RESUMEN

PURPOSE: During the first part of the 20th century, (226)Ra was the most used radionuclide for brachytherapy. Retrospective accurate dosimetry, coupled with patient follow up, is important for advancing knowledge on long-term radiation effects. The purpose of this work was to dosimetrically characterize two (226)Ra sources, commonly used in Sweden during the first half of the 20th century, for retrospective dose-effect studies. METHODS: An 8 mg (226)Ra tube and a 10 mg (226)Ra needle, used at Radiumhemmet (Karolinska University Hospital, Stockholm, Sweden), from 1925 to the 1960s, were modeled in two independent Monte Carlo (MC) radiation transport codes: geant4 and mcnp5. Absorbed dose and collision kerma around the two sources were obtained, from which the TG-43 parameters were derived for the secular equilibrium state. Furthermore, results from this dosimetric formalism were compared with results from a MC simulation with a superficial mould constituted by five needles inside a glass casing, placed over a water phantom, trying to mimic a typical clinical setup. Calculated absorbed doses using the TG-43 formalism were also compared with previously reported measurements and calculations based on the Sievert integral. Finally, the dose rate at large distances from a (226)Ra point-like-source placed in the center of 1 m radius water sphere was calculated with geant4. RESULTS: TG-43 parameters [including gL(r), F(r, θ), Λ, and sK] have been uploaded in spreadsheets as additional material, and the fitting parameters of a mathematical curve that provides the dose rate between 10 and 60 cm from the source have been provided. Results from TG-43 formalism are consistent within the treatment volume with those of a MC simulation of a typical clinical scenario. Comparisons with reported measurements made with thermoluminescent dosimeters show differences up to 13% along the transverse axis of the radium needle. It has been estimated that the uncertainty associated to the absorbed dose within the treatment volume is 10%-15%, whereas uncertainty of absorbed dose to distant organs is roughly 20%-25%. CONCLUSIONS: The results provided here facilitate retrospective dosimetry studies of (226)Ra using modern treatment planning systems, which may be used to improve knowledge on long term radiation effects. It is surely important for the epidemiologic studies to be aware of the estimated uncertainty provided here before extracting their conclusions.

Asunto(s)

Radiometría/métodos , Radio (Elemento)/uso terapéutico , Estudios Retrospectivos , Braquiterapia/instrumentación , Braquiterapia/métodos , Simulación por Computador , Relación Dosis-Respuesta en la Radiación , Diseño de Equipo , Vidrio , Humanos , Modelos Biológicos , Método de Montecarlo , Agujas , Fantasmas de Imagen , Dosificación Radioterapéutica , Radio (Elemento)/efectos adversos , Suecia/epidemiología , Factores de Tiempo , Agua

RESUMEN

BACKGROUND: Episcleral brachytherapy is the most common eye-preserving option for treating uveal melanoma, with ruthenium-106 widely used in Europe. Case series have reported on ocular outcome, but there are very little data on the impact of dose rate. Therefore, we studied the association of dose rate with secondary enucleation. METHODS: Data for all patients in Sweden managed with brachytherapy from 1979 to 2012 were retrieved (962 patients) and divided in quartiles based on dose rates at the tumour apex and at the scleral surface. Kaplan-Meier curves for secondary enucleation were generated independent of dose rate and for each dose rate quartile. Cox regression univariate and multivariate modelling included clinical parameters and dose rates at the tumour apex and the scleral surface. RESULTS: Baseline clinical characteristics were not significantly different across the quartiles except that thinner tumours had higher dose rates at the tumour apex. Dose rates ranged widely, with a near normal distribution at the scleral surface but skewed at the tumour apex. For all quartiles, secondary enucleation was more often caused by tumour progression than by ocular side effects. Univariate and multivariate modelling including clinical parameters showed no association between dose rate and secondary enucleation. CONCLUSIONS: Although dose rates ranged widely, there was no apparent association with secondary enucleation, suggesting that based on ocular survival, current practice of annual replacement of applicators is acceptable, irrespective of the significant reduction in each applicator's dose rate. Nevertheless, patients treated with higher dose rates have shorter plaque exposure and presumably less ocular irritation.

Asunto(s)

Braquiterapia/métodos , Melanoma/radioterapia , Radioisótopos de Rutenio/administración & dosificación , Neoplasias de la Úvea/radioterapia , Enucleación del Ojo , Femenino , Humanos , Masculino , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Modelos Estadísticos , Dosificación Radioterapéutica , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/cirugía

RESUMEN

BACKGROUND: To determine the volumes required for stable haemodynamics and possible effects on the coagulation, we studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer's acetate (RAC) in neurosurgical patients operated on in a sitting position. METHODS: Thirty craniotomy patients were randomised to receive either HES or RAC. Before positioning, SV, measured by arterial pressure waveform analysis, was maximised by boluses of fluid until SV did not increase more than 10%. SV was maintained by repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups during surgery. RESULTS: Comparable haemodynamics were achieved with the mean [standard deviation (SD)] cumulative doses of HES or RAC 271 (47) or 264 (50) ml (P = 0.699) before the sitting position. Mean (SD) doses of HES or RAC at 30 min after the positioning were 343 (94) or 450 (156) ml (P = 0.036), and at the end of surgery 464 (284) or 707 (425) ml, respectively (P = 0.087). The intraoperative fluid balance was more positive in the RAC than in the HES group [P = 0.044, 95% confidence interval (CI) -978 to -14]. Cardiac and stroke volume indexes [CI and stroke volume index (SVI)] increased in the HES group (P < 0.05) but not in the RAC group [non significant (N.S.)]. Neither coagulation profile nor blood loss differed between the groups. CONCLUSION: Fluid filling with HES boluses resulted in a positive response in CI and SVI during the sitting position. The 34% smaller volume of HES than crystalloid and less positive fluid balance in the HES group might be important in craniotomy patients with decreased brain compliance.

Asunto(s)

Craneotomía/métodos , Derivados de Hidroxietil Almidón/administración & dosificación , Soluciones Isotónicas/administración & dosificación , Sustitutos del Plasma/administración & dosificación , Postura , Volumen Sistólico , Adulto , Anestesia General , Coagulación Sanguínea/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Embolia Aérea/prevención & control , Femenino , Fluidoterapia , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Derivados de Hidroxietil Almidón/farmacología , Hipotensión/prevención & control , Presión Intracraneal , Complicaciones Intraoperatorias/prevención & control , Soluciones Isotónicas/farmacología , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente , Sustitutos del Plasma/farmacología , Medicación Preanestésica , Volumen Sistólico/efectos de los fármacos , Tromboelastografía , Venas

RESUMEN

We have isolated and characterized the gene encoding a Drosophila melanogaster homolog of Caenorhabditis elegans UNC-51 (uncoordinated movement-51): Pegarn. Developmental Northern blot shows the Pegarn gene is expressed at all stages of development. The protein is detected throughout the Drosophila third instar larval central nervous system (CNS) in axons projecting out from the ventral ganglion and in the optic anlagen of the optic lobe. Heterozygous Pegarn mutant embryos show defects in larval axonal neuronal patterning, but survive to adulthood. Homozygous mutants have an even more deformed pattern of neuronal development and do not survive through the larval stages. The data from this research suggest the critical roles of Pegarn in CNS and PNS axonal formation in Drosophila melanogaster and indicates its similar role in other multicellular species.

Asunto(s)

Proteínas de Drosophila/genética , Proteínas Serina-Treonina Quinasas/genética , Animales , Homólogo de la Proteína 1 Relacionada con la Autofagia , Axones/química , Proteínas de Caenorhabditis elegans , Proteínas de Drosophila/análisis , Embrión no Mamífero , Regulación del Desarrollo de la Expresión Génica , Estadios del Ciclo de Vida/genética , Neuronas/química , Neuronas/ultraestructura , Proteínas Serina-Treonina Quinasas/análisis , Homología de Secuencia

RESUMEN

The goal of this retrospective study concerning primary carcinoma of the vagina (PCV) was to analyze clinical and histopathologic prognostic factors in one of the largest known material, which comprised 314 patients. PCV is a rare disease, and the majority of published studies are based on small materials; therefore, the established knowledge concerning prognostic factors is insufficient. Routine treatment is based on irradiation with risk for undertreatment or overtreatment, which leads to unnecessary complications in the absence of prognostic factors. The overall 5-year disease-specific survival rate in this study was 45% and in stage I 75%. In the univariate statistical analysis, several factors correlated significantly with disease-specific survival. However, in the multivariate analysis, there were only three factors that independently could predict poor survival-high age at diagnosis, large tumors (> or =4 cm), and advanced stage. Common background factors with no prognostic significance were prior hysterectomy, other gynecological malignancies, and pelvic irradiation. In conclusion, this study has elucidated three strong prognostic factors that might be considered in the choice of therapy and also for modification of the FIGO guidelines. Increased knowledge concerning complementary biologic markers to discriminate between low- and high malignant tumors is however of great importance.

Asunto(s)

Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Neoplasias Vaginales/diagnóstico , Neoplasias Vaginales/patología , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/radioterapia , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias Vaginales/radioterapia

RESUMEN

Exposure to ionizing radiation is a known risk factor for breast cancer and the fertility pattern is a recognized modifier of breast cancer risk. The aim of this study was to elucidate the interaction between these 2 factors. This study is based on a Swedish cohort of 17 202 women who had been irradiated for skin haemangiomas in infancy between 1920 and 1965. The mean age at treatment was 6 months and the median breast dose was 0.05 Gy (range 0-35.8 Gy). Follow-up information on vital status, parity, age at first childbirth and breast cancer incidence was retrieved through record linkage with national population registers for the period 1958-1995. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. In this cohort, the fertility pattern differed from that in the Swedish population, with significantly fewer childbirths overall and before 25 years of age but more childbirth after that age. There were 307 breast cancers in the cohort and the standardized incidence ratio (SIR) was 1.22 (95% CI 1.09-1.36). A linear dose-response model with stratification for fertility pattern and menopausal status resulted in the best fit of the data. ERR/Gy was 0.33 (95% CI 0.17-0.53). In absolute terms this means an excess of 2.1 and 5.4 cases per Gy per 10(4) breast-years in the age groups 40-49 and 50-59 years respectively. The fertility pattern influenced the breast cancer risk in this irradiated population in a similar way to that observed in other studies. SIR at dose = 0 was highest, 2.31, among postmenopausal nulliparous women (95% CI 1.48-3.40, n = 62). SIR at dose = 0 was lowest in pre- or postmenopausal women with a first childbirth before 25 years of age; 0.89 (0.71-1.09) and 0.88 (0.58-1.25) respectively. Thus, in addition to the dose-effect response in the cohort, part of the breast cancer excess could be explained by a different fertility pattern. The estimates of ERR/Gy for the various categories of age at first childbirth, number of children, menopausal status and ovarian dose were very similar, contradicting any interaction effects on the scale of relative risk.

Asunto(s)

Neoplasias de la Mama/etiología , Edad Materna , Neoplasias Inducidas por Radiación/etiología , Paridad , Adulto , Edad de Inicio , Anciano , Tasa de Natalidad , Neoplasias de la Mama/epidemiología , Estudios de Cohortes , Femenino , Hemangioma/radioterapia , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/epidemiología , Dosis de Radiación , Sistema de Registros , Factores de Riesgo , Neoplasias Cutáneas/radioterapia , Suecia/epidemiología

RESUMEN

BACKGROUND: In Langerhans cell histiocytosis (LCH) pulmonary involvement, which is often initially asymptomatic, may contribute to significant morbidity and mortality. To determine the long-term prognosis, a cross-sectional study was undertaken. PROCEDURE: Forty-one patients with > or = 5 years follow-up after the diagnosis of LCH were interviewed and underwent physical examination, blood tests, a chest X-ray and a high-resolution CT (HRCT) of the lungs. All patients included had been referred to the Department of Pediatrics at the Karolinska Hospital in Stockholm between July 1962 and February 1990 (median follow-up 16 years). Biopsies from all patients were reviewed and confirmed to be consistent with LCH. Information on previous clinical features including treatment and the results of chest X-rays were also collected for risk factor analysis. RESULTS: Radiographic abnormalities of the lungs (cysts and/or emphysema), found in 10/41 (24%) at follow-up, were classified into five groups according to the extent of the cysts. These patients had more often suffered from multisystem than from single-system disease (P = 0.01), were significantly older at diagnosis (P < 0.001), and had been more heavily treated with chemotherapy and/or radiotherapy. They were also more frequently smokers (P < 0.0001) and 7/10 (70%) had suffered lung involvement at diagnosis. At the time of diagnosis of the pulmonary involvement, 4/10 (40%) patients had respiratory symptoms, but only 2/10 (20%) had symptoms at follow-up. CONCLUSIONS: Ten (24%) of the 41 patients had abnormal findings on radiological examination of the lungs at long-term follow-up and seven are or had been smokers. It is of great importance that patients with LCH be informed about smoking-related pulmonary morbidity. Prolonged monitoring of the lungs for smokers and patients with known pulmonary involvement is recommended.

Asunto(s)

Histiocitosis de Células de Langerhans/patología , Pulmón/patología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Estudios Transversales , Análisis Factorial , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pronóstico , Factores de Riesgo , Tomografía Computarizada por Rayos X

RESUMEN

Radium applicators and pure beta emitters have been widely used in the past to treat skin haemangioma in early childhood. A well defined relationship between the low doses received from these applicators and radiation-induced cancers requires accurate dosimetry. A human-based CT scan phantom has been used to simulate every patient and treatment condition and then to calculate the source target distance when radium and pure beta applicators were used. The effective transmission factor psi(r) for the gamma spectrum emitted by the radium sources applied on the skin surface was modelled using Monte Carlo simulations. The well-known quantization approach was used to calculate gamma doses delivered from radium applicators to various anatomical points. For 32P, 90Sr/90Y applicators and 90Y needles we have used the apparent exponential attenuation equation. The dose calculation algorithm was integrated into the ICTA software (standing for a model that constructs an Individualized phantom based on CT slices and Auxological data), which has been developed for epidemiological studies of cohorts of patients who received radium and beta-treatments for skin haemangioma. The psi(r) values obtained for radium skin applicators are in good agreement with the available values in the first 10 cm but higher at greater distances. Gamma doses can be calculated with this algorithm at 165 anatomical points throughout the body of patients treated with radium applicators. Lung heterogeneity and air crossed by the gamma rays are considered. Comparison of absorbed doses in water from a 10 mg equivalent radium source simulated by ICTA with those measured at the Radiumhemmet, Karolinska Hospital (RAH) showed good agreement, but ICTA estimation of organ doses did not always correspond those estimated at the RAH. Beta doses from 32P, 90Sr/90Y applicators and 90Y needles are calculated up to the maximum beta range (11 mm).

Asunto(s)

Hemangioma/radioterapia , Radiometría/métodos , Neoplasias Cutáneas/radioterapia , Programas Informáticos , Algoritmos , Niño , Simulación por Computador , Rayos gamma , Hemangioma/epidemiología , Humanos , Pulmón/efectos de la radiación , Método de Montecarlo , Fantasmas de Imagen , Agua

RESUMEN

Development of lens opacities and the measures taken to avoid them have clinical relevance in the fields of oncology, radiotherapy and radiation protection. The aim of this study was to correlate the prevalence of lenticular opacities in individuals exposed to ionizing radiation in childhood with radiation dose and other possible risk factors. Between 1920 and 1959, about 16,500 children (age <18 months) with skin hemangiomas were referred to Radiumhemmet, Karolinska University Hospital, 89% of whom were treated with radiotherapy. A total of 484 exposed individuals and 89 nonexposed controls participated in an ophthalmological examination. Lens opacities were found in 357 (37%) of the 953 lenses examined in the exposed persons. In contrast, lens opacities were observed in only 35 (20%) of the 178 lenses examined in the nonexposed control individuals. It is concluded that the increased prevalence of cortical and posterior subcapsular opacities is related to previous radiotherapy. Age at examination was the strongest modifier of risk. Children exposed to a lenticular dose of 1 Gy had a 50% increased risk (odds ratio 1.50; 95% confidence interval 1.10-2.05) of developing a posterior subcapsular opacity and a 35% increased risk of a cortical opacity (odds ratio 1.35; 95% confidence interval 1. 07- 1.69).

Asunto(s)

Catarata/etiología , Cristalino/efectos de la radiación , Radioterapia/efectos adversos , Adulto , Factores de Edad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Dosis de Radiación , Análisis de Regresión , Luz Solar/efectos adversos

RESUMEN

The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range <0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies.

Asunto(s)

Neoplasias de la Mama/etiología , Hemangioma/radioterapia , Neoplasias Inducidas por Radiación/etiología , Neoplasias Cutáneas/radioterapia , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Persona de Mediana Edad , Radioterapia/efectos adversos

RESUMEN

BACKGROUND AND PURPOSE: Irradiation of advanced ovarian cancer has been performed during the years 1976-1984 with six-field technique. Results of this treatment in a long follow-up have never before been evaluated. MATERIAL AND METHODS: Seventy-five patients with stage IIb-IV of invasive ovarian cancer have been treated with a combination of surgery, radiotherapy and chemotherapy. The results of the treatment were compared with 98 patients treated during the year 1991-1992 with surgery and chemotherapy only. RESULTS: After controlling for the differences in background factors between the groups considered, there was still a significantly better survival rate for the patients treated with radiotherapy. CONCLUSION: The results suggest that the role of radiotherapy in advanced ovarian cancer should be investigated in a prospective randomized trial.

Asunto(s)

Neoplasias Ováricas/radioterapia , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Cisplatino/administración & dosificación , Fraccionamiento de la Dosis de Radiación , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Tablas de Vida , Estudios Longitudinales , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Persona de Mediana Edad , Terapia Neoadyuvante , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Dosificación Radioterapéutica , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia

RESUMEN

The risk of intracranial tumors after exposure to ionizing radiation during infancy has been studied in a pooled analysis of two Swedish hemangioma cohorts (n = 28,008). The mean absorbed intracranial dose was low (7 cGy, range 0-11.5 Gy). The cohorts were followed up in the Swedish Cancer Register for incident intracranial tumors during the period 1958-1993. Eighty-eight tumors were found in 86 individuals compared to 60.72 expected [standardized incidence ratio (SIR) 1.42, 95% confidence interval (CI) 1.13-1.75]. The SIR increased significantly in ascending dose categories (P = 0.02). Dose-response analyses were performed with Poisson regression methods. There was a significant effect of dose, and the dose-effect relationship was negatively modified by age at first treatment. This indicates a higher risk for those exposed earlier in life. A linear dose-response model modified by age at first treatment resulted in the best fit. The excess relative risk (ERR) was 2.7/Gy (95% CI 1.0-5.6). The ERR/Gy was 4.5 if the treatment was given before 5 months of age, 1.5 if it was given at 5-7 months and 0.4 if it was given later. The study thus strongly indicates that there exists a dose-response relationship between absorbed dose in the brain and the subsequent risk of developing an intracranial tumor and that the risk is higher among infants exposed at younger ages.

Asunto(s)

Neoplasias Encefálicas/epidemiología , Hemangioma/radioterapia , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Cutáneas/radioterapia , Adulto , Neoplasias Encefálicas/etiología , Estudios de Cohortes , Relación Dosis-Respuesta en la Radiación , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/etiología , Suecia/epidemiología

RESUMEN

The possible impact of early gonadal irradiation on the results of future pregnancies is unclear. This study is based on the progeny of 17,393 women who were treated with irradiation for skin hemangiomas at the age of 18 months or less. The mean ovarian dose was 6 cGy, and the maximum was 8.55 Gy. Using Swedish central health registers, the outcome of delivery was studied in these women; 19,494 infants born were identified. The treated women deviated from the general population by having a longer education and by smoking less. This may explain a reduced risk for low birth weight and preterm birth (not related to radiation dose). Women with ovarian doses greater than 1 cGy had fewer infants than women with a lower ovarian dose. An excess of perinatal deaths was evident as well as a slight excess in the rate of malformation, but neither was related to dose. There was a statistically significant trend of an increasing rate of neural tube defects with ovarian dose, possibly a chance result of multiple statistical testing. Cleft lip/palate occurred at levels significantly below expectation. No increase in the rate of infants with Down syndrome or in childhood malignancies was detected. No major adverse results in outcome of delivery were seen after ovarian irradiation in childhood with the possible exception of neural tube defects.

Asunto(s)

Hemangioma/radioterapia , Reproducción/efectos de la radiación , Neoplasias Cutáneas/radioterapia , Anomalías Congénitas/epidemiología , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Lactante , Masculino , Neoplasias Inducidas por Radiación/etiología , Ovario/efectos de la radiación , Paridad , Embarazo , Traumatismos por Radiación , Suecia

RESUMEN

During development of the Drosophila nerve cord, neuroblast 7-3 gives rise to a pair of mitotic sister serotonin neurons in each hemisegment. Here we show that the zinc finger gene eagle, which is expressed in neuroblast 7-3, is essential for specifying the fate of serotonin neurons. We find that loss-of-function eagle mutations produce an unusual differential phenotype with respect to the sister serotonin cells and that eagle is necessary for the maintenance of engrailed and zfh-2 expression in the serotonin neurons. We present a model that uniquely identifies all progeny neurons in the neuroblast 7-3 lineage based on the expression of specific molecular markers, position within the nerve cord and the effect of eagle loss-of-function mutations. Although serotonin is an important neurotransmitter conserved throughout the animal kingdom, we show that hypomorphic alleles of eagle can produce viable adults that have a dramatic reduction in the number of serotonin-producing neurons.

Asunto(s)

Proteínas de Drosophila , Drosophila melanogaster/embriología , Neuronas/citología , Neuropéptidos/fisiología , Receptores de Esteroides/fisiología , Serotonina/análisis , Factores de Transcripción , 5-Hidroxitriptófano/metabolismo , Animales , Diferenciación Celular , Sistema Nervioso Central/citología , Sistema Nervioso Central/embriología , Proteínas de Unión al ADN/análisis , Dopa-Decarboxilasa/análisis , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/análisis , Mutación , Neuronas/química , Neuropéptidos/genética , Factores del Dominio POU , Receptores de Esteroides/genética , Proteínas Recombinantes de Fusión/análisis

RESUMEN

The register has been a support for the coordinators in Sweden when the relatives have said one thing and the deceased person another in regards to donation. Most of the staff are positive to the register and the safety regulations around it. Most often it has been a relief for the relatives that the deceased person's wishes also have been documented in the register or in the donor card. Most decisions are still, however, made by relatives. There is still a need for more positive information about transplantation and its value.

Asunto(s)

Sistema de Registros , Donantes de Tejidos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Actitud Frente a la Salud , Familia , Humanos , Encuestas y Cuestionarios , Suecia , Donantes de Tejidos/psicología , Donantes de Tejidos/estadística & datos numéricos , Obtención de Tejidos y Órganos/estadística & datos numéricos

RESUMEN

From 1920 through 1959, 14,624 infants were exposed to ionizing radiation for skin hemangioma at Radiumhemmet. They were all less than 18 months old (mean 6 months) at the time of first exposure. The irradiated hemangiomas were located all over the body. The weighted bone marrow dose was on average 0.13 Gy (range < 0.01-4.6 Gy). During the period 1920-1986, 20 deaths from leukemia (11 childhood and 9 adult) were observed in the cohort compared with 17 expected during the same period. There were no significant associations between childhood leukemia and radiation dose. Despite the relatively large number of infants studied, the low average dose to bone marrow limited the possibility of detecting a small radiation risk as might be predicted from other radiation studies.

Asunto(s)

Hemangioma/radioterapia , Leucemia Inducida por Radiación/mortalidad , Radioterapia/efectos adversos , Neoplasias Cutáneas/radioterapia , Adulto , Anciano , Partículas beta , Niño , Estudios de Cohortes , Femenino , Rayos gamma , Humanos , Lactante , Leucemia Inducida por Radiación/epidemiología , Leucemia Inducida por Radiación/etiología , Persona de Mediana Edad , Embarazo , Efectos Tardíos de la Exposición Prenatal , Radio (Elemento)/efectos adversos , Radio (Elemento)/uso terapéutico , Factores de Riesgo , Rayos X

RESUMEN

Between 1920 and 1959, 9675 women were irradiated in infancy for skin hemangioma at Radiumhemmet, Stockholm. They were exposed to low to moderate doses of ionizing radiation. The mean age at first exposure was 6 months and the mean absorbed dose to the breast anlage was 0.39 Gy (range <0.01-35.8 Gy). The breast cancer incidence was analyzed by record linkage with the Swedish Cancer Register for the period 1958-1986. Seventy-five breast cancers were found [standardized incidence ratio = 1.24; 95% confidence interval (CI) 0.98-1.54] after a mean absorbed dose of 1.5 Gy in the breasts with cancer. The analyses showed a significant dose-response relationship with a linear model estimate for the excess relative risk (ERR) of 0.38 at 1 Gy 95% CI 0.09-0.85). This relationship was not modified significantly by age at exposure or by dose to the ovaries. The ERR increased significantly with time after exposure and for > or = 50 years after exposure the ERR at 1 Gy was 2.25 (95% CI 0.59-5.62). The fitted excess absolute risk (EAR) was 22.9 per 10(4) breast-year gray. The breast absorbed dose and time after exposure were important risk determinants for breast cancer excess risk. Forty to 50 years of follow-up was necessary for the excess risk to be expressed. The study confirms previous findings that the breast anlage of female infants is sensitive to ionizing radiation.

Asunto(s)

Neoplasias de la Mama/etiología , Hemangioma/radioterapia , Neoplasias Inducidas por Radiación/epidemiología , Radioterapia/efectos adversos , Femenino , Estudios de Seguimiento , Rayos gamma , Humanos , Riesgo , Suecia , Factores de Tiempo , Rayos X

RESUMEN

A number of the pattern formation genes expressed in the Drosophila epidermis are also expressed in the developing CNS. It is uncertain how these genes contribute to neuronal differentiation. Here we show that the normal differentiation of the serotonin neurons of the Drosophila nerve cord is dependent on the expression of two pattern formation genes, huckebein (hkb) and engrailed (en). hkb and en gene products coexpress uniquely in the serotonin neurons and in neuroblast 7-3 (NB 7-3), indicating that as in the grasshopper, NB 7-3 is the progenitor for these neurons. Both genes are important for differentiation of this lineage, since loss-of-function alleles for hkb or en eliminate expression of several markers that characterize these cells. hkb appears to act at a step subsequent to NB delamination, since NB 7-3 is detectable in a strain containing a severe hkb allele.

Asunto(s)

Sistema Nervioso Central/metabolismo , Neuronas/metabolismo , Serotonina/metabolismo , Animales , Diferenciación Celular , Drosophila , Expresión Génica/genética , Inmunohistoquímica

RESUMEN

Cancer incidence was studied in 14,351 subjects exposed to ionizing radiation for skin hemangioma at the Radiumhemmet, 1920-1959. Record-linkage was done with the Swedish Cancer Registry for the period 1958-1986. After a mean follow-up of 39 years, 300 cancers were observed and the standardized incidence ratio (SIR) was 1.11 (95% confidence interval (CI) 0.99-1.24). The absorbed dose to different organs varied from < 0.01 Gy to > 40 Gy. The thyroid cancer incidence was significantly increased (SIR = 2.28; 95% CI 1.33-3.65) and for cancer of the breast SIR was 1.24 (95% CI 0.98-1.54). Regarding pancreatic cancer and tumors of the endocrine glands the statistically significantly increased SIRs were based on a small number of cases and might therefore only be a coincidence. No confirmed increased incidence could be established for other cancer sites.

Asunto(s)

Hemangioma/radioterapia , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Cutáneas/radioterapia , Adolescente , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Niño , Estudios de Cohortes , Intervalos de Confianza , Relación Dosis-Respuesta en la Radiación , Neoplasias de las Glándulas Endocrinas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/epidemiología , Radioterapia/efectos adversos , Dosificación Radioterapéutica , Sistema de Registros , Factores de Riesgo , Suecia/epidemiología , Neoplasias de la Tiroides/epidemiología

RESUMEN

Between 1930 and 1959, more than 10,000 infants were treated at Radiumhemmet, Stockholm, with radium (226Ra) needles and/or tubes for hemangioma of the skin. Absorbed dose to the brain, eye lenses, parotid glands, thyroid gland, breast anlage, lungs, stomach, intestine, ovaries, testicles and bone marrow were calculated for each individual. The mean absorbed dose to the different organs ranged from 0.06 to 0.48 Gy. The highest absorbed dose was given to the breast (maximum 47.7 Gy). There was a wide dose range for each organ which was due mainly to differences in the distance between the applicator and the organ. The absorbed dose to all organs decreased on average by 32% during the study period. This was due to a 25% decrease in the treatment time and a change in the distribution of the treatment sites.

Asunto(s)

Hemangioma/radioterapia , Radio (Elemento)/uso terapéutico , Factores de Edad , Braquiterapia , Preescolar , Humanos , Lactante , Modelos Estructurales , Agujas , Dosificación Radioterapéutica