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Current reviews have concluded that internal 226Ra appears not to give rise to leukemia in humans, a conclusion based on incidence in U.S. female radium dial workers. In fact, leukemias have occurred significantly early in female dial workers; males occupationally exposed to radium show an excess of leukemias; and the rare erythrocytic leukemias appear in male workers as they do in Thorotrast case series. It appears more reasonable that Thorotrast data are suitable for projection of leukemogenic risk from radium and plutonium than that no concern for leukemogenic risk is warranted.

Available medical records of plutonium injectees exposed in experimental studies of plutonium biokinetics under Manhattan Engineer District auspices have been reviewed for subsequent medical findings potentially related to the plutonium exposures. Five subjects who had been injected with approximately 11 kBq 239Pu, and one injected with 3.5 kBq 238Pu, had useful follow-up medical data. Bone lesions dominated the findings: none of six subjects with follow-up for bone conditions lacked bone lesions clearly or potentially caused, or worsened, by plutonium. Roentgenograms of three subjects, read by a radiologist experienced reading films of radium cases, demonstrated possible to likely plutonium effects. Two cases of osteoporosis or non-specific degenerative changes were seen, associated with a hip fracture and vertebral fractures. Areas of increased bone density were seen, as well as numerous dystopic calcifications and one unusual case of widespread pathologic calcification on bone surfaces probably due to a plutonium-related calciphylactic reaction. Non-skeletal findings include labyrinthitis with inflammatory mastoid changes, conduction deafness, and a benign neurofibroma directly adjacent to bone. The radium literature contains similar observed findings, but interpretation of these limited clinical observations is hampered by lack of quantitative data on humans exposed to radium with respect to prevalence of non-specific ear, mastoid, and skeletal symptomatologies or x-ray findings, or cumulative incidence rates of bone fractures or of other physical disabilities related to ear, mastoid, or bone damage. Disability and invalidism late in life can be risk factors for earlier mortality.

In industrial society a large number of point sources of pollution exist, such as chemical plants, smelters, and nuclear power plants. Public concern has forced the practising epidemiologist to undertake health surveillance of the usually small populations living around point sources. Although not justifiable as research, such epidemiologic surveillance activities are becoming a routine part of public heath practice, and this trend will continue. This introduction reviews concepts of epidemiologic surveillance, and institutional problems relating to the quality of such applied research.

Over 300 elderly panelists, either well or with reported cardiopulmonary symptoms, participated in a study linking aggravation of symptoms to fluctuations in ambient air pollutants and daily temperature in New York City. Increasing temperatures aggravated symptoms in heart disease panelists; clear and consistent relationships of temperature to symptoms in the well, lung disease, or combined heart and lung disease panelists were not apparent. Elevated levels of suspended nitrates, suspended sulfates, sulfur dioxide, and respirable suspended particulates were associated with exacerbations of symptoms in the well elderly panel; a similar but much weaker pattern of effects on the lung disease panel appeared. It was not possible to identify more precisely the responsible pollutants. Symptoms of heart disease appeared to be related only to suspended nitrate and total suspended particulate levels in addition to temperature. The data did not suggest a threshold for these health effects nor did the data support the hypothesis that those panelists more severely afflicted with cardiopulmonary conditions would be more sensitive to air pollution. The effect of method of panel selection on the estimation of dose-response relationships, and the concept of day-to-day fluctuations in symptom rates were discussed.

A study of the completeness of death ascertainment through the Social Security Administration (SSA) was undertaken. Groups of subjects of known vital status were submitted by the Los Alamos National Laboratory to the SSA for a mortality record search. Correctly ascertained deaths ranged from 77% to 90% among males and from 53% to 76% among females. A duplicate record search one year later raised correct ascertainment to 88% to 94% of male deaths and to 73% to 87% of female deaths. Death ascertainment appeared to be independent of ethnicity (Anglo and Hispanic), cause of death, location of death, and year of death. Age at time of death was strongly related to death ascertainment. Individuals 65 years of age and over were identified much more accurately than persons less than 65 years of age. Lack of incentive to report deaths of persons under retirement age is believed to be responsible. The age of an industrial facility and of the work force may have a major influence on the adequacy of mortality ascertainment through social security.

Due to increasing atmospheric concentrations of participates, five of Allegheny County’s seven monitoring areas were placed on first stage air pollution alert by November 18,1975. The Liberty Borough area reached second stage alert, and then emergency stage the morning of November 19. An investigation was mounted to determine whether these emergency levels of par-ticulates had an effect upon the pulmonary function of school children sufficiently severe that it would require several days for pulmonary function to return to normal. Beginning November 20 in two schools and November 21 in four additional schools, the three-quarter second forced expiratory volume (FEV.75) and the forced vital capacity (FVC) of approximately 270 parochial school children in fourth, fifth, and sixth grades were tested daily through November 26. Two schools, approximately 80 children, were in control areas; the remaining children were exposed to high or very high levels of particulate air pollution with significant levels of sulf...

Panel studies relating illness, such as asthma attacks, cardiopulmonary symptoms, and acute respiratory symptoms, to daily air pollution and weather are important in environmental epidemiology. A study of the practical robustness of multiple linear regression procedures, which have been the preferred statistical models in analyses, is presented. The study is based on data from three asthma panels in Chattanooga, Tennessee, collected in 1972–1973. Linear regression models, commonly used, which incorporate only minimum temperature and an air pollutant were found to be potentially misleading; such models are highly sensitive to reporting trends in the data and do not correct adequately for weather variables. Temporal and spatial control strategies were employed and proved to be useful in detecting problems in the data due to undiscovered intervening variables. True day-to-day relationships estimated by a paired-day analysis were frequently inconsistent with “daily” effects estimated by the usual regression models and suggested that, in fact, the asthma panel data contained no useful information concerning day-to-day relationships.

Selected methods for the study of biologic time series are reviewed and their relative merits are discussed in the light of underlying assumptions. Their potential applications are exemplified in several fields of biology and medicine. The monitoring of environmental integrity, notably of pollution, is investigated. The need for specifying optimal sampling requirements is underlined. An individualized and time-qualified definition of health by the establishment of reference intervals is required for increasingly rational individualized program for the prevention and/or treatment of disease. With these reference intervals and rhythm characteristics available, one can better interpret with single samples or time series an increased risk of a certain disease or the inception of the disease. For all of these aims the monitoring of environmental and/or personal marker rhythms is essential--to obtain large data bases from which information can be more easily derived for monitoring personal health, to recognize risk as well as to diagnose disease early and to optimize treatment by timing according to rhythms.

The female radium dial workers have now experienced significant mortality from cancers other than the bone sarcomas and head carcinomas long known to be radium induced. The relationships of radium exposure to mortality from cancers of the stomach, pancreas, colon, rectum, liver, lung, breast, cervix, and corpus uteri, and from leukemia were studied in 1,285 pre-1930 dial workers. Mortality was compared with that expected from rates for US white females, with and without adjustment for local area mortality rates, and with mortality in dial workers exposed from 1930 to 1949. For the 693 cases whose body content of radium has been measured since 1955, dose-response relationships of cancer to systemic intake of radium and duration of employment were examined. Liver, pancreatic, cervical, and uterine cancers were clearly unrelated to radium exposure. Other cancers of the digestive tract appeared to be indirectly, if at all, associated with work in radium facilities. Lung cancer requires further investigation; inhalation exposures of the dial workers were reviewed. Analyses of the breast cancer data uncovered several observations inconsistent with the previously suggested causal association with radium exposure. Multiple myeloma was also reviewed. A threefold excess risk of death due to multiple myeloma has occurred, but is more closely correlated with duration of employment (a surrogate for external gamma radiation) than with radium intake.

Pulmonary function test results on 224 parochial schoolchildren collected during and after the Pittsburgh air pollution episode of November 1975 were reanalyzed to determine whether a small subgroup of susceptible children could be defined. Individual regressions of three-quarter second forced expiratory volumes (FEV.75) and forced vital capacities (FVC) on time over the six-day study period were calculated, and the distributions of individual slopes for the four exposed and two control schools were compared. Excesses of strong upward trends in the exposed areas would suggest effects of suspended particulate air pollution by indicating significant improvement following the episode. A highly statistically significant excess of strong upward trends in the FVC among exposed students was observed, and was consistent by sex and by school within sex. Approximately 10--15% of the students appear susceptible to an average impairment of about 20% of the FVC. The findings are limited by the small number of subjects with strong post-episode upward trends in the FVC, and by lack of validation by replication of the study design, but do suggest that episode levels of suspended particulates induce lung damage, and that this may occur only in a small susceptible subgroup. Children with low baseline pulmonary function values, histories of asthma, or with acute respiratory symptoms immediately following the episode were not found to be especially susceptible to these effects of suspended particulates.

Cancer among Los Alamos County, New Mexico, male residents, all of whom have worked in or have lived within a few kilometers of a major plutonium plant and other nuclear facilities, has been reviewed with respect to mortality between 1950 and 1969 and incidence between 1969 and 1974. A possible excess of neoplasms of the reticuloendothelial system was detected, but the incidence data suggest that this excess, if real, is no longer occurring. Several potentially causal occupational exposures have existed. Higher than expected incidence, currently, of cancers of the colon and rectum appears to be explained better by socioeconomic than occupational factors. Neither mortality nor incidence data suggest an excess of lung cancer in Los Alamos males. Healthy worker and healthy military effects, white ethnicity, and migration are discussed as intervening variables relevant to interpreting mortality data in counties dominated by a single major facility. The utility of county data bases in the study of single local area mortality rates is reviewed.

Noninhaling of tobacco smoke, and, by implication, use of filter cigarettes, do not appear to reduce the rate of decline of the FEV 1 with age among smokers. The cumulative benefit of not smoking in late adolescence and early adult life appears to be permanently retained despite later smoking. Workers born in Puerto Rico show distinctly lower values for the FEV 1 than other foreign or native-born workers. A possible effect of occupational exposure to air pollution among nonsmoking bus drivers was found. A number of smoking variables beyond current type and amount were shown to contribute to the prediction of the FEV 1 . It is suggested that these, and also sitting height and weight, should be accounted for in analyses of air pollution or other environmental effects on pulmonary function. The use of age and standing height in predicting the FEV 1 for mass screening purposes was shown to be only 90% as sensitive as the use of age, standing height, sitting height, and weight.

The effects of urban residence on prevalence of respiratory symptoms and on pulmonary function in a population of white male nonsmokers are presented. Residence in urban areas of 50,000 + population in childhood was positively related to the PEFR; the effect at age 21 was estimated as approximately +26 liters/min. Residence in urban areas during adult life showed a significant nonlinear relationship to PEFR. Values increased during the first 7 years of urban residence as an adult, and then declined; this effect, at 30 years of urban residence after age 21, was estimated at −44 liters/min. No effect on the FEV 1.0 was found. Results for the prevalence of cough and phlegm are consistent with the results for the PEFR, but numbers were too small to allow definite conclusions to be drawn. The variance about the regressions was studied, and it was discovered that social class and urban residence affected the relationship of the variance about the regression to the age of the respondents.

Stebbings, J. H. (1974).Thorax, 29, 505-510. Fractional carbon monoxide uptake in an employed population. The fractional carbon monoxide uptake in 913 New York City transit workers was studied. A prediction equation for white males, based on nonsmokers, was obtained: fractional CO uptake = 0·58032 − 0·00204 × age + 0·0004 × weight (kilograms). Weight was the index of body size most strongly correlated with the fractional CO uptake. Decline in function with age by amount of tobacco smoked is described. A correction factor for respiration, based on results from 581 workers with two or more tests, was calculated: − 0·123654 × (standard tidal volume − observed tidal volume). Tidal volume was the most important contributor to individual variability of the fractional CO uptake, and minute volume or respiration rate do not add significantly to it. For epidemiological or screening uses, prediction equations are given for the fractional CO uptake corrected to 0·5 1. tidal volume. Respiration variables explain only 1·5% of individual variability, and individual variability over a mean period of 16·6 months was much larger (an individual standard error of 0·07) than the unexplained population variability (a population standard error of 0·01−0·02); thus the usefulness of the fractional CO uptake as a test of respiratory function is in doubt.

The study of microtubule-associated intracellular translocation is, at present, one of the most exciting areas in cell biology. Most of the research has focussed on the translocation which occurs along nerve axons, but other asymmetric cells, such as chromatophores and various protozoa, have also been studied extensively, and the phenomenon probably occurs to some extent in all cells. It is particularly emphasized too in the ovaries of certain insects, and this is the subject of the present chapter.

The telotrophic ovary of Notonecta glauca glauca consists of 7 ovarioles. Each ovanole comprises, from front to rear, a terminal filament, a trophic region, a prefolhcular region, and a series of 10-15 follicles of progressively increasing size The trophic region is largely syncytial and is made up of polyploid trophic nuclei packed around a central trophic core The cytoplasm of the trophic core is continuous with the cytoplasm of each oocyte through a system of trophic tubes. There is one trophic tube per oocyte. The trophic nuclei have large nucleoh. There are a few small nucleoh in the oocyte nuclei The cytoplasm of the trophic core, the trophic tubes, and the oocytes is rich in RNA. Autoradiographs of sections of ovarioles fixed 2 h after injection of PHjundine into animals show label over the trophic nuclei only. Eight-hour autoradiographs show heavy labelling of the trophic region and label over the front ends of the trophic tubes, but little label over the posterior regions of the tubes or the oocyte cytoplasm. Later autoradiographs indicate that label gradually spreads backwards from the trophic core, along the trophic tubes, and progressively builds up in the oocyte cytoplasm These observations are thought to indicate synthesis of RNA in the trophic region and movement of RNA from the trophic core along the trophic tubes to the oocytes The trophic core and tubes show brilliant positive form birefringence with respect to their lengths. This birefringence can be reduced by keeping animals at 2 °C for 12 h, and eliminated by placing ovanoles in 1 % colchicine for 6 h. Electron micrographs of thin sections of ovanoles show that trophic core and tubes are densely and uniformly packed with nbosomes and microtubules The latter are lined up along the trophic tubes. There are about 30000 microtubules evident m a TS through a trophic tube 15 fim wide. Lengths of microtubules up to 2 /*m have been observed. Ribosomes are packed between the microtubules but are excluded from regions where the spacing between adjacent microtubules is less than 25 ran The contribution of the trophic region to the oocytes and the role of the microtubules in maintaining or facilitating the movement of nbosomes along the trophic tubes is discussed

To the Editor.— The article by Lyman et al 1 associating radium in groundwater with leukemia has major flaws. Ecological correlation studies are considered useful explorations of disease causality only where data from cohort (or case-control) studies are lacking. Consistency of correlations over time and space and the effects of socioeconomic and other variables as confounders, and also as "control" variables, are investigated whenever possible. Statistical significance levels cannot be taken literally when spatial autocorrelations exist. Lyman et al 1 appear unaware of this. Two further weaknesses appear in their article. The difficulties, inherent in ecological correlation studies, in linking environmental agents to actual population exposures will not be pursued herein. But the authors' failure to discuss the bone sarcomas and carcinomas of nasal sinuses and mastoid air cells, long known to be induced by radium and present in far larger numbers than are leukemias in the radium-exposed cohorts they