Outcomes and complications of simple layered closure of persistent tracheocutaneous fistula after tracheostomy in childhood.

Background: Up to half of all children who have a tracheostomy will develop a persistent tracheo-cutaneous fistula (TCF) after decannulation. Surgical closure of the TCF is technically easy but post-operative complications can be immediate and life-threatening. These include air leak from the tracheal repair leading to massive surgical emphysema or pneumothorax.

Hypersensitivity of DNA polymerase beta null mouse fibroblasts reflects accumulation of cytotoxic repair intermediates from site-specific alkyl DNA lesions.

Monofunctional alkylating agents react with DNA by S(N)1 or S(N)2 mechanisms resulting in formation of a wide spectrum of cytotoxic base adducts. DNA polymerase beta (beta-pol) is required for efficient base excision repair of N-alkyl adducts, and we make use of the hypersensitivity of beta-pol null mouse fibroblasts to investigate such alkylating agents with a view towards understanding the DNA lesions responsible for the cellular phenotype. The inability of O(6)-benzylguanine to sensitize wild-type or beta-pol null cells to S(N)1-type methylating agents indicates that the observed hypersensitivity is not due to differential repair of cytotoxic O-alkyl adducts.