Publications

Chronic peripheral neuropathic pain is the result of abnormal activity in sensory nerves. It is well recognized that this sensory nerve dysfunction can be caused by traumatic, toxic, or metabolic insult to the nerve. In addition, there is growing recognition that neuropathic pain is a frequent manifestation of neurodegenerative diseases. In this regard, important clues to the cellular mechanisms of neuropathic pain may be found by close examination of neurodegenerative diseases (including Parkinson's disease) in which neuropathic pain is often an underappreciated but important clinical manifestation. This approach identifies specific mitochondrial and cytoskeletal mechanisms, previously implicated in the pathophysiology of neurodegenerative diseases in the central nervous system, that might contribute to neuropathic dysfunction in peripheral sensory nerve fibers. Investigations in preclinical models of common peripheral neuropathic pain conditions have supported the idea that a subset of these cellular mechanisms of neurodegeneration can produce painful hyperactivity in primary afferent nociceptors. Importantly, this emerging concept of neurodegenerative disease mechanisms in the primary afferent nociceptor identifies novel molecular targets for the treatment neuropathic pain.

Predictive and prognostic biomarkers offer a potential means to personalize cancer medicine, although many reach the market-place before they have been validated, and their adoption is often hindered by variable clinical evidence. Because of this variability in supporting evidence, clinical practice guidelines formulated by panels of subspecialty experts may be particularly important in guiding stakeholders' acceptance and use of new personalized medicine biomarker tests and other nascent technologies. This article provides a structured review of the clinical evidence supporting 4 contemporary biomarker tests in colorectal cancer: K-ras and B-raf mutation analyses, mismatch repair protein testing, and the Oncotype DX Colon Cancer Assay. All 4 tests have been evaluated for guideline inclusion by the NCCN Guidelines Panel for Colon Cancer. This case study shows significant variability in the level of clinical evidence associated with these tests. In the cases of B-raf and mismatch repair protein testing, the available evidence is also inconsistent as it pertains to the specific NCCN Guideline recommendation. Based on this uncertainty in the evidence base, the authors conclude that expert clinical judgment, experience, and consensus may be more heavily weighted than published clinical trial data in the evaluation of new personalized medicine biomarker tests. Potential implications of this conclusion and future directions for research are discussed.

We conducted a study designed to evaluate the efficacy and feasibility of a multilevel self-management intervention to improve nutritional intake in a group of older adults receiving Medicare home health services who were at especially high risk for experiencing undernutrition. The Behavioral Nutrition Intervention for Community Elders (B-NICE) trial used a prospective randomized controlled design to determine whether individually tailored counseling focused on social and behavioral aspects of eating resulted in increased caloric intake and improved nutrition-related health outcomes in a high-risk population of older adults. The study was guided by the theoretical approaches of the Ecological Model and Social Cognitive Theory. The development and implementation of the B-NICE protocol, including the theoretical framework, methodology, specific elements of the behavioral intervention, and assurances of the treatment fidelity, as well as the health policy implications of the trial results, are presented in this article.

BACKGROUND

Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present.

OBJECTIVE

We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria.

METHODS

In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements.

RESULTS

Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness.

CONCLUSION

The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.