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OBJECTIVES: To evaluate the prevalence of diarrhea and its association with drug use in elderly outpatients. METHODS: The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. The demographic data, disability, gastrointestinal symptoms, and current medications were evaluated using a structured interview, including the evaluation of the activities of daily living (ADL), the instrumental activities of daily living (IADL), and the gastrointestinal symptoms rating scale (GSRS). RESULTS: The study included 5,387 elderly subjects who regularly completed the structured interview. In total, 488 patients (9.1% of the whole population, 210 men and 278 women, mean age 75.6 6.2 yr, range 65–100 yr) reported diarrhea, that is, items 11 and 12 of the GSRS, during the 7-day period before the interview. The prevalence of diarrhea significantly increased with older age (P= 0.025), the severity of ADL (P < 0.0001) and IADL disability (P < 0.0001), and the number of drugs taken (P= 0.0002). A multivariate analysis demonstrated that the presence of diarrhea was significantly associated with the use of antibiotics (odds ratio [OR] 4.58, 95% confidence interval [CI] 1.95–10.73), proton pump inhibitors (OR 2.97, 95% CI 2.03–4.35), allopurinol (OR 2.19, 95% CI 1.26–3.81), psycholeptics (OR 1.82, 95% CI 1.26–2.61), selective serotonin reuptake inhibitors (OR 1.71, 95% CI 1.01–2.89), and angiotensin II receptor blockers (OR 1.46, 95% CI 1.08–1.99), also accounting for sex, age, and the use of antidiarrheal agents and drugs for functional gastrointestinal disorders. CONCLUSION: Diarrhea is a common problem in elderly outpatients. Its prevalence increases with old age, the severity of disability, and the number of drugs. Monitoring the presence of diarrhea and its complications in elderly patients who need treatments with drugs significantly associated with diarrhea may be clinically useful.

Objective To evaluate the prevalence of drug use by elderly outpatients in Italy and to identify the association between drug use and gastrointestinal symptoms. Study design and setting The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. All consenting elderly patients seen at the GPs’ offices were evaluated for gender, age, disability, current medications, and upper gastrointestinal symptoms. Results The study included 5,515 elderly subjects. The prevalence of drug use was 91.6%, and the mean number of drugs taken was 2.86 per person. Both the prevalence and the mean number of drugs significantly increased with advancing age. Regarding gastrointestinal symptoms, 32.7% of patients reported at least one upper gastrointestinal symptom: 25% with indigestion syndrome, 16.2% with abdominal pain, and 14.2% with reflux symptoms. A significantly higher prevalence of symptoms was observed in females, patients who were taking a higher number of drugs, and those who had higher disability. Adjusted multivariate analysis demonstrated that the use of nonsteroidal antiinflammatory drugs, steroids, psycholeptics, diuretics, selective β2 adrenoreceptor agonists or adrenergics, and antiplatelet drugs was significantly associated with upper gastrointestinal symptoms. Conclusion The prevalence of drug use is very high in this elderly outpatient population. The number of drugs and the use of some specific drug classes are significantly associated with the presence of upper gastrointestinal symptoms.

Summary Background: The association between coxib or non-steroidal anti-inflammatory drug use with gastrointestinal symptoms and drug prescriptions in ambulatory elderly patients is not well defined. Aim: To evaluate the association between non-steroidal anti-inflammatory drug NSAID and coxib use with gastrointestinal symptoms and therapies in elderly subjects managed by their general practitioner. Materials: The study was carried out by 133 general practitioners in Italy. By using a structured interview, sex, age, physical function, current medications, new drug prescriptions and upper gastrointestinal symptoms were registered from all elderly subjects who were referred to their general practitioners during a 2-week period. The numbers of hospitalizations, gastrointestinal bleeding events and gastrointestinal diagnostic procedures occurring during the last 6-month period were recorded. Results: Included in this study were 5515 elderly subjects. The overall prevalence of drug use was 92%. Musculo-skeletal drugs were taken by 15% of patients; NSAIDs were taken by 6%, and coxibs by 3% of patients. A significantly higher prevalence of upper gastrointestinal symptoms was observed in elderly NSAID users compared with coxib users and non-users of musculo-skeletal drugs (44% vs. 33% vs. 32% respectively, P = 0.001). The prescriptions of drugs for acid-related disorders were significantly higher in patients who were concomitantly taking NSAID rather than coxibs (13% vs. 6%, P

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.

Objective Personal exposure to airborne benzene is influenced by various outdoor and indoor sources. The first aim of this study was to assess the benzene exposure of a sample of urban inhabitants living in an inner-city neighborhood of Florence, Italy, excluding exposure from active smoking. The secondary objective was to differentiate the personal exposures according to personal usage patterns of the vehicles. Methods A sample of 67 healthy non-smokers was monitored by passive samplers during two 4-weekday campaigns in winter and late spring. Simultaneously, benzene measurements were also taken for a subset of participants, inside and outside their houses. A 4-day time microenvironment activity diary was completed by each subject during each sampling period. Other relevant exposure data were collected by a questionnaire before the sampling. Additional data on urban ambient air benzene levels were also available from the public air quality network. The passive samplers, after automated thermal desorption, were analyzed by GC-FID. Results Benzene personal exposure levels averaged 6.9 (SD = 2.1) and 2.3 (SD = 0.7) μg/m3 in winter and spring, respectively. Outdoor and indoor levels showed high correlation in winter and poor in spring. In winter the highest benzene personal exposure levels were for people traveling by more public transport, followed by users of only car and by users of only bus respectively. Conclusions The time spent in-transport for work or leisure makes a major contribution to benzene exposure among Florentine non-smoking citizens. Indoor pollution and transportation means contribute significantly to individual exposure levels especially in winter season.

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.

Comprehensive geriatric assessment has become synonymous with geriatric practice. This includes evaluation of the older person's physical and mental health, and the functional and social status. We propose a new way of representing a person's condition, called the "polar diagram". This shows the subject's scores on the evaluation scales that are arranged in radial positions inside a circle. The outer part of the circle corresponds to the best condition. Gaps between the best condition and the actual scores are easily identified. The diagram can be employed to monitor the subject's condition and to assess any changes in outcomes.

The aim of this study was to evaluate factors predicting length of stay in hospital of geriatric patients. Study participants were 402 patients (183 males and 219 females) consecutively admitted to four geriatric wards located in Chieti, Perugia, Pescara and Prato, Italy. Information on potential predictors of length of stay was collected; in particular, we assessed the presence and severity of specific chronic medical conditions, level of physical function, cognitive status, and depressive symptoms. Moreover, information on family and social support was obtained. In general, participants were old, often cognitively impaired and physically disabled. Average length of stay ranged from 9.4±3.3 days (Perugia) to 14.1±7.2 days (Chieti), and was statistically different across centers (p

Summary Functional assessment has a primary role in the evaluation process of Alzheimer patients during clinical trials. In Alzheimer's disease (AD), the severity of functional impairment is directly correlated to mortality. In some cases, functional deficit does not progress at the same pace as behavioral and cognitive deterioration. For these reasons, it is advisable to measure sparately cognitive, behavioral and functional status to obtain a full picture of every patient. In this review, the main instruments used for functional evaluation of AD are illustrated. In the early phases of AD, the scales which evaluate complex activities such as the instrumental activities of daily living (IADL) are preferred, since they allow to reveal also slight impairments of the functional abilities. In the advanced phases, it is better to use some instruments related to the basic activities of daly living (ADL) and the physical self-maintenance scale (PSMS).

15 women with a positive patch test only to nickel (Ni) and without atopy and 10 control women were selected for the study. Blood and urine specimens were collected with a standard procedure either before (at 8 a.m.) or 4 and 24 h after the ingestion of 10 mg of Ni (as Ni sulfate). 7 of the Ni-sensitized patients showed a flare-up of eczema and/or urticaria during the test, while the other women were non-symptomatic. Serum and urine Ni of controls and Ni-sensitized women did not significantly differ. Serum and urine Ni levels determined before the oral Ni challenge were in the range of reference values recently reported by other authors (0.2-2.0 micrograms/l of serum or urine). Ni was greatly augmented in urine and serum 4 h after the challenge (25th-75th percentiles: 43-264 micrograms/l urine Ni and 15-52 micrograms/l serum Ni). 24 h after Ni ingestion, urine Ni was 41-153 micrograms/l and serum Ni 4-17 micrograms/l. Our study confirms a previous investigation showing similar levels of serum and urine Ni following ingestion of the metal in control and Ni-sensitized women without atopy.

There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset Alzheimer’s disease (AD). Early prediction and diagnosis of AD might be improved by the detection of a proteolytic dysfunction in extracts from cultured AD fibroblasts, producing altered isoelectrophoretic forms of the enzyme transketolase (TK-alkaline bands). The TK profile and apolipoprotein E (APOE) genotype were examined in fibroblasts from 36 clinically diagnosed probable late-onset sporadic AD patients and 38 of their asymptomatic relatives, 29 elderly healthy individuals, 12 neurological non-AD patients, and 5 early-onset AD patients. TK alterations occurred in (i) several probable AD patients regardless of age-of-onset and severity of disease; (ii) all early-onset AD patients and APOEε4/4 carriers; and (iii) nearly half of asymptomatic AD relatives. Normal subjects and non-AD patients were all negative. Notably, culture conditions promoting TK alterations were also effective in increasing active BACE1 levels. Overall, the TK assay might represent a low-cost laboratory tool useful for supporting AD differential diagnosis and identifying asymptomatic subjects who are at greater risk of AD and who should enter a follow-up study. Moreover, the cultured fibroblasts were confirmed as a usefulin vitromodel for further studies on the pathogenetic process of 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.

A reliable high-performance liquid chromatographic (HPLC) method which allows the determination in human urine of two important metabolites of N,N-dimethylformamide (DMF), namely N-methylformamide (MMF) and N-methyl-N-(hydroxymethyl)formamide (DMFOH), is reported. A single-step rapid purification of urine was performed on a C18 solid-phase extraction column and the eluate was injected directly on to the HPLC column. HPLC was carried out isocratically on Aminex Ion Exclusion HPX-87H column using 7.5.10(-4) M sulphuric acid as the mobile phase with ultraviolet detection at 196 nm. The method is specific, accurate, precise and sufficiently sensitive to be applied to the biological monitoring of MMF and DMFOH in workers exposed to DMF.

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 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.

Objectives To investigate whether amnestic mild cognitive impairment (aMCI) is characterised by restriction in instrumental activities of daily living (IADL). Further, to examine the role of comorbidity and cognitive performance on IADL changes in aMCI subjects. Methods The study included 132 subjects with aMCI and 249 subjects with no cognitive impairment (NCI), consecutively enrolled as outpatients in a multicentric Italian clinical-based study, the ReGAl Project. All subjects underwent a comprehensive evaluation including clinical examination, laboratory screening, neuroimaging and cognitive and behavioral assessments. Functional status was evaluated by the Lawton's Instrumental Activities of Daily Living (IADL) scale. Comorbidity was evaluated by the Cumulative Illness Rating Scale (CIRS). Cognitive evaluation included tests assessing episodic memory, language, attention/executive functioning and praxis, as well as the the Mini-Mental State Examination (MMSE) as a measure of global cogniton. Results Subjects with aMCI had higher IADL changes than NCI. Among IADL items, aMCI subjects showed a significant impairment in shopping, taking drugs, and handling economy; however also NCI had minor IADL changes regarding cooking, washing and cleaning. IADL restriction in aMCI subjects was significantly associated with cognitive performance, mainly related to executive functioning, but not with comorbidity. On the contrary, in NCI sensory impairment accounts for slight IADL changes. Conclusion In aMCI subjects a mild degree of cognitive deterioration has a stronger impact on IADL than somatic comorbidity. Current diagnostic criteria for MCI should include a mild impairment in IADL. Copyright © 2007 John Wiley & Sons, Ltd.

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.

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.

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.

In this study, the authors evaluated exposure to airborne polycyclic aromatic hydrocarbons (PAHs) in workers exposed to exhaust gas from cars, and they assessed the efficiency of urinary 1-hydroxypyrene as an indicator of exposure to pyrene and PAHs. The authors selected 2 groups of police who worked in 2 areas in the city of Florence: 1 group was highly exposed to high-density traffic emissions during the winter and summer of 1997, and the 2nd group experienced low exposure to traffic emissions during the same period. Ambient monitoring was achieved with personal sampling of airborne PAHs during each workshift. Eight hydrocarbons were used as indicators of pollution caused by PAHs (e.g., pyrene, benzo[a]pyrene, benzo[a]anthracene, dibenzo[a,h]anthracene). Biological monitoring was performed through dosing of 1-hydroxypyrene (pyrene metabolite) in urine samples taken at the end of each workshift. The ambient monitoring revealed that PAH concentrations were influenced by both season of sampling and varying intensities of traffic in the different areas. The median concentration of benzo[a]pyrene in winter was twice as high in the high-density traffic area as in the low-density traffic area (i.e., 4.1 ng/m3 versus 1.8 ng/m3). In summer, the high-density traffic area experienced benzo[a]pyrene concentrations that were 6 times higher than in the low-density traffic area (i.e., 1.2 ng/m3 versus 0.2 ng/m3). Benzo[a]pyrene was also correlated highly (r(s) = .92, p < .0001) with the mixture of total PAHs analyzed, thus confirming its function as a good indicator of exposure to PAHs in an urban environment. Levels of urinary 1-hydroxypyrene appeared to be generally influenced by the intensity of traffic, especially during the winter (i.e., median value in winter was 199.2 ng/gm creatinine in the high-density traffic area and 120.5 ng/gm creatinine in the low-density traffic area). An analysis of the general data revealed that 1-hydroxypyrene was, to some degree, related to pyrene, benzo[a]pyrene, and airborne total PAHs, whereas analysis of separate data for the area and the season revealed an emergence of a closer correlation during the winter in the high-traffic area. Therefore, 1 -hydroxypyrene can be considered a good biological indicator of exposure to airborne PAHs in the urban environment, especially in winter and in high-density traffic areas.

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.

Objectives: This article reports the results obtained with the biological and environmental monitoring of occupational exposure to cyclohexane using 1,2-cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL in urine suggested by a physiologically based pharmacokinetic (PBPK) model was compared with the results obtained in workers. Methods: Individual exposure to cyclohexane was measured in 156 workers employed in shoe and leather factories. The biological monitoring of cyclohexane exposure was done by measurement of 1,2-DIOL and 1,4-DIOL in urine collected on different days of the working week. In all, 29 workers provided urine samples on Monday (before and after the work shift) and 47 workers provided biological samples on Thursday at the end of the shift and on Friday morning. Another 86 workers provided biological samples at the end of the work shift only on Monday or Thursday. Results: Individual exposure to cyclohexane ranged from 7 to 617 mg/m3 (geometric mean value 60 mg/m3). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2, and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically significant correlation was found between environmental exposure to cyclohexane and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday and Friday showed only a poor correlation to exposure with a wide scatter. Both metabolites have a urinary half-life of close to 18 h and accumulate during the working week. Conclusions: Comparison between data obtained from a PBPK model and those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary metabolites suitable for the biological monitoring of industrial exposure to cyclohexane.

Contact dermatitis among hairdressers is common and is one of the most frequent occupational dematoses due to continual exposure to water, detergents, hair dyes, permanent waves and metal equipment. Use of individual protection systems – as gloves – is considered a good measure of prevention. Few data exist about the real permeation resistance (PR) of gloves, also in term of time of PR. We tested two types of djsposable latex gloves different by thickness and density of the manufacture material. We used a permeation cell composed of two separated parts: in the upper part we introduced the hair colouring formulation and in the lower one the collection medium (NaHSO3 1% in water); the two parts were separated by a portion of the glove material. A 100 microL volume of the collection medium was collected and injected onto a HPLC apparatus after 1, 2, 4 and 24 hours. A diode array detector was utilised selecting two wavelengths in the UV range (240 and 275 nm) with a linear concentration gradient up to 60% of methanol/acetonitril mixture. We can simultaneously analyse 9 oxidation dyes and the detection limits were sufficient to determine these substances at very low concentrations. We obtained respectively a breakthrough time less than 24 hours for the lower thickness glove and of over 24 hours for the other one; the latex gloves are suitable for prevent the skin contamination during the preparation of the colourings mixture in the hairdresser activity. The obtained data show those latex gloves, of both thickness, have a very high PR. On the other hand, the use of latex gloves has been associated with the more frequent recognition of immediate-type hypersensitivity responses related to latex products. The prosecution of the study will evaluate the PR of latex-free gloves.

Art glass manufacturing is one of the most interesting examples of exposure to complex mixtures. Among the raw materials used are silica sand, borax, carbonates, nitrates of Ca, Na, K, and a great number of compounds that are mainly oxides of As, Sb, Al, Zn, Cr, Ni, Sn, Se, Cd, Mn, Cu, Co, Fe, Nd, Er, Eu, and La. In six art glass factories that use As or Sb as fining agents, the exposure to these elements was investigated in 32 workers by means of environmental and biological monitoring. Analysis was conducted by atomic absorption spectrometry (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). The results confirmed that As, which is the main carcinogen in glass production, reaches high air concentrations and is generally above the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value-time-weighted average (TLV-TWA) of 10 micrograms/m3. When partly substituted by antimonial compounds, As air concentrations dropped dramatically, while the air levels of Sb (which is considered less toxic but is classified as a class 2B carcinogen by IARC) were relatively low and below the ACGIH TLV-TWA of 500 micrograms/m3. Exposure to As and Sb also differed in the three types of jobs investigated: As was high in oven chargers, Sb was higher in batch mixers, and both elements were low in makers-formers. Eleven to 18 elements were detected: arsenic, Al, Ba, Sb, Pb, and Zn were the elements most frequently measured (in tens, and in some cases hundreds, of micrograms/m3), followed by B, Li, Mn, Se, Sn, Sr, Ce, La, and Nd (in micrograms or in some cases tens of micrograms/m3. The results of biological monitoring for As, Sb, and other elements were in agreement with environmental monitoring data. We concluded that multiple detection of elements is a useful tool (or the evaluation of exposure to complex mixtures such as those used in the art glass industry and that such detection also allows a more accurate evaluation of related epidemiological data.

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.

Some methods for analysing N,N-dimethylformamide and its metabolites [hydroxymethyl-N-methylformamide, hydroxymethylformamide and N-acetyl-S-(N-methylcarbamoyl)cysteine] in the urine of exposed workers are described. Unchanged dimethylformamide was measured after pretreatment of urine (2 ml) with silica gel cartridges and elution with methanol. The gas chromatographic analysis using a nitrogen phosphor detector made it possible to detect N,N-dimethylformamide in urine even when workers were exposed to low concentrations of the solvent (about 1 mg/m3). N-Hydroxymethyl-N-methylformamide and N-hydroxymethylformamide were analysed as N-methylformamide and formamide respectively after direct injection of urine into the gas chromatograph. The injection port temperature played an important role in the gas chromatographic determination of these products. Reliable results were obtained when direct or split injections were performed at 250 degrees C. The splitless injection gave the same reliable results at 150 degrees C. In urine samples from occupationally non-exposed persons, N-methylformamide could not be detected. In contrast, formamide (or its precursor, hydroxymethylformamide) was present in every urine sample. Our results in respect of 19 urine samples analysed with the injection port of the gas chromatograph at 250 degrees C gave a mean of 8.6 mg/l of formamide. N-Acetyl-S-(N-methylcarbamoyl)cysteine was determined using a modified method for analysing organic acid in urine samples. The metabolite was extracted with ethyl ether in an acid environment, treated with a silylating reagent and measured by gas chromatography/mass spectrometry.

In a controlled clinical trial, amantadine 400 mg daily, 200 mg daily and 200 mg daily given with 20 mg of pemoline daily were compared with placebo in the treatment of elderly patients suffering from involutional cerebropathy characterized by psychomotor slowing down. The results showed that amantadine 400 mg daily was superior to placebo but was associated with a high incidence of side-effects (37 per cent), amantadine 200 mg daily was not superior to placebo but when pemolint 20 mg daily was added the combination was superior to placebo and few side-effects were reported.

The urinary excretion of single or multiple oral doses of amantadine hydrochloride by three elderly patients has been studied by gas chromatography. Steady state amounts in urine were about 230–240 mg per day. The half life of urinary excretion was approximately 34,17 hours. Urine collection from aged subjects is difficult.

The aim of the study was to evaluate which characteristics of geriatric patients account for readmission to hospital, 6 months after discharge. All patients (203 females, 176 males) consecutively admitted over a two-month period to four acute geriatric care units, located in the cities of Chieti, Perugia, Pescara and Prato, participated in the study. Data that could potentially explain early and late readmissions were collected for each patient. Prevalence of diseases and comorbidity were assessed with the Cumulative Illness Rating Scale (CIRS); physical function by self-report (ADL, IADL) and objective (Stand and Walking Speed) measures; cognitive level by MMSE; and depressive symptoms by the Geriatric Depression Scale (GDS). Information on family and social support were also obtained. After discharge, data on hospital readmissions were collected for six months. For each readmitted patient (cases), medical records were reviewed, and supplementary information was obtained from families and general practitioners. Readmissions were classified as "early" (within the first three months), "late" (within the third and sixth month), and "multiple" (2 or more readmissions irrespective of the period). Patients not readmitted (alive at home) were considered as controls. Systematic differences between centers and between periods of readmissions were evaluated using one-way analyses of variance, and Pearson's chi 2 test. Factors related to early, late, and multiple readmission were identified in multivariate logistic regression models. On univariate analysis, patients readmitted over the first three-month period were sicker than controls (CIRS classes 3-4: 52.1% vs 34.1%), had more social problems or behavioral symptoms, and were more functionally impaired (ADL dependencies 3.3 +/- 0.4 vs 2.1 +/- 0.2). Patients who were readmitted between the third and the sixth month after discharge had a significantly higher CIRS total score (p = 0.006). Patients with multiple readmissions had more severe diseases, and more social problems. On multivariate analysis, early readmission was associated with unsatisfactory social conditions, living alone, severity of diseases and cognitive impairment, while late readmission was associated with comorbidity only. Multiple readmissions were related only to social factors, and to hospital admission before the baseline evaluation. The findings of this study suggest that interventions aimed at improving unfavorable social conditions may reduce the rate of rehospitalization in geriatric patients.

Some years ago this group suggested that microvascular endothelium may be considered as one of the regulators of kinin metabolism on the basis of the following data: a) Arterial kininogen is slightly higher than that of venous (15). b) Venous recovery of intraarterial bradykinin is very poor, indicating a high capillary clearance (1, 2). c) During the reactive hyperemia following circulatory arrest, kininogen decreases (15).

The mechanism of the pathophysiology of clinical phenomena which follow subarachnoid hemorrhage (SH) is still not fully understood. The hypothesis that the blood displaces or disrupts intracranial structures (10) is not convincing particularly for the headache, stupor and sterile meningitis which follow minimal subarachnoid hemorrhage (10).