Publications

The Leishmania major LACK antigen is a key target of the immune response in susceptible BALB/c mice and remains a viable vaccine candidate for human leishmaniasis. We describe the genomic organization of the four lack genes in the L. major diploid genome together with results of selected lack gene targeting. Parasites containing a single lack gene in either the upstream or downstream locus grew comparably to wild-type promastigotes in vitro, but failed to parasitize BALB/c mice efficiently, even in a T cell-deficient environment. The replication of single copy lack mutants as amastigotes was attenuated in macrophages in vitro, and parasites failed to increase in numbers in immunodeficient mice, despite their persistence over months. Complementation with an additional lack copy was sufficient to induce robust lesion development, which also occurred using parasites with two lack genes. Conversely, attempts to generate lack-null parasites failed, suggesting that LACK is required for parasite viability. These data suggest that LACK is critical for effective mammalian parasitization and thus represents a potential drug target for leishmaniasis.

BACKGROUND & AIMS

In the United States, upper gastrointestinal endoscopy is usually performed using intravenous sedation. Sedation increases the rate of both complications and costs of endoscopy. Unsedated esophagogastroduodenoscopy (EGD) using conventional 8-11-mm endoscopes is an alternative to sedated endoscopy but is generally perceived as unacceptable to many American patients. Unsedated EGD using ultrathin 5-6-mm endoscopes is better tolerated. A randomized trial comparing unsedated ultrathin EGD (UT-EGD) with sedated conventional EGD (C-EGD) in a diverse American population is needed.

METHODS

In this multicenter, randomized, controlled trial, 80 patients scheduled to undergo elective outpatient EGD were randomized to unsedated UT-EGD or sedated C-EGD. The study was carried out at San Francisco General Hospital, San Francisco Veterans Affairs Medical Center, and the Liver and Digestive Health Medical Clinic, San Jose.

RESULTS

Baseline characteristics of patients randomized to unsedated UT-EGD and sedated C-EGD were similar. Moreover, there were no significant differences in overall patient satisfaction and willingness to repeat endoscopy in the same manner among the 2 study groups. There was, however, a significant difference in median total procedure time between the 2 study groups of 1.5 hours (P < 0.0001). The mean (+/- SD) total procedure cost was 512.4 US dollars (+/- 100.8 US dollars) for sedated C-EGD and 328.6 US dollars (+/- 70.3 US dollars) for unsedated UT-EGD (P < 0.0001).

CONCLUSIONS

Patients undergoing unsedated UT-EGD are as satisfied as patients undergoing sedated C-EGD and are just as willing to repeat an unsedated UT-EGD. Unsedated UT-EGD was also faster, less costly, and may allow greater accessibility to this procedure.