High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients.

The physiological role of phosphodiesterase (PDE)11 is unknown and its biochemical characteristics are poorly understood. We have expressed human His-tagged PDE11A4 and purified the enzyme to apparent homogeneity. PDE11A4 displays K(m) values of 0.97 microM for cGMP and 2.4 microM for cAMP, and maximal velocities were 4- to 10-fold higher for cAMP than for cGMP. Given the homology between PDE11 and PDE5, we have compared the biochemical potencies of tadalafil (Cialis, Lilly-ICOS), vardenafil (Levitra, Bayer-GSK), and sildenafil (Viagra, Pfizer Inc.) for PDE11A4 and PDE5A1. PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients.

Cancer mortality (1956-1985) among male employees of Atomic Energy of Canada Limited with respect to occupational exposure to external low-linear-energy-transfer ionizing radiation.

The mortality experience between 1956 and 1985 of 8977 males employed by Atomic Energy of Canada Limited is reported. A total of 4260 men, 47% of the cohort, were exposed to low doses of external ionizing radiation at low dose rates, with a mean cumulative equivalent dose of 52.1 mSv. For cancers as a whole the excess relative risk, based on 227 deaths, was 0.36% per 10 mSv (90% confidence bounds -0.46, 2.45). This is quite comparable to the corresponding estimate based on the atomic bomb survivors study. There was a positive association between radiation dose and death from leukemia (excluding chronic lymphatic leukemia) P = 0.058. However, this was based on only four deaths and hence cannot sensibly be compared to estimates based on high-dose studies. The present results suggest that, for cancer as a whole, risk estimates based on high-dose studies are unlikely to underestimate risks substantially for low-dose and low-dose-rate exposures.

Cancer mortality patterns among hairdressers and barbers in 24 US states, 1984 to 1995.

We evaluated cancer mortality patterns among hairdressers and barbers, according to occupation, coded on 7.2 million death certificates in 24 states from 1984 to 1995. Of the 38,721 deaths among white and black hairdressers and barbers of both sexes, 9495 were from all malignant neoplasms. Mortality odds ratios were significantly elevated for all malignant neoplasms, lung cancer, and all lymphatic and hemopoietic cancers among black and white female hairdressers. White female hairdressers had significant excess mortality from cancers of the stomach, colon, pancreas, breast, and bladder and from non-Hodgkin's lymphoma and lymphoid leukemia; mortality from these cancers was also elevated among black female hairdressers. White male hairdressers had significantly elevated mortality from non-melanoma skin cancer and non-Hodgkin's lymphoma. Mortality from all malignant neoplasms, although significantly elevated among both white and black female hairdressers, was significantly below the null for white male hairdressers. Black and white male barbers had significantly elevated mortality from stomach and pharyngeal cancer, respectively. A significant deficit in mortality from all neoplasms and cancers of the pancreas, lung, and prostate was noted for white male barbers. This large study of cancer mortality among hairdressers and barbers showed some differences in mortality patterns by gender and race. Further studies are required to determine if specific occupational exposures may explain some of the elevated cancer rates.

From explosions to black lung: a history of efforts to control coal mine dust.

Highlights in the history of efforts to prevent occupational lung disease among coal miners in the United States are reviewed. The Federal Coal Mine Health and Safety Act of 1969 is summarized, and the sources and effects of its provisions to prevent coal workers' pneumoconiosis are examined. Descriptions follow of the identification of coal workers' pneumoconiosis as a disease, identification of respirable coal mine dust as its cause, and establishment and enforcement of an exposure limit. The development of prevention efforts focusing on surveillance of both exposure and outcome and of enforcement of dust control methods is examined.

Occupational health and safety regulation in the coal mining industry: public health at the workplace.

The strategy for preventing occupational disease and injury in the coal mining industry employs several elements. Standards are set and enforced; technical assistance, research, and development are provided; and surveillance is conducted. Compensation for black lung is a vivid reminder of the consequences of failure to prevent disease. And, workers are represented by a union that encourages active participation in all aspects of this strategy. There are significant problems in each of these elements. Regulatory reform threatens to weaken many standards, there is a decline in government research budgets, surveillance is not well monitored, and compensation for black lung is significantly more difficult to obtain now than in the past. Moreover, the conservative governments of the past decade are not friendly towards unions. Nevertheless, the fundamental structure of disease and injury prevention remains intact and, more importantly, it has a historical record of success. The Mine Safety and Health Act provided for a wide array of basic public health measures to prevent occupational disease and injury in the mining industry. These measures have been effective in reducing both risk of fatal injury and exposure to respirable coal mine dust. They are also associated with temporary declines in productivity. In recent years, however, productivity has increased, while risk of fatal injury and exposure to respirable dust have declined. At individual mines, productivity with longwall mining methods appear to be associated with increases in exposure to respirable dust. These trends are not inconsistent with similar trends following implementation of regulations by OSHA. When OSHA promulgated regulations to control exposure to vinyl chloride monomer, enforcement of the standard promoted significant efficiencies in vinyl chloride production (5). Similarly, when OSHA promulgated its standard regulating exposure to cotton dust, this effort provoked modernization in the cotton textile industry (14). It is not inevitable that occupational health and safety regulations are associated with negative economic performance. On the contrary, in some instances, public health on the job and productivity are complementary.

Controlling occupational health hazards in construction.

This chapter describes, evaluates, and illustrates generic and conventional industrial hygiene methods for controlling occupational hazards affecting construction workers. Case studies that identify and control exposure to asbestos, lead, crystalline silica, and additives to cement are discussed.

Estimating possible fraud in coal mine operators' samples of respirable dust.

Coal mine operators are required to sample miners' exposure to respirable dust on a regular basis. A method has been developed for screening all operator samples for detecting possible instances of fraud. This method relies on the occurrence of very low concentration (VLC = 0.1 mg/m3) samples more frequently than expected. The number of underground mine sections from which 50% or more of all samples for FY 1990 were VLC (VLC-50 sections) was compared to the expected number, which was estimated by assuming that the occurrence of VLC samples could be described with a binomial probability distribution. Out of 1983 continuous mining sections, there were 147 VLC-50 sections vs. 7.3 expected (O/E = 20.1). Moreover, these 147 sections occurred more frequently than expected among small as opposed to large mines. For sections using conventional mining methods, 19 of 175 were VLC-50 vs. 0.9 expected (O/E = 20.8). There was one VLC-50 longwall section vs. 0.003 expected. For 99 bituminous and anthracite hand-loading sections the observed number of VLC-50 sections was 65 vs. 78 expected (O/E = 0.8). It is suggested that, except for hand-loading and longwall sections, sampling programs should be investigated at mines with VLC-50 sections.

Occupational medicine in Canada: an end or a new beginning?

Occupational medicine is frequently described in the broad context of the provision of occupational health services as a whole. Although this approach reflects the concepts currently underlying the delivery of occupational health services in Canada and in other countries, it is sometimes necessary to consider the problems that relate specifically to occupational medicine and to those who practise in this field. In this article some of these problems are discussed and suggestions made as to the way in which occupational medical practice may develop in Canada.

Controlling injury hazards in construction.

Using information from the U.S. government and the scientific literature, the authors identify preventive strategies for specific types of injuries and categorize features of employers and workers that are associated with low injury rates. They conclude that safe working conditions are possible and are related to the attitudes of workers and management.

Compensation for occupational disease with multiple causes: the case of coal miners' respiratory diseases.

Many diseases associated with occupational exposures are clinically indistinguishable from diseases with non-occupational causes. Given this, how are fair decisions made about eligibility for compensation? This problem is discussed in relation to the federal black lung program. Conflicting definitions of terms--coal workers' pneumoconiosis as defined by the medical profession, pneumoconiosis as defined by the United States Congress, and the popular term, black lung--are important considerations in this discussion. Each is embedded in different logical interpretations of the causes of occupational disease and of disability. Alternative views are presented and critically discussed.

Transport injuries in small coal mines: an exploratory analysis.

Mine Safety and Health Administration (MSHA) surveillance data were analyzed to elucidate mine characteristics or injury characteristics that distinguished mines with high rates of transport-related injuries from mines with lower transport injury rates. The results showed that most high-rate mines are small, high-rate mines have a disproportionate number of injuries involving young and less experienced workers, and injuries in high-rate mines are proportionally more severe. Further analyses of the MSHA injury data showed that smaller mines have a greater share of fatal and permanently disabling injuries, whereas larger mines have a greater share of injuries involving no lost time. Based on these results, we explored two explanations for the small mine injury risk: (1) a suggestion that differences in injury reporting between large and small mines may contribute to an apparent small mine injury risk, and (2) identification of factors contributing to a true difference in transport-related injury risk between small and large mines. Whereas it was true that most high injury rate mines were small, most small mines were actually zero-rate, having reported employment but no injuries to MSHA. An analysis employing binomial probability theory showed that a substantial proportion of small mines reported zero injuries when it was statistically probable that injuries would have occurred. This indicated that small mines may underreport injuries relative to larger mines. The possibility that reporting bias affected the associations found in this study was explored by eliminating the least severe injuries from the data set and evaluating changes in associations. This "adjustment" for reporting bias did not change previously observed relationships. Finally, MSHA injury data were analyzed in concert with mining population data collected by the Bureau of Mines. With such denominator information, the results indicated a disproportionately high risk of injury among workers in their first year at a mine and indicated that higher injury risk in small mines might be explained by the fact that workers at small mines have substantially less experience than workers at large mines. An effect of age was not found in these analyses. These results suggest the potential importance of targeted training programs for newly hired miners. Results also point to the need to explore specific factors contributing to the small mine injury risk, and to the necessity for complete and accurate reporting of injury data.

Chronic hazards and acute enforcement: dilemma for occupational health enforcement policy.

It is a well-understood principle of public health--and of disease control in general--that preventive efforts must be consistent with the natural history of a targeted disease. Governmental standards-setting and enforcement policies in occupational health confuse short-term strategies for safety hazard control with long-term disease control. Recent decisions in mining to rely on "significant and substantial" acute risk are incompatible with medical and epidemiological evidence on the nature and progress of chronic disease in many industries.