Faculty Bibliography

Although colchicine has been a focus of research, debate and controversy for thousands of years, it was only approved by the United States Food and Drug Administration in 2009. Over the past decade, advances in the knowledge of colchicine pharmacology, drug safety and mechanisms of action have led to changes in colchicine dosing and to potential new uses for this very old drug. In this review, we discuss the pharmacologic properties of colchicine and summarize what is currently known about its mechanisms of action. We then discuss and update the use of colchicine in a variety of illnesses, including rheumatic and, most recently cardiovascular diseases.

BACKGROUND: Gout and osteoarthritis (OA) are the most prevalent arthritides, but their relationship is neither well established nor well understood. OBJECTIVES: We assessed whether a diagnosis of gout or asymptomatic hyperuricemia (AH) is associated with increased prevalence/severity of knee OA. METHODS: One hundred nineteen male patients aged 55 to 85 years were sequentially enrolled from the primary care clinics of an urban Veterans Affairs hospital, assessed and categorized into 3 groups: gout (American College of Rheumatology Classification Criteria), AH (serum urate >/=6.8 mg/dL, no gout), and control (serum urate <6.8 mg/dL, no gout). Twenty-five patients from each group subsequently underwent formal assessment of knee OA presence and severity (American College of Rheumatology Clinical/Radiographic Criteria, Kellgren-Lawrence grade). Musculoskeletal ultrasound was used to detect monosodium urate deposition at the knees and first metatarsophalangeal joints. RESULTS: The study showed 68.0% of gout, 52.0% of AH, and 28.0% of age-matched control subjects had knee OA (gout vs control, P = 0.017). Odds ratio for knee OA in gout versus control subjects was 5.46 prior to and 3.80 after adjusting for body mass index. Gout subjects also had higher Kellgren-Lawrence grades than did the control subjects (P = 0.001). Subjects with sonographically detected monosodium urate crystal deposition on cartilage were more likely to have OA than those without (60.0 vs 27.5%, P = 0.037), with crystal deposition at the first metatarsophalangeal joints correlating most closely with OA knee involvement. CONCLUSIONS: Knee OA was more prevalent in gout patients versus control subjects and intermediate in AH. Knee OA was more severe in gout patients versus control subjects.

Senior housestaff and junior faculty are often expected to perform clinical research, yet may not always have the requisite knowledge and skills to do so successfully. Formal degree programs provide such knowledge, but require a significant commitment of time and money. Short-term training programs (days to weeks) provide alternative ways to accrue essential information and acquire fundamental methodological skills. Unfortunately, published information about short-term programs is sparse. To encourage discussion and exchange of ideas regarding such programs, we here share our experience developing and implementing INtensive Training in Research Statistics, Ethics, and Protocol Informatics and Design (INTREPID), a 24-day immersion training program in clinical research methodologies. Designing, planning, and offering INTREPID was feasible, and required significant faculty commitment, support personnel and infrastructure, as well as committed trainees. Clin Trans Sci 2014; Volume #: 1-7.

PURPOSE OF REVIEW: Clinically identified myopathies are frequently a consequence of medication toxicities. However, recognizing drug-induced myopathies is sometimes difficult. Developing a greater understanding of the underlying mechanisms of drug-induced muscle toxicity will promote enhanced awareness and recognition, and improved management of these syndromes. RECENT FINDINGS: The adverse impact of certain drugs on muscle metabolism, muscle cell atrophy, and myocyte apoptosis is increasingly clear. Glucocorticoids impair glucose handling and directly promote protein catabolism. Statins impair mitochondrial function and alter intracellular signaling proteins, which can lead to myocyte apoptosis. Alternatively, statins can induce an autoimmune necrotizing myositis. Several medications impair autophagy, thus limiting access to the needed glycogen stores. SUMMARY: This review provides an overview of the main underlying mechanisms of drug-induced myopathies. These myopathies will most often be related to a drug's ability to alter metabolism and protein balance, induce necrosis, or impair autophagy.