Comparison of a within-day solid-phase immunoradiometric assay with a solution-phase radioimmunoassay for the measurement of alpha-fetoprotein in amniotic fluid.

Using 231 amniotic fluid samples from a Regional Screening Service, the performance of a monoclonal antibody-based solid-phase immunoradiometric assay (IRMA) for alpha-fetoprotein was compared with that of a polyclonal antiserum-based solution phase radioimmunoassay (RIA). alpha-Fetoprotein values determined from these samples by the two methods were in excellent agreement (r = 0.992) and the diagnostic performance of the two assays was identical. However, the IRMA assay displayed a greater working range than the RIA, and in addition was more rapid to perform, allowing within-day turnaround of laboratory results.

The effects of septic complications upon the serum protein changes associated with thermal injury.

The levels of 12 serum proteins including 'acute-phase reactants', immunoglobulins and albumin were measured in 20 patients suffering from thermal burns. The acute-phase reactants: C-reactive protein, alpha-l antitrypsin, alpha-l antichymotrypsin, haptoglobin and orosomucoid, all increased in concentration. Highest levels, which showed significant correlations with injury severity, occurred at 6-8 days post-burn. The levels of albumin, alpha-l lipoprotein and transferrin were decreased. The immunoglobulins IgG, IgA and IgM showed an initial decrease followed by a steady return to normal levels. Four patients, of whom three died, developed serious sepsis. The levels of alpha-l antichymotrypsin and C-reactive protein were much higher in patients with sepsis than in those without sepsis. The highest levels occurred during and often before the episode of sepsis was clinically evident. The immunoglobulins especially IgG and IgA were lower in those patients who developed sepsis than in those who did not. The results suggest that the serum levels of either C-reactive protein or alpha-l antichymotrypsin could be used both as an aid to diagnosis of sepsis and also to monitor the effect of therapy.

A phenytoin assay using dried blood spot samples suitable for domiciliary therapeutic drug monitoring.

A commercially available substrate-labelled fluorescent immunoassay procedure has been modified to create a simple rapid method for the determination of capillary phenytoin concentration in dried filter paper blood spots of patients on phenytoin therapy. The specimens are collected and dispatched to the laboratory by the patient, thus domiciliary monitoring of phenytoin therapy can take place. The technique was validated by comparing the phenytoin results of simultaneously collected capillary dried blood spots and conventional plasma samples. The technique offers a convenient method for overcoming many of the practical problems of monitoring phenytoin therapy in epilepsy.

Thyroxine-binding prealbumin--an index of disease activity or nutritional status in rheumatoid arthritis?

Thyroxine-binding prealbumin (TBPA) concentrations were measured in 54 patients with rheumatoid arthritis (RA) and 50 control subjects. TBPA levels were significantly depressed in the RA patients, of whom 15 had values below the laboratory reference range. Although significant negative correlations were seen between TBPA and the erythrocyte sedimentation rate, C-reactive protein and alpha 1-antichymotrypsin measurements, TBPA levels showed little relationship to disease activity as assessed clinically. On the other hand, RA patients with reduced TBPA had an increased frequency of associated anthropometric and serum visceral protein abnormalities indicating nutritional impairment. TBPA is probably subjected to diverse stimuli in patients with RA and should not be considered to act as a 'pure' negative acute phase reactant.

Nutritional status in patients with rheumatoid arthritis.

A nutritional assessment of 50 patients with rheumatoid arthritis (RA) showed evidence of malnutrition in 13 (26%), while all 50 control subjects had normal nutritional status. Of the anthropometric measurements the body-mass index and triceps skinfold thickness values in men and women were significantly reduced in RA patients compared with controls. Upper arm muscle circumference was significantly less in male but not female rheumatoid patients. In addition all six biochemical determinants of nutrition assayed-serum albumin, transferrin, retinol-binding protein, thyroxine-binding prealbumin, zinc, and folic acid-were significantly lower in the RA group of patients. Malnourished patients had more active disease than the remaining RA patients, with significantly higher ESR, C-reactive protein, and alpha 1 antichymotrypsin measurements. Significant inverse correlations were found between some biochemical measurements of nutrition and indices of disease activity. Our results suggest that in RA the severity of disease adversely affects the nutritional status.

The validation of a fluoroimmunoassay for the determination of theophylline concentration in dried blood spots suitable for domiciliary therapeutic drug monitoring.

A commercially available substrate-labelled fluorescent immunoassay procedure has been modified to create a simple rapid method for the determination of capillary theophylline concentration in the dried filter paper blood spots of patients on theophylline therapy. The specimens are collected and dispatched to the laboratory by the patient; thus domiciliary monitoring of theophylline therapy can take place. The technique offers a convenient method for overcoming many of the practical problems that arise during theophylline therapy in asthmatic patients.

Improved discrimination in the detection of neural tube defects: five biochemical tests compared.

Five biochemical tests, which have been proposed as possible adjuncts to the measurement of amniotic fluid alphafetoprotein for the identification of neural tube defects, have been measured in 49 normal and 46 neural tube defect affected pregnancies. One test, the alphafetoprotein component non-reactive with concanavalin A, was ineffective in differentiating normal and abnormal. The remaining four procedures, the activity of acetyl and total cholinesterase, the concentration of alpha 2 macroglobulin and the electrophoretic identification of acetyl cholinesterase effectively separated the normal and abnormal populations. The relative merits of these four latter tests in the evaluation of false positive and false negative amniotic fluid alphafetoprotein results, as well as in liquor samples with high alphafetoprotein levels associated with abnormalities not of neural origin, are discussed.

Urine cortisol levels after burn injury.

The urinary level of cortisol has been assayed in 19 patients with burn injuries of varying severity over a 10-day period. Urine cortisol was increased in all patients over the initial days post burn when compared to normal health volunteers. In patients with the more severe burns mean cortisol levels correlated with the percentage body surface area of the burn. The overall pattern of cortisol excretion was similar in extent and duration to the changes in the levels of serum cortisol described in a previous study (Batstone et al., 1976). Further, urine cortisol excretion correlated with the levels of urine creatinine, magnesium, potassium and the sodium: potassium ratio lending further evidence to an important role of cortisol in peripheral tissue (particularly muscle). Cortisol output was still significantly raised at the end of the study period emphasizing the duration of the cortisol-induced catabolic drive after burn injury.

Metabolic interactions of glucagon and cortisol in man--studies with somatostatin.

The metabolic response to pathophysiologic concentrations of glucagon, induced by glucagon infusion, has been examined in normal man before and after 36-60 hr hypercortisolaemia, induced by administration of tetracosactrin-depot. Glucagon alone increased serum insulin levels twofold but blood glucose was unaltered. Plasma NEFA and blood ketone body concentrations were decreased by glucagon infusion. Tetracosactrin produced a threefold rise in serum cortisol levels and caused mild fasting hyperglycemia and hyperinsulinaemia. Subsequent glucagon infusion had no effect on circulating insulin, glucose, NEFA or ketone body concentrations. Simultaneous infusion of somatostatin, to produce partial insulin-deficiency, unmasked a hyperglycemic action of glucagon (+ 3.8 +/- 0.2 mmol/l at 90 min, p less than 0.02). This glucagon-induced rise in blood glucose was diminished by prior tetracosactrin administration. Tetracosactrin revealed a mild lipolytic action of glucagon in partial insulin deficiency, not apparent in the euadrenal state. Glucagon was equally hyperketonemic during somatostatin infusion before and after tetracosactrin. Thus the hyperglycemic and hyperketonemic actions of glucagon at pathophysiologic levels are restricted to insulin deficiency. Hypercortisolaemia reveals a lipolytic action of glucagon in insulin-deficient man but does not potentiate the hyperglycemic or hyperketonemic effects.