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Intracellular cholesterol metabolism was reported to modulate amyloid-beta (Abeta) generation in Alzheimer's disease (AD). Results presented herein demonstrated that, like brain cells, cultured skin fibroblasts from AD patients contained more cholesterol esters than fibroblasts from healthy subjects. Particularly, Oil Red-O, Nile Red, and filipin staining highlighted higher levels of neutral lipids which responded to inhibitors of acyl-coenzyme A:cholesterol acyl-transferase (ACAT-1), associated with an increase in free cholesterol. ACAT-1 mRNA levels increased significantly in AD fibroblasts, whereas those of sterol regulatory element binding protein-2, neutral cholesterol ester hydrolase, and ATP-binding cassette transporter member 1 were markedly down-regulated. Instead, mRNA levels of low-density lipoprotein receptor, hydroxy-methyl-glutaryl-coenzyme A reductase, caveolin-1, and amyloid-beta protein precursor (AbetaPP) were virtually unchanged. Notably, mRNA levels of both beta-site AbetaPP-cleaving enzyme 1 (BACE1) and neprilysin were significantly down-regulated. An increase in Abeta(40) and Abeta(42) immunostaining and a decrease in BACE1 active form were also found in AD versus control fibroblasts. Altogether, these findings support the hypothesis that the derangement of cholesterol homeostasis is a systemic alteration involving central but also peripheral cells of AD patients, and point to cholesterol ester levels in AD fibroblasts as an additional metabolic hallmark useful in the laboratory and clinical practice.

In recent years the increasing use of platinum (Pt) both in medical and in industrial applications has caused its growing anthropogenic emission and spread in the environment. Pt is released into the atmosphere by exhaustcatalytic converters, and Pt compounds are often used in antitumour therapies. As a consequence, significant amounts of Pt can be detected in hospital wastewaters. This can lead to an increase in the exposure levels to Pt, especially in urban areas. It is therefore necessary to determine Pt reference values in the general population, by using suitable procedures able to achieve adequate analytical performances. Several measurements of Pt in biological fluids have been reported, but the analytical methods used for the determination of Pt often lack information about the uncertainty of the results, especially for low concentrations of urinary Pt in non-occupationally exposed subjects. The present paper considers the measurement of urinary Pt levels in a general population group from central Italy, by both quadrupole (Q) and sector field (SF) inductively coupled plasma mass spectrometry (ICP-MS). The two procedures were validated and their expanded uncertainties were evaluated. The limits of detection (LODs), calculated taking into account dilution factors, were 0.18 and 0.05 ng L - 1 of Pt for the Q and SF procedures, respectively. The median value observed was 4.13 ng L - 1 of Pt in urine, while the relative combined uncertainty at 5 ng L - 1 was below 20% with both ICP-MS techniques. These data are in good agreement with those reported in the literature for similar studies.

Alzheimer's disease (AD) is a progressive neurodegenerative illness and the most frequent cause of dementia in the elderly. The identification of activated microglia within neuritic plaques, coupled with the presence of numerous inflammatory proteins, suggests that inflammation is an integral part of the pathogenetic process in AD. In the present paper we have investigated the levels of circulating inflammatory mediators as potential AD biomarkers concentrating essentially on (a) soluble CD40 (sCD40), a member of the tumor necrosis factor receptor superfamily lacking the membrane-associated endodomain by alternative splicing, and (b) transforming growth factor (TGF)-beta 1, a cytokine deeply involved in AD and playing a protective role on CNS. Decrease of TGF-beta1 in AD patients could enhance the effects of pro-inflammatory cytokines produced by activated microglia as well as the expression of factors, such as the CD40/CD40 ligand complex, by microglia and astrocytes. Total venous blood samples were obtained from 33 patients with clinical diagnosis of possible late-onset AD, 40 healthy age-matched and 11 healthy young individuals. A significant increase of sCD40 levels plasma of AD patients versus healthy controls was measured, concomitantly with a decrease in TGF-beta1 concentration. These variations, however, showed no correlation with the expression of ApoE epsilon 4 allele, which was determined in order to assess the different frequency of this risk factor between AD and control groups. Since no comparable modifications were detected in patients affected by Parkinson's disease or non-AD-based dementia, we propose that sCD40 and TGF-beta1 plasma levels might represent possible differential biomarkers of AD, and be useful pre-mortem to support the clinical diagnosis of late-onset AD.

Blood lymphocyte subsets and serum immunoglobulins were studied in 15 men (mean age: 35 years), not exposed to toxic agents, and in 15 healthy men, exposed to dust containing several compounds (including lead chromate), working in a factory producing plastic materials. Worker blood lead and urine chromium (Cr) levels were significantly higher than controls, while serum Cr concentration was unchanged. In the worker blood, CD4+ helper-inducer (mainly CD4+-CD45RO- "virgin"), CD5--CD19+ B, CD3--CD25+ activated B and CD3--HLA-DR+ activated B and natural killer (NK) lymphocytes were significantly reduced (about 30-50 %). The investigated workers were exposed to hexavalent Cr, as lead chromate, whereas normal population (control group) was mainly exposed to trivalent Cr. In the control group, urinary Cr showed a significant positive correlation with CD16+-56+ NK, CD5+-CD19+ B and HLA-DR+ activated T, B and NK lymphocytes and a negative correlation with serum IgA immunoglobulins; moreover, serum Cr was significantly correlated with all blood lymphocytes and HLA-DR+, CD3--HLA--DR+ and CD3--CD25+ lymphocyte subsets. These data suggest that trivalent Cr may be involved in mechanisms regulating the immune response in humans.

The present study was performed to evaluate the role of hand and facial contamination in the absorption of soluble nickel compounds in 41 male subjects employed in electroplating operations in 25 small factories in the province of Florence (Italy). Personal exposure to airborne nickel ranged from 0.10 to 42 micrograms/m3; the median (range) urine, hands and face nickel levels were 4.2 (0.7-50) micrograms/l, 39 (1.9-547) micrograms, 9.0 (1.0-86) micrograms, respectively. Face nickel values explained the bulk of the variance in urine nickel levels (42%). In stepwise multiple regression analysis all other variables were not significant. The log-linear model can be expressed as: log (urine-Ni) = 0.295 + 0.593 log (face-Ni). Our results suggest that skin contamination, especially facial skin, plays an important role in nickel absorption in exposed workers.

Purpose The aim of this study has been to compare the Harmonic Scalpel (HS) and the “cold knife” dissection in the treatment of snoring by uvulopalatopharyngoplasty (UPPP). Materials and methods The investigation included 40 adult males with snoring. Patients were assigned to two homogeneous groups (A and B) and UPPP was performed using HS or “cold knife” dissection in groups A and B, respectively. Before and 6 months after surgery, each patient was studied using the apnea-hypopnea index and a visual analogue scale of snore levels. Postoperative assessment of pain was evaluated on postoperative days 1 and 10. All the patients underwent to a perioperative evaluation concerning the duration of surgical dissection, the amount of intraoperative blood loss and days of hospitalization. Results In group A, the HS provided excellent control without side effects on the adjacent structures and postoperative complications. Harmonic Scalpel's group experienced shorter operation time, lesser blood loss, fewer days of hospitalization and lower postoperative pain. Conclusions The use of the HS in UPPP is safe and confers some advantages over conventional methods of UPPP: its use led to diminished bleeding, shorter operation time, lesser pain, and better wound healing in the postoperative period.

The aim of this study was to verify the efficacy and applicability of the Ultracision Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH) in pharyngolaryngectomy with radical neck dissection.This work evaluated the use of the Harmonic Scalpel in otolaryngology as a new and alternative method to overcome some complications of traditional surgery.The study was conducted with 20 patients in the ENT Department of the University of Genoa (Italy) between January 1, 2005, and December 31, 2006.A prospective, randomized study was undertaken on 20 pharyngolaryngectomies with radical neck dissection performed using a Harmonic Scalpel (10 patients) or traditional surgery (10 patients).The evaluation included operation time, intraoperative blood loss, postoperative seroma formation, and pattern of wound healing.In patients treated with Harmonic Scalpel, the mean operation time was significantly shorter, the blood loss was less, laryngeal and neck drainage on the first and second postoperative days was significantly smaller, and no postoperative complications were noted.The use of the Harmonic Scalpel during pharyngolaryngectomy and radical neck dissection led to diminished bleeding, shorter operative time, less seroma formation, and better wound healing in the postoperative period.

The aim of this study was to evaluate changes in acoustic features of speech and voice after uvulopalatopharyngoplasty (UPPP) with the Harmonic Scalpel (HS), using the multidimensional voice program (MDVP) in conjunction with other tests. Before and 6 months after surgery, phonetically balanced sentences and sustained vowels a, e, i were carried out and digitalized with MDVP in all the patients, as an evaluation of nasal resonance (trough the Glatzel and the Gutzmann tests), speech articulation and voice handicap index (VHI). These parameters were estimated: average of fundamental frequency, Jitter, Shimmer, noise-to-harmonics ratio, voice turbulence index, soft phonation index, degree of voiceless, degree of voice breaks and peak amplitude variation. Six months after surgery, improvements in all the acoustic parameters, in nasalance and VHI were achieved. In our experiences UPPP, with the HS, improves speech and voice in patients affected by snoring and/or obstructive sleep apnea syndrome.

This article reports the results of a study, conducted in the framework of the scientific activities of the Italian Society for Reference Values, aimed at defining reference values of urinary trans,trans-muconic acid (t,t-MA) in the general population not occupationally exposed to benzene. t,t-MA concentrations detected in 376 subjects of the resident population in three areas of Italy, two in central (Florence and southern Tuscany) and one in northern Italy (Padua), by three laboratories, compared by repeated interlaboratory controls, showed an interval of 14.4-225.0 microg/L (5th-95th percentile) and a geometric mean of 52.5 microg/L. The concentrations measured were influenced by tobacco smoking in a statistically significant way: Geometric mean concentrations were 44.8 microg/L and 76.1 microg/Ll in nonsmokers (264 subjects) and smokers (112 subjects), respectively. In the nonsmoking population, a significant influence of gender was found when concentrations were corrected for urinary creatinine, geometric mean concentrations being 36.7 microg/g creatinine in males (128 subjects) and 44.7 microg/g creatinine in females (136 subjects). The place of residence of subjects did not seem to influence urinary excretion of the metabolite, although personal inhalation exposure to benzene over a 24-h period showed slightly higher concentrations in Padua and Florence (geometric means of 6.5 microg/m(3) and 6.6 microg/m(3), respectively) than in southern Tuscany (geometric mean of 3.9 microg/m(3)). Concentration of t,t-MA in urine samples collected at the end of personal air sampling showed little relationship to personal inhalation exposure to benzene, confirming the importance of other factors in determining excretion of t,t-MA when concentrations in personal air samples are very low.

Background and aims: Samples of nursing homes in Tuscany (Italy) classify their residents and determine their case-mix according to the Resource Utilization Groups System, Version III (RUG-III). Methods: A large sample of nursing homes was selected, based on willingness to participate, representation of both public and private institutions, and wide geographic representation. Two registered nurses assessed all residents using the RUG questionnaire. The information collected was then used to group residents into 44 RUGs, and facility-specific case-mix indices were calculated using the RUG-specific weights previously validated in Italy. Results: A total of 3981 residents from 93 nursing homes were assessed. Most residents were over 75 years old (87.4%) and women (68.6%). A large percentage was classified into RUGs within the following primary categories: reduced physical function (33.6%), impaired cognition (17.6%) and clinically complex (17.6%). The resulting nursing home case-mix indices ranged from 0.627 to 1.108 (mean 0.807±0.110). No significant association was found between type of facility, level of fees, or extent of staff in the nursing homes and their case-mix indices. Conclusions: RUG-III can provide information on types of nursing home residents and their care needs. This is useful for monitoring and evaluating long-term care services for the elderly, and allows for more effective planning and allocation of staffing and financial resources.

Usually head and neck cancer is treated with combined therapy, applying surgery, if possible, and then radiotherapy and chemotherapy in a sequential or concomitant way. Sequential approach seems to be preferred, because of the high toxicity rate of concomitant therapy. Platinum compounds and 5-fluorouracil are the standard drugs, but new drugs are entering therapeutic arena: gemcitabine and taxanes are the most promising ones. The efficacy of these drugs, especially in association with radiotherapy, must be assessed; moreover it is essential to ascertain how to associate these drugs to radiotherapy and to evaluate drug toxicity when combined with the latter. End point of the study here presented is a preliminar assessment of toxicity and feasibility of concurrent radio-chemoterapy with docetaxel and cisplatinum in patients with head and neck cancer. The number of enrolled patients and the relatively short time of follow up do not allow to evaluate treatment efficacy.

Paving workers are exposed during road paving to several polycyclic aromatic hydrocarbons (PAHs) contained in asphalt fumes. In this study early genotoxic and oxidative effects of exposure to bitumen fumes were evaluated in 19 paving workers and 22 controls. Environmental and biological monitoring of exposure was carried out, measuring, on personal air samples from exposed workers collected during three working days, the concentration of 14 PAHs and urinary OH-pyrene at the end of each of the three working days. Genotoxic effect was evaluated analysing sister chromatid exchange (SCE) frequency and direct-oxidative DNA damage by formamido-pyrimidine-glycosylase (Fpg)-modified comet assay on lymphocytes. Tail moment values from Fpg-enzyme treated cells (TMenz) and from untreated cells (TM) were used as parameters of direct and oxidative DNA damage, respectively. For each subject, the TMenz/TM ratio >2.0 was used to indicate the presence of oxidative damage. DNA damage was also evaluated analysing comet percentage. Personal air samples showed low level of total PAHs (2.843 microg m(-3)) with prevalence of 2-3 ring PAHs (2.693 microg m(-3)). Urinary OH-pyrene after work-shift of the three working days was significantly higher than that found at the beginning of the working week. SCE analysis did not show any difference between two groups while an oxidative DNA damage was found in 37% of exposed with respect to the absence in controls. Comet percentage was significantly higher (P = 0.000 ANOVA) in the exposed than in controls. The results demonstrate the high sensitivity of comet assay to assess early oxidative effects induced by exposure to bitumen fumes at low doses and confirm the suitability of urinary OH-pyrene as a biomarker of PAH exposure. In conclusion the study suggests the use of Fpg-modified comet test as a biomarker of early genotoxic effects and that of urinary OH-pyrene as a biomarker of PAH exposure to furnish indications in terms of characterization, prevention and management of risk in occupational exposure to mixtures of potentially carcinogenic substances.

For many years surgery was the cornerstone of treatment for head and neck cancers and radiotherapy was the treatment of choice in adjuvant and advanced inoperable settings. Recently, induction sequential chemotherapy followed by radiotherapy has shown good tolerability and has prolonged the median overall survival. This phase II trial explored the feasibility of the concurrent association with radiotherapy of a full-dose chemotherapy based on an original schedule of docetaxel and cisplatin.Twenty-four patients with head and neck squamous cell carcinoma (HNSCC) were enrolled. Taxotere (docetaxel) was administered on day 1, weekly for 6 weeks. The dose was 33 mg/m2 /w. Cisplatin was administered on day 2 at the dose of 70 mg/m2. Radiotherapy delivered was 60 Gy divided in 30 administrations over 6 weeks.This schedule of treatment for HNSCC proved feasible. Appropriate support treatment, however, appears to be necessary for the feasibility of this concurrent chemo-radiotherapy.

The wide use of barium (Ba), cesium (Cs), antimony (Sb) and tungsten (W) in many industrial and agricultural fields causes the increased release of these metals into the environment, laying the basis for health risk. To assess the exposure for the general population, the development of adequate and reliable analytical techniques becomes compulsory. This study refers to the quantification of urinary Ba, Cs, Sb and W levels by both quadrupole (Q) and sector field (SF) inductively coupled plasma mass spectrometry (ICP-MS). The two procedures were compared for their performances and their measurement uncertainties. The limits of detection were (Q and SF) 23.0 and 5.21 ng L(-1) for Ba; 21.1 and 7.52 ng L(-1) for Cs; 1.09 and 0.43 ng L(-1) for Sb; and 0.36 and 0.49 ng L(-1) for W. The trueness was better than 93.3% and the precision less than 12% for both techniques. Relative expanded uncertainties of the analytical procedures, at the median levels found in the general population, were below 5% for all the elements with both ICP-MS techniques. The uncertainties related to the calibration and repeatability were the parameters most influencing the final analytical performance. The urinary median values observed in healthy subjects from central Italy were 1146, 4301, 60.8 and 48.5 ng L(-1) for Ba, Cs, Sb and W, respectively.

This study assesses 2,5-hexanedione (2,5-HD) in the urine of subjects exposed to n-hexane solvent between 1991 and 1998, from details obtained from the Registry of Biological Monitoring (BM) at the Florence Local Health Unit, and its development over time. The Registry contains 15,925 samples from 6,650 subjects occupationally exposed to n-hexane, especially in leather (9,099 samples; 3,607 subjects) and shoe (3,865 samples; 1,938 subjects) production. Over the time span studied there was a total reduction of 31.9% in urinary 2,5-HD level. The yearly decrease over the entire period was 5.4%. Dividing the 8 years into three periods: before the introduction of the new legislation for health protection in the workplace (1991–1993), during its transition (1994–1996) and after its complete enforcement (1997–1998), respectively, we observed a marked decrease in the last period. Women and young people (under 30 years) experienced significantly higher absorption levels (respectively, 7.1% and 24.4%). The data suggest that monitoring was more frequent in subjects with higher starting values, and the greatest decrease was reported in this group. Reduction may be due to less n-hexane in the products used, better structural conditions in the factories, and the effectiveness of inspections carried out by the authority for hygiene and safety in the workplace. The results confirm the usefulness of the reporting of risk levels of exposure to industrial toxicants by routine biological monitoring.

Background To evaluate the possible effect of inorganic arsenic (iAs) and of its species on the urinary excretion of porphyrin homologues. Methods Total porphyrins and their homologues (copro, penta, hexa, hepta, uroporphyrins) and arsenic species (trivalent and pentavalent As; monomethyl arsonic acid; dimethyl arsinic acid; arsenobetaine) were measured respectively by HPLC and HPLC-ICP MS in urine from 86 art glass workers exposed to iAs and from 54 controls. Results A significant increase in the excretion of penta and uroporphyrins was demonstrated for workers exposed to As; As3 was the species best correlated with urinary porphyrin excretion. Conclusions The increase of urinary excretion for some porphyrin homologues appears to be consistent with the inhibition by As of URO-decarboxylase in the heme biosynthesis pathway. The determination of urinary porphyrin homologues could be useful to assess, on a group basis, some early effects of arsenic and to demonstrate possible individual susceptibility to the element. Am. J. Ind. Med. 42:180–187, 2002. © 2002 Wiley-Liss, Inc.

This paper presents the results of a polycentric study carried out in seven different areas, organized by the Italian Society of Reference Values (SIVR) for assessing reference values of lead in blood (B-Pb) at the current doses of the metal to general population. The estimated arithmetic mean for B-Pb in males was of 45.1 microg/l and 30.6 microg/l in females; the 95th centile was 100 and 60 for males and females, respectively. The main variables influencing B-Pb levels were gender, age, BMI, outside sport practice, alcohol consumption and smoking habits, while the geographic area and the urban residence did not affect the metal concentration in blood.

The object of this study was to investigate the immune system of 19 women with a mean age of 35 years, for at least 2 years (mean = 13 years) exposed to electromagnetic fields (ELMFs) induced by radiotelevision broadcasting stations in their residential area. In September 1999, the ELMFs (with range 500 KHz-3 GHz) in the balconies of the homes of the women were (mean +/- S.D.) 4.3 +/- 1.4 V/m. Forty-seven women of similar age, smoking habits and atopy composed the control group, with a nearby resident ELMF exposure of < 1.8 V/m. Blood lead and urinary trans-trans muconic acid (a metabolite of benzene), markers of exposure to urban traffic, were higher in the control women. The ELMF exposed group showed a statistically significant reduction of blood NK CD16+-CD56+, cytotoxic CD3(-)-CD8+, B and NK activated CD3(-)-HLA-DR+ and CD3(-)-CD25+ lymphocytes. 'In vitro' production of IL-2 and interferon-gamma (INF-gamma) by peripheral blood mononuclear cells (PBMC) of the ELMF exposed group, incubated either with or without phytohaemoagglutinin (PHA), was significantly lower; the 'in vitro' production of IL-2 was significantly correlated with blood CD16+-CD56+ lymphocytes. The stimulation index (S.I.) of blastogenesis (ratio between cell proliferation with and without PHA) of PBMC of ELMF exposed women was lower than that of the control subjects. The S.I. of blastogenesis of the ELMF exposed group (but not blood NK lymphocytes and the 'in vitro' production of IL-2 and INF-gamma by PBMC) was significantly correlated with the ELMF levels. Blood lead and urinary trans-trans muconic acid were barely correlated with immune parameters: the urinary metabolite of benzene of the control group was only correlated with CD16+-CD56+ cells indicating a slight effect of traffic on the immune system. In conclusion, this study demonstrates that high frequency ELMFs reduce cytotoxic activity in the peripheral blood of women without a dose-response effect.

A great deal of research has revealed a frequent association between hearing impairment and Alzheimer's disease. Many of these studies have, however, been criticized for the lack of statistical significance, for the methodology used and for doubts regarding the diagnostic criteria used. The lack of uniform results prompted the present research. On the basis of some works in the literature, the authors felt that the study of middle and long-latency auditory evoked potentials, and their expression characterized by the P1 and P3 waves, the appropriate instrument for exploring the cortical and subcortical tracts of the auditory system which are most compromised in Alzheimer's disease. In fact, numerous studies have suggested that wave P1 is generated by peduncle-pontine nucleus cells of the tegmentum and that wave P3 is generated by sites located in the temporal lobes and hippocampus. The present study was conducted on 15 subjects suffering from Alzheimer's disease and 15 controls. Four subjects were excluded from the study because they were affected by Alzheimer's disease with severe dementia and were, thus, unable to cooperate. The 15 controls underwent accurate clinical and instrumental evaluation to rule out any neurological and intellectual disorders. The results for wave P1 show a statistically significant difference between the subjects affected by Alzheimer's disease and the controls. In fact, there was a difference in the presence of this potential. Moreover there was a statistically significant difference in P1 between those patients with average dementia and the controls but not between those with slight dementia and the controls. Finally, comparison of the abnormalities in P1 potential and P3 latency showed that in Alzheimer's disease alterations in P3 arise earlier and are more constant than alterations in P1. The physiopathological meaning of these results is discussed.

We report the results obtained in 1992 concerning the determination of blood lead levels (PbB) in 1321 subjects of the general population living in ten villages/towns of the Florence district characterised by the presence of artistic ceramic factories. We reported also the PbB values found in 2330 adults, 280 children, 39 pregnant women and their correspondent umbilical cords, who were examined during the second biological monitoring campaign against the risk of lead intoxication according to the DPR 496/82. Median PbB values were 92.5 micrograms/l (range 15-520 micrograms/l) for males and 62.5 micrograms/l (range 11-343 micrograms/l) for females. The lower PbB median values were found in the district of Livorno (76.25 micrograms/l and 48.25 micrograms/l in males and females, respectively) and Arezzo (80.5 micrograms/l and 52 micrograms/l in males and females, respectively). In comparison with the results obtained for the general Italian population during the previous biological monitoring campaign carried out in 1985-86 we observed PbB median values about 40% lower for both males and females and PbB median values about 55% lower for children. A significant statistic correlation (r = 0.53) was found between PbB of pregnant women and their umbilical cords.

We report the results of 24,475 blood lead determinations (PbB) performed by the Occupational Toxicology Laboratory of Florence between 1976 and 1995. Biological monitoring was carried out in 383 factories localized in the districts of Florence, Prato, Pistoia, Lucca and Pisa. The most represented production fields were colouring ceramic factories, artistic ceramics, transfer-pictures for ceramics, glass factories, typographies, glass decoration factories, chemical factories. In twenty years, the median values of PbB decreased from 48 to 17 micrograms/100 ml in males and from 40 to 8 micrograms/100 ml in females. The 95 degrees centile ranged from 84 to 46 micrograms/100 ml for males and from 63 to 42 micrograms/100 ml for females. In the 1988-95 period, we observed an increase of both the 95 degrees centile and the maximal values because of the inclusion of data from workers employed in factories where the "decorazione a scavo" technique, which is characterized by elevated environmental lead concentrations, was used. In the period 1991-93, the ranges of PbB observed in glass decoration factories were 13-160 micrograms/100 ml for males and 4-80 micrograms/100 ml for females, respectively.

Objective: Determination of the urinary levels of 2.5-hexanedione (2,5-HD) was performed in subjects belonging to the Italian general population to define the reference value for this metabolite. Materials and methods: Urine samples were collected from 123 healthy Italian subjects who had not been occupationally exposed to n-hexane or methyl-n-butyl ketone (60 men and 63 women; 53 living in urban areas and 70 living in rural areas; 36 smokers and 87 nonsmokers; 65 aged above 35 years and 58 aged below 35 years). The determinations were performed by a gas chromatography method using a flame ionization detector (FID). A quality-control step was realized by analysis of 78 of these samples by high-performance liquid chromatography (HPLC) with UV detection. Results and discussion: The distribution of 2,5-HD concentration was log-normal and the corresponding centiles at the 95% confidence interval were as follows: the 50th centile, 0.270 mg/l for men and 0.191 mg/l for women; the 75th centile, 0.352 and 0.330 mg/l, respectively, for men and women; and the 95th centile, 0.762 and 0.582 mg/l, respectively, for men and women. The reference value, calculated as the upper unilateral 95% tolerance interval at 95% of confidence, was 0.795 mg/l for men and 0.627 for women.

The objective of this retrospective, case-series study was to examine the relationship between disability in Instrumental Activities of Daily Living (IADLs) and cognitive impairment measured by the Mini-Mental State Examination (MMSE), and how this relationship was influenced by different levels of formal education. The setting of the study was the Cognitive Disorders Center of the Local Sanitary Unit (USL) No. 4 in Prato (Italy). Independence in IADL was strongly related to MMSE scores. A score of less than 24 at the MMSE was predictive of disability in at least one IADL with 0.82 sensitivity and 0.73 specificity. However, when only people with a very low level of formal education were considered, the best threshold predicting IADL disability was 17 (sensitivity 0.76, specificity 0.75). Thus, scholastic achievement is an effect modifier of the relationship between cognitive status, as measured by the MMSE, and IADL disability. Subjects with low education level and poor performance at the MMSE are often independent in activities making demand on cognitive function, such as IADLs. These results suggest that a lower MMSE cut-off score should be considered when screening for cognitive impairment in these persons.

The paper describes the results of a polycentric study for the assessment of reference values of urinary chromium (U-Cr) in the Italian population.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.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.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.

Blood lymphocyte subset evaluation was performed before after oral challenge with 10 mg of Ni, in 9 healthy women and in 15 allergic to Ni. Following challenge, 7 allergic showed a flare up of eczema and/or urticaria. In the controls, CD4+ lymphocytes were modified 24 hours after Ni challenge: CD4+/CD44RO- "virgin" cells were reduced while CD4+/CD45RO+ "memory" cells increased. The allergic women, not sensitive to oral Ni, showed an increase of B lymphocytes after the test. On the contrary, the oral Ni reacting patients presented a reduction of monocytes 4 hours after Ni ingestion and marked reduction (ranging from 20 to 50%) of T and B lymphocytes after 24 hours. These significant T and B lymphocytes changes suggest a migration of the cells in peripheral tissues, likely skin and GUT mucosa.

Lymphocyte subpopulations were studied in 31 men working in a plant producing plastic materials in relation with control groups of similar age and smoking habit. 8 workers (group A) were exposed to solvents (mainly methylethylketone and dimethylformamide), 8 men (group B) to dust containing particles of calcium carbonate, polyvinylchloride, phtalates, unsaturated oils, paraffin wax, iron oxides, titanium bioxides, barium, zinc and lead and 15 men (group C), working in the same department as group B, were studied after a period of 16 months during which lead chromate was employed in the preparation of colors. The lymphocyte subpopulations were normal in group A, while in B there was a significant increase of HLA-DR + cells (monocytes, B and activated T lymphocytes). In group C, T helper/inducer lymphocytes (mainly CD4(+)-CD45RO- "virgin" lymphocytes), CD19+ B lymphocytes, CD3-HLADR+ and CD3-CD25+ (activated B lymphocytes and monocytes) were significantly reduced without changes of serum IgM, IgG and IgA. Highly significant correlation was found between B lymphocytes (reduced in the workers about 40%) and CD4(+)-CD45R0+ "memory" lymphocytes (reduced about 20%). Moreover, blood lead (correlated with urinary chromium) showed a highly significant negative correlation with the B lymphocytes. This study demonstrates that combined exposure to toxic agents produces specific modifications in the lymphocyte subsets without changes in immunoglobulins and confirms the results of previous researches showing that the exposure to lead or chromate induces reduction of lymphocytes in the peripheral blood.

The influence of not occupational factors (smoking, alcohol, coffee, drugs, sport, sex, age and body weight) on hippuric acid excretion was analyzed in two groups of healthy male subjects. A group was constituted of 710 painters occupied in wood and coach workings and the other one of 109 not occupational. The 5 degrees, 50 degrees, 95 degrees percentiles of the two distribution were 208, 605, 1784 and 153, 538, 1700 mg/g creatinine respectively. The analysis of variance undertaken on exposed subjects showed that there was a significative difference between urinary hippuric acid levels of subjects consuming alcohol and the not ones. Multiple regression analysis on hippuric acid excretion values distribution in not exposed group showed that only the variable "coffee consumption" resulted statistically significative (Ln hippuric acid = 5.0287 + 0.8062; R2 = 01221). Coffee consumption increase excretion rate (mg/hour) of hippuric acid likely an exposure to a toluene air concentration of 50 mg/m3. The authors suggest an action of caffeine on endogenous amount of benzoic acid.

The Authors have studied AST and ALT enzymatic activities in the workers of two firms, the former of which (tannery) with a high and the latter (boot and shoe factory) with a low level of hepatic-toxic risk. The influence of various trouble factors such as age, sex and seniority was eliminated through appropriate statistical techniques. A significant difference was evidenced between AST and ALT levels in two firms, chiefly attributable to the quantity and quality of the substances utilized in the two technological cycles: trichloroethylene, chromium, sulphuric acid, mineral oils, ammonia, N-hexane, pentanes acetone, ciclo hexane, methanol, ethyl acetate, isopropyl acetate, toluene, methylene chloride.

The aim of this pilot study was to determine the most sensitive urinary cotinine level able to assess environmental tobacco smoke (ETS) exposure. 54 Florentine subjects (29 males and 25 females), reporting to be nonsmokers and exposed (E) or not exposed (NE) to ETS at home, at work or in places of recreation, were examined. The urinary cotinine concentration was determined using gaschromatographic analysis in samples collected on three consecutive days. 18 subjects (33.3%) reported to be exposed to ETS had a greater median cotinine concentration than 36 ETS-NE subjects (E = 3.3 pg/L vs NE = 2.2 microg/L, median values), with borderline statistical significance (P = 0.05). The 2.5 microg/L cotinine concentration was the only statistically significant cut-off (P = 0.04) discriminating between ETS-E to ETS-NE subjects, identifying 51.9% of the subjects examined as exposed (E). Considering the expanded uncertainty of measurement of the method used (20%), urinary cotinine concentrations higher than 3.1 microg/L, a value whose confidence interval is higher than our proposed cut-off of 2.5 microg/L, mean that to be sure that a subject is exposed to ETS.

The study assesses the time trend in exposure to nickel among factory workers in Florence, via data on biological monitoring. A data-base of nickel in urinary samples (Ni-U mg/l) was created for the period 1991 to 1998.The data-base contained 2.138 samples, measured by atomic absorption (GF-AAS),from 893 workers. Subjects came from 157 factories in various manufacturing sectors, especially electroplating, mechanical workshops, jewellery.Ni-U levels were correlated with manufacturing sector. The highest levels were found among workers from electroplating industries, where exposure was mainly due to water-soluble nickel compounds. The eight-year time trend showed a statistically significant decrease in Ni-U values, with a sharper drop during the last two-year period. Age, sex and number of samples per subject were not statistically related to this trend.The observed Ni-U decrease could be related to the efficacy of new legislation introduced in Italy during the study period (Law 626/94 and subsequent laws), but also to the intense labour inspection activities that officials of National Health Service performed, which were rightly focused on nickel exposure in different manufacturing sectors. This study confirms the usefulness for occupational risk evaluation of a biological monitoring data-base of routinely collected data.

Aims and background Several chemical compounds included in the group of polycyclic aromatic hydrocarbons (PAH) and benzene are well-known human carcinogens present in the atmosphere of polluted urban areas. Major sources include vehicle traffic and industrial emissions, but also cigarette smoke. Genotoxic damage derived from exposure to PAHs can be measured in healthy adults by specific assays as PAH-DNA adducts. In the frame of EPIC-Italy, we recently carried out a cross-sectional study in different areas of the country (Palli et al., Int J Cancer, 87: 444-451, 2000) and showed that mean DNA adduct levels varied considerably among different centers, being highest in Florence (a large metropolitan area in Tuscany) and lowest in Ragusa (a small town in Sicily). Methods A subgroup of EPIC volunteers, representative of these two local cohorts, agreed to collect 24-h urine samples, and we measured the excretion of two potential biomarkers of exposure to environmental pollutants: t,t-muconic acid (MA), a metabolite of benzene, and 1-hydroxypyrene (1-OHP), a metabolite of pyrene. Overall, 69 24-h urine samples were available for analyses. Results The absolute amounts of 1-OHP and MA excreted in the 24-h urine samples were 169.6 ng and 33.8 μg, respectively. Urinary excretion of both metabolites did not vary according to age or area of residence. Strongly significant differences emerged when current smokers were compared to non-smokers for 1-OHP (P = 0.0001) and MA (P = 0.01), thus confirming that smokers are directly exposed to PAHs and benzene from tobacco smoke, with a dose-dependent effect particularly evident for MA. Multivariate analyses showed positive associations of 1-OHP excretion with male sex, low education and being overweight but not with residence in two areas with contrasting levels of urban pollution; MA excretion tended to be higher in Florence. Conclusions These two urinary metabolites are strongly related to tobacco smoke and do not appear to represent reliable biomarkers of exposure to environmental pollutants in the general population.