Roy E. Albert

Follow-up Study of Patients Treated by X-ray Epilation for Tinea Capitis

This is the second follow-up study of 2,215 persons who during childhood between 1940 and 1959 had been given x-ray therapy for tinea capitis and of 1,395 persons well matched for age, sex, and race who were treated for the same disease during the same period without the use of x-ray therapy. The major finding of the study was an excess incidence in the irradiated cases of tumors of the head and neck including the skin, brain, thyroid, and parotid. However, between the groups there was no difference in death due to malignant neoplasms or any other cause. Among white patients, a 40% excess of treated psychiatric disorders was observed in the irradiated group, but there was no difference among blacks.

The inhalation toxicology of benzene: Incidence of hematopoietic neoplasms and hematotoxicity in AKRJ and C57BL6J mice

Abstract AKR J mice and C57BL 6J mice were given lifetime exposures to 100 and 300 ppm benzene, respectively. Peripheral blood cell counts were obtained biweekly throughout the exposures. Anemia and lymphocytopenia were produced in benzene-exposed AKR mice. Twenty percent of the exposed AKR mice developed bone marrow hypoplasia, compared to 2% for the controls. The benzene exposures did not alter the incidence or induction time of the viral-induced lymphomas commonly seen in AKR mice. In C57BL mice, exposure to benzene produced anemia, lymphocytopenia, and neutrophilia accompanied by a left shift. Thirteen (33%) of the exposed C57BL mice developed bone marrow hyperplasia and in four of these mice, hyperplasia was essentially limited to granulopoietic elements. None of the control C57BL mice developed bone marrow hyperplasia. In benzene-exposed C57BL mice there was a significant increase in the incidence of hematopoietic neoplasms including six cases (15%) of thymic lymphoma. Although two control mice (5%) died with lymphoma neither of these tumors involved the thymus. Thymic lymphoma is rare in C57BL mice but can be produced by ionizing radiation and chemical carcinogens.

Skin Cancer Incidence among Children Irradiated for Ringworm of the Scalp

A series of about 2200 children who received X-ray treatment for ringworm of the scalp (tinea capitis) during the 1940s and 1950s, and a comparable group of 1400 treated without X ray, have been followed by mail questionnaire for an average of 26 years since treatment to tabulate the incidence of skin cancer. The X-ray treatment consisted of 300-380 R to five overlapping fields on the scalp, to cause complete depilation. This delivered doses of 300-600 rad to various portions of the scalp, with lower doses to the skin of the face and neck. In the irradiated group, 41 persons have had one or more basal cell carcinomas of the scalp or face while only three have been diagnosed in controls. There was a high prevalence of multiple skin cancers in the irradiated group (80 lesions among 41 cases). The minimum latent period for radiation-induced skin cancers was long--about 20 years--and this may be attributable to the young age of the population. The skin cancer risk was particularly pronounced on the face, where there would be more UVR exposure in addition to X-ray exposure. Lightness of complexion proved to be an important factor in the skin cancer risk. In addition, skin cancers were found only among caucasians, even though 25% of the study population were blacks. These findings suggest that UVR exposure levels or sensitivity to such exposure interact with ionizing radiation exposure in defining skin cancer risk.

The characteristics of bronchial clearance in humans and the effects of cigarette smoking.

The clearance of radioactive monodisperse ferric oxide aerosols ranging in diameter from 0.8μ to 7.9μ was studied in a total of 117 experiments on 36 subjects. In most normal subjects there were two discrete periods of bronchial clearance, with the first usually completed within one to two hours, and the second within four to ten hours after inhalation. The fraction cleared in each phase was strongly dependent on the size of the inhaled particles, with more first phase clearance for larger particles. The rates of bronchial clearance were expressed in terms of the time required for completion of 50% to 90% bronchial clearance. On the basis of the limited data thus far accumulated, bronchial clearance was impaired in eight out of fourteen cigarette smokers, three out of three former uranium miners, and two out of two emphysema cases.

Effects of sulfuric acid aerosol on respiratory mechanics and mucociliary particle clearance in healthy nonsmoking adults

Ten healthy nonsmokers inhaled 0.5 µm (αg=1.9) H2SO4 at 0 (control), 110,330, and 980 µg/m3 for one hour via nasal mask in random sequence on four separate days. Respiratory mechanical function was assessed before and 1 /2, 2 and 4 hrs after the H2SO4 exposure. A 99mTc tagged Fe2O3 aerosol (7.5 µm aerodynamic diameter, αg≤1.1) was inhaled ∼10 min before each H2SO4 exposure, with flow rate=1.0 L/s, tidal volume=1.0 L and respiratory rate=15/min. Thoracic retention of the deposited radioactivity was monitored using collimated scintillation detectors. A tracheal probe was used to determine the tracheal mucociliary transport rates (TMTRs) of local concentrations of activity. Bronchial mucociliary clearance was markedly altered in a dose dependent pattern in six of the individuals and in the group as a whole. Exposures to 110 µg/m3 resulted in a significant acceleration in mucociliary clearance (group mean tracheobronchial clearance half-time, , decreased from 80 to 50 min). Exposures to 980 µg/m3 caused a si...

Bronchial Deposition and Clearance of Aerosols

The regional deposition and mucociliary clearance kinetics of inhaled particles have been measured by following the retention of inert γ-emitting monodisperse test aerosols. This study extends the previously reported work with quantitative assessment of the extent of intersubject variability and intrasubject reproducibility; and reports on the effects of acute cigarette smoke exposure, abstinence from cigarettes in smokers, and of injected methacholine on particle deposition and clearance. The results are integrated with our previous findings and the work of other investigators into a tentative schema for the pathogenesis of chronic bronchitis.

Dose-Dependent Effects of Submicrometer Sulfuric Acid Aerosol on Particle Clearance from Ciliated Human Lung Airways

We previously showed that 1 hr exposures to submicrometer sulfuric acid (H2SO4) aerosol at 100 and 1000 micrograms/m3 altered the bronchial mucociliary clearance of monodisperse 7.6 micron MMAD 99mTc-labelled ferric oxide (Fe2O3) in healthy, nonsmoking humans. The 7.6 micron particles were primarily deposited in the larger bronchial airways, where submicrometer H2SO4 has very little deposition. To determine the extent that submicrometer H2SO4 aerosol affects clearance from the more distal ciliated airways, we measured the clearance of a monodisperse 4.2 micron MMAD Fe2O3 aerosol in eight other healthy nonsmoking subjects. A greater fraction of 4.2 micron particles deposited in distal conductive airways. Bronchial mucociliary clearance was slower following 1 h nasal H2SO4 inhalations at 100, 300 and 1000 micrograms/m3 than after sham exposures, while mucociliary transport rates within the trachea and indices of respiratory mechanics were unchanged. A comparison of the effects of 1 h exposures at 100 micrograms/m3 on the clearance of 7.6 and 4.2 micron particles suggests greater physiological response in distal ciliated airways than in larger central airways.

Depressions in B- and T-lymphocyte mitogen-induced blastogenesis in mice exposed to low concentrations of benzene

In a short-term (6 h/day X 6 days) benzene inhalation dose-response study, mitogen-induced blastogenesis of both B- and T-lymphocytes in male, C57Bl mice was observed to be significantly depressed at relatively low levels of benzene. Exposure to 10 ppm benzene resulted in a significant depression in femoral lipopolysaccharide (LPS)-induced B-colony-forming ability, while total numbers of B-lymphocytes at this concentration were not significantly depressed. Similarly, splenic phytohemagglutinin (PHA)-induced blastogenesis was significantly depressed at 31 ppm, without a concomitant significant depression in numbers of T-lymphocytes. These data indicate that concentrations of benzene at or near the current standard for occupational exposure (10 ppm) can affect certain immune-associated processes.

Follow-up Study of Patients Treated by X-ray Epilation for Tinea Capitis: I. Population Characteristics, Posttreatment Illnesses, and Mortality Experience

This study compares the illness experience of 2,043 tinea capitis patients during a 12-year period after x-ray epilation with that of 1,413 nonirradiated tinea capitis patients who were also treated during the years 1940 to 1959 at the Skin and Cancer Unit of the New York University Hospital. The irradiated and control groups, surveyed by questionnaire, represented 85% and 79%, respectively, of the total available clinic population of tinea capitis cases and were well matched for age, sex, and race. The major findings of the study included a higher incidence of confirmed cases of cancer and mental illness in the irradiated group.

Acute and chronic dose/response effects of inhaled benzene on multipotential hematopoietic stem (CFU-S) and granulocyte/macrophage progenitor (GM-CFU-C) cells in CD-1 mice

Abstract Many blood dyscrasias are associated with hematopoietic stem cell anomalies. In order to investigate the interaction of inhaled benzene with hematopoietic stem cells, marrow and spleen cells from male CD-1 mice were assayed for CFU-S by the spleen colony method, and for GM-CFU-C by an in vitro agar technique following benzene exposure using a number of regimes. Specifically, these consisted of a 6 hr/day × 5 days exposure to either 1.1, 9.9, 103, 306, 603, 1276, 2416, or 4862 ppm (Experiment 1); a 6 hr/day × 5 days/week × 50 days exposure to 9.6 ppm (Experiment 2); and a 6 hr/day × 5 days/week × 26 weeks exposure to 302 ppm (Experiment 3). In Experiment 1 femoral and splenic cellularites were significantly reduced at concentrations ≥ 103 ppm. Marrow concentration of GM-CFU-C was equivalent to or greater than control values at all levels, however, splenic GM-CFU-C concentration was decreased at 103 ppm and above. Femoral and splenic CFU-S and GM-CFU-C per organ were depressed at 103 ppm and above. No change in colony/cluster ratio was observed. Since changes in stem cell number were detected at 100 ppm, Experiment 2 was designed to compare the effects of a 10-ppm exposure delivered over 50 days with the 100-ppm exposure delivered over 5 days. In Experiment 2, no detectable changes were observed in bone marrow, but splenic cellularity and the number and concentration of splenic CFU-S were elevated vs matched control. Experiment 3 repeated a regime that produced two cases of myeloid leukemia in CD-1 mice and a marked depression was observed in marrow and spleen cellularity. The concentration and number of marrow and spleen CFU-S and marrow GM-CFU-C were also depressed. The number of splenic GM-CFU-C were also reduced, however, splenic GM-CFU-C concentration was increased relative to control. Splenic colony/cluster ratio was also significantly reduced in this experiment. These data demonstrate that 5-day inhalation exposure to benzene concentrations 10 times the current TLV depresses marrow and splenic CFU-S and GM-CFU-C with splenic cells showing greater sensitivity. Stem cell depletion seems, therefore, to be involved in the pathogenesis of benzene-induced hematotoxicity.