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Biomedical subjects

C P Price

Publications and source records attributed to C P Price.

At least 37 records · Page 2Linked to original sources
PubMed2000

How silent is perioperative myocardial ischemia? A hemodynamic, electrocardiographic, and biochemical study in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To analyze the relationship among Holter electrocardiogram (ECG) recordings, hemodynamic measurements indicative of global myocardial oxygen balance, and serum cardiac troponin I concentrations (cTnI) in the early postoperative period after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective observational study. SETTING: University teaching hospital. PARTICIPANTS: Thirty patients undergoing CABG surgery. INTERVENTIONS: ECG measurements consisted of Holter and standard ECG recordings. Hemodynamic measurements included heart rate, systolic and diastolic blood pressure (SBP, DBP), pulmonary capillary wedge pressure, and cardiac index (CI). Derived indices included tension time index (TTI), rate-pressure product, pressure work index (PWI), and endocardial viability ratio (EVR). Serial measurements of cTnI concentrations were measured postoperatively; the area under the cTnI concentration time curve was calculated for each patient (AUC cTnI). MEASUREMENTS AND MAIN RESULTS: Episodes of myocardial ischemia were associated with small but significant rises in SBP (p = 0.01), DBP (p = 0.001), and TTI (p = 0.005) compared with periods without ischemia in the same patients. Serum cTnI concentrations 24 hours after cardiopulmonary bypass (p = 0.03) and AUCcTnI (p = 0.01) values were greater in patients who developed ECG myocardial ischemia compared with patients who did not. CONCLUSIONS: The small changes in hemodynamics seen, although statistically significant, are unlikely to be the primary cause of the ischemia. They more likely reflect an independent process that causes or occurs as a result of ischemic episodes. Ischemic episodes detected by the Holter monitor are associated with significant release of cardiac troponin from the myocardium.

Adult↗
PubMed2000

Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children.

AIM: To establish a reference range in the paediatric population for the new glomerular filtration rate (GFR) marker, cystatin C, and to compare it with that of creatinine. METHODS: Cystatin C and creatinine were measured by particle enhanced nephelometric immunoassay (PENIA) and fixed interval Jaff¿e methods, respectively, in 291 children aged 1 day to 17 years, including 30 premature infants with gestational ages ranging from 24 to 36 weeks. RESULTS: In the premature infants, concentrations of both cystatin C and creatinine were significantly raised compared with term infants, with cystatin C concentrations being between 1.10 and 2.06 mg/litre and creatinine between 32 and 135 micromol/litre. In premature infants, there was no significant relation between gestational age and cystatin C or creatinine concentration. Creatinine concentrations fell to a nadir at 4 months of age, rising gradually to adult values by about 15-17 years of age, in contrast to cystatin C, which fell to a mean concentration of 0.80 mg/litre by the 1st year of life, and remained constant throughout adulthood up to the age of 50 years. Neither analyte showed any influence of sex. CONCLUSION: The measurement of cystatin C, rather than creatinine, is more practical for monitoring GFR changes in the paediatric population.

Adolescent↗
PubMed2000

Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance.

Serum cystatin C measurement has been previously shown by ourselves and others to be a better indicator of changes in glomerular filtration rate (GFR) than serum creatinine. However, the available literature on reference values for cystatin C concentration remains surprisingly sparse; we thus set out to determine an adult reference range. Blood was taken from 309 healthy blood donors and creatinine and cystatin C concentrations were measured using commercially available automated methodologies. In addition, predicted creatinine clearances were calculated using the Cockcroft and Gault formula. The 95% reference intervals for creatinine, predicted creatinine clearance and cystatin C for all blood donors, regardless of gender, were 68-118 mumol/L, 58-120 ml/min/1.73 m2 and 0.51-0.98 mg/L, respectively. For women, the intervals were 68-98 mumol/L, 60-119 ml/min/1.73 m2 and 0.49-0.94 mg/L; for men, they were 78-123 mumol/L, 57-122 ml/min/1.73 m2 and 0.56-0.98 mg/L. This mean 95% reference interval for cystatin C in all donors under 50 years of age was 0.53-0.92 mg/L; for those over 50 years of age it was 0.58-1.02 mg/L. The small difference between make and female ranges meant that a single reference range for cystatin C could be established for all adults under 50 years of age without adjustment for body surface area. Serum cystatin C measurement offers a simpler and more sensitive screening test than serum creatinine for early changes in GFR.

Adult↗
PubMed2000

The early fall in levels of S-100 beta in traumatic brain injury.

Protein S-100 beta has been suggested as a prognostic marker in traumatic brain injury. However, little is known of its behaviour in the immediate post-injury period. With Ethics Committee approval, we recruited 30 patients with a history of head injury presenting to our Accident and Emergency Department. Blood was taken on arrival and at four hours post-injury. Serum S-100 beta was estimated using an immunoluminometric assay. Levels of S-100 beta were seen to fall rapidly with time. Half-time was distributed non-parametrically with a median of 198 minutes. Using the Mann-Whitney U test we found a statistically significant difference between non-desirable (Glasgow Outcome Score 1-3) and desirable (Glasgow Outcome Score 4-5) outcome on admission (p = 0.0155) but not at four hours (p = 0.1336). Levels of S-100 beta fell rapidly after its release following traumatic brain injury. Time after injury is therefore critical in assessing the significance of levels of S-100 beta, and sampling should be as early as possible to gain maximum information. If S-100 beta is to be assessed as a monitor of ongoing brain injury in the intensive therapy unit sampling must be frequent (e.g. every 4 hours) to be able to detect rises in serum levels before they have decayed to baseline.

Brain Injuries↗
PubMed2000

Evidence-based laboratory medicine: supporting decision-making.

There is an implicit acceptance that an evidence-based culture underpins the practice of laboratory medicine, in part because it is perceived as the scientific foundation of medicine. However, several reviews of specific test procedures or technologies have shown that the evidence base is limited and in many cases flawed. One of the key deficiencies in the scientific literature on diagnostic tests often is the absence of an explicit statement of the clinical need, i.e., the clinical or operational question that the use of the test is seeking to answer. Several reviews of the literature on specific procedures have also demonstrated that the experimental methodology used is flawed with, in some cases, significant bias being introduced. Despite these limitations it is recognized that a more evidence-based approach will help in the education and training of health professionals, in the creation of a research agenda, in the production of guidelines, in the support of clinical decision-making, and in resource allocation. Furthermore, as knowledge and technologies continue to be developed, an evidence-based strategy will be critical to harnessing these developments.

Attitude of Health Personnel↗
PubMed1999

Laboratory medicine in the United Kingdom: 1948-1998 and beyond.

The National Health Service in the United Kingdom was created in 1948, effectively becoming the main provider of healthcare and funded by the government from taxation. By the late 1970's, and despite many achievements, it was seen to be approaching a financial crisis. Radical reforms were introduced in the early 1990's bringing in general management, a split between purchaser and provider, and competition. Whilst there has been a change of government more recently several of these initiatives have been retained, with the exception of competition (the internal market) which has been abandoned. There is now a much greater focus on the quality of care with increased clinical and financial accountability. Laboratory medicine (generally termed pathology in the United Kingdom) has evolved to meet the demands of more patients, reducing turnaround times, a greater repertoire of investigations and a continuing improvement in productivity. There is an increasing focus on improved dialogue between the laboratory and the clinician covering interpretation of results, audit of services and outcomes, research and development and continuous education in the pursuit of a high quality service. The major challenges for the future focus on alternative modes of delivery, on issues relating to staffing and on quality of service, in the face of an ever increasing demand.

Benchmarking↗
PubMed1999

Soluble CD8 stabilizes the HLA class I molecule by promoting beta2M exchange: analysis in real-time.

Human soluble CD8 (sCD8) is secreted by activated CD8+/- cytotoxic T lymphocytes (CTLs). The immunological role of sCD8 is poorly defined, however. We have studied the influence of sCD8 on HLA class I interactions by real-time analysis. Using an optical biosensor we demonstrated that the binding of sCD8 to HLA-A2 promotes exchange of beta2-microglobulin (beta2m) in order to stabilize the complex. Kinetic analysis showed that sCD8 significantly increased the affinity (K(A)) of HLA-A2 for immobilized human beta2m; from 1.14 +/- 0.04 x 10(9) M(-1) in its absence, to 2.18 +/- 0.21 x 10(9) M(-1) following preincubation with sCD8. This suggests that the sCD8:HLA class I complex is unlikely to be degraded at the cell surface. Even in the presence of exogenous peptide (HLA-A2 specific or nonspecific), sCD8 has a stabilizing influence on the HLA class I molecule. These findings point to an immunosuppressive role for sCD8, because the binding of sCD8 to HLA class I would block the binding site for CTL-bound CD8 and, therefore, interfere with T cell activation and proliferation. This may have particular significance in pathological situations where elevated levels of sCD8 are found in extracellular fluids, and sCD8 may provide an alternative approach for immunosuppressive therapy.

CD8 Antigens↗
PubMed1999

Evaluation of a new troponin I method on the Bayer Immuno 1 immunoassay analyser.

We have evaluated the analytical and clinical performance of an automated immunoassay for serum cardiac troponin I (Bayer Immuno 1TM, Bayer Diagnostics, Tarrytown, NY). The between batch imprecision was found to be between 1.2 and 3.2% over the concentration range 2.5 - 34.0 microg/L. The analytical range obtained from duplicate analysis of patient samples and defined as a coefficient of variation of 10% or less was 0.3 - 200 microg/L. The detection limit was found to be less than 0.1 microg/L. A method comparison with the Dade Stratus method (Dade Behring, Wilmington, DE) yielded regression statistics with a slope of 0.705 and an intercept of -0.260. An analysis of samples from 40 patients with renal failure demonstrated six with detectable levels of troponin I (0.2 - 1.9 microg/L). Samples from patients with paraproteinaemia did not demonstrate detectable troponin I (from n = 30); however, two patients with elevated rheumatoid factor titers (from n = 20) demonstrated a detectable amount of troponin I (0.1 and 0.2 microg/L). In a study of 100 patients admitted with acute chest pain and a diagnosis of unstable angina, 6 were subsequently diagnosed as having suffered a myocardial infarction. On admission the sensitivity and specificity of the troponin I results were 26.7% and 94.7%, respectively, moving to 100% and 83% 12 hours after admission.

Analysis of Variance↗
PubMed1999

A rapid and sensitive automated light scattering immunoassay for serum C-reactive protein and the definition of a reference range in healthy blood donors.

The increasing interest in the measurement of serum C-reactive protein in relation to the risk stratification of patients with chest pain has demonstrated the need for more sensitive routine methods of measurement and an accurate definition of the reference range. We report the determination of a reference range in serum samples from 491 blood donors using a particle enhanced turbidimetric immunoassay that has been modified to offer better imprecision within the reference range. The median values were found to be 2.40 and 2.20 mg/l for males and females, respectively with 95th percentile range of 1.20-5.20 and 0.40-5.40 mg/l, respectively.

Adult↗
PubMed1999

Performance of a reagent strip device for quantitation of the urine albumin: creatinine ratio in a point of care setting.

AIM: We have evaluated the performance of a reagent strip (Clinitek, Bayer plc, Newbury) incorporating a novel dip and read device for the quantitation of the albumin: creatinine ratio together with their individual concentrations in urine. METHODS: The performance was compared with that of a lateral flow device for the semi-quantitation of albumin (Micral II, Roche Diagnostics, Lewes) and also a laboratory based procedure. The device employs novel methods for both analytes, using a sulphonephthalein dye binding at pH 1.5 for albumin and the peroxidase-like activity of copper creatinine complexes. The color yields of the separate reaction pads are monitored with the Clinitek 50TM bench top urine chemistry analyzer and compared to a pre-programmed calibration algorithm. RESULTS: The imprecision of the device was assessed by observing the discrepancy between duplicates in a total of 144 urine samples collected from patients with diabetes and/or renal disease; there were 10 discrepancies in the case of the albumin estimation (6.9%), 12 in the case of the creatinine estimation (12.5%) and 23 in the case of the albumin: creatinine ratio (16.0%). In the case of the Micral II, where 96 of the urines were analyzed there were 12 discrepancies (12.5%). When considered as a two-class test for albumin with a cut off of 20 mg/L the Clinitek gave a sensitivity of 95.4% with specificity of 78.9% and a positive predictive value of 87.4%. When analyzing four urines (two controls, two patient pools) with replicate analysis on the Clinitek system we found 100% agreement for the albumin estimation, 95% for creatinine and 96.7% for the albumin: creatinine for 60 analysis within a day and 100, 95 and 97.5% on single analyses each day for 20 days for the two urine controls. The discrepant results were always within one color block. When considering the albumin: creatinine ratio with a cut off of < 30 mg/g the Clinitek gave a sensitivity of 76.3% with a specificity of 89.1% and a positive predictive value of 89.7%. CONCLUSION: The Clinitek system provides a reliable means to screen for microalbuminuria with the opportunity of a semi-quantitative assessment when microalbuminuria is found.

Albuminuria↗
PubMed1999

Impact of antibody specificity and calibration material on the measure of agreement between methods for cardiac troponin I.

BACKGROUND: Available assays for cardiac troponin I (cTnI) yield numerically different results. The aim of this study was to compare patient values obtained from four cTnI immunoassays. METHODS: We studied the Stratus(R) II assay, the Opus(R) II assay, the Access(R) assay, and a research-only cTnI heterogeneous immunoassay that uses the Dade Behring aca(R) plus immunoassay system equipped with two new noncommercial monoclonal antibodies. Because the aca plus cTnI assay is for research only, we first evaluated and analytically validated it for serum and citrated plasma. Initially, each method was calibrated using the method-specific calibrator supplied by each manufacturer; however, the aca plus cTnI assay was calibrated using patient serum pools containing cTnI and selected on the basis of increased creatine kinase MB isoenzyme and with values assigned by use of the Stratus cTnI assay. For method comparisons, individual patient sample cTnI values were determined and compared with the Stratus II assay. RESULTS: Passing and Bablock regression analysis yielded slopes of 1.44 (r = 0.96; n = 72) for the Opus II vs Stratus II assays; 0.07 (r = 0.91; n = 72) for the Access vs Stratus II assays; and 0.90 (r = 0.91, n = 72) for the aca plus vs Stratus II assays. The recalibration of each method with a Stratus II-assigned serum pool improved, but did not entirely eliminate, the slope differences between the different assays (range, 1.00-1.16). The observed scatter in the correlation curves remained. CONCLUSION: There is a need to further explore the specificities of these assays with respect to the different circulating forms of cTnI.

Antibodies, Monoclonal↗
PubMed1998

Real-time analysis of cell surface HLA class I interactions.

Characterisation of the kinetics of assembly and dissociation of the HLA class I heterotrimeric complex provides valuable insights into the relative contributions of each element to complex stability. However, to date there has been no real-time binding analysis on whole cells. Here we have developed an optical biosensor model to investigate the binding of class I HLA complexes on whole cells to human beta 2-microglobulin (beta 2m) and the effects of different HLA-specific peptides on this binding. We immobilised beta 2m on an IAsys biosensor surface and established conditions to analyse the binding of this to HLA-A2 expressing cells (T2 cells). Using 721.221 cells as an HLA negative control we showed that HLA-A2 binding was optimal using a) a carboxymethylated dextran surface and b) no growth factors or supplements in the culture medium at the binding event. Using these conditions we verified specificity of binding by inhibition of the reaction with free beta 2m and determined the dissociation rate constant for T2 cell binding to beta 2m (0.03 s-1). In addition, we demonstrated the ability of different HLA specific peptides to modulate cellular HLA-A2 binding to beta 2m. This is the first time that interactions of cell surface HLA class I molecules has been investigated using real-time analysis. Furthermore, our peptide analysis has shown that this model can be used to characterise peptide specific HLA-binding responses on the whole cell surface in real-time.

Cell Line↗
PubMed1998

The matrix effects on kinetic rate constants of antibody-antigen interactions reflect solvent viscosity.

This study describes the influence of different matrices on two model antibody-antigen interactions; that between beta2microglobulin and anti beta2microglobulin, and that of rabbit anti mouse Fc fragment (RAMFc) with mouse IgG. The matrices investigated were; phosphate-buffered saline pH 7.4 containing 0.05% Tween 20 detergent, horse serum, a 50:50 mixture of phosphate-buffered saline/Tween 20 and horse serum, and four glycerol solutions of differing concentrations. A recently developed optical biosensor, the IAsys, was used to monitor the interactions in real-time and provide precise determinations of k(ass), k(diss) and KA values. The results show that the rates of association and dissociation for the two different antibody:antigen models are significantly affected by the surrounding matrix. Glycerol of known viscosity was used as a matrix in both models to show that this effect is attributable to the viscosity as opposed to proteins present in the matrix. The viscosity of the matrix has also been shown to have an apparent influence upon the overall equilibrium/affinity constant for the interaction, with measurements of KA tending to increase with viscosity. The significant effects of matrix on kinetic rate constants for antibody-antigen interactions shown here have important implications in the use of immunoassays where non-equilibrium measurements are made in serum matrices.

Animals↗
PubMed1998

The influence of exogenous peptide on beta2-microglobulin exchange in the HLA complex: analysis in real-time.

We used an optical biosensor to determine the relative binding affinity of peptides to purified HLA class I molecules. In this assay we monitor beta2-microglobulin (beta2m) exchange within the HLA-A2 molecule, whereby native beta2m in the complex is replaced by beta2m immobilized at the surface of the biosensor. Quantitative kinetic measurements permit us to obtain association rate (kass), dissociation rate (kdiss) and affinity constants (KA) for the beta2m exchange reaction, alone, (control) and in the presence of exogenous peptide. We tested a panel of six peptides which had been designed and synthesized with an HLA-A2 binding motif, and had also been tested by the T2-cell binding assay, along with control peptides. The biosensor results demonstrate that exogenous peptide influences the dynamics of beta2m exchange in a sequence-specific manner. Five of six peptides increased the association rate, decreased the dissociation rate, and significantly increased the affinity (KA=1. 55-1.88x10(9) M-1) of HLA-A2 for immobilized beta2m compared with the control (KA =1.14+/-0.04x10(9)M-1), demonstrating stabilization of the complex. One peptide was unable to stabilize the complex, as also shown in the T2 binding assay. However, analysis of peptide sequences demonstrated that the HLA-A2 secondary motif as well as primary motif residues are required for HLA-A2 stabilization. Further experiments demonstrated that beta2m exchange alone cannot stabilize the HLA class I complex at the cell surface until a peptide of sufficient binding affinity is bound. Hence kinetics equal to or below the control values in our biosensor assay probably represent an unstable complex in vivo. Unlike other methods described for the analysis of peptide stabilization, this approach is significantly faster, provides full kinetic analysis, and is simpler, since it requires no labeling of peptides. Furthermore, this may have important implications in the assessment of peptide vaccines.

Biosensing Techniques↗