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J T Whicher

Publications and source records attributed to J T Whicher.

At least 19 recordsLinked to original sources
PubMed1992

Acute phase reactants in predicting disease outcome.

From the studies which are reviewed above, it is generally apparent that in terms of the acute phase response, the initial findings in early inflammatory arthritis (particularly rheumatoid arthritis, with which the majority of such studies are concerned) have little predictive value for either the functional outcome or mortality. The wide interindividual variability in these measurements is also likely to limit their clinical usefulness as predictors of disease outcome. The trend in certain acute phase reactants may be more useful in indicating disease activity, although the number of satisfactory studies in this area is very limited.

Acute-Phase Proteins↗
PubMed1992

Interleukin-6 and its relationship to C-reactive protein and fever in children with febrile neutropenia.

The assessment of febrile neutropenia is problematic. C-reactive protein (CRP) values alone do not differentiate those patients with microbiologically documented infections from those with unexplained fevers. Plasma interleukin-6 (IL-6), measured by ELISA, was correlated with different diagnostic groups in 47 episodes of febrile neutropenia in children. Samples were collected daily from admission until resolution of fever. On admission, the median IL-6 value for gram-negative infections was 1610 pg/ml (range, 896-40,000), for gram-positive infections it was 138 pg/ml (range, 66-1045), and for unexplained fevers it was 50 pg/ml (range, 24-135, with a single high value of 665 pg/ml). These medians were significantly different (P less than .005). There was no significant difference in median CRP values. IL-6 values peaked 24-48 h before CRP values. There was a positive correlation of IL-6 with the presence of fever. Plasma IL-6 may be a more sensitive marker than CRP of acute infection and should prove useful in the assessment of fevers in these patients.

Adolescent↗
PubMed1992

The value of acute phase protein measurements in clinical practice.

There is clearly a role for the measurement of acute phase proteins and other indices of the acute phase reaction but it is equally clear that no one laboratory test is suitable for use in all clinical situations. The choice of acute phase protein measurement depends on the diagnostic sensitivity and specificity of the measurement in the particular clinical situation. The choice of measurement must also include a decision on time of sampling and whether single or serial sampling would be more appropriate. In most situations where acute phase measurement is useful CRP is the assay of choice with alpha 1-antichymotrypsin also being useful in inflammatory bowel disease and other situations where a wider time window is required. The ESR or plasma viscosity can be useful to screen for disease. Cytokine and enzyme-inhibitor complex measurements may be important assays in the future.

Acute-Phase Proteins↗
PubMed1991

Is fatal pancreatitis a consequence of excessive leukocyte stimulation? The role of tumor necrosis factor alpha.

This study examines the possible role of excessive leukocyte stimulation in the pathogenesis of acute pancreatitis. Levels of tumor necrosis factor alpha (TNF-alpha) and elastase-alpha 1 proteinase inhibitor (E-alpha 1PI) have been measured as markers of macrophage and neutrophil activation, respectively, in serial plasma samples from 27 patients with acute pancreatitis. Levels of TNF-alpha did not support the possibility of excessive macrophage activation, but raised levels of E-alpha 1PI in patients with either the mild or severe form of the illness indicated the activation of neutrophils. Whether this is a consequence of the illness or is a contributory factor in the pathogenesis is not clear.

Acute Disease↗
PubMed1991

Insulin modulation of acute-phase protein production in a human hepatoma cell line.

Insulin is widely used as a growth factor in hepatocyte culture but its effect on the production of acute-phase proteins has not been studied. By measuring four positive (fibrinogen, alpha 1-antitrypsin, alpha 1-acid glycoprotein, and alpha 1-antichymotrypsin) and four negative (albumin, prealbumin, transferrin, and retinol binding protein) acute-phase proteins produced by the Hep G2 hepatoma cell line, we have shown that insulin is an important modulator of acute-phase protein production. Our data show that insulin is able to inhibit the synthesis of prealbumin, transferrin, and fibrinogen. The results also show a complex interaction between insulin, interleukin 6, and glucocorticoids because insulin is able to inhibit the dexamethasone induction of alpha 1-antichymotrypsin, and in the presence of interleukin 6, dexamethasone is able to regulate the production of fibrinogen and prealbumin. The regulatory role of insulin in fibrinogen production was confirmed by pulse chase labeling followed by immunoprecipitation and fluorography.

Acute-Phase Proteins↗
PubMed1991

Comparative study of C reactive protein and serum amyloid A protein in experimental inflammation.

The responses of C reactive protein, measured by radial immunodiffusion and radioimmunoassay, and serum amyloid A protein, measured by radial immunodiffusion, were compared in eight subjects with inflammation induced experimentally by intradermal injection of monosodium urate crystals. A significant increase in serum amyloid A was noted after a lag phase of eight hours, the increase in median concentration at 48 hours being about eightfold. A parallel but less marked increase was found in C reactive protein when measured by radioimmunoassay (fourfold increase in median concentration at 48 hours) after a small but significant decrease during the lag phase. The changes in C reactive protein remained within the reference range and were not detectable by radial immunodiffusion.

C-Reactive Protein↗
PubMed1991

Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks.

Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis.

Acute Disease↗
PubMed1991

External quality assessment of total urinary protein estimation in the United Kingdom.

Three surveys of total urinary protein quantitation have been carried out in 350 UK laboratories. The seven specimens comprised buffered saline or normal human urine with added human serum albumin or human serum, or urine from individuals with nephrotic syndrome. Principal method groups were: turbidimetry (57%), dye binding (25%) and biuret (15%). For all surveys, overall between-laboratory agreement was poor (CV 22.8% to 57.1%), with ranges of results from 24-fold (0.83-20 g/L) to 366-fold (0.05-18.3 g/L); there was no improvement with time. The most popular method (sulphosalicylic acid turbidimetry) consistently performed the worst, and performance of the direct biuret procedure was also unacceptable; both methods should be discontinued. There were no significant differences in performance between the other major method groups, and none can be specifically recommended. Within the individual calibrant groups, least variation was observed with human serum. A common calibrant for all participants yielded significantly better between-laboratory agreement for all methods except sulphosalicylic acid turbidimetry.

Biuret Reaction↗
PubMed1991

Calibration is the key to immunoassay but the ideal calibrator is unattainable.

Unlike assays for ions and small molecules protein and peptide measurements depend entirely on comparison of a test sample with a calibrator. Owing to the innate molecular heterogeneity of proteins it is frequently impossible to ensure that the calibrator is identical to the test and this may give rise to dissimilar behaviour in assays. Despite these fundamental limitations it is clear that internationally agreed calibrators are essential and properly used greatly improve homogeneity of reporting of protein values in biological fluids. Unfortunately, only international units can be ascribed to these materials with confidence and the use of mass values which are not internationally agreed has jeopardized the value of international calibrants.

Antibodies↗
PubMed1991

Restricted electrophoretic heterogeneity of immunoglobulin light chains in urine: a cause for confusion with Bence Jones protein.

The detection of Bence Jones protein, an important part of the investigation of suspected myeloma, is most commonly done by agarose or cellulose nitrate electrophoresis followed by immunofixation. Bence Jones protein is recognized as single or multiple bands of one type of light chain. Unfortunately, improvements in sensitivity of these techniques (use of high-affinity antisera and higher resolution electrophoresis) frequently allow detection of multiple light chain bands in the urine of patients who do not have a B-cell dyscrasia. The bands are usually kappa, although they may be accompanied by lambda bands. This pattern may lead to the misdiagnosis of Bence Jones protein and oligoclonal light chain production in patients. Here we show that this pattern is produced by polyclonal light chains; it is present in the urine of all patients with a tubular proteinuria of any etiology and may be induced in healthy individuals by blocking their renal tubular protein reabsorption. Polyclonal light chains separate into monomers and dimers on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and into four major bands with many minor bands by isoelectric focusing. This difference in charge and possibly size results in the banding pattern seen on good-quality electrophoresis and immunofixation.

Aged↗
PubMed1991

Use of immunoglobulin heavy-chain and light-chain measurements in a multicenter trial to investigate monoclonal components: II. Classification by use of computer-based algorithms.

We describe a computer algorithm for classifying serum monoclonal proteins (MC) based on serum protein electrophoresis (SPE) and the automated measurement of kappa and lambda light chains and IgG, IgA, and IgM. We developed the algorithm by using a large database of unselected samples containing MC collected in a multicenter study. The performance of the algorithm was optimized by using iterative computational procedures and was tested on both the development database and on an independent set of MC-containing samples. With the development database, the algorithm correctly classified 50% and misassigned 2.5% of the MC. Where the MC were present in concentrations greater than 10 g/L, the rate of successful classification increased to 72% with 3% misclassification. When the algorithm was tested on a group of 101 MC-containing samples from an independent source, 67% were correctly classified and 8% misclassified, half of the latter being unusual IgD myelomas. We discuss the scope for the application of the algorithm in routine laboratory practice involving personal computer software.

Algorithms↗
PubMed1990

Immunochemical assays of serum proteins: a European external quality assessment survey and the effects of calibration procedures on interlaboratory agreement.

An external quality assessment survey of immunochemical assays of 9 proteins (immunoglobulins G, A and M, complement components C3 and C4, alpha1-antitrypsin, orosomucoid, haptoglobin and transferrin) in 5 European countries (Austria, France, Hungary, Italy and UK) showed inter-country differences in the mean values obtained. Reprocessing of the results using one of the two specimens distributed as a 'calibrant' effectively eliminated or reduced substantially these differences. Consideration of the methods used by participants confirmed previous indications from national surveys that the differences were due to lack of agreement among commercial calibrants. Such interlaboratory variations were also minimised by the 'calibration' in this survey. The role of European working calibration materials in ensuring interlaboratory agreement on an international basis is discussed.

Blood Proteins↗
PubMed1990

Measurement of the 'fast' or complexed form of alpha 2 macroglobulin in biological fluids using a sandwich enzyme immunoassay.

A sandwich enzyme immunoassay has been developed for measuring the 'fast' or complexed form of alpha 2 macroglobulin using a complex-specific monoclonal antibody. The working range of this assay is 1.5-15 micrograms/l and is suitable for use with various biological fluids. Using this assay the normal plasma levels were found to range from 4.2 mg/l to 14.4 mg/l (0.17%-0.70% of total alpha 2 macroglobulin) with a mean value of 7.6 mg/l +/- 2.6 (0.37% +/- 0.12% of total alpha 2 macroglobulin). Elevated levels were seen in plasma samples taken on the day of admission from patients with acute pancreatitis and in some synovial fluid samples from patients with various arthritides.

Antibodies, Monoclonal↗
PubMed1990

Electrophoresis and densitometry of serum and urine in the investigation and significance of monoclonal immunoglobulins.

About 15% of monoclonal components or paraproteins are associated with malignancy when detected by simple electrophoresis on cellulose acetate membranes or agarose gel followed by protein staining. More sensitive methods for detecting monoclonal components result in a lower frequency of association with recognisable underlying disease. The sensitivity is dependent on the system used. Isoelectric focusing is 10 to 40 times more sensitive than simple electrophoresis at detecting monoclonal components. Electrophoretically separated bands may be quantitated densitometrically and at the present time this is the most satisfactory method for measuring monoclonal component concentration. Immunochemical methods for quantitating monoclonal components are limited by failure to react in a similar manner to polyclonal standards and giving problems of antigen excess resulting both in falsely elevated and low results. Electrophoretic methods must always be used in conjunction with these. The normal polyclonal ratio of immunoglobulin kappa:lambda light chain is disturbed by the presence of a monoclonal component. In 260 patients with myeloma we found that serum electrophoresis alone detected 90% while a disturbance in the kappa:lambda ratio detected 98%. However, 50% of monoclonal components less than 3 g/L were missed. Log kappa:lambda ratio correlates well with the densitometric scan of monoclonal components, both in vitro and in patients being monitored for treatment response in myeloma. This approach may complement or even replace densitometry for this purpose in the future.

Adult↗
PubMed1990

Alpha 1-microglobulin, beta 2-microglobulin and retinol binding protein in childhood febrile illness and renal disease.

Serum and urinary levels of alpha-1-microglobulin (A1M), beta-2-microglobulin (B2M) and retinol binding protein (RBP) were measured using a Mancini radial immunodiffusion technique in 52 children with renal disease, 36 with non-renal febrile illness and 29 controls. In controls the mean serum level for A1M was 25 +/- 4.6 (SD) mg/l for B2M 1.7 +/- 0.5 mg/l and for RBP 31 +/- 8 mg/l. A1M levels were not significantly altered by febrile illness while B2M was elevated and RBP markedly depressed. Serum A1M and B2M were elevated in the nephrotic syndrome, while serum B2M was also raised during infancy. Coefficients of log-transformed data with creatinine-derived glomerular filtration rate (GFR) were -0.87 for B2M, -0.71 for RBP, and -0.62 for A1M. In the urine A1M was always measurable in controls while B2M and RBP were undetectable in all but a small number. The urine levels of all three proteins increased in response to non-renal febrile illness, and rose invariably when GFR fell to below 40-50 ml/min per 1.73 m2. Of the three proteins A1M was most frequently elevated in the urine with febrile and renal illness. RBP was rarely detectable when the other two proteins were not. Urinary A1M was consistently elevated in the nephrotic syndrome in contrast to B2M, possibly as a reflection of the increased glomerular permeability. We conclude that serum B2M is superior to A1M and RBP as an index of glomerular filtration, although its levels should be interpreted with caution in febrile disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The acute phase protein response in mice does not show tolerance to recurrent sterile inflammation.

The response of acute phase proteins to repeated inflammatory stimuli was studied in BALB/c mice and Hylyne Dutch rabbits. Inflammation was produced by subcutaneous injections of turpentine/arachis oil twice weekly for three and a half weeks. Serum amyloid-P component (SAP) levels in the mice showed no significant decrease in the level of response following each injection and the pattern of response was the same in mice previously rendered tolerant to endotoxin. Haptoglobin levels in the rabbits also responded equally to repeated injections in two animals and showed a declining response in a third animal which became unwell during the experiment. The ability of experimental animals to continue to respond fully to repeated inflammatory stimuli supports the suggestion that the subnormal responses seen in certain chronic inflammatory conditions may reflect an underlying defect in the acute phase response rather than an adaptive change following chronic inflammation.

Acute-Phase Proteins↗