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CLINICAL NOTES

doi: 10.1097/01.COT.0000293402.84810.83
Department: CLINICAL NOTES
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Study: Sleep Strengthens Memories & Makes Them Resistant to Interfering Information

A study has uncovered new evidence that sleep improves the brain's ability to remember information. The findings, reported by a team led by Jeffrey M. Ellenbogen, MD, a fellow in sleep research at Harvard Medical School, and published in the July 12 issue of Current Biology, showed that memories of recently learned word pairs are improved if sleep intervenes between learning and testing and that this benefit is most pronounced when memory is challenged by competing information.

A news release notes that although there is near-consensus that sleep promotes learning of certain types of perceptual memories (for example, learning to tap numeric sequences on a keyboard), there is ongoing debate about whether sleep benefits so-called declarative memory, a key type of memory that is based in the brain's hippocampus.

In the new work, the researchers studied the influence of sleep on declarative memory in healthy, college students. The results showed a robust effect, that compared with participants who did not sleep during the trials, those who slept between learning and testing were able to recall more of the original words they had learned earlier.

The beneficial influence of sleep was particularly marked when participants were presented with the challenge of “interference”—competing word-pair information—just prior to testing. A follow-up group further demonstrated that this sleep benefit for memory persists over the subsequent waking day.

“This work clarifies and extends previous study of sleep and memory by demonstrating that sleep does not just passively and transiently protect memories,” the researchers said. “Rather, sleep plays an active role in memory consolidation.”

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Bacterial Vector Used to Deliver Cancer Vaccine

Salmonella typhimurium, often associated with food poisoning, was used to safely and effectively deliver a cancer vaccine, according to a study published in the July issue of the Journal of Clinical Investigation.

The researchers, led by Sacha Gnjatic, PhD, from the Ludwig Institute for Cancer Research in New York City, said that the results suggest that delivery of a cancer vaccine using the S. typhimurium Type III secretion system, by which antigens are transported into the cytosol of infected cells, is a promising novel strategy for cancer immunotherapy that would not require prior knowledge of the tumor antigen composition.

The team constructed an avirulent strain of S. typhimurium with the capacity to transport the NY-ESO-1 tumor antigen. This approach was able to elicit NY-ESO-1-specific CD8+ and CD4+ T cells from peripheral blood lymphocytes taken from cancer patients in vitro.

Oral delivery of S. typhimurium-NY-ESO-1 to mice resulted in the regression of preestablished NY-ESO-1-expressing tumors, and the injection of the vaccine strain and tumor antigen to NY-ESO-1-negative tumors in the presence of preexisting NY-ESO-1-specific CD8+ T cells resulted in the delivery of antigen in vivo and led to tumor regression.

Also, the observation of specific T cell responses against at least two unrelated tumor antigens not contained in the vaccine demonstrated epitope spreading.

This vaccination strategy would require the administration of an S. typhimurium strain engineered to deliver antigens against which the patient would have preexisting CD8+ T cells. Those antigens would not need to be expressed in tumor cells, and it is even conceivable that preexisting CD8+ T cells against viral antigens, such as influenza or Epstein-Barr virus, could be used for this purpose, Dr. Gnjatic and his colleagues wrote.

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More Sensitive Cervical Cancer Screening

A new cervical cancer screening method appears to be more sensitive than conventional cytology in young women, according to a study in the July issue of Lancet Oncology.

The New Technologies for Cervical Cancer (NTCC) group conducted a randomized controlled trial of more than 11,810 women age 25 to 34 years at nine centers in Italy—5,808 were randomly assigned to the conventional smear test group, and 6,002 to the experimental group, which had the DNA test for human papillomavirus along with liquid-based cytology.

The experimental procedure was significantly more sensitive than the conventional procedure, but had a lower positive predictive value. This approach with cytology triage was also more sensitive than conventional cytology, the researchers reported.

In the experimental group, more women were classified as having atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion or more severe cytology than in the conventional group.

Overall, 4% of women in the conventional group and 9% in the experimental group had atypical squamous cells of undetermined significance or more.

In the study, led by Guglielmo Ronco, MD, PhD, of the Centre for Cancer Prevention in Turin, Italy, at least one colposcopy was given to 219 (92%) of the 237 referred women in the conventional group and 651 (93%) of the 697 in the experimental group. The frequency of women with unsatisfactory cytology was much lower in the experimental group than in the conventional group if due to obscuring inflammation, but was very similar if cytology was unsatisfactory for other reasons.

However, liquid-based cytology didn't increase the sensitivity for detection of cervical intraepithelial neoplasia of Grade 2 or more and had a significantly lower positive predictive value than conventional cytology.

HPV testing should be used to screen women for cervical cancer, with only women with persistent infections referred to colposcopy, the researchers concluded. This approach increased sensitivity, while avoiding an increase in false positives even in this age group of such high frequency of infections.

“HPV testing alone, with cytology as a backup, seems to be the most reasonable way for using HPV testing as [the] primary screening test,” Dr. Ronco said in a news release.

“Follow-up will provide data on possible overdiagnosis and on the feasibility of extended intervals, which will be crucial for the decision of switching to HPV testing in routine practice for cervical screening.”

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Naming Trials with an Acronym May Enhance Citation Rates

Naming trials with an acronym is becoming increasingly popular, and may enhance citation rates, according to information in the New England Journal of Medicine (2006;355:101-102).

In the study, published as a Letter, Drs. Matthew Stanbrook, Peter Austin, and Donald Redelmeier from the University of Toronto evaluated whether the naming of a trial with an acronym is associated with a distinctive effect on research, which they measured as the citation rate after publication.

The study—cleverly named the Acronym-Named Randomized Trials (ART) in Medicine Study—identified consecutive randomized trials published between 1953 and 2003 from all systematic reviews by the Cochrane Heart Group as of January 31, 2004. The trials were classified as having or not having a name with an acronym.

There were 173 studies identified, 59 of which were named with an acronym (34%). Circulation, the Lancet, and the New England Journal of Medicine accounted for 61% of the acronym-named studies.

The researchers found that acronym-named studies were cited at twice the rate of trials that were not named with acronyms: 13.8 vs. 5.7 citations per year.

Acronym-named studies, as compared with studies without acronym names, had higher scores showing better methodology. These studies also enrolled five times as many patients and had follow-up periods half as long, but were not more likely to report positive results. They were four times as likely to be funded by the pharmaceutical industry and eight times as likely to be authored by an industry employee.

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Gemcitabine Approved for Ovarian Cancer

The FDA has approved the use of gemcitabine (Gemzar) for use in the treatment of recurrent ovarian cancer. This marks the fourth approval for the drug.

In a news release from the manufacturer, Eli Lilly, long-time ovarian cancer researcher Robert Ozols, MD, PhD, Senior Vice President for Medical Science at Fox Chase Cancer Center, said, “Ovarian cancer is marked by one of the highest recurrence rates of all women's cancers, and when it does progress, it is frequently accompanied by significant symptoms that impede daily activities. The Gemzar combination can help us aggressively address this recurrent disease with increased clinical efficacy and generally manageable side effects.”

The FDA approval specifies that gemcitabine be used in combination with carboplatin. “The Gemzar and carboplatin combination offers one of the most active treatment regimens available for a platinum-sensitive disease with less risk of having neurotoxicity and significant alopecia, making this a valuable treatment option for the treatment of recurrent platinum-sensitive ovarian cancer,” said another well-known ovarian cancer researcher, Tate Thigpen, MD, Professor of Medicine and Director of Oncology at the University of Mississippi School of Medicine.

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Targeted Melanoma Education of High-Risk Groups Improves Screening

An intensive educational intervention targeting siblings of recently diagnosed melanoma patients led to sustained improvements in the rate of self skin-examination, according to a study by researchers at Boston University School of Medicine.

The study, scheduled for publication in the August 15 issue of Cancer, found that the diagnosis of melanoma in a family member represents a unique teaching opportunity for lasting behavioral change targeting skin self-examination. The study is the first randomized trial comparing the impact of interventions on skin cancer prevention and screening practices in a high-risk family group.

Over the last 50 years the incidence of melanoma has increased 15-fold, more than any other cancer, and in the last 25 years mortality has increased 28%. Although the risk of melanoma is two to eight times higher among people with a first-degree relative diagnosed with the disease, many high-risk families are never screened by physicians or perform self-examinations.

As described in a news release, the researchers, led by Alan Geller, MPH, RN, of the Department of Dermatology, conducted a trial to evaluate an intensive, personalized intervention to improve screening and prevention practices in siblings of melanoma patients: (1) conducting routine skin self-examinations; (2) receiving skin cancer screening exams by a dermatologist; and (3) using sun protection to prevent cancer.

High-risk siblings were randomly assigned to receive either the intervention or the standard of care and followed for 12 months. Subjects assigned to the intervention received three telephone-counseling sessions and personalized, targeted educational reading material mailings, and were referred to free screening exams. Those in the control arm were notified by their affected sibling and encouraged to see a physician.

After 12 months the intervention was successful in significantly increasing the number of siblings who performed skin self-examinations, including comparing moles and surveying the back, compared with the control group.

There were no differences, however, between the intervention and control groups for either physician examinations or use of sun protection largely because of improved physician screening in the control group. In both the intervention and control groups the use of sunscreen increased.

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© 2006 Lippincott Williams & Wilkins, Inc.
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