Publications

Considerable progress has been made in the development and testing of agents to treat osteoporosis. Most impressive are reports on new antiresorptive agents--both bisphosphonates (ibandronate and zoledronic acid) and monoclonal antibodies (MAbs) (denosumab) directed against receptor activator of nuclear factor kappaB-ligand, a key molecule in the control of commitment and activation of osteoclasts. Bisphosphonates promise convenience and potency at slowing bone loss, whereas denosumab offers powerful suppression of resorption and rapid offset of action. Attention is also shifting from the osteoclast as a target for new therapies to the osteoblast and the osteocyte, with its complex network within the depths of bone. Wnt signaling through the frizzled receptor and its coreceptor, the low-density lipoprotein receptor related protein-5, appears from both molecular and in vivo evidence to be a pivotal pathway for modulating osteoblastic activity, bone formation, and bone strength. The recently identified product of the SOST gene or sclerostin has also been shown to block Wnt signaling. Sclerostin is produced by the osteocytes buried in the bone and is a new target to treat bone loss. Clinical trial reports indicate that the calcimimetic cinacalcet can effectively treat PTH hypersecretion due to primary and secondary hyperparathyroidism and parathyroid carcinoma. Lastly, it is now recognized that the matrix protein dentin matrix protein-1 enhances the release of the phosphate-regulating factor fibroblast growth factor 23 and that mutations in dentin matrix protein-1 play a causative role in a form of hypophosphatemic rickets.

OBJECTIVE

The authors examined the relations between self-reported work tasks, use of cleaning products and latex glove use with new-onset asthma among nurses and other healthcare workers in the European Community Respiratory Health Survey (ECRHS II).

METHODS

In a random population sample of adults from 22 European sites, 332 participants reported working in nursing and other related healthcare jobs during the nine-year ECRHS II follow-up period and responded to a supplemental questionnaire about their principal work settings, occupational tasks, products used at work and respiratory symptoms. Poisson regression models with robust error variances were used to compare the risk of new-onset asthma among healthcare workers with each exposure to that of respondents who reported professional or administrative occupations during the entire follow-up period (n = 2481).

RESULTS

Twenty (6%) healthcare workers and 131 (5%) members of the referent population reported new-onset asthma. Compared to the referent group, the authors observed increased risks among hospital technicians (RR 4.63; 95% CI 1.87 to 11.5) and among those using ammonia and/or bleach at work (RR 2.16; 95% CI 1.03 to 4.53).

CONCLUSIONS

In the ECRHS II cohort, hospital technicians and other healthcare workers experience increased risks of new-onset current asthma, possibly due to specific products used at work.

This review critically evaluates the recent scientific literature relevant to occupational risk factors for chronic obstructive pulmonary disease (COPD) and chronic bronchitis. The 2003 American Thoracic Society statement on the occupational contribution to the burden of airway disease synthesized relevant data on this topic through 1999. Since 2000, 14 separate studies have published values or provide data that allow estimation of the population attributable risk per cent (PAR%) for the proportion of chronic bronchitis or COPD due to work-related factors. Based on data since 2000, the median PAR% value for both chronic bronchitis and COPD is 15%. A number of additional studies have been published that underscore the association between specific occupational exposures and airflow obstruction. In addition, data are emerging that indicate the extent to which COPD is a cause of work disability; limited data raise the possibility that among those with occupational COPD, disability may be even more prominent. This review supports previous analyses concluding that there is a causal association between work-related exposures and COPD.

INTRODUCTION

As part of a larger study assessing the covariates and outcomes of GHB use, we developed a telephone-survey instrument for hospitalized GHB exposed patients identified through poison control center surveillance and for self-identified GHB users recruited from the general public.

METHODS

We used an iterative review process with an interdisciplinary team, including pharmacists, a physician, and a medical anthropologist. In designing the structured, telephone-survey instrument, we prioritized inclusion of validated, drug-specific, and generic questionnaire batteries or individual items related to GHB or to other drugs of abuse. Only one published survey instrument specific to GHB use was identified, which we extensively expanded and modified. We also developed a number of GHB-specific items new to this survey. Finally, we included items from the National Survey on Drug Use & Health, CAGE questionnaire items on alcohol abuse, the SF-12 instrument, and selected National Health Interview items.

RESULTS

The final questionnaire consisted of 272 content items, the majority of which required simple yes or no responses. The bulk of the items (74%) were GHB-specific. The questionnaire was easily administered using computer-assisted telephone interview (CATI) software. A total of 131 interviews were administered with a mean administration time of 33+/-10 minutes. The instrument can also be used in other interview formats.

CONCLUSION

Developing a successful questionnaire calls for a multidisciplinary and systematic process. Structured, telephone administered surveys are particularly suited to expand and explore the basic information obtained by poison centers for case management.

Mammary gland involution is a period of intensive tissue remodeling. Over the course of a relatively brief period, a large proportion of the mammary gland epithelium undergoes programmed cell death and is removed by phagocytes. In addition, the gland is cleared of residual milk fat globules as well as milk and adipocytes become the predominant cell type. The role of the immune system in this process has not been clearly defined. Professional phagocytes derived from the immune system can participate in the clearance of apoptotic and autophagic cells, the removal of residual milk components, and the prevention of mastitis during mammary gland involution. However, many of these functions can also be performed by non-professional phagocytes (e.g. mammary epithelial cells). This review will discuss the evidence that supports a role for innate immune cells in mammary gland remodeling during involution.

The NIH Pharmacogenetics Research Network (PGRN) is a collaborative group of investigators with a wide range of research interests, but all attempting to correlate drug response with genetic variation. Several research groups concentrate on drugs used to treat specific medical disorders (asthma, depression, cardiovascular disease, addiction of nicotine, and cancer), whereas others are focused on specific groups of proteins that interact with drugs (membrane transporters and phase II drug-metabolizing enzymes). The diverse scientific information is stored and annotated in a publicly accessible knowledge base, the Pharmacogenetics and Pharmacogenomics Knowledge base (PharmGKB). This report highlights selected achievements and scientific approaches as well as hypotheses about future directions of each of the groups within the PGRN. Seven major topics are included: informatics (PharmGKB), cardiovascular, pulmonary, addiction, cancer, transport, and metabolism.

BACKGROUND

The clinical and physiologic features of respiratory bronchiolitis (RB)-interstitial lung disease (ILD) have been previously described; however, the natural history and outcome have not been systematically evaluated. The majority of published reports consider RB-ILD to be a nonprogressive ILD that clinically improves with smoking cessation and antiinflammatory treatment. In this study, we sought to determine the outcome of RB-ILD patients with and without smoking cessation and with and without corticosteroid therapy.

METHODS

Thirty-two RB-ILD cases confirmed by surgical lung biopsy were identified from a prospectively enrolled cohort of subjects with ILD. Initial and follow-up data on symptoms, physiology, treatment, and outcome were collected and analyzed.

RESULTS

Kaplan-Meier analysis revealed that at least 75% of RB-ILD patients survived > 7 years after diagnosis. Clinical improvement occurred in only 28% of cases, and physiologic improvement occurred in 10.5% of cases. One patient died of progressive ILD, and two patients died of non-small cell lung cancer. While physiologic improvement was limited to those who had ceased smoking, corticosteroids and/or other immunosuppressive therapy had little effect on symptoms or physiology.

CONCLUSIONS

This study shows that prolonged survival is common in RB-ILD. However, symptomatic and physiologic improvement occurs in only a minority of patients, and neither smoking cessation nor immunosuppressive therapy is regularly associated with clinically significant benefit.