Spectrum of Voriconazole-Induced Periostitis With Review of the Differential Diagnosis.

OBJECTIVE: Voriconazole is an antifungal medication used primarily for the treatment of Candida and Aspergillus infections. A fairly newly described side effect of long-term voriconazole use is periostitis. The purpose of this article is to describe the main differential consideration-hypertrophic osteoarthropathy-and other differential diagnoses, including venous stasis, thyroid acropachy, and hypervitaminosis A. CONCLUSION: With knowledge of imaging appearance, clinical manifestations, and outcomes, radiologists can make an accurate diagnosis of voriconazole-induced periostitis, and clinical teams can initiate appropriate management.

Update on Imaging of Knee Arthroplasties: Normal Findings and Hardware Complications.

Total knee arthroplasty (TKA) is the most common joint replacement performed. This article reviews the normal appearance of TKA including the most common types of arthroplasties as well as complications. Common complications at the present time are infection, aseptic loosening, and instability. Rarer complications such as polyethylene wear, periprosthetic fracture, and soft tissue pathology are also discussed. Although the mainstay of imaging is radiographs, newer techniques in TKA imaging such as computed tomography and magnetic resonance imaging are also reviewed.

Cutting edge: Dexamethasone potentiates the responses of both regulatory T cells and B-1 cells to antigen immunization in the ApoE(-/-) mouse model of atherosclerosis.

The immunosuppressant dexamethasone was shown to preferentially deplete CD4+ effector T cells while sparing regulatory T cells (Tregs) in vivo. In the current study, we show that it also preferentially depletes B-2 cells while sparing B-1 cells. In the ApoE(-/-) mouse model of atherosclerosis, in which both Tregs and B-1 cells are thought to play an atheroprotective role, we show that HSP60-targeted immunization in the presence of dexamethasone raises Ag-reactive Tregs and B-1 cells concomitantly and reduces the severity of atherosclerosis. These results indicate that dexamethasone is an adjuvant that potentiates both the Treg and B-1 responses to immunogens. This study shows that B-1 cells with a specificity for a disease-relevant Ag can be raised in vivo by immunization.

Palmitate-derivatized human IL-2: a potential anticancer immunotherapeutic of low systemic toxicity.

PURPOSE AND EXPERIMENTAL DESIGN: Recombinant human IL-2 (rhIL-2) is a potent cytokine and FDA-approved anticancer drug. However, its clinical use has been limited by severe toxicity, associated primarily with systemic administration with excess protein distributing freely throughout the body. We hypothesized that rhIL-2 in alternate forms permitting more restricted localization may exert stronger antitumor efficacy and less toxicity. Here, we have tested the utility of palmitate-derivatized rhIL-2. rhIL-2 was reacted with N-hydroxysuccinimide palmitate ester. The resultant lipidated rhIL-2 (pIL-2), when mixed with cells, could spontaneously transfer from solution to cell surfaces. Next, anticancer efficacy of pIL-2 was assessed in two modalities. For adoptive T cell therapy, antitumor cytotoxic T cells (CTLs) were protein transferred ("painted") with pIL-2 and injected into mice bearing lymphoma. For in situ therapy, pIL-2 was injected intratumorally into mice bearing melanoma. Tumor growth and IL-2-associated toxicity were determined. RESULTS: In the lymphoma model, painting of the antitumor CTLs with pIL-2 markedly increased their viability and titer. In the melanoma model, intratumoral injection of pIL-2, but not rhIL-2, increased the number of activated CD8(+) T cells (IFN-γ(+)) in the spleen, reduced lung metastasis and prolonged the survival of treated mice. Moreover, while repeated intratumoral injection of rhIL-2 at an excessively high dose (10 injections of 10,000 IU/mouse) caused marked vascular leakage syndrome, the same regimen using pIL-2 caused no detectable toxicity. CONCLUSIONS: Transferring spontaneously from solution to cell surfaces, pIL-2 may bypass the current limitations of rhIL-2 and, thus, serve as a more effective and tolerable anticancer drug.