Zoli Mikoczy

Increased cerebrovascular mortality in patients with hypopituitarism

OBJECTIVE An increased prevalence of atherosclerosis has been shown among patients with hypopituitarism. The aim of the present study was to assess whether patients with hypopituitarism experience increased cardiovascular, in particular cerebrovascular, mortality.

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001

To ascertain the frequency of treatment-related acute myeloid leukemias and myelodysplastic syndromes (t-AML/t-MDS) in an unselected series, we have identified all adult cases analyzed in our department from 1976 to 1993. Further aims were to compare karyotypic features of t-AML/t-MDS with de novo AML/MDS, in our material as well as in 5098 unselected, cyto- genetically abnormal, published cases, and to analyze associations between type of prior therapy and karyotype. Among our 372 AML and 389 MDS, 47 (13%) were t-AML and 62 (16%) were t-MDS. Clonal abnormalities were significantly more common in t-AML and t-MDS than in de novo disease (68% vs 50%, P < 0.05 and 84% vs 45%, P < 0.001, respectively). Among the available 4230 AML and 1629 MDS (the present series and published cases), 14% were t-AML and 15% were t-MDS. In t-AML/t-MDS, the number of anomalies and the ploidy levels differed significantly from de novo cases, with complex and hypodiploid karyotypes being more common in t-AML/t-MDS. In t-AML, unbalanced changes in general, t(1;3), der(1;7), 3p−, −5, 5q−, −7, 7q−, t(9;11), t(11;19), t(11q23), der(12p), −17, der(17p), −18, and −21 were significantly more frequent than in de novo AML. In t-MDS, −5, −7, 7q−, 13q−, der(17p), and −18 were significantly more common. Type of prior treatment correlated significantly with number of anomalies in t-AML and with ploidy levels in t-AML/t-MDS. The frequencies of several aberrations varied with type of therapy, eg, 5q− was more frequent in radiotherapy-associated t-MDS, monosomy 7 was more common in t-AML and t-MDS after treatment with alkylators, and t(11q23) in t-AML was associated with topoisomerase II inhibitors. Abnormalities significantly more common in de novo disease were +8 as a sole anomaly, balanced changes in general, t(8;21), t(9;22), t(15;17), inv(16), and t(21q22) in AML, and −Y, 5q−, and 20q− as sole anomalies and +8 in MDS. The results emphasize the strong association between previous genotoxic exposure and karyotypic features.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour

OBJECTIVE To assess the incidence of second brain tumours in patients operated and irradiated for pituitary tumours.

Incidence of asthma in female Swedish hairdressers

Objective: To investigate the risk of asthma in hairdressers. Methods: The incidence of asthma was retrospectively estimated in a Swedish nationwide study including all female hairdressers certified from vocational schools from 1970 to 1995, and a stratified sample of women from the general population were referents. A postal questionnaire included questions on respiratory tract symptoms, atopy, smoking, working periods as a hairdresser, and number of specific hair treatments performed/week. Reported exposures were validated by occupational hygienists. Rate ratios of incidence (IRRs) of asthma were estimated by Poisson regression, adjusted for calendar year of observation, hay fever, smoking, and region of domicile. Results: The crude incidences of asthma/1000 person-years were: 3.9 during active years as a hairdresser, 2.8 among the hairdressers when not working in the profession, and 3.1 among the referents. The corresponding IRR for being an active hairdresser compared with the referents was 1.3 (95% confidence interval (95% CI) 1.0 to 1.6). Moderate effects on risk of asthma were found both from hairdressing work (IRR=1.6 (1.1 to 2.2) among never-smokers) and from smoking (IRR=1.6 (1.2 to 2.2) among referents). However, the combined effect from hairdressing work and smoking (IRR=1.5 (1.0 to 2.1)) was less than expected (p=0.02). No effect modification by respiratory atopy was found. The hairdressers most often performing hair bleaching treatments (IRR=1.5 (0.7 to 3.0)) or using hair spray (IRR=1.4 (0.8 to 2.4)) had, compared with the most infrequent users, a slightly, but not significantly higher incidence of asthma. Exposure to persulphates in hair bleach was estimated to be 0.04–0.15 mg/m3 during mixing of the powder. Reported average number of bleaching treatments agreed well with those performed according to a diary. Conclusions: Active hairdressing work was associated with a moderately increased incidence of asthma among lifelong non-smokers. The results are moderately supportive, but not conclusive, of associations between asthma and exposure to hair bleach or hair spray.

Incidence of hand eczema in female Swedish hairdressers

Objective: To estimate the occurrence of hand eczema in hairdressers in Sweden. Methods: The occurrence of hand eczema was estimated in a Swedish longitudinal retrospective cohort study including all female graduates from vocational schools for hairdressers from 1970 to 1995. A stratified sample from the general population acted as controls. A self-administered questionnaire including questions on the occurrence of hand eczema, skin atopy, working periods and number of hair treatments performed per week was sent to the participants. Incidence rate ratios (IRRs) of hand eczema were estimated. Results: The incidence rate of hand eczema in hairdressers was 23.8 cases/1000 person-years, whereas in hairdressers who were aged <25 years it was 37.1/1000 person-years. The corresponding IRR for hairdressers compared with controls was 2.5 (95% confidence interval (CI) 2.2 to 2.8), and that for younger hairdressers was 3.1 (95% CI 2.6 to 3.5). The mean age at onset of hand eczema was 21.6 years for hairdressers and 21.2 years for controls. The 1-year prevalence of hand eczema was 18.0% for hairdressers and 12.1% for controls. A large number of hair treatments involving exposure to skin irritants and sensitisers were reported. The incidence rate of hand eczema was higher among individuals with a history of childhood eczema, both for hairdressers and for controls, giving an (age-adjusted) IRR of 1.9 and 2.2, respectively. The attributable fraction of hand eczema from skin atopy was 9.6%. A synergistic effect of skin atopy and hairdressing was found on the occurrence of hand eczema. The relative excess risk due to interaction was 1.21 (95% CI 0.21 to 2.21; p = 0.01). Conclusion: Hairdressers are highly exposed to skin-damaging substances. The self-reported incidence of hand eczema was substantially higher in female hairdressers than in controls from the general population and than that found previously in register-based studies. For many individuals, onset of hand eczema occurs early in life. Only about 10% of the hand eczema cases among hairdressers would be prevented if no one with skin atopy entered the trade.

The usefulness of cytogenetic biomarkers as intermediate endpoints in carcinogenesis

During the last decades, cytogenetic biomarkers in peripheral lymphocytes have been used to assess exposure to carcinogenic or mutagenic agents in occupational settings. The first method in use assessed chromosomal aberrations (CA). It is generally accepted that chromosomal mutations are causal events in the development of neoplasia, and it has earlier been postulated, but not proven, that increased chromosomal damage may reflect an enhanced cancer risk. Two less laborious techniques, sister chromatoid exchanges (SCE) and micronuclei (MN), were introduced later-on in occupational health surveillances. SCE represent symmetrical exchanges between sister chromatids; generally they do not result in alteration of the chromosome morphology. MN represent small, additional nuclei formed by the exclusion of chromosome fragments or whole chromosomes lagging at mitosis. MN rates therefore indirectly reflect chromosome breakage or impairment of the mitotic apparatus. The health significance of increased levels of SCE and MN is poorly understood. The usefulness of these cytogenetic techniques for implementing preventive measures in the workplaces depend on how well they serve as biomarkers of exposure but also on whether they can predict cancer risk or not. Recently performed epidemiological studies show that the CA frequency predicts the overall cancer risk in healthy subjects. Such associations could not been seen for SCE or MN. Age, sex, or time since test did not affect the predictive value of CA. This predictivity was seen irrespective of whether the subjects had been smokers or occupationally exposed to carcinogenic agents. Risk factors such as age, smoking and occupational exposures usually explain only some of the interindividual variation in CA frequency. It seems reasonable that not yet identified individual susceptibility factors explain a large fraction of the interindividual CA variation and also the cancer predictivity of the CA biomarker.

A single-center population-based consecutive series of 1500 cytogenetically investigated adult hematological malignancies: karyotypic features in relation to morphology, age and gender.

Abstract:  During the 18‐yr period 1976–93, a population‐based series of 1586 adults with suspected or confirmed hematological malignancies were successfully cytogenetically investigated at a single center. Eighty‐six cases were excluded due to unretrievable medical records or if analyzed only in remission or at relapse. The remaining 1500 medical records were reviewed regarding morphology and clinical parameters in order to investigate possible associations between karyotypic pattern (normal, 1, 2 or complex anomalies; specific abnormalities) and gender, age and morphological subgroups. The impact of time‐period, i.e. 1976–87 vs. 1988–93, and referring center on cytogenetic findings was also studied. A total of 372 acute myeloid leukemias (AML), 389 myelodysplastic syndromes (MDS), 64 acute lymphoblastic leukemias (ALL) and 262 chronic myeloid leukemias (CML) were identified, altogether 1087 cases. Patients with other (n = 261) or no hematological malignancies (n = 152) were excluded from the present analysis. Cytogenetic abnormalities were detected in 52% AML, 51% MDS, 68% ALL and 97% CML, frequencies that did not differ significantly between the 2 time periods or referring centers. No significant age‐ or gender‐related differences in karyotypic patterns were discerned in AML, MDS, ALL or CML, whereas the karyotypic patterns varied among the FAB groups in both AML (p = 0.001) and MDS (p< 0.001). The specific abnormalities t(8;21), t(15;17) and inv(16) were more common (p<0.001) in younger AML patients and 5q‐ was more frequent in females with MDS (p< 0.001). These findings indicate, in contrast to previous series, that neoplasia‐associated karyotypic aberrations are not more common among older patients or in males.

K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed to wood or leather dust

Of 39 males diagnosed with sinonasal adenocarcinomas over 30 years in the Lund University Hospital catchment area (1.5 million inhabitants), archival tumor tissue was available from 29. Of these, 16 had been exposed to wood dust and three had been exposed to leather dust. The intestinal-type and papillary adenocarcinomas were more common in the exposed patients (P = 0.0002, Fishers exact test). The tumors from all but one of the 29 sinonasal adenocarcinomas could be analyzed for point mutations at codons 12, 13 and 61 of the K-ras gene. Four mutations were detected in the 28 tumors. The three mutations in the patients exposed to wood and leather dust were all G:C --> A:T transitions, with two at position 2 of codon 12 and one at position 2 of codon 13. The high proportion of G:C --> A:T mutations in this rare tumor may reflect a genotoxic agent in wood and leather dust.

Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?

OBJECTIVES To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure—that is, the exposure proportion for each occupational title—was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15–20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.