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Biomedical subjects

A Forni

Publications and source records attributed to A Forni.

At least 19 recordsLinked to original sources

Chromosome aberrations in hospital workers: evidence from surveillance studies in Italy (1963-1993).

Hospital workers are occupationally exposed to various agents known or suspected to induce chromosome damage, the most studied being ionizing radiation. To determine the extent of chromosome damage in peripheral blood lymphocytes in this population, taking into account temporal changes and job titles, a re-analysis of cytogenetic studies performed in four Italian laboratories in the period 1965-1993 was carried out. A total of 871 hospital workers and 617 controls, mainly coming from ad hoc studies or surveillance programs in occupational groups potentially exposed to ionizing radiation, were examined. The exposed to controls frequency ratio of chromosome aberrations was evaluated as the measure of effect within each dataset by job title, using multivariate Poisson regression analysis, which allowed an efficient control of confounding. Increased frequency of chromosome-type aberrations among exposed subjects was found in all datasets, especially in those dealing with older data. Significantly higher frequencies are reported for various job titles, particularly for orthopedists, radiologists, anesthesists, and nurses among paramedical occupations. Decrease in exposure to ionizing radiation in hospital workers was documented through a targeted study in the critical group of radiologists. A similar time-related reduction in the frequency of chromosome-type aberrations also has been reported by the surveillance studies carried out over the most recent decades. These data substantiate the use of chromosome-type aberrations as biomarkers of exposure in this occupational setting in the period evaluated. However, the increases observed also in workers with doubtful exposure to ionizing radiation indicate that other chromosome-damaging agents may be involved and, in turn, suggest the extension of surveillance to a larger number of occupations.

Adult

Age-related increase of baseline frequencies of sister chromatid exchanges, chromosome aberrations, and micronuclei in human lymphocytes.

Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter- and intralaboratory variability. A greater frequency of the mean standardized values by increasing of age was observed for all of the end points. A leveling off was evident in the last age classes in the trend of MN frequencies. Frequency ratios (FRs), which express the increase of the cytogenetic damage with respect to the first age classes, i.e., 1-19 years, were estimated using Poisson regression analysis after adjustment for the potential confounding factors and confirmed the increasing trend by age class for all three end points. The most dramatic increase was observed for MN, with a FR that approaches the value of 2 at the age class 50-59 (FR, 1.97; 95% confidence interval, 1.43-2.71) and remains substantially unchanged thereafter. The trend of FRs for CA is more homogeneous, with a constant rise even in the older classes, whereas the frequency of SCE increases with age to a lesser extent, reaching a plateau in the age class 40-49 and the maximum value of FR in the age class over 70 (FR, 1.14; 95% confidence interval, 1.07-1.23). In conclusion, our results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.

Adolescent

Cytogenetic studies in coke oven workers.

Chromosome aberrations, micronuclei, and sister chromatid exchanges (SCE) were evaluated in cultured lymphocytes of coke oven workers of an Italian steel industry plant, occupationally exposed to polycyclic aromatic hydrocarbons, and in a group of unexposed controls from a non-oven plant in the same area. No differences were found between exposed and controls for rates of total abnormal metaphases (including and excluding gaps), chromatid-type and chromosome-type aberrations, cells with 2 or more breaks, and for micronuclei. On the contrary, SCE were significantly increased in the exposed versus the controls, but, when smoking habits were considered, the increase was significant only for smokers.

Adult

Benzene-induced chromosome aberrations: a follow-up study.

To study the evolution of cytogenetic damage from past exposure to high concentrations of benzene and its health significance, chromosome aberrations (CA) in lymphocytes were reinvestigated after approximately 20 years in four subjects with past severe hemopathy and in seven controls studied in the late 1960s. Increased chromosome-type aberrations were still present up to 30 years after benzene toxicity, but blood counts were normal. The vital status at the end of 1993 was ascertained for 32 subjects with a history of benzene toxicity and for 31 controls studied for CA from 1965 to 1970, who differed significantly for CA rates. Of the 32 benzene-exposed subjects, 1 was lost to follow-up, 20 were still alive, and 11 had died at ages 36 to 83, between 1 and 20 years after the last CA study. Five deaths were from neoplasia (acute erythroleukemia, brain tumor, cancer of lung, paranasal cavity, esophagus). The decreased subjects had significantly higher rates of chromosome-type aberrations than those alive, and those who died of neoplasia had the highest rates of these aberrations in the last study before death or diagnosis of cancer. Out of the 31 controls, 12 had died from 4 to 23 years after the CA study. Three deaths were from neoplasia (two lung cancer, one brain tumor). Even if this is a small sample, the results suggest a higher risk of cancer for the benzene-exposed cohort, who had persistently high CA rates in lymphocytes.

Adult

Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study.

To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death.

Chromosome Aberrations

Influence of sex on cytogenetic end points: evidence from a large human sample and review of the literature.

The planning and evaluation of human cytogenetic studies should contemplate various confounders and effect modifiers, among these, sex and sex-related factors. The association between this variable and cytogenetic damage has been extensively studied, but conclusive evidence has thus far not been reached, especially for the most recent assays, such as the micronucleus test (MN). In the attempt to quantitatively estimate the sex effect on sister chromatid exchange (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we reanalyzed the original data sets of several biomonitoring studies performed over the last decades in 10 Italian laboratories. This approach yielded a very large database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN, respectively. Differences between sexes were expressed in terms of relative risk (RR) of females versus males, after adjustment for age, smoking habits, occupation exposure and inter- and intralaboratory variation. No difference between sexes was found for the frequency of SCE [RR = 1.01; 95% confidence interval (CI) = 0.99-1.03] and CA (RR = 1.00; 95% CI = 0.92-1.08) even if the CI of the RR for SCE includes the 3% excess in females frequently reported by the literature. Conversely, a 29% overall increase of the MN rate in females was observed in the whole data set (RR = 1.29; 95% CI = 1.20-1.38). Different trends by age of the MN rate are described in the two sexes, focusing on the peak observed in females in the menopausal period and on the subsequent decrease.

Adult

Metal determinations in biological specimens of diseased and non-diseased hard metal workers.

Biological monitoring of Co, Ta and W, using mainly neutron activation analysis, was carried out on the urine, blood, pubic hair and toe nails of 251 subjects occupationally exposed to hard metal dusts (23 individuals were diagnosed as 'diseased subjects', affected by asthma and/or lung fibrosis). Airborne dust at hard metal workplaces were also analyzed for Co and W content. Cobalt and tungsten exposure at workplaces varied widely and frequently exceeded the TLV (0.05 mg Co/m3). Cobalt in urine (CoU), which is better than Co in blood (CoB), could represent a valuable indicator in discriminating between exposed groups, but is of little value as an indicator of exposure for single individuals. The high concentrations of cobalt in public hair (CoH) and toe nails (CoN) could also be valuable indicators of exposure although they are not useful, however, in establishing quantitatively the levels of cobalt accumulation. Tungsten and tantalum in pubic hair (WH and TaH) and toe nails (WN and TaN) also seem to be useful indicators in proving hard metal exposure qualitatively. The determination of these two elements, rather than cobalt, in the bronchoalveolar lavage (BAL) is very useful in complementing the diagnosis of hard metal disease proving hard metal exposure. The analysis of the BAL subfractions showed that W and Ta were firmly incorporated into the macrophage fraction while Co was distributed between cellular fraction and supernatant, which suggests a different mobility of hard metals in pulmonary tissue. The metal concentrations determined when submitted to statistical analysis indicated a positive correlation with P < 0.001 for the pairs (CoB-CoU), (Co-W) in urine, and (Co-W) in toe nails. Multielement analysis of biological specimens from diseased subjects suggests that hard metal disease does not relate to Co, W and Ta levels in the specimens considered. The disease does not depend on sex, age, working age and length of hard metal exposure. These findings support the theory on the possible haptenic properties of Co which may induce hypersensitivity and immuno-related toxic effects.

Adolescent

Bronchoalveolar lavage in the diagnosis of hard metal disease.

Bronchoalveolar lavage (BAL) a technique which is not very invasive and which permits investigations of deep lung reactions from various causes, has been demonstrated to be also useful in the diagnosis of lung disorders from hard metals (HM) and/or cobalt, thus overcoming, in most cases, a need for open lung biopsies. Cases with HM interstitial disease show at BAL the signs of a high-intensity alveolitis, characterized by increased total cells with bizarre multinucleated giant cells and increased inflammatory cells. These findings correspond well to the histological pattern of desquamative giant cell interstitial pneumonitis. The persistence of alveolitis and especially high numbers of eosinophils at following BALs, despite cessation of exposure and steroid treatment, has an ominous prognostic significance. The few reported cases of cobalt asthma studied by BAL present either normal findings or increased T lymphocytes with inverted helper/suppressor ratio. This last finding has also been described in some asymptomatic exposed subjects, which indicates a subclinical (or preclinical?) lung reaction. Determination by neutron activation analysis of trace metals (cobalt, tungsten, tantalum) in BAL and other biological specimens may be important in documenting recent or past exposures, but is not discriminant for diagnosis, since no relationship has been found between levels of any metal and the occurrence of the disease.

Asthma

Topical aprotinin in cardiac operations.

We performed a prospective, randomized, double-blind trial of topical aprotinin versus placebo in 100 patients undergoing cardiac operations with cardiopulmonary bypass. Fifty-five patients received aprotinin. Forty underwent coronary artery bypass grafting (CABG) and 15 valve replacement +/- CABG. Of 45 patients in the control group 38 underwent CABG and 7 valve replacement +/- CABG. Aprotinin (50 mL; 70 mg) or placebo was applied topically to the heart, pericardium, and mediastinum before sternal closure. There were five reentries for bleeding with a surgical site identified in four. Mean blood loss was significantly less in the aprotinin group (653 versus 903 mL; p = 0.002), and fewer aprotinin patients received blood as a volume expander (67.5% versus 88%; p = 0.03). In coronary patients alone when aspirin administration was continued until the day of operation there was no difference between treatment and placebo groups (768 versus 879 mL). When aspirin administration was discontinued 2 weeks before operation there was a significant difference (558 versus 884 mL; p = 0.016) as in the group overall. This provides the potential for intrapericardial instillation for patients with excessive postoperative bleeding.

Administration, Topical

Comparison of chromosome aberrations and micronuclei in testing genotoxicity in humans.

Chromosome-type aberrations (CsA) and micronuclei (Mn) rates were compared in conventional 2-day lymphocyte cultures. In 67 healthy controls the mean rate of CsA was 0.54%, and that of Mn 2.38/1000 (median 1.66/1000). Mn were significantly correlated with age. The rate of Mn was higher in the 30 individuals with CsA > or = 1% than in the 37 subjects with no CsA. However, in 40 cadmium (Cd) workers, contrary to that found for CsA, the rates of Mn did not differ from those of the controls matched for age and smoking habits, not even in the subgroup with the highest Cd cumulative exposure index, while an age effect was evident both in the exposed and in the controls.

Adult

Aprotinin and bleeding in profoundly hypothermic perfusion.

Clinical observation led us to believe that aprotinin fails to preserve haemostatic function in patients undergoing deep hypothermic perfusion with or without circulatory arrest. A retrospective study was made of blood loss in 80 consecutive acute Type A dissection patients before and during the aprotinin era (1987-1992). After 1988 all patients were cooled below 20 degrees C pending circulatory arrest. Fourteen patients underwent aortic root replacement and 66 replacements of the ascending aorta. Age distribution (range 22-79 years) and type of operation were similar in the aprotinin and control groups. The impervious Hemashield (Meadox) graft was used for all but five patients. These underwent aortic root replacement with preclotted, valved conduits. Overall the mean blood loss for 27 patients operated without aprotinin was 837 ml per 24 h (standard error +/- 90) and for 53 patients with aprotinin 1,929 ml per 24 h (standard error +/- 90). There was a significant difference between the two groups when profoundly hypothermic perfusion was used, with greater bleeding in aprotinin-treated patients. There were six re-entries in the aprotinin group and none in the control patients. There were ten hospital deaths (11.1%). A greater incidence of bleeding and thrombosis-related deaths was recorded for the aprotinin-treated patients. In addition, four surviving aprotinin patients suffered severe coagulation defect with blood loss greater than 4,500 ml and platelets less than 50 x 10(6). We suggest that aprotinin inhibits the protease enzymes which maintain the fluid state of blood during hypothermic low flow and arrest states. Disseminated intravascular coagulation may consume platelets thereby predisposing to abnormal bleeding and potentially fatal thrombotic events. The use of aprotinin in profoundly hypothermic perfusion should be adopted cautiously.

Adult

Biological monitoring of cadmium exposure--an Italian experience.

Studies carried out over the last 12 years in northern Italy on a case list of 105 cadmium (Cd) workers showed that blood levels (B-Cd) were influenced not only by current exposure but also by body burden, while urinary levels (U-Cd) were influenced predominantly by body burden. Moreover, no advantages were gained by adjusting U-Cd for creatinine or specific gravity. The urinary beta 2-microglobulin levels were within the reference values when B-Cd and U-Cd were below the current threshold values. However, some indicators of early renal effect appeared to be altered. An increase in chromosome-type aberrations in lymphocytes occurred in workers with a heavy cadmium burden. Studies carried out on more than 600 subjects from the general population showed higher B-Cd levels in smokers than in nonsmokers. B-Cd levels were higher in men and in higher age groups. Identifying reference values for B-Cd through meta-analysis studies seems useful.

Cadmium

Reference values for chromosome aberrations in human lymphocytes as indicators of genotoxic effects.

Increased chromosome aberrations (CA) in human cultured lymphocytes are an accepted indicator of early biological effects of exposure to genotoxic agents, which has also been investigated, with conflicting results, in several groups of subjects occupationally exposed to metals known or suspected to be carcinogenic. One of the problems with this indicator is the lack of universally accepted reference values. Difficulty in establishing absolute reference values for CA depends on individual variability in the reference groups (due to several environmental and genetic confounding factors) and on methodological variants at the different stages of the test (culture methods, scoring, classification and reporting of CA). Therefore, at present, CA studies in exposed groups should include proper 'control' groups, matched for the known confounders, investigated in the same laboratory, with the same methods in order to minimize factors of variation. The results of the studies should be statistically compared and evaluated mainly on a group basis.

Carcinogens

Chromosomal effects of cadmium exposure in humans.

Cytogenetic studies on subjects occupationally or environmentally exposed to cadmium are reviewed and discussed. After a first report of increased chromosome aberrations in lymphocytes of itai-itai patients from Japan, several studies on workers occupationally exposed to cadmium gave conflicting results. These differences may perhaps be explained by the action of co-factors (e.g., nutritional deficiencies in itai-itai patients; concomitant exposure to other metals in some occupational groups), or by different levels of exposure. In a study on cadmium workers with a wide range of cumulative exposure, as compared with matched controls, an increase in chromosome-type aberrations in lymphocytes, an indicator of cumulative damage, was found only because of the increased rates in the subgroup with the highest cumulative exposure and cadmium burden. As far as environmental exposure is concerned, of two recent reports, one from China is positive for chromosome aberrations and the other, from Japan, is negative for sister chromatid exchanges.

Adult

Interactions of nucleic acids with distamycins. Binding of Dst-3 to d(CGTTTAAACG)2 and d(CGTACGTACG)2.

The binding between Distamycin 3 and the palindromic duplexes d(CGTTTAAACG)2 and d(CGTACGTACG)2 was investigated by two independent techniques: UV-Vis absorption in the Job's plot approach and Induced Circular Dichroism. Both decamers bind two molecules of peptide per duplex, with close overall affinities. This result indicates that a row of six A:T base pairs can accommodate two molecules of drug and that the minimal binding site of Distamycin 3 can consist of just two A:T base pairs.

Base Sequence

Interactions of nucleic acids with distamycins. The drug monomeric chromophore.

A study of the monomeric chromophore of the oligopeptides netropsin (1), distamycin III (2), and distamycin V (3) by polarization spectroscopy techniques and molecular orbital calculations is reported. Linear dichroism spectra of the monomeric model compounds 1-methyl-2(ethylcarbamoyl)-4-acetamido-pyrrole (4) and 1-methyl-2(ethylcarbamoyl)-pyrrole (5) dissolved and oriented in lyotropic and thermotropic liquid crystals provide, together with the magnetic CD spectra, experimental checks of the theoretical calculations. The polarization directions of the investigated transition obtained by these means in this study allow us to build up in the following paper the exciton states of (1)-(3) and these provide a stereochemical interpretation of the flow linear dichroism spectra of the complexes of DNA with (2) and (3).

DNA