The poor success in controlling small bowel (SB) allograft rejection is partially attributed to the unique immune environment in the donor intestine. We hypothesized that Ag-induced activation of donor-derived T cells contributes to the initiation of SB allograft rejection. To address the role of donor T cell activation in SB transplantation, SB grafts from DO11.10 TCR transgenic mice (BALB/c, H-2Ld+) were transplanted into BALB/c (isografts), or single class I MHC-mismatched (Ld-deficient) BALB/c H-2dm2 (dm2, H-2Ld−) mutant mice (allografts). Graft survival was followed after injection of control or antigenic OVA323–339 peptide. Eighty percent of SB allografts developed severe rejection in mice treated with antigenic peptide, whereas <20% of allografts were rejected in mice treated with control peptide (p < 0.05). Isografts survived >30 days regardless of OVA323–339 administration. Activation of donor T cells increased intragraft expression of proinflammatory cytokine (IFN-γ) and CXC chemokine IFN-γ-inducible protein-10 mRNA and enhanced activation and accumulation of host NK and T cells in SB allografts. Treatment of mice with neutralizing anti-IFN-γ-inducible protein-10 mAb increased SB allograft survival in Ag-treated mice (67%; p < 0.05) and reduced accumulation of host T cells and NK cells in the lamina propria but not mesenteric lymph nodes. These results suggest that activation of donor T cells after SB allotransplantation induces production of a Th1-like profile of cytokines and CXC chemokines that enhance infiltration of host T cells and NK cells in SB allografts. Blocking this pathway may be of therapeutic value in controlling SB allograft rejection.

The pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m 2 receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods. The mean (؎standard deviation) age, height, and weight were 42.2 ؎ 12.2 years, 64.8 ؎ 3.5 in, and 109.5 ؎ 18.2 kg (range, 78.2 to 143.1 kg), respectively. Linezolid pharmacokinetics in this population were best described by a 2-compartment model with nonlinear clearance (original value, 7.6 ؎ 1.9 liters/h), which could be inhibited to 85.5% ؎ 12.2% of its original value depending on the concentration in an empirical inhibition compartment, the volume of the central compartment (24.4 ؎ 9.6 liters), and the intercompartment transfer constants (K 12 and K 21 ) of 8.04 ؎ 6.22 and 7.99 ؎ 5.46 h ؊1 , respectively. The areas under the curve for the 12-h dosing interval (AUC) were similar between moderately obese and morbidly obese groups: 130.3 ؎ 60.1 versus 109.2 ؎ 25.5 g · h/ml (P ‫؍‬ 0.32), and there was no significant relationship between the AUC or clearance and any body size descriptors. A significant positive relationship was observed for the total volume of distribution with total body weight (r 2 ‫؍‬ 0.524), adjusted body weight (r 2 ‫؍‬ 0.587), lean body weight (r 2 ‫؍‬ 0.495), and ideal body weight (r 2 ‫؍‬ 0.398), but not with BMI (r 2 ‫؍‬ 0.171). Linezolid exposure in these obese participants was similar overall to that of nonobese patients, implying that dosage adjustments based on BMI alone are not required, and standard doses for patients with body weights up to approximately 150 kg should provide AUC values similar to those seen in nonobese participants.

The incidence of clinically evident DVT after laparoscopic Roux-en-Y gastric bypass is low when the procedure is accomplished with a relatively short operative time, with the initiation of calf-length pneumatic compression hose before the induction of anesthesia, and with routine early ambulation. No form of heparin anticoagulation is mandatory when these conditions can be met.

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