Disordered Toll-like receptor 2 responses in the pathogenesis of pulmonary sarcoidosis.

In this study, we hypothesized that the granulomatous disorder sarcoidosis is not caused by a single pathogen, but rather results from abnormal responses of Toll-like receptors (TLRs) to conserved bacterial elements. Unsorted bronchoalveolar lavage (BAL) cells from patients with suspected pulmonary sarcoidosis and healthy non-smoking control subjects were stimulated with representative ligands of TLR-2 (in both TLR-2/1 and TLR-2/6 heterodimers) and TLR-4. Responses were determined by assessing resulting production of tumour necrosis factor (TNF)-α and interleukin (IL)-6. BAL cells from patients in whom sarcoidosis was confirmed displayed increased cytokine responses to the TLR-2/1 ligand 19-kDa lipoprotein of Mycobacterium tuberculosis (LpqH) and decreased responses to the TLR-2/6 agonist fibroblast stimulating ligand-1 (FSL)-1. Subsequently, we evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)-associated lung disease induced by heat-killed Propionibacterium acnes. As quantified by blinded scoring of lung pathology, P. acnes-induced granulomatous pulmonary inflammation was markedly attenuated in TLR-2(-/-) mice compared to wild-type C57BL/6 animals. The findings support a potential role for disordered TLR-2 responses in the pathogenesis of pulmonary sarcoidosis.

Mortality patterns among U.S. veterans by occupation. I. Cancer.

The mortality experience of a nation-wide cohort of 293,958 veterans was analyzed by occupation and industry to generate hypotheses in occupational cancer. Results are presented on 107,563 deaths occurring between 1954 and 1970. Information on usual employment (occupation and industry) and smoking habits was available from questionnaires completed in 1954 and 1957. Complete enumeration of these results by occupation and industry is available as special National Cancer Institute monographs from the author (A. B.). This report presents the mortality experience for selected occupations. Excesses of lung cancer among shipyard workers, truck drivers, and plumbers are consistent with previous reports. Elevated risks for stomach cancer among carpenters and machinists may reflect exposure to dusts, abrasives, and cutting oils.

Cancer incidence among cosmetologists.

This cohort study examined cancer incidence in 13,650 Connecticut cosmetologists who had held licenses for 5 years or more and had begun hairdressing school prior to January 1, 1966. Cancer incidence rates for the general Connecticut population, 1935-78, were compared with those for 11,845 female and 1,805 male cosmetologists. The females had a standardized cancer incidence ratio (SIR) of 112 (P less than .01). A significant excess of lung cancer (SIR = 141) and excesses of brain (SIR = 168) and ovarian cancer (SIR = 134) of borderline significance were observed. No significant cancer risk was evident for female cosmetologists licensed since 1935, even for those with 35 years or more of follow-up, although the SIRs for brain cancer, lymphoma, and leukemia were elevated. Female cosmetologists who entered the profession between 1925 and 1934, however, experienced a significant overall cancer incidence (SIR = 129) and significant excesses of respiratory, breast, corpus uterine, and ovarian cancers. Those with 35 years or more from time of first license appeared to be at the highest risk. Among males the overall cancer incidence rate was close to that expected (SIR = 105). Smoking habits and reproductive factors that could not be taken into account may explain some of the excesses among females. Although no specific occupational agent could be identified, the excess numbers of leukemias in females and brain cancers among males and females merit continued surveillance.

Nasopharyngeal cancer, sinonasal cancer, and occupations related to formaldehyde: a case-control study.

Formaldehyde vapor induces cancer of the nasal passages in laboratory animals. In this case-control epidemiologic study, occupational information was obtained for 198 persons with sinonasal cancer (SNC), for 173 with nasopharyngeal cancer (NPC) identified as incident cases by the Connecticut Tumor Registry over 41 years among Connecticut males dying of any cause, and for 605 controls sampled from Connecticut death certificates. City directories and death certificates provided information on job, industry, employer, and year of employment for exposure classification. Without knowledge as to case-control status, an industrial hygienist particularly experienced in epidemiologic studies of formaldehyde classified each study subject with respect to probability and degree of formaldehyde exposure. For those with probable exposure to the high level 20+ years prior to death the odds ratio for NPC was 2.3 [95% confidence limits (CL): 0.9, 6.0], and for those with this same risk factor among men dying at age 68+ (the median study age at death or older) the odds ratio was 4.0 [95% CL: 1.3, 12.0--with two-sided P = .015, unadjusted for multiple significance tests, and with two-sided P = .129 in testing for interaction between this risk factor (never any exposure vs. probable exposure to high level 20+ years prior to death) and age (age less than 68 yr vs. age 68+ yr)]. Odds ratios were close to unity for 9 of 13 industries. Formaldehyde-related occupations in printing appeared to be associated with any type of nasal cancer (either SNC or NPC).

Mortality among industrial workers exposed to formaldehyde.

A historical cohort study evaluated the mortality experience of 26,561 workers employed in 10 formaldehyde-producing or -using facilities. Approximately 600,000 person-years of follow-up accrued as workers were followed to January 1, 1980. Estimates of historical exposure to formaldehyde by job were developed by project industrial hygienists using monitoring data available from participating plants, comments from long-term workers, and comprehensive monitoring data specifically collected for this study. Mortality from all causes combined was about as expected [standardized mortality ratio (SMR) = 96] based on mortality rates of the general U.S. population. Significantly fewer deaths occurred from infective and parasitic diseases (SMR = 51) and from accidents (SMR = 72) than expected. Cancer overall was not related to formaldehyde exposure. Workers exposed to formaldehyde had slight excesses for Hodgkin's disease and cancers of the lung and prostate gland, but these excesses were not consistently related to duration of or average, cumulative, or peak formaldehyde exposure levels. Recent animal studies found nasal cancer among rats exposed to formaldehyde, but no excess of this tumor occurred in this study. Mortality from brain cancer and leukemia among these industrial workers was not excessive in contrast to reported excesses among professional groups (e.g., anatomists, embalmers, and pathologists) with exposure to formaldehyde. Although there was a deficit for cancer of the buccal cavity and pharynx, mortality from certain subsites, i.e., the nasopharynx and oropharynx, was elevated. These subsites did not, however, show a consistently rising risk with level of exposure. These data provide little evidence that mortality from cancer is associated with formaldehyde exposure at levels experienced by workers in this study.

Cancer and other causes of death among embalmers.

To evaluate the potential carcinogenic effects of formaldehyde, we examined the proportionate mortality experience of embalmers licensed to practice in California. Mortality was significantly elevated for total cancer, arteriosclerotic heart disease, and suicide, whereas significant deficits were noted in mortality from diseases of the respiratory and genitourinary systems. Deaths from cancers of the brain, colon, and prostate and leukemia were significantly higher than expected. No increased mortality was seen for cancers of the respiratory tract, including the nasal passages, where an effect might be expected based on animal studies. A parallel mortality survey of embalmers from New York State showed similar findings, with excesses of brain tumors, leukemia, colon cancer, arteriosclerotic heart disease, and cirrhosis. Further investigation is needed to determine whether any of these outcomes is related to formaldehyde exposure.

The Prevalence of MRSA Nasal Carriage in Preoperative Pediatric Orthopaedic Patients.

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) has been described as a risk factor for postsurgical infection. The purpose of this study is to determine the prevalence of MRSA in pediatric orthopaedic patients and whether being a MRSA carrier is a predictor of postoperative infection. Six hundred and ninety-nine consecutive pediatric patients who underwent MRSA nasal screening prior to surgery were studied. Postoperative cultures, total surgical site infections (SSIs), and epidemiological and surgical prophylaxis data were reviewed. Forty-four of 699 patients (6.29%) screened positive for MRSA. Nine of the 44 patients (20.5%) that screened positive for MRSA had a subsequent SSI compared to 10 of the 655 patients (1.52%) that screened negative (p < 0.05). All 9 patients with a SSI had myelomeningocele. The prevalence of MRSA was 6.30% and was predictive of postoperative infection. Children with myelomeningocele were at the highest risk for having a positive MRSA screening and developing SSI.

Experience with ambulatory preoperative bowel preparation at the Johns Hopkins Hospital.

A transition to ambulatory preoperative antibiotic bowel preparation was carried out. The protocol included a liquid diet for 40 hours preceding surgery and coordination of purging with buffered oral saline laxative, 45 mL containing 8 g sodium phosphate and 22 g sodium biphosphate (Fleet Phospho-Soda, C.B. Fleet Co, Lynchburg, Va) and bisacodyl preparation with an oral erythromycin base-neomycin routine. Enemas were omitted. Personnel in the preoperative evaluation center had the responsibility of instructing patients, distributing directions and drugs, and reviewing for compliance and possible problems during the preoperative period. All patients scheduled for any of a variety of gastrointestinal procedures, as well as some other complex operations, were included in this study. Follow-up data were obtained. Surgeons' comments regarding efficacy were highly favorable. In only five cases was there comment regarding liquid stool, and this was no impediment to surgery. This incidence was comparable with that of the inpatient experience, as was the spectrum of postoperative complications. Transfer of responsibility to the department proceeded with ease. Results were entirely comparable with those of the former inpatient experience.

Mortality among retired fur workers. Dyers, dressers (tanners) and service workers.

A retrospective cohort mortality study was conducted on 807 fur dyers, fur dressers (tanners), and fur service workers who were pensioned between 1952 and 1977 by the Fur, Leather and Machine Workers Union of New York City. Workplace exposures of fur workers varied with job category. Dyers were exposed to oxidative dyes used in commercial hair dyes; dressers and service workers were exposed to tanning chemicals. In a comparison with the New York City population, no significant increases in mortality were observed among the fur dyers. Among fur dressers, mortality from all malignant neoplasms [standardized mortality ratio (SMR) 151] and lung cancer (SMR 232) was significantly elevated, as was mortality from cardiovascular disease (SMR 126) among fur service workers. When examined by ethnic origin, the elevated SMR values and directly age-adjusted rate ratios suggested that foreign-born fur dressers and eastern European-born fur workers experienced the highest risks for lung and colorectal cancers, respectively. These data support previous findings of increased mortality from colorectal cancer in the foreign-born population of the United States and suggest a possible occupational etiology for the observed lung cancer excess.

Rapid detection of benzoylecgonine in vitreous humor by enzyme immunoassay.

The usual specimens submitted by a medical examiner for toxicological analysis include blood, urine, bile, vitreous humor, stomach contents, and solid-organ tissue. The detection of drugs in these specimens typically involves a combination of techniques including colorimetry, immunoassay, and gas chromatography. Although many laboratories rely principally on urine for the detection of drugs of abuse by immunoassay, these assays may be applied to other specimen types. An evaluation of Microgenics Corporation's cloned enzyme donor immunoassay (CEDIA) was conducted in order to evaluate its use in the detection of cocaine/cocaine metabolites in vitreous humor specimens. During a 14-month period, 392 vitreous humor specimens were analyzed by the CEDIA DAU Cocaine assay. Instrument parameters were set according to published manufacturer's guidelines. All presumptive positive immunoassay results prompted confirmatory testing and quantitation by gas chromatography-mass spectrometry (GC-MS) of other specimens including blood. Vitreous humor specimens were not tested by GC-MS. Using a approximately 100-ng/mL cutoff, the CEDIA assay produced 23 presumptive positive results, 22 of which were confirmed by GC-MS. The only specimen which could not be confirmed, elicited an immunoassay screen value near the cutoff limit. Routine analysis of blood, urine, bile, and/or bladder wash specimens by gas chromatography-nitrogen phosphorus detection revealed the presence of cocaine/cocaine metabolites in only 7 (31.8%) of the 22 confirmed cases. The concentration ranges of cocaine and benzoylecgonine in the blood specimens were none detected to 337 ng/mL and 17 to 8598 ng/mL, respectively. Cocaethylene was not detected in these cases. Analysis of vitreous humor specimens by CEDIA improved the detection rate of cocaine/cocaine metabolites by 0.7% in the cases submitted to our laboratory during the 14-month period.

Case management--a vital link to performance improvement.

A pilot program in the cardiac surgical service resulted in a $ 1.3 million reduction in patient charges while quality patient outcomes were sustained. Pivotal to the success of the program was the implementation of the case manager role.

Nasal cancer in the U.S. shoe industry: does it exist?

Studies in England and Italy have demonstrated a striking association between employment in the shoemaking industry and cancer of the nasal cavities and sinuses. However, three recent, large-scale proportionate mortality studies of U.S. shoeworkers do not show any deaths from these tumors. This paper reviews the methodology of those studies, emphasizing the underlying data and statistical power. In addition, epidemiologic and other considerations important in assessing and interpreting the apparent absence of a nasal cancer risk in the U.S. shoe industry are discussed.

Proportionate mortality among US shoeworkers, 1966-1977.

Proportionate mortality for various causes was examined among 3,754 decedents (2,144 men, 1,610 women) who had worked in shoe manufacturing plants represented by either of two labor unions in the US. None of the shoeworker deaths were attributed to nasal cancer, whereas 2.2 were expected on the basis of general population data. Mortality from leukemia and cancer of the urinary bladder was not unusual in either sex or either union. However, deaths from cancers of the liver and gallbladder combined were significantly increased among male and female members of one union. Three deaths from mesothelioma were seen among members of this same union. Rectal cancer mortality was higher than expected among men and women in both unions. The findings are at variance with previous reports of high risks of certain cancer sites among shoeworkers. However, results for liver and gallbladder cancer and mesothelioma suggest the possibility that other previously unsuspected hazards may have been present in certain areas of the US shoe industry.

Mortality patterns among embalmers.

In view of recent findings of nasal cancer in rats exposed to formaldehyde vapors, we investigated the proportionate mortality experience of embalmers licensed to practice in New York State. Mortality was significantly elevated for cancers of the skin and colon and for arteriosclerotic heart disease, whereas significant deficits were seen in mortality from respiratory diseases and accidents. Respiratory cancer mortality was not excessive and no deaths were attributed to nasal cancer. Mortality was significantly elevated for cancers of the skin, kidney, and brain among those licensed only as embalmers, whereas mortality patterns were unremarkable among those licensed also as funeral directors (and presumably less exposed to formaldehyde) These preliminary results indicate the need for occupational cohort studies to clarify the carcinogenic potential of formaldehyde.

A survey of the prevalence of epididymitis in an industrial setting.

In response to concerns about the occurrence of epididymitis among employees at a Du Pont textile fibers plant, information was obtained from 1342 (94.8%) active male employees on history of epididymitis and/or orchitis (6.8%), prostatitis (11.5%), other genitourinary conditions, and vasectomy. Vasectomy was associated with an odds ratio of 3.26 (90% confidence interval (CI) = 1.96, 5.43) for subsequent development of epididymitis. History of prostatitis was also a risk factor for epididymitis (odds ratio = 5.02, 90% CI = 2.94, 8.58).

Mortality among workers in a shoe manufacturing company.

Several epidemiologic studies have suggested that leather workers have an elevated risk of bladder cancer, nasal cancer, and leukemia. A case-control analysis of patient files at a large cancer treatment facility in New York State indicated that several bladder cancer patients had worked at a large shoe manufacturing company in upstate New York. A mortality study was initiated to determine whether there was an unusual cancer risk associated with employment in this facility. Because company records were not available, local newspaper obituaries were used to identify former company employees who died between 1960 and 1979. Proportionate mortality (PMR) analyses were conducted by using 4,734 death certificates and the general U.S. population for comparison. There were no excess deaths from nasal cancer or bladder cancer, and mortality from leukemia was slightly lower than expected. Increased relative frequencies of digestive cancers were seen among men and women. There were significant excesses of deaths from multiple myeloma among both men (PMR = 193) and women (PMR = 346).

Comparison of crude and smoking-adjusted standardized mortality ratios.

To systematically evaluate bias in estimating relative risks associated with occupational exposures obtained in the absence of smoking data, the authors compared crude and smoking-adjusted standardized mortality ratios for selected occupations using data from a study of U.S. veterans. Crude and smoking-adjusted SMRs were highly correlated: lung cancer (r = .88), bladder cancer (r = .98), and intestinal cancer (r = .97). Greater differences occurred for lung cancer, which is more strongly related to smoking than bladder or intestinal cancer.