Measurement of urinary N tau-methylhistamine excretion: correlation of a newly developed radioimmunoassay (RIA) with gas chromatography mass spectrometry (GCMS).

A newly developed radioimmunoassay (RIA, Y) for the determination of urinary N tau-methylhistamine concentrations was correlated with gas chromatography mass spectrometry (GCMS, X). In 34 urine samples, with histamine and N tau-methylhistamine levels within our reference values, the correlation was: Y = 1.47X -0.245 mumol/l (r = 0.92; p-slope less than or equal to 0.0001). In 14 pathological urine samples, derived from patients with mastocytosis and having upper reference values, the correlation was: Y = 1.75X - 1.02 mumol/l (r = 0.93; p-slope less than or equal to 0.001). In spite of the greater specificity of the monoclonal antibody for N tau-methylhistamine compared with that of histamine, relatively high urinary histamine concentrations gave a false positive influence on the RIA results, which was 100% when the histamine/N tau-methylhistamine ratio was about 19. Clear cases of mastocytosis can be diagnosed, using the RIA-kit, but for a more precise N tau-methylhistamine value GCMS analyses will remain necessary.

Determination of histamine in human plasma: the European external quality control study 1988.

There is an increasing interest in measuring human plasma histamine levels in various clinical conditions. A variety of 'old' and newly developed techniques are applied to meet this demand. However, the discrepancy between reported reference values for histamine in human plasma measured using this variety of techniques, suggests the existence of a certain degree of inaccuracy and imprecision. We therefore organized an external quality control study on the reliability of current histamine determinations in European laboratories. Three lyophilized plasma quality control samples, in duplicate, covering the normal and pathological range of histamine concentrations (0-45 nmol/l), two different aqueous histamine standard samples and one solvent sample were sent to 10 laboratories for the analysis of their histamine content. The following methods were used: gas chromatography-mass spectrometry (n = 2), enzymatic single isotopic assay (n = 1), fluorometric-fluoroenzymatic assay (n = 3), radioimmunoassay (n = 3) and high performance liquid chromatography (n = 2). The study was performed and evaluated according to the approved recommendations (1983) of the International Federation of Clinical Chemistry (IFCC). The target values +/- s.d. of the three plasma samples were: 39.5 +/- 4.6 nmol/l (CV = 11.6%), 2.3 +/- 2.2 nmol/l (CV = 96%) and 8.9 +/- 1.5 nmol/l (CV = 17%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Reliability of current techniques for histamine determination in human plasma: the European external quality control study 1988.

The increasing importance of measuring histamine in many clinical conditions and the variety of currently used techniques enforced us to organize an external quality control study (ring study) on the reliability of histamine measurements in European laboratories. Three plasma quality control samples in duplicate (lyophilized) with different amounts of histamine (0-5 ng/ml), two different aqueous histamine standard samples and one solvent sample were sent to 10 laboratories for analysis of their histamine content. The following methods were used: gas chromatographic-mass-spectrometric technique (n = 2), single isotope assay (n = 1), fluorometric-fluoroenzymatic assay (n = 3), radioimmunoassay (n = 3), HPLC technique (n = 2). The study was performed and evaluated according to the approved recommendation (1983) of the International Federation of Clinical Chemistry (IFCC). This first report of the study is concentrated on the imprecision and inaccuracy of the different principal methods and laboratories by comparing two unrelated plasma histamine samples of different analyte concentrations (target values and SD: 4.39 +/- 0.51 ng/ml and 0.99 +/- 0.17 ng/ml). This study showed a fairly good agreement between most participants. 7/11 results obtained with 4 different methods were accurate and precise in the plasma range of histamine (Youden plot). Results outside the borderlines turned out to be a problem of the analyst rather than the method itself. It is suggested to define reference values for plasma histamine and to establish reference laboratories and methods according to the IFCC-guidelines.

Increased urinary excretion of the histamine metabolite N tau-methylhistamine during acetylsalicylic acid provocation in chronic urticaria patients.

Seventeen chronic urticaria patients with a history suggestive of acetylsalicylic acid (ASA, Aspirin)-intolerance were challenged with ASA; only 2 patients showed marked clinical reactions. These clinical reactions were accompanied by a significant increase in the urinary excretion of the most important histamine metabolite, N tau-methylhistamine, in comparison with 15 non-responders (p less than or equal to 0.05) and placebo test. These results suggest an involvement of histamine in the pathogenesis of ASA-intolerance in chronic urticaria patients.

Correlation between urinary levels of histamine metabolites in 24-hour urine and morning urine samples of man: influence of histamine-rich food.

In this study, we have determined and correlated the excretion of the 2 most important histamine metabolites, N tau-methylhistamine and N tau-methylimidazoleacetic acid, in 24-hour urine and morning urine samples of 14 normal healthy persons. We found no significant difference between morning urine and 24-hour urine samples, provided that the subjects were on a histamine-poor diet for at least 24 hours. We also studied the influence of the consumption of histamine-rich foodstuffs on the reliability of these parameters. The morning urinary N tau-methylhistamine excretion is less affected by histamine-rich food-stuffs and therefore proposed to be the most reliable parameter for endogeneous histamine release.

Changes in histamine synthesis, tissue content and catabolism in human breast cancer.

The present study in 10 breast cancer patients supports the concept that newly synthetized, nascent histamine is involved in tumour growth. Histidine decarboxylase (HDC) activity is increased in mammary tumour tissue compared to healthy mammary gland-, skin- and muscle tissue in all but one patient studied. The newly formed histamine is probably not stored in the tumour tissue. Significantly decreased histamine concentrations were measured in parallel samples in the tumour tissue. Moreover, the preliminary results from urinary analysis of histamine and N tau-methylhistamine in 3 of the 10 patients studied showed a significant decline after tumour extirpation compared to preoperative values.

Age dependent normal values of histamine and histamine metabolites in human urine.

We collected morning urine samples from normal healthy persons, who had not yet breakfasted, in the age range of 2-61 years and measured urinary excretion of histamine and its metabolites N tau-methyl-histamine and N tau-methylimidazoleacetic acid. The values obtained (expressed in terms of urinary creatinine excretion), were age dependent up to the age of 12. Thereafter, values stabilized and were no longer age dependent.

Histamine metabolism after adverse reactions due to d-tubocurarine administration.

We investigated histamine release in five female patients, submitted for gynaecological surgery, after intravenous administration of the neuromuscular blocking agent d-tubocurarine. In these patients, we measured the plasma levels of histamine and its metabolites, N tau-methylhistamine and N tau-methylimidazoleacetic acid, making use of mass fragmentographic methods. The newly developed determination of plasma N tau-methylimidazoleacetic acid had a within-day coefficient of variation of 2.7% (n = 10). Normal values of N tau-methylimidazoleacetic acid in plasma ranged from 41.3-75.6 nmol/l (n = 13). All five patients developed anaphylactoid reactions: two patients showed severe systemic reactions, one patient a minor systemic reaction and two had skin reactions only. Plasma histamine and N tau-methylhistamine levels appeared to be the most reliable biochemical parameters for confirming both the occurrence and severity of an anaphylactoid reaction. In comparison with plasma histamine, the determination of plasma N tau-methylhistamine is less hampered by artefacts caused by blood collection and plasma preparation. Together with the fact that the increase in plasma N tau-methylhistamine levels after anaphylactoid reactions lasts much longer than the increase in plasma histamine levels, this leads to the conclusion that the determination of plasma N tau-methylhistamine is a useful retrospective parameter for histamine release in this type of pathological state. The plasma N tau-methylimidazoleacetic acid levels fluctuated considerably, showing only a significant increase after administration of d-tubocurarine in the two patients who had severe anaphylactoid reactions. This parameter is, therefore, less useful in such studies.

Urinary histamine excretion in proteinuric states.

The kidney possesses the enzymatic steps required for the biosynthesis of histamine and this autocoid may play a role in modulating renal hemodynamics and the local inflammatory response to immunologic injury. We, therefore, measured urinary histamine. N-methylhistamine and N-methylimidazole acetic acid concentrations in patients with proteinuria due to a variety of disease states-idiopathic nephrotic syndrome (n = 19), systemic lupus erythematosus (n = 10), refractory focal segmental glomerulosclerosis (n = 10) and control patients (n = 16). Urinary histamine concentration was significantly reduced in treatment-responsive idiopathic nephrotic syndrome during disease relapse compared to remission (16.6 +/- 3.6 vs. 28.4 +/- 4.8 mumol/mol creatinine, p less than 0.02). The levels were also depressed in children with other causes of persistent proteinuria, including systemic lupus erythematosus (10.3 +/- 4.0 mumol/mol creatinine) and focal segmental glomerulosclerosis (14.6 +/- 2.8 mumol/mol creatinine) compared to normal controls (31.4 +/- 4.7 mumol/mol creatinine). The decreased urinary excretion of histamine and its metabolites in patients with proteinuria may be a result of immunologically mediated mesangial cell injury or represent a compensatory hemodynamic response to limit urinary protein losses.

Zinc in plasma and serum: influence of contamination due to the collection tubes.

The contamination caused by rubber stoppers of collection tubes preceding the determination of zinc in plasma and serum was investigated. The use of evacuated blood collection tubes (EBC-tubes), normally used for the collection of serum samples, could give rise to an average artificial increase of normal serum zinc concentrations of about 250%. Heparin containing EBC-tubes, used for the collection of plasma, and plain EBC-tubes of an experimental production appeared to be suitable for correct zinc determinations. There was no difference between the serum and plasma zinc levels of fifty volunteers.

Zinc absorption after oral administration of zinc sulfate.

The administration of 200 mg of ZnSO4.7H2O to six normal healthy males gave rise to increased serum zinc levels when this drug was taken in a fasting state, whereas administration during a light meal caused no increased levels.