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

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after the date of enrollment of the last patient, we investigated survival status of each patient and identified a group with recurrence. Results: Among 107 patients, 29 patients developed recurrence with a mean follow-up of 18.1 months (range 14 to 21). P-stage was significantly more advanced in the recurrence group than in the non-recurrence group (p = 0.005). Serum IL-6 levels on POD 1 were significantly higher in the recurrence group than in the non-recurrence group (p = 0.007). In Cox's proportional hazards regression, P-stage and serum IL-6 levels on POD 1 were significant independent predicting factors for postoperative early recurrence (p = 0.006, p = 0.003). Conclusions: The higher the serum IL-6 levels on POD 1, the higher the risk of early postoperative recurrence, even when curative pulmonary resection can be accomplished in lung cancer patients.

APC:T1556fs and STK11 mutations found in duodenal adenomas/ACs highlight the importance of proteins encoded by these genes in tumor development. APC mutations were identified in duodenal adenomas more frequently than in duodenal ACs, which differed from the observations of typical adenoma-carcinoma sequences seen in colorectal cancer, suggesting the limited involvement of this mechanism in duodenal cancer development.