Imaging characteristics of intravascular papillary endothelial hyperplasia.

PURPOSE: Intravascular papillary endothelial hyperplasia (IPEH) is a soft tissue, tumor-like, benign, reactive, vascular proliferation that, although not rare, is uncommonly imaged. We report the imaging findings of intravascular papillary endothelial hyperplasia in 13 patients, highlighting characteristic imaging features. MATERIALS AND METHODS: We retrospectively reviewed 13 patients with IPEH who had corresponding MR and/or ultrasound imaging. MR imaging studies were evaluated for lesion location, shape, size, signal intensity, signal heterogeneity, and enhancement. Ultrasound studies were assessed for lesion shape, size, echogenicity, heterogeneity, and vascularity. Demographic data, including patient age, gender, and clinical history were also reviewed. RESULTS: Most patients (11 of 13) presented with an enlarging mass. The age range was 10-72 years (mean 46) with ten females and three males. Eleven of the 13 lesions were primary IPEH without an associated preexisting vascular lesion. Ten of 13 lesions were in the superficial soft tissues, all of which were primary IPEH. Two of the three lesions in the deep tissues were secondary IPEH, arising within a preexisting vascular lesion. Lesions were small (mean 1.4 cm) and had a rounded shape. All of the primary lesions demonstrated high T2 signal peripherally and variable T2 signal centrally, with most demonstrating superficial location (91 %), peripheral enhancement (89 %) and associated dominant vessel (73 %). The five lesions evaluated by ultrasound were all hypoechoic with either scattered or peripheral vascularity on Doppler. CONCLUSIONS: Primary papillary endothelial hyperplasia is commonly seen in the superficial soft tissues when captured on imaging and has a characteristic imaging appearance.

Differences in the chlorine reactivity of four microcystin analogues.

The presence of microcystin toxins in drinking water is highly undesirable as they have the potential to adversely affect human health. Consequently, effective removal of these toxins from water is a major goal for water authorities. In this study, four microcystin analogues were chlorinated in two treated waters, and two of the analogues were chlorinated in deionised water. The oxidation of the microcystins was related to the chlorine exposure (CT) of the sample waters with the ease of oxidation following the trend: microcystin-YR > microcystin-RR > microcystin-LR > or = microcystin-LA. This trend was in agreement with published data on model compounds and free amino acids. Values of CT of up to 25 mg min L(-1) were required for oxidation of all microcystin analogues to below the World Health Organization guideline value of 1.0 microg L(-1). Results from this study indicate that for some water resources it is important to determine the speciation of the microcystin analogues to optimise chlorination practices.

Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects of levo-alpha-acetylmethadol: importance of clinical investigations to validate in vitro drug metabolism studies.

OBJECTIVE: Levo-alpha-acetylmethadol (LAAM, levacetylmethadol) is a long-acting opioid agonist used for the prevention of opioid withdrawal. LAAM undergoes sequential N-demethylation to norLAAM and dinorLAAM, which are more potent and longer-acting than LAAM. Hepatic and intestinal microsomal N-demethylation in vitro is catalysed mainly by cytochrome P450 (CYP) 3A4; however, the role of CYP3A in LAAM disposition in humans in vivo is unknown. This investigation tested the hypothesis that CYP3A induction (or inhibition) would increase (or decrease) LAAM metabolism and bioactivation and, thus, clinical effects. It also related changes in LAAM disposition during enzyme inhibition or induction to any changes in pharmacological effect. METHODS: Healthy volunteers (n = 13) completed the three-way, randomised, balanced crossover study. Subjects received oral LAAM (0.25 mg/kg) after CYP3A induction (rifampicin [rifampin]), inhibition (troleandomycin) or nothing (controls). Plasma and urine LAAM, norLAAM and dinorLAAM were determined by electrospray high-performance liquid chromatography/mass spectrometry (HPLC/MS). Dark-adapted pupil diameter change from baseline (miosis) was the LAAM effect measure. Results were analysed by noncompartmental methods and by a combined pharmacokinetic/pharmacodynamic model. RESULTS: Compared with controls, CYP3A induction (or inhibition) decreased (or increased) plasma LAAM concentrations and mean area under the plasma concentration-time curve from time zero to infinity (AUC(infinity) 199 +/- 91 [control] versus 11.3 +/- 4.0 [rifampicin] and 731 +/- 229 ng . h/mL [troleandomycin]; p < 0.05), and increased (or decreased) median formation clearances of norLAAM (1740 versus 14 100 and 302 mL/h/kg; p < 0.05) and dinorLAAM (636 versus 7840 and 173 mL/h/kg; p < 0.05). Surprisingly, however, CYP3A induction (or inhibition) decreased (or increased) mean plasma metabolite AUC from 0 to 96 hours (AUC(96)) [norLAAM + dinorLAAM] (859 +/- 241 versus 107 +/- 48 and 1185 +/- 179 ng . h/mL; p < 0.05) and clinical effects (mean miosis AUC(96) 128 +/- 40 versus 22.5 +/- 14.9 and 178 +/- 81 mm . h; p < 0.05). Clinical effects were best correlated with plasma norLAAM concentrations. CONCLUSION: CYP3A mediates human LAAM N-demethylation and bioactivation to norLAAM and dinorLAAM in vivo. Paradoxically, however, CYP3A induction decreased and inhibition increased LAAM active metabolite concentrations and clinical effects. This suggests a CYP3A-mediated metabolic pathway leading to inactive metabolites, which predominates over CYP3A-dependent bioactivation. These results highlight the need for clinical investigations to validate in vitro drug metabolism studies.