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1.
J Radiol Prot ; 39(2): 620-634, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31112514

RESUMO

The potential for adverse health effects from internal exposure to Plutonium has been recognised since its discovery in the 1940s. However, in the absence of specific information, potential risks from Plutonium exposure have always largely been controlled through knowledge of radiation exposure risks in general, much of which comes from external radiation exposures. To try to obtain more direct estimates of potential internal exposure risks, epidemiological studies of Plutonium workers need to be conducted. Such epidemiological analyses require individual Plutonium exposure estimates that are as accurate and unbiased as possible. The UK Sellafield workforce includes one of the world's largest cohorts of Plutonium workers, which constitutes, by some considerable margin, the group of workers most comprehensively monitored for internal exposure to this alpha-particle-emitter. However, for several hundred workers employed at the start of Plutonium work at the facility, during the period from 1952 through to 1963, the historical urinalysis results available cannot provide sufficiently accurate and unbiased exposure assessments needed for use in epidemiological studies. Consequently, these early workers have had to be excluded from epidemiological analyses and this has significantly reduced the power of these studies. A promising quantitative methodology to overcome the issue of missing or deficient exposure data, is to use exposure data from other sources to estimate the average exposure a 'typical worker' would have received, and to collate this information for specific occupations and years. This approach is called a Job-Exposure Matrix (JEM). Work on a pilot study to construct a population-specific quantitative JEM for the early Plutonium workers at Sellafield during 1952-1963, for whom reliable urinalysis results do not exist, has shown the potential for a JEM approach to produce more reliable and useful exposure estimates for epidemiological research.


Assuntos
Centrais Nucleares , Exposição Ocupacional , Plutônio , Exposição à Radiação , Humanos , Exposição Ocupacional/análise , Plutônio/efeitos adversos , Plutônio/urina , Exposição à Radiação/análise , Fatores de Tempo , Reino Unido , Urinálise
2.
Radiat Res ; 191(1): 60-66, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30398393

RESUMO

Plutonium is a radiologically significant alpha-particle emitter. The potential for adverse health effects from internal exposures due to plutonium intakes has been recognized since the 1940s. The workforce of the Sellafield nuclear facility (Cumbria, UK), includes one of the world's most important groups of plutonium-exposed workers for studying the potential health risks of this internal exposure. However, for several hundred workers employed at the start of plutonium work at the facility (1952-1963), historical monitoring records based on measurements of urinary excretion of plutonium are not sufficiently reliable to provide the accurate and unbiased exposure assessments needed for epidemiological studies. Consequently, these early workers have had to be excluded from such studies, significantly reducing their power. We constructed a population-specific quantitative job exposure matrix (JEM) to estimate the average intakes of "typical plutonium workers" in this period, from 1952-1963, and assessed its validity and sensitivity to exposure assessment decisions. We conducted internal cross-validation using an a priori 10% extracted sample to evaluate reliability of estimates, explored JEM sensitivity to assumptions in the exposure assessment, and assessed the impact of uncertainty in urinalysis measurements on the precision of annual intake estimates using Markov Chain Monte Carlo (MCMC) methodology. Pairwise correlations ( RP) of estimated (JEM) and measured (10% sample) annual intakes were moderate to high ( RP > 0.4) for 10 out of 13 JEM groups, while absolute differences were <20% for 11 out of 13 JEM groups. There was little evidence of a temporal trend in correlations ( P = 0.13) or absolute differences ( P = 0.34). The median JEM-derived cumulative intake of 95.2 (IQR, 55.0-130.0) Bq was comparable to those based on alternative assumptions in the exposure assessment (median range, 95.2-100.0 Bq; 75th percentiles, 130.0-146.0 Bq). Measurement error simulation resulted in a 40-60% reduced median cumulative intake but higher maximum cumulative intakes. The JEM finds a balance between reliability and precision that makes it useful for epidemiological purposes and is relatively insensitive to specific choices in the exposure assessment. This JEM will allow the inclusion of workers with longest follow-up and who could not be included up until now in epidemiological studies without introducing significant bias.


Assuntos
Exposição Ocupacional , Plutônio/efeitos adversos , Exposição Ambiental , Humanos , Cadeias de Markov , Método de Monte Carlo , Plutônio/urina , Monitoramento de Radiação , Reprodutibilidade dos Testes , Reino Unido
3.
J Radiol Prot ; 36(1): R1-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26861451

RESUMO

Any potential health effects of radiation emitted from radionuclides deposited in the bodies of workers exposed to radioactive materials can be directly investigated through epidemiological studies. However, estimates of radionuclide exposure and consequent tissue-specific doses, particularly for early workers for whom monitoring was relatively crude but exposures tended to be highest, can be uncertain, limiting the accuracy of risk estimates. We review the use of job-exposure matrices (JEMs) in peer-reviewed epidemiological and exposure assessment studies of nuclear industry workers exposed to radioactive materials as a method for addressing gaps in exposure data, and discuss methodology and comparability between studies. We identified nine studies of nuclear worker cohorts in France, Russia, the USA and the UK that had incorporated JEMs in their exposure assessments. All these JEMs were study or cohort-specific, and although broadly comparable methodologies were used in their construction, this is insufficient to enable the transfer of any one JEM to another study. Moreover there was often inadequate detail on whether, or how, JEMs were validated. JEMs have become more detailed and more quantitative, and this trend may eventually enable better comparison across, and the pooling of, studies. We conclude that JEMs have been shown to be a valuable exposure assessment methodology for imputation of missing exposure data for nuclear worker cohorts with data not missing at random. The next step forward for direct comparison or pooled analysis of complete cohorts would be the use of transparent and transferable methods.


Assuntos
Biometria/métodos , Exposição Ocupacional/análise , Plutônio/efeitos adversos , França , Humanos , Exposição Ocupacional/efeitos adversos , Federação Russa , Reino Unido , Estados Unidos
4.
Am J Med Genet A ; 149A(4): 567-72, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19283854

RESUMO

Two unrelated young women presented with similar dysmorphic features including severe retrognathia, beaked nose, narrow chest, sloping shoulders, and an acrogeric appearance of the hands and feet. Neither had any evidence of skeletal myopathy, but both developed progressive dilated cardiomyopathy, both experienced premature ovarian failure, and both were found to have the same heterozygous novel missense mutation c.176T>G in exon 1 of the LMNA gene, resulting in a leucine to arginine change at codon 59 (Leu59Arg). Mutations in the LMNA gene cause a variety of disorders including dilated cardiomyopathy, muscular dystrophy, familial lipodystrophy, progeria, atypical progeroid syndromes, and mandibuloacral dysplasia. Genotype-phenotype correlation has been reported for some of these conditions. Our patients are the only ones known to have the specific mutation Leu59Arg and also share a set of features not entirely consistent with any of the laminopathies previously described. A previously reported patient with an adjacent mutation (Ala57Pro) had "atypical Werner syndrome" with dilated cardiomyopathy, hypogonadism, and sloping shoulders. While each of these clinical features does occur in other laminopathy syndromes, these patients form a phenotypic cluster distinct from other laminopathies and clinically overlapping with Malouf syndrome. LMNA sequencing should be considered for patients presenting with dilated cardiomyopathy and hypergonadotropic hypogonadism, including those previously diagnosed with Malouf syndrome.


Assuntos
Cardiomiopatia Dilatada/genética , Lamina Tipo A/genética , Lipodistrofia/genética , Insuficiência Ovariana Primária/genética , Adolescente , Substituição de Aminoácidos , Feminino , Genótipo , Heterozigoto , Humanos , Mutação de Sentido Incorreto , Fenótipo , Síndrome , Síndrome de Werner/genética
5.
J Cosmet Laser Ther ; 9(2): 75-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17558756

RESUMO

Several lasers and light sources have been reported to induce dermal collagen remodeling without damaging the epidermis. The intense pulsed light (IPL) system, which emits polychromatic light of wavelengths between 560 and 1200 nm belongs to this group of increasingly popular non-ablative skin rejuvenation devices. Various IPL treatment parameters can be adjusted to achieve optimal dermal remodeling and clinical improvement. The aim of this study was to evaluate variations in IPL treatment parameters and the effect on procollagen I deposition. Marked areas of a live Yorkshire pig's flank skin were irradiated with a single or double pass of an IPL source using a fluence of 30 or 40 J/cm2 and a cut-off wavelength filter of 590 nm. Skin biopsies were performed on postoperative days 1, 7, 14, 21, and 42. A statistically significant increase in procollagen I in treated versus untreated sites was found on postoperative days 21 and 42, but not earlier. There was a uniformly significant increase in procollagen I on day 42 using the 590 nm filter at both 30 and 40 J/cm2 with either a single or double pass. The increase in procollagen was greater with a fluence of 40 J/cm2 compared with 30 J/cm2.


Assuntos
Luz , Pró-Colágeno/metabolismo , Pele/efeitos da radiação , Animais , Biópsia , Técnicas In Vitro , Fototerapia , Pele/metabolismo , Suínos , Fatores de Tempo
6.
Biochem Biophys Res Commun ; 352(3): 603-8, 2007 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-17150192

RESUMO

Laminopathies are a group of genetic disorders caused by LMNA mutations; they include muscular dystrophies, lipodystrophies, and progeroid syndromes. We identified a novel heterozygous LMNA mutation, L59R, in a patient with the general appearance of mandibuloacral dysplasia and progeroid features. Examination of the nuclei of dermal fibroblasts revealed the irregular morphology characteristic of LMNA mutant cells. The nuclear morphological abnormalities of LMNA mutant lymphoblastoid cell lines were less prominent compared to those of primary fibroblasts. Since it has been reported that progeroid features are associated with increased extracellular matrix in dermal tissues, we compared a subset of these components in fibroblast cultures from LMNA mutants with those of control fibroblasts. There was no evidence of intracellular accumulation or altered mobility of collagen chains, or altered conversion of procollagen to collagen, suggesting that skin fibroblast-mediated matrix production may not play a significant role in the pathogenesis of this particular laminopathy.


Assuntos
Síndrome de Cockayne/genética , Síndrome de Cockayne/metabolismo , Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , Lamina Tipo A/genética , Adolescente , Células Cultivadas , Feminino , Predisposição Genética para Doença/genética , Humanos , Lipodistrofia/genética , Lipodistrofia/metabolismo , Mutação
8.
BMC Med Genet ; 6: 16, 2005 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-15850492

RESUMO

BACKGROUND: X-linked mental retardation (XLMR) is the leading cause of mental retardation in males. Mutations in the ARX gene in Xp22.1 have been found in numerous families with both nonsyndromic and syndromic XLMR. The most frequent mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a panel of XLMR families linked to Xp22 was tested for this particular ARX mutation. METHODS: Genomic DNA from XLMR families linked to Xp22.1 was amplified for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were sized using the ALFexpress automated sequencer. RESULTS: A panel of 11 families with X-linked mental retardation was screened for the ARX 24dup mutation. Four nonsyndromic XLMR families - MRX29, MRX32, MRX33 and MRX38 - were found to have this particular gene mutation. CONCLUSION: We have identified 4 additional XLMR families with the ARX dup24 mutation from a panel of 11 XLMR families linked to Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily tested for using an automated sequencer, screening should be considered for any male with nonsyndromic MR of unknown etiology.


Assuntos
Duplicação Gênica , Proteínas de Homeodomínio/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Mutação/genética , Fatores de Transcrição/genética , Cromossomos Humanos X/genética , Feminino , Triagem de Portadores Genéticos , Testes Genéticos , Humanos , Masculino
9.
J Obstet Gynaecol Can ; 25(10): 825-9, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14532950

RESUMO

OBJECTIVE: To compare the utilization of the second trimester maternal serum screen (MSS) of a-fetoprotein, human chorionic gonadotrophin, and unconjugated estriol, in Newfoundland, by practice location, training, and gender. METHODS: Four hundred eighteen anonymous self-reported questionnaires were mailed out to all practising family physicians, general practitioners, and obstetricians in Newfoundland, who were identified through the provincial medical board. The survey included questions on demographic characteristics, provision of antenatal care, gestational age at which MSS is ordered, reasons for offering or not offering MSS, and the use of routine antenatal ultrasound. Categorical data were analyzed using chi-square and Fisher exact tests, as appropriate. RESULTS: Overall, 63% of physicians responded to the survey. Forty percent of respondents had an urban practice. Female physicians, regardless of specialty, were more likely to offer MSS to their patients (89% vs. 78%; P = 0.04), whereas family physicians and obstetricians were more likely to offer screening than general practitioners (85% vs. 83% vs. 25%; P = 0.02). Among physicians offering MSS, 54% offered it only to women 35 years and older. Practice location did not affect whether a woman was offered MSS (P = 0.41). Twenty-five percent of family physicians offering MSS did not offer it at the appropriate gestational age of 15 to 20 weeks. Ninety-four percent of pregnant women were routinely offered an ultrasound during pregnancy. CONCLUSION: The utilization of MSS in Newfoundland is affected by physician training and gender, but not by practice location. Further education of physicians is required to ensure appropriate use and timing of this screening test.


Assuntos
Medicina de Família e Comunidade , Obstetrícia , Padrões de Prática Médica , Diagnóstico Pré-Natal , Adulto , Gonadotropina Coriônica/sangue , Aberrações Cromossômicas , Estriol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terra Nova e Labrador , Gravidez , Segundo Trimestre da Gravidez , alfa-Fetoproteínas/análise
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