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Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 19 recordsLinked to original sources
PubMed2006

The effects of changing temperature correction factors on measures of acidity calculated from gastric and oesophageal pH recordings.

BACKGROUND: Recently, Medtronic notified customers that new correction factors should be used for their Slimline and Zinetics24 single-use, internal-standard pH catheters. AIM AND METHODS: We selected 24-h recordings of oesophageal and gastric pH with the Zinetics24 from our archives for five healthy subjects and for five gastro-oesophageal reflux disease subjects who were studied at baseline and again after 8 days of treatment with a proton-pump inhibitor. All pH values obtained with the old correction factors were rescaled using the new correction factors. Values for median pH, integrated acidity and time pH < or = 4 were then calculated from pH values with old and new correction factors. RESULTS: The new correction factors changed values for median pH, integrated acidity and time pH < or = 4. Values for median pH and integrated acidity changed in a predictable, proportionate way, whereas values for time pH < or = 4 did not. CONCLUSIONS: The new correction factors will not change the interpretation of previously published results with median pH or integrated acidity. In contrast, values for time < or =4 cannot be converted in an obvious way with the new correction factors. Instead, the raw pH data will need to be rescaled and values for time pH < or = 4 recalculated using the rescaled pH data.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Cardiovascular magnetic resonance imaging for non-invasive assessment of vascular function: validation against ultrasound.

Ultrasound is an established modality for quantification of vascular function in clinical studies of cardiovascular disease. We determined whether cardiovascular magnetic resonance imaging (CMR) can provide a comparable assessment of vascular function. In seventeen control subjects, we used CMR to quantify endothelium-dependent (flow mediated dilatation, FMD) and endothelium-independent dilatation of the brachial artery, brachial and carotid distensibility, aortic compliance, and pulse wave velocity. These were compared to brachial and carotid measurements obtained by established ultrasound protocols. Twelve of the volunteers then underwent repeated measurements with both modalities. There was good agreement between imaging modalities for measures of endothelial function and arterial structure in the same subjects (difference between CMR and ultrasound for FMD = 0.14 +/- 6.8%, and brachial artery area = - 0.7 +/- 2.2 mm2, correlation between modalities for FMD = 0.62, p = 0.01 and for area = 0.87, p = < 0.0001). Inter-study reproducibility was also similar (coefficient of variation (CV) for FMD: CMR = 0.3, ultrasound = 0.3, CV for brachial artery area: CMR = 0.1, ultrasound = 0.1). Comparability and reproducibility were not as strong for functional measures if repeated studies were several days apart (CV for FMD by ultrasound on the same day = 0.1 and several days apart = 0.4). CMR and ultrasound show good agreement for quantitative measures of vascular structure and function with good reproducibility for both modalities. The major advantage of CMR is that it allows one-stop integrated assessment of both peripheral and central measures of vascular function.

Adult↗
PubMed2006

An interchangeable Mapleson A-E breathing system is practical and cost effective.

BACKGROUND: In locations where oxygen and anesthesia gas supplies are limited, and where circle systems are not practical, means to reduce fresh gas flow during maintenance of inhalational anesthesia are of potential value. We investigated whether a common transport breathing apparatus could be modified to allow interchange between Mapleson D (Map-D) and Mapleson A (Map A) configurations. METHODS: A common Map-D transport system was converted to a Map-A system by switching positions of the exhaust valve and the elbow connector where fresh gas is delivered; these two breathing systems were compared in this study. The key question was whether rebreathing of CO2 could be eliminated at a lower fresh gas flow rate (FGF) with the Map-A design. A structured protocol was followed. RESULTS: A mean decrease in FGF of 2.8 l/min was seen with the Map-A apparatus when compared with the Map-D (P=0.003). With no significant differences in physiologic or anesthetic variables, FGF/V(E) was significantly lower with the Mapleson A configuration than with the Mapleson D system design (1.1 vs. 1.8; P=0.007). The extent to which FGF could be lowered when switching between Mapleson D and A systems correlated strongly with the patients' respiratory rate while under anesthesia (r=0.45, P<0.01). CONCLUSIONS: Cost and resource savings can be realized through the use of a breathing system modification that achieves appropriate ventilation at lower fresh gas flows.

Adult↗
PubMed2005

The TRENDS Project: development of a methodology to reliably monitor the obesity epidemic in childhood.

AIMS: The government has set a target to halt the rise in childhood obesity in those aged under 11 by 2010, but no system is in place to ascertain if this has been achieved. We aimed to develop a simple and reproducible methodology to monitor trends in childhood obesity. METHODS: A purposive sample of 10 primary schools and three secondary schools was selected. Children were measured with parental "opt out" consent in reception class, year 4, and year 8 (ages 5, 9, and 13 years, respectively). Measurements were compared with those obtained locally in 1996-2001. Calculations were then performed to ascertain the sample size required to confidently identify a halt in the rise in obesity using three growth measures. RESULTS: A total of 999 children were measured with ascertainment of 95% in primary and 85% in secondary schools. The proportion of overweight and obese children aged 9 and 13 years had increased since 1996-2001, although only 9 year olds showed a significant rise. A general trend of an increase in obesity was observed with increasing age. Calculations showed that 1900-2400 children per age group are needed to detect a halt in the rise in obesity based on mean body mass index (BMI) standard deviation scores (SDS) by 2010 with 90% power, whereas 4200-10 500 children are needed for other measures. CONCLUSION: We have developed a simple, cost effective methodology for accurately measuring the epidemic and recommend the use of mean BMI SDS for demonstrating if a halt has been achieved.

Adolescent↗
PubMed2005

The fractal nature of human gastro-oesophageal reflux.

BACKGROUND: We are unaware of the analyses of time series data resulting from 24 h recordings of human gastric or oesophageal pH. As a result, we have no understanding of the quantitative changes in gastric or oesophageal acidity over time, the patterns that might characterize these changes, or the physiological significance of gastro-oesophageal reflux. AIM: To examine the time series for gastric and oesophageal pH. METHODS: Detrended fluctuation analysis and lag analysis were used to analyse data from 24 h recordings of oesophageal and gastric pH in five normal subjects and five subjects with gastro-oesophageal reflux disease. RESULTS: Analyses of the patterns of gastric and oesophageal pH over time in normal subjects and subjects with gastro-oesophageal reflux disease indicate that the fluctuations in pH are self-similar across different time scales and are consistent with an underlying fractal process. Furthermore, there is a significant statistical association between sequential pH values separated by as much as 2.2 h. CONCLUSIONS: We hypothesize that the self-similar, fractal pattern encodes information about gastric acidity and that the oesophagus decodes this information and, when appropriate, may signal the stomach to reduce gastric acidity. Subjects with gastro-oesophageal reflux disease might have an impaired oesophageal-gastric feedback mechanism that results in increased gastric acid, which reflux from the stomach into the oesophagus.

Adolescent↗
PubMed2005

Decreases in phosphoinositide-3-kinase/Akt and extracellular signal-regulated kinase 1/2 signaling activate components of spinal motoneuron death.

Motoneuron dependence on target-derived trophic factors during development is well established, with loss of trophic support leading to the death of these cells. A complete understanding of the intracellular signal transduction machinery associated with extracellular survival signals requires the examination of individual pathways in various cellular and environmental contexts. In cells deprived of trophic support, and hence compromised for survival, phosphoinositide-3-kinase (PI3K) is decreased when compared with healthy cells supplied with trophic support. Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling is dramatically decreased in deprived cells. We have examined the role of these two pathways to understand how changes in their activity regulate motoneuron survival and death. Pharmacological inhibition of PI3K attenuated motoneuron survival and was important in the regulation of Bcl-2 serine phosphorylation, limited release of cytochrome c into the cytoplasm and caspase activation. Bax translocation from cytoplasm to mitochondria was not altered when PI3K was inhibited. High levels of ERK1/2 inhibition robustly attenuated motoneuron survival in cells supplied with trophic support, whereas moderate inhibition of ERK1/2 activation had little effect. ERK1/2 inhibition in these cells decreased Bcl-2 phosphorylation and resulted in release of cytochrome c from the mitochondria. Bax translocation and caspase activation were not affected by ERK1/2 inhibition. These data reveal that changes in PI3K and ERK1/2 signaling lead to individual and overlapping effects on the cell-death machinery. Characterizing the role of these pathways is critical for a fundamental understanding of the development and degeneration of specific neuronal populations.

Animals↗
PubMed2005

Using smart card technology to monitor the eating habits of children in a school cafeteria: 1. Developing and validating the methodology.

OBJECTIVE: The aim of the study was to test the feasibility of using smart card technology to track the eating behaviours of nearly a thousand children in a school cafeteria. METHODS: Within a large boys' school a smart card based system was developed that was capable of providing a full electronic audit of all the individual transactions that occurred within the cafeteria. This dataset was interfaced to an electronic version of the McCance and Widdowson composition of foods dataset. The accuracy of the smart card generated data and the influence of portion size and wastage were determined empirically during two 5-day trials. RESULTS: The smart card system created succeeded in generating precise data on the food choices made by hundreds of children over an indefinite time period. The data was expanded to include a full nutrient analysis of all the foods chosen. The accuracy of this information was only constrained by the limitations facing all food composition research, e.g. variations in recipes, portion sizes, cooking practices, etc. Although technically possible to introduce wastage correction factors into the software, thereby providing information upon foods consumed, this was not seen as universally practical. CONCLUSION: The study demonstrated the power of smart card technology for monitoring food/nutrient choice over limitless time in environments such as school cafeterias. The strengths, limitations and applications of such technology are discussed.

Child↗
PubMed2005

Using smart card technology to monitor the eating habits of children in a school cafeteria: 2. The nutrient contents of all meals chosen by a group of 8- to 11-year-old boys over 78 days.

OBJECTIVE: The aim of the study was to test the abilities of the newly created smart card system to track the nutrient contents of foods chosen over several months by individual diners in a school cafeteria. METHODS: From the food choice and composition of food data sets, an Access database was created encompassing 30 diners (aged 8-11 years), 78 days and eight nutrients. Data were available for a total of 1909 meals. RESULTS: Based upon population mean values the cohort were clearly choosing meals containing higher than the recommended maximum amounts for sugar and lower than the recommended minimum amounts of fibre, iron and vitamin A. Protein and vitamin C contents of meals chosen were well above minimum requirements. Over the 1909 meals, nutrient requirements were met 41% of the time. CONCLUSIONS: The system created was very effective at continually monitoring food choices of individual diners over limitless time. The data generated raised questions on the common practice of presenting nutrient intakes as population mean values calculated over a few days. The impact of heavily fortified foods on such studies in general is discussed.

Child↗
PubMed2005

Using smart card technology to monitor the eating habits of children in a school cafeteria: 3. The nutritional significance of beverage and dessert choices.

OBJECTIVE: The consumption patterns of beverages and desserts features highly in the current debate surrounding children's nutrition. The aim of this study was to continuously monitor the choice of beverages and desserts made by nearly 1000 children in a school cafeteria. METHODS: A newly developed smart card system was used to monitor the food choices of diners (7-16-year-old boys) in a school cafeteria over 89 days. A wide variety of beverages and desserts were on offer daily. RESULTS: Despite coming from an affluent, well-educated demographic group, the boys' choices of beverages and desserts mirrored those of children in general. Buns and cookies were over 10 times more popular than fresh fruits and yogurts. Sugary soft-drinks were over 20 times more popular than fresh fruit drinks and milk combined. Appropriate choices could, over a month, reduce intake of added sugar by over 800 g and fat by over 200 g. CONCLUSION: The smart card system was very effective at monitoring total product choices for nearly 1000 diners. In agreement with a recent national school meal survey, where choice is extensive, children show a preference for products high in fat and/or sugar. The consequences of these preferences are discussed.

Adolescent↗
PubMed2005

Proton pump inhibitors: update on their role in acid-related gastrointestinal diseases.

Gastric acid is pathogenic in many gastrointestinal disorders, such as gastroesophageal reflux disease and peptic ulcer disease. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for serious acid-related conditions. Ample recent data exist to explicate virtually every aspect of the clinical management of acid-peptic disorders with PPIs. Although all PPIs are effective, there are some differences in their clinical performance, particularly in terms of the degree and speed of gastric acid suppression. Rapid onset of acid suppression may be particularly relevant to newer approaches, such as 'on-demand' or intermittent therapy for non-erosive reflux disease and shorter regimens for Helicobacter pylori eradication. New data, in addition, highlight differences in PPI metabolism that may both affect efficacy and predispose patients to drug-drug interactions. PPI selection should involve the awareness of these issues.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

OBJECTIVES: To identify and prioritise key areas of clinical uncertainty regarding the medical management of non-ST elevation acute coronary syndrome (ACS) in current UK practice. DATA SOURCES: Electronic databases. Consultations with clinical advisors. Postal survey of cardiologists. REVIEW METHODS: Potential areas of important uncertainty were identified and 'decision problems' prioritised. A systematic literature review was carried out using standard methods. The constructed decision model consisted of a short-term phase that applied the results of the systematic review and a long-term phase that included relevant information from a UK observational study to extrapolate estimated costs and effects. Sensitivity analyses were undertaken to examine the dependence of the results on baseline parameters, using alternative data sources. Expected value of information analysis was undertaken to estimate the expected value of perfect information associated with the decision problem. This provided an upper bound on the monetary value associated with additional research in the area. RESULTS: Seven current areas of clinical uncertainty (decision problems) in the drug treatment of unstable angina patients were identified. The agents concerned were clopidogrel, low molecular weight heparin, hirudin and intravenous glycoprotein antagonists (GPAs). Twelve published clinical guidelines for unstable angina or non-ST elevation ACS were identified, but few contained recommendations about the specified decision problems. The postal survey of clinicians showed that the greatest disagreement existed for the use of small molecule GPAs, and the greatest uncertainty existed for decisions relating to the use of abciximab (a large molecule GPA). Overall, decision problems concerning the GPA class of drugs were considered to be the highest priority for further study. Selected papers describing the clinical efficacy of treatment were divided into three groups, each representing an alternative strategy. The strategy involving the use of GPAs as part of the initial medical management of all non-ST elevation ACS was the optimal choice, with an incremental cost-effectiveness ratio (ICER) of 5738 pounds per quality-adjusted life-year (QALY) compared with no use of GPAs. Stochastic analysis showed that if the health service is willing to pay 10,000 pounds per additional QALY, the probability of this strategy being cost-effective was around 82%, increasing to 95% at a threshold of 50,000 pounds per QALY. A sensitivity analysis including an additional strategy of using GPAs as part of initial medical management only in patients at particular high risk (as defined by age, ST depression or diabetes) showed that this additional strategy was yet more cost-effective, with an ICER of 3996 pounds per QALY compared with no treatment with GPA. Value of information analysis suggested that there was considerable merit in additional research to reduce the level of uncertainty in the optimal decision. At a threshold of 10,000 pounds per QALY, the maximum potential value of such research in the base case was calculated as 12.7 million pounds per annum for the UK as a whole. Taking account of the greater uncertainty in the sensitivity analyses including clopidogrel, this figure was increased to approximately 50 million pounds. CONCLUSIONS: This study suggests the use of GPAs in all non-ST elevation ACS patients as part of their initial medical management. Sensitivity analysis showed that virtually all of the benefit could be realised by treating only high-risk patients. Further clarification of the optimum role of GPAs in the UK NHS depends on the availability of further high-quality observational and trial data. Value of information analysis derived from the model suggests that a relatively large investment in such research may be worthwhile. Further research should focus on the identification of the characteristics of patients who benefit most from GPAs as part of medical management, the comparison of GPAs with clopidogrel as an adjunct to standard care, follow-up cohort studies of the costs and outcomes of high-risk non-ST elevation ACS over several years, and exploring how clinicians' decisions combine a normative evidence-based decision model with their own personal behavioural perspective.

Acute Disease↗
PubMed2004

Cleft sternum: case report and literature review.

The isolated sternal cleft is a rare congenital anomaly that presents from birth to adulthood. We describe the late presentation and management in a child with this condition. The modern investigative and operative options are reviewed.

Bone Transplantation↗
PubMed2004

FLRT3 is expressed in sensory neurons after peripheral nerve injury and regulates neurite outgrowth.

We used a molecular screen to identify genes upregulated in regenerating adult rat dorsal root ganglion cells. FLRT3 mRNA and protein characterized by a fibronectin type III domain and a leucine-rich repeat motif was upregulated in damaged sensory neurons. The protein was then transported into their peripheral and central processes where the FLRT3 protein was localized to presynaptic axon terminals. In vitro, the FLRT3 protein was expressed at the cell surface, regulated neurite outgrowth in sensory neurons, but did not exhibit homophilic binding. FLRT3 was widely expressed in the developing embryo, particularly in the central nervous system and somites. However, in the adult, we found no evidence for accumulation or reexpression of the FLRT3 protein in damaged axons of the central nervous system. We conclude that FLRT3 codes for a putative cell surface receptor implicated in both the development of the nervous system and in the regeneration of the peripheral nervous system (PNS).

Amino Acid Sequence↗
PubMed2004

Role of two angiotensinogen polymorphisms in blood pressure variation.

Genetic analysis of hypertension has yielded inconsistent results, making it difficult to draw clear conclusions regarding the impact of specific variants on blood pressure regulation. Among the most studied of the candidate genes for blood pressure regulation is angiotensinogen (AGT), but as with other candidate loci associations with blood pressure have been inconsistent. We examined the contributions of two AGT polymorphisms (T174M and M235T) to detect the effects of each on blood pressure variation, using single-site and two-site analyses. We analysed data from a study of 177 subjects from Accra, Ghana. We observed significant single-locus associations of the T174M polymorphism with average systolic (SBP) and diastolic blood pressure (DBP) when age was used as a covariate (P<0.001 and P=0.010, respectively). Also, we observed a significant association of the M235T polymorphism with SBPs and DBPs (P<0.001 and P=0.014, respectively). Finally, we observed a simultaneous significant association of the two polymorphisms with SBP and DBP (P<0.001 and P=0.026, respectively), although the two-loci model is not significantly better than either single-locus model. However, for SBP the two-loci model is marginally better (P=0.08 in comparison to both single-locus models). These results suggest that variants at these two AGT sites together, in conjunction with age, may be significantly associated with elevated SBP, whereas the single-site models are as good models of DBP. It is possible that earlier inconsistent results with these AGT polymorphisms with hypertension in African-derived populations may have resulted from an 'incomplete' model in the different study populations. Given the inconclusive nature of our two-loci results, this possibility requires further investigation.

Aging↗
PubMed2004

Review article: the pharmacodynamics and pharmacokinetics of proton pump inhibitors--overview and clinical implications.

During the past two decades, enormous changes occurred in the management of gastric acid-related diseases. First, the histamine2-receptor antagonists were introduced, offering patients the first single-agent therapy that effectively reduced gastric acid secretion. Proton pump inhibitors became widely available in the early 1990s, and they generally appeared to be superior to the histamine2-receptor antagonists in acid-suppressing activity, symptom control and healing. Most physicians now use proton pump inhibitors as first-line treatment for many patients with acid-peptic disorders, including erosive gastro-oesophageal reflux disease (GERD), nonerosive reflux disease (NERD) and duodenal and gastric ulcers. Although proton pump inhibitors are often thought to be interchangeable, some differences have emerged in their pharmacological properties, which may be reflected in some aspects of clinical efficacy. Such differences include potency, speed of onset and duration of pH 'holding times'. Helicobacter pylori has now been recognized as an important factor in the pathogenesis of acid-peptic disorders. It is clear that H. pylori eradication can dramatically reduce the chronicity of gastric and duodenal ulcers, and accepted therapeutic regimens for H. pylori eradication now include proton pump inhibitors and two or more antibiotics. Although all accepted proton pump inhibitor-based 'triple therapies' are roughly equivalent in efficacy, there is now a shortened regimen available that will potentially enhance compliance and decrease cost. This review examines the relative advantages of proton pump inhibitors vs. histamine2-receptor antagonists in the context of acid suppression and in various gastric acid-related diseases. A brief overview presents the pharmacodynamics and pharmacokinetics of the proton pump inhibitors with particular attention paid to rabeprazole, one of the newer drugs in its class.

Gastric Acid↗
PubMed2004

Review article: pH, healing and symptom relief with rabeprazole treatment in acid-related disorders.

Control of gastric acid secretion by antisecretory agents has been the cornerstone of therapy in the successful management of all acid-related disorders, including gastro-oesophageal reflux disease (GERD), and duodenal and gastric ulcer. Treatment efficacy has been strongly correlated with degree and duration of acid suppression within the 24-h period and with total duration of therapy. All proton pump inhibitors are highly effective for the healing of ulcers and erosive oesophagitis. All have closely similar mechanisms of action, yet important pharmacological differences exist, which can significantly impact certain aspects of their clinical efficacy. Rabeprazole's rapid activation over a wide pH range may be the explanation for its early onset of effective acid inhibition compared with other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole. Like rabeprazole, esomeprazole is also a potent inhibitor of gastric acid at steady state, although it is thought that rabeprazole may provide enhanced first-day acid suppression compared with esomeprazole. First-day antisecretory efficacy should produce faster symptom relief, a hypothesis supported by clinical data. Moreover, drugs with pharmacological profiles that include both rapid onset and potent antisecretory effects should help control healthcare costs by reducing the need for otherwise commonly used twice-daily proton pump inhibitor administration.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Oesophageal pH has a power-law distribution in control and gastro-oesophageal reflux disease subjects.

BACKGROUND: We are unaware of any solid theoretical or pathophysiological basis for selecting pH 4 or any other pH value to assess oesophageal acid exposure or to define oesophageal reflux episodes. AIM: To examine the frequency of different oesophageal pH values in control and GERD subjects. METHODS: Oesophageal pH was measured for 24 h in 57 gastro-oesophageal reflux disease subjects and 26 control subjects. Histograms were constructed using the 21,600 values from each recording and bins of 0.25 pH units. RESULTS: Compared with controls, gastro-oesophageal reflux disease subjects had significantly more low pH values and significantly fewer high pH values. In both gastro-oesophageal reflux disease and control subjects, the frequency of oesophageal pH values was characterized by a power-law distribution indicating that the same relationship that describes low pH values also describes high pH values, as well as all values in between. CONCLUSIONS: The distribution of oesophageal pH values indicates that a variety of different pH values can be used to assess oesophageal acid exposure, but raises important questions regarding how oesophageal reflux episodes are defined.

Adolescent↗