RESUMEN
The assessment and management of risks associated with exposures to ionising radiation are defined by the general radiological protection system, proposed by the International Commission on Radiological Protection (ICRP). This system is regarded by a large majority of users as a robust system although there are a number of dissenting voices, claiming that it is not suitable for estimating the risks resulting from internal exposures. One of the specific issues of internal exposure involves short-range radiations such as Auger and beta particles. Auger- and beta-emitting radionuclides can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to their chemical nature and the vector with which they are associated. Given the limited range of the low-energy electrons in biological matter, this heterogeneous distribution can generate highly localised energy depositions and exacerbate radiotoxic responses at cellular level. These particularities in energy distribution and cellular responses are not taken into account by the conventional methods for the assessment of risk.Alternative systems have been proposed, based on dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy deposition occurring within the DNA molecule. However, calculation of absorbed doses at the molecular level is not sufficient to ensure a better assessment of the risks incurred. Favouring such a microdosimetric approach for the risk assessments would require a comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and the mechanisms leading from cellular energy deposition to the appearance of a health detriment. The required knowledge is not fully available today and it is not yet possible to link an intracellular energy deposition to a probability of occurrence of health effects or to use methods based on cellular dosimetry directly.The imperfections of the alternative approaches proposed so far should not discourage efforts. Protection against exposure to Auger and low-energy beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of the radionuclides in various cellular structures, but also from radiotoxicological studies to define the relative biological effectiveness of the various Auger emitters used in medicine and of certain low-energy beta emitters, whose behaviour may depend greatly on their chemical form during intake. The scientific expertise, as well as the human and physical resources needed to conduct these studies, is available. They could be now mobilised into international low-dose research programmes, in order to ultimately improve the protection of people exposed to these specific radionuclides.
Asunto(s)
Exposición a Riesgos Ambientales/análisis , Traumatismos por Radiación/etiología , Traumatismos por Radiación/fisiopatología , Monitoreo de Radiación/métodos , Protección Radiológica/métodos , Radioisótopos/efectos adversos , Medición de Riesgo/métodos , Animales , Partículas beta , Humanos , Traumatismos por Radiación/prevención & control , Proyectos de Investigación/tendencias , Medición de Riesgo/tendenciasRESUMEN
A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.
Asunto(s)
Industrias/estadística & datos numéricos , Neoplasias Inducidas por Radiación/mortalidad , Reactores Nucleares/estadística & datos numéricos , Enfermedades Profesionales/mortalidad , Exposición Profesional/estadística & datos numéricos , Medición de Riesgo/métodos , Recuento Corporal Total/estadística & datos numéricos , Adulto , Estudios de Cohortes , Empleo/estadística & datos numéricos , Femenino , Humanos , Cooperación Internacional , Masculino , Dosis de Radiación , Factores de Riesgo , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
201Tl is widely used in nuclear medicine to carry out myocardial perfusion imaging (MPI). However, very limited data is available on long-term distribution in the body, excretion and corresponding dose. In this study we performed a 2 month follow-up of a patient who underwent MPI, by urine analysis and in vivo measurements. The biological half-life of thallium was consequently estimated to be 11.6-27 d, which is in partial agreement with previous studies. We also estimated excretion and retention of 200Tl, 201Tl and 202Tl isotopes using the biokinetic parameters from ICRP publication 53 and compared the forecast result with actual measurements. The latter demonstrated a higher urinary excretion and a higher body retention than what was expected. Our results therefore suggest that the long-term retention and consequently the effective dose coefficient for 201Tl considered in ICRP publications 53 and 80 may be slightly underestimated.
Asunto(s)
Isquemia Miocárdica/diagnóstico por imagen , Radiofármacos/farmacocinética , Radioisótopos de Talio/farmacocinética , Talio/farmacocinética , Anciano , Transporte Biológico , Circulación Coronaria , Humanos , Masculino , Tasa de Depuración Metabólica , Isquemia Miocárdica/orina , Cintigrafía , Radiofármacos/administración & dosificación , Talio/administración & dosificación , Radioisótopos de Talio/administración & dosificaciónRESUMEN
BACKGROUND: Prospective study of survival and AIDS or death progression in a cohort of 251 HIV infected patients whose seroconversion time is unknown, with a main objective: To analyse p24 antigen plasmatic levels and viral load as surrogate markers. PATIENTS: 251 patients were included, most of them undergoing antiretroviral therapy, and were followed-up consecutively in the HIV/AIDS Unity of Internal Medicine Service of the Hospital Universitario Arnau de Vilanova in Lleida. METHODS: We made clinical and analytical baseline studies and every 3 months thereafter. Related to p24 antigen 3 group were established: group I, < 20 pg/mL, group 2, 20-39 pg/mL, group 3, 40 or more pg/mL. We studied survival and progression according to baseline levels over 4 year period. Regard to viral load, we just compared this with p24 antigen in the last phase of the study (third and fourth year) for technical reasons. Survival analysis was made by Kaplan-Meier estimation. Relative risk was calculated by Cox's proportional hazards model. RESULTS: During the 48 months of follow-up 55 patients died. AIDS progression risk or death was 4.8 times higher for the p24 antigen > = 40 pg/mL group than for the p24 antigen < 20 pg/mL one; the relative risk of patients with p24 antigen between 20-39 pg/mL was 2.5 times higher than those included in the group of p24 antigen < 20 pg/mL. Related to progression study, 34 patients progressed. AIDS progression risk or death for p24 antigen > = 40 pg/mL group was 7.69 times higher compared with group 2 (p24 antigen levels between 20-39 pg/mL). The comparison with viral load by PCR determination shows controversial results. CONCLUSIONS: p24 antigen plasma level is a good survival and AIDS progress or death surrogate markers in HIV infected patients, and it is useful for 4 years or more. An isolated value < 20 pg/mL is a sign of good prognosis. Parallelism between p24 antigen plasmatic level and viral load has not been observed.
Asunto(s)
Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/sangre , Infecciones por VIH/mortalidad , Adulto , Biomarcadores/sangre , Progresión de la Enfermedad , Estudios de Seguimiento , Infecciones por VIH/virología , Humanos , Pronóstico , Tasa de Supervivencia , Factores de Tiempo , Carga ViralRESUMEN
BACKGROUND: Prospective study of AIDS or death progression in a cohort of 251 HIV infected patients whose time of seroconversion is unknown, with 2 main objectives: 1. To analyse plasma level p24 antigen as a marker of progression. 2. To evaluate stability of plasma levels of p24 antigen as a marker of progression. PATIENTS AND METHODS: 251 patients were studied, most on antiretroviral therapy, who were attended at HIV/AIDS Unit of Internal Medicine Service of the Hospital Universitario Arnau de Vilanova de Lleida. Mean initial CD4 cell count were 376 x 10(6)/L (range: 0.8-1350) 51 cases had been diagnosed previously with AIDS, their were therefore excluded. Analysis of survival, according to initial plasma p24 antigen and Cd4 cell count as well as the stability of plasma level p24 antigen was performed by Kaplan-Meier test. Relative risk were calculate by Cox's proportional hazard model. RESULTS: During a follow-up period of 24 months, 38 patients progressed to AIDS or died. Relative risk (RR) of progression to AIDS or death related to the group with p24 antigen < 40 pg/ml was 5.48 when p24 antigen => 40 pg/ml (p < 0.0005). Relative risk of progression to AIDS or death for the patients with unstable plasmatic level of p24 antigen related to the group with stable plasmatic level was 4.25 (p < 0.0005). CONCLUSIONS: Plasma level and stability of p24 antigen are useful as a markers of risk of AIDS progression or death and they behaves as an independent prognostic markers in our patients. p24 antigen < 40 pg/ml is associated with a better prognosis.
Asunto(s)
Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/inmunología , VIH-1 , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Biomarcadores/sangre , Linfocitos T CD4-Positivos/inmunología , Estudios de Cohortes , Progresión de la Enfermedad , Infecciones por VIH/mortalidad , Humanos , Análisis Multivariante , Pronóstico , Estudios Prospectivos , Factores de Tiempo , Carga ViralRESUMEN
OBJECTIVE: To analyse plasma p24 antigen as a marker of survival in a cohort of HIV-infected patients whose time of seroconversion is unknown. DESIGN: Prospective cohort study. SETTING: AIDS Unit in a teaching hospital. PATIENTS: 251 patients were studied, most on antiretroviral therapy. Mean initial CD4 cell counts were 376 x 106/ 1 (range: 0.8-1350). 51 cases had been diagnosed previously with AIDS. METHODS: Analysis of survival, according to initial plasma p24 antigen was performed by Kaplan-Meier test. Relative risks were calculated by Cox's proportional hazards model. RESULTS: During a follow-up period of 24 months, 46 patients died. Relative risk (RR) of death related to the group with p24 antigen = < 40 pg/ml was 3.32 when p24 antigen > 40 pg/ml (p = 0.0001). CD4+ cell levels adjusting, the result was 2.47 (CI 95% 1.37-4.46) (p = 0.0027). CONCLUSIONS: Plasma levels of p24 antigen is useful as a marker of the risk of death and it behaves as a independent prognostic marker in our patients. P24 antigen = < 40 pg/ml is associated with a better prognosis.
Asunto(s)
Proteína p24 del Núcleo del VIH/sangre , Seropositividad para VIH/mortalidad , Biomarcadores , Recuento de Linfocito CD4 , Estudios de Cohortes , Interpretación Estadística de Datos , Estudios de Seguimiento , Seropositividad para VIH/inmunología , Humanos , Pronóstico , Estudios Prospectivos , Riesgo , Análisis de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Prospective study of survival and AIDS or death progression in a cohort of 251 HIV infected patients whose seroconversion time is unknown, with 1 main objective: To analyse CD4+ lymphocytes count, p24 antigen plasmatic levels and viral load as surrogate markers. PATIENTS AND METHODS: 251 patients were included, most of them undergoing antiretroviral therapy, followed consecutively in the HIV/AIDS Unity of Internal Medicine Service of the Hospital Universitario Arnau de Vilanova in Lleida. We made clinical and analytical baseline studies and every 3 months thereafter. In relation to CD4+ lymphocytes, 3 groups were established: group I, 500 or more cells/mL; group II, 200-499 cells/mL and group III, < 200 cells/mL. In the same way, with p24 antigen we established 3 group: group I, < 20 pg/mL, group II, 20-39 pg/mL, group III 40 or more pg/mL. We studied survival in relation to baseline levels and stability, the latter being understood as persistent levels in the initial group, or better, over 3 year period. Survival analysis was made by Kaplan-Meier estimation. Relative risk was calculated by Cox's proportional hazards model. RESULTS: During the 36 months of follow-up 53 patients died. AIDS progression risk or death was 4.8 times higher for the p24 antigen > = 40 pg/mL group than for the p24 antigen < 20 pg/mL one; patients with p24 antigen between 20-39 pg/mL relative risk was 2.5 times higher than those included in p24 antigen < 20 pg/mL group. These results emphasize that if we take into account the p24 antigen stability during these 36 months. In relation to progression study, 36 patients progressed. AIDS progression risk or death for p24 antigen > = 40 pg/mL group was 7.69 times higher in relation to that with p24 antigen levels between 20-39 pg/mL. The bivariable study shows that CD4 lymphocytes counts and p24 antigen level have quite an independent value. The comparison with viral load by PCR determination makes manifest discrepancy, difficult to explain. CONCLUSIONS: p24 antigen plasma level is a good survival and AIDS progress or death surrogate markers in HIV infected patients, and it is useful for 3 years or more. An isolated value < 20 pg/mL and, furthermore, the stability in successive controls under this concentration is a sign of good prognosis. Its value is emphasized with CD4+ lymphocytes count. It seem necessary that more comparative studies with viral load are required.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/mortalidad , VIH-1 , Carga Viral/estadística & datos numéricos , Adulto , Fármacos Anti-VIH/uso terapéutico , Biomarcadores/sangre , Estudios de Cohortes , Progresión de la Enfermedad , Quimioterapia Combinada , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Humanos , Pronóstico , Riesgo , Análisis de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.