Biomedical subjects
Publications and source records attributed to L Maestri.
Pancreatic tumors are rarely present in childhood. The authors present a case of papillary-cystic tumor in a 13-year-old girl, treated by partial pancreatoduodenectomy, with preservation of the pylorus. The histologic pattern was of a papillary cystic tumor without evident atypical nuclei. One year after operation, the girl is well without any finding of disease.
In order to investigate a role of acetone in urine (AcU, mg/l) as an indicator of occupational exposure to isopropyl alcohol (IPA, ppm), AcU was measured in 80 male workers exposed to this substance in a plastic factory. The exposure concentration of solvent was also monitored personal diffusive sampling in the individuals during morning 4-hr shift. Urine samples were collected near the end of the shift and were analyzed for acetone by head-space gas chromatography. The correlation between airbornre concentration of IPA and its urinary metabolite acetone was significant: AcU (mg/l) = 0.031 x IPA (ppm) + 0.608, r = 0.75, n = 80, P < 0.001. We established 44 ppm as the lowest airborne concentration of IPA that caused excessive urinary excretion of acetone which could be discriminated from the endogenous production of acetone in non-exposed people. This concentration was as low as one ninth to one tenth of the current exposure limit of 400 ppm. At higher concentrations than 44 ppm, AcU was found to be a useful index for monitoring occupational exposure to IPA.
Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure. However, urinary phenol cannot be used to monitor low-level exposures. New biological indexes for exposure to low levels of benzene are thus needed. The aim of this study was to investigate the relations between exposure to benzene (A-benzene, ppm), as measured by personal air sampling, and the excretion of benzene (U-benzene, ng/l), trans,trans-muconic acid (MA, mg/g creatinine), and S-phenylmercapturic acid (PMA, micrograms/g creatinine) in urine. The subjects of the study were 145 workers exposed to benzene in a chemical plant. The geometric mean exposure level was 0.1 ppm (geometric standard deviation = 4.16). After logarithmic transformation of the data the following linear regressions were found: log (U-benzene, ng/l) = 0.681 log (A-benzene ppm) + 4.018; log (MA, mg/g creatinine) = 0.429 log (A-benzen ppm) - 0.304; and log (PMA, micrograms/g creatinine) = 0.712 log (A-benzene ppm) + 1.664. The correlation coefficients were, respectively, 0.66, 0.58, and 0.74. On the basis of the equations it was possible to establish tentative biological limit values corresponding to the respective occupational exposure limit values. In conclusion, the concentrations of benzene, mercapturic acid, and muconic acid in urine proved to be good parameters for monitoring low benzene exposure at the workplace.
A sensitive method for the determination of free and total urinary 2,5-hexandione (2,5-HD) using high-performance liquid chromatography with fluorescence detection was developed. After purification of urine with a disposable C18 cartridge, 2,5-HD was derivatized with dansylhydrazine; 1,3-diacetyl benzene (1,3-DAB) was added to the samples, as internal standard, prior to extraction. The resulting fluorescent adducts were separated on a reversed-phase column with a gradient mobile phase of 25 mM phosphate buffer (pH 6.4) and acetonitrile. The retention times of the 2,5-HD and 1,3-DAB derivatives were 9.4 and 13.7 min, respectively. The derivatives were detected by a fluorescence detector (excitation 340 nm, emission 525 nm). The mean recoveries of 2,5-HD and 1,3-DAB were 92.0 and 94.0%, respectively; the detection limit of 2,5-HD (signal-to-noise ratio of 3) was 5 micrograms/l in urine without hydrolysis and ca. 12 micrograms/l in hydrolyzed samples. The method was applied to 39 urine samples from workers exposed to n-hexane; the mean values were 2.597 mg/l (S.D. = +/- 0.758) for total 2,5-HD and 0.179 mg/l (S.D. = +/- 0.086) for free 2,5-HD. Urine samples of 22 non-exposed subjects showed a mean concentration of 0.437 mg/l (S.D. = +/- 0.109) and 0.022 mg/l (S.D. = +/- 0.011) for total and free 2,5-HD, respectively.
Benzene concentrations in urine samples (Cu, ng/L) from 110 workers exposed to benzene in chemical plants and gasoline pumps were determined by injecting urine supernate into a gas chromatograph. The urine was saturated with anhydrous N2SO4 to facilitate the passage of benzene in the air over the urine. The solvent was stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap tube) by means of a suction pump (flow rate 150 ml/m). Wash-up of the head space was achieved by simultaneous intake of filtered air through charcoal. Benzene was thermically desorbed and injected in a column (thermal tube disorder, Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1, 60 m length, 0.75 mm ID, 1 microns film thickness; GC Dani 8580-FID). Benzene concentrations in the urine from 40 non-exposed subjects (20 smokers > 20 cigarette/d and 20 nonsmokers) were also determined [median value of 790 ng/L (10.17 nmol/L) and 131 ng/L (1.70 nmol/L), respectively]. The 8-h time-weighted exposure intensity (Cl, micrograms/m3) of individual workers was monitored by means of charcoal tubes. The median value for exposure to benzene was 736 micrograms/m3 (9.42 mumol/m3) [geometric standard deviation (GSD) = 2.99; range 64 micrograms/m3 (0.82 mumol/m3) to 13,387 micrograms/m3) (171.30 mumol/m3)]. The following linear correlation was found between benzene concentrations in urine (Cu, ng/L) and benzene concentrations in the breathing zone (Cl, micrograms/m3): log(Cu) = 0.645 x log(Cl) + 1.399 r = .559, n = 110, p < .0001 With exclusion of workers who smoked from the study, the correlation between air benzene concentration and benzene measured in urine was: log(Cu) = 0.872 x log(Cl) + 0.6 r = .763, n = 63, p < .0001 The study results indicate that the urinary level of benzene is an indicator of occupational exposure to benzene.
In pediatric gynecology, inflammatory vulvo-vaginitis are very common. Their diagnosis cannot be based either on the symptoms (itching or pain) or on the signs (leucoxanthorrhea) for these classifications are "non-specific". At the Consulting Room of pediatric gynecology of the Vittore Buzzi Hospital, 215 "non-specific" vulvo-vaginitis cases have been analyzed through bacteriological and microscopical examinations of vaginal secretions. The vaginal tampon resulted negative in 53% of the cases and positive in the remaining 47%. Comparing these results with microscopical examinations we obtain: 81.8% of sensibility, 77.4% of specificity, 87.8% of negative predictive value and 62.2% of positive predictive value. In particular, this last figure is influenced by the high number of false positives of the vaginal tampons, due to the growth "in vitro" of opportunist germs momentarily quiescent "in vivo". Thus it is useful to associated the microscopical examination (that will indicate all the cases in need of treatment) and the bacteriological examination (that will indicate the right cure).
The hepatic effects of 1,2-dichloropropane (DCP) were investigated in male Wistar rats exposed to 15, 50, 100, 250, 450, 1000, 1300, 1800 or 4900 mg DCP m-3. At the end of a 4-h period of exposure, average blood DCP levels were 0.025 and 5.38 micrograms ml-1 in animals treated with 15 and 1300 mg m-3, respectively. Blood DCP concentrations were correlated with the air DCP concentrations in the inhalation chamber. At DCP concentrations of 100 mg m-3 or higher, the liver non-protein thiol (NPT) content was significantly reduced. Assays performed 20 h after 4-h DCP exposure showed that exposure to 100-1000 mg DCP m-3 had no effect on hepatic NPT levels. The NPT content increased only in the liver of rats exposed to higher (1300-4900 mg m-3) DCP concentrations. Treatment with DCP did not cause hepatic lipid peroxidation and did not modify total protein content. The observed changes in liver cell thiol homeostasis are likely to reflect the action of reactive intermediates formed during DCP metabolism. These changes can occur in rats following exposure to considerably low levels of DCP vapour.
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Esophageal motor dysfunction in patients with collagen disease, although rather frequent, presents difficult etiopathogenetic arrangement. By means of esophageal manometric evaluation and immunopathologic study the Authors observed 44 patients with Raynaud's phenomenon idiopathic or joined with Scleroderma. From collected data the utility of esophageal manometry in early diagnosis is pointed out.
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Data obtained by means of rapid pull-through manometry in cases of hiatal hernia with or without gastro-oesophageal reflux are presented. Particular reference is made to lower oesophageal sphincter pressure in reflux symptomatologies irrespective of the presence of hiatal hernia. A relation between age and lower oesophageal pressure was noted. Hypotonia of the sphincter was observed in younger subjects, whose reflux symptoms are more marked and often unassociated with hiatal hernia. In the patients, sphincter dysfunction appears to be related to an error in the neurohormonal control mechanism of this functional complex. Stress is also laid on the rôle of pull-through manometry in the diagnostic, therapeutic and prognostic approach to diseases of this type.
Previous studies have indicated that ethanol may affect styrene metabolism and toxicity in target tissues (e.g. brain). Morphological and biochemical changes have been reported in the respiratory tract of laboratory animals exposed to styrene either by inhalation or i.p. injection. The aim of the present study was, therefore, to investigate the influence of subchronic ethanol administration (5% in a Lieber-DeCarli liquid diet) on the morphological alterations of the respiratory tract induced by styrene inhalation (300 ppm, 6 h day(-1), 5 days a week for 2 weeks) in rats. Levels of reduced glutathione (GSH) in lung and liver tissues as well as in erythrocytes and whole blood were studied as indicators of overall GSH status, and urinary levels of the styrene metabolites-mandelic acid and phenylglyoxylic acid-were also measured as indicators of styrene-absorbed dose. Rats exposed to 300 ppm styrene presented morphological alterations throughout the respiratory tract. Electron microscopy analysis showed diffuse cell damage involving the tracheal, bronchiolar and alveolar epithelium. These abnormalities were accompanied by 40% depletion of GSH in the lung tissue and also 35% depletion in hepatic GSH in the absence of alteration of the GSH content in blood. Styrene metabolism was apparently induced by subchronic ethanol treatment, as indicated by an increased excretion of urinary mandelic (+140%, P < 0.05) and phenylglyoxylic (+50%) acids. However, repeated ethanol administration did not exacerbate the lung GSH depletion nor the damaging effect to the respiratory tract induced by the 2-week exposure to styrene alone. The lack of effects of ethanol on styrene pulmonary toxicity after combined exposure may be due to the different tissue distribution of the cytochrome P-450 isoforms involved in the styrene biotransformation to styrene-7,8-oxide, and their different induction by ethanol.
Until now, high-performance liquid chromatography (HPLC) and gas chromatography (GC) have been shown the most useful techniques for the determination of urinary mercapturic acids in humans. Preliminary sample treatment is often necessary, including liquid-liquid, solid phase (SPE) or on-line extraction, in order to obtain highly purified samples. The use of derivatizing reagents coupled with specific and sensitive detectors allowed to develop methods suitable for the measurement of mercapturic acids specific for a large number of xenobiotics. At present, however, the use of urinary mercapturic acid tests for biomonitoring purposes is limited because of the high costs and complexity of analyses. Further improvements, in terms of cost reduction, could come from the introduction of fully automated systems.
S-Phenylmercapturic acid (PMA), a urinary metabolite which derives from the conjugation of benzene epoxide with glutathione, has been recently included in the list of the biological markers of benzene exposure. We have evaluated the urinary PMA levels in 145 workers exposed to benzene and in 87 subjects not occupationally exposed to the solvent (45 smokers and 42 non-smokers). In non-exposed persons, the background PMA excretion was nearly constant during one day (urine samples were collected in the morning, afternoon, and evening) and in smokers the mean PMA levels were higher than in non-smokers (9.6 vs 1.3 micrograms/g creatinine). This difference was presumably due to the extra-exposure to benzene (from cigarette smoke) in smokers compared with non-smokers, in fact a close relationship was found between PMA excretion and urinary benzene concentration (r = 0.86). Urine samples from workers exposed to benzene (airborne mean concentration = 0.52 ppm) showed higher mean levels of PMA (37.6 micrograms/g creatinine) than samples taken from not occupationally exposed subjects, both smokers and non-smokers. The mean biotransformation rate of benzene to PMA was 0.073%, with a large inter-individual variability (range = 0.002-0.21%). Also, statistical analysis of data revealed a clear bimodal distribution pattern of the conversion rate frequencies in the population examined: this is consistent with the hypothesis of the presence of "slow" and "fast" converters, due to the polymorphism of glutathione-S-transferase isozymes.
The biological monitoring of styrene exposure is currently performed by the measurement of the urinary excretion of mandelic acid (MA) and phenylglyoxylic acid (PGA), which originate from the conversion of styrene 7,8-epoxide (SO), an electrophilic compound considered responsible for most toxic effects of styrene. In rats, an alternative pathway in the detoxification processes of SO has been shown, which involves its conjugation with glutathione (GSH), leading to the excretion of N-acetyl-S-(1-phenyl-2-hydroxyethyl)-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-cysteine (M2). Giving the chiral nature of SO, which is present in two enantiomeric forms (R and S), both M1 and M2 consist of two diastereoisomers: thus, four specific mercapturic acids are excreted in styrene-exposed rats, namely M1-R, M1-S, M2-R and M2-S. Until now, the excretion of these compounds in man has not been confirmed directly, giving the analytical difficulties in measuring the low levels of urinary mercapturic acids which are expected following styrene exposure in the working environment. In the present study we applied an analytical method, based on HPLC with fluorometric detection, to measure the excretion of M1-R, M1-S, and M2 in post-shift urines from 22 workers exposed to styrene and in 10 unexposed subjects. The results clearly demonstrated that the GSH pathway is involved in the detoxification processes of styrene, even if to a low extent (the biotransformation rates of styrene to mercapturic acids varied from 0.021 to 0.325%) and that M1 and M2 are specific for styrene exposure, in fact unexposed subjects showed no detectable amounts of these metabolites. In spite of the marked interindividual variability, significative correlations were found between mercapturic acids excretion and environmental styrene concentration or urinary levels of MA and PGA. The urinary levels of M1-S and M1-R were significantly different, thus indicating a stereoselectivity of the enzymes involved in the biotransformation of styrene to mercapturic acids.
Sevoflurane has been used in the last few years in brief surgical operations, either alone or in combination with nitrous oxide. Occupationally exposed groups include anesthesiologists, surgeons and operating room nurses. In 1977 the National Institute for Occupational Safety and Health (NIOSH) recommended that occupational exposure to halogenated anesthetic agents (halothane, enflurane, and isoflurane), when used as the sole anesthetic, should be controlled so that no worker would be exposed to time-weighted average concentrations greater than 2 ppm during anesthetic administration. When halogenated anesthetics are associated with nitrous oxide, NIOSH recommends that the limit value should not exceed 0.5 ppm. We think these recommendations can be extended to sevoflurane. Metabolism of sevoflurane is catalyzed by cytochrome P-450; this involves oxidation of the fluoromethyl side chain of the molecule, followed by glucuronidation. Two urinary metabolites of sevoflurane have been identified: inorganic fluoride (which, however, is not specific) and a non-volatile compound that yields hexafluoroisopropanol (HFIP) when digested with the enzyme beta-glucuronidase. In order to investigate the role of urinary HFIP as an indicator of occupational exposure to sevoflurane (CI, ppm), CI was measured in 145 members of 18 operating room staffs. The measurements of the time-weighted average of CI in the breathing zone were made by means of diffusive personal samplers. Each sampler was exposed during the whole working period. Sevoflurane was desorbed with CS2 from charcoal and the concentrations were measured on a gas chromatograph (GC) equipped with a mass selective detector (MSD). The GC was equipped with a 25 meter cross-linked phenylmethylsilicon column (internal diameter 0.2 mm). GC conditions were as follows: injector column temperature = 200 degrees C; column temperature = 30 degrees C; carrier gas = helium; injection technique of samples = splitless. The analytical conditions for the MSD were the following: ion mass monitored = 131 m/e; dwell time = 50 msec; selected ion monitoring window time = 0.1 amu; electromultiplier = 400 V. Urine samples were collected near the end of the shift and were analyzed for HFIP by head-space gas chromatography after glucuronide hydrolysis. 0.5 ml of urine and 1.5 ml of 10 M sulfuric acid were added to 21.8 ml headspace vials. The vials were immediately capped, vortexed, and loaded into the headspace autosampler. Samples were maintained at 100 degrees C for 30 min, after which glucuronide hydrolysis was 99% complete. Analyses were performed on a GC equipped with a MSD. The analytical conditions for urine analysis were as follows: cross-linked 5% phenylmethylsilicon column (internal diameter 0.2 mm, length 25 m); column temperature = 35 degrees C; carrier gas = helium. The analytical conditions for the MSD were: monitored ions = 51.05 and 99; dwell time = 100 ms; selected ion monitoring window time = 0.1 amu; electromultiplier voltage = 2000 Volt. With our analytical procedure, the detection limit of HFIP in urine was 20 micrograms/L. The variation coefficient (CV) for HFIP measurement in urine was 8.7% (on 10 determinations; mean value = 1000 micrograms/L). The median value of CI was 0.77 ppm (Geometric Standard Deviation = 4.08; range = 0.05-27.9 ppm). The correlation between CI and HFIP (Cu, microgram/L) was: Log Cu (microgram/L) = 0.813 x Log CI (ppm) + 2.517 (r = 0.79, n = 145, p < 0.0001). On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for sevoflurane. According to our experimental results, HFIP values of 488 micrograms/L and 160 micrograms/L correspond to airborne sevoflurane concentrations of 2 and 0.5 ppm respectively.