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Objective: To determine the prevalence, distribution, and histopathological conditions of skin abnormalities in neurofibromatosis 2 (NF2). Design: Case series. Setting: Hospital neurology department. Patients: Consecutive sample of 88 patients with NF2 referred through workshops and publications, genetic counseling, and referral from neurosurgical departments; 81 patients met the National Institutes of Health, Bethesda, Md, NF2 diagnostic criteria and the diagnosis was established by mutation or segregation analyses in 7 patients. Main Outcome Measures: Prevalence, distribution, and type of skin abnormalities; histopathological features of 29 skin tumors selected primarily for medical indications. Results: Fifty-two patients (59.1%) had 458 skin tumors, which were the first presenting sign in 27.3% of patients and usually appeared as flat dysplastic tumors or subcutaneous spherical nodular tumors of the peripheral nerves, on the limbs and trunk. Although 29 patients (33.0%) had cafe au lait spots, only 2 patients had as many as 6 spots. Compared with patients with milder disease, patients with more severe disease had a significantly greater prevalence of skin tumors (24.0% and 71.0%, P P =.004), flat dysplastic skin tumors (8.0% and 54.8%, P P =.004). The histologically analyzed tumors were predominantly schwannomas, but 5 were neurofibromas and 2 were mixed tumors. Conclusions: The prevalence of some skin tumor types in NF2 is high and varies with disease severity, and schwannomas predominate in sampled tumors. The occurrence of neurofibromas is surprising, but could be explained by an interaction between neurofibromin and the NF2 gene product in regulating the ras proto-oncogene. Arch Dermatol. 1997;133:1539-1543

To determine if increased lead absorption was associated with sperm count suppression or perterbation of the hypothalamopituitary system, we compared battery workers (N = 18), who were exposed to high airborne lead levels, with cement workers (N = 18), who were exposed to ambient lead levels. Blood lead, urinary lead, semen lead, and zinc protoporphyrin concentrations were markedly elevated (p less than .001) in battery workers. Battery workers had a significantly shifted (p less than .025) frequency distribution of sperm count (median count, 45 vs. 73 X 10(6) cells/cc, respectively). There were no significant differences between the two groups in mean follicle-stimulating hormone, testosterone, prolactin, luteinizing hormone, or total neutral 17-ketosteroid levels. Potential confounding factors (alcohol, cigarette, and coffee consumption, frequency of intercourse, and days of abstinence prior to semen donation) were not significantly different between the two groups. These results suggest a direct toxic effect of increased lead absorption on sperm production or transport in man.

This report describes a spectrum of respiratory illnesses associated with eosinophilia which occurred in a group of workers exposed to fumes from a synthetic rubber-based curing operation. Respiratory syndromes induced by this exposure included an acute sensitizing illness with dyspnea and wheezing in some workers and pulmonary infiltrates with eosinophilia in others. Another worker developed chronic obstruction of the airways with recurrent bronchitic illnesses. Mild to marked peripheral eosinophilia, up to 3,000/cu mm, was usually present in the symptomatic workers and in 11 of 30 asymptomatic workers. These cases illustrate the diversity of respiratory illnesses which may result from a common workplace exposure and reinforce the importance of considering occupational exposures in the differential diagnosis of peripheral eosinophilia.

To evaluate a suspected association between an outbreak of acute respiratory illness and eosinophilia and employment as a rubber worker, we performed a retrospective review of medical records of rubber workers employed from September 1983 to July 1984 in a plant housing a thermoinjection process. Twenty-five workers met the case definition of a respiratory illness requiring a physician visit. The predominant respiratory illness was acute in onset with cough, chest tightness, and dyspnea. Peripheral eosinophilia, up to 40% of white blood cells in a peripheral smear, was seen in 10 of 18 (56%) cases. Twenty-one of 25 white males with respiratory symptoms were employed in the thermoinjection process (odds ratio = 22, p less than .001). Smoking and employment in this process contributed independently to an increased risk of being a case as determined by a logistic regression analysis. Return to the plant building caused recurrence of symptoms in most cases, and these workers have been transferred or left the company. We conclude that a strong previously unrecognized association exists between employment in this neoprene rubber thermoinjection process and the development of an acute respiratory illness.

Silicates causing pneumoconiosis function as Fenton catalysts to generate hydroxyl radicals (.OH) when incubated with hydrogen peroxide and a reducing substance. In contrast, silicates which do not cause pneumoconiosis demonstrate no Fenton activity. Catalytic activity is decreased by pretreatment of silicates with the iron chelators deferoxamine or transferrin. Hemolysis from silicates is decreased by interventions which remove superoxide anion or hydrogen peroxide from the medium, or by pretreatment of dusts with iron chelators. Thus, asbestos and nonfibrous silicates may cause pneumoconiosis through a common oxidant mechanism by catalyzing production of toxic .OH radicals in the lung.

To investigate the origin of differences in previously published pulmonary function studies of workers in kaolin plants in Georgia, spirometric and radiographic data collected in a cross sectional survey of two large plants were analysed. As compared with workers in plant 2, workers in plant 1 had a 2.7-fold greater prevalence of pneumoconiosis and a mean 0.361 decrement in adjusted forced vital capacity. Our previous finding that exposure to kaolin was not associated with a decrement in lung function may have resulted from failure to consider differences between the plants.

Results of a cross-sectional study of ventilatory lung function (VLF) in a group of 307 working men showed that the leukocyte count in peripheral blood is more closely associated with the relative position (percentile) of a person in the frequency distribution of VLF than is smoking intensity. Leukocyte count is significantly (and inversely) correlated with VLF in nonsmokers as well as in smokers. A multiple regression analysis indicated that, after accounting for the effect of height and age, white blood cell (WBC) count explains more of the VLF variance than many other health determinants. Moreover, WBC count is the only variable, apart from height and age, that contributes significantly to the regression. Current smokers with elevated leukocyte count in peripheral blood may constitute a defined high-risk group because they demonstrate more negative regression age coefficients when compared with smokers without elevated WBC or with nonsmokers. Mechanisms that may explain these findings are discussed.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.