Based on a study of 752 French patients who underwent either lung or heart-lung transplantation, investigators revealed a close relationship between graft ischemic time and long-term survival after single or double lung transplantation. (Graft ischemic time was defined as the interval between the application of the aortic cross clamp during donor organ removal and the reperfusion (restoration of blood flow) in the graft of the recipient.) According to the authors, a cutoff time of 330 minutes was found to best discriminate between long-term survivors and nonsurvivors. The median time for the entire group in the transplant study was 240 minutes. Results were unaffected by the organ preservation fluid used. The investigators believe that expected graft ischemic time should be incorporated into the decision-making process at the time of graft acceptance. The investigators note that the effect of graft ischemic time on the relative risk of death seemed to peak in the first year after transplantation, and to wear off quickly thereafter. During the study period, from January 1987 to December 1998, patient survival at the seven French transplantation centers which were involved in the study ran 84.2 percent at day 30, 63.3 percent at 1 year, 45.9 percent at 3 years, and 38.1 percent at 5 years. The research study appears in the first issue for April 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.
100 YEARS OF PROGRESS IN TUBERCULOSIS TREATMENT
Over the past century, the use of anti-tuberculosis drugs has changed tuberculosis from a disease with a 50 percent mortality rate, which was treated by collapsing the affected lung and rest in a sanitarium, to a condition successfully cured by use of chemotherapy. The initial key step in the development of modern chemotherapy for tuberculosis was the demonstration in clinical trials, starting in 1946, that the antibiotic streptomycin might be a viable drug for the disease. The results of early British trials showed a substantial benefit to the streptomycin arm of the trial; however, soon many patients developed antibiotic resistant strains and little ultimate benefit came to those treated. The next big movement forward came with the introduction of a combination of drugs, including streptomycin, to prevent the emergence of drug-resistant Mycobacterium tuberculosis. By 1955, clinical trials in Great Britain showed that almost all tuberculosis strains had primary resistance to only one drug. Treatment with a 2- to 3-month three-drug phase, followed by 2 drugs, became the world standard. Yet patients had to take the regimen for 12 months. In 1956, researchers in Madras, India, found that results from those who were treated with tuberculosis drugs at home compared equally well with those treated at a sanitarium. Furthermore, they discovered that family members who were in contact with the tuberculosis case daily were no more liable to develop the disease than were relatives of those who were treated at a sanitarium. Then, using a drug called pyrazinamide discovered in 1952, U.S. researchers working with experimental tuberculosis in mice showed that as bacterial metabolism slowed down from the action of other drugs, pyrazinamide worked with more bactericidal effect. Out of the multiplicity of random clinical trials that were carried out over the years, two drug regimens emerged as treatments of choice. The first was a 6-month regimen in which rifampin (a potent sterilizing agent) was given throughout the time period. Patients began treatment with 2 months of streptomycin, isoniazid, and pyrazinamide, followed by 4 months of isoniazid, and, as stated, rifampin. (Streptomycin has been replaced with ethambutol in many settings.) The second treatment choice was an 8-month regimen of a combination of these drugs, which a recent randomized clinical trial has shown to be "distinctly inferior to the 6-month regimen with rifampin throughout." The article about the remarkable history of tuberculosis treatment appears in the first issue for April 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.
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Journal
American Journal of Respiratory and Critical Care Medicine