Fig. 3. Plasma homocysteine concentration in patients with very long nitrous oxide exposure (> 4 h) (n = 16). Postoperative homocysteine concentrations were significantly higher compared with preoperative: 8.1 (7.3–10.0)  versus 14.60 (13.1–22.8) μm [median (lower–upper quartile)],  P < 0.001, Wilcoxon signed rank test. A solid black box (▪) indicates the two patients who were double wild type, indicating that the effects of very long exposure to nitrous oxide are also operant in patients without  MTHFR mutation.