Biomedical subjects

P Apostoli

Publications and source records attributed to P Apostoli.

At least 73 records · Page 4Linked to original sources

PubMed1996

Quality assurance in occupational and environmental laboratory medicine.

In a medical laboratory service, quality assurance (QA) concerns all those actions necessary to provide confidence that the results of laboratory tests will satisfy defined standards for quality. Taking into account the type of testing concerned and the techniques involved, quality assurance will encompass all steps taken to ensure that laboratory results are reliable. It covers the use of scientifically and technically sound practices for laboratory investigations, including selection, collection, transport, identification, storage, preparation and manipulation of specimens and recording, reporting and interpretation of the results. QA refers also to other activities designed to improve the reliability of investigations such as staff training and management, evaluation of the adequacy of the laboratory environment, maintenance and calibration of instruments and the use of technically validated and properly documented methods. All these activities should be described in a quality manual. This document is a prerequisite to obtain certification of the quality system or laboratory accreditation, according to the International Standard ISO 29000 series or the European Standard EN 45001, respectively.

Accreditation↗

PubMed1996

Inductively coupled plasma mass spectroscopy quantitation of platinum-DNA adducts in peripheral blood leukocytes of patients receiving cisplatin- or carboplatin-based chemotherapy.

Platinum-DNA adducts can be assayed in peripheral blood leukocytes by means of atomic absorption spectroscopy and ELISA, and high adduct levels have been correlated previously with favorable clinical response to platinum-based chemotherapy. Our purpose was to study adduct formation in peripheral blood leukocytes by means of a new method, inductively coupled plasma mass spectroscopy (ICP-MS), and to correlate adduct formation with clinical response and toxicity. Platinum (Pt)-DNA adducts were measured by means of ICP-MS in leukocytes of 66 patients receiving a cisplatin- or carboplatin-based chemotherapy, collected either before the beginning of treatment and incubated in vitro with cisplatin or 1 and 24 h after the administration of drug to the patient. The Pt-DNA adduct level in leukocytes from patients exposed to drug in vitro was 14.33 +/- 14.71 fmol/microgram DNA (mean +/- SD), which was not significantly different from the value of 23.4 +/- 19.53 fmol/microgram DNA observed in leukocytes from nine healthy volunteers. In samples collected after the administration of chemotherapy, Pt-DNA adducts ranged from 1.91 +/- 3.59 fmol/microgram DNA (mean +/- SD) at the 1-h time point to 2.61 +/- 3.35 fmol/microgram DNA at 24 h (P > 0.05). Adduct levels in leukocytes exposed in vitro did not correlate with adduct levels from patients treated with cisplatin-based chemotherapy (r = 0.085 and 0.011 at 1 and 24 h, respectively). At 24 h, adduct levels in patients receiving cisplatin (3.15 +/- 3.64 fmol/microgram DNA, mean +/- SD) were significantly higher (P = 0.02) than those observed in patients treated with standard dose carboplatin (0.57 +/- 0.73 fmol/microgram DNA) and also higher than those in patients receiving high-dose carboplatin (1.18 +/- 1.06 fmol/microgram DNA), although the latter difference did not reach statistical significance (P = 0.071). No differences in adduct levels (mean +/- SD) were evident between patients responsive (3.23 +/- 3.51 fmol/microgram DNA) and nonresponsive (2.34 +/- 3.01 fmol/microgram DNA) to chemotherapy. In the homogeneous group of patients treated with combination of cisplatin and 5FU, received dose intensity, hemoglobin decrease, and posttreatment creatinine could not be linked with the extent of leukocyte adduct formation. The data presented here demonstrate that ICP-MS allows the detection of adducts in patients treated with cisplatin or carboplatin and suggest that adduct formation in leukocytes is not a major determinant of response or toxicity.

Adult↗

PubMed1995

Influence of individual factors and personal habits on the levels of biological indicators of exposure.

The progressive improvement of hygienic conditions in the workplace has increased the importance of obtaining detailed information on extra-occupational factors that might influence the levels of the biological indicators. This information is indispensable both when subjects belonging to the general population are selected for establishing 'reference values' and when subjects occupationally exposed to specific chemical substances are studied. In non-occupationally exposed subjects the biological indicator levels may be influenced by circumstances which enhance absorption of the substance in question. Examples of interference factors considered for biological indicators of main metals are: gender, age, smoking habits, alcohol consumption and dietary habits. In occupationally exposed subjects the levels of the biological indicators can be influenced by factors that interfere with the metabolism of the substances absorbed in the workplace. In particular, factors such as alcohol, drugs and tobacco appear to play an important role in modifying the biological indicator levels in the occupationally exposed. Ethanol can inhibit as well as induce the metabolism of solvents. Inhibition occurs after excessive ingestion of ethanol, whereas induction occurs in subjects who regularly consume alcohol. There are several examples of inhibition of the metabolism of solvents by alcohol in man, occurring at levels of exposure frequently encountered in the workplace, also within the 'occupational exposure limits', (OEL). Conversely, there are very few studies on the effects of induction, which presumably occur only when the exposure levels greatly exceed OEL. Among drugs, analgesics seem to play a particular role in interfering with the metabolism of solvents. Since cigarette smoking is frequently associated with alcohol ingestion at present it is difficult to extrapolate the isolated effect of smoking on the metabolism of solvents. In order to facilitate interpretation of the results of biological monitoring, we propose to prepare informative sheets for the main substances which will contain information on factors that can influence the levels of the indicators.

Biomarkers↗

PubMed1995

Quality assurance in biomarker measurement.

Quality assurance (QA) concerns the validity of all the analytical processes (from collection of the samples to interpretation of the results). It is not an abstract concept but must be adapted to the different situations such as the different exposure levels, the different analytical methods, and the context of use (risk assessment procedures, research, routine determinations). The main requirements in QA programmes regard the control of all the known sources of preanalytical and analytical variations, while the instruments with which adequate QA can be implemented are the certified materials and the quality control programmes (quality manual, internal and external quality controls). Another important concept in QA is that measurements must be placed a different metrological levels: at the highest there are the methods (definitive, reference) to be used for assessing accuracy of routine methods. QA programmes should enable a grading of biomarkers (from experimental only to full evaluated) and of the laboratories in order to identify the significance of the test and to assess the level at which a laboratory could operate.

Biomarkers↗

PubMed1995

Peripheral markers of catecholamine metabolism among workers occupationally exposed to manganese (Mn).

In a preliminary study of 11 men randomly selected in a ferro-alloy plant and of 15 control subjects, platelet monoamine oxidase (MAO) and serum dopamine beta-hydroxylase (DBH) activities were measured. A tendency towards lower MAO-B activity in the exposed workers as compared to control subjects (t = 1.95; P = 0.06) was found whereas DBH activity was similar. In the exposed group, a dose-effect relationship was noted between a manganese (Mn) cumulative exposure index (CEI) and DBH activity (R2 = 0.40, P < 0.05). Since DBH is an expression of catecholamine release, the relative increase in such activity could be envisaged as a compensatory mechanism to a reduced turnover rate as reflected by MAO-B activity. Owing to the limited sample size, these findings should be confirmed by further epidemiological and experimental studies.

Adult↗

PubMed1995

Cisplatin pharmacokinetics using a five-day schedule during repeated courses of chemotherapy in germ cell tumors.

Total and ultrafilterable platinum (Pt) disposition was investigated during 49 courses of chemotherapy in 13 patients with germ cell tumor treated with cisplatin (DDP), 20 mg/m2/day on 5 consecutive days. The following pharmacokinetic parameters were analyzed: distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives, total body clearance (ClT), renal clearance (ClR), and areas under the concentration versus time curve (AUCs). Blood samples were collected immediately before and after DDP infusion (Day 1 through Day 5); in addition, on Day 5, samples were collected at 0.25, 0.5, 1, 8, 24, and 48 h after DDP infusion. Urine was collected during each day of treatment and up to 48 h after the last DDP dose. During each chemotherapy cycle plasma levels of total and ultrafilterable Pt progressively increased from the first to the last day of treatment. At the first cycle, total Pt concentrations ranged from 0.67 to 1.46 micrograms/ml (mean increase, 118%), and those of ultrafilterable Pt from 0.117 to 0.205 micrograms/ml (mean increase, 75%). Mean +/- SD total Pt plasma levels immediately postinfusion increased from 0.67 +/- 0.20 microgram/ml at the first cycle (first day of therapy) to 1.13 +/- 0.21 microgram/ml at the same time point at the fourth cycle. Mean total Pt peak levels were reached at the end of infusion on the last day of each cycle, and increased from 1.46 +/- 0.29 microgram/ml (first cycle) to 1.89 +/- 0.40 microgram/ml (fourth cycle). Total Pt was detectable in plasma before the beginning of all cycles following the first. As a result, AUC significantly increased and ClR significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure.

OBJECTIVES: The goal of this study was to assess long-term neurobehavioral effects associated with low airborne concentrations of manganese in a ferroalloy plant. METHODS: During a period of forced cessation of work (1 to 42 d) neurobehavioral performance on tests of simple reaction time, finger tapping, digit span, additions, symbol digit, and shapes comparison was evaluated for 58 workers exposed from 1 to 28 (mean 13, SD 7) years to manganese. Airborne manganese concentrations in total dust had been reduced in the last 10 years from 70-159 micrograms x m-3 (geometric means in different areas) to 27-270 micrograms x m-3. For each worker, manganese concentrations in blood and urine were measured, and a cumulative exposure index was also calculated. RESULTS: Blood manganese and urinary manganese ranged from 4 to 18 micrograms x 1-1 (0.07 to 0.03 mumol x 1-1) and from 0.7 to 7 micrograms x 1-1 (0.01 to 0.13 mumol x 1-1) respectively. Significant relationships were found between the blood manganese and urinary manganese levels and between these biological measures and the cumulative exposure index. Correlations were also found between the blood manganese level, the urinary manganese level, and the cumulative exposure index and the following tests: finger tapping, symbol digit, digit span, and additions. The correlation coefficients increased as the latency time after the cessation of exposure and work seniority increased. CONCLUSIONS: The results support the hypothesis that the neurobehavioral effects observed at exposure levels well below current occupational standards are related to manganese body burden, which is better reflected by the blood manganese level after the cessation of exposure.

Adult↗

PubMed1995

[Reference values for trace elements in biological fluids].

The assessment of reliable reference ranges for the concentrations of elements in biological fluids is necessary to evaluate the risks deriving from occupational and environmental exposure. For the production of reference ranges in this field it is necessary to adhere to strict criteria for the selection of individuals, the procedures for sample collection, the control of analytical variability and the statistical treatment of results. The factors affecting analytical and biological variability of the concentrations to be determined, such as the route of absorption, the presence of sources of environmental pollution in certain areas of residence, physiological variables and life-styles, are discussed.

Animals↗

PubMed1994

Estimation of pooled reference values for cadmium in blood using meta-analysis and TRACY criteria.

Reference values for blood-cadmium levels (B-Cd) are available for only a limited number of geographical areas and for particular population strata (sex, age, smoking habits). This paper, in agreement with the TRACY guidelines, describes and discusses the criteria used to rank published papers on reference values for cadmium retrieved by Medline and Toxline between 1976 and 1991. The TRACY criteria deal with the grading of published papers in terms of their suitability for calculating provisional reference values. Only four out of 18 papers were considered suitable for the TRACY project. The four articles were finally used via meta-analysis to provide provisional reference values for smokers and non-smokers. The comparison of results obtained using published statistics and individual data is used to discuss the appropriateness of meta-analysis in the case of cadmium. Due to the availability of large enough studies and to the clear differences across countries, the suitability of a compound upper reference limit to B-Cd levels seems limited.

Adult↗

PubMed1994

Urinary cobalt excretion in short time occupational exposure to cobalt powders.

In order to evaluate the urinary excretion of cobalt, a study was carried out in two plants producing diamond segments and sintered wires for stone cutting. In both plants, the highest Co exposures were found during mixing and granulation of Co powders, generally performed 1-2 times per week for 1-2 h in the first plant and 3-4 h in the other. Environmental hygiene conditions were good in the first plant and poor in the other with environmental Co concentrations around the ACGIH TLV (50 micrograms/m3) in the first and many times higher (up to 8000 micrograms/m3) in the second. In two workers employed in the above mentioned jobs. Cobalt in urine (CoU) was determined in samples collected during the first day, before shift and about 2, 4, 7 and 10 h after the beginning of exposure; samples were also collected on the 2nd, 3rd and 4th day, before and at the end of the shift. The study showed that Co in urine rapidly increased in the hours following the cessation of exposure, with a peak of elimination about 2-4 h after exposure, and a subsequent decrease (more rapid for the first 24 h) in the following days. Such a pattern was apparently independent of the degree of exposure, since it was detected in both plants and confirmed also in an industrial hygienist with lower Co exposure. The data indicate that for a correct evaluation of Co exposure through CoU determination, variables such as type and characteristics of the job and most importantly, the times at which biological samples are collected should be carefully considered.

Cobalt↗

PubMed1994

Non-occupational lead exposure and hypertension in northern Italy.

BACKGROUND: Previous research has addressed the issue that low-level blood lead concentration could be associated with an increased risk of hypertension. METHODS: This paper examines the cross-sectional association between blood lead and hypertension in 630 adult males not employed in activities characterized by specific exposure to lead and living in two Northern Italian cities (Verona and Brescia). The participants, aged 26-69 years, constituted a random sample of the patients in the practice of a general practitioner (Verona) and of regular blood donors (Brescia). Logistic regression analysis was used to evaluate the effects of selected variables (blood lead, blood cadmium, zinc erythroprotoporphyrin, haemoglobin, whole blood viscosity, age, body mass index, smoking habits and alcohol consumption) on the probability of being hypertensive. RESULTS: The blood lead concentration (range: 4.3-46.9 micrograms/dl; median: 14.8 micrograms/dl) was very similar in the two samples, whereas the prevalence of hypertension was significantly higher in the Verona sample than in the Brescia sample (20.4% versus 8.3%). Hypertensive subjects showed significantly higher blood lead levels than normotensive ones. In a preliminary (univariate) analysis blood lead levels, body mass index (BMI) and age were each significantly related to the prevalence of hypertension. After adjusting for age and/or BMI, statistical significance of the relationship between blood lead and hypertension was lost.CONCLUSIONS. The present study showed that blood lead is weakly related to hypertension in non-occupationally exposed men. The statistical significance of this association disappeared when age and BMI were used to make adjustments.

Adult↗

PubMed1994

Cisplatin pharmacokinetics in elderly patients.

The treatment of elderly patients with cancer may be difficult because of the narrow therapeutic index of antineoplastic drugs, the decline in the performance of organs and functions, and frequent comorbidity. In these patients, therapeutic drug monitoring may be useful in optimizing chemotherapy. Six patients older than 70 years with a variety of solid tumors received a total of 21 cycles of cisplatin (DDP)-based chemotherapy program (DDP dose, 50-65 mg/m2). Total and ultrafilterable platinum (Pt) were determined in plasma and urine during the first cycle of the therapy by means of atomic absorption spectroscopy. Pharmacokinetic parameters were analyzed with use of a two-compartment open model. The treatment was generally well tolerated. The most important side effects were a significant increase in serum creatinine level (from 0.98 to 1.23 mg/dl) and a decrease in creatinine clearance (from 44.4 to 38.9 ml/min) in comparison with pretreatment values. The mean decrease in hemoglobin levels was slight. The values of the main pharmacokinetic parameters of total Pt agreed well with the data obtained with other adult patients. Total and ultrafilterable Pt had a short distribution phase (t1/2 alpha = 0.35 and 0.54 h, respectively) followed by a prolonged elimination phase (t1/2 beta = 63.08 and 58.91 h, respectively). A reduced ability to clear ultrafilterable Pt (ClT = 123.52 ml h-1 kg-1) was evident and, as a result, the area under the curve increased (15.47 mg h L-1). The limited number of patients and the concomitant use of other agents prevent any firm conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

The utility of health education among lead workers: the experience of one program.

Health education represents a fundamental tool in the prevention of occupational diseases. For lead-exposed workers, work practices, personal hygiene, and life habits are certainly influences in the amount of the metal absorbed in the body. This study evaluated the effectiveness of a health education program in 50 workers exposed to inorganic lead employed in seven small factories. The study was performed in 3 phases over one year. Before the program, blood lead levels were measured, and a questionnaire was administered in order to evaluate the baseline knowledge of the workers about lead poisoning and its prevention. After the health education program, the blood lead levels decreased (from 38.2 to 32.3 micrograms/dl) and the questionnaire scores improved in a highly significant manner (p < 0.001). These results were obtained both in the short (4 months) and in the medium term (1 year). The reduction of blood lead concentrations seemed to be due to changes in hygienic behaviors and life habits, such as alcohol consumption or cigarette smoking, probably induced by an increase in specific knowledge about the prevention of lead damages.

Adult↗

PubMed1993

Increases in polycyclic aromatic hydrocarbon content and mutagenicity in a cutting fluid as a consequence of its use.

The aim of this study was to evaluate the relationships between the length of time a cutting fluid was used, its content in polycyclic aromatic hydrocarbons (PAHs) and its mutagenic potential. The PAH concentrations were determined by means of a high-resolution gas chromatograph-mass spectrometer in samples of new cutting fluid and in samples used for 3, 6 and 9 months. The following PAHs were measured: phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene+triphenylene, benzo[e]pyrene, benzo[a]pyrene and perylene. Mutagenicity assays were carried out on the aforementioned samples using the Ames test. Salmonella typhimurium TA98 was used as an indicator to show up mutagens capable of inducing frame-shift genetic changes, and Escherichia coli WP2 uvrA was used as an indicator to detect mutagens capable of inducing base pair genetic changes. The mutagenic tests were carried out with and without microsomal activation, using 1:1, 1:10, 1:20 and 1:50 dilutions of cutting fluid samples. An increase in the concentrations of total PAHs over time was observed in the samples of cutting fluid used for 3, 6 and 9 months. The highest percentage increase in PAH concentrations was observed in the 6-month-old sample (10 times the initial concentration, from 45 to 411.8 micrograms of oil). None of the samples were mutagenic to S. typhimurium without metabolic activation or to E. coli with and without metabolic activation. All samples except for the 1:1 diluted sample showed moderate but significant mutagenic activity in the S. typhimurium test with metabolic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Industrial Oils↗

PubMed1993

Biological monitoring of cadmium exposure--an Italian experience.

Studies carried out over the last 12 years in northern Italy on a case list of 105 cadmium (Cd) workers showed that blood levels (B-Cd) were influenced not only by current exposure but also by body burden, while urinary levels (U-Cd) were influenced predominantly by body burden. Moreover, no advantages were gained by adjusting U-Cd for creatinine or specific gravity. The urinary beta 2-microglobulin levels were within the reference values when B-Cd and U-Cd were below the current threshold values. However, some indicators of early renal effect appeared to be altered. An increase in chromosome-type aberrations in lymphocytes occurred in workers with a heavy cadmium burden. Studies carried out on more than 600 subjects from the general population showed higher B-Cd levels in smokers than in nonsmokers. B-Cd levels were higher in men and in higher age groups. Identifying reference values for B-Cd through meta-analysis studies seems useful.

Cadmium↗

PubMed1992

Criteria for the definition of reference values for toxic metals.

Two types of selection are used to identify subjects who make up reference groups: 'a posteriori' selection starting from a large number of subjects who are then subsequently selected and 'a priori' selection wherein the group to be examined is defined on the basis of preestablished criteria. The main variability factors are biological and those depending on the modalities of selection of groups and determination of the analysis. The nature of the element is also particularly important, i.e. whether an essential element must be considered only a micropollutant or whether it should be considered essential and at the same time a micropollutant. In addition two other factors which play an important role are the temporo-spatial modifications induced by natural or anthropogenic phenomena which influence the modality and degree of exposure in man. Two criteria are generally used in the production of reference groups: exclusion/inclusion and partitioning criteria. While in clinical chemistry the health status represents an important exclusion factor, in the case of metals, the environmental conditions and the function of organs and apparatuses involved in the toxicokinetics of metals can be considered as main criteria. All the other variables such as sex, age, life-style are partitioning criteria and enable us to obtain reference values for more and more homogeneous subgroups.

Adult↗

PubMed1992

Is hypertension a confounding factor in the assessment of blood lead reference values?

In order to evaluate whether hypertension can be considered as a confounding factor in the setting up of reference values for blood lead, we examined the results of a cross sectional study which evaluated the relationship between lead in blood and hypertension in a sample of 254 males and 271 females of a general population not occupationally exposed to lead. The statistical analysis and in particular the multiple logistic regression showed that, even if some well-known confounding factors such as age, sex, overweight, smoking and alcohol are taken into account, blood lead levels are well correlated with hypertension. The results suggest that even modest lead absorption is able to influence the probability of being hypertensive. The relationship between blood lead and hypertension and their relationship with the main confounding factors involved in the determination of reference values of metals in blood are discussed.

Adult↗

PubMed1992

Ten-year follow-up of biological monitoring of cadmium-exposed workers.

In this study, 105 workers exposed to cadmium for over 10 years were subjected periodically to environmental monitoring, biological monitoring and medical surveillance. They were divided into subgroups, one in which Cd-B and Cd-U exceeded 10 micrograms/l and 10 micrograms/g creatinine respectively and the other in which they were below these proposed biological exposure indices. Urinary beta 2-microglobulin was used as an indicator of tubular damage. Over the past 3 years 12 workers had raised urinary beta 2-microglobulin values (above 250 micrograms/l). Among workers with Cd-B and Cd-U levels always below the above limits, less than 3% had increased urinary excretion of beta 2-microglobulin, a percentage comparable with that of the reference population. When Cd-B exceeds 10 micrograms/l and Cd-U 10 micrograms/g creatinine on one or more occasions (although the median value still remains below this level), the frequency of tubular damage seems to be considerably higher (8.4 and 7.5% respectively). Thus the Cd-B and Cd-U limits proposed appear to be quite safe if strictly respected. However, median values appear too high to rule out the possibility of an increased incidence of tubular alterations.

Adult↗