Immune response in chronic hepatitis C-infected patients undergoing interferon treatment.
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Hepatitis C, Chronic↗
Biomedical subjects
C Magnani
Publications and source records attributed to C Magnani.
Amyotrophic lateral sclerosis among the migrant population to Piemonte, northwestern Italy.
Recent surveys indicate a decreasing north-to-south gradient in the mortality and incidence rates of amyotrophic lateral sclerosis (ALS) in Italy, possibly indicating a different susceptibility to ALS in these populations. Piemonte, a region of northwestern Italy, experienced a considerable migration from other regions in Italy between 1940 and 1975; we therefore analyzed the effects of place of birth and migration upon the risk of developing ALS. Data on all ALS cases occurring in Piemonte during the period 1971-1990 were collected. Standardized incidence ratios (SIRs) for patients born outside Piemonte were calculated, using the Piemonte-born population as reference. A total of 962 ALS cases were identified during the study period, corresponding to a mean annual crude incidence rate of 1.37/100,000 population (95% confidence interval, 1.29-1.46). The SIRs of patients born in three southern Italian regions and of foreign-born persons were significantly higher than those of persons born in Piemonte and or other regions in Italy, and increased with age. This observation may be explained by an interaction between environmental and genetic factors or by selective migration.
Adult↗
Asbestos and cancer: An overview of current trends in Europe.
This review assesses the contribution of occupational asbestos exposure to the occurrence of mesothelioma and lung cancer in Europe. Available information on national asbestos consumption, proportions of the population exposed, and exposure levels is summarized. Population-based studies from various European regions on occupational asbestos exposure, mesothelioma, and lung cancer are reviewed. Asbestos consumption in 1994 ranged, per capita, between 0. 004 kg in northern Europe and 2.4 kg in the former Soviet Union. Population surveys from northern Europe indicate that 15 to 30% of the male (and a few percent of the female) population has ever had occupational exposure to asbestos, mainly in construction (75% in Finland) or in shipyards. Studies on mesothelioma combining occupational history with biologic exposure indices indicate occupational asbestos exposure in 62 to 85% of the cases. Population attributable risks for lung cancer among males range between 2 and 50% for definite asbestos exposure. After exclusion of the most extreme values because of methodologic aspects, most of the remaining estimates are within the range of 10 to 20%. Estimates of women are lower. Extrapolation of the results to national figures would decrease the estimates. Norwegian estimates indicate that one-third of expected asbestos-related lung cancers might be avoided if former asbestos workers quit smoking. The combination of a current high asbestos consumption per capita, high exposure levels, and high underlying lung cancer rates in Central Europe and the former Soviet Union suggests that the lung cancers will arise from the smoking-asbestos interaction should be a major concern.
Asbestos↗
Prevalence of Parkinson's disease in Northwestern Italy: comparison of tracer methodology and clinical ascertainment of cases.
The prevalence of idiopathic Parkinson's disease (PD) in an area of Northwestern Italy (Socio-Sanitary District of Cossato, 61,830 inhabitants) was analyzed and the reliability of "drug tracer methodology" evaluated. The patients were identified by both conventional epidemiological methodology (general practitioners, consultant neurologist, computerized archives) and drug tracer methodology (registered levodopa prescriptions). The diagnosis of PD was clinically verified by examining all patients. Of 146 patients examined, 104 were affected by PD; the remaining by other types of parkinsonism. The crude point prevalence rate (October 20, 1991) was 168 per 100,000 population (95% confidence interval [95% CI] 138-204), with a progressive increase up to the 80-89 age group. Using "tracer" methodology, the estimated crude point prevalence rate was 196 (95% CI 163-235), with an overestimation of the prevalence in older patients and women and an underestimation in younger and less seriously affected cases. The uneven distribution of PD in Italy appears to be the result of, at least in part, methodological factors. "Tracer" methodology may cause biases in the evaluation of the epidemiological characteristics of PD, especially if the clinical diagnosis of cases identified by this method is not carefully verified. Nevertheless, it appears useful as an additional source of cases for descriptive surveys.
Aged↗
Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin. EUROCLUS project.
The EUROCLUS project included information on residence at diagnosis for 13351 cases of childhood leukaemia diagnosed in the period 1980-89 in defined geographical regions in 17 countries. A formal algorithm permits identification of small census areas as containing case excesses. The present analysis examines spatial-temporal patterns of the cases (n = 970) within these clustered areas. The objectives were, first, to compare these results with those from an analysis conducted for UK data for the period 1966-83, and, second, to extend them to consider infant leukaemias. A modification of the Knox test investigates, within the small areas, temporal overlap between cases in a subgroup of interest at a putative critical time and all other cases at any time between birth and diagnosis. Critical times were specified in advance as follows: for cases of acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months after birth. Each of the analyses found evidence of excess space-time overlap compared with that expected; these were 10% (P = 0.005), 15% (P= 0.0002) and 26% (P= 0.03) respectively. The results are interpreted in terms of an infectious origin of childhood leukaemia.
Adolescent↗
Asbestos lung burden and asbestosis after occupational and environmental exposure in an asbestos cement manufacturing area: a necropsy study.
OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs). METHODS: The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4. RESULTS: Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL. CONCLUSION: The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.
Adult↗
Mortality from lung cancer and population risk attributable to asbestos in an asbestos cement manufacturing town in Italy.
OBJECTIVE: To estimate mortality from lung cancer and the risk attributable to asbestos separately for asbestos cement workers and for the general (non-occupationally exposed) population in the town of Casale Monferrato, where the largest Italian asbestos cement factory had been in operation in 1907-86. According to cancer registry data, in the same town the incidence of malignant mesothelioma in the general population is about 10 times higher than in comparable Italian provinces. METHOD: Decedents from lung cancer in 1989-95 were nominally identified in the list of decedents kept at the Local Health Authority of Casale Monferrato. Workers in the asbestos cement factory have been identified with a search in the nominal list of workers and the same was done for the wives of asbestos cement workers. These lists have already been used in cohort studies. Sensitivity and specificity of the linkage procedure with occupational activity in asbestos cement production have been evaluated in a previous study. Population at risk was estimated on the basis of official figures and on the results of the cohort study of asbestos cement workers. RESULTS: 227 deaths from lung cancer were included (184 men and 43 women). Among the asbestos cement workers mortalities were 234.0 x 100,000 person-years among men and 35.5 among women. Corresponding figures in the general (non-occupationally exposed) population in Casale Monferrato were 80.6 and 18.7. The rates in the general population were not higher than in the rest of the region. Attributable risk (AR) among the asbestos cement workers (and wives) is 67.5% (95% confidence interval (95% CI) 56.8 to 78.2) for men and 51.3% (95% CI 14.9 to 87.8) among women. Population AR to occupational or paraoccupational exposure in the asbestos cement production is 18.3% (95% CI 11.1 to 25.6) among men and 10.1% (95% CI 0 to 24.6) among women. CONCLUSION: This work did not show an increase in mortality from lung cancer for the population not exposed occupationally, but a large excess was found among men and women occupationally exposed in asbestos cement production. The total burden of lung cancer due to occupational exposure to asbestos may be underestimated, as only occupational exposure in asbestos cement production was taken into consideration. Nevertheless even a single factory can be responsible for a considerable proportion of deaths from lung cancer in a population.
Adolescent↗
Generalizability of the added benefits of guided tissue regeneration in the treatment of deep intrabony defects. Evaluation in a multi-center randomized controlled clinical trial.
BACKGROUND: Several studies have shown that GTR therapy of intrabony defects results in significantly better outcomes than access flap alone. Most of the available data, however, have been produced in highly controlled research environments by a small group of investigators. Generalizability of results to different clinicians and different subject populations has not been evaluated so far. METHODS: This parallel group study involved 143 patients recruited in a practice-based research network of 11 offices in 7 countries. It was designed to evaluate: 1) the applicability of the documented added benefits of GTR in the treatment of intrabony defects to different populations, and 2) the generalizability of the expected results to different clinicians. GTR was compared to access flap alone. Defects, one in each patient, were accessed with a previously described papilla preservation flap in both the test and control group. In addition, GTR sites received application of a bioabsorbable poly-D,L-lactide-co-glycolide membrane. A stringent plaque control regimen was enforced in all patients during the 1-year observation period. Outcomes included gains in clinical attachment (CAL) and reductions in probing depth. RESULTS: Observed gains in CAL were 2.18 +/- 1.46 mm for access flap and 3.04 +/- 1.64 mm for the GTR-treated group. The treatment-associated difference was statistically significant (P = 0.03) after correcting for both center effect and defect anatomy. Among the various centers, a 1.73 mm difference in CAL gain was observed. This is a clinically relevant amount, which underlines the significance of center variability in the outcome of periodontal surgical procedures. A frequency distribution analysis of the obtained CAL gains indicated that GTR treatment of deep intrabony defects decreased, with respect to the access flap control, the probability of obtaining only a modest attachment gain at 1 year. Conversely, CAL gains of 4 mm or more were observed in more than 40% of GTR-treated defects and in less than 20% of the controls (P < 0.0001). CONCLUSIONS: These data indicate that GTR therapy of deep intrabony defects performed by different clinicians on various patient populations resulted in both greater amounts and improved predictability of CAL gains than access flap alone.
Absorbable Implants↗
Sinonasal cancer and occupation. Results from the reanalysis of twelve case-control studies.
A pooled reanalysis of twelve case-control studies on sinonasal cancer and occupation from seven countries was conducted in order to study associations with occupations other than wood- and leather-related occupations. The pooled data set included a total of 930 cases (680 men and 250 women) and 3,136 controls (2,349 men and 787 women). All the studies included a detailed occupational history for cases and controls. Each job was coded using the same classifications for occupation and industry. Two approaches were used in the analysis: systematic analysis of occupations; a priori analysis using a preestablished list of occupations and industries. The results confirmed associations observed in several studies not included in this analysis. For agricultural workers, significant excesses were observed for squamous cell carcinoma among women (OR = 1.69) and men (OR = 3.72 for ten years or more of employment as an orchard worker), and adenocarcinomas among men (OR = 2.98 for ten years or more of employment). Associations with textile occupations were observed for adenocarcinoma among women (OR = 2.60) and squamous cell carcinoma among men (OR = 5.09 for fiber preparers, 3.01 for bleachers). Elevated risks for both histologic types were observed among men employed in food manufacturing (OR = 3.25, adenocarcinoma), or as food preservers (OR = 13.9, squamous cell carcinoma), and among men employed as cooks (OR = 1.99, squamous cell carcinoma). A positive association with squamous cell carcinoma was observed for male transport equipment operators (OR = 1.21), and also with adenocarcinoma for male motor-vehicle drivers (OR = 2.50). A number of other associations were observed in the systematic analysis.
Adenocarcinoma↗
Pelvic ultrasonography in patients with Turner syndrome: age-related findings in different karyotypes.
Real-time ultrasonography was performed in 142 patients with Turner syndrome, aged 0.57 to 21 years, with different karyotypes (45,X [4896], X mosaicism [17%], and X structural abnormalities [35%]). Ovarian and uterine volumes were calculated and the data collected in a mixed longitudinal and cross-sectional mode. Thirty-eight patients were followed longitudinally during pubertal age (10 to 18 years bone age) for ovarian data. Patients with Turner syndrome were divided into two groups according to the presence or absence of detectable ovaries. Patients with Turner syndrome with detectable ovaries showed the first increase in ovarian volume at about 9 years of bone age; this increase was continuous and more evident only after 14 years of age and appeared later than in control subjects. When followed longitudinally during puberty, the ovaries showed a hormonal function in some cases. Girls with X mosaicism had the highest percentage of bilateral detectable ovaries and the greatest total ovarian volume; about 50% of them had spontaneous breast appearance and 38.5% had spontaneous menarche. They showed also the lowest gonadotropin levels, when bilateral ovaries were present during puberty. On the contrary, patients with the 45,X karyotype had the lowest percentage of detectable ovaries, ovarian volume, and spontaneous breast appearance. In our patients with Turner syndrome, uterine measures increased significantly with age and this was more evident in subjects with detectable ovaries after 13 years of bone age. Compared with control subjects, they showed significantly lower uterine measures, and patients with X mosaicism had greater and more progressive increments. In conclusion, pelvic ultrasonography in Turner syndrome is particularly useful in detecting ovaries and their possible increase in volume. These data, linked with karyotype pattern and gonadotropin levels, have prognostic value in predicting the future sexual development of these patients.
Adolescent↗
Malignant mesothelioma of the pleura. The reproducibility of the immunohistological diagnosis.
The reproducibility of the histopathological diagnosis of pleural malignant mesothelioma (MM), after supplementing routine H&E stain by immunohistochemistry (IH) in 77 cases of original diagnoses of MM, was assessed by examining interobserver variation between five pathologists. A battery of commercial antibodies (cytokeratins, vimentin, HMFG-2, anti Leu-M1 [CD15], BerEP4, B72.3 [TAG-72], carcinoembyonic antigen), considered to be useful in enhancing diagnostic accuracy, was used. The number of definitively classified tumors (accepted MM plus rejected MM) increased from 57 on H&E stain to 60 after IH, with 59 (76.6%) cases being accepted as true MM. Based on IH, the chance-adjusted interobserver agreement was poor (kappa w = 0.29) and lower than that observed on previous H&E alone. The intraobserver agreement for four of the five pathologists was rather good (kappa w = 0.54-0.56). The inter- and intraobserver concordance was higher in accepting than excluding the cases as MM. A larger number of cases were classified by all reviewers as mixed or sarcomatous variants after IH. In the interpretation of each immunostain, kappa values ranged from 0.19 for B72.3 to 0.62 for HMFG-2, which were respectively the least and the most consistently interpreted immunostains. The information additionally contributed by IH did not seem to change the pathologists' diagnoses very much in comparison with those made by routine H&E stain. Until highly specific and sensitive probes for the positive identification of MM become available, a careful scrutiny of routinely stained preparations still remains the most rewarding component of the diagnostic pathway.
Clinical Laboratory Techniques↗
Incidence of second primary malignancies after a malignant tumor in childhood: a population-based survey in Piedmont (Italy).
We have studied the frequency of second primary malignancies (SPM) among the 2,328 children registered in 1967-1969 at the Childhood Cancer Registry of Piedmont, the largest population-based childhood cancer registry in Southern Europe. Since the population of Piedmont is not served by a conventional cancer registry covering all ages, SPMs were identified through a number of ad hoc surveys within a variety of sources. Eighteen SPM (all histologically diagnosed) were observed after a thorough survey conducted in the ontological departments in Piedmont and after a postal questionnaire addressed to general practitioners. Death certificates were also examined. The crude incidence rate was 116.5 per 100,000 person-years. Risk was higher among children whose first malignancy was diagnosed more recently (SIR = 9.8 for diagnoses in 1983-1989 vs. 4.5 for diagnoses in 1967-1974). The same tendency was confirmed in analyses restricted to children in whom leukemia was diagnosed as the first cancer. Clinical data regarding the treatment of the first malignancy were available for 16 children out of 18: 15 had received chemotherapy and 12 radiotherapy (9 SPM originated in the irradiation field). The interest of measuring the risk of SPM on a population basis (and not only in clinical series) and the advantage of close cooperation between epidemiologists and clinical oncologists are underlined.
Adolescent↗
Urinary tract abnormalities (UTA) and associated malformations: data of the Emilia-Romagna Registry. IMER Group. Emilia-Romagna Registry on Congenital Malformations.
An epidemiological study on the urinary tract anomalies (UTA) associated with other congenital malformations or syndromes ascertained by the Emilia-Romagna Registry on Congenital Malformations (IMER) among 209,882 consecutive births monitored during the period 1981-1990 is presented. UTA were ascertained in 349 infants for a rate at birth of 16.6 per 10,000 total births, or one case for every 600 births. The occurrence rate of UTA increased significantly during the ten years of monitoring passing from 6.1 per 10,000 in 1981-1982 to 25.1 in 1989-1990 (r = 0.85; p < 0.001). This increase is in connection with a progressively higher notification of isolated cases of UTA, directly related to the impact of the prenatal diagnosis. Among the 349 cases, 106 (30.4%) were associated with other conditions, including 18 who had chromosomal aberrations (ChrA). The incidence in the total number of the ChrA registered was 43.6 per 1,000. Genetic syndromes (GS) in 33 cases with a specific rate of 150 per 1,000, and 55 cases of multiples with a specific rate of 205.2 per 1,000. In multiples we observed some preferential associations of UTA with intestinal defects and severe ear defects (p < 0.001) and for Central Nervous System and heart defects (p < 0.05). UTA are often associated with other extrarenal defects and sometimes are a component of syndromes that are difficult to identify and for which genetic implications are great and genetic counselling necessary. Pediatricians need to be aware of the possible involvement of the kidney in specific and rare syndromes, and pediatric nephrologists must recognize the association of renal diseases with abnormalities in other physiological systems.
Abnormalities, Multiple↗
Short direct repeats at the breakpoints of a novel large deletion in the CFTR gene suggest a likely slipped mispairing mechanism.
In the cystic fibrosis conductance transmembrane regulator (CFTR) gene a few small deletions and only a large, complex, 50-kb deletion have been described so far. We report a second large deletion, which had been hypothesized in a patient affected by cystic fibrosis on the basis of an abnormal pattern of inheritance of the intragenic microsatellites IVS17b/TA and IVS17b/CA. Southern blot analysis revealed the presence of an anomalous band in the patient and her father, in the region encompassing exons 13 - 19, approximately 0.6 kb shorten than the one present in normal controls, in addition to the band of the correct size. Cloning and sequencing the DNA fragments spanning the region of interest demonstrated the presence of a 703-bp deletion causing complete removal of exon 17b in the paternal cystic fibrosis chromosome. This analysis revealed the presence of two short direct repeats flanking the breakpoints. The 3' repeat partially overlapped the IVS17b/CA microsatellite and the number of CA repeated units present in the paternal cystic fibrosis allele was the shortest ever found among chromosomes so far analyzed. These data may suggest that the mechanism for the generation of the deletion may have involved a slipped mispairing during DNA replication, which has not previously been described in the CFTR gene.
Adult↗
Childhood leukaemia in Europe after Chernobyl: 5 year follow-up.
The European Childhood Leukaemia - Lymphoma Incidence Study (ECLIS) is designed to address concerns about a possible increase in the risk of cancer in Europe following the nuclear accident in Chernobyle in 1986. This paper reports results of surveillance of childhood leukaemia in cancer registry populations from 1980 up to the end of 1991. There was a slight increase in the incidence of childhood leukaemia in Europe during this period, but the overall geographical pattern of change bears no relation to estimated exposure to radiation resulting from the accident. We conclude that at this stage of follow-up any changes in incidence consequent upon the Chernobyl accident remain undetectable against the usual background rates. Our results are consistent with current estimates of the leukaemogenic risk of radiation exposure, which, outside the immediate vicinity of the accident, was small.
Child↗
[Audit of histopathological activities in the laboratories of 7 general hospitals. 1. Types of resources and quantitative aspects of the workload].
Following a major reorganization of the National Health Service, competition for resources will depend to a great extent on the quality of the service offered, and audit will be of increasing importance. The present investigation deals with the quantitative aspects of the histopathology workload. A retrospective analysis of the biopsy handling of 1,000 consecutive cases was conducted in each histopathology lab of seven general hospitals. The data collected included information on specimen type, diagnosis, block/section/stain details for each specimen, as well as information about human resources, total workload and technical equipment. Among the seven labs, the histopathology workload ranged between 6,600 and 15,600 cases/year. The workload per person/year ranged between 1,400 and 2,600 (mean 1,900) for pathologists, between 800 and 3,000 (mean 1,500) for technicians, and between 2,200 and 8,300 (mean 4,400) for secretarial staff. The prevalence of biopsy fragments (endoscopic, endometrial curettage , etc.), "small" surgery (skin, appendix, gallbladder, etc.) and surgery was, respectively, between 42 and 50%, 34 and 47%, 9 and 21%. In all labs but one, 80% of cases were within 1-3 blocks; the seven labs had a mean of blocks/case ranging from 1.8 to 4.0 (total mean = 2.8). Differences in performing special stains were astonishing: one lab performed special stains in about 40%, and another in only 0.6% of cases (mean of the seven labs = 15%). Finally, the labs performed immunohistochemical stains within a range of 2.7-8% of cases (mean of the seven labs = 4.6%). The data we have collected provided baseline information on the laboratory running, and this is likely to be an integral part of laboratory administration in the near future.
Biopsy↗
[Audit of histopathology activities at the pathology departments of 7 general hospitals. 2. Response time].
A retrospective analysis of 1,000 consecutive cases was conducted in each histopathology lab of seven general hospitals. The collected information included the date of specimen withdrawal (six labs only), receipt in the laboratory, and reporting. Time intervals between withdrawal and receipt. Two labs, received 3/4 of cases the same day, while the others had a very low prevalence of receipt. All labs but one, received 80-90% of cases within 48 hours. In one lab, 17% of cases arrived five days after from the withdrawal. Time intervals between receipt and reporting. The mean observed in the seven labs ranged from 3.1 to 6.1 days. Two labs were able to report within 24 hours, but this occurred only in 6% of their cases. The reporting prevalence within three days ranged between 5 and 64%, with a mean for the seven labs of 37%. The reporting prevalence within 6 days was about 95% (four labs), 60-70% (two labs) and 20% (one lab). All labs but one reported 95-100% of cases within ten days. Time intervals between withdrawal and reporting. Our labs were not able to report within 24 hours from the withdrawal (frozen sections excluded). The reporting prevalence within 2-3 days was about 35-40% (three labs), 16% (one lab), 2% (two labs), and within six days it was about 90% (three labs), and 61%, 38% and 14% (the remaining). These latter reported 95% of their cases within twenty days. The turnaround times we found are unsatisfactory. Probably, there are many sources of delay, and these are multifactorial. However, a major factor involved in these delays seems to be related to poor arrangements in the allocation and managing of human resources.
Hospitals, General↗
Analysis of linkage disequilibrium between different cystic fibrosis mutations and three intragenic microsatellites in the Italian population.
Three intragenic microsatellites of the CFTR gene, a TA and a CA repeats, namely IVS17bTA and IVS17bCA, located in intron 17b and a CA repeat (IVS8CA) located in intron 8 of the CFTR gene, were analyzed in a large sample of Italian cystic fibrosis (CF) and normal chromosomes. Linkage disequilibrium was evaluated between each marker and difference CF mutations on a total of 377 CF and 358 normal chromosomes. Our results are consistent with the hypothesis that all delta F508 chromosomes derive from a single mutational event. The same hypothesis is valid for mutations G542X, N1303K, 1717-1G-->A, which might have been originated more recently than delta F508.
Cystic Fibrosis↗