We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl‐methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d‐MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l‐MPH, and (3) will l‐MPH enantioselectively interact with ethanol to yield l‐ethylphenidate (l‐EPH)? Mice were dosed with MTS (¼ of a 12.5 cm2 patch on shaved skin) or a comparable oral dl‐MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic–mass spectrometry monitoring of N‐(S)‐prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l‐MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l‐EPH and to an elevation in d‐MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route‐dependent drug absorption rate differences, MTS was associated with significant MPH–ethanol interactions. Ethanol‐mediated increases in circulating concentrations of d‐MPH carry toxicological and abuse liability implications should this animal model hold for ethanol‐consuming attention‐deficit hyperactivity disorder patients or coabusers. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2966–2978, 2011

Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

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Epicardial adipose tissue (EAT) is metabolically bioactive fat. The present study aimed to clarify the relationship between EAT amount and early impairment of left ventricular (LV) systolic function in patients with preserved ejection fraction (EF), all evaluated echocardiographically. Participants comprised 62 elderly women (mean age ± standard deviation, 68 ± 11 years) with lifestyle-related diseases and EF ≥ 60 %. EAT amount was evaluated as thickness. Parameters suggesting early impairment of systolic function such as decreases in systolic mitral annular velocity (S') and tissue mitral annular displacement percentage (TMAD %) were evaluated along with EF. Correlations between EAT thickness and these LV systolic functions were assessed. Influences of various factors on the resultant significant relationships were also assessed. EAT thickness correlated inversely with S' and TMAD % (r = -0.402, p = 0.001 and r = -0.585, p < 0.001, respectively), but did not correlate with EF (r = 0.054, not significant). These significant relationships were maintained after considering factors such as body mass index, age, presence of lifestyle-related diseases and blood test results. A significant relationship existed between EAT amount and early impairment of LV systolic function in patients with preserved EF. Accumulation of EAT might contribute to the initial development of LV systolic dysfunction.

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The V843I mutation contributes to tumorigenesis by promoting phosphorylation of EGFR and its downstream signaling proteins. This mutation also appears to provide resistance to EGFR-TKIs through structural modification of EGFR. These features are comparable with those in EGFR T790M mutation, suggesting that cases with germ-line V843I or T790M mutations could be categorized as a class of familial lung cancer syndrome with resistance to EGFR-TKIs.

Background:Ultrasonography is useful for distinguishing between benign and malignant soft-tissue tumors. However, no study has focused on its usefulness in the differential diagnosis between low-grade and high-grade soft-tissue sarcomas. We conducted a retrospective study to determine the usefulness of the parameters of ultrasonograph and to develop a practical scoring system for distinguishing between high-grade and low-grade sarcomas.Methods:Twenty-two cases of low-grade and 43 cases of high-grade malignant soft-tissue sarcoma were enrolled. Ultrasonography parameters including the longest diameter, depth of the tumor, echogenicity, tumor margin, and vascularity defined according to Giovagnorio’s criteria were analyzed as factors to distinguish between the two types of sarcoma. Significant factors were entered into a multivariate model to define the scores for distinction according to the odds ratio. The usefulness of the score was analyzed via receiver operating characteristic analyses.Results:In univariate analysis, tumor margin, echogenicity, and vascularity were significantly different between low- and high-grade sarcomas. In the multivariate regression model, the odds ratio for high-grade vs. low-grade sarcoma was 8.8 for tumor margin, 69 for echogenicity, and 8.3 for vascularity. Scores for the risk factors were defined as follows: 1, ill-defined margin; 2, hypoechoic echogenicity; and 1, type IV in Giovagnorio’s criteria. The sum of each score was confirmed by receiver operating characteristic analysis. The area under the curve was 0.95, with a cut-off score of 3, indicating that the scoring system was useful.Conclusion:The ultrasonography parameters of tumor margin, echogenicity, and vascularity are useful for distinguishing between low- and high-grade sarcomas.

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