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Biomedical subjects

Callum G Fraser

Publications and source records attributed to Callum G Fraser.

10 recordsLinked to original sources
PubMed2006

The influence of mode of delivery and ACE genotype on serum angiotensin converting enzyme (ACE) activity in the mother and infant at term.

OBJECTIVE: Angiotensin converting enzyme (ACE) and its genotype have been shown to play a role in the pathophysiology of pregnancy complications such as pre-eclampsia and intrauterine growth restriction and possibly in adult onset chronic diseases. The physiological changes of ACE and the influence of its genotype during the intrapartum period are not well known. Hence the aim of this study was to assess serum ACE activity and its genotype in mothers and infants at term in relation to labour and mode of delivery. STUDY DESIGN: A cross sectional study of 99 women who laboured and 27 women who delivered by elective caesarean section after 36 completed weeks gestation with uncomplicated pregnancies. Venous cord bloods were obtained immediately after delivery of the placenta for serum ACE activity, ACE genotype and acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. Univariate analyses were performed using parametric tests for normally distributed data and nonparametric tests for the data that were not normally distributed. A multiple regression model was developed to adjust for potential confounding factors. RESULTS: The umbilical venous ACE activity was similar for infants delivered following labour compared to those delivered by elective caesarean section, 47.2 U/L (35-64) versus 40.1 U/L (31-60) (adjusted p=0.21). Maternal ACE activities were 28.9 U/L (22-35) and 32.1 U/L (22-40) respectively (adjusted p=0.17). The ACE activity in infants was higher than that of mothers 46 U/L versus 22 U/L, respectively (p= or <0.001). Neither the mode of delivery nor the presence of suspected fetal compromise influenced maternal or infant ACE activity. There was no influence of the infants' genotype on ACE activity in relation to mode of delivery. The DD genotype was associated with higher ACE activity in mothers (p=0.001) but not in infants (p=0.56). CONCLUSIONS: This study shows that intrapartum events do not affect ACE activity. These results will enhance our ability to investigate the role of ACE and its genotype in abnormal fetal growth and in subsequent adult onset chronic disease.

Acidosis↗
PubMed2006

Immunochemical testing of individuals positive for guaiac faecal occult blood test in a screening programme for colorectal cancer: an observational study.

BACKGROUND: Screening for colorectal cancer by use of guaiac-based faecal occult blood tests (FOBT) reduces disease-specific mortality. However, due to imperfect specificity, about half of individuals positive for guaiac FOBT are negative for neoplasia on colonoscopy. We aimed to assess whether the testing of individuals positive for guaiac FOBT in a screening programme for colorectal cancer by use of a sensitive immunochemical FOBT could select more appropriately those who should receive colonoscopy. METHODS: We invited individuals who were guaiac FOBT positive in the second screening round of a pilot study in Scotland, UK, to give two samples, each from separate stools, for immunochemical FOBT while awaiting colonoscopy. Results were classed as: both samples negative (N/N), one sample negative and one positive (N/P), and both samples positive (P/P); data were assessed for sampling bias. We compared immunochemical findings with those from colonoscopy using odds ratios of positive samples (P/P) versus negative (N/N and N/P). Sensitivity, specificity, and positive and negative likelihood ratios for cancer, and for cancer and high-risk adenomatous polyps were also calculated. FINDINGS: 1486 participants were invited and 801 (54%) sets of duplicate samples were returned. We found no evidence of sampling bias with regard to sex, age, or degree of positivity on guaiac FOBT. Of 800 sets returned with consent and analysed, 173 (22%) were N/N, 129 (16%) were N/P, and 498 (62%) were P/P. Chi2 test showed a highly significant positive correlation between degree of positivity on guaiac FOBT and on immunochemical FOBT (p<0.003). 795 individuals had data for colonoscopy: one (<1%) of 171 N/N participants and one (<1%) of 127 N/P participants had colorectal cancer, compared with 38 (8%) of 497 P/P participants; adenomatous polyps were found in 28 (16%) N/N individuals, 24 (19%) N/P individuals, and 193 (39%) P/P individuals. Normal colonoscopy was less common in the P/P group (85 [17%]) than in the N/N (67 [39%]) and N/P (49 [39%]) groups. The odds ratio for P/P being associated with cancer was 7.57 (95% CI 1.84-31.4) and with high-risk adenomatous polyps was 3.11 (1.86-5.18). Sensitivity of a P/P result for cancer was 95.0% (81.8-99.1), and for cancer and high-risk adenomatous polyps was 90.1% (84.4-94.0); specificity was 39.5% (36.0-43.1) and 47.8% (43.9-51.8), respectively. INTERPRETATION: Immunochemical FOBT for individuals with positive guaiac FOBT could decrease substantially the number of false positives in a screening programme for colorectal cancer.

Aged↗
PubMed2004

Test result variation and the quality of evidence-based clinical guidelines.

BACKGROUND: There is a plethora of supposedly evidence-based published clinical guidelines, most often prepared under the auspices of professional bodies. Many guidelines contain numerical laboratory test results as criteria for clinical action, very often simply quoted as single numbers. Every test result is subject to a number of sources of variation. Analytical imprecision and within-subject biological variation are particularly important. The influence of both of these on the dispersion of a single test result and on the number of samples required to make clinical decisions can be easily calculated using simple formulae. The effect of performing replicate analyses of one sample and of taking multiple samples can also be easily investigated. Authors of scientific statements, clinical guidelines, and practice recommendations should undertake such calculations before promulgating their efforts in the public domain. Guidelines on cholesterol and high sensitivity C-reactive protein have been examined using these approaches and these investigations allow the following conclusions. CONCLUSIONS: Analytical imprecision should be made low. If analytical imprecision is generally greater than biological variation, then reduction in analytical imprecision is valuable. If biological variation is greater than imprecision, then collection of more than one sample from an individual prior to decision-making is useful.

C-Reactive Protein↗
PubMed2004

Inherent biological variation and reference values.

There is a need for revisiting theoretical concepts and practical applications of conventional population-based reference values to make for better clinical use of laboratory data. Knowledge of the underlying biological variation of quantities examined in medical laboratories is vital to understanding the proper generation and application of traditional population-based reference values. Appreciation of the biological changes that occur over the span of life is a necessary prerequisite to deciding whether stratification of reference values according to age is likely to be necessary. Knowledge of the detail of predictable biological cyclical rhythms is required for correct clinical interpretation of laboratory data and appropriate collection of specimens at times relevant to the clinical purpose. Quantitative data on inherent within- and between-subject biological components of variation have shown the marked individuality of most quantities of interest in laboratory medicine. This individuality casts light on why examinations are not generally very successfully applied in population screening or case-finding. Consideration of individuality demonstrates why stratification of reference values is often very advantageous. Individuality provides an indisputable argument for better use of individual specific reference values.

Humans↗
PubMed2002

Does renal dysfunction predict mortality after acute stroke? A 7-year follow-up study.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate renal function as a long-term predictor of mortality in patients hospitalized for acute stroke. METHODS: This was a cohort study done in a Scottish tertiary teaching hospital. Participants included 2042 (993 male) unselected consecutive stroke patients (mean age, 73 years) admitted to hospital within 48 hours of stroke between 1988 and 1994. Follow-up was up to 7 years. Main outcome measure was all-cause mortality. RESULTS: The total number of deaths at the end of follow-up was 1026. Most subjects (1512) had creatinine <124 micromol/L. The mean calculated creatinine clearance was 54.8 mL/min (SD, 23 mL/min). Renal function indexes were analyzed by quartiles with Cox proportional-hazards model. Stroke survivors had higher calculated creatinine clearance and lower serum creatinine, urea, and ratios of urea to creatinine. Calculated creatinine clearance > or =51.27 mL/min significantly predicted better long-term survival in these stroke patients even after adjustment for confounders (age, neurological score, ischemic heart disease, hypertension, smoking, and diuretic use). Similarly, creatinine > or =119 micromol/L "relative risk (RR), 1.59; 95% confidence interval (CI), 1.32 to 1.92", urea 6.8 to 8.9 mmol/L (RR, 1.34; 95% CI, 1.09 to 1.65) or > or =9 mmol/L (RR, 1.74; 95% CI, 1.42 to 2.13), and ratio of urea to creatinine > or =0.08573 mmol/micromol (RR, 1.24; 95% CI, 1.03 to 1.50) remained significant predictors of mortality after adjustment for confounders. CONCLUSIONS: After acute stroke, patients with reduced admission calculated creatinine clearance, raised serum creatinine and urea concentrations (even within conventional reference intervals), and raised ratio of urea to creatinine had a higher mortality risk. This finding may be used to stratify risk and target interventions, eg, the use of angiotensin-converting enzyme inhibitors.

Aged↗
PubMed2002

Combination of analytical quality specifications based on biological within- and between-subject variation.

At a conference on 'Strategies to Set Global Analytical Quality Specifications in Laboratory Medicine' in Stockholm 1999, a hierarchy of models to set analytical quality specifications was decided. The consensus agreement from the conference defined the highest level as 'evaluation of the effect of analytical performance on clinical outcomes in specific clinical settings' and the second level as 'data based on components of biological variation'. Here, the many proposals for analytical quality specifications based on biological variation are examined and the outcomes of the different models for maximum allowable combined analytical imprecision and bias are illustrated graphically. The following models were investigated. (1) The Cotlove et al. (1970) model defining analytical imprecision (%CVA) in relation to the within-subject biological variation (%CV(W-S)) as: %CVA < or = 0.5 x %CV(W-S) (where %CV is percentage coefficient of variation). (2) The Gowans et al. (1988) concept, which defines a functional relationship between analytical imprecision and bias for the maximum allowable combination of errors for the purpose of sharing common reference intervals. (3) The European Group for the Evaluation of Reagents and Analytical Systems in Laboratory Medicine (EGE Lab) Working Group concept, which combines the Cotlove model with the Gowans concept using the maximal acceptable bias. (4) The External Quality Assessment (EQA) Organizers Working Group concept, which is close to the EGE Lab Working Group concept, but follows the Gowans et al. concept of imprecision up to the limit defined by the model of Cotlove et al. (5) The 'three-level' concept classifying analytical quality into three levels: optimum, desirable and minimum. The figures created clearly demonstrated that the results obtained were determined by the basic assumptions made. When %CV(W-S) is small compared with the population-based coefficient of variation [%CV(P) = (%CV2(W-S) +%CV2(B-S))(1/2)], the EGE Lab and EQA Organizers Working Group concepts become similar. Examples of analytical quality specifications based on biological variations are listed and an application on external quality control is illustrated for plasma creatinine.

Bias↗
PubMed2002

Objective criteria for partitioning Gaussian-distributed reference values into subgroups.

BACKGROUND: The aim of this study was to develop new and useful criteria for partitioning reference values into subgroups applicable to gaussian distributions and to distributions that can be transformed to gaussian distributions. METHODS: The proposed criteria relate to percentages of the subgroups outside each of the reference limits of the combined distribution. Critical values suggested as partitioning criteria for these percentages were derived from analytical bias quality specifications for using common reference intervals throughout a geographic area. As alternative partitioning criteria to the actual percentages, these were transformed mathematically to critical distances between the reference limits of the subgroup distributions, to be applied to each pair of reference limits, the upper and the lower, at a time. The new criteria were tested using data on various plasma proteins collected from approximately 500 reference individuals, and the outcomes were compared with those given by the currently widely applied and recommended partitioning model of Harris and Boyd, the "Harris-Boyd model". RESULTS: We suggest 4.1% as the critical minimum percentage outside that would justify partitioning into subgroups, and 3.2% as the critical maximum percentage outside that would justify combining them. Percentages between these two values should be classified as marginal, implying that nonstatistical considerations are required to make the final decision on partitioning. The correlation between the critical percentages and the critical distances was mathematically precise in the new model, whereas this correlation is rather approximate in the Harris-Boyd model because focus on the difference between means in this model makes high precision hard to achieve. The application examples suggested that the new model is more radical than the Harris-Boyd model. CONCLUSIONS: New percentage and distance criteria, to be used for partitioning gaussian-distributed data, have been developed. The distance criteria, applied separately to both reference limit pairs of the subgroup distributions, seemed more reliable and correlated more accurately with the critical percentages than the distance criteria of the Harris-Boyd model. As opposed to the Harris-Boyd model, the new model is easily adjustable to new critical values of the percentages, should they need to be changed in the future.

Clinical Laboratory Techniques↗