The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin.

BACKGROUND: Iron deficiency (ID) is the main cause of hyporesponsiveness to erythropoietin in haemodialysis patients and its detection is of value since it is easily corrected by intravenous iron. Markers of iron supply to the erythron, including erythrocyte zinc protoporphyrin (Er-ZPP), percentage of hypochromic erythrocytes (Hypo), reticulocyte haemoglobin content (CHr) and soluble transferrin receptor (sTfR), may be more accurate predictors of ID than ferritin (Fer) and transferrin saturation (TSat), but relative diagnostic power and best threshold values are not yet established. METHODS: In 125 haemodialysis patients on maintenance erythropoietin, the diagnostic power of the above parameters was evaluated by ROC curve, multivariate regression, and stepwise discriminant analyses. Diagnosis of ID was based on haemoglobin response to intravenous iron (992 mg as sodium ferric gluconate complex over an 8-week period). RESULTS: Fifty-one patients were considered iron deficient (haemoglobin increase by 1.9+/-0.5 g/dl) and 74 as iron replete (haemoglobin increase by 0.4+/-0.3 g/dl). ROC curve analysis showed that all tests had discriminative ability with the following hierarchy: Hypo (area under curve W=0.930, efficiency 89.6% at cut-off >6%), CHr (W=0.798, efficiency 78.4% at cut-off < or =29 pg), sTfR (W=0.783, efficiency 72.4% at cut-off >1.5 mg/l), Er-ZPP (W=0.773, efficiency 73.0% at cut-off >52 micromol/mol haem), TSat (W=0.758, efficiency 70.4% at cut-off <19%) and ferritin (W=0.633, efficiency 64.0% at cut-off <50 ng/ml). Stepwise discriminant analysis identified Hypo as the only variable with independent diagnostic value, able to classify 87.2% of patients correctly. Additional tests did not substantially improve diagnostic efficiency of Hypo >6% alone. CONCLUSIONS: In haemodialysis patients on maintenance erythropoietin, Hypo >6% is the best currently available marker to identify those who will improve their response after intravenous iron. Cost-effectiveness suggests that this parameter should be a first-line tool to monitor iron requirements in clinical practice.

Dextromethorphan test for evaluation of congenital predisposition to lung cancer.

We report the results of an investigation conducted in 992 healthy control subjects (854 adults and 138 adolescents) and in 116 subjects with lung cancer (LC) for the purpose of detecting those individuals with a possible genetic predisposition to lung cancer. The test consists of the oral administration of 64 mumol of dextromethorphan (DMP) with collection of urine samples over the following 8-h period and urine assay of the drug (DMP) and its main metabolite, dextrorphan (DOP). The ratio of the urinary concentrations of DMP to those of DOP is called the metabolic ratio (DMP/DOP) and is inversely proportional to the DMP demethylation rate. The pattern of the metabolic ratio (Log10 DMP/DOP) allowed, using a maximum likelihood approach, the identification of three subpopulations in the 854 control subjects (adults): (1) probable homozygous extensive metabolizers with Log10 DMP/DOP < -1.74 (73.1 percent); (2) probable heterozygous intermediate metabolizers with Log10 DMP/DOP in the -1.74 to -0.40 range (22.3 percent); and (3) probable homozygous poor metabolizers with Log10 DMP/DOP > -0.4 (4.6 percent). Most of the patients with LC (89 percent) were probable homozygous extensive metabolizers. As the latter have a cancer risk that is 2.54-fold greater than that of intermediate metabolizers (95 percent confidence interval [CI]: 1.37 to 4.73) and 7.43-fold greater than that of poor metabolizers (95 percent CI: 1.01 to 54.5), their identification by means of the DMP test may be particularly useful for subjects exposed to environmental and occupational carcinogens. The phenotype test used is similar to that of the debrisoquin test, but presents the advantage that DMP is a widely used, harmless drug with a faster and simpler urinary assay procedure.

Predisposition to LDL oxidation in patients with and without angiographically established coronary artery disease.

Oxidative modification of low density lipoprotein (LDL) may play an important role in the mechanism of atherosclerotic damage to blood vessels. In the present study the LDL isolated from the plasmas of 73 coronary artery disease (CAD) patients, 28 valvular heart disease (VHD) patients, 59 subjects affected by type IIa hyperlipoproteinemia and 71 controls was oxidatively modified by incubation with copper ions. In 15 CAD and 15 Type IIa patients and 15 controls the LDL chemical composition and polyunsaturated fatty acid (PUFA) content were also measured. Differences in the LDL susceptibilities to lipid peroxidation were studied by measuring the changes of fluorescence intensity. The lag phase in the CAD patients was found to be significantly lower than in the VHD and controls (P < 0.001). The lag phase in the type IIa patients was significantly higher than in the CAD patients (P < 0.01), and significantly lower than the VHD and controls (P < 0.01). The LDL isolated from the type IIa patients had an increase in the relative content of free and esterified cholesterol (P < 0.05), while the CAD patients had a decrease in the relative content of free cholesterol (P < 0.05), and an increase in the relative content of protein (P < 0.05). The lowest value of the LDL cholesterol to protein ratio and LDL size, was found in the CAD patients (P < 0.05). When expressed in micrograms/mg LDL cholesterol, the concentration of the LDL PUFAs was significantly higher in the CAD group than in the others (P < 0.05). The LDL alpha-tocopherol concentration was quite similar in the different groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzene in the blood and breath of normal people and occupationally exposed workers.

Benzene was measured in blood and alveolar air of 168 men, aged 20-58 years, subdivided into four groups: blood donors, hospital staff, chemical workers occupationally exposed to benzene, and chemical workers not occupationally exposed to benzene. The group of exposed workers was employed in work places with a mean environmental exposure to benzene of 1.62 mg/M3 (8 hr TWA). Non-exposed workers were employed elsewhere in the same plant, with an environmental exposure to benzene lower than 0.1 mg/M3. Blood and alveolar air samples were collected in the morning, before the start of the work shift for the chemical workers. The group of exposed workers was found to be significantly different from the other three groups, both for blood and alveolar benzene concentrations. The mean blood benzene concentration was 789 ng/l in the exposed workers, 307 ng/l in the non-exposed workers, 332 ng/l in the hospital staff, and 196 ng/l in the blood donors. Apart from the exposed workers, blood benzene concentration was significantly higher in smokers than in non-smokers. The mean alveolar benzene concentration was 92 ng/l in the exposed workers, 42 ng/l in the non-exposed workers, 22 ng/l in the hospital staff, and 11 ng/l in the blood donors. Alveolar benzene concentration was significantly higher in smokers than in non-smokers in the groups of the hospital staff and non-exposed workers, but not in the blood donors and exposed workers. In the three groups without occupational exposure considered altogether, the alveolar benzene concentration correlated significantly with environmental benzene concentration measured at the moment of the individual examinations, both in the smokers (r = .636; p less than .001) and non-smokers (r = .628; p less than .001). In the same three groups and in the exposed workers, alveolar benzene concentration showed a significant correlation with the blood benzene concentration.

Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure.

Benzene, toluene, cumene and styrene were measured in the breath and blood of two groups of individuals. The first group included individuals belonging to a hospital staff, the second group included chemical workers who were not exposed to the abovementioned chemicals. The chemical workers were examined in plant infirmaries on the morning before the start of the workshift, and the hospital staff in the hospital infirmaries. One environmental air sample was taken in the infirmaries for each individual at the moment of the biological samplings. The environmental concentrations of benzene and styrene were significantly higher in the infirmaries of the chemical plant than in the infirmaries of the hospital. On the other hand, the environmental concentrations of toluene and cumene were not significantly different in the plant infirmaries and in the hospital infirmaries. In the hospital staff the alveolar concentrations of benzene, toluene and styrene were significantly lower than those in the chemical workers. In the hospital staff the blood concentrations of benzene, toluene and styrene were not significantly different from those in the chemical workers. Only the blood cumene concentration was significantly higher in the chemical workers. In hospital staff, smokers showed alveolar and blood concentrations of benzene and toluene that were significantly higher than those measured in the non smoker hospital staff. With reference to chemical workers, only alveolar benzene concentration was significantly higher in smokers than in non smokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental and occupational exposure to benzene by analysis of breath and blood.

Benzene exposure of chemical workers was studied, during the entire workshift, by continuous monitoring of workplace benzene concentration, and 16 hours after the end of the workshift by the measurement of alveolar and blood benzene concentrations and excretion of urinary phenol. Exposure of hospital staff was studied by measuring benzene concentrations in the alveolar and blood samples collected during the hospital workshift. Instantaneous environmental air samples were also collected, at the moment of the biological sampling, for all the subjects tested. A group of 34 chemical workers showed an eight hour exposure to benzene, as a geometric mean, of 1.12 micrograms/l which corresponded, 16 hours after the end of the workshift, to a geometric mean benzene concentration of 70 ng/l in the alveolar air and 597 ng/l in the blood. Another group of 27 chemical workers (group A) turned out to be exposed to an indeterminable eight hour exposure to benzene that corresponded, the morning after, to a geometric mean benzene concentration of 28 ng/l in the alveolar air and 256 ng/l in the blood. The group of hospital staff (group B) had a benzene concentration of 14 ng/l in the alveolar air and 269 ng/l in the blood. Instantaneous environmental samples showed that in the infirmaries the geometric mean benzene concentration was 58 ng/l during the examination of the 34 chemical workers, 36 ng/l during the examination of the 27 chemical workers (group A), and 5 ng/l during the examination of the 19 subjects of the hospital staff (group B). Statistical analysis showed that the alveolar and blood benzene concentrations in the 34 workers exposed to 1.12 microgram/l of benzene differed significantly from those in groups A and B. It was found, moreover, that the alveolar and blood benzene concentrations were higher in the smokers in groups A and B but not in the smokers in the group of 34 chemical workers. The slope of the linear correlation between the alveolar and the instantaneous environmental benzene concentrations suggested a benzene alveolar retention of about 55%. Blood and alveolar benzene concentrations showed a highly significant correlation and the blood/air partition coefficient, obtained from the slope of the regression line, was 7.4. In the group of the 34 chemical workers no correlation was found between the TWA benzene exposure and the urinary phenol excretion.

Ethylene oxide exposure. Biological monitoring by analysis of alveolar air and blood.

Occupational exposure to ethylene oxide (ETO) was studied in ten workers employed in a hospital sterilizer unit by testing environmental air, alveolar air and blood during and at the end of the workshift. Alveolar (Ca) and blood (Cb) ETO concentrations were correlated with each other (r = 0.744, n = 36, P less than 0.001) and both with the environmental (Ci) concentrations (r = 0.947, n = 144, P less than 0.001; r = 0.827, n = 36, P less than 0.001). The alveolar retention of ETO (1-Ca/Ci) was equal to 75-80% of the inhaled ETO. In comparison with a blood/air partition coefficient equal in vitro to 90 (SD = 20), the mean Cb/Ca ratio found in the exposed workers was equal to 12-17. During work the blood ETO concentration was, on average, three times the environmental ETO concentration.