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Biomedical subjects

R H Jones

Publications and source records attributed to R H Jones.

At least 19 recordsLinked to original sources

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism.

AIMS/HYPOTHESIS: It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. SUBJECTS AND METHODS: We randomised 17 sedentary overweight male subjects (age 50 +/- 2.6 years, BMI 27.6 +/- 0.5 kg/m(2)) to a 6-week exercise programme (n = 10) or control group (n = 7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic-euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg(-1) min(-1)]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. RESULTS: After 6 weeks, fasting glycerol, palmitic acid Ra (p = 0.003, p = 0.042) and NEFA concentration (p = 0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p = 0.026; p = 0.007 and p = 0.04). There was no change in muscle triacylglycerol and liver fat in either group. CONCLUSIONS/INTERPRETATION: Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.

Blood Glucose↗

Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial.

OBJECTIVES: To determine whether cognitive behavioural therapy (CBT) in addition to antispasmodic treatment offers a cost-effective benefit to primary care patients with irritable bowel syndrome (IBS) and to identify predictors of outcome. DESIGN: This was a randomised controlled trial in primary care of the addition of CBT to standard general practice management of IBS, using the antispasmodic agent mebeverine hydrochloride. The study set out to compare the addition of a standardised package of IBS-specific CBT to treatment with mebeverine hydrochloride. SETTING: Ten general practices, serving a population of around 45,000 patients, located principally in south London, with some patients resident in north London. PARTICIPANTS: Patients identified as having IBS by their GPs, aged between 17 and 54 (mean 34) years and predominantly white; 82% were female and half had had IBS for more than 5 years. INTERVENTIONS: Practice nurses delivered CBT in a randomised trial of the addition of CBT to mebeverine in patients who had IBS of moderate or greater severity after 2 weeks of GP care and 4 weeks of mebeverine. The Symptom Severity Scale (SSS) was used to identify patients with moderate or severe IBS. Patients who continued to report moderate or severe IBS after 4 weeks of mebeverine at a dose of 270 mg three times a day were randomised to receive six sessions of CBT in addition to mebeverine (72 patients) or mebeverine alone (77 patients). These patients were followed at 3, 6 and 12 months after treatment. As part of the baseline evaluation, blood tests for antiendomysial and antigliadin antibodies were carried out on 141 patients to determine the prevalence of coeliac disease in this population. MAIN OUTCOME MEASURES: The principal outcome measure was the SSS. Others included the Hospital Anxiety and Depression Scale, psychopathology, the Work and Social Adjustment Scale (WASA, disability), a modified version of the Illness Perception Questionnaire (illness perceptions), the Beliefs about Medicine Questionnaire (attitudes to medication), the Reported Adherence to Medication Scale (adherence to prescribed medication), the Client Service Receipt Inventory (economic analysis), the Cognitive Scale for Functional Bowel Disorders (illness cognitions) and the Behaviour Scale for IBS (IBS coping behaviour). RESULTS: The addition of CBT produced a significant benefit compared with the mebeverine-only group at 3 months after treatment on all outcome measures, except for the adherence to medication scales. The difference between the groups was 107.8 points on the SSS, 24.5 points on question 4 of the SSS and 6.3 points on the WASA, representing therapeutic gains of approximately 20%, 28% and 40%, respectively. However, there was also evidence that these improvements began to wane, so that at 6 and 12 months follow-up significant therapeutic benefit of the addition of CBT could only be detected on question 4 of the SSS and on the WASA. The behaviour scale for IBS detected significant, positive changes in coping behaviours at up to 6 months after treatment. Three factors predicting a poor outcome were identified: male gender, believing that IBS had serious consequences and belief in an external aetiology, all of which were associated with greater than average disability at follow-up. The addition of CBT to mebeverine did not reduce overall treatment or social costs. The nested study on testing for coeliac disease provides cautious support for the inclusion of antiendomysial and antigliadin antibody testing in the investigation of patients thought to have IBS. CONCLUSIONS: Specially trained practice nurses can provide effective CBT to primary care patients with a clinical diagnosis of IBS, which although effective does not reduce service or social costs. Using a variety of measures the beneficial therapeutic effects of the addition of CBT to antispasmodic therapy persist for up to 6 months. Future research might include studies of the long-term follow-up of IBS patients treated with CBT, cost-benefit analyses comparing CBT with other therapeutic approaches to IBS, and evaluating means of training both non-specialist health professionals and GPs to deliver CBT.

Adolescent↗

The use of softer X-rays in the structure elucidation of microporous materials.

Microporous materials, such as zeolites and aluminophosphates, have many applications as molecular sieves and shape-selective catalysts. This is due to their three-dimensional frameworks, which contain regular pores and channels, to their high acidity, arising from Brønsted and Lewis acid active sites, and to the incorporation of transition metal atoms into framework sites. This review firstly provides an introduction into the nature and properties of these materials, and their important applications; the difficulties in their full characterization and possible methods of elucidating their structures are then outlined; finally, methods of characterization, utilizing 'softer X-rays' are introduced. The first method is the determination of low concentrations of transition metals, incorporated into the frameworks using single crystal anomalous dispersion crystallography; synchrotron radiation is used to tune to the absorption edge of the metal atom in question, in order to change its signal relative to that of the rest of the structure, thereby allowing the pinpointing of its positions and the determination of its concentration at each site in the framework. Secondly, the use of longer wavelengths in powder diffraction studies is described, which, by stretching out the powder pattern, thereby reduces the overlapping of the diffraction peaks, thus allowing the structure to be solved by conventional direct methods. Finally, the use of X-ray absorption spectroscopy to determine the metal incorporation and the nature of coordination at the metal atom sites, in Mn silicalite-1 and FAPO-36, are described.

Ceramics↗

The performances of vegetative treatment systems for highway runoff during dry and wet conditions.

The performances of two different highway runoff treatment systems, a horizontal subsurface flow-constructed wetland and a vegetated balancing pond, are described. Both systems have been assessed by collecting inlet and outlet grab samples during wet and dry weather conditions, and automatically controlled storm event samples have been obtained for the constructed wetland. Removal efficiencies are discussed for BOD (grab samples only), suspended solids, Cd, Cr, Cu, Ni, Pb, Zn, nitrate and sulphate, and explanations are offered for the trends observed under different weather conditions. The large variabilities in the removal efficiencies derived for both treatment systems, based on the analyses of grab samples, make accurate comparisons of the performances difficult and also raise concerns about using this type of sampling approach for this purpose. Treatment systems are required to function satisfactorily during the increased inlet loadings experienced during storm events, and this is shown to be the case for the constructed wetland for the majority of the monitored pollutants. The large removal efficiency ranges for five separate storm events, exhibited by Cu and Pb, are discussed and compared to the other monitored pollutants which showed positive median wet weather removal efficiencies of between 43% and 85%. Despite the existence of performance fluctuations, the generally low monitored inlet concentrations in the highway runoff indicated that the pond discharges did not threaten the environmental quality of the receiving waters.

Biodegradation, Environmental↗

The dynamic desorption of krypton from the zeolite chabazite.

Single crystal diffraction studies of the zeolite chabazite show that at high loading krypton atoms are forced to occupy sites with unfavourable interatomic Kr-Kr separations but upon desorption of Kr the remaining Kr atoms can now occupy sites with no such unfavourable separations.

Journal Article↗

New directions in testicular cancer; molecular determinants of oncogenesis and treatment success.

Metastatic testicular cancer is highly curable with conventional cytotoxic drugs. This is in contrast to most other metastatic solid tumours which can only be palliated with chemotherapy achieving only a modest impact on overall survival. If we could understand at the molecular level why chemotherapy is so effective in the treatment of testicular cancer, we may be better able to move other forms of metastatic cancer into the curable bracket. Most cytotoxic drugs appear to induce cell death by activating intracellular apoptotic mechanisms. Thus, the ability of a cancer to activate and execute such mechanisms in response to treatment is paramount in determining the effectiveness of chemotherapy. The basic study of cancer molecular biology is providing some insight into the proteins involved in this process and the ability to apply this information to actual human tumours is essential to rationalise clinical treatment failures at a molecular level. Testicular cancer provides an excellent model system in this analysis. Whereas there are large numbers of patients that are cured by chemotherapy, there are some whose cancers become resistant to treatment. An understanding of testicular cancer molecular biology may allow the identification of the genes regulating such a crucial behavioural switch. It may then be possible to manipulate specific signalling pathways to overcome drug resistance. This review focuses on recent developments in our understanding of the molecular biology of testicular cancer. A number of key players have been implicated including p53, pRb, cyclin D2, p INK proteins, c-kit and the bcl-2 family of proteins. The exact manner by which cellular transformation occurs has still not been established, but it is clear that many of the above proteins also have important roles in normal spermatogenesis. This is a developmental phase when the generation of genetic diversity is at a premium, but when selective apoptotic mechanisms are paramount. We discuss why this may be relevant to the behaviour of germ cell tumours and address possible reasons why they can become resistant to conventional therapy.

Antineoplastic Agents↗

An irritable bowel syndrome-specific symptom questionnaire: development and validation.

BACKGROUND: No self-assessment instruments are available to assess symptoms of irritable bowel syndrome (IBS). Our aim was to develop a disease-specific symptom questionnaire for use in patients with IBS. METHODS: Two-hundred-and-thirty-four patients (77% F) with a mean age of 44 years took part in a psychometric evaluation using the previously validated Gastrointestinal Symptom Rating Scale modified for use in patients with IBS (GSRS-IBS). This version was tested against several disease-specific health-related quality of life (HRQL) questionnaires. Items with a high ceiling effect, items that measured a different construct, and items showing high correlation (>0.80) to another item were removed. A confirmatory factor analysis was also performed. RESULTS: The final questionnaire included 13 items depicting problems with satiety, abdominal pain, diarrhoea, constipation and bloating. The internal consistency reliability was high, ranging from 0.74 (pain) to 0.85 (satiety). The associations between similar constructs in the GSRS-IBS and the various HRQL scores confirmed the construct validity. Pain, bloating and diarrhoea were the symptom clusters that impaired HRQL the most. CONCLUSION: The GSRS-IBS is a short and user-friendly instrument with excellent psychometric properties.

Adult↗

Outcome measures in irritable bowel syndrome: comparison of psychometric and methodological characteristics.

OBJECTIVES: Although there is growing interest in irritable bowel syndrome (IBS) research, there is as yet no consensus regarding the preferred outcome measure. We aimed to evaluate and to compare the validity and appropriateness of available IBS outcome measures. METHODS: IBS symptom and IBS health-related quality of life (HRQOL) scales were identified through a literature search. In a panel evaluation, six reviewers independently rated the scales according to predetermined psychometric and methodological validation criteria. RESULTS: Five IBS symptom scales and five IBS HRQOL instruments were identified. Two of the symptom scales were rated as good. The Adequate Relief question scored best. This scale demonstrates responsiveness as well as face and construct validity, and its score was considered easy to interpret and appropriate for use. According to the reviewers, the IBS Severity Scoring System performed well with regard to psychometric capacities, but its practical utility was considered debatable. The properties of the other three symptom scales were suboptimal. The practical utility of the five IBS-specific HRQOL scales was considered poor. However, the reviewers agreed that, at present, the IBS Quality of Life measurement (Patrick et al.) is the best choice, because it has been the most extensively validated and shows appropriate psychometric quality. CONCLUSIONS: The Adequate Relief question is the measure of first choice when assessing global symptomatology as an outcome in IBS studies. For a more detailed IBS symptom assessment, the IBS Severity Scoring System is preferable. Finally, the IBS Quality of Life measurement scale can be used to establish changes in health-related quality of life.

Colonic Diseases, Functional↗

Approaches to uninvestigated dyspepsia.

Uninvestigated dyspepsia refers to patients with new or recurrent dyspeptic symptoms in whom no investigations have previously been undertaken. These patients are much more likely to present in primary than in secondary care. It is particularly important to be able to offer effective symptom relief to support the explanation, reassurance, and advice provided to patients, and low dose or standard dose proton pump inhibitor therapy appears to offer the most effective approach to empirical therapy of this kind.

Anti-Ulcer Agents↗

Improving the fit of bivariate smoothing splines when estimating longitudinal immunological and virological markers in HIV patients with individual antiretroviral treatment strategies.

CD4+ lymphocyte count and HIV RNA plasma viral load are longitudinally monitored in patients with HIV infection. Because data collection intervals may be unequally spaced and these markers experience high within-patient variability, they may be smoothed before use in subsequent models. Estimation strategies must be able to accommodate the drastic changes in viral load which may occur when an individual's treatment strategy is updated. Because these treatment changes are not regimented, these dynamics cannot be modelled using standard methods. We propose univariate and bivariate cubic smoothing splines to fit CD4+ count and viral load over time. The method is developed using state space equations, and the Kalman filter is used to calculate the log-likelihood. Non-linear optimization is used to obtain the maximum likelihood estimates. A modification of the Kalman filter allows non-informative or diffuse priors at the initial observation. Since treatment changes are expected to alter the shape of the curve, we further extend the Kalman filter to permit greater flexibility in the smoothing spline at these time points. The method produces smoothed estimates of the viral load and CD4+ count curves over time.

Anti-HIV Agents↗

Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery.

BACKGROUND: Cognitive decline complicates early recovery after coronary-artery bypass grafting (CABG) and may be evident in as many as three quarters of patients at the time of discharge from the hospital and a third of patients after six months. We sought to determine the course of cognitive change during the five years after CABG and the effect of perioperative decline on long-term cognitive function. METHODS: In 261 patients who underwent CABG, neurocognitive tests were performed preoperatively (at base line), before discharge, and six weeks, six months, and five years after CABG surgery. Decline in postoperative function was defined as a drop of 1 SD or more in the scores on tests of any one of four domains of cognitive function. (A reduction of 1 SD represents a decline in function of approximately 20 percent.) Overall neurocognitive status was assessed with a composite cognitive index score representing the sum of the scores for the individual domains. Factors predicting long-term cognitive decline were determined by multivariable logistic and linear regression. RESULTS: Among the patients studied, the incidence of cognitive decline was 53 percent at discharge, 36 percent at six weeks, 24 percent at six months, and 42 percent at five years. We investigated predictors of cognitive decline at five years and found that cognitive function at discharge was a significant predictor of long-term function (P<0.001). CONCLUSIONS: These results confirm the relatively high prevalence and persistence of cognitive decline after CABG and suggest a pattern of early improvement followed by a later decline that is predicted by the presence of early postoperative cognitive decline. Interventions to prevent or reduce short- and long-term cognitive decline after cardiac surgery are warranted.

Cardiopulmonary Bypass↗

Ageing with spinal cord injury: cross-sectional and longitudinal effects.

STUDY DESIGN: Longitudinal and cross-sectional. OBJECTIVE: To determine whether, for studies of ageing with a spinal cord injury, the cross-sectional differences in outcomes across both age and years post injury (YPI) differ from the longitudinal change. SETTING: Two SCI centres in England: the National Spinal Injuries Centre in Aylesbury, and the Regional Spinal Injuries Centre in Southport. METHODS: A total of 315 people who sustained spinal cord injuries prior to 1971 underwent comprehensive health and psychosocial status interviews at one or more of the study assessments (1990, 1993, 1996, and 1999). A range of continuous and dichotomous outcomes was analyzed to detect both cross-sectional differences by age and average individual changes over multiple measurements. RESULTS: Frequently, outcomes changed longitudinally without showing any cross-sectional differences. Cross-sectional age was more commonly associated with the worsening of a condition while cross-sectional YPI was commonly associated with improvement. After controlling for cross-sectional effects, psychological measures generally showed minor deterioration, measures of community integration both improved and deteriorated, upper extremity pain increased, lower enxtremity pain decreased, and participants tended to quit smoking. CONCLUSION: Using longitudinal findings that control for cross-sectional differences produces a more complete description of ageing with a spinal cord injury.

Activities of Daily Living↗

Review article: managing the dyspeptic patient--an interactive discussion.

Dyspepsia, a common disorder, can present some difficult clinical dilemmas. Physicians should explore some of the more challenging cases of dyspepsia in a setting that fosters interactive dialogue among colleagues, as was the case at the interactive discussion reported below. A panel of experts presented and discussed three case histories. The audience was able to choose from among several options for diagnosis or treatment and recorded their votes by means of an electronic handset. The first case concerned the relationship between continued non-steroidal anti-inflammatory drug (NSAID) use and recurrent upper gastrointestinal (GI) symptoms without ulcer or Helicobacter pylori infection. The second was a woman with complex upper GI symptoms including heartburn. The last featured a young man with dyspepsia and no alarm symptoms. The first case showed that a standard dose of proton pump inhibitor (PPI) is the best treatment for patients with gastritis who continue to use NSAIDs. The second case revealed that 24-h pH monitoring can be used to establish a relationship between symptoms and reflux episodes. The third case demonstrated that it can be difficult to make a definitive diagnosis based on clinical symptoms, and that patients with endoscopy-negative reflux disease usually respond well to PPI therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials.

BACKGROUND: Variation in the characteristics of irritable bowel syndrome patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results. AIM: To describe and compare the characteristics of three different groups of irritable bowel syndrome patients recruited into a 'mock clinical trial.' METHODS: We enrolled 245 irritable bowel syndrome patients from three sources: (i) 121 from British primary practitioners; (ii) 72 from California newspaper advertisements; and (iii) 52 from a California gastroenterologist's practice. We obtained demographic, clinical, and Hospital Anxiety and Depression (HAD) Scale data. RESULTS: Most patients were young to middle-aged women; the majority reported symptoms for > 5 years in all three groups. Subject characteristics varied among the groups. Typically, primary care patients were anxious, smokers and daily alcohol drinkers who had sought care recently for irritable bowel syndrome and tried antispasmodic drugs. Their symptoms were intermediate in severity between those of the other two groups. Advertisement subjects were the oldest, most highly educated, most often depressed, and were least likely to have sought care recently for symptoms, which were almost uniformly only moderate in severity. Gastroenterologist patients tended to be anxious and had nearly all sought care recently for symptoms, which were the most severe and most likely to include all three pain-related Rome I criteria. CONCLUSION: Recruitment methodology affects important characteristics of an irritable bowel syndrome study group.

Adolescent↗

Differential survival after coronary revascularization procedures among patients with renal insufficiency.

BACKGROUND: Acute myocardial infarction, cardiac arrest, and other cardiac events are the major cause of mortality among patients with renal insufficiency. Previous studies of interventions for coronary artery disease among patients with renal insufficiency have not controlled for potentially confounding factors such as coronary artery disease severity and left ventricular function. This study investigates the comparative survival for patients with renal insufficiency and coronary artery disease following coronary artery bypass graft (CABG) surgery as compared with percutaneous coronary artery intervention (PCI), while controlling for confounding factors. METHODS: This retrospective cohort study of patients undergoing CABG surgery or PCI discharged between 1993 and 1995 uses the New York Department of Health databases and Cox proportional hazards analyses to estimate the mortality risk associated with CABG as compared with PCI for patients with renal insufficiency. Renal function was categorized as creatinine <2.5 mg/dL (N = 58,329), creatinine > or =2.5 mg/dL (N = 840), and end-stage renal disease (ESRD) requiring dialysis (N = 407). RESULTS: Patients with either ESRD or serum creatinine > or =2.5 mg/dL had more severe coronary artery disease and a greater frequency of comorbid conditions as compared with patients with creatinine <2.5 mg/dL. Creatinine > or =2.5 mg/dL and ESRD were both associated with an increased mortality risk among all distributions of coronary artery disease anatomy. Among patients with ESRD, the risk ratio (RR) of mortality for patients undergoing CABG compared with PCI was 0.39 (95% CI, 0.22 to 0.67, P = 0.0006). Among patients with creatinine > or =2.5 mg/dL, CABG surgery did not convey a survival benefit over PCI (RR, 0.86, 95% CI, 0.56 to 1.33, P = 0.50). CONCLUSIONS: This study demonstrates a survival benefit among patients with ESRD undergoing CABG surgery as compared with PCI, while controlling for severity of coronary artery disease, left ventricular dysfunction, and other comorbid conditions. These results suggest that management decisions among patients with coronary artery disease should be made in the context of not only location and severity of coronary artery lesions, but also on the presence and severity of renal dysfunction.

Aged↗

Unilateral mandibular condylectomy in lambs.

The purpose of this experimental study was to investigate the degree of regeneration of the mandibular condyle after unilateral condylectomy in 10-week-old lambs. The lambs were killed three months after the operation, and the joints examined radiologically and histologically. Scoring systems were used to assess the radiological changes and histological regeneration of the condyle. All joints showed regeneration of the condylar head postoperatively. The maximum degree of regeneration occurred on the medial side rather than the central or lateral areas. There was a significant correlation among the medial, central, and lateral planes (P<0.05). The reformed articular cartilage was irregular and thin (P<0.01), and the disc was thick in the central plane (P<0.01) compared with the control joints. The temporal bone was normal. This study shows that unilateral condylectomy in the growing period results in some condylar regeneration particularly on the medial side and reformation of some irregular and thin articular cartilage.

Animals↗

Apolipoprotein E polymorphisms and age at first coronary artery bypass graft.

UNLABELLED: Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol. The impact of apoE4 genotypes on the severity of atherosclerosis has been debated; however, recent studies have identified a correlation between apoE4 genotype and atherosclerosis. We assessed the impact of apoE4 genotype on age at first coronary artery bypass graft (CABG), hypothesizing that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary revascularization. We assessed individual apoE genotypes and age in 560 patients undergoing primary CABG, by using analysis of variance (ANOVA) and controlling for gender. Because of the small number of patients in individual genotype groups, we compared patients with one or more copies of the apoE4 allele with those having no copies of the allele, again controlling for gender. A comparison of patients with one or more copies of the apoE4 allele with patients without the allele showed an earlier age at first CABG for those with the allele (P: = 0.032). Gene-dose analysis was also significant (P: = 0.012); patients with two copies of the allele presented at 54.2 +/- 6.9 yr. We report that the apoE4 allele is linked to age at first CABG. Identifying at-risk individuals may help prevent atherosclerosis. Further study is needed to define the mechanism of this association, and to define which coronary intervention is appropriate, based on long-term outcome. IMPLICATIONS: A correlation exists between apolipoprotein E (apoE) genotypes and the severity of atherosclerosis. We hypothesized that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary artery bypass graft (CABG). Individuals with the apoE4 allele presented earlier for CABG, and the apoE4 allele is linked to age at first CABG.

Age Factors↗