Medical Research Blog

Watching comedy films boosts blood flow to the heart, finds a small study in the journal Heart. Researchers asked 20 healthy young adults to watch 15 to 30 minute segments of sad and humorous films, a minimum of 48 hours apart.

Examples of sad films included the opening scene of Saving Private Ryan and examples of comedy films included There’s Something About Mary.

Participants were asked to abstain from drinking alcohol, using vitamins or herbs, or taking aerobic exercise the evening before the experiment, as all these can affect blood flow.

In all, 160 measurements of brachial artery blood flow were taken before and one minute after phases of laughter or sadness. The brachial artery runs from the shoulder to the elbow, and is a good indicator of blood flow around the body.

Brachial artery blood flow was reduced in 14 of the 20 participants after watching movie clips that caused distress. But it was increased in 19 of the 20 participants after watching movie clips that elicited laughter. The difference in flow between sad and happy responses exceeded 50 per cent.

The extent of the impact of watching a sad film was of the same magnitude as remembering episodes of anger and doing mental arithmetic, say the authors, while the impact of watching a funny film was equivalent to a bout of aerobic exercise or starting on statin treatment.

The absence of a key protein may lead to infertility.

Researchers at the University of Illinois at Urbana-Champaign report that experiments involving mice — to be detailed in the Proceedings of the National Academy of Sciences — indicate that the transcription factor protein C/EBPb must be present in the uterus for pregnancy to occur. The study appears online this week at the PNAS Web site.

Without it, they say, an embryo cannot survive in uterine tissue or attach to a mother’s blood supply. Other genes also play roles, but C/EBPb is critical for implantation of an embryo, said Milan K. Bagchi, a professor of molecular and integrative physiology.

C/EBPb is scientifically known as CCAAT/Enhancer Binding Protein beta. It is regulated by the hormones estrogen and progesterone. In normal conditions, the protein, driven mostly by progesterone, is expressed rapidly and in large quantities during the critical four-day implantation period in mice, Bagchi said.

During this period, an embryo attaches to the wall of the uterus, advances into it and eventually attaches to the blood supply and forms the placenta. For a successful pregnancy to occur, stromal cells of the uterus must be transformed into decidual cells, which secrete nutrients that allow the embryo to survive until it plugs into the blood supply. C/EBPb is necessary for decidualization, the researchers discovered.

“This protein in the mouse is also in humans,” Bagchi said. “We believe it plays a critical role in human pregnancy. It is expressed in the human endometrium at a time that coincides with the time of implantation. We have demonstrated very clearly in the mouse that in the absence of C/EBPb there is no decidualization. We transferred viable mouse embryos from healthy mice into mice lacking the gene, and pregnancy failed.”

The project began more than four years ago. First, researchers used DNA microarrays to identify gene expression under normal and abnormal conditions during implantation. After messenger RNA profiling zeroed in on C/EBPb’s activity, the researchers collaborated with Peter F. Johnson of the National Cancer Institute’s Laboratory of Protein Dynamics and Signaling, who created mice that lacked the protein.

The experimental mice were then used to observe the relationships of the hormones and their receptors with the protein under varying conditions during the critical implantation period. In doing so, researchers determined that C/EBPb is a critical mediator of steroid hormone responsiveness in the uterus.

“This gene is expressed when the uterus is ready for embryo attachment,” said co-author Indrani C. Bagchi, a professor of veterinary biosciences in the College of Veterinary Medicine at Illinois. “Its presence indicates a window for success.”

If the findings are replicated in human tissue, as expected, she said, the protein’s presence could become a vital gene marker for predicting uterine readiness for pregnancy.

“The success rate for the practice of in vitro fertilization currently is, on average, about 25 percent,” she said. “The major problem is that the conditions occurring when the embryo is transferred often are not the best in the uterus. It’s not known if the uterus is ready to accept an embryo, so often multiple embryos are transferred in hopes that one will attach. In future studies, confirmation of C/EBPb as a marker that correctly indicates uterine readiness for implantation in the human is likely to alleviate these shortcomings.”

Other co-authors of the paper were doctoral student Srinivasa Raju Mantena, postdoctoral researchers Athilakshmi Kannan and Yong-Pil Cheon, and research scientist Quanxi Li, all in Indrani Bagchi’s veterinary biosciences laboratory.

Quality of life measured one year after treatment for head and neck cancer appears to be associated with longer-term survival, according to a study in the January issue of Archives of Otolaryngology – Head & Neck Surgery, one of the JAMA/Archives journals.

Several studies have provided evidence that quality of life (QOL) might be associated with long-term survival in cancer patients, according to background information in the article. However, many studies have examined QOL in patients whose cancers were advanced and were in palliative care, so their results might not apply to people undergoing treatment to cure their cancer. Previous studies on head and neck cancer patients had assessed their QOL before they entered treatment and found no association with survival, the authors report.

Hisham M. Mehanna, B.Med.Sc. (Hon), M.B. Ch.B. (Hon), F.R.C.S., of University Hospitals Coventry and Warwickshire, England, and Randall P. Morton, M.B., B.S., M.Sc., F.R.A.C.S., Auckland City Hospital, New Zealand, assessed whether pretreatment and post-treatment QOL is associated with long-term survival in patients with head and neck cancers. A group of 200 consecutive patients with these types of cancers completed a QOL questionnaire when they were diagnosed with their disease, and again 12 months later, after treatment, if they were free of recurrent cancer.

After 10 years, 136 (68 percent) of the patients died, 48 were alive and the status of 16 was unknown. Those who had a lower QOL one year after treatment–as well as those who had head and neck pain–were more likely to have died.

“We hypothesized that, intuitively, it is more likely that the steady-state QOL, after patients had adjusted to the effects of the diagnosis and of treatment and had mobilized their coping strategies accordingly, would be the determinant of long-term survival, rather than pretreatment QOL,” the authors report. “This was based on the observations that QOL status usually decreases noticeably during and in the period immediately after treatment and that patients return to a steady-state QOL at about one year after diagnosis. The findings of this study seem to corroborate this premise.”

“However, the observed associations between survival benefit and one-year QOL may be confounded by comorbidity, which was not measured and deserves further investigation,” they conclude.

A new Mayo Clinic study finds that vertebroplasty, a procedure used to treat painful compression fractures in the spinal vertebrae due to osteoporosis, appears to increase the risk for new fractures in adjacent vertebrae. The study also found vertebrae adjacent to fractures treated with vertebroplasty fracture significantly sooner than more distant vertebrae. Findings will be published in the January issue of American Journal of Neuroradiology (http://www.ajnr.org).

The researchers discovered that following vertebroplasty, which involves injecting bone cement into the vertebrae to stabilize fractures, patients’ risk for new fractures in vertebrae adjacent to those treated was 4.62 times the risk for nonadjacent vertebral fractures. In addition, they found that new fractures occurred in adjacent vertebrae sooner than in nonadjacent vertebrae: a median of 55 days following vertebroplasty for adjacent fractures and 127 days for nonadjacent vertebral fractures. This is the largest study ever to address the risk of new fractures post-vertebroplasty and the first study to examine whether there is a difference in time course between the development of new fractures adjacent and nonadjacent to the original fracture after treatment with vertebroplasty.

“Everyone involved in vertebroplasty research is concerned about the possibility that placement of cement into fractures will actually increase the risk of fractures in other bones nearby,” says Dr. Kallmes. “Of course we do not want to cause new fractures by treating existing fractures, so we are studying treated patients to see if their bones are fracturing sooner or more frequently than would otherwise be expected.”

“We consider the findings of the current study provocative,” he says. “Our findings suggest vertebroplasty speeds — and possibly facilitates — the fracture of adjacent vertebrae. This is not definitive evidence, but should be considered when discussing risks with patients before embarking on vertebroplasty.”

At this point in the research, Dr. Kallmes still practices vertebroplasty and believes the potential advantages outweigh the risks. Dr. Kallmes recommends that patients considering vertebroplasty for unhealed vertebral fractures consider all potential risks with their physicians, including risks of new fractures in adjacent vertebrae, prior to undergoing the treatment.

The increased risk of adjacent vertebral fractures post-vertebroplasty in some patients could be due to throwing off the biomechanics of the spine by introducing cement, or it could relate to the especially weakened nature of the bones in some patients or the type of cement used in the procedure, say the researchers.

This study involved a retrospective analysis of the risk and timing of subsequent fractures in 432 Mayo Clinic patients previously treated with vertebroplasty. From this group, 186 new fractures occurred post-vertebroplasty in 86 patients; 77 of the fractures were located in vertebrae adjacent to the vertebroplasty-treated vertebrae.

Vertebroplasty is used to treat patients with osteoporosis or a similar condition who have suffered compression of their spines with no or minimal injury. Osteoporotic patients can fracture their vertebrae with simple, everyday movements such as bending over to tie their shoes or turning over in bed, because their bones are weakened. Each year, 700,000 people suffer this injury. For four out of five patients, the fracture heals and the accompanying pain goes away in approximately four weeks with bed rest and analgesics. However, for the other one out of five patients, the fracture does not heal and the pain persists, requiring treatment. Surgery is not an option for these patients, as their bones are too weak. Vertebroplasty is the only available treatment option for patients in this condition. Vertebroplasty is not appropriate for patients with back pain due to ligament injuries, joint disease or narrowing of the spinal canal, says Dr. Kallmes.

Women have yet another reason to stop smoking while pregnant. In the largest study of its kind, plastic surgeons found smoking during pregnancy significantly elevates the risk of having a child with excess, webbed or missing fingers and toes, according to the January issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). In fact, the study found that smoking just half a pack per day increases the risk of having a child born with a toe or finger defect by 29 percent.

“Reconstructive surgery to repair limb, toe and finger abnormalities in children represents a large portion of my practice – it is the most common issue I treat,” said Benjamin Chang, MD, ASPS member and study author. “Parents would ask why this happened to their child, but I didn’t have an answer. This study shows that even minimal smoking during pregnancy can significantly increase the risk of having a child with various toe and finger defects.”

Researchers examined the records of more than 6.8 million live births in the United States during 2001 and 2002, finding 5,171 children born with a digital anomaly where the mother smoked during pregnancy but did not suffer from other medical complications, such as heart disease, diabetes or high blood pressure.

The study authors discovered pregnant women who smoked one to 10 cigarettes per day increased the risk of having a child with a toe or finger deformity by 29 percent. The more a woman smoked, the higher the risk became. Women who smoked 11 to 20 cigarettes a day raised the risk 38 percent, and women who smoked 21 or more cigarettes per day raised the risk 78 percent.

Known as polydactyly, syndactyly and adactyly, these deformities are the most common congenital limb abnormalities. Polydactyly is the presence of more than five digits on the hands or feet. Syndactyly is having fused or webbed fingers or toes. Adactyly is the absence of fingers or toes.

Webbed fingers or toes occur one in every 2,000 to 2,500 live births and excess fingers or toes occur one in every 600 live births. Webbed fingers or toes occur twice as often in boys and are more common in Caucasians than African Americans. Excess digits, however, are 10 times more common in African Americans and are only slightly prevalent in boys. Nevertheless, the majority of these defects occur without any family history and most causes are unknown which has lead researchers to investigate environmental causes, such as smoking, for these anomalies.

“The results of this study were interesting. We suspected that smoking was a cause of digital anomalies but didn’t expect the results to be so dramatic,” said Dr. Chang. “Smoking is so addictive that pregnant women often can’t stop the habit, no matter what the consequences. Our hope is this study will show expectant mothers another danger of lighting up.”

According to exciting new research, which will be published in the March 2006 issue of Integrative Cancer Therapies - dogs can actually smell cancer on humans. We all know about the amazing ability of dogs to smell things that humans cannot and dogs have long been used to help rescue people, or discover drugs but now scientists have documented the amazing ability of dogs to distinguish people with both early and late stage lung and breast cancers from people who don’t.

Other scientific studies have documented the abilities of dogs to identify chemicals that are diluted as low as parts per trillion. The clinical implications of canine olfaction first came to light in the case report of a dog alerting its owner to the presence of a melanoma by constantly sniffing the skin lesion. Subsequent studies published in major medical journals confirmed the ability of trained dogs to detect both melanomas and bladder cancers. The new study, led by Michael McCulloch of the Pine Street Foundation in San Anselmo, California, and Tadeusz Jezierski of the Polish Academy of Sciences, Institute of Genetics and Animal Breeding, is the first to test whether dogs can detect cancers only by sniffing the exhaled breath of cancer patients.

In this study, five household dogs were trained within a short 3-week period to detect lung or breast cancer by sniffing the breath of cancer participants. The trial itself was comprised of 86 cancer patients (55 with lung cancer and 31 with breast cancer) and a control sample of 83 healthy patients. All cancer patients had recently been diagnosed with cancer through biopsy-confirmed conventional methods such as a mammogram, or CAT scan and had not yet undergone any chemotherapy treatment. During the study, the dogs were presented with breath samples from the cancer patients and the controls, captured in a special tube. Dogs were trained to give a positive identification of a cancer patient by sitting or lying down directly in front of a test station containing a cancer patient sample, while ignoring control samples. Standard, humane methods of dog training employing food rewards and a clicker, as well as assessment of the dog’s behavior by observers blinded to the identity of the cancer patient and control samples, were used in the experiment.

The results of the study showed that dogs can detect breast and lung cancer with sensitivity and specificity between 88% and 97%. The high accuracy persisted even after results were adjusted to take into account whether the lung cancer patients were currently smokers. Moreover, the study also confirmed that the trained dogs could even detect the early stages of lung cancer, as well as early breast cancer. The researchers concluded that breath analysis has the potential to provide a substantial reduction in the uncertainty currently seen in cancer diagnosis, once further work has been carried out to standardize and expand this methodology.

Liver disease is often associated with “sickness behaviors,” such as malaise, listlessness, anorexia, difficulty concentrating, and fatigue. In cholestatic liver diseases (where bile production is impaired) such as primary biliary cirrhosis, fatigue occurs in up to 86 percent of patients. Previous studies have suggested that these symptoms originate from changes to the central nervous system (CNS), but little is understood about how these changes occur or the pathways involved.

In a study led by Steven M. Kerfoot of the Immunology Research Group at the University of Calgary in Canada and published in the January 2006 issue of Hepatology, researchers speculated that cholestatic liver damage may be associated with an immune response affecting the central nervous system, specifically the brain, which could represent a novel and potentially important pathway.

Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc. is available online via Wiley InterScience here.

A new study suggests that antibody-based cancer drugs might help patients more if they are given with substances that stimulate the immune system.

This new study is the first to indicate that the drug trastuzumab, also known as Herceptin, may work better when it is followed by injections of interleukin (IL) 2 or IL-12. Both substances trigger the activity of immune cells known as natural killer (NK) cells.

The research, by scientists at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, is published in the Jan. 1 issue of the journal Cancer Research.

The drug trastuzumab consists of an antibody that targets the protein HER2, which is present on cancer cells of many breast tumors. NK cells are the body’s first line of defense against many infections, and they also attack tumor cells.

NK cells rush into action when they encounter bacteria or other foreign agents in the body that are coated with antibodies, large proteins released by immune cells in response to the presence of foreign material in the body.

Trastuzumab is used to treat advanced breast cancer cases that over-produce the HER2 protein. The drug coats the tumor cells with antibodies, but it is unclear exactly what happens next.

Presently, researchers believe that when the trastuzumab antibodies join with the HER2 protein, they trigger changes within the tumor cells that cause the cells to die or to grow more slowly. In this scenario, the immune system plays a relatively minor role in slowing the tumor’s growth.

“But our results show that the immune system really can play an important role in this therapy and that the outcome of patients treated with antibody-based drugs might be improved by activating the patient’s immune system with agents such as IL-12,” says principal investigator William E. Carson, III, associate professor of surgery and director for clinical research at the OSU Comprehensive Cancer Center.

First author Julie M. Roda, a graduate research associate in Carson ’s laboratory, explained why this is so.

“The findings suggest that using trastuzumab and the IL-12 together makes the body think an infection is under way, and this activates cells of the immune system to eliminate tumor cells in the same way they would eliminate an infection,” says Roda.

The investigators found that the combination of antibody-coated cells and IL-2 or IL-12 causes the NK cells to release substances that attract more potent immune cells – mainly killer T cells – thereby trigging a larger and more effective immune response against the tumor.

“Trastuzumab was not designed to mimic an infectious condition, but we think that’s exactly what is happening,” Roda says.

Carson, Roda and their colleagues came to their conclusions following several types of experiments.

For example, the researchers added human NK cells and IL-2 or IL-12 to cultures of breast-cancer cells with HER2 and coated with trastuzumab antibodies. In response, the NK cells produced a range of substances (known as cytokines and chemokines) known to attract killer T cells to sites of infection. When the experiment was repeated using cancer cells that lacked HER2 (and therefore were not coated with trastuzumab), however, the NK cells produced little of the T-cell-attracting substances.

The researchers also injected IL-12 and trastuzumab-coated mouse-tumor cells into mice and found that it raised the blood levels of the immune-stimulating substances produced by NK cells.

In addition, the researchers analyzed plasma samples from 15 patients with different types of cancer who were participating in a phase-I clinical trial of trastuzumab plus IL-12. The samples showed short-term increases in immune-stimulating substances produced by NK cells, and long-term increases in three patients who responded to the therapy.

“This is a preliminary study and the findings must be verified,” Carson says, “but overall, the evidence supports the use of immune-stimulating agents in patients who receive antibody-based drugs such as trastuzumab.”

We all wonder what is in the air for 2006 - but for people with asthma and other breathing problems, advance knowledge of air pollution levels is very important. An ESA-backed project is forecasting daily forecasts via text message to selected individuals in parts of London and the London borough of Croydon.

As the video above recounts, the service anticipated especially high levels of air pollution during late June 2005, when a concentrated air pollution mass formed over central Europe. The winds carried that pollution to England, with ozone reaching harmful levels in London on 24 to 26 June.

However as part of a portfolio of services called PROMOTE, this development was predicted by the sophisticated French air quality modelling service PREV’AIR. Another PROMOTE service, YourAir, then included these inputs when modelling local air quality in the London borough of Croydon. Then, through a trial system called AirTEXT, a warning was sent via SMS text messages to around a thousand people with asthma or other vulnerable conditions, one day in advance of the elevated ozone levels.

The YourAir service combines regional air quality forecasts from PROMOTE partners with information on local road traffic patterns. The regional air quality information is important because not all pollution affecting a city actually originates there – studies show that up to half may originate elsewhere.

The forecasts include predictions of overall effects on health on an index from one to ten. The YourAir service resolves air pollution down to the scale of individual streets – highest levels are often found along routes with heavy traffic or other pollution sources, so information on street-by-street changes in pollution help vulnerable people make informed choices about their movements.

The prototype service covers Central London and Croydon in South London, which is one of the city’s largest boroughs by area and the largest by population, with 330 000 inhabitants.

The pollution peak shown occurred in the summer, but air quality is a year-round problem. Some of the highest pollution events occur when the meteorological situation means local pollution remains trapped close to the ground to combine with drifting pollution from elsewhere. In London this can often happen during the winter.

Maria Ryan, a young mother of three, lives on the edge of Croydon. A mild asthmatic, she is participating in the AirTEXT project: “I’m living close to a main road, and though I don’t know if it is connected or not, my asthma has got bad again during the last few years.

“I check the pollution levels in the newspaper but now I get a forecast by text message a day beforehand. I am glad to get it as a warning to be prepared and take my inhaler with me on a bad day. Going out without it would not be good!”

For the more than 18 million Americans who suffer from depressive illnesses, the best pharmacological treatments are those that increase levels of serotonin, the brain chemical that regulates mood, sleep and memory. New research by an international team of scientists, led by Rockefeller University researchers in Paul Greengard’s laboratory of Molecular and Cellular Neuroscience, shows that a gene called p11 is closely related to serotonin transmission in the brain — and may play a key role in determining a person’s susceptibility to depression.

The newly discovered link between depression and the serotonin system, reported in the January 6 issue of the journal Science, could lead to new treatments for these mental disorders.

“We have shown that a gene called p11 is involved in the multiple complex changes that underlie depression,” says Per Svenningsson, a research assistant professor and first-author on the paper. “Our findings demonstrate that patients with depression, and mice that model this disease, have decreased levels of p11 protein, and they suggest that drugs that increase p11 are likely to have anti-depressant properties.”

Serotonin binds to 14 different receptors on a cell’s surface. One receptor in particular, known as 1B, plays a crucial role in regulating serotonin transmission in the brain. Recent studies have suggested a role for the serotonin 1B receptor in depression, as well as in obsessive-compulsive disorder, drug addiction, anxiety, aggression and sleep.

Intrigued by these studies, Svenningsson and colleagues at Rockefeller, the Karolinska Institute, the University of Rouen in France and Eli Lilly and Company, used a blind screen called a yeast two-hybrid screen to identify proteins that associate with the serotonin 1B receptor. They found an association with a protein called p11, a protein previously identified as a regulator of the localization of several proteins on the cell’s surface.

The researchers analyzed tissue from a mouse model of depression as well as post-mortem tissue from depressed human patients, and found decreased levels of p11 protein in both cases. On the other hand, p11 levels increased in rats and mice that were treated with anti-depressant medications or electroconvulsive therapy.

To further test the connection, Svenningsson and his colleagues genetically engineered two strains of mice: one that produced more p11 than normal and another that produced no p11 at all. They found that mice that overexpress p11 were hyperactive and, in a test designed to identify depression in rodents, acted just like mice that were on anti-depressant medication. Mice that lacked p11, meanwhile, acted depressed and showed less responsivity to anti-depressant medications.

Taken together, the findings point to p11 as a new target for developing depression treatments.

“In addition to exploring ways to increase p11 in depressed patients, it may also be possible to develop peptide-based compounds that can mimic the action of p11 to achieve a new class of anti-depressant compounds,” Svenningsson says.