Carbohydrate-deficient transferrin in relation to the menopausal status of women.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) has been reported as an excellent marker for male alcohol abuse. Little is known about its validity among women, in whom rather conflicting data concerning the efficiency of the CDT marker and its biochemical mechanism have been reported. Moreover, it is not clear why the reference ranges are different for women (0 to 26 Units per liter) and men (0 to 20 Units per liter). METHODS: In this population-based study, we examined the normal CDT values measured by CDTect in 331 healthy female teetotalers, randomly selected from a large cohort. They were divided into four groups: premenopausal women (n = 76), perimenopausal women (n = 86), postmenopausal women (n = 84), and users of estrogens/progestagens (n = 85). RESULTS: The mean of the CDT value in the premenopausal group (15.2 Units per liter) was significantly higher than the mean in the postmenopausal group (13.6 Units per liter; p < 0.016). In pre- and perimenopausal women, higher CDT levels were associated with the last period of menstruation; for women menstruating less than 1 month ago versus longer ago, the mean serum CDT value was 15.4 vs. 13.0 Units per liter (p < 0.01). CONCLUSIONS: The premenopausal state seems to increase serum levels of CDT, probably due to the amount and frequency of blood loss during the menstrual period, and should be considered when interpreting CDT values in women.

Test characteristics of carbohydrate-deficient transferrin and gamma-glutamyltransferase in alcohol-using perimenopausal women.

BACKGROUND: The application of biochemical markers to detect heavy alcohol use in women has shown disappointing results until now. We evaluated carbohydrate-deficient transferrin (CDT) by the CDTect method and gamma-glutamyltransferase (GGT) in a large cohort of alcohol-using perimenopausal women studied primarily for osteoporosis. METHODS: CDT and GGT were measured in 431 women aged 46 to 54 years, who were selected from a large cohort (n = 8503) of pre-, peri-, and postmenopausal women. Their alcohol intake was known from questionnaires and face-to-face interviews. Three groups were constructed for statistical analysis: those drinking on average less than 7 alcoholic drinks per week (n = 103), those drinking 7 to 34 per week (n = 280), and those drinking at least 35 per week (n = 48). RESULTS: The mean values of CDT and GGT of the three groups increased with an increasing alcohol intake, but there was a poor correlation between CDT and GGT in the complete study group (r = 0.3). The specificities of CDT and GGT were comparable, 83% and 78%, respectively. The sensitivities for CDT and GGT were 30% and 50%, respectively. A logistic regression model could assign, overall, 77% of the women correctly in relation to their alcohol intake: 43% of the women drinking at least 35 drinks per week and 92% of the women drinking less than 7 drinks per week. CONCLUSIONS: The test characteristics of both GGT and CDT are not good enough to be used as biochemical markers for detecting heavy alcohol use in women. The use of a logistic regression model offers an advantage, because both numeric values of CDT and GGT are taken into account instead of arbitrary cutoff values.

The prevalence of low bone mineral density in Dutch perimenopausal women: the Eindhoven perimenopausal osteoporosis study.

The aim of this study was to estimate the prevalence of osteopenia and osteoporosis in perimenopausal women, and to assess determinants of low bone mineral density (BMD). All women born between 1941 and 1947 (aged between 46 and 54 years) living in the city of Eindhoven were invited to participate in the study: 5896 white Dutch women, representing 73% of the total number of Dutch women in this age group, were studied. Of these, 24% were using estrogen preparations and 19% had undergone hysterectomy, with or without oophorectomy. All women were interviewed and bone mineral density (BMD) of the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA). Osteopenia and osteoporosis were defined according to the criteria proposed by a WHO working group. In the population studied the prevalence of osteopenia and osteoporosis was 27.3% and 4.1%, respectively. With progression from premenopause to menopause, the prevalence of osteoporosis increased from 0.4% to 12.7%, and that of osteopenia from 14.5% to 42.8%. An increased risk for low BMD (osteopenia and osteoporosis) was associated with age, menopausal status and smoking, while alcohol consumption, high body mass index (BMI) and use of estrogens had a protective effect. This study of a large population-based cohort of perimenopausal women revealed a high prevalence of low bone mass and, therefore, a higher risk for osteoporotic fractures. The data further suggest that, when issues on the long-term efficacy and safety of preventive treatments are resolved, it may be possible to identify women at higher risk who are most likely to benefit from screening strategies.

The effect of transrectal ultrasonography (TRUS) including digital rectal examination (DRE) of the prostate on the level of prostate specific antigen (PSA).

OBJECTIVE: To study the effect of transrectal ultrasonography (TRUS) including digital rectal examination (DRE) of the prostate on serum prostate specific antigen (PSA). PATIENTS AND METHODS: In a diagnostic centre for general practitioners serum PSA was determined in patients before, immediately after, and one week after TRUS including DRE. In a small group of patients PSA was determined at various times after DRE and TRUS. RESULTS: The PSA levels showed a statistically significant rise of 20% immediately after DRE and TRUS. After 7 days the PSA levels had returned to their initial levels. This decrease appeared to occur within the first 24 h. CONCLUSION: When applying the diagnostic triad PSA, DRE and TRUS blood samples for PSA should preferably be taken before DRE and TRUS. If blood samples are taken afterwards, it is safe to do so after seven days.

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)

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.

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.

The beta-adrenergic system of non-allergic patients with chronic airflow obstruction and early morning dyspnoea.

Lymphocyte beta-adrenergic receptor function and urinary excretion of catecholamines were measured in eight non-allergic patients with partially reversible chronic airflow obstruction (CAO) and early morning dyspnoea (EMD), and in eight matched healthy control subjects. In order to establish a possible relationship between the early morning dyspnoea and a reduced beta-adrenergic activity, these parameters were measured during the "morning dip" in FEV1 and in the afternoon, when lung function is maximal. No differences were observed for lymphocyte beta-adrenergic receptor characteristics (beta-receptor number, Kd, for 3H-dihydroalprenolol, and cAMP response to isoproterenol) between patients and controls, when determined at 8 AM or at 4 PM. Nor was there a significant circadian variation in these parameters present in both groups. By contrast, the patients showed a significantly reduced urinary excretion of epinephrine and norepinephrine, as measured in four-hourly urine portions collected between 8 and 12 AM and between 4 and 8 PM, respectively. In addition, the urinary excretion of epinephrine showed a significant circadian variation in the patients, which was correlated with the FEV1 (% predicted). Such a relationship was not found for norepinephrine. The results suggest that a (generalized) dysfunction of the beta-adrenergic receptor is not involved in the pathogenesis of CAO or EMD. However, reduced beta-adrenergic receptor stimulation due to decreased levels of catecholamines may contribute to the observed (variation in) airflow obstruction of the patients.

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.

Effects of isoprenaline and terbutaline on urinary excretion of histamine and its two main metabolites in systemic mastocytosis.

Both short-term and long-term effects of the beta-sympathomimetic drugs isoprenaline and terbutaline on the urinary excretion of histamine and its two main metabolites were evaluated in patients with systemic mastocytosis. In a short-term study isoprenaline and terbutaline were given intravenously during five hours to three and two patients, respectively. Compared with placebo infusion Nt-methylhistamine excretion fell during terbutaline administration, whereas during isoprenaline no changes were observed. In a long-term study three patients received a treatment with orally administered terbutaline for 24 days. In one patient a slight reduction of the excretion of the histamine metabolites was found. In another patient the excretion of histamine and its metabolites decreased especially during the eight days observation period after the end of the treatment. In this study we saw occasionally large and rapid changes occurring simultaneously in all three urinary parameters of histamine release. In conclusion, terbutaline can reduce histamine release in systemic mastocytosis. However, because of the small symptomatic and biochemical effects found in our patients, the clinical significance of beta-sympathomimetic drug treatment in this disease has yet to be established.

Influence of slow-release terbutaline on the circadian variation of catecholamines, histamine, and lung function in nonallergic patients with partly reversible airflow obstruction.

In order to study the mechanism underlying early morning dyspnea in patients with chronic airflow obstruction, the relation was assessed between the diurnal variation of FEV1, plasma and urinary catecholamines, and urinary histamine (metabolites) in eight nonallergic patients (mean age, 53 years). These parameters were measured both after administration of placebo and slow-release terbutaline tablets during 1 week. The fall in FEV1 at 4 A.M. coincided with a fall in both plasma and urinary epinephrine levels, whereas no correlation between pulmonary function and norepinephrine levels was observed. Histamine and N tau -methylhistamine excretion were found within the normal range without a circadian rhythm, suggesting no important role for histamine in the occurrence of early morning dyspnea in this nonallergic patient group. Administration of slow-release terbutaline during 1 week prevented the nocturnal fall in FEV1. Terbutaline treatment suppressed plasma and urinary levels of epinephrine significantly without any effect on norepinephrine. We conclude that epinephrine appears to be an important factor in the regulation of the bronchial smooth muscle tone in patients with early morning dyspnea.

Influence of the parasympathetic and sympathetic nervous system on nocturnal bronchial obstruction.

To determine whether an autonomic nervous system imbalance might underlie the nocturnal dyspnoea in patients with chronic airflow obstruction (CAO), we determined FEV1, sinus arrhythmia gap (SA gap), heart rate and urinary adrenaline and noradrenaline excretion every 4 h over 24 h. Measurements were performed in eight non-allergic patients with CAO and eight age- and sex-matched normal controls. The amplitude of the circadian changes in FEV1 in patients and controls was 27 +/- 2% and 7 +/- 1% respectively (P less than 0.001). Both an increased SA gap and a decreased heart rate are features of increased vagal activity. This vagal activity was significantly increased in patients, compared with normal controls (difference P less than 0.01), the difference being maximal at night. This increased activity might contribute to a bronchial obstruction in these patients. Urinary adrenaline excretion was significantly higher by day than by night in both patients and normal controls (P less than 0.01). The urinary levels of adrenaline in the patients were significantly decreased at all hours of observation as compared with levels in normal controls (P less than 0.05). Urinary noradrenaline levels were significantly lower in patients as compared with normal subjects (P less than 0.01), and lower by night than by day. Urinary histamine and Nt-methylhistamine excretion were in the normal range in each individual. Urinary levels, however, were significantly higher in patients at all hours of observation (P less than 0.05). No circadian rhythm was shown. Plasma cortisol levels showed a normal circadian variation, similar in patients and normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of N tau-methylhistamine concentrations in plasma and urine as a parameter for histamine release during anaphylactoid reactions.

N tau-methylhistamine concentrations in plasma and urine were determined using a newly developed simultaneous determination for histamine and N tau-methylhistamine, based on isotope dilution mass fragmentography. Three groups of patients were investigated: patients receiving intravenously-administered iodamide for excretory urography, patients receiving a wasp-sting challenge, and patients treated with an intravenously-administered muscle relaxant. In all patients showing a distinct systemic anaphylactic or anaphylactoid reaction histamine and N tau-methylhistamine concentrations were found to be elevated. From the results of this study it can be concluded that N tau-methylhistamine in plasma and urine is a good parameter for histamine release, and that the determination of this histamine metabolite are less hampered by possible artefacts (due to basophil disrupture, a very short half-life time or bacterial production) than determinations of histamine itself.

Histamine in late asthmatic reactions following house-dust mite inhalation.

In order to investigate the role of histamine in the late asthmatic reaction (LAR) following house-dust mite (HDM) inhalation, we studied, with hourly intervals, urinary N tau-methylhistamine (an important metabolite of histamine) in 14 allergic asthmatic patients before and after broncho provocation with HDM. Four patients showed an early asthmatic reaction (EAR), while 10 patients developed a LAR as well. In the hour following the EAR a significant increase in urinary N tau-methylhistamine was observed as compared to the control day (0.01 less than p less than 0.05). During the LAR no increase of this metabolite was detected in the urine of the patients. Additionally, histamine was measured in broncho alveolar lavage fluid (BAF) obtained from 6 patients during the HDM-provoked LAR and compared to histamine levels in BAF from patients without a LAR, following broncho provocation. In the LAR group higher histamine levels were found than in the other patient and control groups. For the whole patient group no correlation was found between the degree of bronchial obstruction during the LAR and the BAF histamine values. No difference was found in N tau-methylhistamine in BAF between patients with LAR and controls. Thus histamine metabolite studies in the urine failed to provide evidence of involvement of histamine in the LAR, while further data are needed to interpret the results of local sampling in the lung.

Effect of beta-adrenergic stimulation on the circulatory lymphocyte count: studies in normals and in patients with chronic airflow obstruction.

In eight non-allergic patients with chronic airflow obstruction (CAO) and eight age and sex matched, healthy control subjects the circadian variation in circulatory lymphocyte count was studied in relation to serum cortisol and urinary epinephrine levels. In addition, we investigated the effect of the beta-adrenergic agent terbutaline on the lymphocyte count in two ways: as a long-term effect after 8 days of oral slow-release terbutaline with constant diurnal and nocturnal serum levels in patients, and as a short-term effect by a constant rate infusion of 0.2 micrograms/min over 4 hr in normals. Both patients and controls showed similar circadian patterns of urinary epinephrine excretion and lymphocyte counts. Patients with CAO, however, had significantly lower epinephrine levels and significantly higher lymphocyte counts at all hours of observation (every 4 hr from 0800 to 0800 hr the next day), as compared with normal controls. After 8 days of slow-release terbutaline the lymphocyte count in the patient group decreased to levels not significantly different from that of normals. The circadian rhythm of the lymphocytes, however, persisted under terbutaline therapy. No correlation existed between the lymphocyte count modulating factor, serum cortisol and the lymphocyte count over 24 hr. On placebo infusion in the control persons an increase of lymphocytes over 4 hr occurred, as a consequence of circadian rhythmicity. On terbutaline infusion a significant increase of lymphocytes after 1 hr was followed by a decrease to levels significantly below those on the placebo day. The same pattern was found in the leucocyte count. From this study it is concluded that beta-adrenergic stimulation corrects the relative lymphocytosis to counts comparable with normals. Other coinciding factors must regulate, however, the circadian rhythmicity.

Effect of oral slow-release terbutaline on early morning dyspnoea.

Eight male patients with partly reversible airflow obstruction, who had a diurnal variation in peak expiratory flow rate (PEFR) of more than 20% were treated with placebo and slow-release terbutaline tablets (5 mg at 08.00 hours and 10 mg at 20.00 hours) for 8 days. On Day 8 of each period, PEFR and serum terbutaline were measured at 4 and 2-h intervals, respectively. PEFR on the terbutaline day showed a significant increase at 08.00, 12.00, 24.00, 04.00 and 08.00 hours as compared to the placebo day. Slow-release terbutaline prevented early morning dyspnoea. The serum concentration was 3.3 ng/ml during the day and 3.5 ng/ml during the night. During terbutaline therapy the patients reported fewer complaints than during the placebo period. It was concluded that slow-release terbutaline tablets are suitable for twice daily treatment.

Urinary excretion of histamine and some of its metabolites in man: influence of the diet.

Urinary excretions of histamine, N tau-methylhistamine and N tau-methylimidazoleacetic acid have been determined in 10 normal subjects on 3 different diets, containing a very low protein, a low protein and a high protein amount. Foodstuffs which could contain histamine were excluded. The mean excretion of N tau-methylhistamine on the second day of each diet amounted to 0.861 mumol/24 h, 1.051 mumol/24 h and 1.378 mumol/24 h, respectively. The excretions of histamine and N tau-methylimidazoleacetic acid were not affected. In 6 normal persons on a protein low diet, the excretions of histamine, N tau-methylhistamine and N tau-methylimidazoleacetic acid have been determined for 10 days. On the fifth day, to 3 persons 200 mumol of histamine was given orally, the other 3 persons received a high protein diet. The persons receiving histamine showed a strongly enhanced excretion of N tau-methylimidazoleacetic acid, corresponding to 36.1% of the administered histamine, whereas the urinary excretions of histamine and N tau-methylhistamine were only slightly elevated. On the high protein diet, only the excretion of N tau-methylhistamine was slightly elevated. The urinary excretions of histamine in the female subjects sometimes showed unexpectedly high values. Most probably, this phenomenon is attributable to bacterial histamine production in the urogenital tract.

Influence of decontamination of the digestive tract on the urinary excretion of histamine and some of its metabolites.

Urinary excretions of histamine, N tau-methylhistamine and N tau-methylimidazoleacetic acid have been determined for 8 healthy volunteers during 14 consecutive days. Selective decontamination of the digestive tract was performed from day 3 to day 6, followed by total decontamination from day 7 to day 10. Urinary excretions of N tau-methylhistamine and N tau-methylimidazoleacetic acid decreased to a small though significant degree (about 15-20%) after total decontamination, suggesting a histamine production by anaerobic bacteria. Cadaverine decreased for about 70% under both selective and total decontamination, suggesting that this amine in human urine mainly originates from aerobic bacteria in the intestinal tract.