Activity of cytochrome P450 1A2 in relation to hepatic iron accumulation in transfusion-dependent ß-thalassaemia major patients.

BACKGROUND: Cytochrome P450 1A2 (CYP1A2) is a cytochrome enzyme with a pivotal role in hepatic drug metabolism. Data from CYP1A2((-/-)) mouse suggest that CYP1A2 plays a role in aspects of hepatic iron toxicity. The aim of this study was to assess the activity of CYP1A2 in relation to hepatic iron load in patients with transfusion-dependent ß-thalassaemia major. METHODS: The (13) C-methacetin continuous breath test was performed on 30 consecutive patients with transfusion-dependent ß-thalassaemia major. CYP1A2 activity was measured by the rate at which the (13) C substrate is metabolized and exhaled expressed as percentage dose recovery (PDR) per hour. CYP1A2 activity was correlated with clinical and laboratory parameters and hepatic iron accumulation by T2* magnetic resonance imaging (T2*MRI). RESULTS: Cytochrome P450 1A2 activity in patients with transfusion-dependent ß- thalassaemia major was positivity correlated with plasma ferritin levels. No correlation was found with age, duration and amount of red blood cell transfusion and type of iron chelation therapy. Low CYP1A2 activity was negatively associated with hepatic iron accumulation (T2*MRI ≤ 6.3 ms); adjusted odds ratio (OR; 95% CI) for hepatic iron accumulation in patients with low CYP1A2 activity was 0.047 (0.003-0.72; P = 0.021). Of the six patients with decreased activity of CYP1A2, five had no hepatic iron accumulation and one had mild hepatic iron accumulation by T2*MRI. CONCLUSION: Activity of CYP1A2 is associated with hepatic iron accumulation in patients with transfusion-depended ß-thalassaemia major. Further studies are needed to assess the exact role of CYP1A2 in iron metabolism in human.

[Volume reduction surgery in emphysema].

Volume reduction surgery (VRS) is a new procedure based on the concept that relieving hyperinflation in emphysema improves diaphragmatic and chest wall mechanics and ventilation perfusion mismatch. We present our early experience with 16 patients who underwent VRS from August 1995 to June 1996. Patient selection was based on: PFT, CT scan, V/Q scan, ABG's and 6-min walk. After pulmonary rehabilitation, operation was by median sternotomy and bilateral lung shaving. Pulmonary function improved significantly. FEV1 increased from 0.68 +/- 0.2 to 1.0 +/- 0.2 L (p < 0.01) and FVC increased from 1.7 +/- 0.5 to 2.7 +/- 0.5 L (p < 0.017). Total lung capacity decreased from 129% +/- 24% to 108% +/- 20% (p < 0.03). 6-min walk increased from 221 +/- 90 to 404 +/- 123 meters (p < 0.001). Complications included 1 death, prolonged air leak in 7 cases and infection in 2. Quality of life improved substantially in 12 of the 16 cases; in 3 cases there was only slight improvement and in 1 the condition became worse. Volume reduction surgery is a promising surgical solution in selected patients with advanced emphysema.