CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(-) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(-). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR=6.28; m2/GSTM1(-), OR=3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/C, OR=1.39; m2/c2, OR=2.00; val/C, OR=1.45; val/c2, OR=0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(-), 7.38 for m2/val and 3.68 for m2/GSTM1(-), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.

Steroids have been a cornerstone in renal transplant immunosuppression. New immunosuppressive drugs have led to protocols using early steroid withdrawal or complete avoidance. A prospective protocol in 23 pediatric renal transplant (ages 2-14 yr) who received decreasing steroid doses stopping at day 7 post-Tx, FK, and MMF were compared with a CsA, AZT, historically matched steroid-based control group. Basiliximab was used in two doses. Anthropometric, biochemical variables, AR rates, and CMV infection were evaluated and compared using Student's t-test and regression analysis. A better growth pattern was seen in steroid withdrawal group. GFR rate and serum glucose were similar in both groups. Total serum cholesterol levels were significantly lower in steroid withdrawal group. The incidence of AR at 12 months was 4.3% in steroid withdrawal group vs. 8.6% in steroid-based group (p = ns). No difference in CMV infection was observed. Hemoglobin levels were low during the first months in both groups; reached normal values after six months. SBP became higher at 12 months in steroid-based group. Patient and graft survival was 98% in both groups at one-yr post-transplant. Early steroid withdrawal was efficacious, safe, and did not increase risk of rejection, preserving optimal growth, renal function, and reducing cardiovascular risk factors.

No abstract

Between 1989 and 2003, 100 transplants were performed in 96 patients at the pediatric nephrology unit of the Calvo Mackenna Children's Hospital. Mean age 10.9 +/- 3.9 yr (1-17.6), 30% from LD. Donors were younger than 5 yr in five patients and all recipients received an 'en bloc' graft. Original disease was hypo/dysplasia 27%, reflux nephropathy 22 and 17% chronic glomerulonephritis. The immunosuppressive protocol during the first period (n = 56, 1989-2000): Cyclosporine, steroids and azathioprine, and during the second period (n = 44, 2001-2003): FK, steroids, MMF and anti-CD25 antibody (mAbs). AR was reported in 22 patients, 11% in LD, 31% in DD (p < 0.01). The AR rate decreased from 40 to 8% after anti-CD25 monoclonal induction. Patient actuarial survival rate at 1, 3 and 5 yr was 100% for LD and 96% for DD. The overall actuarial graft survival at 1,3, and 5 yr was 96.7, 96.7 and 71% for LD and 89, 76 and 73% for DD donors. Graft survival rate improved from the first period (1989-2000) to the second period (2001-2003; p = 0.05). No difference in graft survival rate with HLA-A,B,DR matching was found. Graft survival rate was better when cold ischemia time was <24 h (p < 0.01). CMV infections increased from 19 to 40% when MMF and anti-CD25 Ab were introduced (p < 0.01). The height/age Z score at 1, 3 and 5 yr post-transplant was -2.2, -2.1, -2.2, respectively, for children older than 7 yr and -1.8, -1.9, -2.1 for those transplanted younger than 7 yr of age who were switched to alternate day steroids (p < 0.01). The cause of graft lost was: chronic rejection eight, non-adherence four, AR four and vascular thrombosis two. The cause of death in two patients was fungus septicemia and accelerated rejection. Pediatric renal transplantation can be performed in our group with acceptable morbidity, low mortality and graft survival rates similar to other reports in North America and Western Europe. Graft survival rate improved with newer immunosuppression and greater experience at the center. Management of non-adherence and chronic rejection remain the major challenges.