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1.
COPD ; 6(4): 256-62, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19811384

ABSTRACT

This study aims to compare diagnostic and clinical outcomes of Chronic Obstructive Pulmonary Disease (COPD) from the gender perspective using retrospective health care data and patient reported outcomes in a real-world setting. An electronic database was constructed from complete medical records of 844 COPD patients who were recruited in Helsinki and Turku University Central Hospitals during the years 2005-07. The patients were identified from the hospital discharge registries by ICD10 code J44.8 in the age group of 18-75 years of age. The medical history was obtained from all healthcare providers who had treated these patients during the previous 5-10 years; the study intends to continue their follow-up annually for the next 10 years. Thirty-six percent (N = 266) of the participants were women. The COPD diagnosis had been made at the same age for both genders. Women, however, reported significantly less pack-years than men. Compared to the men, the women displayed less advanced airway obstruction, but more severe gas transfer impairment. Parenchymal damage when evaluated by diffusion capacity correlated significantly stronger with FEV(1) (% of predicted) in women than men. The BMI index of the women was lower than that of the men. Cardiovascular diseases, diabetes and alcoholism were significantly more common in men, but women suffered more psychiatric conditions, especially depression. This cohort showed several significant gender dependent differences in the clinical presentation that need to taken under consideration in the assessment of COPD progression and the disease management.


Subject(s)
Pulmonary Disease, Chronic Obstructive/epidemiology , Smoking/epidemiology , Adolescent , Adult , Aged , Chi-Square Distribution , Comorbidity , Disease Progression , Female , Finland/epidemiology , Humans , Interviews as Topic , Male , Middle Aged , Phenotype , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests , Retrospective Studies , Risk Factors , Severity of Illness Index , Sex Factors , Statistics, Nonparametric
2.
Allergy ; 62(6): 648-54, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17508969

ABSTRACT

BACKGROUND: Case reports of occupational asthma in dental personnel have been published, but there is little data on the risk of respiratory disorders related to occupational exposure to methacrylates in dental assistants. The objective of this study was to investigate the relation of exposure to methacrylates to occurrence of respiratory symptoms and diseases among dental assistants. METHODS: A cross-sectional study of female dental assistants from the membership register of the Finnish Association of Dental Hygienists and Assistants was conducted in the Helsinki metropolitan area. A CATI was carried out to collect information on health and exposures. A total of 799 dental assistants participated (response rate 87%). RESULTS: Daily use of methacrylates was related to a significantly increased risk of adult-onset asthma (adjusted OR 2.65, 95% CI 1.14-7.24), nasal symptoms (1.37, 1.02-1.84), and work-related cough or phlegm (1.69, 1.08-2.71). Nasal symptoms showed a dose-response relation with increasing years of exposure to methacrylates, and those with >10 years of exposure had also increased risk of hoarseness, dyspnoea, and wheezing with dyspnoea. Dental assistants with a history of atopic diseases were particularly susceptible to exposure to methacrylates, the adjusted OR for adult asthma being in this group 4.18 (95% CI 1.02-28.55) and for nasal symptoms 2.11 (1.08-4.19). CONCLUSIONS: This study provides new evidence that the risk of adult-onset asthma, nasal symptoms and other respiratory symptoms increase significantly with daily use of methacrylates in dental assistants' work. The results suggest that exposure to methacrylates poses an important occupational hazard for dental assistants.


Subject(s)
Dental Assistants , Methacrylates/adverse effects , Occupational Exposure/adverse effects , Respiratory Tract Diseases/chemically induced , Adult , Asthma/chemically induced , Cough/chemically induced , Cross-Sectional Studies , Female , Humans , Hypersensitivity, Immediate/complications , Middle Aged , Nose Diseases/chemically induced , Occupational Diseases/chemically induced , Respiratory Sounds/etiology
3.
Eur Respir J ; 22(2): 305-9, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12952265

ABSTRACT

This population-based cross-sectional survey assessed the prevalence of work-aggravated asthma symptoms and the effect of the work environment on the aggravation of symptoms of established asthma. A questionnaire was sent to 2,613 persons (aged 20-65 yrs) with asthma. The analyses were restricted to the 969 respondents who were currently employed. The effect of occupational exposure on the aggravation of asthma symptoms at work was assessed according to both self-reported and expert-evaluated exposure. Approximately 21% of the respondents reported work-aggravated asthma symptoms at least weekly during the past month. The prevalence of those with work-aggravated symptoms increased by age, self-reported occupational exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals, and expert-evaluated probability of daily occupational exposure to airborne dusts, gases or fumes. Aggravation of asthma symptoms at work is common among employed adults with asthma. Both self-reported and expert-evaluated exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals explained the significant worsening of symptoms. The findings suggest a marked role of the work environment in the aggravation of symptoms of established asthma.


Subject(s)
Asthma/epidemiology , Occupational Diseases/epidemiology , Occupational Exposure/adverse effects , Workplace , Adult , Aged , Air Pollutants, Occupational/adverse effects , Asthma/etiology , Cross-Sectional Studies , Environment , Finland/epidemiology , Humans , Middle Aged , Occupational Diseases/etiology , Prevalence , Severity of Illness Index
4.
Br J Cancer ; 81(7): 1111-5, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10584869

ABSTRACT

Previous molecular cytogenetic studies by comparative genomic hybridization (CGH) on primary tumours of human malignant mesothelioma have revealed that loss of genetic material at chromosome 14q is one of the most frequently occurring aberrations. Here we further verify the frequency and pattern of deletions at 14q in mesothelioma. A high-resolution deletion mapping analysis of 23 microsatellite markers was performed on 18 primary mesothelioma tumours. Eight of these had previously been analysed by CGH. Loss of heterozygosity or allelic imbalance with at least one marker was detected in ten of 18 tumours (56%). Partial deletions of varying lengths were more common than loss of all informative markers, which occurred in only one tumour. The highest number of tumours with deletions at a specific marker was detected at 14q11.1-q12 with markers D14S283 (five tumours), D14S972 (seven tumours) and D14S64 (five tumours) and at 14q23-q24 with markers D14S258 (five tumours), D14S77 (five tumours) and D14S284 (six tumours). We conclude from these data that genomic deletions at 14q are more common than previously reported in mesothelioma. Furthermore, confirmation of previous CGH results was obtained in all tumours but one. This tumour showed deletions by allelotyping, but did not show any DNA copy number change at 14q by CGH. Although the number of tumours allelotyped was small and the deletion pattern was complex, 14q11.1-q12 and 14q23-q24 were found to be the most involved regions in deletions. These regions provide a good basis for further molecular analyses and may highlight chromosomal locations of tumour suppressor genes that could be important in the tumorigenesis of malignant mesothelioma.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 14 , Mesothelioma/genetics , Microsatellite Repeats , Adult , Aged , Humans , Loss of Heterozygosity , Middle Aged , Polymerase Chain Reaction
5.
Mol Carcinog ; 26(2): 93-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10506753

ABSTRACT

Occupational asbestos exposure can be demonstrated in 80% of mesothelioma cases. A possible role of simian virus 40 (SV40) in the etiology of mesothelioma was raised because several studies reported the presence and expression of SV40-like DNA sequences in human mesotheliomas. It is also known that expression of SV40 large T antigen inhibits cellular Rb and p53. This suggests that SV40 might render infected cells more susceptible to asbestos carcinogenicity. The SV40-like sequences are suggested to have arisen from contaminated polio vaccines. Millions of people in the United States and most European countries were inoculated with SV40-contaminated polio vaccine in 1955-1963. However, in Finland, where polio vaccination started in 1957, no SV40-contaminated vaccine was used. We used a polymerase chain reaction-based method to test for the presence of SV40-like sequences in DNA extracted from the frozen tumor tissues of 49 Finnish mesothelioma patients, most of whom had been occupationally exposed to asbestos. All of the Finnish tumor tissues tested negative for SV40-like sequences. The results suggest that the SV40-like sequences detected in mesothelioma tissue in some previous studies may indeed originate from SV40-contaminated polio vaccines. It is a matter of speculation whether the absence of SV40 infection has contributed to the relatively low incidence of mesothelioma in Finland (1/10(5) in 1990-1995).


Subject(s)
Mesothelioma/virology , Pleural Neoplasms/virology , Poliovirus Vaccine, Inactivated/adverse effects , Simian virus 40/genetics , Simian virus 40/isolation & purification , Adult , Aged , Asbestos/adverse effects , Blotting, Southern , Cocarcinogenesis , DNA, Viral/analysis , Drug Contamination , Female , Finland , Humans , Male , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction , Time Factors
6.
Br J Cancer ; 80(11): 1781-5, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10468296

ABSTRACT

Twenty six patients with pleural mesothelioma of UICC stage I-IV excluding M1 disease (46% of whom had stage I disease and 38% stage III disease) were treated intravenously with high dose MTX (3 g) and calcium folinate rescue three times at intervals of 2 weeks and three times at intervals of 3 weeks. Natural interferon (IFN)-alpha (3 MIU days 2-10) and recombinant IFN-gamma1b (50 microg m(-2) on days 2, 6 and 10) were injected subcutaneously after each MTX dose. At the end of MTX treatment the IFNs were continued as maintenance therapy until disease progression. Seven partial responses were observed among 24 patients evaluable for response (response rate 29%, 95% confidence interval 13-51%). Median duration of response was 10 months (range 3-24 months). Median survival was 17 months and 1-year and 2-year survival rates 62% and 31% respectively. The toxicity of the chemo-immunotherapy was acceptable. Treatment was stopped in one patient who developed grade IV neurological toxicity. MTX dose reductions were rare (two patients with grade 1-2 renal toxicity). The combination of high dose MTX and IFN-alpha and IFN-gamma is active against malignant pleural mesothelioma and well-tolerated. The survival rates are encouraging.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Interferon-alpha/therapeutic use , Mesothelioma/therapy , Methotrexate/therapeutic use , Pleural Neoplasms/therapy , Adolescent , Adult , Aged , Antimetabolites, Antineoplastic/adverse effects , Combined Modality Therapy , Female , Humans , Interferon-alpha/adverse effects , Male , Mesothelioma/mortality , Mesothelioma/pathology , Methotrexate/adverse effects , Middle Aged , Neoplasm Staging , Pleural Neoplasms/mortality , Pleural Neoplasms/pathology , Survival Analysis
7.
Scand J Work Environ Health ; 24(5): 398-406, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9869312

ABSTRACT

OBJECTIVES: The occurrence and causes of hairdressers' occupational skin and respiratory diseases were studied. METHODS: Of a random sample of 500 female hairdressers aged 15-54 years, 355 were available for study. Of the 189 reporting work-related skin and respiratory symptoms in a computer-aided telephone interview on exposure and health, 130 underwent a physical examination, lung function tests, prick and patch testing, and nasal and lung provocation tests. An occupational disease was diagnosed when the causality between exposure and disease was probable and the clinical tests supported the diagnosis. RESULTS: The telephone interview revealed a life-time prevalence of 16.9% for hand dermatoses, 16.9% for allergic rhinitis, and 4.5% for asthma among the hairdressers. In the clinical investigations, the prevalence was 2.8% for occupational dermatoses, 1.7% for occupational rhinitis, and 0.8% for occupational asthma. Ammonium persulfate caused 90% of the respiratory diseases and 27% of the hand dermatoses. Paraphenylenediamine, natural rubber latex, and skin irritation were also causes of hand dermatitis. Allergy to human dandruff (8.6%) and Pityrosporum ovale (12.1%) was common. Previously diagnosed atopic diseases increased the risk for occupational skin or respiratory disease 3-fold (odds ratio 2.9, 95% confidence interval 1.1-7.9). Of the cases, 37.5% (6 of 16 persons) had to change occupations during a 3-year follow-up. CONCLUSIONS: Work-related skin and respiratory symptoms are common among hairdressers. Often a specific cause (eg, ammonium persulfate) can be found if occupational diseases are suspected and diagnosed. Hairdressers with atopic diseases are at risk of developing occupational skin and respiratory diseases.


Subject(s)
Hair Preparations/adverse effects , Hand Dermatoses/epidemiology , Lung Diseases/epidemiology , Occupational Diseases/epidemiology , Adult , Aged , Data Collection/methods , Dermatitis, Occupational/diagnosis , Dermatitis, Occupational/epidemiology , Dermatitis, Occupational/etiology , Female , Finland/epidemiology , Hand Dermatoses/chemically induced , Hand Dermatoses/diagnosis , Humans , Lung Diseases/chemically induced , Lung Diseases/diagnosis , Middle Aged , Occupational Diseases/chemically induced , Occupational Diseases/diagnosis , Patch Tests , Prevalence , Rhinitis/chemically induced , Rhinitis/diagnosis , Rhinitis/epidemiology
8.
Genes Chromosomes Cancer ; 22(1): 79-82, 1998 May.
Article in English | MEDLINE | ID: mdl-9591638

ABSTRACT

We performed a comparative genomic hybridization study on 25 samples of adenocarcinoma and 19 samples of squamous cell carcinoma of the lung to detect recurrent changes in the genetic material. DNA copy number changes were found in 16 squamous cell carcinoma samples and 17 adenocarcinoma samples. The most common changes were gains of DNA sequences in 3q (43%), 1q (34%), 8q (32%), 5p, (30%), 7p (25%), and 12p (25%). Of the squamous cell carcinoma samples with DNA copy number changes, 94% (15/16) had a gain in 3q (minimal common region of overlap q24-qter), whereas only 24% (4/17) of the adenocarcinoma samples with DNA copy number changes showed a gain in 3q (q22-qter) (P < 0.001). Six high-level amplifications in 3q (q26.2-q26.3) were detected in the squamous cell carcinoma samples but none were observed in the adenocarcinoma samples. Our results suggest that amplification of genes in 3q may be important in the tumorigenesis of squamous cell carcinoma but not necessarily of adenocarcinoma.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Squamous Cell/genetics , Chromosomes, Human, Pair 3/genetics , DNA, Neoplasm/genetics , Lung Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Chromosome Deletion , Gene Amplification , Gene Dosage , Humans , Male , Middle Aged , Nucleic Acid Hybridization/methods
9.
Br J Cancer ; 77(2): 260-9, 1998.
Article in English | MEDLINE | ID: mdl-9460997

ABSTRACT

The differential diagnosis of mesothelioma, primary adenocarcinomas and pleural metastases frequently causes problems. We have used the comparative genomic hybridization (CGH) technique on 34 malignant mesotheliomas and 30 primary lung carcinomas (adenocarcinoma, including bronchoalveolar carcinoma and large-cell anaplastic carcinoma) to compare their copy number changes and to evaluate the use of CGH to distinguish between these two types of tumour. In mesothelioma, gains of genetic material occurred as frequently as losses, whereas gains predominated over losses in carcinoma. In mesothelioma, the most frequent changes were losses in 4q, 6q and 14q and gains in 15q and 7p, whereas gains in 8q, 1q, 7p, 5p and 6p were the most common changes in carcinoma. Amplification of KRAS2 was detected in two adenocarcinomas by Southern blot analysis. CGH showed gains in 12p in the same tumours. Statistically significant differences between the two types of tumour were detected in chromosomes X, 1, 2p, 4, 8q, 10q, 12p, 14q, 15q and 18q. When comparing the frequency of gains and losses between mesothelioma and lung carcinoma using discriminant analysis, the sensitivity of CGH to differentiate mesotheliomas from lung carcinomas was 81% and the specificity 77%. The differences in DNA copy number changes between the two types of tumour suggest that they are genetically different tumour entities. Although CGH cannot be used as a definitive discriminatory method, we were able to distinguish between mesothelioma and lung carcinoma in a large proportion of the abnormal cases.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Large Cell/genetics , DNA, Neoplasm/genetics , Lung Neoplasms/genetics , Mesothelioma/genetics , Chromosome Mapping , Humans , In Situ Hybridization, Fluorescence , Multivariate Analysis , Pleural Neoplasms/genetics
10.
Scand J Work Environ Health ; 23(4): 266-70, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9322817

ABSTRACT

OBJECTIVES: The study analyzed the recent trend in the incidence of mesothelioma in Finland and evaluated the coverage of reporting work-related mesothelioma. METHODS: The incidence of mesothelioma in 1960-1995 was retrieved from the Finnish Cancer Registry, and the number of asbestos-associated work-related mesotheliomas were taken from the Finnish Register of Occupational Diseases. RESULTS: The annual number of mesotheliomas increased rapidly in 1975-1990. In the 1990s, the age-adjusted incidence remained relatively stable for Finnish men. The annual number of cases still increased among men over 65 years of age, but decreased slightly among men under 55 years of age and among women. About 35 annual cases were diagnosed among men and 10-15 among women in the mid-1990s. The reporting of work-related mesotheliomas improved during the Finnish asbestos program in 1987-1992. In 1993-1995 about 30 annual cases (ie, about 90% of all pleural and 50% of the peritoneal mesotheliomas in men) were reported to be work-related. CONCLUSIONS: The increasing trend in the incidence of mesothelioma in Finland has slowed down in the 1990s, and the maximum of asbestos-related cases in the early 2000s will probably be clearly less than the 100 annual cases estimated in the early 1990s. If the observed trend continues up to 2010, about 40-50 cases among men and 10-20 among women will then be diagnosed annually. Altogether 40-50 of these cases would be related to occupational asbestos exposure.


Subject(s)
Mesothelioma/epidemiology , Occupational Diseases/epidemiology , Peritoneal Neoplasms/epidemiology , Pleural Neoplasms/epidemiology , Aged , Female , Finland/epidemiology , Humans , Incidence , Male , Middle Aged
11.
J Occup Environ Med ; 39(6): 534-9, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9211211

ABSTRACT

We carried out a retrospective cohort study using a self-administered questionnaire to assess the risk of hairdressers to develop asthma and chronic bronchitis. A representative sample of 4433 female hairdressers and an equal number of shop personnel in employment in 1980 was drawn from the Longitudinal Census Data File of Statistics Finland. Physician-diagnosed asthma, chronic bronchitis, and other respiratory diseases in 1980 and 1995 were inquired about in the respiratory part of the questionnaire. The response rate to the questionnaire was 82% for the hairdressers (n = 3484) and 79% for the referents (n = 3357). The prevalence of asthma among the hairdressers was 5.6% in 1980 and 10.1% in 1995, and the prevalence of chronic bronchitis was 3.9% in 1980 and 5.6% in 1995. The relative risk for asthma (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.3 to 2.3 in 1980; and OR: 1.7, 95% CI: 1.4 to 2.2 in 1995) and for chronic bronchitis (OR: 2.2, 95% CI: 1.5 to 3.2 in 1980; and OR: 1.9, 95% CI: 1.4 to 2.6 in 1995) among hairdressers was almost twice that in the reference group. The incidence rate of asthma in 1980 through 1995 was 2.2 and of chronic bronchitis was 1.1 cases per 1000 person-years among hairdressers, whereas the rate in the reference group was 1.3 asthma cases and 0.9 chronic bronchitis cases per 1000 person-years. The relative risk for developing asthma during the 15 years observation time was 1.7 (95% CI: 1.1 to 2.5) and for chronic bronchitis was 1.2 (95% CI: 0.7 to 1.9) among hairdressers, compared with referents. Our results indicate that hairdressers are at higher risk for developing asthma.


Subject(s)
Asthma/epidemiology , Barbering , Bronchitis/epidemiology , Occupational Diseases/epidemiology , Adult , Aged , Aged, 80 and over , Cause of Death , Chronic Disease , Cohort Studies , Confidence Intervals , Female , Finland/epidemiology , Humans , Incidence , Longitudinal Studies , Middle Aged , Odds Ratio , Prevalence , Retrospective Studies , Risk Assessment , Surveys and Questionnaires
12.
Occup Environ Med ; 54(6): 452-5, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9245953

ABSTRACT

OBJECTIVES: Hairdressers are exposed to many irritative and allergenic substances capable of causing occupational respiratory symptoms and diseases. The self reported prevalence of respiratory symptoms and diseases was studied, and the risks among hairdressers compared with saleswomen was estimated. METHODS: A cross sectional prevalence study of respiratory symptoms and diseases was carried out among hairdressers and supermarket saleswomen, with a computer assisted telephone interview method (CATI). The study population comprised all the female hairdressers and supermarket saleswomen aged 15-54 years in the Helsinki metropolitan area, Finland. Disproportionate random samples of female hairdressers and sales-women were drawn from the trade union membership registers. The interviews were carried out between February and April 1994. A response rate of 80.5% (355/440) was obtained for hairdressers and 82.2% (583/709) for saleswomen. Atopy, smoking, chronic illnesses, type of work, working hours, working conditions, personal and professional use of hair products, and the use of personal protective devices were assessed. The outcome variables were self reported symptoms of the upper and lower respiratory tract. These were used to define chronic bronchitis, and asthma, laryngitis, and allergic rhinitis diagnosed by a physician. RESULTS: There was a considerable difference in the prevalence of chronic bronchitis; 6.8% in hairdressers versus 1.9% in saleswomen. The odds ratio (OR) adjusted for age, smoking, and atopy for chronic bronchitis indicated an increased risk of chronic bronchitis (OR 4.8, 95% confidence interval (95% CI) 2.2 to 10.1). No association was found between work as a hairdresser and asthma, laryngitis, and allergic rhinitis. Also the prevalence of rhinitis, rhinitis with eye symptoms, cough with phlegm, dyspnoea, and dyspnoea accompanied by cough was increased among hairdressers. The corresponding adjusted risk ORs were 1.7 (95% CI 1.3 to 2.3) for rhinitis, 1.9 (95% CI 1.4 to 2.6) for rhinitis with eye symptoms, 1.4 (CI 1.1 to 1.9) for cough with phlegm, 1.5 (95% CI 1.0 to 2.2) for dyspnoea, and 1.6 (95% CI 1.0 to 2.7) for dyspnoea with cough. CONCLUSIONS: Our results indicate an increased prevalence of upper and lower respiratory symptoms among hairdressers. Allergenic and irritative chemicals in hairdressing are likely candidates explaining the difference found between the hairdressers and controls. Work related reasons should be considered when a hairdresser presents with airway symptoms. Preventive actions are needed to improve the working conditions and personal protection.


Subject(s)
Barbering , Occupational Diseases/epidemiology , Respiratory Tract Diseases/epidemiology , Adolescent , Adult , Bronchitis/epidemiology , Cross-Sectional Studies , Female , Finland/epidemiology , Humans , Hypersensitivity, Immediate/epidemiology , Logistic Models , Middle Aged , Multivariate Analysis , Occupational Diseases/etiology , Odds Ratio , Prevalence , Respiratory Tract Diseases/etiology , Smoking/adverse effects
13.
Br J Cancer ; 75(4): 523-7, 1997.
Article in English | MEDLINE | ID: mdl-9052404

ABSTRACT

Comparative genomic hybridization (CGH) analyses were performed on 27 human pleural mesothelioma tumour specimens, consisting of 18 frozen tumours and nine paraffin-embedded tumours, to screen for gains and losses of DNA sequences. Copy number changes were detected in 15 of the 27 specimens with a range from one to eight per specimen. On average, more losses than gains of genetic material were observed. The loss of DNA sequences occurred most commonly in the short arm of chromosome 9 (p21-pter), in 60% of the abnormal specimens. Other losses among the abnormal specimens were frequently detected in the long arms of chromosomes 4 (q31.1-qter, 20%), 6 (q22-q24, 33%), 13 (33%),14 (q24-qter, 33%) and 22 (q13, 20%). A gain in DNA sequences was found in the long arm of chromosome 1 (cen-qter) in 33% of the abnormal specimens. Our analysis is the first genome-wide screening for gains and losses of DNA sequences using comparative genomic hybridization in malignant pleural mesothelioma tumours. The recurrent DNA sequence changes detected in this study suggest that the corresponding chromosomal areas most probably contain genes important for the initiation and progression of mesothelioma.


Subject(s)
Mesothelioma/genetics , Pleural Neoplasms/genetics , Sequence Analysis, DNA , Sequence Deletion , Adult , Aged , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 22/genetics , Chromosomes, Human, Pair 4/genetics , Chromosomes, Human, Pair 6/genetics , Chromosomes, Human, Pair 9/genetics , DNA, Neoplasm/genetics , Female , Humans , Male , Middle Aged , Nucleic Acid Hybridization
14.
Eur J Cancer ; 33(13): 2211-5, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9470808

ABSTRACT

Intravenous and oral etoposide (VP 16-213) were tested in two sequential phase II trials in chemotherapy-naive patients with malignant pleural mesothelioma. In the first trial, etoposide was given intravenously (i.v.) at a dose of 150 mg/m2 on days 1, 3 and 5 every 3 weeks. The second trial investigated a daily oral dose of 100 mg for 21 days followed by a 2-week treatment-free period, and then recycling. In both trials, the treatment was given until disease progression, intolerable toxicity or patient refusal. In the i.v. trial, 49 patients were included, 2 patients were ineligible. The oral trial recruited 45 patients, 4 patients were not eligible. In both trials, the main side-effects were moderate leucopenia, alopecia, nausea and vomiting. Two partial responses (4%) and three partial responses (7%) were reported in the i.v. and oral trials, respectively. The median survival was 29 weeks and 38 weeks in the i.v. and oral trials, respectively. In conclusion, further investigation of etoposide in malignant mesothelioma is not recommended.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Etoposide/therapeutic use , Mesothelioma/drug therapy , Pleural Neoplasms/drug therapy , Administration, Oral , Adult , Aged , Antineoplastic Agents, Phytogenic/adverse effects , Drug Administration Schedule , Etoposide/adverse effects , Female , Humans , Infusions, Intravenous , Male , Mesothelioma/pathology , Middle Aged , Pleural Neoplasms/pathology , Survival Rate
15.
Br J Cancer ; 74(10): 1534-40, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8932331

ABSTRACT

Prior analysis of 20 human mesothelioma cell lines for p53 status revealed only two mutations and one p53 null cell line, although p53 expression was detected in most cell lines. In addition, mRNA and protein expression of the retinoblastoma gene product in human mesothelioma cell lines is similar to normal controls. We have tested for p53 induction after exposure to ionising radiation and demonstrate this induction and, to a lesser extent, p21(WAF1) induction, in both normal mesothelial cells and p53-positive mesothelioma cell lines. We postulated that high levels of MDM2 might alter p53 and retinoblastoma tumour-suppressor function in mesothelioma. However, Southern blot analysis for mdm2 indicated that no amplification had occurred in 18 mesothelioma cell lines tested. Steady-state mRNA and protein levels also did not indicate overexpression. These results indicate that high levels of MDM2 are not responsible for inactivating the functions of wild-type p53 or the retinoblastoma gene product during the pathogenesis of malignant mesothelioma.


Subject(s)
Mesothelioma/metabolism , Neoplasm Proteins/metabolism , Nuclear Proteins , Proto-Oncogene Proteins/metabolism , Tumor Suppressor Protein p53/metabolism , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Gene Amplification , Gene Expression , Genes, p53 , Humans , Mesothelioma/genetics , Mutation , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Proto-Oncogene Proteins/biosynthesis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-mdm2 , RNA, Messenger/metabolism , Tumor Cells, Cultured , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/genetics
16.
Cancer Genet Cytogenet ; 89(1): 7-13, 1996 Jul 01.
Article in English | MEDLINE | ID: mdl-8689616

ABSTRACT

The molecular basis of malignant mesothelioma is poorly known. We examined genetic changes in 11 mesothelioma specimens by comparative genomic hybridization (CGH). Five DNA specimens originated from uncultured tumor tissues and six from cell lines established from the same patients. Findings from the classical karyotypic characterization of both primary tumors and cell lines have been reported previously. In the CGH analyses the most common genetic alterations in the 11 mesothelioma specimens were losses of chromosomal regions in 1p, 8p, 14q, and 22q and gains of 5p, 6p, 8q, 15q, 17q, and 20. The cell lines had on average a much higher total number of genetic changes than the uncultured tumor specimens. Clonal relationship between the cell lines and the uncultured tissue specimens could not usually be demonstrated even though they originated from the same patient. The observed differences may partly be due to high frequency of chromosomal rearrangements, which CGH cannot detect, partly due to contamination of tumor specimens with normal tissue, and partly due to genetic evolution in tumor cell lines.


Subject(s)
Chromosome Aberrations , DNA, Neoplasm/chemistry , Mesothelioma/genetics , Humans , Nucleic Acid Hybridization , Tumor Cells, Cultured
17.
Cancer Res ; 55(14): 2981-3, 1995 Jul 15.
Article in English | MEDLINE | ID: mdl-7606714

ABSTRACT

Besides asbestos exposure, the factors that determine susceptibility to malignant mesothelioma are unknown. We evaluated the risk of GSTM1 null genotype and slow acetylation-associated NAT2 genotype for malignant mesothelioma in relation to asbestos exposure. Both the GSTM1 null genotype and the NAT2 slow acetylator genotype placed individuals at about 2-fold increased risk of developing malignant mesothelioma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.0-3.5 and OR = 2.1, 95% CI = 1.1-4.1, for the GSTM1 and NAT2 genes, respectively]. When the patients were divided into low/moderate and high exposure groups according to their asbestos exposure histories, the effect of the at-risk genotypes was mostly attributable to the high exposure groups (OR = 2.3, 95% CI = 1.0-5.6 and OR = 3.7, 95% CI = 1.3-10.2, for the GSTM1 and NAT2 genes, respectively). The individuals with combined GSTM1 and NAT2 defects had about a 4-fold risk of developing malignant mesothelioma compared to those with the GSTM1 gene and NAT2 fast acetylator genotype (OR = 3.6; 95% CI = 1.3-9.6). Moreover, the risk among subjects highly exposed to asbestos with the double at-risk genotype was more than 7-fold greater compared to those with the more beneficial genotypes of both GSTM1 and NAT2 genes (OR = 7.4; 95% CI = 1.6-34.0).


Subject(s)
Arylamine N-Acetyltransferase/genetics , Asbestos/adverse effects , Cocarcinogenesis , Glutathione Transferase/genetics , Isoenzymes/genetics , Mesothelioma/etiology , Mesothelioma/genetics , Adult , Aged , Evaluation Studies as Topic , Female , Genes, Regulator , Genotype , Humans , Male , Mesothelioma/enzymology , Middle Aged , Polymorphism, Genetic/genetics , Risk Factors
18.
Lung Cancer ; 12(1-2): 25-34, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7600028

ABSTRACT

There is no universally-recognised method for staging malignant mesothelioma, although the use of computed tomograph (CT) scanning has improved the staging of non-invasive disease. The International Union against Cancer has recently proposed using the Tumour Node Metastases (TNM) staging system for mesothelioma, but in clinical practice it is difficult to assess tumour and nodal involvement due to the unique plate-like growth pattern of this tumour. In order to evaluate TNM staging we analysed pre-operative CT scans from 88 patients with histologically-confirmed malignant pleural mesothelioma, all from the same institution. The median age of the patients was 56 years (range 38-79). There were 70 men and 18 women, and 33 had tumours with epithelial histology. The median survival time was 10 months (range 0.2-110), from the date of histological confirmation of mesothelioma. The same radiologist analysed all the CT scans according to the TNM staging system. Actuarial survival curves were constructed by the Kaplan-Meier method. Survival curves for the different TNM categories were compared using the log-rank test. Node evaluation could not be completed in eight cases because the tumour had encompassed the hilum and mediastinum. In multivariate analysis, significant differences in prognosis correlated with the different T categories (P < 0.01), and the different TNM stages (P < 0.05), but not the N categories or the M categories. Larger studies are needed to assess the importance of TNM staging in the selection of treatment and as a prognostic factor for malignant mesothelioma.


Subject(s)
Mesothelioma/pathology , Neoplasm Staging/methods , Pleural Neoplasms/pathology , Adult , Aged , Female , Humans , Lymphatic Metastasis , Male , Mesothelioma/diagnostic imaging , Mesothelioma/mortality , Middle Aged , Multivariate Analysis , Pleural Neoplasms/diagnostic imaging , Pleural Neoplasms/mortality , Prognosis , Radiography , Survival Rate , Tomography Scanners, X-Ray Computed
19.
Occup Environ Med ; 52(2): 134-7, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7757167

ABSTRACT

OBJECTIVES: This study prospectively evaluated factors of working conditions and lifestyle in the development of chronic non-specific lung disease (CNSLD). METHODS: Baseline data were collected in 1981 from 5386 municipal employees born in 1923-35 who had no diagnosed CNSLD. The subjects were studied again in 1985 with a postal questionnaire. The predictors of CNSLD were selected by multivariate logistic regression analysis. RESULTS: 159 (3%) reported the development of CNSLD confirmed by a physician. During the 4.6 year follow up period the average annual incidence was 6.5/1000 subjects. In men the logit model followed was: smoking (odds ratio (OR) 1.17, 95% confidence interval (95% CI) 1.06-1.29), tight work schedule (OR 1.31, 95% CI 1.03-1.65), loss of a close friend (OR 2.21, 95% CI 1.13-4.31), and retirement of a spouse (OR 3.31, 95% CI 1.35-8.11). In women the selected risk factors were: smoking (OR 1.22, 95% CI 1.01-1.38), atopy (OR 1.99, 95% CI 1.12-3.53), physically heavy work (OR 1.65, 95% CI 1.09-2.29), poor physical working conditions such as heat, cold, changing temperature (OR 1.41, 95% CI 1.13-1.75), and infrequent communication with other people at work (OR 1.25, 95% CI 1.05-1.49). CONCLUSION: The differences in the predictors of the incidence of CNSLD between men and women were partly explained by different smoking habits, frequency of atopy, and working conditions. In men the significance of life events (loss of close friend and retirement of wife) need further investigation.


Subject(s)
Employment , Life Style , Lung Diseases/etiology , Occupational Diseases/etiology , Adult , Chronic Disease , Female , Finland/epidemiology , Humans , Incidence , Life Change Events , Logistic Models , Lung Diseases/epidemiology , Male , Middle Aged , Occupational Diseases/epidemiology , Prospective Studies , Risk Factors , Smoking/adverse effects
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