Cardiotoxicidad de los quimioterapéuticos diferentes a antraciclinas de la lista oficial de medicamentosde la Caja Costarricense del Seguro Social / Cardiotoxicity of chemotherapeutics other than anthracyclines from the official list of medications of the Costa Rican Social Security Fund

Resumen La Cardio-oncología es una nueva disciplina que busca enfocarse en el tamizaje, monitoreo y tratamiento de los pacientes con cáncer que presentan enfermedad cardiaca durante o después de recibir tratamiento. Esto debido a que el efecto cardiotóxico asociado a los quimioterapéuticos es ampliamente conocido y respaldado por abundantes estudios clínicos. Sin embargo, no es hasta épocas recientes que en Costa Rica se desarrollaron por primera vez Unidades Cardio-oncológicas, los cuales actualmente se ubican en diversos centros médicos de nuestro sistema de salud público. A continuación, se presenta un resumen de las manifestaciones clínicas de las diversas terapias oncológicas diferentes a las antraciclinas que tenemos a disposición en la Caja Costarricense del Seguro Social (CCSS).

Abstract Cardio-oncology is a new discipline that looks to focus on the screening, monitoring and treatment of patients withcancer that show up with heart disease during and after their treatment. This is due to the fact that the cardiotoxic effectsassociated to chemotherapeutics is widely known and backed up with abundant clinical trials. Nevertheless, it is not untilrecently that in Costa Rica the Cardio-oncologic Units were created for the first time, which now can be found in multiplemedical centers of our public health system. Up next, we present a summary of the clinical manifestations of the diversenon-anthracycline oncologic therapies that are available in the "Caja Costarricense del Seguro Social".

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.

Dynamic contrast-enhanced MRI detects acute radiotherapy-induced alterations in mandibular microvasculature: prospective assessment of imaging biomarkers of normal tissue injury.

Normal tissue toxicity is an important consideration in the continued development of more effective external beam radiotherapy (EBRT) regimens for head and neck tumors. The ability to detect EBRT-induced changes in mandibular bone vascularity represents a crucial step in decreasing potential toxicity. To date, no imaging modality has been shown to detect changes in bone vascularity in real time during treatment. Based on our institutional experience with multi-parametric MRI, we hypothesized that DCE-MRI can provide in-treatment information regarding EBRT-induced changes in mandibular vascularity. Thirty-two patients undergoing EBRT treatment for head and neck cancer were prospectively imaged prior to, mid-course, and following treatment. DCE-MRI scans were co-registered to dosimetric maps to correlate EBRT dose and change in mandibular bone vascularity as measured by Ktrans and Ve. DCE-MRI was able to detect dose-dependent changes in both Ktrans and Ve in a subset of patients. One patient who developed ORN during the study period demonstrated decreases in Ktrans and Ve following treatment completion. We demonstrate, in a prospective imaging trial, that DCE-MRI can detect dose-dependent alterations in mandibular bone vascularity during chemoradiotherapy, providing biomarkers that are physiological correlates of acute of acute mandibular vascular injury and recovery temporal kinetics.

Quantitative and noninvasive assessment of prenatal X-ray-induced CNS abnormalities using magnetic resonance imaging.

Our purpose was to noninvasively assess formation of the microvasculature, blood-brain barrier (BBB) and blood-CSF barrier formation of prenatal X-ray-induced CNS abnormalities using quantitative MRI. Eight pregnant female Sprague-Dawley rats were divided into two groups consisting of control and X-irradiated animals. After birth, 20 neonatal male rats were divided into four groups of five rats. To evaluate the development of the BBB, changes in T(1) induced by Gd-DTPA were compared quantitatively in normal and prenatally irradiated animals in the formative period 1 to 2 weeks after birth. To assess the abnormalities of the microvasculature, quantitative perfusion MRI and MR angiography were also used. Histology was also performed to evaluate the BBB (albumin) and vascular endothelial cells (laminin). Decreased cerebral blood flow (CBF) and angioarchitectonic abnormalities were observed in the prenatally irradiated rats. However, abnormalities of the BBB and blood-CSF barrier were not observed using Gd-enhanced MRI and albumin staining. Quantitative perfusion MRI, MR angiography and Gd-enhanced T(1) mapping are useful for assessing CNS disturbance after prenatal exposure to radiation. These techniques provide important diagnostic information for assessing the condition of patients during the early stages of life after accidental or unavoidable prenatal exposure to radiation.

Lauriston S. Taylor lecture: fifty years of scientific research: the importance of scholarship and the influence of politics and controversy.

Over the past 50 years our laboratory has performed and published many studies in the fields of teratology, radiation biology and radiation embryology. The early work took place when I was a research employee at the University of Rochester Manhattan Project in 1944 and where I had my introduction to embryology and genetics. Over the years our lab has provided consultations dealing with the risks of various environmental toxicant exposures during pregnancy. With the advent of the Internet, consulting has become more rapid and efficient. In the past year our pregnancy Web site of the Health Physics Society received approximately 154,000 hits, of which over a thousand contacts were still quite anxious after reading the Web site answers and requested a personal consultation. From this extensive experience we have learned that many physicians and other counselors are not prepared to counsel patients concerning radiation risks. Approximately 8% of the patient contacts who have consulted a professional have been provided with inaccurate information that would have resulted in an unnecessary interruption of a wanted pregnancy. There are five areas of radiation embryology that are considered to be controversial. 1) Can the fetus be harmed by ionizing radiation if the fetus is not directly exposed? 2) Is the production of mental retardation from radiation during pregnancy a threshold phenomenon? 3) Does fractionation and protraction of radiation decrease the magnitude of the reproductive and developmental risks? 4) Is there a period during pregnancy when radiation will result in an increased mortality but not an increase in malformations? 5) How sensitive is the fetus to the oncogenic effects of radiation? We utilize the scientific information obtained from studies in these five areas to counsel patients concerning pregnancy radiation risks. The willingness and persistence of scientists to debate the controversial aspects of this research and apply the best available scientific information to assist patients in turmoil about the risks of radiation to themselves and their offspring has saved thousand of lives and changed family histories.

Cover-up of the effects of internal exposure by residual radiation from the atomic bombing of Hiroshima and Nagasaki.

The criteria certifying atomic bomb disease adopted by the Japanese government are very different from the actual state of the survivors. The criteria are based on epidemiological research by the Radiation Effects Research Foundation, the successor to the Atomic Bomb Casualty Commission (ABCC). The ABCC studied only the effects of primary radiation from the atomic bombing on the survivors of Hiroshima and Nagasaki, and ignored the damage from residual radiation. Analysis of the incidence of acute radiation disease, the rate of chromosomal aberrations, and the relative risks of chronic disease among the survivors, shows that the effects of residual radiation from fallout exceeds that of primary radiation in the area more than 1.5-1.7 km distant from the hypocentre of the Hiroshima bombing. The effects of internal exposure due to intake of tiny radioactive particles are more severe than those of external exposure, explaining the difference between the official criteria and the actual state of the survivors.

Clinical validation of the LKB model and parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy.

The choice of the appropriate model and parameter set in determining the relation between the incidence of radiation pneumonitis and dose distribution in the lung is of great importance, especially in the case of breast radiotherapy where the observed incidence is fairly low. From our previous study based on 150 breast cancer patients, where the fits of dose-volume models to clinical data were estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the relative seriality is significantly better than the LKB NTCP model. However, the estimation of the different NTCP models was based on their goodness-of-fit on clinical data, using various sets of published parameters from other groups, and this fact may provisionally justify the results. Hence, we sought to investigate further the LKB model, by applying different published parameter sets for the very same group of patients, in order to be able to compare the results. It was shown that, depending on the parameter set applied, the LKB model is able to predict the incidence of radiation pneumonitis with acceptable accuracy, especially when implemented on a sub-group of patients (120) receiving [see text]|EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain radiobiological model on a given clinical case is closely related to the selection of the proper scoring criteria and parameter set as well as to the compatibility of the clinical case from which the data were derived.

Is it safe to work with iodine-131 if you are pregnant? A risk assessment for nuclear medicine staff involved with cleaning and decontamination.

In the UK, Regulation 8(5) of the Ionising Radiation Regulations 1999 (In: Work with ionising radiation. London: HSE Books, 2000) requires employers to ensure that the dose to the foetus of a pregnant worker is unlikely to exceed 1 mSv. Risk assessments are required which are capable of predicting the total foetal dose. Work involving 131I is a particular problem. Foetal dose coefficients from the maternal intake of 131I for all stages of pregnancy have been published (Phipps AW, Smith TJ, Fell TP, Harrison JD. Doses to the embryo/fetus and neonate from intake of radionuclides by the mother. NRPB contract research report 397/2001. Didcot, Oxon.: National Radiological Protection Board (NRPB), 2001. Available on website www.hse.gov.uk/research/crr_pdf/2001/crr01397.pdf), and range from 0.08 microSv x kBq(-1) at conception to 55 microSv x kBq(-1) at week 35. This paper examines one aspect of work in a nuclear medicine department in which the source of 131I is uncontrolled to determine whether the risk assessment indicates that restrictions should apply to a pregnant member of staff. Following in-patient treatment with 131I, rooms are checked and decontaminated before being decontrolled. Cleaning staff were monitored immediately after the cleaning process with hand-held detectors and by whole-body monitoring. Total body contamination ranged up to 3.2 kBq; after a change of clothing, the maximum remaining activity was 0.68 kBq. Acquired contamination correlated with the total activity administered to the patient. Hand-held monitoring rarely detected contamination. Whole-body monitoring indicated that the levels of contamination encountered could lead to a dose limit for the foetus being exceeded. These levels are very difficult to detect with hand-held monitoring. The conclusion to be drawn is that pregnant staff should be excluded from situations in which accidents could arise, or where the source of 131I is uncontrolled or unpredictable.

[Sanitary assessment of radon hazards in residential buildings]. / Gigienicheskaia otsenka opasnosti radona v zhilykh pomeshcheniiakh.

The authors have constructed models including that of dose-effect of the content of decay products, that of the volumetric activity of radon in the apartments, and that of biological human responses. They have found specific features of female reproduction dysfunction, perinatal, general, and cancer morbidity and mortality. The maximum ineffective radon concentration upon chronic exposure has been established by using dosage simulation of the frequency of genetic disorders (small malformations).

[Experimental assessment of adaptive possibilities after chronic prenatal exposure to gamma irradiation at various absorbed doses]. / Eksperimental'naia otsenka adaptivnykh vozmozhnostei organizma posle antenatal'nogo khronicheskogo deistviia gamma-izlucheniia v raznykh pogloshchennykh dozakh.

The purpose of the investigation is the study of dose-response relationship at the antenatal exposure of low level ionizing radiation (137Cs, 1.0-1.25; 1.7-1.9 and 2.3-2.5 Gy during 20 days). The decrease of body weight in pregnant females and antenatal embryonic mortality at the doses 2.3-2.5 Gy are revealed. Physical postnatal anomalies with decrease of the adaptation were estimated by the strength endurance after antenatal exposure of gamma-rays at the doses of 1.0-2.5 Gy.

Tritium risk assessment.

Estimates of the health risks in humans from low-level exposure to tritium are presented. The health risks considered are those for cancer, genetic effects, and developmental abnormalities from exposures in utero. Because direct risk information for these effects is not available from human exposures to tritium, the following approach was used. Excess risks for the effects given following low-level exposure to x rays or gamma rays were estimated from available human epidemiological data using appropriate dose-rate effectiveness factors. These human-risk estimates for low-level x rays or gamma rays were then multiplied by the appropriate best-estimate relative biological effectiveness for tritium, taking into account differences in effectiveness of comparison radiations. The resultant lifetime risk coefficients for low-level exposure to tritiated water are as follows. For cancer mortality, the most probable risk (50th percentile) is 81 x 10(-6) mGy-1 and the 90% confidence interval is 38 to 185 x 10(-6) mGy-1. For genetic effects in the first generation after exposure the risk is 7.9 x 10(-6) mGy-1, with a 90% confidence interval of 3.8 to 16.3 x 10(-6) mGy-1. For developmental effects from low-level tritiated water exposures in utero, the risk is uncertain but is estimated to be < 400 x 10(-6) mGy-1. The risks from exposure to organically bound tritiated molecules are estimated to range from values that are similar to those for tritiated water to about a factor of 2 higher.

1992 assessment of radiation risk from dental radiography.

Recent studies suggest that the lifetime cancer risks from exposure to low levels of ionizing radiation may be greater than previously estimated. This review first summarizes the findings of these studies as they pertain to dental radiology, then uses their concepts in combination with dosimetry from the dental literature to estimate the radiation risk from dental radiology. Estimation of risk from groups of exposed individuals requires use of mathematical models that fit the epidemiological data. The ICRP estimates that a single brief whole-body exposure of 1 Gy to 10,000 people results in about 500 additional cancer deaths over the lifetime of the exposed individuals, assuming a dose rate effectiveness factor of 2 for cancers other than leukaemia. Leukaemias are seen as a wave from 5 to 30 years following exposure. Cancers other than leukaemia typically start to appear about 10 years following exposure and remain in excess for as long as most exposed populations are followed, presumably for the lifetime of the exposed individuals. The gonadal dose is so small from dental radiography that the risk of heritable defects is negligible in comparison with the somatic risk. The dental literature contains several studies reporting sufficient dosimetric data for radiosensitive sites in the head and neck to allow estimation of the risk of fatal cancers from intra-oral and panoramic radiography. The highest estimated risks (using the ICRP data) are for leukaemia (bone marrow), thyroid and bone surface cancer. The total risk is estimated to be 2.5 fatal malignancies per 10(6) full-mouth examinations made with D-speed film and round collimation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Environmental pollution and congenital abnormalities according to the data of environmental health monitoring]. / Zagriaznenie okruzhaiushchei sredy i vrozhdennye poroki razvitiia po materialam gigienicheskogo monitoringa.

Study of the environmental pollution (ambient air, drinking water, food and fodder) in southern Ukraine industrial region and study of congenital developmental defects were carried out. 78,678 newborns were examined. The most significant environmental factors responsible for congenital developmental defects, as authors proposed, were the ambient air pollution and environmental radioactivity.

Pregnancy outcome in Finland after the Chernobyl accident.

The explosion at the Chernobyl nuclear power plant caused radioactive fallout in Finland in April-May 1986. The fallout was unevenly distributed geographically, and, accordingly, the country was divided into 3 fallout zones. Whole-body radioactivity measurements of randomly chosen persons showed that the regional differences prevailed throughout the following 2 years. Data for legal abortions, registered congenital malformations as well as preterm births and stillbirths of malformed children were collected. The corresponding expected figures were obtained from statistics from 1984 and 1985. No differences in the expected/observed rates of the above parameters were detected.

PIP: The effects of the 1986 Chernobyl accident on Finland are reported. Legal abortions, registered congenital malformations, preterm births, and stillbirths showed no differences in observed vs. expected rates after the accident. The limitations are that the population base is small, the detection system is incomplete, no reliable data are available on early abortions, and germinal mutations were not presently analyzed. Measurement of radiocesium (Cs 134 and 137) was accomplished by the Research Institute for Social Security with a stratified random sample of 380 people. 5 fallout zones differentiated groups, which were then collapsed into 3 groups. Regional differences in levels persisted into 1988. The Finnish Register of Congenital Malformations provided the compulsory data on congenital malformations. The 3 groups (children born before the accident in 1984-85, in the latter half of 1986, and in 1987) were analyzed in the 3 zones during 2 study periods (August-December 1986 and January-December 1987). Monthly analysis of induced abortions showed no increase following the accident. There was a slight decrease in births between January and March 1987, which is believed to be related to anxiety reinforced by public advice. There were no differences between expected and observed congenital defects in the 2 study periods. Preterm and stillbirths followed a similar pattern. The analysis showed no association between the temporal and spatial variations in radioactivity and variable incidence of congenital malformations.

The inclusion of an assay for inherited congenital malformations in the assessment of mutagenicity.

A number of national guidelines and regulations on the mutagenicity of chemical substances mandate the assessment of inherited genetic effects. While inherited congenital malformations represent a major component of genetically-based adverse human health effects, tests for such effects are not used by regulatory agencies to evaluate inherited genetic effects. This paper is intended to highlight some of the salient characteristics of inherited congenital malformations which promote a rationale for their use in a regulatory context.