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β-blockers could improve outcome for coronary artery bypass patients
SCIENCE AND MEDICINE
-blockers could improve outcome for coronary artery bypass patients the hormones epinephrine and Center, Durham, NC, USA). The norepinephrine, which trigger only adverse effect noticed was stress—or “fight or increased mortality flight”—responses in among patients whose human beings. These hearts were pumping responses include at 30% or less of Rights were not increased heart rates, capacity—but this findgranted to include which boost oxygen ing was not significant. demand by the heart, Stephen Gottlieb this image in and increased respira(University of Maryelectronic media. tion rates as the body land School of Please refer to the tries to increase oxygen Medicine, Baltimore, printed journal. uptake. Peterson thinks MD, USA) is somethat the drugs might what skeptical of the help coronary bypass results, however. “This patients by reducing is an uncontrolled study, which limits Better postoperative outlook? oxygen demand at a time when the body is its utility”, he says. unable to obtain much. “While previous data would suggest William Nugent (Dartmouthbenefit of -blockade perioperaHitchcock Medical Center, tively, the use of -blockers in Lebanon, NH, USA) thinks the this study was affected by many results will help convince more factors which cannot be controlled surgeons that -blockers should be for.” used in bypass patients. “There was Peterson points out that there are resistance to using the drug 10 years no controlled studies on the use of ago”, Nugent says. “There wasn’t -blockers in coronary bypass any good data until now that it was a patients. “I think that surgeons will good drug to use in the surgical be happy that we are providing some population.” evidence where there was none before”, he says. -blockers work by inhibiting David Lawrence Science Photo Library
atients who have a number of cardiovascular problems, such as high blood pressure, chest pain, and irregular heartbeats, have been shown to benefit from -blockers. A study published this week suggests that use of -blockers before coronary artery bypass surgery could improve the postoperative outlook for these patients as well. A team of researchers from Louisiana State University Health Sciences Center, Duke University Medical Center, and the Society of Thoracic Surgeons (STS) analysed data from the STS-administered National Adult Cardiac Surgery Database on more than 600 000 patients who had bypass surgery at 500 hospitals in the USA and Canada from 1996–99. They reported that the 30-day mortality rate in patients who received -blockers was 2·8%, compared with 3·4% for patients who did not (JAMA 2002; 287: 2221–27). For most patients, -blockers also reduced the likelihood of other complications, such as kidney failure or prolonged time on ventilators, says one of the investigators, Eric Peterson (Duke University Medical
P
New treatment for inflammatory bowel disease could soon enter clinical trials
I
mmunostimulatory bacterial DNA sequences could provide a new treatment for inflammatory bowel disease (IBD), an international team of researchers suggests this week. Daniel Rachmilewitz (Shaare Zedek Medical Center, Jerusalem, Israel) and colleagues report that in three experimental and one spontaneous mouse model of colitis, administration of immunostimulatory bacterial DNA reduced colonic inflammation. In addition, the same DNAs inhibited in-vitro release of proinflammatory mediators from biopsy material from patients with either Crohn’s disease or ulcerative colitis (Gastroenterology 2002; 122: 1428–41). “I think these data justify a speedy move into clinical studies”, says senior researcher Eyal Raz (University of California, San Diego, CA, USA), adding that his Israeli colleagues are actively planning such trials. IBD comprises two related inflammatory disorders of the intestinal tract—Crohn’s disease
and ulcerative colitis. The exact cause of IBD remains unclear, but susceptibility genes and environmental factors have been implicated in its aetiology. Progress in the overall management of IBD is being made, but to date few innovative treatments have been described. In their search for such a new treatment, the researchers investigated the effects of small synthetic DNAs containing CpG motifs from bacterial genomes previously shown to have an immunostimulatory effect. “It was somewhat counterintuitive to try these molecules —ISS-ODNs [immunostimulatory oligonucleotides]—but we discovered that they had a strong anti-inflammatory effect in animal models for IBD”, explains Raz. ISS-ODN was effective when injected or given orally, but a single dose did not provide long-term protection against colitis. “In clinical terms, this might mean that patients would need to take the drug orally every week or two”, says Raz. “This is interesting work”,
THE LANCET • Vol 359 • May 4, 2002 • www.thelancet.com
comments Sander van Deventer (Academic Medical Center, Amsterdam, Netherlands), “and DNAs of this type have been used as immunostimulators in several diseases. But”, he cautions, “there remain many unknowns in relation to the use of ISS-ODNs in IBD. For example, it is unclear which cells in the intestinal mucosa are stimulated by administration of ISS-ODNs.” Raz agrees that it is unclear how immunostimulatory DNAs work in IBD but suggests that they could be both stimulating innate immunity and helping to protect the mucosal barrier. “ISS-ODNs could limit the invasion of commensal bacteria and/or their inflammatory products into the colonic mucosa and thus reduce mucosal inflammation. ISS-ODNs”, he adds, “might actually work in an equivalent way to probiotics, which have been shown to be effective against colitis in clinical trials and could have the potential for providing a more controlled therapy for IBD”. Jane Bradbury
1583
For personal use. Only reproduce with permission from The Lancet publishing Group.
-blockers could improve outcome for coronary artery bypass patients the hormones epinephrine and Center, Durham, NC, USA). The norepinephrine, which trigger only adverse effect noticed was stress—or “fight or increased mortality flight”—responses in among patients whose human beings. These hearts were pumping responses include at 30% or less of Rights were not increased heart rates, capacity—but this findgranted to include which boost oxygen ing was not significant. demand by the heart, Stephen Gottlieb this image in and increased respira(University of Maryelectronic media. tion rates as the body land School of Please refer to the tries to increase oxygen Medicine, Baltimore, printed journal. uptake. Peterson thinks MD, USA) is somethat the drugs might what skeptical of the help coronary bypass results, however. “This patients by reducing is an uncontrolled study, which limits Better postoperative outlook? oxygen demand at a time when the body is its utility”, he says. unable to obtain much. “While previous data would suggest William Nugent (Dartmouthbenefit of -blockade perioperaHitchcock Medical Center, tively, the use of -blockers in Lebanon, NH, USA) thinks the this study was affected by many results will help convince more factors which cannot be controlled surgeons that -blockers should be for.” used in bypass patients. “There was Peterson points out that there are resistance to using the drug 10 years no controlled studies on the use of ago”, Nugent says. “There wasn’t -blockers in coronary bypass any good data until now that it was a patients. “I think that surgeons will good drug to use in the surgical be happy that we are providing some population.” evidence where there was none before”, he says. -blockers work by inhibiting David Lawrence Science Photo Library
atients who have a number of cardiovascular problems, such as high blood pressure, chest pain, and irregular heartbeats, have been shown to benefit from -blockers. A study published this week suggests that use of -blockers before coronary artery bypass surgery could improve the postoperative outlook for these patients as well. A team of researchers from Louisiana State University Health Sciences Center, Duke University Medical Center, and the Society of Thoracic Surgeons (STS) analysed data from the STS-administered National Adult Cardiac Surgery Database on more than 600 000 patients who had bypass surgery at 500 hospitals in the USA and Canada from 1996–99. They reported that the 30-day mortality rate in patients who received -blockers was 2·8%, compared with 3·4% for patients who did not (JAMA 2002; 287: 2221–27). For most patients, -blockers also reduced the likelihood of other complications, such as kidney failure or prolonged time on ventilators, says one of the investigators, Eric Peterson (Duke University Medical
P
New treatment for inflammatory bowel disease could soon enter clinical trials
I
mmunostimulatory bacterial DNA sequences could provide a new treatment for inflammatory bowel disease (IBD), an international team of researchers suggests this week. Daniel Rachmilewitz (Shaare Zedek Medical Center, Jerusalem, Israel) and colleagues report that in three experimental and one spontaneous mouse model of colitis, administration of immunostimulatory bacterial DNA reduced colonic inflammation. In addition, the same DNAs inhibited in-vitro release of proinflammatory mediators from biopsy material from patients with either Crohn’s disease or ulcerative colitis (Gastroenterology 2002; 122: 1428–41). “I think these data justify a speedy move into clinical studies”, says senior researcher Eyal Raz (University of California, San Diego, CA, USA), adding that his Israeli colleagues are actively planning such trials. IBD comprises two related inflammatory disorders of the intestinal tract—Crohn’s disease
and ulcerative colitis. The exact cause of IBD remains unclear, but susceptibility genes and environmental factors have been implicated in its aetiology. Progress in the overall management of IBD is being made, but to date few innovative treatments have been described. In their search for such a new treatment, the researchers investigated the effects of small synthetic DNAs containing CpG motifs from bacterial genomes previously shown to have an immunostimulatory effect. “It was somewhat counterintuitive to try these molecules —ISS-ODNs [immunostimulatory oligonucleotides]—but we discovered that they had a strong anti-inflammatory effect in animal models for IBD”, explains Raz. ISS-ODN was effective when injected or given orally, but a single dose did not provide long-term protection against colitis. “In clinical terms, this might mean that patients would need to take the drug orally every week or two”, says Raz. “This is interesting work”,
THE LANCET • Vol 359 • May 4, 2002 • www.thelancet.com
comments Sander van Deventer (Academic Medical Center, Amsterdam, Netherlands), “and DNAs of this type have been used as immunostimulators in several diseases. But”, he cautions, “there remain many unknowns in relation to the use of ISS-ODNs in IBD. For example, it is unclear which cells in the intestinal mucosa are stimulated by administration of ISS-ODNs.” Raz agrees that it is unclear how immunostimulatory DNAs work in IBD but suggests that they could be both stimulating innate immunity and helping to protect the mucosal barrier. “ISS-ODNs could limit the invasion of commensal bacteria and/or their inflammatory products into the colonic mucosa and thus reduce mucosal inflammation. ISS-ODNs”, he adds, “might actually work in an equivalent way to probiotics, which have been shown to be effective against colitis in clinical trials and could have the potential for providing a more controlled therapy for IBD”. Jane Bradbury
1583
For personal use. Only reproduce with permission from The Lancet publishing Group.