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Biomedical subjects

A Murray

Publications and source records attributed to A Murray.

At least 19 recordsLinked to original sources

Autonomic dysfunction in dementia.

BACKGROUND: There are no studies of autonomic function comparing Alzheimer's disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). AIMS: To assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing's battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing's classification. RESULTS: There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p<0.001) and AD (all p<0.03). DLB showed impairment of parasympathetic function (all p<0.05) and one of the sympathetic tests in comparison with controls (orthostasis; p = 0.02). PDD had significantly more impairment than DLB in some autonomic parameters (Valsalva ratio: p = 0.024; response to isometric exercise: p = 0.002). Patients with VAD showed impairment in two parasympathetic tests (orthostasis: p = 0.02; Valsalva ratio: p = 0.08) and one sympathetic test (orthostasis: p = 0.04). These results were in contrast with AD patients who only showed impairment in one sympathetic response (orthostasis: p = 0.004). The prevalence of orthostatic hypotension and autonomic neuropathies was higher in all dementias than in controls (all p<0.05). CONCLUSION: Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications.

Aged↗

'Ovar-Mhc' - ovine major histocompatibility complex: structure and gene polymorphisms.

The major histocompatibility complex (MHC) in sheep, Ovar-Mhc, is poorly characterised, when compared to other domestic animals. However, its basic structure is similar to that of other mammals, comprising class I, II and III regions. Currently, there is evidence for the existence of four class I loci. The class II region is better characterised, with evidence of one DRA, four DRB (one coding and three non-coding), one DQA1, two DQA2, and one each of the DQB1, DQB2, DNA, DOB, DYA, DYB, DMA, and DMB genes in the region. The class III region is the least characterised, with the known presence of complement cascade (C4, C2 and Bf), TNFalpha and CYP21 genes. Products of the class I and II genes, MHC molecules, play a pivotal role in antigen presentation required for eliciting immune responses against invading pathogens. Several studies have focused on polymorphisms of Ovar-Mhc genes and their association with disease resistance. However, more research emphasis is needed on characterising the remaining Ovar-Mhc genes and developing simplified and cost-effective methods to score gene polymorphisms. Haplotype screening, employing multiple markers rather than single genes, would be more meaningful in MHC-disease association studies, as it is well known that most of the MHC loci are tightly linked, exhibiting very little recombination. This review summarises the current knowledge of the structure of Ovar-Mhc and polymorphisms of genes located in the complex.

Animals↗

Microbial growth in vials of Botulinum toxin following use in clinic.

PURPOSE: Botulinum toxin has various applications in ophthalmology and is used in the outpatient department, where it is often exposed to room temperatures for 3-4 h. The manufacturer's recommendations are that the reconstituted toxin be stored in a refrigerator when not in use and discarded 4 h after reconstitution. The aim of our study was to examine such used bottles of Botulinum toxin for microbial growth after 4 h at room temperature. METHODS AND RESULTS: Eleven consecutive bottles of Botulinum toxin used with aseptic precautions in the Ophthalmology outpatient clinics were exposed to room temperatures for 4 h. These were subsequently analysed for microbial growth. No growth was directly obtained from any of the Botulinum toxin bottles during our study. CONCLUSIONS: This pilot study suggests that if aseptic precautions are followed during the use of Botulinum toxin, the contents of the bottle remain sterile despite being exposed to room temperatures for up to 4 h. This has implications on the use of the reconstituted toxin after the recommended 4 h.

Asepsis↗

Factors affecting the use of cumulative sums in the analysis of circadian blood pressure.

The assessment of circadian blood pressure change by ambulatory blood pressure monitoring has potential as a predictor for cardiovascular events, but its evaluation is problematic due to the difficulty in defining day and night periods for individual subjects. The cumulative sums (cusums) method has the advantage of simplicity over mathematical modelling techniques and is reported to give more reproducible results than methods that use time-dependent sleep and wake periods. However, cusum parameters (cusum-derived circadian alteration magnitude (CDCAM) and cusum plot height (CPH)) are affected by the implementation of the method and by the quality of ambulatory blood pressure recordings. This study quantifies the effects of using interval blood pressure values, changing the time used for calculating the cusum plot slope (CPS) and using incomplete data recordings. Significant effects are reported in all cases. Using interval rather than recorded blood pressures causes a mean reduction in CPH and CDCAM of approximately 6%. Altering the CPS time by 1 h (from 6 h) results in a mean change in CDCAM of approximately 7%. In recordings with hourly readings, the coefficient of variation in CPH and CDCAM ranges from 4% (one missing reading) to 13% (five missing readings).

Aged↗

The practice of bilateral, simultaneous total knee replacement in Scotland over the last decade. Data from the Scottish Arthroplasty Project.

The issue of the safety of performing simultaneous, bilateral total knee replacement (SBTKR) for patients with bilateral knee osteoarthritis remains controversial. Several small series have reported inconclusive findings and the few large series published are contradictory. We present data retrieved from the Scottish Arthroplasty Project on over 19,000 total knee replacements (TKR) performed in Scotland between 1989 and 1999. The trends in the practice of SBTKR are shown together with the associated mortality from the procedure compared with unilateral or staged, bilateral TKR. The data shows that there was no statistically significant difference in the 90-day mortality between unilateral TKR, staged TKR or SBTKR. In addition, the length of stay for SBTKR has reduced, equaling that of unilateral TKR since 1993. Despite an initial increase in the percentage of consultants performing SBTKR early in the decade, since 1993, only approximately 25% of knee arthroplasty surgeons in Scotland per year ever performed a SBTKR.

Arthritis↗

In vivo assessment of coronary artery angioplasty and stent deployment from balloon pressure-volume data.

This study assessed the clinical and practical value of angioplasty balloon pressure-volume data, obtained by a computer-controlled balloon inflation device, during standard percutaneous coronary intervention (PCI) procedures. Stent deployment was studied for 57 lesions in 34 patients. Angiographic predilation data were available in 9 patients. Vessel lumen improvement with pre-dilation was determined using the area difference under the pressure-volume curves of two consecutive inflations and compared to the angiographically determined lumen improvement. Stent opening pressure, the inflation volume needed to unfold the stent and the shape of the pressure-volume curve were assessed for differences between stent sizes (diameter, length) and manufacturer types. A Pearson correlation of 0.8 between the pressure-volume area difference and the angiographic lumen improvement was significant (p = 0.01), confirming that pressure-volume curves are useful in assessing lumen improvement after pre-dilation. There was a significant difference in stent opening pressure between stent types but not between different stent sizes (length, diameter). The inflation volume measured during the unfolding process of the stent correlated with the calculated stent lumen when deployed (Pearson correlation: 0.65, p = 0.001). The shape of the pressure-volume curve during stent deployment illustrated differences between different stent sizes (length, diameter) during inflation. Pressure-volume curves obtained from an automatic balloon inflation device have shown their usefulness in providing additional feedback about lumen improvement and the mechanical characteristics and quality of stent deployment.

Angioplasty, Balloon, Coronary↗

Rapid onset and offset of circulatory adaptations to exercise training in men.

Chronic aerobic exercise lowers blood pressure (BP), peripheral resistance and cardiac work, and is used widely in antihypertensive and cardiac rehabilitation programmes. In this study, we tested the hypothesis that the cardiovascular benefits of training would occur progressively over several weeks and would diminish over a similar time course on termination of training. In all, 17 young, healthy men undertook a 4-week programme of cycle ergometry (30 min at 60% VO2peak 3-4 times/week) and 13 subjects matched for age, body mass index and fitness acted as controls. Resting BP and rate-pressure product (RPP) had fallen significantly after only 1 week's training and reached a nadir after 2 weeks training. At this time, BP had fallen from 121+/-7/66+/-6 to 110+/-5/57+/-7 mmHg and resting RPP had fallen from 85+/-10 to 71+/-9 (mmHg (beats min-1))-2 (P<0.001 each). In parallel, resting forearm conductance had risen from 0.026+/-0.010 to 0.052+/-0.029 (ml min-1) 100 ml-1 mmHg-1 and peak reactive hyperaemia following 3 min brachial artery occlusion was increased from 0.105+/-0.031 to 0.209+/-0.041 (ml min-1) 100 ml-1 mmHg-1 (P<0.001 each). No significant further circulatory changes occurred over weeks 3-4 of training. On cessation of training, all values returned to pretraining levels within between 1 (SBP, RPP, vascular conductance) and 2 (DBP, MAP, heart rate, reactive hyperaemia) weeks. The results indicate that the optimal cardiovascular benefits of moderate exercise occur rapidly. At least with short training programmes, the benefits regress once training stops just as quickly as they appeared.

Adaptation, Physiological↗

Ovar-Mhc--ovine major histocompatibility complex: role in genetic resistance to diseases.

Research on the structure of the ovine major histocompatibility complex (MHC), Ovar-Mhc, and its association with resistance to various diseases in sheep has received increasing attention during recent years. The term 'resistance' is used to denote the capacity of an animal to defend itself against disease or to withstand the effects of a harmful environmental agent. The Ovar-Mhc is poorly characterised when compared to MHCs of other domestic animals. However, its basic structure is similar to that of other animals, comprising Class I, II and III regions. Products of the Class I and II genes, the histocompatibility molecules, are of paramount importance as these present antigens to T-lymphocytes, thereby eliciting immune responses. Several studies have been conducted in sheep on the involvement of MHC genes/antigens in genetic resistance to diseases, the majority being concerned with gastrointestinal nematodes. Studies on resistance to footrot, Johne's disease and bovine leukaemia virus (BLV)-induced leukaemogenesis have also been reported. Genes of all three regions were implicated in the disease association studies. In addition to disease resistance, Ovar-Mhc genes have been found to be associated with traits such as marbling and birthweight. The use of genetic markers from within the Ovar-Mhc may be useful, via marker-assisted selection, for increasing resistance to various diseases provided they do not impact negatively on other economically-important traits. This review summarises current knowledge of the role of Ovar-Mhc in genetic resistance to diseases in sheep.

Animals↗

Carriage, quantification, and predominance of methanogens and sulfate-reducing bacteria in faecal samples.

AIMS: To determine carriage rates and densities of methanogens and sulfate-reducing bacteria in adults and children using molecular methods, and to also determine if a reciprocal relationship exists between these organisms. METHODS AND RESULTS: Real-time PCR was used to detect and quantify methanogens and sulfate-reducing bacteria. Real-time PCR was more sensitive than breath methane measurements. Real-time PCR assays were applied to faecal DNA samples collected from 40 children and 12 adults. Methanogens were present in 25% of the children and 42% of the adults studied, and sulfate-reducing bacteria were detected in 15% of the children and 58% of the adults. High levels of sulfate-reducing bacteria were found in two methanogenic adults. CONCLUSIONS: Carriage rates and densities of methanogens and sulfate-reducing bacteria are greater in adults than in children. Competition does not necessarily lead to the predominance of one group in the faecal microflora. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes sensitive, molecular assays that could be used to monitor these organisms in gastrointestinal disease. Therapeutic exclusion of one group from the bowel would not necessarily lead to the expansion of the other, as there does not appear to be a reciprocal relationship between these groups.

Adult↗

An investigation of FRAXA intermediate allele phenotype in a longitudinal sample.

The FRAXA trinucleotide repeat at Xq27.3 gives rise to fragile X syndrome when fully expanded, and both premature ovarian failure (POF) and fragile X tremor and ataxia syndrome (FXTAS) when in the premutation range. Reports of phenotypic effects extending into the intermediate repeat range are inconsistent but some studies suggest that these smaller expansions predispose to special educational needs (SEN). This study utilises the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort to investigate cognitive and behavioural variables that might be associated with FRAXA intermediate alleles. The current study failed to find any strong evidence of association of FRAXA intermediate alleles with SEN, behavioural problems or cognitive difficulties. However, our findings illustrate some of the difficulties encountered in identifying individuals with SEN. The power to identify specific components of cognitive and behavioural difficulties was reduced due to elective drop-out, which is characteristic of longitudinal studies. Our findings demonstrate the non-random loss of participants from this cohort and highlight problems that may arise when such data are used in genetic association studies.

Alleles↗

Clinical effectiveness and cost-effectiveness of laparoscopic surgery for colorectal cancer: systematic reviews and economic evaluation.

OBJECTIVE: The aim of this study was to determine the clinical effectiveness and cost-effectiveness of laparoscopic, laparoscopically assisted (hereafter together described as laparoscopic surgery) and hand-assisted laparoscopic surgery (HALS) in comparison with open surgery for the treatment of colorectal cancer. DATA SOURCES: Electronic databases were searched from 2000 to May 2005. A review of economic evaluations was undertaken by the National Institute for Health and Clinical Excellence in 2001. This review was updated from 2000 until July 2005. REVIEW METHODS: Data from selected studies were extracted and assessed. Dichotomous outcome data from individual trials were combined using the relative risk method and continuous outcomes were combined using the Mantel-Haenszel weighted mean difference method. Summaries of the results from individual patient data (IPD) meta-analyses were also presented. An economic evaluation was also carried out using a Markov model incorporating the data from the systematic review. The results were first presented as a balance sheet for comparison of the surgical techniques. It was then used to estimate cost-effectiveness measured in terms of incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) for a time horizon up to 25 years. RESULTS: Forty-six reports on 20 studies [19 randomised controlled trials (RCTs) and one IPD meta-analysis] were included in the review of clinical effectiveness. The RCTs were of generally moderate quality with the number of participants varying between 16 and 1082, with 10 having less than 100 participants. The total numbers of trial participants who underwent laparoscopic or open surgery were 2429 and 2139, respectively. A systematic review of four papers suggested that laparoscopic surgery is more costly than open surgery. However, the data they provided on effectiveness was poorer than the evidence from the review of effectiveness. The estimates from the systematic review of clinical effectiveness were incorporated into a Markov model used to estimate cost-effectiveness for a time horizon of up to 25 years. In terms of incremental cost per life-year, laparoscopic surgery was found to be more costly and no more effective than open surgery. With respect to incremental cost per QALY, few data were available to differentiate between laparoscopic and open surgery. The results of the base-case analysis indicate that there is an approximately 40% chance that laparoscopic surgery is the more cost-effective intervention at a threshold willingness to pay for a QALY of pound 30,000. A second analysis assuming equal mortality and disease-free survival found that there was an approximately 50% likelihood at a similar threshold value. Broadly similar results were found in the sensitivity analyses. A threshold analysis was performed to investigate the magnitude of QALY gain associated with quicker recovery following laparoscopic surgery required to provide an incremental cost per QALY of pound 30,000. The implied number of additional QALYs required would be 0.009-0.010 compared with open surgery. CONCLUSIONS: Laparoscopic resection is associated with a quicker recovery (shorter time to return to usual activities and length of hospitalisation) and no evidence of a difference in mortality or disease-free survival up to 3 years following surgery. However, operation times are longer and a significant number of procedures initiated laparoscopically may need to be converted to open surgery. The rate of conversion may be dependent on experience in terms of both patient selection and performing the technique. Laparoscopic resection appears more costly to the health service than open resection, with an estimated extra total cost of between pound 250 and pound 300 per patient. In terms of relative cost-effectiveness, laparoscopic resection is associated with a modest additional cost, short-term benefits associated with more rapid recovery and similar long-term outcomes in terms of survival and cure rates up to 3 years. Assuming equivalence of long-term outcomes, a judgement is required as to whether the benefits associated with earlier recovery are worth this extra cost. The long-term follow-up of the RCT cohorts would be very useful further research and ideally these data should be incorporated into a wider IPD meta-analysis. Data on the long-term complications of surgery such as incisional hernias and differences in outcomes such as persisting pain would also be valuable. Once available, further data on both costs and utilities should be included in an updated model. At this point, further consideration should then be given as to whether additional data should be collected within ongoing trials. Few data were available to assess the relative merits of HALS. Ideally, there should be more data from methodologically sound RCTs. Further research is needed on whether the balance of advantages and disadvantages of laparoscopic surgery varies within subgroups based on the different stages and locations of disease. Research relating to the effect of experience on performance is also required.

Colorectal Neoplasms↗

Differential expression of proteins in cold-adapted log-phase cultures of Escherichia coli incubated at 8, 6 or 2 degrees C.

Temperature is used to control the growth of microorganisms in foods. The minimum temperature for sustained growth of Escherichia coli is 7 degrees C. E. coli cells in the logarithmic phase of growth at 15 degrees C were incubated at 8, 6 or 2 degrees C. The cells grew with the formation of filaments at the two higher temperatures, but did not grow at 2 degrees C. In order to investigate more thoroughly the nature of filament formation in E. coli at temperatures near the minimum temperature for sustained growth, cells were harvested after 1 day at 2 degrees C or at times up to 4 or 8 days at 8 or 6 degrees C, respectively. Proteins extracted from the cells were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), and spots containing differentially expressed proteins were identified by quadropole time-of-flight tandem (Q-ToF-2) mass spectrometry. For most of the identified proteins, the amounts were not substantially different in cells grown at 15 degrees C or incubated at 2 degrees C. In cells incubated at 8 or 6 degrees C, proteins associated with stress responses, the tricarboxylic acid cycle and electron transport were present in substantially greater amounts, and proteins associated with protein synthesis were present in substantially smaller amounts than in cells grown at 15 degrees C. These findings suggest that the stringent response is induced in E. coli incubated at temperatures near the minimum for growth, so the formation of filaments at those temperatures may be a result of the stringent response.

Cold Temperature↗

Ciprofloxacin resistance in non-typhoidal Salmonella serotypes in Scotland, 1993-2003.

OBJECTIVES: To determine the levels of resistance to ciprofloxacin among non-typhoidal salmonellae in Scotland. METHODS: Etest strips were used to determine the ciprofloxacin MICs for nalidixic acid-resistant salmonellae isolated from humans during 1993-2003. RESULTS: The percentage of nalidixic acid-resistant salmonellae isolated from human infection in Scotland has increased from 1.4% in 1993, to 8.8% in 1998 and 21.3% in 2003. Of 493 strains of nalidixic acid-resistant Salmonella tested, a single isolate of Salmonella Typhimurium RDNC was resistant to ciprofloxacin at the NCCLS breakpoint of 4 mg/L. Eleven isolates were resistant at the Scottish Salmonella Reference Laboratory breakpoint of 0.5 mg/L, while 466 isolates (94.5%) had reduced susceptibility with MICs of > or =0.125 mg/L and <0.5 mg/L. CONCLUSIONS: These results show that very few non-typhoidal isolates of Salmonella in Scotland that are resistant to nalidixic acid are also resistant to ciprofloxacin at the NCCLS recommended breakpoint of 4 mg/L. The majority of isolates examined, however, do show reduced susceptibility at 0.125 mg/L. This confirms the necessity for continuing antimicrobial surveillance of resistance to this important antibiotic.

Ciprofloxacin↗

Low-cost oscillometric non-invasive blood pressure monitors: device repeatability and device differences.

Automated non-invasive blood pressure measuring devices based on the oscillometric technique are used widely for self-measurement and are often used in clinics in place of the manual, auscultatory method. Oscillometry was originally developed for monitoring purposes and there are questions over its suitability for making diagnostic measurements. This study measured the differences between automated devices, in the absence of physiological variability. We studied 19 low-cost, automated, non-invasive blood pressure devices, using a repeatable artificial arm simulator, and measured the within-device repeatability and between-device differences. We found that the devices were repeatable (mean within-device difference 1 mmHg), but between-device differences were 4.4 mmHg (systolic pressure) and 3.6 mmHg (diastolic pressure), for normal and high-normal blood pressures. Individual devices are sufficiently repeatable for clinical trend use, but differences between devices are sufficiently large that they may be misinterpreted as clinically significant.

Blood Pressure Determination↗

The effect of towing a range of relative resistances on sprint performance.

The aim of this study was to compare sprint performance over 10 and 20 m when participants ran while towing resistances, weighing between 0 and 30% of body mass. The sample of 33 participants consisted of male rugby and soccer players (age 21.1 +/- 1.8 years, body mass 83.6 +/- 13.1 kg, height 1.82 +/- 0.1 m; mean +/- s). Each participant performed two sets of seven sprints over 20 m using a Latin rectangular design. The times were recorded at 10 and 20 m using electronic speed gates. The sprints of 13 players were video-recorded to allow calculation of stride length and frequency. For both sprints, a quadratic relationship was observed between sprint time and resistance as sprint time increased from 2.94 s to 3.80 s from 0 to 30% resistance. This relationship was statistically significant but considered not to be meaningful for performance because, over the range of resistances used in this study, the quadratic model was never more than 1% (in terms of sprint time) from the linear model. As resistance increased, the stride length shortened, with mean values of 1.63 +/- 0.13 m at 0% body mass and 1.33 +/- 0.13 m at 30% of body mass. There was no significant change in stride frequency with increasing resistance. The results show that in general there is an increase in sprint time with an increase in resistance. No particular resistance in the range tested (0 - 30%) can be recommended for practice.

Adult↗