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Six acute phase proteins (haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, C reactive protein and transferrin) have been measured in the sera of chronic liver disease (CLD) patients with different aetiology (viral, autoimmune and alcoholic) and histology (steatosis, chronic persistent hepatitis, chronic active hepatitis, cirrhosis), and in patients with liver cancer. 1) The most striking changes concerned alpha 2-macroglobulin (increased) and haptoglobin (decreased) levels. 2) Transferrin was lower in alcoholic liver disease than in viral CLD, CRP was lower in autoimmune than in viral or alcoholic CLD, and alpha 1-acid glycoprotein was lower in viral and alcoholic CLD than in autoimmune CLD. Acute phase protein assay may prove useful in differential diagnosis, particularly when specific markers are not available (autoimmune, non A, non B, alcoholic liver diseases). 3) No significant differences related to aetiology (B, non A non B, D viruses) were observed in viral CLD. 4) Patients who progressed to CLD after acute viral hepatitis type B or non A non B did not show different APP levels from those who had recovered when tested 8-12 months after the acute phase. 5) The pattern of APP changes observed in primary liver cell carcinoma was different from both the cirrhotic pattern and the pattern presented by other tumours with or without liver metastasis.

Stima del potenziale cancerogeno • L’insieme degli studi disponibili indica che le evidenze di cancerogenicità per l’uomo sono limitate e concernono la leucemia infantile, mentre sono inadeguate per le altre sedi tumorali, e che la relazione tra esposizione ai tipi di campi presi in considerazione e rischio di tumori non è sufficientemente chiara. • In tal senso si è anche espressa la IARC che, sulla base dei dati disponibili nel 2001, ha così valutato le associazioni tra esposizione a campi elettrici e magnetici e insorgenza di tumore: - Vi è limitata evidenza di cancerogenicità per l’uomo del campo magnetico a frequenze estremamente basse, per quanto riguarda la leucemia infantile. - Vi è inadeguata evidenza di cancerogenicità per l’uomo del campo magnetico a frequenze estremamente basse, per quanto riguarda gli altri tumori. - Vi è inadeguata evidenza di cancerogenicità per l’uomo dei campi elettrici e magnetici statici e del campo elettrico a frequenze estremamente basse. Campi elettrici e magnetici statici e a frequenze estremamente basse (ELF) - Rischio cancerogeno - Vi è inadeguata evidenza di cancerogenicità per l’animale sperimentale del campo magnetico a frequenze estremamente basse. - Non vi sono dati di rilievo sulla cancerogenicità per l’animale sperimentale dei campi elettrici e magnetici statici e del campo elettrico a frequenze estremamente basse. Sulla base di tali valutazioni il campo magnetico a frequenze estremamente basse è stato classificato come “possibile cancerogeno per l’uomo” (Gruppo 2B) e i campi elettrici e magnetici statici e il campo elettrico a frequenze estremamente basse sono stati valutati come “non classificabili per la loro cancerogenicità per l’uomo” (Gruppo 3). Non sono emerse successivamente informazioni tali da modificare, a giudizio della Commissione, il parere della IARC sulla pericolosità in senso cancerogeno del campo magnetico a frequenze estremamente basse e, in particolare, alle frequenze industriali di 50/60 Hz. Pertanto, la Commissione, allo stato attuale delle conoscenze, condivide la precedente valutazione.

International audience; A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI

More and more citizens urge public health authorities to investigate reports of disease excess in their neighbourhood. These environmental concerns are legitimate and it is part of good public health practice to respond to these complaints. However, the methodological and practical problems are severe and a lot of controversy exists about the usefulness of these investigations. To clarify the possibilities and limitations in this situation, this paper proposes a typology of cluster studies. According to this framework, cluster response is distinguished from two other types of cluster studies: Cluster monitoring. screening proactively for clusters to act as an early warning system, and cluster research, scrutinizing clustering to generate and test aetiological hypotheses. To each of these three types of cluster studies corresponds a different public health context; respectively public health action, public health surveillance and public health research. Probably, part of the controversy mentioned stems from not acknowledging sufficiently the corresponding intrinsic differences in rationality and practical constraints. Cluster response is crisis management and not scientific research. In a relatively short time, an informed decision should be taken by a multidisciplinary team of experts using readily available information and knowledge. In accordance with this point of view, cluster reports should be handled stepwise and the role of statistics is to quantify a cluster exploring different points of view as an input to the decision process.

FOREGROUND: A national deprivation index suitable for geographical analysis of inequalities in health is not yet available in Italy, although the link between deprivation and health has been clearly demonstrated in our country in a number of studies.1) To describe a deprivation index in Italy at municipal level, based on the percentage of selected census variables (simple components) 2) To analyse general mortality according to deprivation categories at municipal level in Italy 3) To measure the size of ecological bias using the Turin Longitudinal Study.Italy (1-2), Turin (3).1) 1991 census data base at municipal level 2) General mortality in Italy by municipality and age bands in 1990-92. 3) Turin Longitudinal study 1991-1995.1) Percentages of selected indicators of inequalities for all the 8.100 Italian municipalities present at 1991 census were calculated. Factorial analysis were performed in order to help in selecting the most valuable ones. The final choice led to five indicators (low education, unemployment, rented occupier housing, no indoor bathroom, lone parent with childhood). A simple additive index was computed using the method of the sum of normal standard deviates of each component 2) Correlation of indexes with mortality was performed; SMR for each deprivation category were computed; 3) Computation of the index at different levels: individual (one million individuals), census ward (3657 wards), statistic zone (92 statistic zones), two neighborough levels (23 and 10 neighboroughs) was conducted; differential analysis was performed for each level and index category, allowing for comparison among results, adjusting for age.Increasing deprivation was significantly associated with mortality from all causes: there was up to a 20 percent increase in mortality between the highest and lowest quintile. The relationship was linear with no apparent threshold. The slope of the relationship between deprivation and mortality varied among regions. Differentials in inequalities measured by individual and census tract level resulted to be very small; ecological bias arises when larger areas are taken into account.An area based measure of deprivation has proved a valuable tool in examining differentials in death and is likely to prove of continuing value to health authorities in planning the delivery of health care.

Mortality from malignant pleural neoplasms in Italy, 1980-87, was studied in order to detect areas at risk. The number of observed deaths occurring in each of the 8000 Italian municipalities was contrasted to the expected figure obtained from regional and/or national rates; whenever a significant increase, based on at least three observed cases, was detected, the municipality was included in the study. The main findings in Piedmont concern the city of Casale Monferrato, where an important asbestos cement factory is located, and some areas characterized by the presence of the textile industry. Genoa and other harbours of the northwestern coast, where important shipyards are located, were detected. In Lombardy an increased in risk concerning women was observed in several municipalities. Major increases in risk were seen in Venice. Trieste and Monfalcone, where important shipyards are located. In Tuscany, the highest risk was reported in Leghorn and surrounding areas; naval industry and chemical industries should be considered. In southern Italy, several cities with industrial harbours were shown to be at risk.

Objectives: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. Design: Multinational retrospective cohort study of cancer mortality. Setting: Cohorts of workers in the nuclear industry in 15 countries. Participants: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. Main outcome measurements: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. Results: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. Conclusions: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

The morphological and immunohistochemical findings in lymph nodes of nine patients with the acquired immunodeficiency syndrome (AIDS) and 81 patients with the AIDS-related complex (ARC) are presented. Three basic histological patterns were observed: follicular hyperplasia (29 cases), mixed hyperplasia (49 cases) and lymphocyte depletion (12 cases). While the first two variants were detected in typical ARC patients, lymphocyte depletion was always associated with AIDS. Immunohistochemistry on frozen sections showed that the number of B-cells varied throughout the series, being higher in the follicular type and significantly lower in the lymphocyte depletion nodes. The content of T-lymphocytes of the helper/inducer (T4) phenotype was reduced in all instances; this reduction was more pronounced in the germinal centres in follicular hyperplasia, while it involved all compartments of the node in the mixed and lymphocyte depletion types. In contrast the cytotoxic/suppressor (T8) subset was increased in the follicular and mixed hyperplasias only. Partial disintegration of the dendritic network in at least some of the follicles could be demonstrated in all lymph nodes. In the follicular and mixed hyperplasias there was a high number of proliferating B-cells in the germinal centres. Our data indicate the usefulness of grading the changes occurring in lymph nodes of patients with ARC and AIDS, and allow speculation as to the pathophysiology of these conditions.

A further experimental study on changes produced in rabbits by low dosage contraceptives is presented. The administration has been continued for six months. Serum biochemical and hepatic ultrastructural findings are in agreements with literature data. On the contrary the early changes of cardiac microcirculation and chiefly renal glomerular tuft seem to be rather unusual. The weight to be attached to the knowledges descending from the presented data in assessing allowance of contraceptive treatments in human subjects and aiming preventive medicine purposes is emphasized.

The clinical features of our cases demonstrated some of the already known characteristics of the variable spectrum of HIV infection. DA are the most important risk category in Italy. 10% of the ARC cases evolved into AIDS during a 12-month follow-up, on average. The most frequent OI in our AIDS cases were PCP, C. albicans esophagitis and chronic mucocutaneous ulcers. An high percentage of neurologic involvement from HIV was observed, and malignancies were encountered in AIDS (3 KS and 1 undifferentiated B lymphoma) as well as in ARC (1 Hodgkin's lymphoma). Statistically, significant worsening of the immunologic situation is evident as the disease progresses from LAS to AIDS. Activated B lymphocytes represent most of the cells of the germinal center during the hyperplastic stage of lymphadenopathy. Reversal of the T4/T8 ratio appears early during the initial stage of lymphadenopathy and is due to a decrease of CD4 and a relative increase of CD8. Also, destruction of the follicular dendritic cells is an early feature which becomes more evident as the disease advances and the lymph node evolves toward progressive involution. Activated B-lymphocyte augmentation with polyclonal Ig secretion appears to be related to T-independent B stimulation by coinfection such as CMV, EBV and HBV. The increase of cytotoxic/suppressor lymphocytes seems to be partly related to the excessive activation of B lymphocytes and partially directed to the cells infected by HIV or coated with its proteins (6,7,8,9). The destruction of follicular dendritic cells has been interpreted not only as a killer effect of the virus but also as a result of the intervention of CTL sensitized to the cells containing the virus (10,11). Their destruction may contribute to the impaired recognition of soluble antigen which is one of the main features of the immune deficiency of HIV infection (9,13,16).