Twenty-two of 83 silicotic sandblasters in the New Orleans area had complicating mycobacterial infections: 10 with Mycobacterium tuberculosis, 9 with M. kansasii, and 3 with M. intracellulare. The place of residence was related to the variety of atypical infection. The mean age of the patients was 44 years and the average exposure to silica was less than 10 years. Sputum conversion occurred in all 18 patients with positive cultures, but 8 died in respiratory failure secondary to progressive silicosis. The roentgenographic features of the disease were often atypical: Lower lobe involvement occurred in 6 patients, hilar adenopathy without calcification in 8, and diffuse filling of air spaces in 5. Pulmonary function studies usually showed a mixed pattern of obstruction and restriction associated with impaired gas transfer. Pulmonary function often declined over relatively short intervals of time with corresponding adverse chest roentgenographic alterations.

Purpose: Controversy exists whether patients diagnosed with Crohn's disease require increasing doses of infliximab overtime. We studied the impact of multiple parameters on infliximab dosing derived from a large reimbursement database. Methods: Infusion data based on 28,932 Crohn's cases, entered into a nationwide reimbursement database between 2002–2003, were analyzed. A multivariate regression model evaluated the dose of infliximab by patient weight, age, gender, site of infusion (in-office vs. non), infusion status (initial vs. subsequent), payer status (commercial vs. non), and year of administration. Nonlinearities inherent in the data were extracted and potential issues of multicollinearity among the regressors, specifically age and payer status, were investigated. For purposes of the model, the intended dose was assumed to be the dose subsequently administered. Results: Among the 28,932 cases, 10,942 were initial infliximab infusions and 17,990 subsequent infusions. The mean dose per initial infusion versus subsequent infusion was 5.56 mg/kg (SD = 0.93) and 5.71 mg/kg (SD = 1.13), respectively, with the median number of vials 4 (IQR = 3–5) and 4 (IQR= 4–5). Across all cases, the average amount of infliximab administered was 423.81 mg, resulting in an annual, average cost of maintenance therapy of $16,194. The regression model estimated the average dose to be 2.71% higher for a subsequent infusion versus an initial infusion and 1.15% higher for those patients infused in 2003 versus 2002. The average dose for females was 0.9% less than males, while infusions in an office based setting were 1.99% higher than those in other settings. An increase in age by 1 year resulted in a dose decrease of 0.03%. Payer status did not have a statistically significant effect on dosing. All other regressors were found to be highly signficant at a 99% confidence level. Conclusions: Infliximab dose only marginally increases with duration of therapy, and varies little by site of infusion or insurer status. Dosing patterns for infliximab remain stable and predictable over time.

Rabbit alveolar macrophages were exposed in culture medium to asbestos, beryllium sulfate, and beryllium oxide. The specific activities of the lysosomal hydrolases, acid phosphatase beta-N-acetylglucosaminidase and beta-glucuronidase plus the glycolytic enzyme, phosphohexose isomerase were determined in the medium, whole-cell homogenates, mitochondrial fractions, and supernatant. These hydrolases increased significantly in the medium but not in the mitochondrial fraction of cells exposed to dusts. Asbestos and beryllium sulfate were highly cytotoxic for alveolar macrophages in vitro and the data suggested that these agents were not associated with an increase in enzyme synthesis but rather a direct cytotoxic effect at the macrophage membrane level. For induction of enzyme release in vitro, a higher concentration of beryllium oxide was needed when compared with asbestos and beryllium sulfate. The cytotoxicity and enzyme release induced by these agents may represent an important nonspecific mechanism by which they induce inflammation and perhaps local proliferation of fibroblasts.

More than 130 cases of silicosis among sandblasters with an average exposure to free silica of 10 years have been studied in Louisiana. The mortality was approximately 25%. Examination of 180 gravimetric respirable dust samples from the breathing zones of sandblasters and other associated workers in two steel fabrication yards showed extensive dust exposure (up to 42.8 times the threshold limit value). The silica fraction of the respirable dust was determined either by X-ray diffraction or by a modified colorimetric technique based on that of Talvitie and Hyslop (Amer. Indust. Hyg. Assoc. J. 19, 54–58, 1958). Sandblasters wearing non-air-supplied defective hoods were at the greatest risk. Their exposure to silica dust varied greatly depending on the type of hood, maintenance, proper fit, and atmospheric dust concentrations during nonblasting periods when they were unhooded. The development of so-called accelerated silicosis is related to ordinary and faulty characteristics of sandblasting: high free-silica content of sand, use of inadequate or faulty protective devices, carelessness, and incomplete safety training.

Selected parameters of cell-mediated immunity were determined in a group of 16 patients with silicosis. The results were compared with those of a control group of 13 subjects without silica exposure. There were no group differences in the mean number of delayed hypersensitivity skin tests to a battery of recall antigens (purified protein derivative, candida, streptokinase-streptodornase, and trichophyton) or in the mean number of peripheral blood lymphocytes. Lymphocyte responsiveness to phytohemagglutinin, pokeweed mitogen, and the antigens listed, and the percentage of lymphocytes that formed sheep red blood cell rosettes (t cells) and complement rosettes (B cells) were also similar in both groups; however, the silica-exposed group demonstrated depressed lymphocyte stimulation in response to low concentrations of concanavalin A.

Of 39 silicotic sandblasters evaluated in 1972 and 1973, 17 (44 per cent) had positive serum antinuclear antibody reactions. This prevalence is higher than those reported for other pneumonconioses. Comparison of the groups positive and negative for antinuclear antibodies showed that patients positive for antinuclear antibodies were unlikely to have normal ventilatory function and were more likely to have roentgenograms showing large opacities. Both groups had similar proportions showing lobar cavitation or contraction.

A new plant manufacturing toluene diisocyanate (TDI) has provided a unique opportunity to investigate the effects of TDI vapor inhalation on respiratory health in a group of exposed workers who have been studied prior to the start of plant operation. In order to establish dose-response relationships and determine host factors, complete biologic monitoring, including pulmonary function and immunologic studies, has been performed concurrently with a comprehensive environmental monitoring program including continuous sampling for atmospheric concentrations of TDI. Study groups include workers with regular exposure to TDI in production jobs (83), workers with intermittent contact with this vapor, usually in maintenance (28), and a control group of workers employed outside the TDI area (55). This population is being followed for a period of 5 yr. The plant began operations in August 1973 with start-up procedures completed by the end of October. TDI spills occurred for numerous reasons, usually attributed to pump failure and resultant line blockage. Significant exposures also occurred in the drumming operation. The influence of these malfunctions is noted in the continuous monitoring data on atmospheric TDI concentrations which continue to reveal frequent excursions above the threshold limit value (TLV) of 0.02 ppm ceiling. These data are presented in relation to time and plant location. Although the first full year follow-up following initial exposure was not complete, certain preliminary clinical observations were made. A number of workers had episodes of acute respiratory symptoms related to single exposure to an irritant gas at work, usually either TDI or phosgene. It appears that two or three workers in the study population have become "clinically sensitized" to TDI and have been removed from regular TDI exposure. To date, the total number of workers who report the presence of recurring respiratory symptoms has not increased in comparison with the pre-exposure survey. Pulmonary function data after one full year of TDI exposure are not yet available. Pre- and post-shift ventilatory function studies do not indicate significant differences between the exposed and control groups. Selected individuals had carefully controlled inhalation challenge tests to monitored concentrations of TDI vapor under laboratory conditions. In workers suspected of having become "sensitized", immediate and/or late air flow obstruction was demonstrated and could be related to dose of inhaled TDI.

Several types of respiratory protective hoods used by sandblasters were investigated in two steel fabrication yards. MSA Gravimetric Dust Samplers were used to collect respirable dust samples outside and inside hoods during sandblasting. Colorimetric and x-ray diffraction techniques were applied to the samples for free-silica determination. The majority of the sandblasters, who wore various types of air-supplied hoods, were exposed to an average level of silica dust several times higher than the TLV. Sandblasters wearing non-air-supplied hoods were at the greatest risk. Modern well maintained and properly worn air-supplied hoods offered fair protection during sandblasting periods, but the concentration of suspended respirable dust in ambient air during non-blasting intervals exceeded the TLV by several times.