibility study led to substantial changes to both the content and delivery of the proposed intervention, which is now subject to testing for effectiveness in a large community randomized trial.

Adolescent↗

AGT and RH blood group polymorphisms affect blood pressure and lipids in Afro-Caribbeans.

Population blood pressure variation is most likely due to multiple genes. This is likely the reason why monogenic testing with the angiotensinogen (AGT) gene polymorphisms on chromosome 1 (1q42-43), especially M235T, has met with negative results, especially in those of African descent. The RH blood group system, also on chromosome 1 (1 p36.2-34), has likewise been associated with blood pressure variation in African-Americans and with the rise in blood pressure with age in whites. Using a random sample of the population, we investigated the combined effects of single and combined variation of the AGTN M235T and RH genotypes on blood pressure, lipids, and lipoprotein concentrations in Afro-Caribbeans aged 18-60 years from the island nation of Dominica. In monogenic analysis, AGT M235T was not associated with blood pressure. However, it was associated with HDL (MM 42+/-23, MT 44+/-12, TT 52+/-14 (P=0.002)). RH genotype was significantly associated with systolic blood pressure (P=0.006) and Apo-A (P=0.003). These effects remained after adjustment for age, gender, weight, and BMI. In the polygenetic analysis, AGT M235T and RH were significantly associated with systolic blood pressure (P=0.037; interaction effects, P=0.068). The association of the AGT M235T with blood pressure across RH blood group haplotypes was then tested. Of the five RH haplotypes available for analysis, the AGT M235T was significantly associated with blood pressure within the "D" haplotype (P=0.01). The RH blood group and gender were significantly associated with systolic blood pressure and Apo-A levels (P=0.005 and 0.012, respectively). All interactions were independent of age and weight. In conclusion, we demonstrate a significant association of AGT M235T with blood pressure and cholesterol metabolism in an Afro-Caribbean population in the "genetic context" of the RH blood group system. Further investigation of these interactions may help understand the effects of genetic factors on cardiovascular risk in African-derived and other populations.

Adult↗

Effects of music on work-rate distribution during a cycling time trial.

Previous research work on the ergogenic effects of music has mainly involved constant power tests to exhaustion as dependent variables. Time trials are more externally valid than constant power tests, may be more reliable and allow the distribution of self-selected work-rate to be explored. We examined whether music improved starting, finishing and/or overall power during a 10-km cycling time trial, and whether heart rate and subjective responses to this time trial were altered by music. Sixteen participants performed two 10-km time trials on a Cybex cycle ergometer with, and without, the presence of a form of dance music known as "trance" (tempo = 142 beats x min (-1), volume at ear = 87 dB). Participants also completed the Brunel music rating inventory (BMRI) after each time trial in the music condition. The mean +/- SD time to complete the time trial was 1030 +/- 79 s in the music condition compared to 1052 +/- 77 s without music (95 % CI of difference = 10 to 34 s, p = 0.001). Nevertheless, ratings of perceived exertion were consistently (0.8 units) higher throughout the time trial with music (p < 0.0005). The interaction between distance and condition was significant for cycling speed measured during the time trial (p = 0.007). The largest music-induced increases in cycling speed and heart rate were observed in the first 3 km of the time trial. After completion of the BMRI, participants rated the "tempo" and "rhythm" of the music as more motivating than the "harmony" and "melody" aspects. These results suggest that music improves cycling speed mostly in the first few minutes of a 10-km time trial. In contrast to the findings of previous research, which suggested that music lowers perceived exertion at a constant work-rate, the participants in our time trials selected higher work-rates with music, whilst at the same time perceived these work-rates as being harder than without music.

Adult↗

Effect of twisting hamstring tendon grafts on strength and joint laxity through the range of knee movement.

Twisting or braiding of hamstring tendon grafts for use in anterior cruciate ligament reconstructions has been advocated to increase their strength and stiffness under load. In this study, a two-dimensional model was used to determine the failure strength of twisted and parallel grafts and associated knee laxity under simulated physiological loading conditions. For validation, mechanical tests of tendon grafts were also simulated with these models. The simulated physiological loading of the graft models showed that knees with twisted grafts had greater laxity than knees with parallel grafts, although there was little difference in failure load between the two graft configurations. The tensile loading of the graft models showed little difference in failure load when the tendons were modelled using line segments. When the tendons were considered as three-dimensional helical elements, which more accurately describe the tendon structure, the failure load of the twisted graft decreased significantly. This research provided no evidence to support the belief that a twisted tendon graft is a superior graft configuration relative to a parallel tendon graft.

Cadaver↗

Post-mortem collection of human joint tissues for research.

OBJECTIVE: A feasibility study aiming to obtain post-mortem knee joint tissues from 10 donors for research. METHODS: Next of kin were approached by bereavement officers then informed about the project by the study nurse. Written consent was sought to collect bone, cartilage and soft tissue from both knees, and to extract data from medical notes. RESULTS: During the 4-month study period 259 families attended the King's Mill Hospital Bereavement Centre, 36 of whom met with the study nurse, 10 of whom consented to joint tissue collecting. The process of seeking consent required approximately 1 h of direct contact. Participants often looked to this as an extension of the bereavement counselling process and many expressed gratitude that some good might be derived from the death. Reasons for non-recruitment included operational restraints and relatives' distress. Donors were more likely to be male (90%) than were non-donors (49%, Z = -2.6, P < 0.01). Coroner's post-mortem examinations took place on similar proportions of donors (20%) and non-donors (19%, Z = -0.06, P = 0.96). CONCLUSIONS: Post-mortem joint tissue collection for research remains feasible in the presence of a skilled, well co-ordinated, multidisciplinary team, even when post-mortem examination would not otherwise be required.

Aged↗

A double-blind randomised, placebo-controlled trial evaluating the influence of oral long-acting muscle relaxant (Mebeverine MR), and insufflation with CO(2) on pain associated with barium enema.

Previous investigators have shown significant benefit using CO(2) for bowel insufflation. Others have suggested that the long-acting smooth muscle relaxant, Mebeverine, may be of benefit. We subjected this to a randomised double-blind trial. A total of 181 outpatients were randomised to receive either Mebeverine or placebo as pre-medication, and either air or CO(2) for bowel insufflation, thus creating four treatment groups. Visual-analogue lines were used to record pain scores before, during, and up to 8 h following the enema. All groups showed increased pain scores during the enema, with peak pain scores at the end of the examination, falling to baseline scores by 8 h. Patients receiving the combination of C0(2) and placebo had significantly lower pain scores at 1 and 4 h ( P=0.00 and P=0.014, respectively; Kruskal-Wallis test) compared with all other groups. Having Mebeverine as a pre-medication did not significantly lower pain scores compared with placebo, and decreased the amount of benefit received from the CO(2). We confirm that CO(2) is of benefit in decreasing pain during barium enema, and we recommend its routine use to improve the comfort of patients. Mebeverine is not of benefit, and its use as a pre-medication for enemas is not recommended.

Administration, Oral↗

Inflammation and angiogenesis in osteoarthritis.

OBJECTIVE: To quantify the relationship between inflammation and angiogenesis in synovial tissue from patients with osteoarthritis (OA). METHODS: Hematoxylin and eosin staining and histologic grading for inflammation were performed for 104 patients who met the American College of Rheumatology criteria for OA and had undergone total joint replacement or arthroscopy. A purposive sample of synovial specimens obtained from 70 patients was used for further analysis. Vascular endothelium, endothelial cell (EC) proliferating nuclei, macrophages, and vascular endothelial growth factor (VEGF) were detected by immunohistochemical analysis. Angiogenesis (EC proliferation, EC fractional area), macrophage fractional area, and VEGF immunoreactivity were measured using computer-assisted image analysis. Double immunofluorescence histochemical analysis was used to determine the cellular localization of VEGF. Radiographic scores for joint space narrowing and osteophyte formation in the knee were also assessed. RESULTS: Synovial tissue samples from 32 (31%) of 104 patients with OA showed severe inflammation; thickened intimal lining and associated lymphoid aggregates were often observed. The EC fractional area, EC proliferation, and VEGF immunoreactivity all increased with increasing histologic inflammation grade and increasing macrophage fractional area. In the synovial intimal lining, VEGF immunoreactivity was localized to macrophages and increased with increasing EC fractional area and angiogenesis. No inflammation or angiogenic indices were significantly correlated with radiographic scores. CONCLUSION: Inflammation and angiogenesis in the synovium are associated with OA. The angiogenic growth factor VEGF generated by the inflamed synovium may promote angiogenesis, thereby contributing to inflammation in OA.

Aged↗

Performance of the CELSS Antarctic Analog Project (CAAP) crop production system.

Regenerative life support systems potentially offer a level of self-sufficiency and a decrease in logistics and associated costs in support of space exploration and habitation missions. Current state-of-the-art in plant-based, regenerative life support requires resources in excess of allocation proposed for candidate mission scenarios. Feasibility thresholds have been identified for candidate exploration missions. The goal of this paper is to review recent advances in performance achieved in the CELSS Antarctic Analog Project (CAAP) in light of the likely resource constraints. A prototype CAAP crop production chamber has been constructed and operated at the Ames Research Center. The chamber includes a number of unique hardware and software components focused on attempts to increase production efficiency, increase energy efficiency, and control the flow of energy and mass through the system. Both single crop, batch production and continuous cultivation of mixed crops production studies have been completed. The crop productivity as well as engineering performance of the chamber are described. For each scenario, energy required and partitioned for lighting, cooling, pumping, fans, etc. is quantified. Crop production and the resulting lighting efficiency and energy conversion efficiencies are presented. In the mixed-crop scenario, with 27 different crops under cultivation, 17 m2 of crop area provided a mean of 515 g edible biomass per day (85% of the approximate 620 g required for one person). Enhanced engineering and crop production performance achieved with the CAAP chamber, compared with current state-of-the-art, places plant-based life support systems at the threshold of feasibility.

Agriculture↗

The effect of biological effective dose on time to symptom progression in metastatic renal cell carcinoma.

AIMS: Renal cell carcinoma is commonly thought to be a radioresistant malignancy. Retrospective studies report conflicting results on the effect of radiotherapy dose escalation on response and time to progression in symptomatic metastatic disease; studies using the linear quadratic model have used alpha/beta ratios that are inappropriate for slow growing tumours. We aim to describe our experience with palliative radiotherapy in this context, relating Biological Effective Dose to outcome. MATERIALS AND METHODS: From December 1995 to April 2001, 143 independent palliative radiotherapy treatments were delivered to 78 patients in a single institution. Retrospective data was obtained on the radiotherapy schedule used, symptom response and time to symptom progression. The biological effective dose (BED) was calculated using alpha/beta ratios of 3 and 7 Gy (BED3 and BED7). The Log-Rank test was used to assess any differences in time to progression, and the Cox Proportional Hazards analysis to determine prognostic factors of time to progression. RESULTS: Overall symptomatic response rate was 73%, with most responses being partial (67%). Forty-three (38%) patients had symptomatic progression after a median follow-up of 425 days. BED (BED3 or BED7) was not significantly different across response types (complete, partial or no response; P=0.90 and 0.88, respectively) and was not predictive for time to symptomatic progression (P=0.99 for BED3 and P=0.70 for BED7). Patients with bone metastases received less total dose (P=0.001), less BED (BED3, P=0.0013, and BED7, P=0.0005) and had a significantly longer time to progression than other sites of metastases (hazard ratio (HR) 0.4; 95% confidence interval (CI) 0.2-0.7; P=0.004). Initial treatment with interferon-alpha alone in patients presenting with metastatic disease, before palliative radiotherapy, was also associated with a shorter time to symptom progression (HR 4.6; 95% CI 1.5-14.1; P=0.007). On removal of these criteria, brain metastases became a significant predictor of progression time, with an HR of 2.5 (95% CI 1.0-5.9; P=0.05), showing an increased risk of progression with brain metastases compared with metastases elsewhere. Time from primary diagnosis to development of metastatic disease was not predictive of time to symptom progression (P=0.29). CONCLUSION: Despite the widespread assumption that renal cell carcinoma is radioresistant, retrospective assessment showed high response rates to palliative radiotherapy. On the basis of our data, higher BED does not seem to be a predictor of response or of duration of response in the palliative treatment of renal cell carcinoma. Palliation of bone pain seems to be particularly durable compared with the palliation of symptoms at other sites of metastases. A trend for shorter duration of palliative effect of whole-brain radiotherapy was noted.

Adult↗

Expression of a novel regenerating gene product, Reg IV, by high density fermentation in Pichia pastoris: production, purification, and characterization.

Human regenerating (Reg) gene products are regionally expressed by gut-derived tissues, and are markedly up-regulated in cancer and in diseases characterized by mucosal injury. We recently identified Reg IV, a novel regenerating gene product that is uniquely expressed by the normal distal gastrointestinal mucosa. The function remains poorly understood due to the lack of significant purified Reg IV for biochemical and functional studies. Recombinant human Reg IV was efficiently expressed under the control of the AOX1 gene promoter in Pichia pastoris using the MutS strain KM71H. We describe the unique conditions that are required for efficient production of Reg IV protein in high density fermentation. Optimal protein expression was obtained by reduction of the fermentation temperature and addition of casamino acids as a supplemental nitrogen source and to minimize the activity of yeast produced proteases. Recombinant Reg IV protein was purified by tangential flow filtration and reverse phase chromatography. The purified protein was characterized by amino terminus sequence analysis and MALDI-TOFMS showing that the engineered protein had the expected sequence and molecular weight without secondary modification. Recombinant Reg IV was further characterized by specific monoclonal and polyclonal reagents that function for Western blot analysis and for immunolocalization studies.

Amino Acid Sequence↗