Reliability of reported occupational history information for US coal miners, 1969-1977.

For estimating reliable exposure-response relations it is necessary that random variation in both the response and the exposure variables be sufficiently small. Variability in cumulative exposures can arise from uncertainties in self-reported work histories from interviews. In most epidemiologic surveys, the information gathered from questionnaires is used without knowing the validity or reproducibility of these data. This paper investigates the reliability of occupational histories reported by the same individuals on two occasions separated by 9 years in the US National Study of Coal Workers' Pneumoconiosis and its implications on the exposure-response relation for simple coal workers' pneumoconiosis. For 480 coal miners, from whom occupational histories were obtained twice (in 1969-1971 and 1977-1981), the reliability (intraclass correlation coefficient) of the cumulative exposures generated from each work history was 87%. Logistic model fitting of simple coal workers' pneumoconiosis prevalence to the cumulative coal dust exposure produced almost identical results. After accounting for intersurvey variability in the occupational histories, the authors found that the exposure-response coefficients estimated from information reported at the surveys were attenuated by 12%. In epidemiologic studies, knowledge of the reproducibility of self-reported occupational history information is important to ascertain whether the true exposure effect is underestimated.

Radiographic and pathologic correlation of coal workers' pneumoconiosis.

The relationships between chest radiographs (CXR) and corresponding pathology were investigated in 430 autopsied coal miners from West Virginia. Whole-lung sections were reviewed and graded on four-point severity scales for the following lesions of coal workers' pneumoconiosis (CWP): macules, micro- and macronodules (small and large fibrotic nodules), and progressive massive fibrosis (PMF). Antemortem CXR were classified by three B readers using the 1971 International Labor Office (ILO) U/C classification (6). On pathologic examination, 96% of miners had macules, 70% micronodules, 45% macronodules, 15% silicosis, and 28% PMF. By CXR, 69% of the miners had small, rounded opacity profusions of category > or = 0/1. Data analysis revealed increasing odds that small opacities of category > or = 0/1 would be detected with increasing grade of nodules. Profusion category 0/0 was often reported for cases with macules of mild to moderate grade and mild levels of micronodules. Overall, q-type opacities were associated with macules and micronodules, whereas the large r-type opacities were associated with macronodules. By CXR, large opacities showed good correlation with pathologic PMF. However, about one-third of cases identified as having large opacities by CXR were not substantiated as PMF by pathology. One-fourth of these cases could be explained by lung lesions such as Caplan's nodules, tuberculosis scars, and tumors. Similarly, 22% of cases classified as PMF on pathology had no large opacities by CXR. In half of these cases, the radiologists had noted other abnormalities (cancer, tuberculosis) by CXR as large opacities. Overall, the study showed good agreement (Somer's d = 0.64) between the predicted probabilities and observed responses of a profusion category > or = 0/1 for pathologic CWP lesions. However, the study also showed that CXR were insensitive for detecting minimal CWP lesions, and were unreliable indicators in the presence of concomitant pulmonary pathology.

Biochemical studies of mammalian oogenesis: possible existence of a ribosomal and poly(A)-containing RNA-protein supramolecular complex in mouse oocytes.

Mouse follicles were labeled with [3H]uridine and then cultured in vitro for 3 days. When oocytes were disrupted, about 40% of the total radiolabeled RNA could be sedimented at 9,000g. Fractionation of this RNA on poly(U)-Sepharose revealed that about 30% and 60% of the total amount of radiolabeled poly(A)- and poly(A)+ RNA, respectively, were in the pellet fraction. Treatments that disrupt protein structure reduced the amount of 9,000g sedimentable RNA and affected to the same extent the distribution of Poly(A)- and poly(A)+ RNA in the pellet and supernatant fractions. CsCl centrifugation of formaldehyde-fixed pellets revealed that virtually all of the radiolabeled RNA had a density significantly lower than that of ribosomes. The sedimentable RNA appeared not to be polysomal, membrane bound or associated wih a cytoskeleton. Agarose gel electrophoresis after poly(U)-Sepharose fractionation of either the pellet or supernatant revealed the presence of 28S, 18S, 5S + 4S, and heterodisperse poly(A)+ RNA. The size of distribution of poly(A)+ RNA in the pellet and supernatant fractions was fairly similar. Pulse-chase experiments revealed that the stability of poly(A)- RNA in the pellet and supernatant fractions was the same within the experimental error and a similar situation was found for poly(A)+ RNA. RNA in pellet translated in vitro coded for discrete size classes of protein. Since the relative band intensities were similar for both total and pellet RNA translated in vitro there seemed to be no major partitioning of specific size classes of mRNA into the pellet fraction. These results are discussed in terms of a possible composition of the lattice structures that accumulate during mouse oocyte growth and have been postulated to be a storage form for ribosome (Burkholder et al., '71).

Urinary tract abnormalities presenting as a result of blunt abdominal trauma.

Fourteen patients with unsuspected urinary tract abnormalities had their disorders diagnosed at the time of their evaluation for blunt abdominal trauma. The trauma was generally inconsequential but all of the patients had gross or microscopic hematuria. The diagnosis could be made by intravenous pyelography or physical examination in all of these patients, although in some patients the abnormality was not evident until the patient had an arteriogram. These disorders are usually detected in children, but 12 of our 14 patients were 19 years of age or older. The importance of the urogram for all patients with hematuria and minor abdominal trauma is emphasized by this group of patients.

Immunotherapy of cancer with "immune" RNA. A preliminary report.

A phase I clinical trial of immunotherapy with "Immune" RNA was undertaken fifteen months ago. Twenty-six cancer patients were treated with RNA extracted from the lymphoid organs of sheep immunized with either autologous tumor cells or allogeneic tumor cells of the same histologic type. Eighteen patients had gross disease and eight had minimum residual disease. RNA was administered weekly, intradermally, at doses up to 9 mg/week without any significant local or systemic toxicity. Four patients improved, thirteen achieved stability of disease or possible improvement, seven were treatment failures, and two are indeterminate. Lymphocyte-mediated cytotoxicity to allogeneic tumor target cells of the same histologic type were monitored in eleven patients. In seven patients, cytotoxicity increased after "Immune" RNA therapy; no change was observed in three patients; a decrease was noted in one patient. There appeared to be a possible correlation between cytotoxicity assessed in vitro and clinical response. There is some evidence that these responses may be specific for the particular tumor used to immunize the RNA donor.

Immune cytolysis of human renal carcinoma mediated by xenogeneic immune ribonucleic acid.

With a microcytotoxicity assay it was shown that normal, non-immune human lymphocytes were converted to effector cells specifically cytotoxic to human renal carcinoma cells after incubation with xenogeneic immune ribonucleic acids. The ribonucleic acid was extracted from the lymphoid tissues of sheep that had been immunized with human renal carcinoma tissue. Lymphocytes incubated without ribonucleic acid from or with ribonucleic acid sheep immunized with Freund's adjuvant alone did not increase cytotoxicity. Immunotherapy with immune ribonucleic acid increased cytotoxic activity of lymphocytes from a patient with metastatic renal carcinoma. The microcytotoxicity assay may be a useful method to assessing the cellular immune response in patients receiving immunotherapy and seems to correlate with their clinical course.

Advanced renal cell carcinoma: treatment with xenogeneic immune ribonucleic acid and appropriate surgical resection.

Herein we describe the first clinical treatment of renal cell carcinoma in humans with xenogeneic immune ribonucleic acid. Twelve patients with advanced renal cell carcinoma have been treated by appropriate operations to remove tumor bulk followed by specific passive immunotherapy. Xenogeneic specific immune ribonucleic acid was prepared from the spleen of normal sheep that had received 4 weekly injections of a homogenate of renal cell carcinoma. Results indicate that 1) xenogeneic specific immune ribonucleic acid can safely be given to humans without local or systemic toxicity, 2) there is a suggestion of clinical benefit, since only 2 patients have had progression of known metastases during treatment with immune ribonucleic acid and 3) xenogeneic immune ribonucleic acid can enhance the immune response to renal cell carcinoma, as demonstrated by in vitro lymphocytoxicity tests.