Neutrophil activation identifies patients with active polyarticular gout.

BACKGROUND: Gout is the most prevalent inflammatory arthritis in developed countries. A gout flare is mediated by phagocytosis of monosodium urate crystals by macrophages and neutrophils leading to subsequent activation of neutrophils contributing to synovitis, local joint destruction, and systemic inflammation. We hypothesize that biomarkers from activated neutrophils reflect gout disease activity. The objective of this study therefore was to investigate the clinical utility of neutrophil-derived biomarkers in gout disease activity. METHODS: Plasma samples from 75 gout patients participating in the "Reade gout cohort Amsterdam" were compared with 30 healthy controls (HC). Levels of neutrophil extracellular traps (NETs) and neutrophil activation markers (calprotectin and peroxidase activity) were analyzed by ELISA and fluorimetry, compared to healthy controls, and related to markers of inflammation and disease activity. RESULTS: Levels of NETs, as well as neutrophil activation markers, were increased in gout patients compared to HC (p < 0.01). No associations were found between markers of cell death (cell-free DNA and NETs) and disease activity. Cell-free levels of genomic DNA were elevated among gout patients compared to HC (p < 0.05) and related to the number of gout attacks in the last year (ß = 0.35, p < 0.01). Peroxidase activity correlated with disease activity (RAPID score: ß = 0.49, p < 0.01, MHAQ: ß = 0.66, p < 0.01) and inflammation markers (CRP: ß = 0.25, p = 0.04, and ESR: ß = 0.57, p < 0.001). Involvement of ankle or wrist resulted in significant higher peroxidase levels compared to mono-articular disease (ß = 0.34, p < 0.01), indicating that peroxidase activity is a marker of poly-articular gout. Calprotectin (S100A8/A9) correlated with the inflammation marker CRP (ß = 0.23, p = 0.05) and morning stiffness, especially in patients with chronic poly-articular gout (ß = 0.71, p < 0.01). CONCLUSIONS: Neutrophil activation markers are associated with characteristics of active, polyarticular gout. Furthermore, NETs are present in the peripheral blood of gout patients. However, NETs do not associate with markers of disease activity or inflammation. Future research should point out if peroxidase and calprotectin could be used in clinical practice as biomarkers for monitoring gout disease activity.

Interactive effects of dietary wheat bran and lard on N-methyl-N'-nitro-N-nitrosoguanidine-induced colon carcinogenesis in rats.

A 3 x 3 factorial experiment was conducted to examine how dietary fiber (wheat bran) and fat (lard) interactively affect the genesis of N-methyl-N'-nitro-N-nitrosoguanidine-induced colon cancer in rats. Groups of 30 male 4-week-old Wistar rats were fed ad libitum one of nine experimental diets containing either 15 (low), 27.5 (medium), or 40% (high) energy as fat in combination with 0.7 (low), 2.2 (medium), or 3.8 g (high) fiber/100 kcal for a period of 37 weeks. After 4 weeks, each rat received a total of five weekly intrarectal instillations of 6 mg N-methyl-N'-nitro-N-nitrosoguanidine/kg. The highest colon carcinoma incidence and the highest total number of carcinomas of the colon were observed in the animals fed the medium-fat/medium-fiber diet. The highest number of polyps and a relatively high polyp incidence occurred in the animals on the high-fat/low-fiber diet. An enhancing effect of fat on both the tumor incidence and tumor multiplicity was clearly present for the low-fiber diets, whereas fat had no effect when the fiber content of the diet was high. In general, the results showed a nonlinear dose-response relationship for fiber and fat. These results indicate that both dietary fiber and fat affect colon carcinogenesis in a complex, interactive manner.

Limb salvage in a diabetic with necrotizing fasciitis: case report and literature review.

Necrotizing fasciitis must be considered in a diabetic with cutaneous ulceration. A case report of limb salvage in a 48-year-old diabetic female with progressive necrotizing fasciitis is presented. Methods of early diagnosis including clinical signs, radiographs, and soft tissue biopsy of the involved extremity are reviewed. The microbiology of the disease is also discussed. A modification of the Orr technique using infrequent dressing changes in the management of necrotizing fasciitis is presented. In our case this resulted in preservation of life and a functional limb.

Localization of 99mTc-methylene diphosphonate in skin lesions of pseudoxanthoma elasticum.

Increased uptake of 99mTc-methylene diphosphonate (MDP) is demonstrated in a patient with pseudoxanthoma elasticum (PXE) at the affected site. PXE is a hereditary disease with variable expression. Calification of dermal elastic fibers is a characteristic feature of affected skin. Recently, apatite crystals were identified in the affected skin of the patients with PXE. The mechanism of uptake of 99mTc-MDP is probably related to chemisorption of the tracer onto hydroxyapatite crystals in the affected dermis.

The team approach in salvage of the diabetic foot.

Various problems encountered in dealing with diabetic feet are discussed from the point of view of the orthopedist, the vascular surgeon, and the specialist in infectious disease. In our hospital, each new diabetic patient with a compromised extremity is evaluated by the team, and joint decisions are made concerning therapy. Treatment may be tedious and time consuming, but under these optimum conditions, we feel our salvage rate has been much improved. When it is realized that 30 percent of all diabetics with an amputation of one extremity come to amputation of the other extremity within three years, the rationale for this additional attention and care becomes obvious.