RESUMEN
To develop a benchmark measure of US physicians' level of knowledge and extent of use of pharmacogenomic testing, we conducted an anonymous, cross-sectional, fax-based, national survey. Of 397,832 physicians receiving the survey questionnaire, 10,303 (3%) completed and returned it; the respondents were representative of the overall US physician population. The factors associated with the decision to test were evaluated using χ(2) and multivariate logistic regression. Overall, 97.6% of responding physicians agreed that genetic variations may influence drug response, but only 10.3% felt adequately informed about pharmacogenomic testing. Only 12.9% of physicians had ordered a test in the previous 6 months, and 26.4% anticipated ordering a test in the next 6 months. Early and future adopters of testing were more likely to have received training in pharmacogenomics, but only 29.0% of physicians overall had received any education in the field. Our findings highlight the need for more effective physician education on the clinical value, availability, and interpretation of pharmacogenomic tests.
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Actitud del Personal de Salud , Pruebas Genéticas/métodos , Conocimientos, Actitudes y Práctica en Salud , Farmacogenética , Pautas de la Práctica en Medicina , Adulto , Anciano , Estudios Transversales/métodos , Recolección de Datos/métodos , Femenino , Variación Genética , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Encuestas y Cuestionarios , Estados Unidos , Adulto JovenRESUMEN
Women with renal disease who conceive and continue a pregnancy are at significant risk for adverse maternal and fetal outcomes. Risk is inversely related to the degree of renal insufficiency. Pregnancy-induced changes in the urinary tract can temporarily increase renal function compromise, such as nephrosis, but most often results in no net increase in dysfunction. Common complications of pregnancy--such as hypertension and hypovolemia--can be associated with acute renal injury or aggravation of pre-existing disease.
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Fallo Renal Crónico , Complicaciones del Embarazo , Femenino , Humanos , Riñón/fisiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Atención Preconceptiva , Embarazo/fisiología , Complicaciones del Embarazo/fisiopatología , Resultado del Embarazo , Atención PrenatalRESUMEN
This article discusses safe sedation for pediatric imaging. Emphasis is placed upon implementation of an institutional sedation program according to guidelines of the American Academy of Pediatrics. Standards for patient assessment and preparation, sedative administration, monitoring, and discharge are reviewed. A comparison of available sedative agents is also provided.
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Sedación Consciente , Diagnóstico por Imagen , Hipnóticos y Sedantes/uso terapéutico , Periodo de Recuperación de la Anestesia , Anestésicos Intravenosos/administración & dosificación , Niño , Preescolar , Sedación Consciente/métodos , Humanos , Hipnóticos y Sedantes/administración & dosificación , Lactante , Monitoreo Fisiológico , Alta del Paciente , Guías de Práctica Clínica como Asunto , Medición de RiesgoRESUMEN
OBJECTIVE: To study the effect of an educational intervention on the management of hospitalized infants with bronchiolitis. DESIGN: Sequential, prospective cohort study. SETTING: A 235-bed children's hospital with nearly all private rooms. PATIENTS: Consecutively admitted, previously healthy children younger than 24 months with symptoms of bronchiolitis. The first cohort was enrolled between January 1 and January 21, 1996; the second cohort between January 29 and February 18, 1996, following a 1-week intervention period; the third (follow-up) cohort between December 1996 and February 1997. INTERVENTION: Educational program and practice guidelines aimed at appropriate utilization of diagnostic tests, decreased antibiotic and bronchodilator use, increased compliance with isolation, decreased length of stay, and maintenance of quality care. MAIN OUTCOME MEASURES: Utilization of respiratory syncytial virus (RSV) enzyme immunoassay, initiation and duration of parenteral antibiotic therapy, number of nebulized bronchodilator treatments, isolation orders, length of stay, and readmission rate. RESULTS: A total of 90 patients were studied preintervention, 63 postintervention, and 90 during the follow-up period. The groups were comparable in demographic and clinical features. No patient had a documented serious bacterial infection; however, almost half in each group received parenteral antibiotics, despite recommendations against this. Immediately postintervention, children with positive RSV test results received antibiotics on fewer days than other children (median 0.6 vs 2.4 days; P=.004), suggesting that physicians stopped treatment with antibiotics once a viral diagnosis was confirmed. This effect did not persist into the follow-up period. Viral testing was reduced and isolation orders increased. Use of bronchodilators was reduced from 91% preintervention to 80% during the follow-up period (P=.046), and the median number of treatments was reduced from 15.0 to 10.0 (P=.005). There was no change in length of stay, which was 2 to 3 days, or in readmission rate, which was 1% to 4%. CONCLUSION: Educational efforts centered around practice guidelines can improve some aspects of the treatment of patients hospitalized with bronchiolitis.
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Bronquiolitis Viral/terapia , Antibacterianos/uso terapéutico , Bronquiolitis Viral/diagnóstico , Broncodilatadores/uso terapéutico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Adhesión a Directriz , Hospitalización , Humanos , Lactante , Masculino , Aislamiento de Pacientes , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/diagnósticoRESUMEN
The use of continuous SvO2 monitoring in the critically ill pediatric patient helps guide the critical care nurse to make clinical decisions that individualize care and improve patient outcome. This article examines SvO2 and its components, oxygen delivery and oxygen consumption, as they apply to the pediatric intensive care patient.
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Cuidados Críticos/métodos , Unidades de Cuidado Intensivo Pediátrico , Oxígeno/sangre , Niño , Preescolar , Femenino , Humanos , OximetríaRESUMEN
Pulmonary carcinogenesis was compared in female F344 and Wistar rats after inhalation of high-fired 239PuO2. Plutonium particle aggregation, as determined by quantitative light and scanning electron microscopic autoradiography, was greater for the F344 strain than for the Wistar strain. The median survival times were similar in control and low-dose (0.8-1.0 Gy) groups of both strains, but were significantly decreased in the high-dose (34-37 Gy) groups of both strains. Squamous metaplasia was not found in control or low-dose groups of either strain, but was found in 62-65% of high-dose groups of both strains. Adenomatous metaplasia was considerably higher in control and low-dose groups of F344 rats than in Wistar rats. A total of 87 lung tumors were found in 140 exposed F344 rats and 46 lung tumors in 176 exposed Wistar rats. The incidence of lung tumors in F344 rats was 1.7% in controls, 20% in the low-dose group and 82% in the high-dose group. The incidence of lung tumors in Wistar rats was 0.1% in controls, nil in the low-dose group and 68% in the high-dose group. About half of all lung tumors in both strains were considered to be the primary cause of death. The median survival times of rats of both strains in the high-dose groups that died with lung tumors were greater compared with rats in these groups that died without lung tumors. In contrast, these differences did not occur among rats in the low-dose groups. The absolute risk was 1900 lung tumors per 10(4) Rat-Gy for F344 rats receiving low doses and nil for Wistar rats receiving low doses, but about 210 lung tumors per 10(4) Rat-Gy for high-dose groups of both strains. The adenomatous tumor phenotype predominated in the F344 strain, while the squamous tumor phenotype predominated in the Wistar strain. Risk of squamous tumors was similar for both strains. Overall, the F344 strain appears to be more "sensitive" than the Wistar strain to formation of lung tumors at low to moderate doses from inhaled 239PuO2 due mostly to an increased incidence of adenomatous phenotype tumors.
Asunto(s)
Carcinoma/etiología , Neoplasias Pulmonares/etiología , Plutonio , Sarcoma Experimental/etiología , Aerosoles , Animales , Carcinoma/patología , Relación Dosis-Respuesta en la Radiación , Epitelio/patología , Femenino , Neoplasias Pulmonares/patología , Neoplasias Inducidas por Radiación/patología , Plutonio/administración & dosificación , Ratas , Ratas Endogámicas F344 , Ratas Wistar , Sarcoma Experimental/patologíaRESUMEN
Female, young adult, Wistar rats were given a single inhalation exposure to a submicron sized aerosol of high-fired 239PuO2 and observed during their lifespan for primary lung tumours. Rats were distributed among sham-control (n = 1052) and exposed (n = 2105) groups. Survival was significantly reduced only in rats with lung doses > 30 Gy. A total of 99 primary lung tumours were found, of which 92% were malignant and 80% were carcinomas. Of malignant lung tumours, 49 were squamous cell carcinoma, 23 adenocarcinoma, nine hemangiosarcoma, seven adenosquamous carcinoma, and three fibrosarcoma. One adenocarcinoma was found in controls and only four adenomas were seen in the exposed rat at lung doses < 1.5 Gy. The lowest doses at which lung tumours appeared in exposed rats were 1.5 Gy for squamous cell carcinoma, 3.1 Gy for adenocarcinoma. 4.1 Gy for hemangiosarcoma, and about 9 Gy for adenosquamous carcinoma and fibrosarcoma. Pulmonary squamous metaplasia was not seen in controls and was first seen in exposed rats only at lung doses > 1 Gy. Primary lung tumours were the presumed cause of death (fatal) in 60% of rats with malignant lung tumours; causes of death were equally distributed among all tumour types and doses. The incidence of all lung tumours was 0.095% in control rats, 0.21% in 1877 rats with lung doses < 1 Gy, and 41% in 228 rats with doses > 1 Gy. Lung tumour incidence increased in a linear manner from 6.9% at 2.3 Gy to an incidence of 64-88% at 16-44 Gy. Absolute malignant lung tumour risk averaged 270 lung tumours per 10(4) rat-Gy above a lung dose of 1 Gy. All types of malignant lung tumours induced by inhaled 239PuO2 exhibited a threshold at a lung dose > 1 Gy.
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Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación/etiología , Plutonio/administración & dosificación , Traumatismos Experimentales por Radiación , Adenocarcinoma/etiología , Adenoma/etiología , Administración por Inhalación , Aerosoles , Animales , Carcinoma Adenoescamoso/etiología , Carcinoma de Células Escamosas/etiología , Femenino , Fibrosarcoma/etiología , Hemangiosarcoma/etiología , Traumatismos Experimentales por Radiación/mortalidad , Ratas , Ratas Wistar , Análisis de SupervivenciaRESUMEN
Spatial-temporal dose-distribution patterns in the lung continually change following inhalation of radionuclides. Lung clearance, microdosimetry, and radiation dose were examined in female Wistar rats exposed to high-fired 169Yb2O3-239PuO2 aerosols. Whole-body counting for 169Yb at 14 d postexposure provided an accurate (r = 0.99) estimate of 239Pu lung content. Alpha irradiation of tracheal epithelium was at least 50 times less than for bronchiolar epithelium due principally to preferential retention of 239PuO2 in peribronchiolar alveoli as compared to other alveolar regions. The formation of large aggregates (> 25 particles) increased linearly with initial lung burden starting at 0.4 kBq; mean dose rate to these focal alveolar regions was 120 Gy d-1. Concentration of 239PuO2 in pulmonary macrophages and in aggregates, along with the limited penetration of alpha particles in tissue, resulted in a highly nonhomogeneous dose distribution pattern. Alveolar clearance was best represented by a biphasic clearance curve comprised of a rapid early phase (80% initial lung burden) and a slow late phase (20% initial lung burden). Studies with intratracheally instilled 237PuO2-239PuO2 and with inhaled 239PuO2 showed that alveolar clearance was inversely proportional to initial lung burden. A single clearance function was derived from experimentally determined clearance curves for inhaled 239PuO2 that was used to accurately estimate lung dose at all initial lung burden levels. Lung doses were calculated for 2,105 exposed lifespan rats based on individually determined initial lung burden, survival time, and individually computed clearance function.
Asunto(s)
Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación/etiología , Plutonio/administración & dosificación , Administración por Inhalación , Aerosoles , Animales , Femenino , Esperanza de Vida , Ratas , Ratas WistarRESUMEN
Pleural mesothelioma was an infrequent observation following deposition of 239PuO2 in the lung or pleural cavity. Only five tumors were found in 2,105 rats exposed to 239PuO2 aerosols in the present study, while four tumors were found in 527 rats that inhaled 239PuO2 in previously published lifespan studies. Risk of pleural mesothelioma was not significantly increased by intrapleural injection of 30 kBq 239PuO2. In contrast, a much higher incidence of peritoneal mesothelioma was seen following intraperitoneal injection of 239PuO2 due to aggregation of 239PuO2 particles on mesothelial surfaces. It was concluded that the lack of 239PuO2 aggregation on pleural surfaces is responsible for small numbers of pleural mesothelioma observed following deposition of 239PuO2.
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Mesotelioma/etiología , Neoplasias Inducidas por Radiación , Neoplasias Pleurales/etiología , Plutonio/administración & dosificación , Administración por Inhalación , Aerosoles , Animales , Femenino , Ratas , Ratas WistarRESUMEN
Female young adult, SPF, Wistar rats, obtained from the same supplier over an 18-month period, were examined in a life-span study with inhaled 239PuO2. Nonpulmonary tumors were evaluated both in 1052 rats comprising 16 controls groups and in 2105 exposed rats. Tumors in the pituitary gland, mammary glands, uterus, and thyroid glands, in order of decreasing prevalence, accounted for 90% of all tumors. Uterine tumors comprised 55% of all nonpulmonary malignant tumors. A substantial variability in tumor incidence was seen in most organs and for most tumor types among the 16 cohort subgroups, which was not explained by husbandry conditions or mortality patterns. The incidence of thyroid tumors ranged from 0 to 21% and uterine tumors from 14 to 45% among control cohorts. Pulmonary metastases were seen in 12% of all rats irrespective of treatment, two thirds of which were uterine adenocarcinomas that appeared histologically similar to some primary lung adenocarcinomas. A tumor incidence of about 1.5% was associated with metal identification ear tags. Except in the lung, no significant difference was found in tumor location or type between control and exposed rats. A twofold or greater increase in tumors in exposed rats was found in Zymbal gland, bladder, brain, and liver; tumor incidence in each organ was < 1%.
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Neoplasias Pulmonares/secundario , Neoplasias Inducidas por Radiación/etiología , Plutonio/efectos adversos , Adenocarcinoma/etiología , Adenocarcinoma/secundario , Aerosoles , Animales , Femenino , Longevidad/efectos de los fármacos , Neoplasias Mamarias Experimentales/etiología , Neoplasias Hipofisarias/etiología , Plutonio/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Wistar , Neoplasias Cutáneas/etiología , Neoplasias de la Tiroides/etiología , Neoplasias Uterinas/etiologíaRESUMEN
Incidence of brain tumours was investigated in 3390 female and male Wistar rats exposed to an aerosol of 239PuO2, or as sham-exposed controls. Lung doses ranged from 0.05 to 22 Gy. In females, six brain tumours were found in 1058 control rats (incidence, 0.6%) and 24 brain tumours in 2134 rats exposed to Pu (incidence, 1.1%); the survival-adjusted level of significance was p = 0.29 for comparing control with exposed females. In males, two brain tumours were found in 60 control rats (incidence, 3.3%) and seven brain tumours in 138 rats exposed to Pu (incidence, 5.1%); the survival-adjusted level of significance was p = 0.33. Brain tumour incidence was about five times greater in male than in female rats (p = 0.0001), demonstrating a highly significant sex difference in brain tumour incidence. Tumour types were distributed similarly among control and Pu-exposed groups of both sexes; most tumours were astrocytomas. Mean lifespans for rats with brain tumours were not significantly different between control and Pu-exposed rats. Plutonium was not detected on autoradiograms of the brain. These results, like those for plutonium workers, show an increase of brain tumours which cannot be demonstrated statistically to be related to radiation exposure.
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Astrocitoma/etiología , Neoplasias Encefálicas/etiología , Neoplasias Meníngeas/etiología , Meningioma/etiología , Neoplasias Inducidas por Radiación/epidemiología , Oligodendroglioma/etiología , Plutonio/administración & dosificación , Administración por Inhalación , Aerosoles , Animales , Astrocitoma/epidemiología , Neoplasias Encefálicas/epidemiología , Femenino , Masculino , Neoplasias Meníngeas/epidemiología , Meningioma/epidemiología , Oligodendroglioma/epidemiología , Ratas , Ratas Endogámicas , Organismos Libres de Patógenos EspecíficosRESUMEN
The malignancy of pulmonary lesions induced by inhaled 239PuO2 in the Syrian hamster was tested by transplantation in the hamster cheek pouch. Serving as negative and positive controls, 42 female hamsters were given either 0.9% sodium chloride (NaCl), ferric oxide suspended in NaCl (Fe2O3), or benzo(a)pyrene + Fe2O3 suspended in NaCl (BP), by intratracheal instillation. One hundred female hamsters were given a single, nose-only inhalation exposure to high-fired 239PuO2 (initial lung burden, 2.4 kBq). At intervals from 160 to 425 days after Pu inhalation or instillation, ten 1-mm3 tissue cubes were removed from the lung of each hamster and transplanted into the cheek pouch of male hamsters, for a total of 1320 transplantations. None of the lung transplants from hamsters receiving 239PuO2, NaCl, or Fe2O3 grew in recipient cheek pouches, but 14% of transplants from BP hamsters grew rapidly in the cheek pouch. Lung carcinomas were histologically identified only in BP hamsters and BP transplants. It was concluded that proliferative pulmonary lesions induced by a-irradiation of the lung of hamsters were not malignant, and that the malignancy of lung lesions in the hamster induced by ionizing radiation should be evaluated by transplantation.
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Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación/patología , Plutonio/toxicidad , Adenocarcinoma/etiología , Administración por Inhalación , Animales , Carcinoma de Células Escamosas/etiología , Mejilla/cirugía , Cricetinae , Femenino , Hiperplasia , Pulmón/patología , Pulmón/efectos de la radiación , Pulmón/cirugía , Neoplasias Pulmonares/patología , Mesocricetus , Trasplante de Neoplasias , Plutonio/administración & dosificaciónRESUMEN
Rats were given single or multiple (10 exposures at about 21-d intervals) inhalation exposures to 244CmO2 starting at 70 d of age. Mean lung and bone doses (+/- standard deviation) were 1.4 +/- 1.3 and 0.74 +/- 1.1 Gy, respectively, in the single exposure group, and 1.8 +/- 2.9 and 0.53 +/- 0.74 Gy, respectively, in the multiple exposure group. After cessation of exposure in the multiple exposure group, mean cumulative lifetime radiation doses to lung and skeleton were not significantly different in the two groups. The percentages of rats with lung and bone tumors were 9.1 and 12%, respectively, in the single exposure group, and 20 and 24%, respectively, in the multiple exposure group. However, the multiple exposure regimen did not significantly alter survival times or tumor incidences in lung or bone from a single inhalation exposure to 244CmO2 when survival patterns were taken into account.
Asunto(s)
Neoplasias Óseas/etiología , Carcinógenos , Curio/toxicidad , Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación , Administración por Inhalación , Aerosoles , Animales , Distribución de Chi-Cuadrado , Curio/administración & dosificación , Curio/farmacocinética , Relación Dosis-Respuesta en la Radiación , Femenino , Ratas , Ratas EndogámicasRESUMEN
Pulmonary aggregation of inhaled 239PuO2 particles leads to a cellular evolution of focal inflammation, fibrosis, epithelial dysplasia and lung tumor formation. Female Wistar rats were exposed to an aerosol of high-fired 239PuO2 (initial lung burden, 3.9 kBq) and the lungs examined at intervals from 1 day to 700 days after exposure by light and scanning electron microscopy and autoradiography. Peribronchiolar Pu particle aggregation increased with time, resulting in well-defined focal inflammatory lesions after 120 days and fibrotic lesions after 180 days. A generalized hypertrophy and hyperplasia of nonciliated bronchiolar cells was seen at 15 days and type II cell hyperplasia by 30 days after exposure. Focal dysplastic changes in type II alveolar epithelium and terminal nonciliated bronchiolar epithelium preceded carcinoma formation. Alveolar bronchiolarization was first noted at 120 days, squamous metaplasia at 210 days, squamous carcinoma at 270 days and adenocarcinoma at 600 days after exposure.
Asunto(s)
Partículas alfa , Pulmón/efectos de la radiación , Pulmón/ultraestructura , Animales , Femenino , Hiperplasia , Pulmón/patología , Neoplasias Pulmonares/patología , Microscopía Electrónica de Rastreo , Neoplasias Inducidas por Radiación/patología , Ratas , Ratas EndogámicasRESUMEN
The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis.
Asunto(s)
Bronquios/metabolismo , Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación , Plutonio/farmacocinética , Alveolos Pulmonares/metabolismo , Administración por Inhalación , Animales , Autorradiografía , Epitelio/metabolismo , Femenino , Pulmón/metabolismo , Neoplasias Pulmonares/metabolismo , Membrana Mucosa/metabolismo , Plutonio/administración & dosificación , Ratas , Ratas Endogámicas , Distribución Tisular , Tráquea/metabolismoRESUMEN
We have applied the scanning electron microscope (SEM) to obtain autoradiographs of particles of 239PuO2 deposited in rat lung. The technique was used to obtain quantitative information on the clearance rates of particles from the alveoli, bronchioles and trachea up to 240 d after exposure. At all times, the concentration of particles on the surface of the bronchioles was an order of magnitude greater than on the tracheal surface. The clearance of Pu from both regions followed a biphasic pattern, similar to that obtained by radiometric analysis of the whole lung. Most of the radiation dose to the bronchiolar epithelium originated from Pu particles in peribronchiolar alveoli in which they were preferentially retained, compared to other alveolar regions. The prolonged retention of particles in the peribronchiolar alveoli may be a significant factor in the induction of lung carcinomas.
Asunto(s)
Pulmón/efectos de la radiación , Plutonio/administración & dosificación , Administración por Inhalación , Aerosoles , Animales , Autorradiografía , Microscopía Electrónica de Rastreo , Dosis de Radiación , Ratas , Ratas EndogámicasRESUMEN
Promotion of lung tumor formation from inhaled 239PuO2 in rats may be associated with aggregation of plutonium particles near bronchioles. The relationship of plutonium particle aggregation in the lung and the development of lung tumors after inhalation of 239PuO2 was studied in 664 life span rats with mean lung doses ranging from 0.35 to 20 Gy. Plutonium particle concentration and aggregation were determined from autoradiographic sections of the left lung lobe. The increase in particles/cm2 and mean number of particles per aggregate up to 20 Gy were directly proportional to lung dose. Aggregates with greater than 25 particles increased linearly with dose from 0.2% at 1.4 Gy to 8.2% at 20 Gy, in a pattern similar to increasing severity of pulmonary fibrosis and incidence of lung tumors. Lung tumor incidence increased from about 6% at 1.4 Gy to 83% at 8 Gy; no further increase in lung tumors was seen at doses greater than 8 Gy. Maximum lung tumor incidence at 8 Gy corresponded to a particle concentration of 130/cm2 and four particles/aggregate with 4% of aggregates having greater than 25 particles. Aggregation of inhaled plutonium particles in clusters of greater than 25 particles resulted in daily doses of only a few centigray to focal tissue regions containing clustered particles, yet these doses appeared sufficient to cause pulmonary fibrosis and promotion of pulmonary carcinogenesis.
Asunto(s)
Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación/etiología , Plutonio/administración & dosificación , Administración por Inhalación , Animales , Femenino , Ratas , Ratas Endogámicas , Organismos Libres de Patógenos EspecíficosRESUMEN
Scanning electron microscopic (SEM) autoradiography of the lung is being used to determine the distribution of inhaled, alpha particle-emitting, plutonium dioxide particles. SEM autoradiography provides high visual impact views of alpha activity. Particles irradiating the bronchiolar epithelium were detected both on the bronchiolar surface and in peribronchiolar alveoli. The technique is being used to obtain quantitative data on the clearance rates of plutonium particles from bronchi and bronchioles.
Asunto(s)
Pulmón/análisis , Plutonio/análisis , Animales , Autorradiografía , Bronquios/metabolismo , Femenino , Pulmón/metabolismo , Pulmón/ultraestructura , Microscopía Electrónica de Rastreo , Plutonio/farmacocinética , Ratas , Ratas Endogámicas , Organismos Libres de Patógenos Específicos , Distribución TisularRESUMEN
Multistage models of cancer induction have been accepted in chemical and radiation carcinogenesis for many years. Most models assume that both initiating and promoting events are required for greatest expression of tumor incidence. The sequence of events is important in determining the shape of the dose-response curve. A total of 1058 female, SPF, Wistar, sham-exposed rats and 2134 rats given a single inhalation to 169Yb, 239PuO2 are being studied for lung tumor formation in a life-span study. Histopathological analyses have been completed on 1149 rats. Similar dose-response curves are seen for pulmonary fibrosis pulmonary metaplasia and lung tumor formation. Lung tumor incidences were: 0.6% (0 Gy), 0.5% (0.06 Gy), 0% (0.11 Gy), 0% (0.23 Gy), 4.5% (0.46 Gy), 0% (0.84 Gy), 13.8% (1.9 Gy), 18.6% (3.5 Gy), 72.5% (7.4 Gy), and 84.9% (15 Gy). The dose lung-tumor curve was best fit by a quadratic function and was not well fit by a linear function. It is proposed that the low-dose portion of the quadratic curve represents promotion event(s) due to increasing 239PuO2 particle clustering in subpleural regions, leading to a cellular evolution of focally intense inflammation, fibrosis, epithelial metaplasia and carcinoma formation. A defined, practical threshold dose may be useful with respect to setting radiation protection guidelines for lung tumor induction.
Asunto(s)
Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación/patología , Plutonio/administración & dosificación , Administración por Inhalación , Animales , Femenino , Neoplasias Pulmonares/patología , Plutonio/toxicidad , Dosis de Radiación , Ratas , Ratas EndogámicasRESUMEN
Aggregation of inhaled 239PuO2 particles in the pulmonary region of the lung may be required for promotion of pulmonary carcinogenesis in rats. Female Wistar rats were exposed to an aerosol of 239PuO2 and their lungs examined by scanning electron microscopic (SEM) autoradiography. SEM autoradiography provides a rapid and inexpensive method for viewing a large lung tissue volume for alpha tracks. Evidence of particle aggregation was seen by 28 days postinhalation and was marked by 90 to 150 days post-inhalation. Subpleural plutonium particles resulted in exposure into the pleural cavity. Peribronchiolar, alveolar plutonium particles and particle aggregates gave the greatest radiation dose to the bronchiolar epithelium. High-dose, overlapping, alpha-track, radiation zones in bronchiolar epithelium may be required for maximum development of lung tumors.