Mortality of a young population after accidental exposure to 2,3,7,8-tetrachlorodibenzodioxin.

The mortality experience of 19,637 people aged 1-19 years living in an area around Seveso, Italy, contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after an accidental explosion in a chemical plant was examined for the period 1976-1986. For comparison, the mortality of the population of nearly 100,000 people living in the surrounding districts was examined. People who left the study area were followed up. Vital status ascertainment was successful in over 99% of the cases. A group of 186 children who contracted chloracne, a reversible marker of TCDD intoxication, shortly after the accident were in the study: none of them died during the observation period. Among the exposed, mortality owing to all causes, to all accidents and to all cancers failed to show major departure from expectations. Five leukaemia deaths were observed, four among males and one among females; the corresponding relative risks were 2.1 (95% confidence interval (CI): 0.7-6.9), and 2.5 (95% CI: 0.2-27.0), respectively. Two lymphatic leukaemias among males yielded a RR = 9.6 (95% CI: 0.9-106.0). Mortality owing to congenital anomalies showed a nearly twofold increase in the contaminated area; however, five out of seven observed cases were born before the accident. Interpretation is limited by the small number of deaths, short latency period and low validity of death certificate information for certain causes, and by the definition of exposure which was based merely on residence. The follow-up is continuing. A cancer morbidity study is in progress.

Computerized slow-staged freezing of semen from men with testicular tumors or Hodgkin's disease preserves sperm better than standard vapor freezing.

Two methods of freezing semen taken from patients with testicular tumors or Hodgkin's disease before treatment were compared. Many patients already have semen abnormalities, so an optimal method is extremely important. Ejaculates from 8 patients with testicular tumors and 20 with Hodgkin's disease were frozen by fast-freezing or by slow-staged freezing. Effects of motility, viability, and swelling after thawing were significantly impaired with both methods. However, cryosurvival was better after slow- than fast-freezing: motility 24% +/- 12.4% versus 15% +/- 11.2%; viability 24.1% +/- 11.4% versus 17.3% +/- 10.4%, swelling 33.3% +/- 11% versus 27.6% +/- 12.8%. The effects were equal for normal and abnormal sperm. Sperm from tumor patients should be frozen by slow-staged freezing method in spite of the higher cost and longer time.

[Mortality: various measurements compared]. / Mortalità: alcune misure a confronto.

SMR (Standardized Mortality Ratio) is a useful epidemiological measure but it cannot be computed when person-years distributions (denominators) are not available. In this situation PMR (Proportionate Mortality Ratio) and MOR (Mortality Odds Ratio) represent possible alternatives. Definitions of PMR and MOR are presented, and properties and drawbacks of these measures are discussed in relation to SMR's estimates. Fictitious data representing factual situations are used as working examples.

[Carcinogenic risk for resin producers exposed to formaldehyde: extension of follow-up]. / Rischio cancerogeno per i produttori di resine esposti a formaldeide: estensione del follow-up.

A significant increase in lung cancer was observed in a previous study on the mortality experience of a cohort of 1332 male workers employed between 1959 and 1980 in a resin manufacturing plant. Due to the limited exposure and an inadequate follow-up, it was not possible to make a thorough analysis of the potential association of this elevated risk with exposure to formaldehyde. The study was therefore continued and extended for a further six years (1980-1986), in order to overcome the limitations. Despite these attempts, however, there were still 219 workers whose specific exposure could not be identified. Lung cancer risk in the whole cohort (27,202 person-years) was equal to that of the local population (observed = 24; expected = 23.9). Among those definitely exposed to formaldehyde, 6 lung cancer cases were observed and 8.7 were expected, while those with non-specified exposure exhibited an increase risk (observed = 9; SMR = 211); they were mainly short-term workers employed at the beginning of operations. The previously suggested increase in haematologic neoplasms was confirmed (observed = 7; SMR = 143); the risk was highest among formaldehyde-exposed workers (observed = 3; SMR = 173). Five deaths due to primary liver cancer were observed, while 2.0 would have been expected from the local population rates (SMR = 244); the increased risk was fairly evenly distributed across the exposure categories (exposed to formaldehyde, SMR = 244; non-exposed to formaldehyde, SMR = 227; non-specified exposure = 287); however, all cases were first exposed at the age of 45 years or older. A noteworthy finding was a 50% increase in mortality from respiratory diseases. The increase was mainly apparent among those with longest and earliest exposure, employed in operations classified as involving exposures other than formaldehyde (observed = 9; SMR = 224). Overall, the results of this extended study do not provide sufficient grounds for associating work in formaldehyde resin production in this plant with increased carcinogenic risk; however, limitations in the individual exposure classification and suggestions of an increased risk for certain tumours preclude considering the study as negative. The numerous airborne irritative agents present in the plant environment appeared to have increased the risk of respiratory disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Mortality in an area contaminated by TCDD following an industrial incident.

The mortality experience of the population, aged 20-74 years, living in an area contaminated by TCDD after an industrial accident in 1976, was examined in the period 1976-1986 and compared with the mortality of the population of the surrounding noncontaminated territory. People who left the area during the study period were followed up, and vital status was successfully ascertained for over 99% of the cohort members. An increased mortality, from chronic ischemic heart disease (males) and hypertensive disease (females), which could not be explained in terms of chance, confounding, or bias, was noted in the exposed population. The stressful experience of the population in the aftermath of the disaster was deemed relevant to the interpretation of these findings. Overall, cancer mortality was not increased. Suggestive increases, however, were seen for melanoma, brain cancer, soft tissue sarcomas and certain hematologic neoplasms, whereas mortality from breast cancer and cancer of the liver was noticeably decreased. Further research is in progress in order to thoroughly investigate the association, if any, of cancer occurrence with TCDD contamination.

[A follow-up study of 304 cases of suspected pathology caused by benzene seen in 1950-71]. / Studio a distanza di 304 casi di sospetta patologia da benzene osservati negli anni 1950-1971.

A group of 304 subjects admitted to the Institutes of Occupational Health of Milan and Pavia (Italy) between 1951 and 1970 for suspected benzene intoxication were retrieved from hospital records and their mortality experience was examined up to 31 December, 1986. The aims of the study were: 1) to estimate, in quantitative terms, the risk associated with benzene exposure in that area in the time period considered (these risks had already been reported, but merely as case reports); 2) to investigate the possibility of an increased frequency of neoplasms other than leukaemia; and 3) to further investigate the exposure history of these subjects. In the absence of data on the population at risk, mortality was analysed via the mortality odds ratio (MOR) method. A local population mortality experience was used as reference. Twenty-eight malignant neoplasms were observed (MOR = 2.2; 95% confidence interval = 1.3-3.7), 15 of which were haematologic neoplasms (MOR = 13.3; 95% confidence interval = 8.0-22.2). No odds ratio increases were observed for any of the other tumour sites or types. Eleven observed blood diseases represented a large numerical increase in the odds ratio. For all the haematologic neoplasms there had been an estimated exposure to airborne benzene concentrations above 20 ppm. However, no conclusions on dose-response relationships can be drawn from these data because of the approximate evaluation of individual exposure and, especially, because the study group most probably consisted of a highly selected sample of the exposed population.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic analysis prior to selective fetal reduction in multiple pregnancy: technical aspects and clinical outcome.

Multiple pregnancies resulting from ovarian stimulation are at a higher risk of carrying at least one fetus affected by Mendelian or chromosomal anomalies, the incidence of which is directly related to the order of multiples. Genetic analysis before fetal reduction was offered to both high- and low-risk pregnant women carrying two or more fetuses after ovulation induction. Chorionic villus sampling (CVS) and fetal reduction were achieved by transabdominal needling. The use of short-term culture, the polymerase chain reaction and fresh tissue enzymatic analyses have made it possible for genetic diagnosis to be available in a few days. A total of 100 patients had multifetal pregnancy reduction performed by a single operator; all of them completed pregnancy and none was lost at follow-up. The total fetal loss before 24 weeks was 7% and no statistically significant relationship was found with the final number of fetuses and CVS. Perinatal losses (3.9%) were only present in the series with a final number of two fetuses. Pregnancy duration and birthweight were significantly higher in singletons than in twins, but were not related to CVS. The rate of chromosomal disorders was higher (7.2%) in the study series than in singleton pregnancies not undergoing fetal reduction. Diagnostic error due to incorrect sampling was reported in 1.5% of cases. These data support fetal reduction as a valuable strategy to improve the outcome of multiple pregnancy. The outcome of pregnancies reduced to singletons was significantly better than of those reduced to twins, and was not related to CVS.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the various techniques of identifying human spermatozoa morphology.

The morphology of 100 subjects' spermatozoa was examined with 6 different methods of identification. Mean results obtained were compared with each other, analyzing variances for two criteria of classification. Analysis of statistics shows that these 6 methods make a heterogeneous group. In particular, observations carried out with phase contrast and with Testsimplets self-colouring slides showed a significantly higher number of anomalies than with other methods. Papanicolau, hematoxylin-eosin and modified Giemsa staining gave an intermediate number of anomalies, which were statistically indistinguishable from each other. Hemaquick rapid staining agents for hematology gave the lowest percentage of anomalies. Differentiated analysis of anomalous heads, necks and tails showed that the 6 methods may differ in their capacity to identify the various anomalies. Given that the percentage of observed normal forms is inversely proportional to the effectiveness of a specific method in identifying anomalies, then it is evident that the choice of method is the decisive factor when defining criteria of normality.

Outcome of first-trimester chorionic villus sampling for genetic investigation in multiple pregnancy.

OBJECTIVES: To evaluate the efficacy of and risk associated with chorionic villus sampling for genetic investigations in multiple pregnancies, and to evaluate the accuracy of the ultrasonographic detection of chorionicity during the first trimester. PATIENTS AND METHODS: A total of 198 sets of twins and nine sets of triplets from 10 087 consecutive first-trimester pregnancies undergoing chorionic villus sampling were considered. Gestational age ranged from 7 to 12.6 weeks. Assessment and confirmation of chorionicity was based on a multiplicity of features. Dichorionicity was established in 169 sets of twins (85.3%) and trichorionicity in all triplet cases, while 29 twins were considered monochorionic. Chorionic villus sampling was performed transabdominally in all but one case, and identification of the placental insertion of the umbilical cord was the main benchmark for sampling. Sampling risks were evaluated by comparing clinical outcome with that of a control population of 63 dichorionic twin pregnancies which underwent no invasive procedure. RESULTS: Determination of the presence or absence of the lambda sign led to a correct assignment of chorionicity in all cases, while the presence of a membrane thickness of 2 mm or more reflected a 100% specificity with a 22% false negative rate. Sampling was successfully performed in all cases and in only four cases (1.0%) were two needle insertions needed. At follow-up no evidence of incorrect sampling was reported. Karyotyping was provided to all patients, and in 94.1% of cases both short and long-term culture methods were carried out. No difference in fetal and perinatal losses between the study and control populations was found, but a higher rate of deliveries before 37 weeks and of low birth weight babies was noted amongst controls. CONCLUSIONS: Chorionicity in twin pregnancy can be determined with certainty between 7 and 12 weeks of gestation; in cases of confluent placentas reliability is provided by determining the presence or absence of the lambda sign. This study indicates that first-trimester transabdominal chorionic villus sampling is a highly efficient, reliable, and relatively safe approach for genetic diagnosis in twin pregnancies. Although a precise evaluation of the relative risks of chorionic villus sampling and mid-trimester amniocentesis in twins must await randomized control studies, the advantages of a first-trimester diagnosis to enable early decision-making about selective fetal reduction are obvious.

[Semiautomatic procedure for determining urine iron in subjects treated with deferoxamine B]. / Procedimento semiautomatico per la determinazione del ferro urinario in soggetti trattati con deferossamina B.

A semiautomatic method for the determination of urine iron during treatment with deferoxamine B has been evaluated: samples were diluted 1:10 with a TCA 10% and thioglycolic acid 1.1% solution and processed after centrifugation by the aca III discrete clinical analyzer Du Pont. In this way an overestimation of values depending on the turbidity caused by proteins is avoided and the bad smell is limited thanks to the very low concentration of the thioglycolic acid solution. A good correlation with the atomic absorption spectrophotometry, specially for values less than or equal to 20 mg/l, was observed examining urine samples of 150 patients treated with deferoxamine B.

Changes in cervical mucus after diathermocoagulation of the cervix.

We have studied the principal chemophysical properties of cervical mucus obtained before and after diathermocoagulation (DTC) in 35 patients participating in a program for prevention of cervical carcinoma. Two months after DTC there were significant decreases in the cervical scores for both exo- and endo-cervical mucus (Moghissi scale). Twelve patients with favorable pre-DTC scores, whose condition had deteriorated 2 months subsequent to treatment, again displayed normal scores in both sites 1 year after DTC. We feel, therefore, that DTC does not cause any permanent change in the chemophysical properties of the cervical mucus, but instead only temporary deterioration during the repair phase.

Feto-maternal transfusion after chorionic villus sampling: clinical implications.

Feto-maternal transfusion following chorionic villus sampling (CVS) in the first trimester of pregnancy was evaluated by alpha-fetoprotein (AFP) level determination in maternal serum before and after sampling. Some fetal haemorrhage was suggested in 72% of 283 continuing pregnancies by a significant increase of maternal AFP level. Fetal bleeding appeared to stop a short time after CVS, and did not complicate detection of neural tube defects (NTDs) in the second trimester. The change in the maternal serum AFP level was correlated with the size of the chorionic tissue specimen, but no association was observed between fetal and neonatal outcome. The risk of maternal rhesus (Rh) iso-immunization must be taken into account, and anti-D immunoglobulin administrated after CVS. Maternal Rh immunization should be considered as a contraindication to CVS.

Dioxin exposure and non-malignant health effects: a mortality study.

OBJECTIVE: To investigate, in a population heavily exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the possible unusual occurrence of diseases other than cancer. METHODS: Five year extension of the follow up of the cohort involved in the Seveso accident. Soil measurements identified three exposure zones: (A) highest contamination, (B) substantial, and (R) low but higher than background contamination. Blood TCDD measurements, although limited in number, confirmed zone exposure ranking. The 15 year mortality in the exposed cohort was compared with that of a large population in the surrounding non-contaminated territory. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated with Poisson regression techniques. RESULTS: The already noted increased occurrence of cardiovascular deaths was confirmed, in particular in zone A, among males for chronic ischaemic heart disease (five deaths, RR 3.0, 95% CI 1.2 to 7.3), and among females for hypertensive disease (three deaths, RR 3.6, 95% CI 1.2 to 11.4) and chronic rheumatic heart disease. Novel findings were the increase of chronic obstructive pulmonary disease, most notably among males in zone A (four deaths, RR 3.7, 95% CI 1.4 to 9.9) and females in zone B (seven deaths, RR 2.4, 95% CI 1.1 to 5.1); and from diabetes, which was significantly increased in females in zone B (13 deaths, RR 1.9, 95% CI 1.1 to 3.2). In zone R, chronic ischaemic heart disease (males and females), hypertension (females), and diabetes (females) showed less pronounced, although significant excesses. CONCLUSIONS: As well as high TCDD exposure, the accident caused a severe burden of strain in the population. Both these factors might have contributed to the noted increased risks (in particular, circulatory and respiratory). The cardiovascular and immune toxicity of TCDD, as well as its complex interaction with the endocrine system, might be relevant to the explanations of these findings. These results, although not conclusive, concur with previous data in suggesting cardiopulmonary and endocrine effects in humans highly exposed to TCDD.

Ten-year mortality study of the population involved in the Seveso incident in 1976.

In 1976, an accidental explosion in a plant near Seveso, Italy, caused the contamination of a populated area by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The area was subdivided into three zones (A, B, and R) having decreasing mean levels of TCDD soil contamination. This study examines the mortality between 1976 and 1986 among the subjects, aged 20-74 years, who were resident in the area since the accident (n = 556 in zone A, n = 3,920 in zone B, n = 26,227 in zone R). Subjects' exposure was classified by residence. A referent cohort of 167,391 subjects who lived in the immediate surroundings was concurrently examined. Vital status ascertainment was successful for over 99% of the subjects. Increased mortality from cardiovascular causes was found; incident-related stressors were considered more relevant to increased mortality than was TCDD exposure. Mortality from several cancers was elevated. The increases in biliary cancer (females), brain cancer, and lymphatic and hemopoietic neoplasms (particularly leukemia in males) did not appear to result from chance, confounding, or information/comparison bias. However, no definite patterns related to exposure classification were apparent. Merely suggestive increases in soft tissue tumors and melanoma were also noted. Liver and breast cancer mortality tended to be below expectations. Interpretation is hampered by the short observation period, small number of deaths from certain causes, and poor exposure definition. Further research is in progress.

Morphological selection of human spermatozoa in cervical mucus "in vivo".

Spermatozoa morphology at two levels in the cervical canal was compared, at the external and internal uterine orifices, in samples taken "in vivo" during 21 postcoital tests (P.C.T.s). P.C.T.s with cervical mucus, with Moghissi scores lower than 10 and exo- and endocervical pH less than 7 were excluded. At the upper level of the cervical canal, 12 of the 21 P.C.T. showed more than 5% more normal spermatozoa than at the lower level of the canal (in 5 of these P.C.T. the increase was greater than 10%). Selection for normal heads was seen in 2 and for normal tails in 4. The P.C.T. that selected for normal tails all had greater than 10% abnormal tails at the external orifice. These results confirm that there is some selection of spermatozoa during passage through the cervical canal. Above all, the selection appears to exclude those spermatozoa with defective locomotive mechanisms (abnormal tails), which indicates that the mucus acts as a "passive filter" with selection depending on the spermatozoa themselves in relation to motility.

Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident".

Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental animals, whereas the evidence in humans is limited. We examined cancer mortality from 1976 to 1991 among residents of Seveso, Italy, which was highly contaminated after an industrial accident. The area was divided into zones with decreasing exposure to dioxin (A = highest, B = lower, R = lowest). The population of a surrounding noncontaminated area was used as a reference group. Zone A was small (11,516 person-years); in that zone, we saw a moderate increase in mortality from digestive cancer among women [relative risk (RR) = 1.5; 95% confidence interval (CI) = 0.5-3.5]. In zone B, we also saw excesses at digestive sites (83,610 person-years), 10 years after the accident. Women had an increased mortality from stomach cancer (RR = 2.4; 95% CI = 0.8-5.7), and men had increased mortality from rectal cancer (RR = 6.2; 95% CI = 1.7-15.9). Hematologic neoplasms were increased. The highest risks were seen in zone B for leukemia in men (RR = 3.1; 95% CI = 1.3-6.4), multiple myeloma in women (RR = 6.6; 95% CI = 1.8-16.8), and Hodgkin's disease in both genders (RR = 3.3; 95% CI = 0.4-11.9 in men; and RR = 6.5; 95% CI = 0.7-23.5 in women). Soft tissue sarcoma was elevated only among zone R males (256,408 person-years; RR = 2.1; 95% CI = 0.6-5.4). We found no increase for all-cancer mortality or major specific sites (for example, respiratory among males, breast among females). The specific excesses that we observed were not explained by bias or confounding, and their association with dioxin exposure is plausible. The follow-up is continuing.