Chronic beryllium disease in a precious metal refinery. Clinical epidemiologic and immunologic evidence for continuing risk from exposure to low level beryllium fume

Five workers at a precious metal refinery developed granulomatous lung disease between 1972 and 1985. The original diagnosis was sarcoidosis, but 4 of the workers were subsequently proved to have hypersensitivity to beryllium by in vitro proliferative responses of lymphocytes obtained by bronchoalveolar lavage. Review of medical records of coworkers and extensive industrial hygiene surveillance of the plant demonstrated that 4 cases occurred in the furnace area where air concentrations of beryllium fume were consistently below the permissible exposure limit of 2 micrograms/M3. A single case has been recognized from parts of the refinery where exposures to cold beryllium dust often exceeded the standard by as much as 20-fold. These data demonstrate that chronic beryllium disease still occurs and confirm the importance of specific immunologic testing in patients suspected of having sarcoidosis but with potential exposure to beryllium. The data raise concern about the adequacy of modern industrial controls, especially in the setting of exposure to highly respirable beryllium fume.     

The binding of monomeric IgG to human blood monocytes and alveolar macrophages

Macrophage receptor sites for IgG are important in the immune clearance of particles both from the blood and lung. We studied the number, affinity, and density of binding sites for monomeric IgG on human blood monocytes and alveolar macrophages. Monocytes and alveolar macrophages had a similar affinity for monomeric IgG at 37 degrees and 4 degrees C. The half-time for dissociation of the IgG-receptor complex was also similar for both cells. However, alveolar macrophages expressed approximately 5-fold more IgG binding sites than monocytes at both 37 degrees and 4 degrees C. Nevertheless, when cell surface area was estimated, these cells expressed a similar density of IgG binding sites (monocytes = 110 +/- 14.8 IgG binding sites/square micron; pulmonary macrophages = 138 +/- 46.9 IgG binding sites/square micron; p greater than 0.50). Gamma interferon increased the number and density of monocyte binding sites for monomeric IgG by 162 +/- 89%. Furthermore, patients with sarcoidosis, a disorder in which gamma interferon is spontaneously elaborated, expressed a similar increase in the number of IgG binding sites per monocyte, from 24,968 +/- 1,361 for normal subjects to 44,860 +/- 6,652 for patients with sarcoidosis. However, alveolar macrophages from 5 patients with sarcoidosis expressed a normal number of IgG binding sites. These data suggest that there is no major alteration in the Fc(IgG) receptor as monocytes differentiate into alveolar macrophages. Both gamma interferon treatment and sarcoidosis are associated with enhanced expression of the Fc(IgG) receptor on monocytes.     

Occultocarpon, a new monotypic genus of Gnomoniaceae on Alnus nepalensis from China

Microfungi in the Gnomoniaceae (Diaporthales, Ascomycetes) comprise species commonly reported as pathogens and endophytes on trees and herbaceous hosts primarily from temperate forests of North America, Europe, and Japan. The diversity of Gnomoniaceae in China is poorly known, although several plant families that occur there specifically the Betulaceae are considered important hosts. An exploratory trip to Yunnan, China, resulted in the discovery of several members of the Gnomoniaceae. In this paper a new monotypic genus, Occultocarpon and its species, O. ailaoshanense, are described and illustrated. A phylogeny based on three genes (LSU, rpb2, tef1-??) reveals that O. ailaoshanense belongs to the Gnomoniaceae and forms a branch distinct from the currently known genera. Occultocarpon ailaoshanense is characterized by perithecia with thin, central to eccentric necks in groups embedded in a stroma and oblong elliptical-elongated, one-septate ascospores. Occultocarpon ailaoshanense occurs on the bark of branches of Alnus nepalensis (Betulaceae) in Yunnan, China.     

Nasal polyposis: in search of a viral etiology using DNA hybridization.

The etiology of nasal polyps is unknown. Numerous theories have been proposed, with allergic and infectious causes predominant. A viral theory was postulated almost 40 years ago. In a pilot project, we studied 15 subjects comprising six controls and nine patients with nasal polyps. No known viruses were cultured from the nasal polyp tissue or nasal mucosal biopsies from the control subjects. DNA Hybridization for Epstein-Barr Virus, Herpes simplex virus, adenovirus type V, and Chlamydia trachomatis were also negative for all tissue studied. The use of molecular biological techniques is not widespread in otolaryngology and this is the first report, to the best of our knowledge, of the application of these techniques for the investigation of the viral etiology of nasal polyps.     

Dual-action penems and carbapenems.

Two new series of dual-action antibacterial agents were synthesized in which penems and carbapenems were linked at the 2'-position to quinolones through either an ester or a carbamate moiety. Potent, broad-spectrum antibacterial activity was observed for both classes of compounds, indicative of a dual-mode of action.     

Bone imaging after acute knee hemarthrosis

Follow-up evaluations were carried out in 84 patients examined 5–8 years after sustaining an acute traumatic hemarthrosis of the knee. The initial examination performed within 2 weeks of injury had revealed 18 patients with a stable knee and 66 with anterior instability. Twelve of the patients underwent anterior cruciate ligament reconstruction within 3 months of injury and 11 more did so between 1 and 3 years after injury. To document joint deterioration at follow-up, bone scintigraphy and conventional anteroposterior, lateral, and tunnel X-rays were taken. Medial, lateral, patellofemoral and patellar uptake in bone seintigraphy was graded from 0 to 4. Six radiological variables were graded at eight different sites. Sixty-three patients (75%) had a positive bone scan and 69 patients (82%) showed radiological changes. Bone scan and X-ray scores were both significantly higher in the reconstructed knees.Funded by NIH grant AR 39359-03     

Interstitial thermoradiotherapy of brain tumors: preliminary results of a phase I clinical trial

A Phase I clinical trial has been initiated to determine the feasibility, tolerance, and toxicity of interstitial thermoradiotherapy in the treatment of high-grade supratentorial brain gliomas. Hyperthermia was delivered by means of thermally-regulating ferromagnetic implants afterloaded into stereotactically placed plastic catheters. Heat treatments were given immediately before interstitial irradiation; in addition, five patients received a second heat treatment at the completion of brachytherapy. The desired target temperature for the 60-minute hyperthermia session was between 42 degrees C and 45 degrees C. Following hyperthermia, the catheters were afterloaded with Ir-192, which delivered a variable radiation dose of 14-50 Gy depending on the clinical situation. Interstitial irradiation was supplemented with external beam radiotherapy (40-41.4 Gy) in patients with previously untreated tumors. A total of 14 patients (4 males, 10 females) have been treated to date on this protocol. Eleven of the patients had a diagnosis of glioblastoma multiforme, whereas three had anaplastic astrocytoma. The mean implant volume was 61.5 cm3 (range: 9-119 cm3); the median number of interstitial treatment catheters implanted was 19 (range: 7-33). Continuous temperature monitoring was performed by means of multisensor thermocouple probes inserted in the center as well as in the periphery of the tumor. Of the 175 monitored intratumoral points, 83 (47%) had time-averaged mean temperatures of greater than 42 degrees C, and only 12 sensors (7%) exceeded a temperature of 45 degrees C. Among the 19 heat treatments attempted, there have been four minor acute toxicities, all of which resolved with conservative medical management and one major complication resulting in the demise of a patient. These preliminary results indicate that ferromagnetic implants offer a promising new approach to treating brain tumors with hyperthermia.     

The genetic toxicology of metal compounds: I. Induction of λ prophage in E coli WP2S(λ)

A number of metal compounds have been shown to be human carcinogens. Others, while not proven human carcinogens, are able to cause tumors in laboratory animals. Short-term bacterial assays for genotoxic effects have not been successful in predicting the carcinogenicity of metal compounds. We report here the ability of some metal compounds to cause the induction of λ prophage in E coli WP2_S(λ). By far the strongest inducing ability was observed with K2CrO4, followed by Pb(N0₃)₂ > MnCl₂ > Ni(OOCCH₃)₂ > CrCl₂ > NaWO₄ > Na₂MoO₄ > KMnO₄. With the exception of chromate, long-term exposures in a narrow, subtoxic dose range were required in order to demonstrate phage induction. A new microtiter assay for λ prophage induction, which incorporates these features, is described. This system also was able to detect very small amounts of organic carcinogens.