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1.
Occup Med (Lond) ; 74(1): 63-70, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-37133767

RESUMO

BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.


Assuntos
COVID-19 , Humanos , Masculino , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Ocupações , Local de Trabalho , Dinamarca/epidemiologia
2.
Int J Obes (Lond) ; 43(3): 533-544, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30181653

RESUMO

BACKGROUND/OBJECTIVES: Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. SUBJECTS/METHODS: A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. RESULTS: Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm3 vs. 879 (775-1086) mm3; P < 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (rs = -0.67; P < .001; rs = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm3 increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P < 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. CONCLUSIONS: A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.


Assuntos
Craniofaringioma , Hipotálamo , Obesidade/complicações , Neoplasias Hipofisárias , Adolescente , Adulto , Craniofaringioma/complicações , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/epidemiologia , Craniofaringioma/patologia , Estudos Transversais , Feminino , Humanos , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Fatores de Risco , Adulto Jovem
3.
Diabetologia ; 56(8): 1689-95, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23699990

RESUMO

AIMS/HYPOTHESIS: The primary aim of the study was to investigate the risk of developing gestational diabetes in women who were exposed to tobacco smoke in utero. Secondary aims were to assess the risk of obesity and non-gestational diabetes. METHODS: Data were retrieved from the Medical Birth Register of Sweden for women who were born in 1982 (when smoking data were first registered) or later and who had given birth to at least one child; 80,189 pregnancies were included. The associations between in utero smoking exposure (three categories: non-smokers, 1-9 cigarettes/day [moderately exposed] and >9 cigarettes/day [heavily exposed]) and subsequent gestational diabetes (n = 291), non-gestational diabetes (n = 280) and obesity (n = 7,300) were assessed. RESULTS: The adjusted ORs (aORs) of gestational diabetes were increased among women who were moderately (1.62, 95% CI 1.24, 2.13) and heavily (1.52, 95% CI 1.12, 2.06) exposed. The corresponding aORs of obesity were 1.36 (95% CI 1.28, 1.44) and 1.58 (95% CI 1.48, 1.68), respectively. A reduced OR for non-gestational diabetes was seen in the offspring of heavy smokers (aOR 0.66, 95% CI 0.45, 0.96). CONCLUSIONS/INTERPRETATION: Women exposed to smoking during fetal life were at higher risk of developing gestational diabetes and obesity.


Assuntos
Diabetes Gestacional/epidemiologia , Obesidade/epidemiologia , Fumar/efeitos adversos , Adulto , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Adulto Jovem
4.
Hum Reprod ; 27(8): 2532-40, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22647447

RESUMO

BACKGROUND: Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality. METHODS: PFCs were measured in serum from 588 partners of pregnant women from Greenland, Poland and Ukraine who provided a semen sample, using liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) could be detected in >97% of the samples. The associations between levels of these compounds and semen volume, sperm concentration, total sperm count, motility and morphology were assessed. RESULTS: Across countries, sperm concentration, total sperm count and semen volume were not consistently associated with PFOS, PFOA, PFHxS or PFNA levels. The proportion of morphologically normal cells was 35% lower [95% confidence interval (CI): 4-66%) for the third tertile of PFOS exposure as compared with the first. A similar reduction was found in relation to increasing PFHxS levels. At the third PFOA exposure tertile, the percentage of motile spermatozoa was 19% (95% CI: 1 to 39%) higher than in the first. CONCLUSIONS: The most robust finding in the present study was the negative associations between PFOS exposure and sperm morphology suggesting adverse effects of PFOS on semen quality, possibly due to interference with the endocrine activity or sperm membrane function. It cannot be excluded that this association and the positive association between PFOA and semen motility, which was not consistent across countries, might represent a chance finding due to the multiple statistical tests being performed.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Fluorocarbonos/toxicidade , Análise do Sêmen , Sêmen/efeitos dos fármacos , Ácidos Sulfônicos/toxicidade , Adulto , Regiões Árticas , Cromatografia Líquida/métodos , Poluentes Ambientais/toxicidade , Europa (Continente) , Feminino , Groenlândia , Humanos , Masculino , Espectrometria de Massas/métodos , Polônia , Gravidez , Contagem de Espermatozoides , Ucrânia
5.
Hum Reprod ; 26(5): 1012-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21382832

RESUMO

INTRODUCTION: Based on historical data, a decline in sperm counts during the years 1940-1990 has been suggested and aetiologically linked to a concomitant increase in the incidence of testicular cancer. This study, focusing on possible changes in sperm parameters among young Swedish men, during the past 10 years, was specifically designed in order to answer the question of whether there is a continuing decline in sperm counts. METHODS: During the period 2008-2010, 295 young (17-20 years; median 18) men born and raised in Sweden were recruited at the age they were supposed to undergo medical examination prior to military service. The participants filled in questionnaires, underwent andrological examination and delivered an ejaculate. Their semen parameters were compared with those of a similar cohort of men (n = 216) recruited in the year 2000-2001. RESULTS: No significant changes (means; 2000-2001 versus 2008-2010) in sperm concentration (78 × 106/ml versus 82 × 106/ml; P = 0.54), semen volume (3.1 ml versus 3.0 ml; P = 0.26) or total sperm counts (220 × 106 versus 250 × 106; P = 0.18) were found. The proportion of progressively motile spermatozoa also remained unchanged. CONCLUSIONS: Between the years 2000 and 2010 we found no evidence of time-related deterioration of semen parameters among young Swedish men from the general population. This finding does not exclude that such a decrease may have taken place before year 2000. If the risk of testicular cancer is linked to the sperm counts, the increase in incidence of this malignancy should be levelling off in southern Sweden in the next 10-15 years.


Assuntos
Contagem de Espermatozoides , Espermatozoides/fisiologia , Adolescente , Adulto , Estudos de Coortes , Doenças dos Genitais Masculinos/epidemiologia , Humanos , Masculino , Fatores de Risco , Análise do Sêmen , Suécia , Fatores de Tempo
6.
Sci Total Environ ; 751: 141476, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32871309

RESUMO

BACKGROUND: More women in reproductive ages are entering occupations where exposure to whole body vibrations (WBV) is common (e.g. in transportation and construction). Previous studies based on self-assessed exposure suggest increased risks of adverse birth outcomes, but it is unclear at what exposure levels and if the current exposure guidelines are appropriate during pregnancy. OBJECTIVES: To investigate whether occupational WBV-exposure increases the risk of preterm birth, low birth weight, and/or small-for-gestational age, in a large, nationwide, prospective, cohort study. DESIGN: The Fetal Air Pollution Exposure cohort (FAIR) was formed by merging data from multiple, national registers, and the present study includes singletons born 1994-2014 to working women in Sweden (n = 1,091,080 births). WBV-exposure was assessed quantitatively using a job-exposure matrix based on measurements, and calculated odds ratios were adjusted for potential confounders such as smoking and BMI, and other occupational exposures like noise, combustion particles, and physically and psychologically strenuous work. Data on absence from work (full-/part time, sick leave, parental leave, etc.) was also used. RESULTS: Exposure to WBV during pregnancy, among women with low absence from work (n = 476,419), was associated with an increased risk of preterm birth, below the occupational exposure limit (1.15 m/s2). Compared to unexposed mothers, the OR was 1.38 (95% CI: 1.05, 1.83) for exposure ≥0.5 m/s2, corresponding to an increase from 47/1000 cases to 65/1000 cases. No increased risk was found for small-for-gestational age. CONCLUSIONS: Exposure to WBV was associated with an increased risk of preterm birth. The results suggest that the current permissible exposure and action levels for WBV-exposure do not adequately protect pregnant women with continuous exposure.


Assuntos
Exposição Ocupacional , Nascimento Prematuro , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Exposição Ocupacional/efeitos adversos , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Suécia/epidemiologia , Vibração/efeitos adversos
7.
Mol Hum Reprod ; 16(3): 153-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19884136

RESUMO

A negative linear association between androgen receptor (AR) function and the CAG repeat numbers is generally assumed. However, in vivo data concerning the association between CAG number and androgenic effects have been conflicting. Since former in vitro studies mostly have been based on extreme CAG lengths and reporter-systems containing viral promoters, the objective of this study was to investigate ARs with CAG lengths within normal range (16, 22 and 28) in a reporter-assay with the human prostate specific antigen promoter as target. We also wished to elucidate whether the interpretation of the results was depending on the methods used for adjustment of transfection efficiency and protein content. With beta-galactosidase as transfection control, 22CAG had the highest activity (set to 100%) compared with 16CAG [mean 78% (range 41-132), P = 0.005] and 28CAG [68% (26-162), P = 0.006], whereas renilla-luciferase resulted in 16CAG behaving similar to 22CAG [104% (56-165), P = 0.7] and 28CAG having lower activity [59% (33-101), P = 0.004]. In these experiments, also the empty vector displayed considerable background activity. When adjusting for AR protein, the 22CAG genotype had the highest activity; 16CAG and 28CAG displaying 20% (10-47, P < 0.0001) and 12% (5-21, P < 0.0001) thereof. Similar results were obtained with adjustment for total protein. Thus, by normalizing for AR-content, contrary to various control vectors, the highest AR activity was confined to the 22CAG and not 16 CAG, which may at least partly explain the discrepancy in data aiming to link physiological conditions to CAG repeat length.


Assuntos
Receptores Androgênicos/metabolismo , Repetições de Trinucleotídeos/genética , Animais , Células COS , Chlorocebus aethiops , Ensaio de Imunoadsorção Enzimática , Vetores Genéticos/genética , Humanos , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Polimorfismo Genético/fisiologia , Regiões Promotoras Genéticas/genética , Antígeno Prostático Específico/genética , Receptores Androgênicos/genética
8.
Occup Environ Med ; 66(3): 198-204, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19017705

RESUMO

OBJECTIVES: To investigate birth weight and fetal growth in female hairdressers, while controlling for intergenerational effects and effects related to childhood exposures. METHODS: A cohort of women who had attended vocational schools for hairdressers were compared to their sisters with respect to birth weight and fetal growth (measured as small for gestational age (SGA) or large for gestational age (LGA), respectively) in their infants. In total, 6223 infants born to 3137 hairdressers and 8388 infants born to 3952 hairdressers' sisters were studied. RESULTS: Among the infants born to the hairdressers' sisters, the distribution of birth weights were wider than that among the infants born to the hairdressers. This was also reflected in that hairdresser cohort affiliation tended to be protective against both SGA (odds ratio 0.80; 95% confidence interval 0.49 to 1.31) and LGA (0.77; 0.54 to 1.09). For LGA, this effect was even more pronounced among women who had actually worked as hairdressers during at least one pregnancy (0.60; 0.39 to 0.92). The infants born to these women also had a significantly lower mean birth weight (3387 g vs 3419 g; p = 0.033). CONCLUSIONS: The results from the present study suggest that infants born to hairdressers have a decreased risk of being LGA. This is most likely not caused by a shift in birth weight distribution or abnormal glucose metabolism.


Assuntos
Barbearia , Peso ao Nascer , Desenvolvimento Fetal , Adulto , Estudos de Casos e Controles , Feminino , Macrossomia Fetal , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Saúde Ocupacional , Razão de Chances , Gravidez , Resultado da Gravidez , Risco , Irmãos
9.
Andrology ; 7(1): 76-81, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30525303

RESUMO

BACKGROUND: Evaluation of male fertility includes standard semen analysis; however, there is uncertainty about the value of sperm parameters in predicting fertility. OBJECTIVE: To evaluate the association between semen parameters and fatherhood during a long-time period. MATERIALS AND METHODS: Semen parameters (total sperm count, concentration, motility, and morphology) and sperm DNA fragmentation Index (DFI) assessed on samples collected from 195 Norwegian men from the general population in 2001/2002 were matched with information about fatherhood until 2015, obtained from the Medical Birth Register. The parameters were dichotomized as normal vs. abnormal according to the WHO reference values from 1999 and 2010. Cut-offs at 20% and 30% were used for DFI. RESULTS: Among men who had no children before 2003, those with normal progressive sperm motility had more often become fathers (WHO 1999, cut-off ≥50%, adjusted OR 2.8, 95% CI 1.3-6.1 and WHO 2010, cut-off ≥32%; aOR 4.2, 95% CI 1.1-15). Based on the WHO 1999 reference value, men with normal sperm concentration (≥20 × 106 /mL) had more often become fathers (aOR 3.1, 95% CI 1.1-8.6). Men with progressive sperm motility ≥50% and concentration ≥20 × 106 /mL did more often achieve fatherhood (aOR 8.4, 95% CI 2.1-34). For DFI, there was a borderline significance at cut-off 20% in the group of men who had ever been fathers (OR 2.7, 95% CI 1.0-7.0 p < 0.05). DISCUSSION: The results indicate that sperm progressive motility, sperm concentration, and DFI are associated with fatherhood during a longer time period, with sperm motility being most consistent. Although the sample size is relatively small and our results should be replicated in larger studies, they may be of clinical relevance. CONCLUSION: Semen parameters may have a diagnostic value not only in a short time frame but also for predicting future fertility potential.


Assuntos
Infertilidade Masculina/diagnóstico , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Cromatina/ultraestrutura , Humanos , Masculino , Resultado do Tratamento
10.
Eur J Endocrinol ; 178(6): 577-587, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29599407

RESUMO

CONTEXT: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. OBJECTIVE: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. DESIGN: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. SETTING: The South Medical Region of Sweden (2.5 million inhabitants). PARTICIPANTS: Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. MAIN OUTCOME MEASURES: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. RESULTS: Right uncinate fasciculus was significantly altered (P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. CONCLUSIONS: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Craniofaringioma/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Craniofaringioma/epidemiologia , Craniofaringioma/psicologia , Estudos Transversais , Imagem de Tensor de Difusão/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/psicologia , Distribuição Aleatória , Adulto Jovem
11.
Eur J Endocrinol ; 155(2): 347-54, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16868150

RESUMO

BACKGROUND: The human androgen receptor (AR) gene contains two polymorphisms of CAG and GGN repeats respectively. The GGN repeat function is still largely unknown and to date there are no in vivo data on this segment with respect to the general population. METHODS: We investigated the impact of CAG and GGN repeats on male reproductive function, one by one and in interaction with each other, in 220 adolescent men from the general Swedish population. Physical examination and semen analysis, including accessory sex gland markers and measurement of reproductive hormone levels, were performed. Lifestyle-associated factors, including maternal smoking during pregnancy, were recorded. GGN and CAG repeat lengths were determined by sequencing. RESULTS: GGN<23 was associated with lower semen volume when compared to GGN=23 (mean difference -0.6 ml, P=0.02) and GGN>23 (mean difference -0.9 ml, P=0.002). Men with GGN<23, exposed to maternal smoking during pregnancy, had higher body mass index compared to men with other GGN lengths, no matter whether their mother had smoked or not during pregnancy (mean difference 4.8 kg/m2, P<0.001). CONCLUSIONS: Short GGN repeats seem to be associated with decreased semen volume, possibly due to suboptimal AR activity. Body composition may be influenced by the combination of fetal exposure to maternal smoking and certain AR genotypes.


Assuntos
Polimorfismo Genético , Receptores Androgênicos/genética , Reprodução/genética , Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Biomarcadores , Índice de Massa Corporal , Feminino , Genótipo , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Sêmen , Fumar , Suécia
12.
Leukemia ; 14(6): 1039-43, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10865970

RESUMO

A consecutive population-based series of 372 adult acute myeloid leukemias, successfully cytogenetically investigated at a single center between 1976 and 1993, is reported. All medical records were reviewed in order to ascertain the prognostic impact of karyotype, divided into three groups; favorable (t(8;21), t(15;17), and inv(16) irrespective of karyotypic complexity; n = 40), poor (der(1;7), inv(3), -5, del(5q), -7, t(9;22), and complex karyotypes including whole or partial losses of chromosomes 5 and/or 7; n = 56), and intermediate (other abnormalities or normal karyotype; n = 276). The possible modification by age, gender, time period, morphologic subtype, and bone marrow transplantation (BMT) on this prognostic impact was also determined. The chemotherapy regimens used were heterogeneous over time but principally the same at any given point in time. The majority of the patients were treated with combinations including an anthracycline and cytarabine with curative intent. Gender, morphology, and BMT did not significantly modify the effect of cytogenetic patterns on survival time, whereas age and time period did. The hazard ratios for the subgroups favorable, intermediate, and poor were 1.0, 1.2 and 1.9 at age 20-49; 1.0, 2.5 and 4.5 at age 50-64; 1.0, 4.1 and 11.4 at age 65-74; 1.0, 1.4 and 2.2 for the time period 1976-1987 and 1.0, 2.0 and 6.7 for 1988-1993. The salient feature of the Kaplan-Meier curves was the improved survival during the later time period for patients with favorable and intermediate cytogenetic abnormalities. The present findings thus suggest that it is mainly these patient groups that have benefited from advances in therapy, including supportive care.


Assuntos
Leucemia Mieloide/genética , Leucemia Mieloide/mortalidade , Doença Aguda , Adulto , Idoso , Transplante de Medula Óssea , Feminino , Humanos , Cariotipagem , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
13.
Leukemia ; 16(12): 2366-78, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12454741

RESUMO

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.


Assuntos
Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Segunda Neoplasia Primária/genética , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Aberrações Cromossômicas , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Cariotipagem , Leucemia Mieloide/epidemiologia , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/mortalidade , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Radioterapia/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida , Inibidores da Topoisomerase II
14.
Artigo em Inglês | MEDLINE | ID: mdl-8672995

RESUMO

The fate of carcinogens differs among individuals who have different activities of drug-metabolizing enzymes that are important in activating and detoxifying carcinogens. A drug that profoundly alters the metabolism of the drugs and carcinogens is the anticonvulsive agent phenobarbital. To investigate why epileptic patients appear to have a low risk of cancer of the urinary bladder, and on the basis of the observation that levels of aromatic amine-hemoglobin adducts are strongly associated with various risk factors for cancer at that site, we determined aromatic amine-hemoglobin adducts in 62 epileptic patients as a surrogate measure of the reaction of carcinogenic metabolites with DNA in target tissue. Although adducts were detected in all subjects, the levels were proportional to daily tobacco consumption. When the subjects were stratified into groups smoking 20 g tobacco/day or more, smoking <20 g/day, and not smoking, an effect of medication was detected. Epileptic patients treated chronically with phenobarbital or primidone, which is effectively metabolized to phenobarbital, were found to have lower levels of 4-aminobiphenyl adducts than patients on the other treatment (P = 0.02; ANOVA). In nonsmokers, no effect of medication could be demonstrated above background variation; however, an increasing effect was seen with tobacco consumption with only one-half the increase in adducts per g of tobacco smoked as epileptic patients on other treatment. The difference in the increases (slopes of regression lines) was highly significant statistically. This reduction in the level of hemoglobin-aromatic amine adducts is probably due to induction of detoxification enzymes in the patients treated with phenobarbital.


Assuntos
Anticonvulsivantes/metabolismo , Epilepsia/metabolismo , Hemoglobinas/metabolismo , Fenobarbital/metabolismo , Neoplasias da Bexiga Urinária/etiologia , Análise de Variância , Epilepsia/tratamento farmacológico , Humanos , Entrevistas como Assunto , Fatores de Risco , Fumar/efeitos adversos , Fumar/metabolismo , Neoplasias da Bexiga Urinária/metabolismo
15.
Toxicol Lett ; 77(1-3): 363-9, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7618163

RESUMO

Experimental data indicate that active oxygen species may be casually involved in the development of asbestos-related disease. Thus, it was hypothesized that individual differences in glutathione transferase activity, which may affect the ability to inactivate molecules formed in relation to oxidative stress, could influence the biological response to asbestos exposure. We could, however, not demonstrate an increased risk for radiographic changes or reduced lung function among asbestos cement workers deficient for glutathione transferase theta (GSTT1), glutathione transferase mu (GSTM1), or having a combined deficiency of enzyme activity.


Assuntos
Asbestose/diagnóstico por imagem , Asbestose/enzimologia , Glutationa Transferase/análise , Isoenzimas/análise , Pulmão/fisiopatologia , Exposição Ocupacional/efeitos adversos , Idoso , Amianto/efeitos adversos , Asbestose/fisiopatologia , Glutationa Transferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Radiografia , Testes de Função Respiratória , Fumar/efeitos adversos
16.
Toxicol In Vitro ; 9(1): 67-74, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20650064

RESUMO

Cell cultures are a potentially useful model to predict in vivo oral mucosa irritation. To this end, oral mucosa organ equivalent cultures (OMOEC) and skin equivalent cultures (SEC), both derived from human tissue, were evaluated for their responsiveness to test dentifrices with graded degrees of irritation potential. OMOEC and SEC were treated with test dentifrices and responses were evaluated by histopathology, cell viability (MTT incorporation), and cytotoxicity [release of aspartate aminotransferase (AST)]. Cell viability in OMOEC and SEC was reduced in a dose- and time-dependent manner in response to the test dentifrices. Correspondingly, AST release was increased in a dose- and time-dependent manner in response to the test dentifrices. These results demonstrate that OMOEC and SEC systems respond linearly to graded degrees of irritation potential as represented by generic dentifrices. Such results in an in vitro model of oral mucosa irritation allow direct comparison of in vitro responses with those obtained in an in vivo model, thus providing the groundwork for a tiered approach to assessment of irritation potential of oral care products.

17.
J Toxicol Environ Health A ; 64(6): 485-98, 2001 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-11732699

RESUMO

The purpose of this study was to assess the association between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma, a biomarker of exposure to polychlorinated biphenyls (PCB), and time to pregnancy (TTP) in a group of women with a varying dietary exposure to PCB. For 121 Swedish east coast fishermen's wives (median year of birth 1956, range 1945-1968), information on selt-reported TTP for the first planned pregnancy (median 2 mo, range 0-48) and CB-153 concentrations from blood samples drawn in 1995 (median 144 ng/g lipid, range 16-566) were available. Each woman's CB-153 concentration in plasma at the time immediately preceding her pregnancy was estimated, taking into account reduction of body burden of CB-153 due to lactation, the yearly reduction of PCB in Baltic Sea fish, as well as the biological half-life of CB-153. Based on the estimated CB-153 concentrations, subjects were categorized into tertiles as low (37-206 ng/g lipid), medium (207-330 ng/g lipid), and high (331-,1036 ng/g lipid) exposure groups. TTP in the medium- and high-exposure groups were then compared to TTP in the low-exposure group by estimating the corresponding success rate (i.e., the number of pregnancies per person month) ratios (SuRR) using discrete Cox regression, taking into account essential confounders. No obvious association between estimated CB-153 concentration and TTP was observed (medium vs. low: SuRR 0.77 [95% CI 0.47-1.28] and high vs. low: SuRR 0.95 10.74-1.23]). The present data give no support for a negative association between the plasma CB-153 concentrations observed in the present study and TTP. It should, however, be borne in mind that the study group was rather small and mainly included relatively young women, likely to have been only moderately exposed.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Fertilidade , Bifenilos Policlorados/sangue , Adolescente , Adulto , Animais , Carga Corporal (Radioterapia) , Estudos de Casos e Controles , Estudos de Coortes , Dieta , Feminino , Peixes , Contaminação de Alimentos , Humanos , Lactação/metabolismo , Pessoa de Meia-Idade , Gravidez , Suécia/epidemiologia , Fatores de Tempo
18.
Scand J Work Environ Health ; 26(3): 207-12, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10901112

RESUMO

OBJECTIVES: The present study aimed to investigate whether boys who had been pre- and postnatally exposed to persistent organochlorine compounds through the consumption of contaminated fatty fish from the Baltic Sea (on the east coast of Sweden) had medical or psychometric impairments in the compulsory conscript examination at 18 years of age. METHODS: Boys born in 1973 to 1975 to fishermen's wives and fishermen's sisters from the Swedish east coast were examined at 18 years of age. For relevant comparisons a corresponding group from the Swedish west coast, where the fish are less contaminated, were used. In addition, comparisons were made with expected values based on conscript examination data for the general population in the same geographic areas. RESULTS: The boys in the 2 cohorts did not, during the conscript testing, significantly differ in the results of the psychometric tests. On the other hand, the boys from the eastcoast cohort were somewhat shorter and had more visual and hearing impairments than the boys from the west coast. However, the eastcoast boys did not differ from the regional reference population with respect to visual and hearing ability. CONCLUSIONS: Although no individual exposure data were available, the present results do not support any harmful long-term impact of pre- and postnatal exposure to persistent organochlorine compounds from mothers' fish consumption on the psychometric functions of boys in their conscript examinations.


Assuntos
Peixes , Contaminação de Alimentos , Nível de Saúde , Hidrocarbonetos Clorados/efeitos adversos , Dibenzodioxinas Policloradas/análogos & derivados , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Animais , Benzofuranos/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Deficiências do Desenvolvimento/induzido quimicamente , Deficiências do Desenvolvimento/epidemiologia , Dibenzofuranos Policlorados , Feminino , Transtornos do Crescimento/induzido quimicamente , Transtornos do Crescimento/epidemiologia , Transtornos da Audição/induzido quimicamente , Transtornos da Audição/epidemiologia , Humanos , Masculino , Militares/estatística & dados numéricos , Razão de Chances , Bifenilos Policlorados/efeitos adversos , Dibenzodioxinas Policloradas/efeitos adversos , Gravidez , Estatísticas não Paramétricas , Suécia/epidemiologia , Transtornos da Visão/induzido quimicamente , Transtornos da Visão/epidemiologia
19.
Scand J Work Environ Health ; 21(6): 419-26, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8824747

RESUMO

OBJECTIVES: The purpose of this study was to assess cancer incidence and cardiovascular mortality among women with a high dietary intake of fatty fish from the Baltic Sea (on the Swedish east coast), contaminated with persistent organochlorine compounds. MATERIAL AND METHODS: Cohorts of fishermen's wives from the Swedish east (1989 subjects) and west (6605 subjects) coasts were established. The mortality and cancer incidence were studied in these cohorts, and comparisons were made with respective regional populations and between the cohorts. Dietary interviews were made with 200 randomly selected cohort women and equally many women from the general population. The interviewed east- and westcoast cohort women ate locally caught fatty fish at least twice as often as their referents. RESULTS: Compared with that of the regional population, the breast cancer incidence was higher than expected in the eastcoast cohort [standardized incidence ratio (SIR) 1.29, 95% confidence interval (95% CI) 0.96-1.71], whereas it was lower in the westcoast cohort (SIR 0.89; 95% CI 0.77-1.04). When a direct comparison was made between the two cohorts, the eastcoast women displayed an increased breast cancer incidence (incidence rate ratio 1.35, 95% CI 0.98-1.86). No obvious difference was seen between the two cohorts concerning cardiovascular mortality. CONCLUSIONS: The results support, but do not prove, the hypothesis of an association between exposure to a mixture of persistent organochlorine compounds through fish consumption and an increased risk for breast cancer.


Assuntos
Doenças Cardiovasculares/etiologia , Dieta , Contaminação de Alimentos , Hidrocarbonetos Clorados/efeitos adversos , Neoplasias/etiologia , Adulto , Animais , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Estudos de Coortes , Feminino , Peixes , Indústria de Processamento de Alimentos , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Suécia/epidemiologia
20.
Scand J Work Environ Health ; 21(5): 368-75, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8571093

RESUMO

OBJECTIVES: The purpose of the study was to assess reproductive outcomes, especially birthweight, and the consumption of fatty fish from the Baltic Sea, contaminated with persistent organochlorine compounds, among women from the Swedish east coast. MATERIAL AND METHODS: Cohorts of fishermen's wives from the Swedish east and west coasts were established and linked to the Swedish Medical Birth Register for 1973-1991; 1501 children were born in the eastcoast cohort and 3553 in the westcoast cohort. Comparisons were made with regional populations and between the cohorts. Dietary interviews were made with 69 randomly selected women from the cohorts and 69 referents. RESULTS: The women interviewed from the east- and westcoast cohorts ate locally caught fish more than twice as often as their referents. Compared with the regional population, the women in the eastcoast cohort gave birth to an increased number of infants with low birthweights (< 3000 g), whereas the opposite was seen in the westcoast cohort. Infants in the eastcoast cohort had significantly lower birthweights than infants from the westcoast cohort (median 3530 versus 3610 g, P < 0.001). Even after adjustment for potential confounders, eastcoast affiliation showed an increased risk for low birthweight (odds ratio 1.44, 95% confidence interval 1.18-1.76). The effect was more conspicuous for boys (odds ratio 1.95) and heavy smokers (odds ratio 3.00). CONCLUSIONS: The present data support, but do not prove, an association between a high consumption of contaminated fish from the Baltic Sea and an increased risk for low birthweight.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Peixes , Contaminação de Alimentos , Bifenilos Policlorados/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , Adolescente , Adulto , Animais , Benzofuranos/efeitos adversos , Estudos de Coortes , Dibenzofuranos Policlorados , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Oceanos e Mares , Dibenzodioxinas Policloradas/efeitos adversos , Dibenzodioxinas Policloradas/análogos & derivados , Gravidez , Fatores de Risco , Suécia
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