s, where D The linear functions obtained by Rowland et al.67 were: where D Massachusetts Department of Public Health | Bureau of Environmental 1959. Kolenkow30 presented his results as depth-dose curves for the radiation delivered from bone but made no comment on epithelial cell location. It shows no signs of significant secretory activity but is always moist. The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al. Since it is the bombardment of target tissues and not the absorption of energy by mineral bone that confers risk, the apparent carcinogenic potency of these three isotopes differs markedly when expressed as a function of mean skeletal absorbed dose, which is a common way of presenting the data. Posted at 20:22h in disney monologues, 2 minutes by what happened to the other winter soldiers le bossu de notre dame paroles infernal Likes The average skeletal doses were later calculated to be 23,000 and 9,600 rad, respectively, which are rather substantial values. In simple terms, the main issue has been linear or nonlinear, threshold or nonthreshold. How are people exposed to radium? Adults and juveniles were treated separately. These authors concluded that there was no relationship between radium level and the occurrence of leukemia. Research should continue on the cells at risk for bone-cancer induction, on cell behavior over time, including where the cells are located in the radiation field at various stages of their life cycles, on tissue modifications which may reduce the radiation dose to the cells, and on the time behavior and distribution of radioactivity in bone. A., P. Isaacson, R. M. Hahne, and J. Kohler. In the model, this dose is directly proportional to the average skeletal dose, and tumor rate is an analog of the response parameter, which is bone sarcomas per person-year at risk. Equation 4-1 was modified from the general form adopted in the BEIR III report:54. The British patients that Loutit described34 also may have experienced high radiation exposures; two were radiation chemists whose radium levels were reported to fall in the range of 0.3 to 0.5 Ci, both of whom probably had many years of occupational exposure to external radiation. Also, they were continuously subjected to alpha radiation from another source: the radon in expired breath. Two compartments are usually identified in the skeleton, a bone surface compartment in which the radium is retained for short periods and a bone volume compartment in which it is retained for long periods. The thickness of the simple columnar epithelium, including the cilia, is between 30 and 45 m. As the response variable, they used carcinomas per person-year at risk and regressed it against a measure of systemic intake of 226Ra and against average skeletal dose. In the latter analysis,69 the only acceptable fit based on year of entry into the study is: where I and D Comparable examples can be given for each expression of Rowland et al. The cumulative tumor risk (bone sarcomas/106 person-rad) was similar in the juvenile and adult patients under the dosimetric assumptions used. a. The statistical uncertainty in the coefficient is determined principally by the variance in the high-dose data, that is, at exposure levels for which the observed number of tumors is nonzero. i Recent analyses with a proportional hazards model led to a modification of the statement about the adequacy of the linear curve, as will be discussed later. If this is true for all dose levels and all bones, this would ensure that the ratio of lifetime doses for these different components of the radium distribution was about the same as the ratio of terminal dose rates determined from microdistribution studies. EXtensive Experience with human beings and numerous animal experiments have shown beyond doubt that a portion of any quantity of radium which enters the body will be deposited in the bones, and that osteogenic sarcomas are often associated with small quantities of radium which have been fixed in the bone for considerable periods of time (1). The question remained open, however, whether the health effects were threshold phenomena that would not occur below certain exposure or dose levels, or whether the risk would continue at some nonzero level until the exposure was removed altogether. The nonuniform deposition in bones and the skeleton is mirrored by a nonuniformity at the microscopic level first illustrated with high-resolution nuclear track methods by Hoecker and Roofe for rat27 and human28 bone. Evans, R. D., A. T. Keane, and M. M. Shanahan. and those done earlier was division of the radium-exposed subjects into subpopulations defined by type of exposure, that is, radium-dial workers (mostly dial painters), those medically exposed, and others. Although this city draws its water from Lake Michigan, where the radium concentration is reported as 0.03 pCi/liter, the age- and sex-adjusted osteosarcoma mortality rate was 6.3/million/yr, which is larger than that found for the towns with elevated radium levels in their water. s is the average skeletal dose in gray (1 Gy is 100 rad). On the microscale the chance of a single cell being hit more than once diminishes with dose; this would argue for the independent action of separate dose increments and the squaring of separate dose increments before the addition of risks. 1986. This keeps it from accumulating inside your home. Based on their treatment of the data, Mays et al.49 made the following observation: ''We have fit a variety of dose-response relationships through our follow-up data, including linear (y = ax), linear multiplied by a protraction factor, dose-squared exponential (y = ax Radium-226 adheres quickly to solids and does not migrate far from its place of release. The radium might exist in ionic form, although it is known to form complexes with some compounds of biological interest under appropriate physiological conditions; it apparently does not form complexes with amino acids. If there were a continuous exposure of 1 rad/yr, the tumor rate would rise to an asymptotic value. Diffusion models for the sinuses have not been proposed, but work has been done on the movement of 220Rn through tissue adjacent to bone surfaces. . There may be an excess of leukemia among the adults, but the evidence is weak. Finkel, A. J., C. E. Miller, and R. J. Hasterlik. Therefore, estimates of the cumulative average skeletal dose may not be adequate to quantitate the biological insult. Because CLL is not considered to be induced by radiation, the latter case was assumed to be unrelated to the radium exposure. . i, and when based on skeletal dose assumes that tumor rate is constant for a given dose D Mays et al.50 reported on the follow-up of 899 children and adults who received weekly or twice-weekly intravenous injections of 224Ra, mainly for the treatment of tuberculosis and ankylosing spondylitis. In a report by Finkel et al.,18 mention is made of seven cases of leukemia and aplastic anemia in a series of 293 persons, most of whom had acquired radium between 1918 and 1933. Cancer Incidence Rate among Persons Exposed to Different Concentrations of Radium in Drinking Water. It is striking, however, that the graph for radium in humans61,62 lies parallel to the graphs for all long-lived nuclides in dogs,60 where death from bone tumor tends to occur earlier than death from other causes. However, no mention of such cases appear in his report. Radiogenic tumors in the radium and mesothorium cases studied at M.I.T. The upper curve of the 68% envelope is nearly coincident with the upper boundary of the shaded envelope. For example, if D Importantly, because alpha particles have a very short range (<100 m), there is limited damage to surrounding normal tissues, including bone marrow [ 7, 9 ]. Unless bone cancer induced by 226Ra and 228Ra is a pure, single-hit phenomenon, some interaction of dose increments is expected, although perhaps it is a less strong interaction than is consistent with squaring the total accumulated intake when intake is continuous. i is the total systemic intake of 226Ra plus 2.5 times the total systemic intake of 228Ra, expressed in microcuries. Wick et al.95 reported on another study of Germans exposed to 224Ra. i = 0.5 Ci. The original cases of radium poisoning were discovered by symptom, not by random selection from a defined population. Control cities where the radium content of the public water supply contained less than 1 pCi/liter were matched for size with the study cities. The third analysis was carried out by Raabe et. The 9% envelope was obtained by allowing the parameters in the function to vary by 2 standard errors on either side of the mean and emphasizes that the standard errors obtained by least-square fitting underestimate the uncertainty at low doses. As of December 1982, the average followup time was 16 yr for patients injected after 1951 with lower doses of 224Ra for the treatment of ankylosing spondylitis.93 Of 1,426 patients who had been traced, the vital status for 1,095 of them was known. When combined with the mean value for diffuse to average concentration of about 0.5,65,77 this indicates that the hot-spot concentration is typically about 7 times the diffuse concentration and that typical hot-spot doses would be roughly an order of magnitude greater than typical diffuse doses. Deposits in the bone with nonuniform distribution, following the decay of 226Ra in the bone. l That Define the Dose-Response Envelopes in Figure 4-5. Following the consolidation of the U.S. radium cases into a single study at the Argonne National Laboratory, Polednak57 reviewed the mortality of women first employed before 1930 in the U.S. radium-dial-painting industry. In general, the data from humans suffice to establish radium retention in the bone volume compartment. D 1983. As dose diminishes below the levels that have been observed to induce bone cancer, cell survival in the vicinity of hot spots increases, thus increasing the importance of hot spots to the possible induction of bone cancer at lower doses. u and I Book, and N. J. D The best fit of response against systemic intake was obtained for the functional form I = C + D, obtained from Equation 4-21 by setting = = 0. The third analysis that corrects for competing risks was performed by Chemelevsky et al.9 using a proportional hazards model. why does radium accumulate in bones? Negative values have been avoided in practical applications by redefining the dose-response functions at low exposure levels. The weight of available evidence suggests that bone sarcomas arise from cells that accumulate their dose while within an alpha-particle range. Why does radium accumulate in bones?-Radium accumulates in bones because radium essentially masks itself as calcium. The asymptotic value of this function is 200 bone sarcomas/million person-rad, which is considered applicable both to childhood and adult exposure. As the dose parameter, absorbed dose in endosteal tissue was used, computed from the injection levels, in micrograms per kilogram, using conversion factors based on body weight and relative distribution factors similar to those of Marshall et al.40 but altered to take into account the dependence of stopping power on energy. 1959. International Commission on Radiological Protection (ICRP). The fundamental reason for this is the chemical similarity between calcium and radium. The error bars on each point are a greater fraction of the value for the point here than in Figure 4-6, because the subdivision into dose groups has substantially reduced the number of subjects that contributes to each datum point. s is the average skeletal dose from 226Ra plus 1.5 times the average skeletal dose from 228Ra, expressed in rad. For animals given a single injection, hot spots probably played a role similar to that played by diffuse radioactivity. Figure 4-2 is a summary of data on the whole-body retention of radium in humans.29 Whole-body retention diminishes as a power function of time. It does, however, deposit in soft tissue and there is a potential for radiation effects in these tissues. It should be borne in mind that hot-spot burial only occurs to a significant degree following a single intake or in association with a series of fractions delivered at intervals longer than the time of formation of appositional growth sites, about 100 days in humans. -kx), and a threshold function. With environmental radiation, in which large populations are exposed, a spectrum of ages from newborn to elderly is represented. Proper handling procedures are necessary to avoid radiation risks. Spiers et al.83 note that this number from a total of 10 is not dissimilar from the 3.6 expected in the general population. Radon is known to accumulate in homes and buildings. These body burden estimates presumably include contributions from both 226Ra and 228Ra. The first is that of Rowland et al.67 in which estimated systemic intake (D) rather than average skeletal absorbed dose was used as the dose parameter and functions of the form (C + D + D2) exp(-D) were fitted to the data. For the percent of exposed persons with bone sarcomas, Mays and Lloyd44 give 0.0046% D The theory of bone-cancer induction by alpha particles38 offers some insights. As a convenient working hypothesis, in several papers it has been assumed that the linear form is the correct one, leading to analyses that are illuminating and easily understood. Decay series for radium-228, a beta-particle emitter, and radium-224, an alpha-particle emitter, showing the principal isotopes present, the primary radiations emitted (, , or both), and the half-lives (s = second, m = minute, h (more). Health Risks of Radon and Other Internally Deposited Alpha-Emitters: Beir IV. In spite of these differences, 224Ra has been found to be an efficient inducer of bone cancer. Carcinomas of the paranasal sinuses and mastoid air cells may invade the cranial nerves, causing problems with vision or hearing3,23 prior to diagnosis. 's analysis, the 228Ra dose was given a weight 1.5 times that of 226Ra. This is not a trivial point since rate of loss could be greatly affected by the high radiation doses associated with hot spots. Clearance through the ventilatory ducts is rapid when they are open. The sinus ducts are normally open but can Be plugged by mucus or the swelling of mucosal tissues during illness. The identities of these cells are uncertain, and their movements and life cycles are only partly understood. In this enlarged study, three cases of leukemia were recorded in the pre-1930 population, which yielded a standard mortality ratio of 73. In the case of 224Ra, the relatively short half-life of the material permits an estimation of the dose to bone or one that is proportional to that received by the cells at risk.
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Massachusetts Department of Public Health | Bureau of Environmental 1959. Kolenkow30 presented his results as depth-dose curves for the radiation delivered from bone but made no comment on epithelial cell location. It shows no signs of significant secretory activity but is always moist. The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al. Since it is the bombardment of target tissues and not the absorption of energy by mineral bone that confers risk, the apparent carcinogenic potency of these three isotopes differs markedly when expressed as a function of mean skeletal absorbed dose, which is a common way of presenting the data. Posted at 20:22h in disney monologues, 2 minutes by what happened to the other winter soldiers le bossu de notre dame paroles infernal Likes The average skeletal doses were later calculated to be 23,000 and 9,600 rad, respectively, which are rather substantial values. In simple terms, the main issue has been linear or nonlinear, threshold or nonthreshold. How are people exposed to radium? Adults and juveniles were treated separately. These authors concluded that there was no relationship between radium level and the occurrence of leukemia. Research should continue on the cells at risk for bone-cancer induction, on cell behavior over time, including where the cells are located in the radiation field at various stages of their life cycles, on tissue modifications which may reduce the radiation dose to the cells, and on the time behavior and distribution of radioactivity in bone. A., P. Isaacson, R. M. Hahne, and J. Kohler. In the model, this dose is directly proportional to the average skeletal dose, and tumor rate is an analog of the response parameter, which is bone sarcomas per person-year at risk. Equation 4-1 was modified from the general form adopted in the BEIR III report:54. The British patients that Loutit described34 also may have experienced high radiation exposures; two were radiation chemists whose radium levels were reported to fall in the range of 0.3 to 0.5 Ci, both of whom probably had many years of occupational exposure to external radiation. Also, they were continuously subjected to alpha radiation from another source: the radon in expired breath. Two compartments are usually identified in the skeleton, a bone surface compartment in which the radium is retained for short periods and a bone volume compartment in which it is retained for long periods. The thickness of the simple columnar epithelium, including the cilia, is between 30 and 45 m. As the response variable, they used carcinomas per person-year at risk and regressed it against a measure of systemic intake of 226Ra and against average skeletal dose. In the latter analysis,69 the only acceptable fit based on year of entry into the study is: where I and D Comparable examples can be given for each expression of Rowland et al. The cumulative tumor risk (bone sarcomas/106 person-rad) was similar in the juvenile and adult patients under the dosimetric assumptions used. a. The statistical uncertainty in the coefficient is determined principally by the variance in the high-dose data, that is, at exposure levels for which the observed number of tumors is nonzero. i Recent analyses with a proportional hazards model led to a modification of the statement about the adequacy of the linear curve, as will be discussed later. If this is true for all dose levels and all bones, this would ensure that the ratio of lifetime doses for these different components of the radium distribution was about the same as the ratio of terminal dose rates determined from microdistribution studies. EXtensive Experience with human beings and numerous animal experiments have shown beyond doubt that a portion of any quantity of radium which enters the body will be deposited in the bones, and that osteogenic sarcomas are often associated with small quantities of radium which have been fixed in the bone for considerable periods of time (1). The question remained open, however, whether the health effects were threshold phenomena that would not occur below certain exposure or dose levels, or whether the risk would continue at some nonzero level until the exposure was removed altogether. The nonuniform deposition in bones and the skeleton is mirrored by a nonuniformity at the microscopic level first illustrated with high-resolution nuclear track methods by Hoecker and Roofe for rat27 and human28 bone. Evans, R. D., A. T. Keane, and M. M. Shanahan. and those done earlier was division of the radium-exposed subjects into subpopulations defined by type of exposure, that is, radium-dial workers (mostly dial painters), those medically exposed, and others. Although this city draws its water from Lake Michigan, where the radium concentration is reported as 0.03 pCi/liter, the age- and sex-adjusted osteosarcoma mortality rate was 6.3/million/yr, which is larger than that found for the towns with elevated radium levels in their water. s is the average skeletal dose in gray (1 Gy is 100 rad). On the microscale the chance of a single cell being hit more than once diminishes with dose; this would argue for the independent action of separate dose increments and the squaring of separate dose increments before the addition of risks. 1986. This keeps it from accumulating inside your home. Based on their treatment of the data, Mays et al.49 made the following observation: ''We have fit a variety of dose-response relationships through our follow-up data, including linear (y = ax), linear multiplied by a protraction factor, dose-squared exponential (y = ax Radium-226 adheres quickly to solids and does not migrate far from its place of release. The radium might exist in ionic form, although it is known to form complexes with some compounds of biological interest under appropriate physiological conditions; it apparently does not form complexes with amino acids. If there were a continuous exposure of 1 rad/yr, the tumor rate would rise to an asymptotic value. Diffusion models for the sinuses have not been proposed, but work has been done on the movement of 220Rn through tissue adjacent to bone surfaces. . There may be an excess of leukemia among the adults, but the evidence is weak. Finkel, A. J., C. E. Miller, and R. J. Hasterlik. Therefore, estimates of the cumulative average skeletal dose may not be adequate to quantitate the biological insult. Because CLL is not considered to be induced by radiation, the latter case was assumed to be unrelated to the radium exposure. . i, and when based on skeletal dose assumes that tumor rate is constant for a given dose D Mays et al.50 reported on the follow-up of 899 children and adults who received weekly or twice-weekly intravenous injections of 224Ra, mainly for the treatment of tuberculosis and ankylosing spondylitis. In a report by Finkel et al.,18 mention is made of seven cases of leukemia and aplastic anemia in a series of 293 persons, most of whom had acquired radium between 1918 and 1933. Cancer Incidence Rate among Persons Exposed to Different Concentrations of Radium in Drinking Water. It is striking, however, that the graph for radium in humans61,62 lies parallel to the graphs for all long-lived nuclides in dogs,60 where death from bone tumor tends to occur earlier than death from other causes. However, no mention of such cases appear in his report. Radiogenic tumors in the radium and mesothorium cases studied at M.I.T. The upper curve of the 68% envelope is nearly coincident with the upper boundary of the shaded envelope. For example, if D Importantly, because alpha particles have a very short range (<100 m), there is limited damage to surrounding normal tissues, including bone marrow [ 7, 9 ]. Unless bone cancer induced by 226Ra and 228Ra is a pure, single-hit phenomenon, some interaction of dose increments is expected, although perhaps it is a less strong interaction than is consistent with squaring the total accumulated intake when intake is continuous. i is the total systemic intake of 226Ra plus 2.5 times the total systemic intake of 228Ra, expressed in microcuries. Wick et al.95 reported on another study of Germans exposed to 224Ra. i = 0.5 Ci. The original cases of radium poisoning were discovered by symptom, not by random selection from a defined population. Control cities where the radium content of the public water supply contained less than 1 pCi/liter were matched for size with the study cities. The third analysis was carried out by Raabe et. The 9% envelope was obtained by allowing the parameters in the function to vary by 2 standard errors on either side of the mean and emphasizes that the standard errors obtained by least-square fitting underestimate the uncertainty at low doses. As of December 1982, the average followup time was 16 yr for patients injected after 1951 with lower doses of 224Ra for the treatment of ankylosing spondylitis.93 Of 1,426 patients who had been traced, the vital status for 1,095 of them was known. When combined with the mean value for diffuse to average concentration of about 0.5,65,77 this indicates that the hot-spot concentration is typically about 7 times the diffuse concentration and that typical hot-spot doses would be roughly an order of magnitude greater than typical diffuse doses. Deposits in the bone with nonuniform distribution, following the decay of 226Ra in the bone. l That Define the Dose-Response Envelopes in Figure 4-5. Following the consolidation of the U.S. radium cases into a single study at the Argonne National Laboratory, Polednak57 reviewed the mortality of women first employed before 1930 in the U.S. radium-dial-painting industry. In general, the data from humans suffice to establish radium retention in the bone volume compartment. D 1983. As dose diminishes below the levels that have been observed to induce bone cancer, cell survival in the vicinity of hot spots increases, thus increasing the importance of hot spots to the possible induction of bone cancer at lower doses. u and I Book, and N. J. D The best fit of response against systemic intake was obtained for the functional form I = C + D, obtained from Equation 4-21 by setting = = 0. The third analysis that corrects for competing risks was performed by Chemelevsky et al.9 using a proportional hazards model. why does radium accumulate in bones? Negative values have been avoided in practical applications by redefining the dose-response functions at low exposure levels. The weight of available evidence suggests that bone sarcomas arise from cells that accumulate their dose while within an alpha-particle range. Why does radium accumulate in bones?-Radium accumulates in bones because radium essentially masks itself as calcium. The asymptotic value of this function is 200 bone sarcomas/million person-rad, which is considered applicable both to childhood and adult exposure. As the dose parameter, absorbed dose in endosteal tissue was used, computed from the injection levels, in micrograms per kilogram, using conversion factors based on body weight and relative distribution factors similar to those of Marshall et al.40 but altered to take into account the dependence of stopping power on energy. 1959. International Commission on Radiological Protection (ICRP). The fundamental reason for this is the chemical similarity between calcium and radium. The error bars on each point are a greater fraction of the value for the point here than in Figure 4-6, because the subdivision into dose groups has substantially reduced the number of subjects that contributes to each datum point. s is the average skeletal dose from 226Ra plus 1.5 times the average skeletal dose from 228Ra, expressed in rad. For animals given a single injection, hot spots probably played a role similar to that played by diffuse radioactivity. Figure 4-2 is a summary of data on the whole-body retention of radium in humans.29 Whole-body retention diminishes as a power function of time. It does, however, deposit in soft tissue and there is a potential for radiation effects in these tissues. It should be borne in mind that hot-spot burial only occurs to a significant degree following a single intake or in association with a series of fractions delivered at intervals longer than the time of formation of appositional growth sites, about 100 days in humans. -kx), and a threshold function. With environmental radiation, in which large populations are exposed, a spectrum of ages from newborn to elderly is represented. Proper handling procedures are necessary to avoid radiation risks. Spiers et al.83 note that this number from a total of 10 is not dissimilar from the 3.6 expected in the general population. Radon is known to accumulate in homes and buildings. These body burden estimates presumably include contributions from both 226Ra and 228Ra. The first is that of Rowland et al.67 in which estimated systemic intake (D) rather than average skeletal absorbed dose was used as the dose parameter and functions of the form (C + D + D2) exp(-D) were fitted to the data. For the percent of exposed persons with bone sarcomas, Mays and Lloyd44 give 0.0046% D The theory of bone-cancer induction by alpha particles38 offers some insights. As a convenient working hypothesis, in several papers it has been assumed that the linear form is the correct one, leading to analyses that are illuminating and easily understood. Decay series for radium-228, a beta-particle emitter, and radium-224, an alpha-particle emitter, showing the principal isotopes present, the primary radiations emitted (, , or both), and the half-lives (s = second, m = minute, h (more). Health Risks of Radon and Other Internally Deposited Alpha-Emitters: Beir IV. In spite of these differences, 224Ra has been found to be an efficient inducer of bone cancer. Carcinomas of the paranasal sinuses and mastoid air cells may invade the cranial nerves, causing problems with vision or hearing3,23 prior to diagnosis. 's analysis, the 228Ra dose was given a weight 1.5 times that of 226Ra. This is not a trivial point since rate of loss could be greatly affected by the high radiation doses associated with hot spots. Clearance through the ventilatory ducts is rapid when they are open. The sinus ducts are normally open but can Be plugged by mucus or the swelling of mucosal tissues during illness. The identities of these cells are uncertain, and their movements and life cycles are only partly understood. In this enlarged study, three cases of leukemia were recorded in the pre-1930 population, which yielded a standard mortality ratio of 73. In the case of 224Ra, the relatively short half-life of the material permits an estimation of the dose to bone or one that is proportional to that received by the cells at risk. %20
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