Intervention: Transmetatarsal amputations performed in all patients.Main Outcome Measures: Transmetatarsal amputation healing, ambulation, living status, and survival. Demographic characteristics, preoperative vascular status, and perioperative variables were analyzed as predictor variables. Univariate and multivariate analyses were performed to determine predictors of healing and survival.Results: Sixty-two TMAs were performed in 57 patients. Healing occurred in 33 TMAs (53%), with 22 TMAs (35%) in patients who proceeded to below-knee amputation and 7 TMAs (11%) in patients who died without healing. No demographic or perioperative variables significantly predicted healing. Independent ambulation was achieved in 24 patients with healed TMAs (73%) but in only 4 patients with nonhealed TMAs (14%) (P Ͻ.001). Mean survival was 16.5 months (range, 0-94 months), with no difference between patients with healed and those with nonhealed TMA. Significant predictors of mortality were dialysis-dependent renal failure (odds ratio, 4.85; 95% confidence interval, 1.01-23.30) (P = .047), nonindependent living (17.80; 3.03-104.80) (P =.001), and need for preoperative revascularization (4.80; 1.24-18.50) (P =.02).Conclusions: Transmetatarsal amputations have low healing rates, and patient demographic characteristics and preoperative assessment do not help predict healing. Transmetatarsal amputation healing, however, significantly predicts subsequent ambulatory status and should be pursued in patients with good rehabilitation potential.

Methadone is administered as a racemic mixture, although its analgesic and respiratory effects are attributed to R-isomer activity at the mu-opioid receptor (MOP). Recently, we observed a fourfold increase in inspiratory time in three-day old guinea pigs following an injection of racemic methadone. We hypothesized that this effect was due to augmentation of R-methadone induced respiratory depression by the S-methadone isomer. In the current longitudinal study, we injected three-, seven-, and fourteen-day old neonatal guinea pigs with saline, R-methadone, S-methadone, or R-plus S-methadone in order to characterize the roles of the individual isomers, as well as the synergistic effects of co-administration. Using plethysmography, we measured respiratory parameters while breathing room air and during a 5% CO 2 challenge. S-methadone alone had no respiratory effects. However, the R-plus S-methadone group showed greater respiratory depression and increased inspiratory time than the R-methadone group in the youngest animals, suggesting that the respiratory effects of R-methadone are augmented by S-methadone in early development.