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Researchers at the National Institutes of Health have identified a genetic mutation that accounts for a perplexing condition found in people with an inherited immunodeficiency. The disorder, called combined immunodeficiency, is characterized by a constellation of severe health problems, including persistent bacterial and viral skin infections, severe eczema, acute allergies and asthma, and cancer.

The team that made the discovery was led by Helen Su, M.D., Ph.D., at the National Institute of Allergy and Infectious Diseases (NIAID), and included collaborators from NIAID and the National Cancer Institute (NCI). The research is reported in this week’s New England Journal of Medicine.

“NIH clinicians have cared for people with unusual and difficult-to-treat immune disorders for decades,” says NIAID Director Anthony S. Fauci, M.D. “This study exemplifies their commitment to improving the lives of people with these diseases by trying to uncover the causes of these disorders and thereby better understanding how to treat them.”

Combined immunodeficiency is a type of primary immune deficiency disease (PIDD) in which several parts of the immune system are affected. This inherited disorder is characterized by increased susceptibility to bacterial, viral and fungal infections of various organs of the body. In some cases, susceptibility to cancers also may be seen.

There are 150 known PIDDs. Approximately 500,000 people in the United States have been diagnosed with a PIDD, while many more remain undiagnosed.

The NIAID and NCI investigators recognized that certain patients with an undefined form of combined immunodeficiency shared enough clinical features to make it likely that the cause might be a common genetic mutation. Originally, these individuals were thought to have a variant form of hyper-immunoglobulinema E syndrome (HIES), a disorder characterized by increased levels of a class of antibodies known as immunoglobulin E, superficial and systemic bacterial and fungal infections, and atopic dermatitis, also known as eczema.

This newly described group, however, had far more severe eczema than is typical in people with variant HIES. They also had extensive and difficult-to-manage viral infections of the skin, such as warts, molluscum contagiosum — a type of poxvirus that only infects the skin — and herpes simplex. Some in this group also developed skin cancers, as well as lymphoma of the skin.

“Even though these individuals were diagnosed with a more uncommon form of HIES, they were still considered to have a mystery disease, because they had severe allergies and had developed cancers,” says Dr. Su.

Using a technique called comparative genomic hybridization, a process by which large amounts of DNA are fixed to a computer chip and analyzed for changes in the genes, scientists examined the genes in the tissue samples from five different groups: the 11 individuals with the unknown immunodeficiencies, people with the variant form of HIES, people with classic HIES, those with other immunological diseases, and healthy individuals.

The researchers discovered that people with the unique form of HIES had mutations in a gene called DOCK8 that led to deletions in parts of the gene. The normal function of DOCK8 is currently unknown.

When compared with healthy individuals, the people with DOCK 8 mutations had fewer CD8 positive T cells, immune cells needed to fight viral infections; fewer antibody-producing B cells; and increased numbers of eosinophils — immune cells associated with allergy.

According to Dr. Su, these findings indicate that DOCK8 is essential for defense against viral infections and for preventing the development of cancer and allergies.

Although further study is required to determine if DOCK8 mutations occur in other people with similar disease symptoms, DOCK8 immunodeficiency syndrome may be a new PIDD. These findings mean that individuals with this rare disease will be able to receive a more accurate diagnosis. Identifying a genetic cause for the disease provided comfort to some of those diagnosed who had battled an unknown immune disease for years, according to Dr. Su.

“The study of inherited disorders and the genetic alterations that are responsible for their complex array of disease symptoms has often resulted in the discovery of causative genes that play a role in cancer initiation,” said NCI Director John E. Niederhuber, M.D. “The disease mutations found in this study in the DOCK8 gene exemplify that kind of important finding. As with any discovery of a genetic defect, the challenge going forward is to develop a complete knowledge of the cascading pathways of biological function for which DOCK8 is responsible.”

Chemotherapy can save the lives of people with cancer, but new research suggests it may have devastating effects on the brain.

Many cancer patients who receive chemotherapy report “chemobrain” — a range of symptoms including a loss of memory and the ability to concentrate, and other problems such as difficulty thinking.

The stories of women who survived breast cancer but suffered from weakened brain power are told in a study published online Sept. 16 in the Journal of Cancer Survivorship.

Saskia Subramanian, from the Center for Culture and Health at the University of California — Los Angeles, and colleagues interviewed 74 women who had completed cancer treatment at least a year earlier. The women described a variety of emotions, including fear, frustration and emotional exhaustion.

In some cases, women stated that they feared losing their independence because they wouldn’t be able to take care of themselves like before. They sometimes devoted less time to work and to social activities, and felt that the medical community didn’t pay enough attention to their symptoms of chemobrain, according to a news release about the study.

At the workplace, the side effects of chemotherapy robbed their ability to focus, potentially making it less likely that they’d be promoted, the study authors pointed out.

“These data underscore the very serious ways in which chemobrain can affect the life experiences of cancer survivors — emotionally, psychologically and economically,” the researchers concluded. “A clear understanding of the cognitive impairments experienced by survivors will aid researchers in developing targeted therapies and interventions aimed at improving or mitigating these post-treatment side effects.”

There’s no bad time of the day, week or year to have elective coronary artery bypass surgery, say researchers who analyzed how 18,597 people fared after having the procedure.

The Cleveland Clinic team conducted the study to determine whether working off-hours and long shifts might affect the performance of surgeons and other medical staff. Other studies have shown that lack of sleep, prolonged work hours and natural body-rhythm disturbances reduce the performance of drivers and pilots.

“We started the study believing that timing was likely to influence outcome,” senior investigator Dr. Allen Bashour said in a news release from the American Society of Anesthesiologists. “If so, hospitals could intervene with precautions to improve patient safety during high-risk periods.”

The researchers also looked at the phases of the moon because it’s widely believed that a full moon can increase the number of accidents and emergency room visits.

“However, our results showed that serious complications were rare and that the timing of elective surgery did not influence the outcome,” Bashour said.

Coronary artery bypass graft surgery was studied because it’s the most common heart surgery and because there are well-established protocols for the surgery, the researchers said.

Overall, people in the study had a 4.8 percent major complication rate and a 1.4 percent death rate. The rates were similar for each weekday and each month, and for each phase of the moon, according to the study.

“The study found that elective coronary artery bypass surgery can be scheduled anytime throughout the workday, any day of the week, and in any month of the year with equally good outcomes,” Dr. Daniel I. Sessler, chairman of the Department of Outcomes Research at the Cleveland Clinic and a researcher on the study, said in the news release.

“Our results also suggest that the supposed effect of moon phase on medical complications is merely an urban legend,” he said.

If you have the choice between a seasonal flu vaccine that comes in a nasal spray or an injection, go for the injection, new research shows.

In a study of adults tracked over one flu season, vaccines made from inactivated, or “killed,” flu virus — the injectable form — provided better protection against the seasonal flu than vaccines made from live attenuated virus, the type of vaccine available in a nasal spray.

“The nasal spray vaccine is effective but isn’t as effective as the injected vaccine,” said lead study author Arnold S. Monto, an epidemiology professor at the University of Michigan School of Public Health. “But it’s better to get some vaccine than no vaccine, so if you’re averse to getting an injection, get the nasal spray.”

The researchers stressed that their findings, published in the Sept. 24 issue of the New England Journal of Medicine, applied to seasonal flu vaccine efficacy in adults only. The same may not hold true for children, who may respond just as well to a nasal spray vaccine, or for the H1N1 swine flu vaccines that are on the way.

Researchers gave 1,952 adults aged 18 to 49 either an injected flu vaccine, a placebo injection, a flu vaccine nasal spray or a placebo nasal spray during the 2007-2008 flu season. That season, vaccines were well-matched to the predominant flu in circulation, according to the study.

Participants were reminded each week to come in for an exam and lab tests if they showed signs of respiratory illness. About 6.1 percent of participants, 119 in all, got the flu, mostly influenza A/H3N2.

Among those who got sick, participants who’d received the injected flu vaccine were 68 percent less likely to have the flu compared to those who’d received a placebo, according to the study. The flu virus was confirmed using lab tests.

Participants who’d received the nasal spray vaccine were 36 percent less likely to get the flu than those who’d received a placebo.

The injection was 50 percent better in preventing the flu than the nasal spray, according to the study.

Though researchers did not test vaccines in children, nasal sprays may work just as well in children as injections, Monto said.

There are two different types of vaccines, usually referred to as live attenuated, which contain very weakened or modified live virus, and inactivated, which contain bits of dead virus.

Live attenuated influenza vaccine, which comes in nasal sprays, must replicate in the body in order to provoke the immune system to produce antibodies against the virus. In adults who may already have some immunity against that or other flu strains, the live attenuated virus may not be strong enough to cause that response, Monto said.

Children are more likely to lack antibodies to the virus. Without any natural immunity, the nasal spray may be equally effective, Monto said.

Live attenuated vaccines “must infect in order to protect,” Monto said. “Adults, unlike children, have antibodies to the virus included in the vaccine. They are not infected by it and therefore are not protected. This would explain why the LAIV [live attenuated influenza vaccine] is highly effective in younger children.”

In some cases, the live attenuated influenza vaccine may even provide enhanced protection, said Dr. Kenneth Bromberg, director of the Vaccine Research Center at the Brooklyn Hospital Center in New York City.

In addition to immunity involving antibodies, live attenuated vaccines can also provide cell-mediated immunity, an added type of immune response that can boost effectiveness.

“They are different approaches, and in the case of a well-matched strain, the inactivated vaccine worked better than the live attenuated,” Bromberg said. “There could be situations, such as with a mismatched strain, in which the live attenuated could perform just as well, or perhaps even better, than the injected.”

And what about for H1N1 swine flu vaccines?

With the swine flu, vaccines made with live attenuated virus may work just as well as injected vaccines because children and most adults have no antibodies or natural immunity to the new strain, Monto noted.

“We are totally susceptible,” he said. “That’s why we are having these school outbreaks with high attack rates.”