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Biomedical subjects

R L Holder

Publications and source records attributed to R L Holder.

At least 37 records · Page 2Linked to original sources
PubMed1999

Helicobacter pylori-associated antibodies in patients with duodenal ulcer, gastric and oesophageal adenocarcinoma.

OBJECTIVE: To associate Helicobacter pylori-associated antibodies with clinical disease in groups of patients with duodenal ulcer, gastric adenocarcinoma, oesophageal adenocarcinoma and normal mucosa. DESIGN: Prospective observational sero-epidemiology study. Identification of consecutive in-patients with duodenal ulcer, gastric adenocarcinoma, oesophageal adenocarcinoma and normal mucosa. Analyses of sera for antibodies to whole H. pylori, Cag A and Vac A antigens using ELISA and Western blot. Statistical analyses. SETTING: Walsgrave Hospital, Coventry, a district general hospital that serves a population of 350,000. PARTICIPANTS: Consecutive in-patients with an endoscopic diagnosis of duodenal ulcer (n = 31), gastric adenocarcinoma (n = 31), oesophageal adenocarcinoma (n = 40) and normal mucosa (n = 46). MAIN OUTCOME MEASURES: A profile of antibodies was constructed for each patient group and between-group comparisons were made. A logistic regression model determined the H. pylori-associated antibody that could best predict a patient's diagnosis. A discriminatory power for each antibody was calculated. RESULTS: Whole H. pylori, Cag A and Vac A antibodies are found more commonly in duodenal ulcer patients when compared to oesophageal adenocarcinoma (P < 0.003) and normal mucosa patients (P < 0.015). Similarly, gastric adenocarcinoma patients have antibodies to whole H. pylori, Cag A and Vac A more frequently than oesophageal adenocarcinoma (P< 0.002) and normal mucosa patients (P < 0.006). Vac A antibodies discriminate between duodenal ulcer/gastric adenocarcinoma and oesophageal adenocarcinoma/normal mucosa patients (odds ratio 5.56, log likelihood -90.06, P < 0.001) more effectively than Cag A antibodies (odds ratio 4.17, log likelihood -91.88, P < 0.001). CONCLUSIONS: Similar profiles of H. pylori-associated antibodies are seen in patients with duodenal ulcer and gastric adenocarcinoma, confirming that virulent H. pylori are involved in the pathogenesis of both diseases. Antibodies to Vac A could be used to identify patients at increased risk of developing H. pylori-associated disease.

Adenocarcinoma↗
PubMed1999

The development of Graves' disease and the CTLA-4 gene on chromosome 2q33.

Case-control studies suggest that the CTLA-4 gene may be a susceptibility locus for Graves' disease. The previously reported A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene was, therefore, investigated in a case-control (n = 743) and family-based (n = 179) dataset of white Caucasian subjects with Graves' disease. The relationship between CTLA-4 genotype and severity of thyroid dysfunction at diagnosis was also investigated. An increase in frequency of the G (alanine) allele was seen in Graves' patients compared with control subjects (42% vs. 31.5%, respectively; corrected P<0.0002; odds ratio = 1.58), and a significant difference in the distribution of GG, GA, and AA genotypes was observed between the groups (chi2 = 21.7; corrected P<0.00003). Increased transmission of the G allele was seen from heterozygous parents to affected offspring compared to unaffected offspring (chi2 = 5.7; P = 0.025). Circulating free T4 concentrations at diagnosis were significantly associated with CTLA-4 genotype (F = 3.26; P = 0.04). These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease.

Abatacept↗
PubMed1999

Home advantage in sport: an overview of studies on the advantage of playing at home.

This review identifies the most likely causes of home advantage. The results of previous studies have identified 4 factors thought to be responsible for the home advantage. These can be categorised under the general headings of crowd, learning, travel and rule factors. From the accumulated evidence, rule factors were found to play only a minor role (in a limited number of sports) in contributing to home advantage. Studies investigating the effect of learning factors found that little benefit was to be gained from being familiar with the local conditions when playing at home. There was evidence to suggest that travel factors were responsible for part of the home advantage, provided the journey involved crossing a number of time zones. However, since high levels of home advantage are observed within countries where travel distances are not great. travel factors were not thought to be a major cause of home advantage. The evidence from studies investigating crowd factors appeared to provide the most dominant causes of home advantage. A number of studies provide strong evidence that home advantage increases with crowd size, until the crowd reaches a certain size or consistency (a more balanced number of home and away supporters), after which a peak in home advantage is observed. Two possible mechanisms were proposed to explain these observations: either (i) the crowd is able to raise the performance of the home competitors relative to the away competitors; or (ii) the crowd is able to influence the officials to subconsciously favour the home team. The literature supports the latter to be the most important and dominant explanation. Clearly, it only takes 2 or 3 crucial decisions to go against the away team or in favour of the home team to give the side playing at home the 'edge'.

Humans↗
PubMed1998

Association of atherogenic low-density lipoprotein subfractions with carotid atherosclerosis.

Patients with carotid atherosclerosis are at increased risk of both stroke and ischaemic heart disease. Low-density lipoprotein (LDL) is a heterogeneous group of particles, with small, dense particles being more atherogenic. We studied 79 patients (51 men, mean +/- SD age 62.4 +/- 11.7 years) referred for Doppler ultrasound assessment of the carotid arteries. Evidence of carotid atherosclerosis, defined as the presence of atherosclerotic plaque, stenosis or occlusion in one or more of the six carotid artery segments examined, was found in 44 patients (56%). LDL subfractions were analysed by disc polyacrylamide gel electrophoresis with prior ultracentrifugation of serum to remove chylomicrons. This method produces a LDL score; the higher the score, the greater the proportion of the more atherogenic LDL subfractions. Mean LDL score was significantly higher in diseased patients (mean +/- SD, 1.56 +/- 0.61) than the normal group (1.26 +/- 0.65) (t = 2.12, p = 0.037). There was no significant association between LDL score and severity of carotid artery stenosis. Age (adjusted odds ratio 1.09, 95% CI 1.03-1.15) and smoking history (2.09, 95% CI 1.10-3.98) predicted carotid atherosclerosis in logistic regression analysis, with LDL score achieving borderline significance (2.20, 95% CI 0.91-5.29). Small, dense LDL subfractions are associated with carotid atherosclerosis and may be a modifiable risk factor for stroke as well as ischaemic heart disease.

Age Factors↗
PubMed1998

Modeling developmental changes in strength and aerobic power in children.

The present study examined two contrasting multilevel model structures to describe the developmental (longitudinal) changes in strength and aerobic power in children: 1) an additive polynomial structure and 2) a multiplicative structure with allometric body size components. On the basis of the maximum log-likelihood criterion, the multiplicative "allometric" model was shown to be superior to the additive polynomial model when fitted to the data from two published longitudinal studies and to provide more plausible solutions within and beyond the range of observations. The multilevel regression analysis of study 1 confirmed that aerobic power develops approximately in proportion to body mass, m1/3. The analyses from study 2 identified a significant increase in quadriceps and biceps strength, in proportion to body size, plus an additional contribution from age, centered at about peak height velocity (PHV). The positive "age" term for boys suggested that at PHV the boys were becoming stronger in the quadriceps and biceps in relation to their body size. In contrast, the girls' age term was either negligible (quadriceps) or negative (biceps), indicating that at PHV the girls' strength was developing in proportion to or, in the case of the biceps, was becoming weaker in relation to their body size.

Adolescent↗
PubMed1997

Identifying home advantage in international tennis and golf tournaments.

A regression analysis of competitors' tournament results in relation to their world rankings was proposed to identify the effect of home advantage in international 'grand-slam' tennis and 'major' golf tournaments. The results provided little evidence of home advantage in either the grand-slam tennis or the golf tournaments held in 1993. The only possible evidence of home advantage was found in the Wimbledon tennis and the US Open golf championships. Even these findings can be explained, at least partially, by (1) the availability of information concerning the low world rankings of the British tennis players competing at Wimbledon, and (2) selective entry, allowing only the world's top-ranked foreign golfers into the US open golf tournament. In both cases, the lower ranking home competitors have a greater opportunity to perform above their anticipated world rankings. Therefore, provided entry into tennis and golf tournaments is truly 'open' to both the host nation's representatives and foreign competitors alike, home advantage does not appear to be a major factor influencing the competitors' performance in such competitions. These findings may be explained by the relatively objective nature of the scoring systems used in tennis and golf, unlike the subjective influence of refereeing decisions on the results of team-games such as soccer.

Analysis of Variance↗
PubMed1996

Investigation of low density lipoprotein subfractions as a coronary risk factor in normotriglyceridaemic men.

There is an increasing interest in low density lipoprotein (LDL) subfractions since some of them are associated with a higher risk for coronary artery disease (CAD). Small LDL particles are particularly atherogenic and more of those are produced in hypertriglyceridaemia. However, high triglyceride concentrations are not the only explanation for the predominance of small LDL particles and other influences, including genetic factors, are also responsible for LDL particle size. We investigated LDL subfraction profiles in two groups: 46 men with and 21 men without CAD proven angiographically. For the separation of LDL subfractions, we used continuous disc polyacrylamide gel electrophoresis (PAGE) that is rapid and easier to perform than the other methods usually used which, although more precise in terms of measuring particle diameter, are much more demanding of time and equipment. The described method is suitable for routine use in assessing large numbers of patients. All studied men had triglyceride concentrations below 2.3 mmol/l. LDL scores were calculated on the basis of all LDL subfractions present in a particular profile; the higher the score, the greater the proportion of small LDL particles. LDL cholesterol (P < 0.05) and LDL score (P < 0.001) were the only significant discriminators between two groups. LDL score was significantly correlated with CAD, even after adjusting for triglyceride and HDL cholesterol concentrations and it was the best discriminant factor for the presence of CAD.

Coronary Disease↗
PubMed1996

A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration.

OBJECTIVE: The aim was to establish the potential efficacy, tolerability and side-effect profile of electromagnetic therapy as an adjunct to conventional dressings in the treatment of venous leg ulcers. METHOD: A prospective, randomized, double blind controlled clinical trial was carried out in a dedicated leg ulcer clinic based in one urban general practice. Nineteen patients with leg ulcers of confirmed venous aetiology were assessed. The main outcome measures were rate and scale of venous leg ulcer healing, changes in patient-reported pain levels, quality of life, degree of mobility, side effect profile and acceptability to patients and staff. RESULTS: Sixty-eight per cent of patients attending this dedicated clinic achieved improvements in the size of their ulcer (4, 21%, healed fully) and in reduced pain levels (P < 0.05) during the trial, despite the chronicity of ulcer histories. Patients treated with electromagnetic therapy at 800 Hz were found at day 50 to have significantly greater healing (P < 0.05) and pain control (P < 0.05) than placebo therapy or treatment with 600 Hz. All patients reported improved mobility at the end of the study. The electromagnetic therapy was well tolerated by patients, with no differences between groups in reporting adverse events, and proved acceptable to staff. CONCLUSIONS: Despite the small numbers in this pilot study, electromagnetic therapy provided significant gains in the healing of venous leg ulcers and reduction in pain.

Adult↗
PubMed1996

Reliability and feasibility of a near patient test for C-reactive protein in primary care.

BACKGROUND: The applications of new diagnostic technologies such as near patient tests are relevant to the further development and potential of primary care. Through their use, doctors in the community may increase the accuracy of their diagnoses and improve their ability to monitor disease. A reliable indicator of disease activity in various clinical conditions is C-reactive protein (CRP) and a near patient test for this is now available, although there is little information on its use outside hospitals. AIM: A study was set up to evaluate the feasibility of using a novel near patient test for CRP in primary care to validate the results against the laboratory "gold standard' for CRP (Beckman Array) and to compare results with the usual inflammation test used in general practice. METHOD: Prospective recording of CRP as a near patient test on an "intention to investigate' basis, with validation of results against the Beckman Array system for CRP and hospital laboratory erythrocyte sedimentation rate results, in six general medical practices in Birmingham. Main outcome measures were change in local laboratory usage, characteristics of patients chosen for testing, use of quality control, and comparison of readings with results from the same sample sent to an independent laboratory. RESULTS: Tests of CRP levels were rarely requested before the study was undertaken. During the 3-month study period, 181 near patient tests were carried out, 146 (81%) to establish a diagnosis and the remainder for disease monitoring. Out of the tests, 67% were performed by general practitioners, mostly during the consultation itself. Using a cut-off level of 10 mg I-1, the near patient test and the Beckman Array gave results which agreed in 84% of cases. The sensitivity and specificity of the near patient test results were 97 and 79%, respectively. The predictive value of a positive result was 59% and that of a negative result was 99%. Cohen's Kappa was 62% and the overall mean bias for results in the range of the test was 6.11 mg I-1 (SE = 3.07 mg I-1). Each test took 6 min on average to perform, including all preparations, blood letting, performing the test and averaging the time for quality control estimations. The cost per test averaged pounds 1.72, rising to pounds 4.17 including labour, capital costs, quality controls and consumables (general practitioner performing the assay at average frequency found in this study). CONCLUSIONS: Measurement of CRP is rarely used in primary care and awareness of its value could be raised. This near patient test proved feasible for use by general practitioners and practice nurses. Its reliability compared with a laboratory result was satisfactory overall, and excellent with adequate operator technique.

Biomarkers↗
PubMed1995

Body mass index: a measure of fatness or leanness?

The relationship between body fat and stature-adjusted weight indices was explored. Assuming the term height2 is a valid indicator of a subject's lean body mass, height2/weight was shown to be an accurate measure of percentage lean body mass and, as such, a better predictor of percentage body fat than the traditional body mass index (BMI; weight/height2). The name, lean body mass index (LBMI), is proposed for the index height2/weight. These assumptions were confirmed empirically using the results from the Allied Dunbar National Fitness Survey (ADNFS). Using simple allometric modelling, the term heightp explained 74% of the variance in lean body mass compared with less than 40% in body weight. For the majority of ADNFS subjects the fitted exponent from both analyses was approximately p = 2, the only exception being the female subjects aged 55 years and over, where the exponent was found to be significantly less than 2. Using estimates of percentage body fat as the dependent variable, regression analysis was able to confirm that LBMI was empirically, as well as theoretically, superior to the traditional BMI. Finally, when the distributional properties of the two indices were compared, BMI was positively skewed and hence deviated considerably from a normal distribution. In contrast, LBMI was found to be both symmetric and normally distributed. When height and weight are recorded in centimetres and kilograms respectively, the suggested working normal range for LBMI is 300-500 with the median at 400.

Actuarial Analysis↗
PubMed1995

Scaling, normalizing, and per ratio standards: an allometric modeling approach.

The practice of scaling or normalizing physiological variables (Y) by dividing the variable by an appropriate body size variable (X) to produce what is known as a "per ratio standard" (Y/ X), has come under strong criticism from various authors. These authors propose an alternative regression standard based on the linear regression of (Y) on (X) as the predictor variable. However, if linear regression is to be used to adjust such physiological measurements (Y), the residual errors should have a constant variance and, in order to carry out parametric tests of significance, be normally distributed. Unfortunately, since neither of these assumptions appear to be satisfied for many physiological variables, e.g., maximum oxygen uptake, peak and mean power, an alternative approach is proposed of using allometric modeling where the concept of a ratio is an integral part of the model form. These allometric models naturally help to overcome the heteroscedasticity and skewness observed with per ratio variables. Furthermore, if per ratio standards are to be incorporated in regression models to predict other dependent variables, the allometric or log-linear model form is shown to be more appropriate than linear models. By using multiple regression, simply by taking logarithms of the dependent variable and entering the logarithmic transformed per ratio variables as separate independent variables, the resulting estimated log-linear multiple-regression model will automatically provide the most appropriate per ratio standard to reflect the dependent variable, based on the proposed allometric model.

Exercise↗
PubMed1994

Generalised bone loss in patients with early rheumatoid arthritis.

Generalised osteoporosis is a feature of established rheumatoid arthritis but whether this is a consequence of treatment, immobility, or disease activity has been unclear. We estimated bone mineral density by dual energy x-ray absorptiometry on 148 patients with early rheumatoid arthritis before treatment with corticosteroids or disease-modifying drugs and 730 normal controls. Scans were done at 12-month intervals in patients and at 0 and 12 months on 50 of the controls matched for menopausal status. At presentation, bone mineral density of patients did not differ from controls. However, patients with disease for less than 6 months had significantly higher spinal bone mineral density than those of longer duration. Over the next 12 months, bone mineral density loss was greater in patients with rheumatoid arthritis compared with controls; significantly so for early disease (eg, -2.4 [0.8] vs -0.6 [0.4] g/cm2, p < 0.05 in the spine and -4.3 [0.8] vs -0.4 [0.5] g/cm2, p < 0.001 in the trochanter). For the lumbar spine, only disease activity was significantly associated with this bone mineral density loss. For patients with active disease over 2 years, mean bone mineral density loss at each site was between 5.5 and 10% (p < 0.01 compared to patients with inactive disease). Suppression of disease activity stabilised this bone loss. In patients with rheumatoid arthritis significant amounts of generalised skeletal bone were lost early in the disease and the loss was associated with disease activity. These findings have implications for the management of patients with rheumatoid arthritis and possibly other inflammatory diseases.

Absorptiometry, Photon↗
PubMed1994

Post-operative blood loss following cardio-pulmonary bypass in children.

Significant post-operative bleeding may occur following cardio-pulmonary bypass, sometimes necessitating early re-exploration. Two questions were asked by this study. Firstly, in children undergoing cardio-pulmonary bypass, can pre-operative, operative and immediately post-operative variables be used to predict post-operative blood loss? Secondly, in the same patient group, can the same variables be used to predict the surgical intervention of re-exploration for excessive bleeding within 12 h of surgery? In a prospective study of patients operated on in a 9-month period, bleeding fell rapidly in the first 3 h after surgery and early re-exploration for bleeding was necessary in 8 of the 206 patients. The only significant predictor of post-operative blood loss was minimum oesophageal temperature, low values being associated with greater blood loss (correlation r = -0.19 (P < 0.05)). With regard to re-exploration for bleeding, a long bypass time (P < 0.05) and abnormal pre-operative coagulation indices (P < 0.01) were significant and independent predictors. The data were also used to create a practical nomogram relating re-exploration for bleeding to hourly post-operative blood loss.

Body Temperature↗
PubMed1994

Excretion of pyridinium crosslinks correlates with disease activity and appendicular bone loss in early rheumatoid arthritis.

OBJECTIVE: To establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (RA), are useful markers of bone loss in this disease. METHODS: Eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. Bone mineral density (BMD), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. RESULTS: The rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p < 0.001). Pyridinoline excretion was associated with increased disease activity (ESR/CRP) but not disability (HAQ score/Functional Grade), and correlated with BMD loss at the femoral neck (p < 0.01). CONCLUSION: The excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with RA.

Acute Disease↗
PubMed1992

Modelling bivariate relationships when repeated measurements are recorded on more than one subject.

This paper examines the problems of modelling bivariate relationships when repeated observations are recorded for each subject. The statistical methods required to test for a common group model were introduced using an example from exercise physiology, where the oxygen cost of running at four different speeds was recorded for a group of 30 recreationally active males. When data for each subject were studied individually, both the plots and correlations suggested the relationship to be linear. Hence, the homogeneity of the subjects' regression lines was compared using the appropriate ANOVA test. The analysis revealed a significant difference in the slopes and intercepts of the lines, thus precluding the use of a single linear model to represent the group. If the subjects were divided into two groups according to the median maximum oxygen consumption (VO2max), a multivariate analysis of variance of the slope and intercept parameters helped to explain some of this heterogeneity (P less than 0.05). However, for physiological rather than statistical reasons, it was necessary to re-analyse the data without the fourth running speed. The revised analysis suggested that the subjects' lines would be better modelled with a common slope but separate intercepts. As before, by dividing the subjects into two groups according to the median VO2max score, a simple t-test indicated that differences in the subjects' intercept parameters were not significant (P = 0.08). Notwithstanding the relatively homogeneous nature of the 30 subjects in terms of VO2max, the statistical methods showed that differences in running economy are, to some extent, dependent on VO2max.

Adolescent↗
PubMed1983

An evaluation of the Technicon H6000 haematology system.

The Technicon H6000 haematology system combines haemoglobinometry with cell counting including differential counts of leucocytes. Evaluation confirmed it to be safe, precise and free from carry-over of practical significance. Comparability with standard reference methods showed a difference with mean cell volume (MCV) and packed cell volume (PCV) but the haemoglobin, red cell count and mean haemoglobin concentration (MCH) were comparable. Total white cell counts and differential counts were comparable apart from eosinophils and basophils. Platelet counts were higher at both ends of the range. Throughput was confirmed at 90 samples per hour. The system was shown to be cost-effective when taking into consideration staff costs, materials and maintenance but expensive with regard to materials alone.

Autoanalysis↗
PubMed1980

Variability in the adsorption properties of microtitre plates used as solid supports in enzyme immunoassay.

We evaluated the variability in the amount of protein adsorbed onto the surface of individual wells of an assortment of microtitre plates by use of procedures involving enzyme-protein conjugates. Coefficients of variation in adsorbed protein ranged from 5.2 to 29.5%. Microtitre plates show a distinct "edge effect"; wells at the edges of a plate adsorb more protein than those in the interior, which markedly affects results from immunoassays involving such plates. In a sandwich enzyme immunoassay the results for an individual sample varied by +/- 18%; in a competitive assay, values read from different calibration curves in the same plate varied by +/- 11%. Scanning electron microscopy and birefringence studies demonstrated no marked physical differences between individual wells on a plate. The variability in the amount of protein adsorbed onto the surface of individual wells on the same microtitre plate seriously affects the reliability and interpretation of results of immunoassays in which such plates are used as solid supports.

Alkaline Phosphatase↗