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Dose-response analyses of osteonecrosis in New Jersey radium workers point to roles for other alpha emitters.

A previous study of 25 radium workers reported radium osteonecrosis to be common down to that study's lower limit of detection of 226Ra. This paper reanalyzes those data using Poisson and linear regression to obtain quantitative dose-response estimates for radium osteonecrosis. A quadratic, supralinear response of the necrosis ratio to skeletal dose and preterminal 226Ra burden was observed at a high level of statistical significance. At low dose the response was linear. Clearly observable necrosis, that appearing in 4% of tissue blocks, was seen in femurs at approximately 0.8 Gy skeletal dose. Comparable effects from plutonium in spongy bone might therefore be expected in the 0.01-0.02 Gy dose range. Prediction equations are presented for preterminal 226Ra burden, for skeletal dose, and, at low doses where the response can be taken as linear, for dose from and uptakes of both 226Ra and 228Ra. Male New Jersey workers in the radium refinery were observed to have necrosis not explained by the 226Ra uptakes, but compatible with skeletal doses from other internal emitters, in the range 0.25-1.2 Gy lifetime dose acquired per year of employment. 210Po, inhaled directly or from inhaled 210Pb, is the most likely source of this dose.

Body Burden↗

William Duane and the radium cow: an American contribution to an emerging atomic age.

In 1912 many physicians considered radium a cure for cancer but few could afford it because radium cost a fortune. William Duane, Marie Curie's associate, discovered that "radium milk" (later officially named radon) was easier for physicians to use. In 1915 he built Boston's first radium "cow" and thousands of patients were treated with its "milk." But because radon decayed with high-energy alpha emissions, it also became the first "atom smasher." Making radon available to nuclear scientists was one of America's major contributions to an evolving nuclear age.

Boston↗

Historic development and medical use of nasopharyngeal radium irradiation treatments.

Nasopharyngeal radium irradiation was a medical treatment that replaced eustachian tube inflation and was itself replaced by tympanotomy tubes. Research and development began in 1924 when Samuel J. Crowe was awarded funds to develop an otologic research laboratory. He observed that recurring adenoids and serous otitis were associated with childhood deafness. In collaboration with Curtis Burnam, he developed a nasopharyngeal radon applicator in the 1930s. This was modified in the 1940s to a nasopharyngeal radium applicator, which had a much longer half-life and did not need treatment lengths recalculated twice each day. Numerous reports on the clinical use of nasopharyngeal radium irradiation in the United States were published. Papers have cautioned against possible dangers of nasopharyngeal radium irradiation, but there have been no substantiated reports. This report ends with three concluding suggestions for research.

History, 20th Century↗

The discovery of radium in 1898 by Maria Sklodowska-Curie (1867-1934) and Pierre Curie (1859-1906) with commentary on their life and times.

This review celebrates the events of 100 years ago to the month of publication of this December 1998 issue of the British Journal of Radiology, when radium was discovered by the Curies. This followed the earlier discovery in November 1895 of X-rays by Röntgen, which has already been reviewed in the British Journal of Radiology [1] and the discovery in March 1896, by Becquerel, of the phenomenon of radioactivity, which introduces this review. This is particularly relevant as Marie Curie was in 1897 a research student in Becquerel's laboratory. Marie Curie's life in Poland prior to her 1891 departure for Paris is included in this review as are other aspects of her life and work such as her work in World War I with radiological ambulances (known as "Little Curies") on the battlefields of France and Belgium, early experiments with radium and the founding of the Institut du Radium in Paris and of the Radium Institute in Warsaw. Wherever possible I have included appropriate quotations in Marie Curie's own words [2-4] and each section is related in some way to the life and work of Maria or Pierre. This review is completed with details of the re-interment of the bodies of Pierre and Marie on 20 April 1995 in The Panthéon, Paris.

France↗

Prognosis of endometrial carcinoma stage I in two Swedish regions. A study with special regard to the effects of intracavitary irradiation with high dose-rate afterloading technique or with low dose-rate radium.

A high dose-rate afterloading technique (60Co) was compared with a low dose-rate packing method (226Ra) in the treatment of endometrial carcinoma stage I. In all, 1,021 patients treated during the period 1977-1986 at two Swedish gynecologic oncology centers were analyzed regarding treatment set-up, histopathologic outcome in the operative specimens, recurrence rates, survival rates and radiation side effects. Complete tumor eradication in the operative specimen was achieved in 80% after radium therapy and in 60% after irradiation by the high dose-rate technique. The overall recurrence rate was 15.7% in the radium packing series and 11.5% after cobalt afterloading treatment. The risk of pelvic recurrences increased by 2.1-2.6 if hysterectomy was replaced by dilatation and curettage. The two radiation techniques seemed to be comparable with regard to the risk of both pelvic recurrences and distant metastases. The 5-year crude survival rates were 85% in the afterloading series and 82% in the radium series. The corrected survival rates were similar (90%) for the two techniques. Age, tumor grade and uterine size were significant prognostic factors with regard to the probability of death due to cancer. Early radiation reactions had quite similar rates in the two series, whereas late radiation reactions were more frequent in the high dose-rate afterloading group in the 10-12 Gy dose fraction range, but not in the 5-8 Gy range. The radium packing method seemed to give a higher frequency of tumor-free operative specimens in this study, but with regard to recurrence rates and survival probabilities the techniques were comparable. Since the different proportion of surgery in the two series and the histopathologic evaluation might have influenced the rate of local tumor eradication in the operative specimens and the risk of pelvic recurrences the results must be assessed with great caution and only a crude comparison of the two treatment techniques could be made.

Adult↗

Pathology of radium-induced bone tumors: new aspects of histopathology and histogenesis.

A revision of bone tumor pathology in patients treated with multiple injections of the short-lived alpha-particle emitter radium-224, predominantly for tuberculosis and ankylosing spondylitis, revealed an unexpectedly high proportion of bone sarcomas of the fibrous connective tissue type. This included the first case of malignant fibrous histiocytoma of bone described after internal irradiation. A comparison of bone tumor types in the radium-224 patients and bone sarcoma after incorporation of radium-226 and radium-228 and external irradiation and in tumors arising at sites of pre-existing bone lesions showed the same spectrum of tumors. The high incidence of bone tumors of the fibroblastic and fibrohistiocytic type was observed in all these "secondary" bone sarcomas. These results suggest that a close histogenetic relationship exists between disorder of the local milieu caused by deterministic radiation damage accompanied by disturbances of the remodeling process. The reactive proliferation of the predominantly fibroblastic tissue could be the presumptive origin of these special types of radiation-induced bone sarcomas.

Bone Neoplasms↗

Alteration of the c-mos locus in "normal" tissues from humans exposed to radium.

The structure of a number of human protooncogenes of persons with internal systemic exposure to radium was analyzed by restriction enzyme digestion and Southern blotting of their DNA. Two extra c-mos EcoRI restriction fragment length bands of 5.0 and 5.5 kilobases were found in tissue DNA from six of seven such individuals. The extra c-mos bands were detected in DNA from many, but not all, of the tissues of the individuals exposed to radium. Kidney DNA, however, from three of four individuals exposed to radium contained these alterations; kidney DNA from six age-matched controls did not. The 5.0- and 5.5-kilobase bands, which were of a similar intensity, varied in their intensity with respect to that of the normal 2.5-kilobase band of the c-mos gene. The DNAs that have the polymorphic bands also appear to have a more complex c-mos methylation pattern. Our results suggest that the c-mos restriction fragment length alterations found in individuals exposed to radium were induced rather than inherited, are epigenetic in origin, and most likely result from changes in the methylation of bases surrounding the single exon of the c-mos protooncogene.

Aged↗

Breast cancer in female radium dial workers first employed before 1930.

Female radium dial workers first employed before 1930 were analyzed for breast cancer mortality and incidence using method and rate tables described by Monson and the Mantel-Haenszel summary chi-square test for significance. Of 1,180 located women, 736 were measured to estimate radium intake. This measured group was analyzed for breast cancer mortality and incidence according to four possible risk factors: radium intake dose, duration of employment, age at first exposure, and parity. The located women had a mortality ratio of 1.51 (p < 0.05). The measured women showed a significant excess of breast cancer incidence and mortality only among those women with a radium intake of 50 microCi or greater. Although the differences were not significant, incidence and mortality ratios were slightly higher for nulliparous women.

Adult↗

Occurrence of mammary tumors in beagles given radium-226.

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon-->polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. Results of this study are potentially useful in understanding risks of radium-induced breast cancers in humans.

Age Factors↗

Radium, Marie Curie and modern science.

In 1898, the discovery of two new elements, polonium and radium, reawakened interest in the topic of uranic rays discovered 2 years before by H. Becquerel. Radioactivity, a name coined by Marie Curie, became a major research field for decades. The contrasting personalities of Pierre Curie, already a first-rank physicist, and of the young Marie Curie-Sklodowska as they undertook their common work are described. It is shown how a well-chosen quantitative method and a systematic approach combining physics and chemistry led to the discovery within less than 1 year. The special role of radium and the determination of its atomic weight by Marie Curie followed by her long-term program for accumulating pure radium salts are emphasized. The first woman with a full professorship at a French University, Marie Curie created and managed the Radium Institute.

Academies and Institutes↗

Estimates of numbers of civilians treated with nasopharyngeal radium irradiation in the United States.

Nasopharyngeal radium irradiation was used 35 to 50 years ago for treatment of hearing loss, chronic ear infections, asthma, and other conditions. I reviewed the medical literature for published articles on the nonmilitary use of nasopharyngeal radium irradiation. Four years have minimum documented numbers of radium applicators in use (1946, 600; 1948, 1000; 1958, 2000; 1961, 2000). Two levels of physician use were assumed, a high estimate of 25 patients per week and a low estimate of 5 patients per week. It was assumed that physicians used the applicators 50 weeks per year. Typical treatments involved two applicators at a time (one for each nostril) for three sessions. Using a formula reflecting the number of applicators in use, the number of patients a physician would treat in a week, the number of weeks in a year an applicator would be used, and the number of applicators and sessions per patient, I then estimated the number of children who might have been treated. This estimate is that approximately 500,000 to 2.5 million persons might have been treated with nasopharyngeal radium. Because the lack of documentation for numerous parts of the equation required that I make a large number of assumptions, this estimate should be considered a rough approximation of the number of civilians treated.

Asthma↗

Early stage carcinoma of the uterine cervix. Effects of intracavitary radium treatment on lymphoid cells in blood and pelvic lymph nodes.

Sixteen patients with early stage carcinoma of the uterine cervix treated with primary radical hysterectomy and pelvic lymphadenectomy were compared with 17 patients who four to six weeks before the operation received intracavitary treatment with radium. The calculated radiation dose to the pelvic wall was approximately 10 Gy. The distribution of lymphoid cells in blood and pelvic lymph nodes was studied by an indirect immunofluorescence technique using monoclonal antibodies. The radium treated group showed a significant reduction of circulating OKT4+ (T helper) and OKT8+ (T suppressor/cytotoxic) lymphocytes. The number of Leu7+ (natural killer) cells and 1D5+ cells (monocytes) was not changed, but the ratio between monocytes and T cells was increased after radium therapy. In cell suspensions obtained from the pelvic lymph nodes, the radium treatment induced a significant reduction of the OKT4+ cell fraction. It is concluded that this low dose rate regimen of intracavitary treatment induces changes in the immune system which are of the same type as those seen after external field irradiation.

Adult↗

A preloaded radium needle implant device for maintenance of needle spacing.

A small stainless steel bar was machined to accept radium needles. The stainless steel bar will hold a rack of two, three, four, or five radium needles in a single plane. The crossing needle may be affixed to the bar so that textbook-like geometry is possible. The stainless steel bar remains in place during the entire implant. Spacing between needles is close to perfect. The time required to insers the implant is reduced compared to free-hand insertions, and less variation in dose is seen on computer-assisted calculations. Two years' experience in the use and development of the radium needle holder will be reviewed.

Head and Neck Neoplasms↗

A mortality follow-up study of WW II submariners who received nasopharyngeal radium irradiation treatment.

BACKGROUND: During World War II, large numbers of submarine trainees received nasopharyngeal radium irradiation therapy to treat aerotitis media or middle ear barotrauma. METHODS: Using a life table and the Cox proportional hazards model, mortality risk of 1, 214 submariners believed to have received treatment for aerotitis media was compared to 3,176 "untreated" submariners. RESULTS: "Treated" submariners had a significant increased mortality risk for all causes (odds ratio (OR) = 1.32; 95% confidence interval (CI) = 1. 14-1.53) and circulatory diseases (OR = 1.51; 95% CI = 1.20-1.90), and a non-significant increased mortality risk of head and neck cancer (OR = 1.40; 95% CI = 0.54-3.58). CONCLUSIONS: While the excess risk was not statistically significant by conventional standards, the finding does suggest that those who received NP radium irradiation therapy may be at increased risk of death due to head and neck cancers. Due to the lack of data the role of risk factors other than radium exposure cannot be assessed.

Aged↗

Treatment of penis carcinoma with interstitially administered iridium; comparison with radium therapy.

The results of treatment of 30 patients with penis carcinoma cured with radium and 18 patients treated with 192Ir were compared. In both groups of patients, core assessed at 3 years was obtained for a similar percentage of patients (89% and 83%). After treatment with 192Ir, radiation necrosis was observed in 16%, and after treatment with radium in 50% of patients. In both groups a similar high percentage of patients (88%) with organs preserved after treatment was found. In group of patients treated with 192Ir the percentage of very good functional effects (69%) was much higher in the group of patients treated with radium (28%).

Adult↗

Radiological impact assessment of an abandoned radium salts factory.

A radiological assessment has been in progress, since 1978, on the environmental implications of an abandoned radium salts factory, operating in Portugal from 1912 to 1944. Some aspects of the study performed at the site are briefly described. They include the analysis of radium-226 concentrations in water and foodstuff and the identification of critical pathways. The resulting dose equivalents due to radium intake and external irradiation are evaluated for the two most exposed groups of the population, and compared with values from other regions. Their sensitivity to some of the factors assumed is also discussed.

Adult↗

Can juvenile scoliosis be corrected by circumscribed radium-irradiation of the spine?

In 1936 scoliosis was produced in growing animals by exposing one side of one or more vertebrae to radium action. The purpose of this treatment was to recurve existing curvatures of the spine on the same principle. No attempt has been made so far to correct congenital scoliosis of infants by this method. Hundreds of infants treated by X-ray for Wilms' tumor developed incidental spinal curvatures. In none of these cases was there any recorded mention of damage to the spinal cord or any other organ. Since the epiphyseal plate is much more sensitive to radiation than is the Wilms' tumor and radium radiation can be more easily controlled than X-radiation, it is suggested that scoliosis of genetic or other etiology might be successfully treated by radium or possibly other gamma rays. The choice of the rays and the dosage must be left to the experts.

Animals↗

Groundwater radon, radium and uranium concentrations in Região dos Lagos, Rio de Janeiro State, Brazil.

Ground water from Região dos Lagos, a coastal area of Rio de Janeiro state, was analysed for (226)Ra, (228)Ra, (222)Rn, (238)U, major ion concentrations, and physico-chemical parameters were also measured. Concentrations values ranged from <0.002 to 0.492 Bq l(-1) for (226)Ra, from <0.01 to 1.50 Bq l(-1) for (228)Ra and from < 1.0 x 10(-4) to 8.0 x 10(-2) Bq l(-1) for (238)U. Detectable (222)Rn concentrations (>3 Bq l(-1)) were found only in two samples. The spatial distribution of Ra concentration delineated one distinct area and some hot spots with high Ra concentration. Low pH value is the most important water parameter linked to high radium concentration. This is probably related to limited adsorption of radium on soil ferric oxides and hydroxides at low pH range. There was a significant correlation between uranium concentrations and electrical conductivity values, and also between uranium concentrations and concentrations of Ca, Mg, Na, K, and Cl, indicating sea water impact. Uranium concentrations were lower than maximum contaminant level for drinking water, whereas 17 out of the 88 ground water samples had levels of radium that exceeded the maximum contaminant level for tap water. The total annual effective dose for adult due to the water consumption reaches values up to 0.8 mSv.

Adult↗