Trafficking of human immunodeficiency virus type 1-specific CD8+ T cells to gut-associated lymphoid tissue during chronic infection.

Gut-associated lymphoid tissue (GALT) is a significant but understudied lymphoid organ, harboring a majority of the body's total lymphocyte population. GALT is also an important portal of entry for human immunodeficiency virus (HIV), a major site of viral replication and CD4(+) T-cell depletion, and a frequent site of AIDS-related opportunistic infections and neoplasms. However, little is known about HIV-specific cell-mediated immune responses in GALT. Using lymphocytes isolated from rectal biopsies, we have determined the frequency and phenotype of HIV-specific CD8(+) T cells in human GALT. GALT CD8(+) T cells were predominantly CD45RO(+) and expressed CXCR4 and CCR5. In 10 clinically stable, chronically infected individuals, the frequency of HIV Gag (SL9)-specific CD8(+) T cells was increased in GALT relative to peripheral blood mononuclear cells by up to 4.6-fold, while that of cytomegalovirus (CMV)-specific CD8(+) T cells was significantly reduced (P = 0.012). Both HIV- and CMV-specific CD8(+) T cells in GALT expressed CCR5, but only HIV-specific CD8(+) T cells expressed alpha E beta 7 integrin, suggesting that mucosal priming may account for their retention in GALT. Chronically infected individuals exhibited striking depletion of GALT CD4(+) T cells expressing CXCR4, CCR5, and alpha E beta 7 integrin, but CD4(+)/CD8(+) T-cell ratios in blood and GALT were similar. The percentage of GALT CD8(+) T cells expressing alpha E beta 7 was significantly decreased in infected individuals, suggesting that HIV infection may perturb lymphocyte retention in GALT. These studies demonstrate the feasibility of using tetramers to assess HIV-specific T cells in GALT and reveal that GALT is the site of an active CD8(+) T-cell response during chronic infection.

Unsedated ultrathin EGD is well accepted when compared with conventional sedated EGD: a multicenter randomized trial.

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.

The Stretta procedure for the treatment of GERD: 6 and 12 month follow-up of the U.S. open label trial.

BACKGROUND: This multicenter prospective study investigated the longer-term (12 month) safety and efficacy of radiofrequency energy delivery for the treatment of GERD. METHODS: A prospective study was conducted of 118 patients with chronic heartburn and/or regurgitation who required antisecretory medication daily and had demonstrated pathologic esophageal acid exposure, a sliding hiatal hernia (