[Hearing disability in relation to audiometric threshold values: hypothesis on the determination of the onset of hearing loss]. / Disability uditiva in rapporto alla soglia audiometrica: ipotesi sulla determinazione di insorgenza dell'indebolimento del senso dell'udito.

BACKGROUND: The term auditory disability (AD) means the presence of auditory symptoms due to hearing loss. Until now the audiometric threshold cut-off between the presence or absence of AD was not clear. OBJECTIVES: In this study we attempted to define the value of audiometric threshold that could be considered as the limit between the presence or absence of weakness of auditory function, considered as the threshold as the 95th percentile of subjects that did not report AD. METHODS: The study group consisted of 1641 males, 891 normally hearing and 750 affected by noise-induced hearing loss (NIHL) Each subject was submitted to a questionnaire specifically created in order to determine the presence of AD. RESULTS: Statistical analysis confirmed the reliability of answers to items. AD was present in 577 subjects, not all affected by NIHL. Audiometric threshold and age correlated significatively with the degree of AD. CONCLUSIONS: The results obtained allowed the audiometric threshold values to be determined at the 95th percentile of subjects who did not report AD, in relation to the average of frequencies normally used in hearing loss evaluation.

Cancer risk among male farmers: a multi-site case-control study.

Farmers may experience exposure to several hazardous substances, and cancer risk in this occupational group is considered an important public health issue. In order to examine the association between cancer and farming among male agricultural workers, a hospital-based case-control study was conducted in five Italian rural areas. The cancer sites selected for the study were: lip, oral cavity and oropharynx, oesophagus, stomach, colon, rectum, lung, skin melanoma, skin non-melanoma, prostate, bladder, kidney, and non-Hodgkin's lymphoma. In all, 1525 newly diagnosed cases, aged 20-75 years, were ascertained in hospital records, covering the period between March 1990 and September 1992, and for 1279 of them, a detailed exposure information was collected by a standard questionnaire. Data analyses were performed comparing each cancer site to a control group, including a subset of the other cancer sites in the study. Unconditional logistic regression models were used in the statistical analyses. Increased risks of cancer associated with agricultural work were found for stomach (OR = 1.4, 95%CI:0.9-2.0), rectum (OR = 1.5, 95%CI:0.8-2.7), larynx (OR = 1.4, 95%CI:0.8-2.5), and prostate (OR = 1.4, 95%CI:1.0-2.1). The excess of prostate cancer was specifically related to application of pesticides (OR = 1.7, 95%CI:1.2-2.6).

Cancer risk among female agricultural workers: a multi-center case-control study.

BACKGROUND: Cancer risk among women engaged in farming has been poorly investigated. This group of female workers is of particular interest, however, since they may experience exposure to several potential agricultural hazards. METHODS: A hospital-based case-control study was conducted in five Italian rural areas to examine the association between cancer and farming among women. The areas selected were located in three different regions (i.e., Piedmont, Tuscany, and Emilia-Romagna). The following cancer sites were selected for the study: stomach, colon, rectum, lung, skin melanoma, skin non-melanoma, breast, cervix and corpus uteri, ovary, bladder, kidney. Cases of non-Hodgkin's lymphoma were also included. Altogether, 1,044 newly diagnosed cases aged 20-75 years were ascertained from hospital records from March 1990 to September 1992, and for 945 of them detailed information was collected by a standard questionnaire. The analyses of data were performed comparing each case series to a reference group drawn from among the other sites. Unconditional logistic regression models were used in the statistical analyses. RESULTS: Statistically significant increased risks in association with farming were estimated for skin melanoma (OR 2.7, 95% CI 1.2-5.8) and bladder cancer (OR 2.7, 95% CI 1.2-6.1). Lung cancer was also found increased but not at a statistically significant level (OR 1.7, 95% CI 0.7-4.4). An OR lower than unity was observed for postmenopausal breast cancer (OR 0.4, 95% CI 0.3-0.7). CONCLUSIONS: The present study suggests that women in farming might experience increased risk of cancers, not usually found in excess among male farmers, as well as a protective effect for postmenopausal breast cancer. The role of different patterns of exposure or gender specific responses should be considered in further studies.

Effects of the ionophore antibiotic monensin on hepatic biotransformations and target organ morphology in rats.

As a preliminary in vivo approach in order to study the mechanism of toxicity of the veterinary anticoccidial monensin, male Wistar rats were orally administered 0, 2 and 12 mg kg-1 body wt. day-1 of monensin for 7 days. At the end of the experiment, effects of the ionophore on serum creatine kinase, lactic dehydrogenase and selected drug metabolising enzyme activities were investigated. Furthermore, liver, heart and quadriceps femoris muscle samples were submitted to morphological investigations. Clinical signs or increasing levels of enzymic markers of muscle injury attributable to monensin toxicosis have never been observed in treated animals. As a matter of fact all drug metabolising enzymes activities checked have not shown significant changes, except for a significant decrease of ethoxyresorufin O-deethylase (up to 31%) and aminopyrine N-demethylase (17%) activities. Morphologically, mitochondrial cristae fragmentation and initial formation of 'myelinic sheaths-like' structures have been noticed in heart and muscle fibres. As far as rat study is concerned, these results confirm heart and muscle as target organs of monensin toxicity. In addition, these findings suggest that the inhibition of hepatic biotransformation processes following the i.p. administration of the ionophore, as reported previously by other authors, might reflect unspecific cellular toxic effects rather than a specific enzyme damage.

Gender differences in ethanol oxidation and cytochrome P4502E1 content and functions in hepatic microsomes from alcohol-preferring and non-preferring rats.

1. We have studied the hepatic microsomal metabolism of ethanol (MEOS), CYP2E1 expression and catalytic activity, and the response to phenobarbital (PB) induction or CCl4 challenge in rats of either sex genetically selected for their preference (P) or aversion (NP) for ethanol. 2. In P versus NP females, the amount of both total cytochrome P450 and P450 binding to metyrapone was lower, whereas the activities of MEOS, aniline 4-hydroxylase (4-AOH), and 4-nitrophenol hydroxylase (PNP-OH) as well as the level of immunodetectable CYP2E1 content were consistently higher. By contrast, no substantial differences were observed between P and NP males. 3. Despite an apparent down-regulation of CYP2E1 expression occurring in all rats as a result of PB induction, P females maintained higher 2E1 levels and showed enhanced MEOS, 4-AOH and PNP-OH activities with respect to NP females. No such changes were detected in the male counterparts. 4. No sex-related differences in CCl4-mediated inhibition of monooxygenase or MEOS activities were evident between P and NP animals. 5. These results indicate that, in females only, the behavioural trait of ethanol preference is apparently associated not only with higher constitutive levels of CYP2E1 and rate of microsomal metabolism of ethanol but also with altered susceptibility to PB induction.

Experimental model of cirrhosis in rabbits exposed to carbon tetrachloride by inhalation.

Orthotopic hepatic transplantation is the most diffused surgical treatment used when attempting to substitute an irreversibly damaged liver. However, this practice faces two main problems. Firstly, surgeons need to explant the organ from the donor who is a just deceased human being, with all the implications involved. Secondly, the host patient must be rendered immunologically tolerant to the graft, through pharmacological suppression. Some hepatic alterations allow a structural and functional compensation by means of an autotransplant, but liver cirrhosis, which is widely diffused in humans and easily produced in experimental animals, has not yet been treated with this technique. This research was undertaken with the aim of procuring hepatic cirrhosis in a medium-sized animal--the rabbit--exposed for some months to CCl4 vapours. Preliminary experiments were performed in order to shorten the challenge period by means of liver induction. This approach was unsuccessful because of the natural susceptibility of this species, which was heightened by the barbiturate administration (0.05% sodium phenobarbital in drinking water, for one week). However, induction, rendered impossible the survival after carbon tetrachloride given orally (125 microliters/kg body weight) or by inhalation (1000 ppm for 2 hours). Finally, CCl4 was administered to normal rabbits by inhalation at the initial concentration of 100 ppm, for 2 hours twice a week. The level of the hepatotoxin was subsequently raised stepwise, according to the body weight curve, up to the maximum of 600 ppm by week 23. At the fourth week of intoxication, the metabolic activity of liver microsomes appeared severely depressed, as shown by the 300% increase of hexobarbital sleeping time. The observation of the surface of liver in situ, performed through an explorative laparatomy, showed initial but clear signs of hepatic fibrosis. At sacrifice, after six or ten months of cirrhogenic treatment, the histopathology examination of the liver demonstrated severe and massive cirrhosis, respectively for the two different steps. This experimental schedule appears to be suitable for producing hepatic cirrhosis in a medium-sized animal, which could be used as a model for pioneering attempts of liver autotransplantation. Furthermore, we point out two important aspects of these results. First, the poison has been inhaled by the experimental animals as it generally happens for humans in the environment. Second, the ratio between the length of exposure versus the life span of rabbits--6 months and 8 years, respectively--parallels that reported for human cirrhosis due to halogenated hydrocarbons--5 or 10 years versus 60 or 80 years.

[Toxicologic effects of cadmium on gametes and embryonal kinetics of paracentrotus lividus]. / Effetti tossicologici da cadmio sui gameti e sulla cinetica embrionale del paracentrotus lividus.

The adverse effects of cadmium chloride or cadmium sulphate on both fertilization of sea urchin eggs by spermatozoa and cadmium treated embryos have been studied. Cd treated ova can be fertilized by control spermatozoa. On the contrary, the preliminary treatment of spermatozoa with CdCl2 or CdSO4 succeeds in reducing the fertilization rate of control eggs at concentrations as low as 2 micrograms/ml. Cd sulphate appears to be more noxious than Cd chloride. The study of the residual motility of sea urchin embryos exposed to either CdCl2 or CdSO4 has evidenced a fairly effect at 21 hours after fertilization. On the contrary, concentrations of 25 micrograms/ml Cd chloride or Cd sulphate significantly affect the motility of 48 hours embryos. Higher levels of cadmium, for example, 150 or 200 micrograms/ml, completely block the translation of developing organisms. In this instance, Cd chloride is more effective than Cd sulphate. In addition, a few embryos are affected by malformations and are underdeveloped. These results are interpreted on the basis of the inhibitory effect of cadmium on the CaCO3 uptake by tissues and structures which physiologically need to be calcified in order to develop and function. Further, they give support to the predictive significance of the toxicological tests on the sea urchin plutei in monitoring environmental hazards.

[Protective effect on nephropathy and on cataract in the streptozotocin-diabetic rat of the vanadium-lazaroid combination]. / Azione protettiva sulla nefropatia e sulla cataratta nel ratto diabetico da streptozotocina da parte della combinazione Vanadio-Lazaroide.

Experimental work from our laboratory has confirmed the protective power of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, the diabetic cataract too has been partially prevented. The protection slightly increased, when vanadium was administered in combination with vitamin E. This investigation has introduced a combination of Na3VO4 plus the lazaroid U-83836E, a liposoluble antioxidant much more efficacious than tocopherol, in order to improve the insufficient protection when vitamin E was used. Male Wistar rats, rendered diabetic with STZ, were treated for 12 weeks with Na3VO4 in drinking water, U-83836E carried by the food, or both. The most significant metabolic parameters (food and fluid intake, diuresis and excreted feces) were studied monthly by means of metabolic cages. Body weight, glycemia, glycosuria and proteinuria were also recorded. At week 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled. Circulation glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG) and fluorescent peroxides were evaluated at the end of the experiment. After the first month of treatment U-83836E improved significantly the protective effect of vanadate alone on polydipsia and polyuria, but more efficiently on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was observed also on HbA1c, NAG and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered per os, in a non invasive manner.

Amelioration of diabetes and cataract by Na3VO4 plus U-83836E in streptozotocin treated rats.

Experimental work in our laboratory has confirmed the protective activity of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, diabetic cataract has also been partially prevented. Nevertheless, the combination of a natural antioxidant, vitamin E, with Na3 VO4 has not further enhanced this ameliorating effect. Our experimental approach has been an attempt to block the prooxidant activity of both STZ and vanadate, with the purpose of eliciting the best possible antidiabetic protection. More recently, a lipid soluble synthetic antioxidant U-78517F, a 2-methylaminochroman, has been reported to have a significant protective effect against brain injury and ischemia. This compound inhibits the iron-dependent lipid peroxidation 100 times more effectively than vitamin E. This investigation has introduced a combination of the vanadium compound plus the aforesaid lazaroid, as its (-) enantiomer, U-83836E, in order to improve the insufficient protection when vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with STZ, were administered Na3VO4 in drinking water along with the lazaroid carried by the food. Four, eight and twelve weeks after the beginning of the protective treatment, fluid and food intake, diuresis and excreted feces, glycosuria and proteinuria were determined on biological samples obtained in metabolic cages; body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled and registered. At the end of the experiment, circulating glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG), and fluorescent peroxides were evaluated. Within the first month of treatment, protection by the combination paralleled that elicited by vanadate alone. At subsequent steps, U-83836E significantly improved the protective effect of vanadate alone on polydipsia and polyuria, but especially on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was also observed on HbA1c and NAG, and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered orally in food, in a non invasive manner.

[Behavior of 8000 Hz audiometric threshold in chronic acoustic trauma]. / Comportamento della soglia audiometrica a 8000 Hz nel trauma acustico cronico.

The paper analyzes the 8 KHz threshold in subjects with noise-induced hearing loss. The study group consisted of 315 subjects occupationally exposed to noise and suffering from acoustic trauma, which was considered as a mean threshold of more than 25 dB at 2, 3 and 4 KHz. The mean shape of audiograms was characterized by a neurosensory deficit which was more elevated at 4 and 6 KHz whereas the threshold at 8 KHz was better. However, this pattern was found in 60% of the cases whereas in the remaining 40% the threshold at 8 KHz was worse. Subjects with the most impaired audiometric threshold at 8 KHz were mainly older, although cases were found in a low percentage of younger subjects. The results demonstrate that in individual cases it is impossible, on the basis of the shape of the audiogram, to establish whether a hearing loss is due to noise or age.

Malignant peritoneal mesothelioma in a 17-year-old boy with evidence of previous exposure to chrysotile and tremolite asbestos.

We describe a case of malignant peritoneal mesothelioma arising in a 17-year-old boy. The diagnosis was based on a comprehensive study including light microscopy, histochemistry, immunohistochemistry, evaluation of the clinical course, and autopsy examination. Analytical transmission electron microscopy showed a concentration of 510,000 asbestos fibers/g dry lung tissue. The fibers were represented by chrysotile (62%) and tremolite (38%) asbestos. About 40% of the total fibers were longer than 5 microns. The presence of tremolite fibers was probably due to environmental exposure to contaminated cosmetic talc. This is the first reported case of pathologically proven exposure to asbestos dust in malignant mesothelioma of childhood and adolescence.

[Relationship between auditory disability and auditory threshold in acute acoustic trauma: pilot study]. / Rapporto tra disability uditiva e soglia audiometrica nel trauma acustico cronico: studio pilota.

The aim of this study was to determine the relationship existing between auditory disability, according to WHO 1980, and pure tone audiometry threshold in noise induced hearing loss. Disability was evaluated on the basis of a questionnaire submitted to 286 subjects with acoustic trauma. Answers obtained were considered reliable on the basis of statistical analysis. Results showed that subjects with disability have an higher pure tone threshold than subjects without auditory disability. However it appears difficult to determine a precise threshold level ever which auditory disability may be considered present. The Authors suggest that this limit could be determined on the basis of pure tone threshold at the 10th centile of the group of subjects with disability or at the 90th centile of subjects without disability.

Using reference values in pulmonary ventilation studies.

The aim of this study was to examine the discriminating power of six widely used, or recently introduced, reference values in the interpretation of pulmonary ventilation (FVC and FEV1) in occupational health surveys. These six reference values were applied to a sample of 400 Italian males; 200 of the sample were foundry workers and the other 200 were workers who were not occupationally exposed to dusts; 50% of each group were smokers. The relationship between the reference values and their capacity to discriminate between the workers occupationally exposed to dusts and the workers who smoked in each group was evaluated. The results showed very significant differences among the various reference values. Generally speaking these differences may be determined by the different selection criteria of the subjects under study, or may be a result of the different characteristics of the population included in the various studies. Our conclusions show the need for a critical approach to the use of reference values, particularly during screening tests.

Clobetasone treatment of allergic conjunctivitis: a comparative double blind study.

Glucocorticosteroids are often included in the treatment of allergic conjunctivitis. The present study compares the efficacy on clinical and cytological parameters and safety of topical clobetasone butyrate compared to placebo. The trial, designed as double blind, randomized and parallel group treatment, was carried out in 30 patients, suffering from seasonal allergic conjunctivitis due to Grass pollen, during the pollen season (June 1992). Patients received clobetasone butyrate 0.1% eye drops or placebo eye drops, two drops each eye, t.i.d. for 10 days. The clinical and cytological evidences were investigated on admission and at the end of treatment by clinicians and by patients on a dairy card. The steroid group showed a rapid and significant clinical improvement and at the end of the trial a statistically significant difference was evidenced between the active drug treated group and placebo treated group. No serious side effects were observed. The results show the clinical efficacy of clobetasone butyrate in the treatment of pollen-induced allergic conjunctivitis.

Cancer risk in a cohort of licensed pesticide users.

First admissions to the hospital among 25,945 men living in southern Piedmont and holding a license authorizing them to use pesticides were analyzed in a study of the cancer risk related to exposure to pesticides. Standardized incidence ratios significantly higher than one were encountered for malignant skin cancers and lymphomas. The risk of lymphoma was particularly high in predominantly arable areas. The standardized incidence ratios for tumors of the nervous system and hematopoietic tissue showed an interesting age-related pattern and a higher risk in areas primarily devoted to forest tree plantation, but did not reach significance. Certain hypotheses are advanced to explain these findings.

[Hepatitis A and B virus infections in refuse workers in Asti]. / Infezioni da virus delle epatiti A e B negli addetti alla raccolta rifiuti di Asti.

The authors have examined Hepatitis A and B virus infection risk in 93 dustmen and sewer workers. It has non been found a risk correlated with employment, though for some of them, with peculiar functions, the HBV and/or HAV serological markers prevalence rates were higher than in the remaining of the studied population.