Dose Fractionation During Puberty Is More Detrimental to Mammary Gland Development Than an Equivalent Acute Dose of Radiation Exposure.

PURPOSE: Computed tomographic (CT) scans in adolescents have increased dramatically in recent years. However, the effects of cumulative low-dose exposures on the development of radiation sensitive organs, such as the mammary gland, is unknown. The purpose of this work was to define the effects of dose rate on mammary organ formation during puberty, an especially sensitive window in mammary development. We used a fractionated low-dose x-ray exposure to mimic multiple higher dose CT scans, and we hypothesized that fractionated exposure would have less of an effect on the number of mammary gland defects compared with an acute exposure. METHODS AND MATERIALS: Female mice were subjected to fractionated low-dose x-ray exposure (10 cGy/d for 5 days), acute x-ray exposure (1 × 50 cGy), or sham exposure. As the wide genetic diversity in humans can play a role in a person's response to irradiation, 2 genetically diverse mouse strains differing in radiation sensitivity (BALB/c-sensitive; C57BL/6-resistant) were used to investigate the role of genetic background on the magnitude of the effect. RESULTS: Unexpectedly, our data reveal that multiple low-dose exposures produce greater immune and mammary defects for weeks after exposure compared with controls. The most pronounced defects being increased ductal branching in both strains and a greater percentage of terminal end buds in the BALB/c strain of mice exposed to fractionated radiation compared with sham. Radiation-induced defects near the terminal end bud were also increased in both strains. CONCLUSIONS: The findings suggest that fractionated low-dose exposures are potentially more damaging to organ development compared with an equivalent, single acute exposure and that genetic background is an important parameter modifying the severity of these effects.

Associations of clinical and dosimetric parameters with late rectal toxicities after radical intensity-modulated radiation therapy for prostate cancer: a single-centre retrospective study.

INTRODUCTION: This study assessed the incidence of late rectal toxicities and evaluated potential predictive factors for late proctitis in patients treated with prostate-specific intensity-modulated radiotherapy in Hong Kong. METHODS: This retrospective longitudinal observational study included patients with localised prostate cancer who were treated with intensity-modulated radiation therapy in an oncology unit in Hong Kong between January 2007 and December 2011, and who had >1 year of follow-up. Clinical, pharmacological, and radiation parameters were recorded. Toxicities were measured by Common Terminology Criteria for Adverse Events version 4. RESULTS: In total, 232 patients were included in this analysis. The mean follow-up time was 7.3 ± 2.1 years and 46.5% of the patients had late rectal toxicities. Late proctitis occurred in 30.5% of patients; 25% of the patients with late proctitis exhibited grade ≥2 toxicity. Median onset times for late proctitis and rectal bleeding were 15 and 18.4 months, respectively. Multivariable regression showed increased odds for the occurrence of late proctitis in patients with older age (odds ratio [OR]=1.11, 95% confidence interval [CI]=1.04-1.19, P=0.003), higher V70 (OR=1.08, 95% CI=1.01-1.15, P=0.027), and presence of acute rectal toxicities (OR=4.47, 95% CI=2.37-8.43, P<0.001). Antiplatelet use was not significantly associated with the occurrence of late proctitis (OR=1.98, 95% CI=0.95-4.14, P=0.07). CONCLUSIONS: The incidence of late rectal toxicities was considerable among patients in this study. Clinicians should consider the possibility of late proctitis for patients with older age, acute rectal toxicities, and higher V70. High doses to rectal volumes should be limited because of the significant association with V70.

Autologous fat graft in irradiated orbit postenucleation for retinoblastoma.

Autologous fat grafting has been extensively and successfully adopted in a number of pathologic conditions in regenerative surgery especially on irradiated fields in order to improve pain symptoms and tissue trophism promoting scar release. In the present study, we report our experience with autologous fat grafting for the treatment of postirradiation fibrosis and pain on three consecutive patients undergoing orbital enucleation for locally advanced retinoblastoma (RB) and subsequent radiotherapy. We selected three consecutive patients who underwent orbital enucleation for locally advanced RB and subsequent local radiotherapy showing severe reduction in orbital volume and eyelid length and retraction due to fibrosis, spontaneous local pain exacerbated after digital pressure with no possibility to place an ocular implant. They underwent autologous fat grafting in the orbital cavity and results were evaluated by clinical examination at 5 and 14 days, and 1, 3, 6 months, and 1 year after surgery. A significant release of scar retraction, reduction of fibrosis and orbital rim contraction together with an important improvement of pain symptoms was observed in all patients. The local changes observed enabled an ease placement of an ocular prosthetic implant (implant). No local or systemic complication occurred. Fat grafting is a promising treatment for patients showing radiotherapy related complication in the orbital area and it should be adopted by all oculoplastic surgeon in order to improve pain syndrome creating the ideal local conditions for the placement of an ocular prosthetic implant.

Memantine prevents acute radiation-induced toxicities at hippocampal excitatory synapses.

Background: Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity. Methods: Hippocampal cultures expressing enhanced green fluorescent protein were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy. Excitatory synapses, defined by co-localization of the pre- and postsynaptic markers vesicular glutamate transporter 1 and postsynaptic density protein 95, were also analyzed. Neurons were pretreated with vehicle, the N-methyl-d-aspartate-type glutamate receptor antagonist memantine, or the glutamate scavenger glutamate pyruvate transaminase to assess glutamate signaling. For animal studies, Thy-1-YFP mice were treated with whole-brain radiotherapy or sham with or without memantine. Results: Unlike previously reported long-term losses of dendritic spines, we found that the acute response to radiation is an initial increase in spines and excitatory synapses followed by a decrease in spine/synapse density with altered spine dynamics. Memantine pre-administration prevented this radiation-induced synaptic remodeling. Conclusion: These results demonstrate that radiation causes rapid, dynamic changes in synaptic structural plasticity, implicate abnormal glutamate signaling in cognitive dysfunction following brain irradiation, and describe a protective mechanism of memantine.

Prevalence and Characterization of Thyroid Hemiagenesis in Japan: The Fukushima Health Management Survey.

BACKGROUND: Thyroid hemiagenesis is a rare congenital variant characterized by the lack of development of one thyroid lobe with no clinical manifestations. METHODS: This study was performed to determine the prevalence and characteristics of thyroid hemiagenesis in a normal Japanese population. This cross-sectional study was performed from October 9, 2011, to April 30, 2015. In total, 299,908 children and young adults in the Fukushima Health Management Survey were examined to determine the presence of thyroid agenesis or hemiagenesis. Thyroid width, thickness, and length were measured in 292,452 of these subjects. RESULTS: Thyroid agenesis was diagnosed in 13 subjects, and hemiagenesis was detected in 67 subjects (0.02%; 22.3/100,000 individuals). Although there was no significant sex-related difference (p = 0.067), the female:male ratio was 1.67:1.00. Females were significantly dominant in right hemiagenesis, while there was no difference in left hemiagenesis between males and females. The thyroid volumes at the 2.5th and 97.5th percentiles for age and body surface area were determined for each sex. Multivariate regression analysis showed that a large hemithyroid volume was independently associated with the presence of contralateral hemiagenesis (p < 0.001). CONCLUSION: The prevalence of thyroid hemiagenesis in the present study is in agreement with that reported in other countries. The prevalence of right hemiagenesis was higher in females, and the larger contralateral lobe in patients with rather than without hemiagenesis may have been caused by a compensatory feedback mechanism to prevent hypothyroidism. In addition, the prevalence of hemiagenesis, especially right hemiagenesis, may be affected by sex-related factors similar to those in patients with an ectopic thyroid gland.

[Radiotherapy during pregnancy]. / Radiothérapie et grossesse.

The diagnostic of cancer during pregnancy is a rare and delicate situation. As the developments of the embryo and the human fetus are extremely sensitive to ionizing radiations, the treatment of these tumors should be discussed. The studies - preclinical and clinical - based mostly on exposure accidents show that subdiaphragmatic treatments are possible during pregnancy. When radiotherapy is used, phantom estimations of the dose to the fetus, confirmed by in vivo measurements are required. Irradiation and imaging techniques should be arranged to decrease as much as possible the dose delivered to the fetus and hold below the threshold of 0.1Gy.

Social behavioral testing and brain magnetic resonance imaging in chicks exposed to mobile phone radiation during development.

BACKGROUND: The potential adverse effect of mobile phone radiation is currently an area of great concern in the field of public health. In the present study, we aimed to investigate the effect of mobile phone radiation (900 MHz radiofrequency) during hatching on postnatal social behaviors in chicks, as well as the effect on brain size and structural maturity estimated using 3.0 T magnetic resonance imaging. At day 4 of incubation, 76 normally developing chick embryos were divided into the control group (n = 39) and the radiation group (n = 37). Eggs in the radiation group were exposed to mobile phone radiation for 10 h each day from day 4 to 19 of incubation. Behavioral tests were performed 4 days after hatching. T2-weighted MR imaging and diffusion tensor imaging (DTI) were subsequently performed. The size of different brain subdivisions (telencephalon, optic lobe, brain stem, and cerebellum) and corresponding DTI parameters were measured. The Chi-square test and the student's t test were used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: Compared with controls, chicks in the radiation group showed significantly slower aggregation responses (14.87 ± 10.06 vs. 7.48 ± 4.31 s, respectively; P < 0.05), lower belongingness (23.71 ± 8.72 vs. 11.45 ± 6.53 s, respectively; P < 0.05), and weaker vocalization (53.23 ± 8.60 vs. 60.01 ± 10.45 dB/30 s, respectively; P < 0.05). No significant differences were found between the radiation and control group for brain size and structural maturity, except for cerebellum size, which was significantly smaller in the radiation group (28.40 ± 1.95 vs. 29.95 ± 1.41 cm(2), P < 0.05). The hatching and heteroplasia rates were also calculated and no significant difference was found between the two groups. CONCLUSIONS: Mobile phone radiation exposure during chick embryogenesis impaired social behaviors after hatching and possibly induced cerebellar retardation. This indicates potential adverse effects of mobile phone radiation on brain development.

Maternal occupational exposure to ionizing radiation and major structural birth defects.

BACKGROUND: Ionizing radiation (IR) is known to be carcinogenic and mutagenic, but little is known about the association between maternal occupational exposure to IR and birth defects. METHODS: We studied 38,009 mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. We assessed odds ratios [ORs] for the association between maternal occupations with potential exposure to IR and 39 birth defects. RESULTS: We observed significant odds ratios (ORs) for isolated hydrocephaly (adjusted OR [AOR], 2.1; 95% confidence interval [CI], 1.1-4.2), isolated anotia/microtia (AOR, 2.0; 95% CI, 1.0-4.0), isolated colonic atresia (crude OR, 7.5; 95% CI, 2.5-22.3), isolated omphalocele (AOR, 2.3; 95% CI, 1.1-4.6) and isolated anencephaly (crude OR, 0.23; 95% CI, 0.06-0.94). We also observed a nonsignificant OR for birth defects in aggregate (AOR, 2.0; 95% CI, 0.9-4.6) among mothers with potential occupational exposure to fluoroscopy. CONCLUSION: We assessed 39 birth defects, observing that maternal occupations with potential exposure to IR were associated with a significantly increased risk for 4 birth defects and a significantly protected risk for 1 birth defect. These results should be interpreted cautiously because our measurement of exposure is qualitative, some of these associations may be due to occupational exposures that are correlated with IR and some may be due to chance. However, these findings serve as the first evaluation of these relationships in a large study and may be useful for generating hypotheses for future studies.

Blastopathies and microcephaly in a Chornobyl impacted region of Ukraine.

This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors.

The fisherman's cards: how to address past and future radiation exposures in clinical decision making.

OBJECTIVE. The purpose of this article is to describe how to address patients' past-and future potential-radiation exposures when making an imaging decision in a given situation. CONCLUSION. The Biologic Effects of Ionizing Radiation committee has endorsed a linear no-threshold model to explain the relationship between radiation exposure and cancer risk. This model implies that past and future potential exposures should not impact current decisions. We present an analogy that deconstructs these counterintuitive conclusions and facilitates translation of key radiation risk principles to practice.

Radiation effects on human heredity.

In experimental organisms such as fruit flies and mice, increased frequencies in germ cell mutations have been detected following exposure to ionizing radiation. In contrast, there has been no clear evidence for radiation-induced germ cell mutations in humans that lead to birth defects, chromosome aberrations, Mendelian disorders, etc. This situation exists partly because no sensitive and practical genetic marker is available for human studies and also because the number of people exposed to large doses of radiation and subsequently having offspring was small until childhood cancer survivors became an important study population. In addition, the genome of apparently normal individuals seems to contain large numbers of alterations, including dozens to hundreds of nonfunctional alleles. With the number of mutational events in protein-coding genes estimated as less than one per genome after 1 gray (Gy) exposure, it is unsurprising that genetic effects from radiation have not yet been detected conclusively in humans.

The effect of extremely low frequency electromagnetic fields on pregnancy and fetal growth, and development.

BACKGROUND: Exposure to electromagnetic fields (EMFs) and its effects at different frequencies on living beings has been investigated for decades. However, there are fewer studies that have been conducted on humans, thus this study aims to determine the effect of extremely low frequency (ELF) -EMFs on pregnancy, fetal growth and development in humans. MATERIAL: In this epidemiologic analytical cohort study, cases included pregnant women and their newborns. There were 222 women exposed to ELF-EMFs from high voltage electricity towers and cables during pregnancy and 158 women who had no exposure during pregnancy. Data that included pregnancy duration, neonatal birth weight, length, head circumference, gender and congenital malformations were collected through direct questions, measurements and referral to the registered data of related hospital or health center documents. Collected data was analyzed by SPSS-16. P < 0.05 was considered significant. RESULTS: No significant difference was found in pregnancy duration and preterm labor, neonatal birth weight, length, head circumference and congenital malformations in the two studied groups. CONCLUSION: Although the results of this study have shown no significant effects of ELF-EMFs on human pregnancy, fetal growth and development, taking precautionary measures to reduce exposure to EMFs by pregnant women seems logical. Conducting similar studies is strongly recommended.

Vagus nerve stimulation inhibits seizure activity and protects blood-brain barrier integrity in kindled rats with cortical dysplasia.

AIMS: This study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood-brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD). MAIN METHODS: Pregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed. KEY FINDINGS: Kindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P<0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus. SIGNIFICANCE: The results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD.

Pregnancy after successful cancer treatment: what needs to be considered?

Over the last decade, advances in oncology led to improved treatment results and increasing numbers of long-term cancer survivors. Fulfilling the desire to have children is important for many patients after cancer treatment. Consequently, oncologists, gynecologists and obstetricians are seeing more patients who wish to conceive after treatment. The necessary prerequisites that should be considered when supporting a planned pregnancy after cancer treatment are discussed in this article. The possible consequences of chemotherapy and radiotherapy on the course of pregnancy and the health of the offspring, as well as the interactions between cancer and pregnancy, are reviewed with the focus on childhood cancer, malignant lymphomas, and breast cancer. Despite chemo- or radiotherapy, neither the teratogenic risk nor the risk of adventitious cancers appears to be increased for the offspring of cancer survivors. However, there is a slightly higher risk of miscarriage after chemotherapy. In case of radiation to the uterus, there is a higher risk of premature birth, intrauterine growth retardation, and increased perinatal mortality. The effect is more pronounced after prepubertal radiation than for postpubertal radiation. The former cancer patient's desire to conceive can nevertheless be supported, given that pregnancy and birth are closely monitored.

Prenatal radiation exposure: background material for counseling pregnant patients following exposure to radiation.

Fetal sensitivity to radiation-induced health effects is related to gestational age, and it is highly dependent on fetal dose. Typical fetal doses from diagnostic radiology are usually below any level of concern. Although rare, significant fetal radiation doses can result from interventional medical exposures (fluoroscopically guided techniques), radiation therapy, or radiological or nuclear incidents, including terrorism. The potential health effects from these large radiation doses (possibly large enough to result in acute radiation syndrome in the expectant mother) include growth retardation, malformations, impaired brain function, and neoplasia. If exposure occurs during blastogenesis (and the embryo survives), there is a low risk for congenital abnormalities. (In all stages of gestation, radiation-induced noncancer health effects have not been reported for fetal doses below about 0.05 Gy [5 rad].) The additional risk for childhood cancer from prenatal radiation exposure is about 12% per Gy (0.12%/rad) above the background incidence.

SCAI consensus document on occupational radiation exposure to the pregnant cardiologist and technical personnel.

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterization procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterization personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the fetus of pregnant women in the cardiac catheterization laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterization laboratory. However, radiation exposure among pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted.

[Principal inferences from studies of radiobiological effects for radiation protection purposes].

The most recent Recommendations (Publication 103) issued by the International Commission for Radiological Protection (ICRP) are based on the data that have been published since 1990 up to now. The basic task of the ICRP Committee 1 was to formulate the key implications of studies on radiobiological effects for the purposes of radiological protection. Presented in the paper are the new achievements in the field of biology, radiobiology and radiation epidemiology which were taken into account by the ICRP in the process of Publication 103 preparation. The Recommendations provide present-day values of weighting factors for radiation exposure and tissue weighting factors, as well as radiation detriment and radiogenic risk factors for cancer and genetic diseases. Also considered are tissue reactions to radiation exposure, consequences of in utero exposure and the risks of developing non-cancer diseases for exposed individuals. It should be noted that the key inferences and recommendations are to a considerable degree related to biological effects accounted for by acute and chronic exposure to ionizing radiation in the range of small doses (up to 100 mSv).