Trends in cigarette smoking among refinery and petrochemical plant employees with a discussion of the potential impact on lung cancer.

OBJECTIVE: To examine trends in cigarette smoking prevalence and intensity among petroleum industry employees over a 22-year period, from 1976 to 1997, and to evaluate the hypothesis that the (about 20%) lower lung cancer mortality, when compared with the general population, among these workers is due to lower average cigarette consumption. METHODS: Self-reported smoking prevalence and intensity (number of cigarettes smoked per day) data were available from the Shell Health Surveillance System for approximately 5,400 employees in the 1970s, 11,000 in the 1980s, and 8,300 in the 1990s. Data were analyzed by gender, time period, and work status (production vs. staff). RESULTS: During the 22-year study period, smoking prevalence dropped significantly in this working population. When compared with the general US population, smoking prevalence trends were very similar. For the entire employee population, smoking prevalence was highest for women working in production (hourly) jobs. While smoking prevalence was higher among production employees than among staff employees, daily cigarette consumption was slightly lower. Cigarette consumption among Shell employees was similar to that in the US in the 1970s, but lower in the 1980s and 1990s. By applying smoking consumption data from the 1970s, the ratio of weighted lung cancer relative risks for Shell employees and the US general population was 0.98. In other words, the lung cancer mortality rate of refinery and petrochemical employees would be adjusted upward by 2% if one were to remove the influence of smoking consumption by Shell employees. CONCLUSIONS: Based on our data, it is unlikely that differences in smoking prevalence and intensity between refinery/petrochemical workers and the general population could account for the lower risk of lung cancer mortality reported in the literature.

Expression of endoplasmic reticulum stress proteins during skeletal muscle disuse atrophy.

Disuse atrophy of skeletal muscle leads to an upregulation of genes encoding sarcoplasmic reticulum (SR) calcium-handling proteins. Because many of the proteins that are induced with endoplasmic reticulum (ER) stress are ER calcium-handling proteins, we sought to determine whether soleus muscle atrophy was associated with a prototypical ER stress response. Seven days of rat hindlimb unloading did not alter expression of ubiquitous ER stress proteins such as Grp78, calreticulin, and CHOP/GADD-153, nor other proteins that have been shown to be activated by ER stressors such as vinculin, the type I D-myo-inositol 1,4,5-trisphosphate receptor, or protein kinase R, a eukaryotic initiation factor 2 alpha kinase. On the other hand, expression of heme oxygenase-1 (HO-1), an antioxidant ER stress protein, was significantly increased 2.2-fold. In addition, unloading led to an increase in calsequestrin, the muscle-specific SR calcium-binding protein, at both the mRNA (68%) and protein (24%) levels. Although disuse atrophy is associated with a significant remodeling of muscle-specific proteins controlling SR calcium flux, it is not characterized by a prototypical ER stress response. However, the upregulation of HO-1 may indicate ER adaptation to oxidative stress during muscle unloading.

Regulation of translation factors during hindlimb unloading and denervation of skeletal muscle in rats.

In the rat, denervation and hindlimb unloading are two commonly employed models used to study skeletal muscle atrophy. In these models, muscle atrophy is generally produced by a decrease in protein synthesis and an increase in protein degradation. The decrease in protein synthesis has been suggested to occur by an inhibition at the level of protein translation. To better characterize the regulation of protein translation, we investigated the changes that occur in various translation initiation and elongation factors. We demonstrated that both hindlimb unloading and denervation produce alterations in the phosphorylation and/or total amount of the 70-kDa ribosomal S6 kinase, eukaryotic initiation factor 2 alpha-subunit, and eukaryotic elongation factor 2. Our findings indicate that the regulation of these protein translation factors differs between the models of atrophy studied and between the muscles evaluated (e.g., soleus vs. extensor digitorum longus).

The calcineurin-NFAT pathway and muscle fiber-type gene expression.

To test for a role of the calcineurin-NFAT (nuclear factor of activated T cells) pathway in the regulation of fiber type-specific gene expression, slow and fast muscle-specific promoters were examined in C2C12 myotubes and in slow and fast muscle in the presence of calcineurin or NFAT2 expression plasmids. Overexpression of active calcineurin in myotubes induced both fast and slow muscle-specific promoters but not non-muscle-specific reporters. Overexpression of NFAT2 in myotubes did not activate muscle-specific promoters, although it strongly activated an NFAT reporter. Thus overexpression of active calcineurin activates transcription of muscle-specific promoters in vitro but likely not via the NFAT2 transcription factor. Slow myosin light chain 2 (MLC2) and fast sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) reporter genes injected into rat soleus (slow) and extensor digitorum longus (EDL) (fast) muscles were not activated by coinjection of activated calcineurin or NFAT2 expression plasmids. However, an NFAT reporter was strongly activated by overexpression of NFAT2 in both muscle types. Calcineurin and NFAT protein expression and binding activity to NFAT oligonucleotides were different in slow vs. fast muscle. Taken together, these results indicate that neither calcineurin nor NFAT appear to have dominant roles in the induction and/or maintenance of slow or fast fiber type in adult skeletal muscle. Furthermore, different pathways may be involved in muscle-specific gene expression in vitro vs. in vivo.

Identification of weight-bearing-responsive elements in the skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) gene.

The skeletal muscle sarco(endo)plasmic reticulum calcium ATPase (SERCA1) gene is transactivated as early as 2 days after the removal of weight-bearing (Peters, D. G., Mitchell-Felton, H., and Kandarian, S. C. (1999) Am. J. Physiol. 276, C1218-C1225), but the transcriptional mechanisms are elusive. Here, the rat SERCA1 5' flank and promoter region (-3636 to +172 base pairs) was comprehensively examined using in vivo somatic gene transfer into rat soleus muscles (n = 804) to identify region(s) that are both necessary and sufficient for sensitivity to weight-bearing. In all, 40 different SERCA1 reporter plasmids were constructed and tested. Several different regions of the SERCA1 5' flank were sufficient to confer a transcriptional response to 7 days of muscle unloading when placed upstream of a heterologous promoter. Two of these regions were analyzed further because they were necessary for the unloading response of -3636 to +172, as demonstrated using internal deletion constructs. Deletion analysis of these regions (-1373 to -1158 and -330 to +172) suggested that unloading responsiveness corresponded to CACC sites and E-boxes. Mutagenesis of cis-elements in the first region showed that a specific CACC box (-1262) was involved in SERCA1 transactivation and a nearby E-box (-1248) was also implicated. Constructs containing trimerized CACC sites and E-boxes showed that the presence of both elements is required to activate transcription. This is the first identification of specific cis-elements required for the regulation of a Ca(2+) handling gene by changes in muscle loading condition.

Building strategic partnerships between employers and managed care firms to enhance quality of care.

The challenges of integrating behavioral healthcare delivery and the demand for better management of behavioral healthcare benefits require corporate risk managers to focus on issues of quality and outcomes. A strategic partnership between the employer and a managed care organization is one tool for reducing risk and improving the quality of services for beneficiaries, using the techniques of total quality management. The following article describes a six-step process for launching such a strategic partnership, along with some potential pitfalls.

Psychiatric complications associated with geriatric surgery.

Detection of pre-existing psychopathologic problems in the geriatric surgical patient can often preclude further psychiatric complications. When complications such as delirium arise, collaboration between the surgeon and the psychiatrist enhances a satisfactory outcome.

Role of the pharmacist in an allergy clinic.

The duties performed by pharmacy residents assigned to an allergy clinic, on a rotating basis, are described. The pharmacists are responsible for preparation and control of allergenic extracts, obtaining patient histories, performing allergy testing procedures, refering patients to community health clinics, and patient consultation.