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Biomedical subjects

P Apostoli

Publications and source records attributed to P Apostoli.

At least 19 recordsLinked to original sources

Significance and utility of reference values in occupational medicine.

Although it is generally accepted that reference values can be included among the instruments of modern occupational medicine, problems arise when applying them from clinical chemistry to the needs of occupational medicine. Here some general aspects regarding reference values beginning from their theoretical basis, their significance and importance and their possible use in occupational medicine are reviewed. Furthermore, their relationship with other more familiar 'guideline values', such as action levels and limit values, is demonstrated.

Guidelines as Topic

Urinary 1-hydroxypyrene as a marker of exposure to pyrene: an epidemiological survey on a general population group.

Urinary levels of 1-hydroxypyrene in a general adult population group are studied. Experimental data are not normally distributed; statistical analysis required a base 10 logarithmic transformation of data. The concentrations of urinary 1-hydroxypyrene measured were expressed as microgram g-1 urinary creatinine and are comparable with those reported by other authors, both for smoker and non-smoker subgroups. Multiple regression analysis shows that, for smokers, the number of cigarettes smoked per day and the body mass index (BMI) significantly influence the levels of urinary 1-hydroxypyrene expressed as microgram g-1 urinary creatinine, whereas no personal or behavioural variable (age, sex, alcohol consumption, dietary intake of pyrene, BMI) modified the 1-hydroxypyrene levels for non-smokers.

Adult

Effects of lead and manganese on the release of lysosomal enzymes in vitro and in vivo.

In this study we evaluated the effects of two heavy metals, lead and manganese, on the release of some glycohydrolases of lysosomal origin. N-acetyl-beta-D-glucosaminidase and its major isoenzymes, beta-D-glucuronidase and alpha-D-galactosidase. We have studied release of these enzymes in vitro from peripheral mitogen-activated lymphocytes from healthy subjects after addition of Pb or Mn to the medium and their plasma levels in individuals exposed at work to Pb (31 subjects) or to manganese (36 subjects), versus matched controls. We also determined the plasma levels in a general population (417 subjects). The enzymatic activities were assayed fluorimetrically with 4-methylumbelliferyl-glycosides as substrates. Particular attention was given to some technical aspects: enzymatic activity was preserved by addition of ethylene glycol and stable liquid material was employed for calibration purposes. N-acetyl-beta-D-glucosaminidase isoenzymes were separated by a routine chromatofocusing procedure on PBE 94. The addition of both metals to lymphocytes inhibits lysosomal enzyme release. These data were supported by the plasma levels for the exposed subjects, in which enzyme levels were significantly decreased after either type of exposure. In the general population of subjects not professionally exposed, the effect of lead appears to be masked by concomitant effects of alcohol consumption. Undoubtedly, some heavy metals can alter distribution of glycohydrolases of lysosomal origin between the intra- and extracellular environment, probably interfering with membrane mechanisms. Lysosomal enzymes seem to behave as sensitive biomarkers for early subclinical changes that might later lead to clinical disease.

Acetylglucosaminidase

Acute arsine intoxication as a consequence of metal burnishing operations.

The report concerns a 30-year-old factory worker, employed in a small galvanizing plant for over ten years in the burnishing, copper- and nickel-plating of small metal articles for the shoe industry. Acute arsine poisoning was attributed to the use of a dilute solution of CuSO4 (3%), HCl (32%), and As2O3 (2%) for burnishing metal (Fe-Zn) shoelace eyelet holes, in the absence of local exhaust ventilation and with no respiratory protection. Arsine caused severe intravascular hemolysis with a rapid drop in hematocrit and hemoglobin levels. Other body organs were involved as a result of the hypoxic effect of anemia and hemolysis, or as a direct toxic effect of the arsine itself. Our experience confirms that exchange transfusion is capable of rapidly arresting the adverse effects of arsine. The importance of preventive measures and worker information to avoid acute arsine poisoning is emphasized.

Adult

Motor function, olfactory threshold, and hematological indices in manganese-exposed ferroalloy workers.

A cross-sectional study was conducted in 35 male subjects randomly selected from workers of a ferroalloy production plant and exposed to manganese (Mn) oxides; the objective was to detect early signs of neurologic impairment. The subjects' mean age was 39.4 years (SD, 8. 4); the average exposure duration was 14.5 years (range, 5-29 years). A control group of industrial workers not exposed to neurotoxic chemicals and comparable in age and confounding factors was recruited. The intensity of Mn exposure was moderate, as reflected by airborne Mn concentrations in total dust averaging 193 [corrected] micro g/m3. Mn levels in blood (MnB) and urine (MnU) were significantly higher in the Mn-exposed workers than in control workers. A relationship (not found with MnU) was found between MnB and a cumulative exposure index calculated on the basis of air concentration and exposure history for each subject (r = 0.52; r2 = 0.27; P = 0.002). Psychomotor function scores were lower among Mn-exposed subjects. The Aiming score was negatively correlated with MnB in the exposed group. The olfactory threshold did not differ between the two groups, although it was negatively associated with MnU in the exposed group. The white blood cell count results were significantly higher in Mn-exposed subjects than in controls. These findings show that an increase in Mn body burden is associated with an impairment of motor functions, whereas the increased excretion of Mn is related to an increased olfactory perception. Changes in numbers of leukocytes could indicate possible interferences of Mn with the immunological system.

Air Pollutants, Occupational

Reference values of urinary chromium in Italy.

OBJECTIVES: The paper describes the results of a polycentric study for the assessment of reference values of urinary chromium (U-Cr) in the Italian population. METHOD: A total of 890 subjects (58.3% males and 41.7% females) were selected on the basis of standardized criteria in eight different areas of Italy. Urinary chromium was determined on morning spot samples collected using standardized procedures. The U-Cr was determined independently by three laboratories using an Electrothermic atomization-Atomic Absorption Spectrometry (ETA-AAS) method with a detection limit of 0.05 microgram/l, adopting-for the statistical analysis-the median value of the results of the three laboratories. The between-laboratories within-subjects standard deviation was 0.049 microgram/l. Due to the high proportion (approx, 28%) of undetectable chromium levels, the geometric mean (GM) and geometric standard deviation (GSD) were estimated using a procedure of linear interpolation. The analysis of the effects of some variables (sex, age, center, residence, smoking and drinking habits) on the U-Cr values, was also performed, by multiple regression analysis after logarithmic transformation, using GM and SD. RESULTS: The reference value of U-Cr was of 0.08 microgram/l as an estimated GM, whereas the expected distribution ranged from not detectable (nd) (95% CI = nd-0.06) to 0.24 microgram/l (95th percentile; 95% CI = 0.20-0.31). Among the variables studied, only geographical area and sex significantly influenced the U-Cr levels. In subjects selected in the provinces of Bari and Venice values of U-Cr were significantly lower than those determined in subjects residing in other areas. CONCLUSIONS: From our investigation the reference values for U-Cr were lower than those obtained in previous investigations. In addition it confirms a further reduction in U-Cr levels following the previous decline reported in the 1970s and 1980s. In over 20 years U-Cr values in the general population dropped from values greater than 1 microgram/l to values between 0.5 and 0.2 microgram/l. The reasons of this progressive decline cannot be attributed in our opinion to a reduced intake of the metal, but mainly to the improvement in analytical instrumentation and methods. A further decrease may be ascribed to a more accurate definition of the reference groups and to a better control of pre-analytical factors. Considering that the reference values for U-Cr are much lower than those determined some decades ago, toxicological studies in order to verify the significance of biological limit values currently suggested for chromium seem to be necessary.

Adult

Metabolism of arsenic after acute occupational arsine intoxication.

Among the elements of toxicological relevance, inorganic arsenic (As) probably exhibits the most complex metabolism, and we deemed it interesting to identify and quantify the different As species excreted after an occupational acute intoxication with arsine. For this purpose total As and five As species were determined using an hybrid analytical method coupling liquid chromatography with inductively coupled plasma mass spectrometry. The highest urinary elimination of total As was observed in the first 5 d after admission. The As species mostly excreted were monomethylarsonate (MMA), dimethylarsinate (DMA), As3+, arsenobetaine (AsB), and to a lesser extent As5+. The amount of AsB excreted in urine by the subject does not appear to be completely justified by AsB intake through food. Arsenic is excreted mainly via the urine with a clearance of 7.8 ml/h/kg and follows a triphasic model with periods of 28 h, 59 h, and 9 d, respectively. The evidence that DMA excretion culminates after a few days, when the excretion of the inorganic form is substantially reduced (while that of MMA is still elevated), seems to confirm the existence of two successive methylating enzyme activities. Furthermore, the elimination rate of As from blood follows a three-phase model and the half-lives of different species vary from about 27 to 86 h with the following gradient As5+ < MMA < As3+ < DMA < AsB.

Adult

Continuous infusion of carboplatin during conventional radiotherapy treatment in advanced squamous carcinoma of the cervix uteri IIB-IIIB (UICC). A phase I/II and pharmacokinetic study.

OBJECTIVE: A prospective, single-arm phase-I/II trial performed to assess the efficacy and toxicity of the concomitant use continuous infusion of low-dose carboplatin and pelvic conventional radiotherapy in patients with locally advanced squamous cell carcinoma of the cervix. MATERIALS AND METHODS: Between January and July 1994, a total of 12 patients consecutively diagnosed to have squamous cell carcinoma of the cervix uteri stages IIB-IIIB UICC-TNM (five patients, IIB; and seven patients, IIIB) entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pretreatment staging procedures. Radiation was delivered with 10-MeV photon beams with the shrinking-field technique. The patients received 2 Gy radiotherapy daily, 5 fractions per week, up to a planned total of 60 Gy in 6 weeks to the primary tumor and 46 Gy in 4 weeks to the whole pelvis. Irradiation was performed using four fixed orthogonal fields. One intracavitary insertion, 8 Gy to point A (dose rate, 1.1 Gy/h), was performed immediately after external pelvic irradiation. Carboplatin (12 mg/m2/day) was also administered in a continuous infusion, starting 1 day before the first fraction of radiotherapy. The platinum in plasma and urine, as well as the platinum concentration in the cytosols of lymphocytes and tumor, was measured weekly. RESULTS: A complete response was seen in nine (75%) of the 12 patients. Of the nine patients who achieved a complete remission, only one had subsequent failure in the pelvis. The total pelvic failure rate was 33.3% (four of 12 patients). With a median follow-up time of 20 months, the actuarial survival rate at 24 months was 64.8%. All patients completed the treatment without major protocol violations. Grade-2 leukopenia (in nine patients) and grade-1 nausea and vomiting (in five) were the most common acute toxicities. There was one grade-3 hematologic toxicity. Grade-3 late complications were observed in 16.6% of cases (two of 12 patients). On days 28 and 42 of the treatment, the mean total platinum plasma concentrations were 491 micrograms/L (SD = 129) and 672 micrograms/L (SD = 160), and the ultrafilterable fraction was 8-10%. At the same time points, the concentration in lymphocytes was constant at 21 picograms (pg) platinum/lymphocyte. The levels of platinum concentration measured on days 14 and 28 in the cytosols of tumor cells were 0.3 microgram/g (SD = 0.1) and 0.93 microgram/g (SD = 0.2). CONCLUSION: The combination of continuous infusion of carboplatin and radiotherapy at the aforementioned doses in patients with locally advanced cervical carcinoma resulted in a relatively low frequency of significant acute and late complications. Platinum in normal tissue (picograms per lymphocyte) was stable from week 1 of treatment, whereas the platinum steady state in plasma and in tumor cells was not reached in 6 weeks and was below that required in vitro to produce radiopotentiation. Further studies to determine the optimal dose of carboplatin and irradiation are needed prior to the initiation of phase-III studies.

Adult

Changes over a workshift in aesthesiometric and vibrotactile perception thresholds of workers exposed to intermittent hand transmitted vibration from impact wrenches.

OBJECTIVES: To investigate the changes over a workshift in fingertip tactile perception thresholds in users of impact wrenches exposed to intermittent hand transmitted vibration. A further aim was to assess the relation between acute changes in tactile sensation, sensorineural disorders, and vibration dose. METHODS: The study populations consisted of 30 workers exposed to vibration (16 men and 14 women) and 25 control manual workers (10 men and 15 women). Sensorineural disorders in the fingers and hands were graded according to the staging system of the Stockholm workshop scale. Tactile function was tested by measuring aesthesiometric thresholds (two point discrimination and depth sense perception) and vibrotactile perception thresholds at 16, 31.5, and 125 Hz before and after a workshift. Temporary threshold shift was then calculated as the difference between threshold measures before and after the shift. The measurement and assessment of exposure to vibration were made according to the international standard ISO 5349. The vibration dose accumulated over a workshift (m2s-4h) was estimated for each user of impact wrenches. Daily exposure to vibration was also expressed in terms of eight hour energy equivalent frequency weighted acceleration ((ahw)eq(8) in ms-2 rms). RESULTS: After adjustment for age and alcohol consumption, vibrotactile perception thresholds before exposure were greater in the workers exposed to vibration than in the controls. No differences in aesthesiometric thresholds before the shift were found between the study groups. Sensorineural disorders were mild in the workers exposed to vibration and minor neurological abnormalities were detected at the physical examination. Owing to the intermittent use of impact wrenches, the estimated mean (ahw)eq(8) for the subjects exposed to vibration was low (1.3 ms-2 rms). A significant temporary threshold shift in vibration perception at all test frequencies was found in the workers exposed to vibration but not in the controls. A significant increase in depth sense perception thresholds was found in the men exposed to vibration. The temporary threshold shift in vibration perception at 125 Hz, and to a lesser extent at 16 and 31.5 Hz, was associated with the severity of sensorineural disorders. In the workers exposed to vibration the temporary threshold shift in vibration sense at all test frequencies was positively related to the estimated dose of vibration received over a workshift. No significant relation was found between aesthesiometric threshold changes and vibration dose. CONCLUSIONS: Intermittent exposure to hand transmitted vibration over a workshift can cause a deterioration of tactile perception in the fingers of users of impact wrenches. Acute tactile dysfunction was related to both the estimated dose of vibration and the severity of sensorineural symptoms. The temporary threshold shift in vibration perception suggested that fast adapting skin mechanoreceptors such as Pacinian and Meissner corpuscles were mainly involved in the acute sensory impairment to the fingertips of the workers exposed to vibration. Changes in tactile perception can occur in workers with daily exposure to vibration that is considered to be associated with a minimal risk of adverse health effects induced by vibration.

Adult

Proposal of a method for identifying exposure to hazardous chemicals in biomedical laboratories.

Controlling occupational exposure to chemical substances in biomedical laboratories is very complex because of the high number of compounds involved, and the rapid changes in analytical techniques and methods. On the other hand, evidence of increased mortality for malignant lymphoma and leukemia has been observed in laboratory technicians. This calls for more precise procedures of risk assessment to identify the specific substances that may be responsible for these effects. A model of hazard identification is presented, which includes the following steps: identification, classification and periodical updating of the chemical substances used in each analytical technique; evaluation of the variables that can influence the exposure; quantification of exposure using environmental measurements. The availability of such a procedure can be useful for the organization of health and epidemiological surveillance programs for the laboratory workers.

Clinical Laboratory Information Systems

Manganese effects on the human neuroblastoma cell line SK-ER3.

SK-ER3 cells were recently demonstrated to represent a valuable model for the study of estrogen-inducible differentiation of neural cells in culture. This system may constitute an important tool also for the analysis of the effects of neurotoxic drugs. The present study demonstrates that short term exposure to Mn causes increased proliferation rate of SK-ER3 cells regardless of their differentiation. Long term treatment causes cell death in undifferentiated cells at concentrations of the metal as low as 100 nM. When the cells are differentiated with estrogens, death is observed only with a Mn concentration two orders of magnitude higher. Measurement of neurite extension and quantitation of tyrosine hydroxylase content after long-term exposure to the metal allow the conclusion that Mn does not alter the state of differentiation of SK-ER3 cells induced by the treatment with the hormone. The study underlines the importance of studying the effect of Mn in proliferating neural cells and demonstrates the toxic role of micromolar concentrations of the metal in fully differentiated neural cells. Since other authors produced evidence of effects of the metal on cell death and proliferation only at millimolar concentrations, and none described its proliferative activity, the model utilized in the present study seems to be of particular interest.

Cell Differentiation

Standard reference materials and data quality assurance in the biomedical analysis of trace elements.

Accurate and precise analytical data of the concentrations of bio-analytes in bioclinical studies are of fundamental importance. Quality assurance procedures should always be performed to check the overall analytical work. This can be conveniently performed if appropriate standard reference materials with known concentrations of the analyte object of study are available. This paper underlines the key points related to the production and use of biological standard materials for trace element analysis. In particular, the present situation in the field of trace element determination in human biological fluids and the related problems are illustrated. The considerations given in this work may contribute to the preparation of the new biomarker standard materials.

Biomarkers

Interferences of urinary tract infection in the measurement of urinary nitrous oxide.

OBJECTIVES: To investigate the effective role of micro-organisms in producing N2O. METHODS: The N2O in either urine samples inoculated with 24 microbial strains or urine samples from patients with urinary tract infections were measured. RESULTS: Gram negative bacilli generally produced high amounts of nitrous oxide (N2O), whereas Gram positive cocci and yeasts did not. The production of N2O depends on the incubation time and follows exponential kinetics, reaching a plateau at 48 hours. Furthermore, the results of urinocultures agreed well with N2O concentrations found in urine samples: samples negative for bacteria were found to contain very low concentrations of N2O whereas those positive--for example, for Enterobacteriaceae--gave highest N2O values. CONCLUSION: The urinary tract infections caused by Gram negative bacilli are important confounding factors in biological monitoring practices of exposure to inhalation anaesthetics. The current methods adopted to avoid these factors (urine acidification, storage of samples at 4 degrees C) are not good enough because of the relative acid tolerance of some strains and the production of N2O directly into the bladder.

Anesthetics, Inhalation

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

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

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