Bench to Bedside

After the initial dramatic effects, observed in a Lewis lung carcinoma animal model, using a combination of thymosin alpha 1 (T� 1) and interferon (IFN) after cyclophosphamide, a number of other preclin- ical models in mice (Friend erythroleukemia and B16 melanoma) and in rats (DHD/K12 colorectal cancer liver metastasis) have confirmed the efficacy of the combination therapy with T� 1 and either IFN or IL-2 plus chemotherapy. These results provided the scientific founda- tion for the first clinical trials using T� 1 in combination with BRMs and/or chemotherapy. Pivotal trials in advanced non-small cell lung cancer (NSCLC) and melanoma with T� 1 and IFN-� low doses after cis-platinum or dacarbazine produced the first evidence of the high po- tentiality of this approach in the treatment of human cancer. The com- bination of T� 1 and IFN-� was also used in patients affected by chronic B and C hepatitis including IFN-nonresponders and infected by precore mutants or genotype 1b. Further studies demonstrated additional bio- logical activities clarifying the mechanism of action of T� 1, partially explaining the synergism with IFN. It has been shown the capacity of ac- tivating infected dendritic cells through Toll-like receptor signaling, thus influencing the inflammation balance, and of increasing the expression of tumor, viral, and major histocompatibility complex (MHC) I antigens. Dose-response studies suggested the possibility of improving the efficacy of this molecule reducing the overall toxic. Based on these information

-containing 45 genes that contribute to antibiotic resistance. Many of these genes are of types not seen before, and their various roles in antibiotic resistance still need to be verified.
Analysis of these "resistance" genes revealed similarities with species of Pseudomonas, Escherichia and Salmonella, which suggests that exchanges of genetic information have likely occurred. Since all of these bacteria are commonly found in aqueous environments in hospitals, Fournier and colleagues suggest that antimicrobial pressure in such settings probably promotes genetic exchanges between and among these pathogens. Moreover, the areas around the resistance genes seem to be primed to capture additional genes, which perhaps explains why the organism has been so quick to develop drug resistance.
Antibiotic resistance in human pathogens is a major clinical problem; genome comparisons will illuminate some aspects of how this occurs. Our understanding of these mechanisms is crucial to the development of novel agents to overcome these pathogens' defenses. -Compiled by David Secko, Vancouver

New mechanisms of antibiotic resistance
In the 1970s the bacterium Acinetobacter baumannii was sensitive to most antibiotics; but over the last 35 years, some A. baumannii strains have become resistant to virtually all antibacterial drugs. In some countries, infections with this organism have become a public health problem: A. baumannii is responsible for up to 10% of all gram-negative infections in intensive care units in Europe.
So what has changed? Pierre-Edouard Fournier and colleagues recently attempted to answer this question when they compared the genomes of 2 strains of A. baumannii: one from an outbreak in France that is resistant to virtually all antibiotics versus one associated with human body lice that is extremely susceptible (PLoS Genetics 2006;2(1):e7 BC was the top performer in terms of overall population and health outcomes, but posted second-lowest in terms of patient satisfaction. The report also compared Canada's health performance to the 23 leading OECD countries, finding, once again, that Canada places in the middle range at number 11, tied with Iceland, Luxembourg and the Netherlands. The Conference Board of Canada is an independent, not-forprofit applied research organization.
Premium increase: Nova Scotia seniors will see their annual pharmacare premium rise to $400 a year as of Apr. 1, an increase of $10 a year. The province is also raising the annual cap on seniors' co-payments on each prescription by $10, to $360 per year. In total, the province anticipates it will spend $172 million in 2006-07 for the Seniors' Pharmacare program. It serves more than 95 000 people in the province. Thousands of low-income seniors, including those who receive the federal Guaranteed Income Supplement, are either exempt from paying the premiums, or else pay a reduced amount. "The Seniors' Pharmacare program is an important part of the health care system that must remain both affordable to seniors and sustainable over time," Health Minister Chris d'Entremont said in a statement announcing the increases. "As prescription drug costs continue to rise, a model increase in the fees will allow the program to continue to provide benefits to the greatest number of seniors." -Compiled by Barbara Sibbald and Laura Eggertson, CMAJ