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Thursday, January 31, 2008

Cough and Cold Medicines put 7,000 American Children a Year in The Emergency Department

Over 7,000 children in the US end up in emergency departments every year because of complications from taking cough and cold medicines, found researchers who did a nationwide study of the problem. They said there is an urgent need for fresh ideas to tackle the problem, especially since the largest proportion of emergency cases are the result of children getting hold of and taking cough and cold medicines unsupervised.

The study was carried out by researchers from the US Centers for Disease Control and Prevention (CDC) and is published in the 28th January online issue of Pediatrics.

The researchers, led by Daniel S. Budnitz, observed that adverse events resulting from children ingesting cough and cold drugs is a not insignificant public health problem, and decided to investigate this on a national level, to help policy makers and health professionals put together age-appropriate measures to tackle the issue.

They looked at records dated from the beginning of 2004 to the end of 2005, of adverse events related to cough and cold medications in children under 12 years of age from 63 US emergency departments.

The results showed that:

* An estimated 7,091 children under 12 were treated every year in emergency departments for adverse events related to cough and cold medications.

* This number accounts for 5.7 per cent of emergency department visits for all medications in this age group.

* Most of the visits (64 per cent) were by children aged between 2 and 5 years.

* Most of the visits were caused by children taking the medications by themselves (66 per cent).

* This is significantly higher than the proportion of "unsupervised ingestions" recorded for other medications (47 per cent).

* Also, most of the unsupervised ingestions of cough and cold medicines that led to emergency department visits were by children aged between 2 and 5 (77 per cent).

* The vast majority of children (93 per cent) did not require hospitalization or extended observation.

The researchers concluded that:

"Timely national surveillance data can help target education, enforcement, and engineering strategies for reducing adverse events attributable to cough and cold medications among children."

They suggested that preventing children taking cough and cold remedies without supervision was the area that most needed fresh ideas, since this was the biggest cause of adverse events. The ideas could also be applied to other children's medication.

This comes in the wake of a new Public Health Advisory from the US Food and Drug Administration (FDA) recommending children under 2 years of age are not given over the counter cough and cold medicines, because of question marks over their effectiveness and safety.

The FDA said it is also reviewing the case for making such a recommendation for older children and will make a further announcement when it has completed its evaluation of OTC cough and cold medications in older populations.

This study received a warm welcome from a number of groups concerned about what they describe as the high risk versus the questionable benefits of cough and cold medicines for young children.

Speaking to the Washington Post, Baltimore's public health commissioner, Joshua M. Sharfstein, who led the group that petitioned the FDA to restrict marketing of the medicines for children, said it was time to pull the plug on these products, commenting that:

"This is a lot of trips to the emergency room for products that have no known benefit."

Industry representatives on the other hand, pointed to lack of parental understanding about the right dose, or failing to keep the medicines out of the reach of children, as the main problem, and that the products were safe and effective when used correctly.

See Full Article

Tuesday, January 29, 2008

Hong Kong Flu

Compiled and Summarized by Anthony
Hong Kong flu is a pandemic of influenza A (H3N2) in 1968-69. This virus was first detected in Hong Kong in early 1968 and spread to the United States later that year. where it caused about 34,000 deaths, making it the mildest pandemic in the 20th century. Also known as Hong Kong influenza.

There could be several reasons why fewer people in the US died due to this virus. First, the Hong Kong flu virus was similar in some ways to the Asian flu virus that circulated between 1957 and 1968. Earlier infections by the Asian flu virus might have provided some immunity against the Hong Kong flu virus that may have helped to reduce the severity of illness during the Hong Kong pandemic.

Second, instead of peaking in September or October, like pandemic influenza had in the previous two pandemics, this pandemic did not gain momentum until near the school holidays in December. Since children were at home and did not infect one another at school, the rate of influenza illness among schoolchildren and their families declined.

Third, improved medical care and antibiotics that are more effective for secondary bacterial infections were available for those who became ill.

Signs and Symptoms

The list of signs and symptoms mentioned in various sources for Flu includes the 20 symptoms listed below:

· Headache
· Fever
· Chills
· Sneezing
· Runny nose
· Nasal inflammation
· Blocked nose
· Dry cough
· Sore throat
· Sweating
· Body aches
· Muscle aches
· Limb pain
· Joint pain
· Loss of appetite
· Prostration
· Exhaustion
· Fatigue
· Weakness
· Myalgia

Note that Flu symptoms usually refers to various symptoms known to a patient, but the phrase Flu signs may refer to those signs only noticeable by a doctor.

Causative Agent

Influenza A (H3N2)

Mode of Transmission

H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtype arose in pigs co-infected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported re-assortment of divergent subtypes. However, other hosts appear capable of similar co-infection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible.

As an Influenza virus, it predominately transmitted by airborne spread in aerosols but can also be transferred by direct contact with droplets. Nasal inoculation after hand contamination with the virus is also an important mode of transmission.

Direct contact is important, as the virus will survive some hours in dried mucus particularly in cold and dry environments.


Laboratory diagnosis depends upon the demonstration of the virus or its components or a rising antibody titre. The following tests are available:

· Direct antigen detection
· RT-PCR for viral RNA
· Virus culture
(nasal pharyngeal aspirate preferably within 3 days of onset, other specimens, such as stool and rectal swabs may be considered.)

· Serological tests for detection of specific antibody.
(blood test within 7 days of onset and repeated at least 2 weeks after onset.)

Incubation Period

The incubation period of a case will probably be one to four days.


Infection of pigs with influenza A viruses is of substantial importance to the swine industry and to the epidemiology of human influenza. At present, three main subtypes of influenza viruses are circulating in the swine population throughout the world: subtypes H1N1, H3N2, and H1N2. In North America, influenza virus outbreaks among pigs have historically been due almost exclusively to infection with H1N1 viruses. Since 1997-1998, however, H3N2 viruses have emerged and spread widely within the swine population. Triple-reassortant H3N2 viruses containing hemagglutinin (HA), neuraminidase (NA), and PB1 polymerase genes of human influenza virus origin, the matrix (M), nucleoprotein (NP), and nonstructural (NS) genes of classical swine influenza virus origin, and the PA and PB2 polymerase genes of avian influenza virus origin have been isolated widely throughout the United States. These viruses have been associated with outbreaks of respiratory disease in pigs of all ages and abortions in pregnant sows. In addition, reassortment between these viruses and classical H1N1 viruses has led to the subsequent development of H1N2 viruses, which have also spread throughout the swine population of the United States. In contrast, an H3N2 virus in which all eight RNA segments were of human influenza virus origin was isolated from a single baby pig in 1997 on a farm in Ontario, Canada. This virus did not spread within the farm of origin and has not been recovered from pigs subsequent to its initial isolation.

Influenza A viruses have been isolated from various species, including humans, pigs, horses, birds, sea mammals, and mink. However, wild waterfowl serve as the reservoir from which all influenza viruses are thought to have emerged. Despite their common origin, influenza A viruses are generally restricted in host range. In particular, avian influenza viruses replicate poorly in humans and nonhuman primates and human influenza viruses do not replicate well in birds. In contrast, swine influenza viruses have been shown repeatedly to infect humans as zoonotic infections, and conversely, human influenza viruses have also been isolated from pigs.

The host range restriction of influenza viruses is a polygenic trait, but the HA gene is considered to be a particularly important determinant since HA is responsible for attachment of the virus to sialic acid receptors on the host cell surface. While human influenza viruses preferentially bind to sialic acid bound to galactose by α2,6 linkages, avian viruses preferentially recognize sialic acid bound by α2,3 linkages. This is consistent with the fact that human tracheal epithelial cells predominantly express α2,6-linked receptors, whereas avian intestinal cells predominantly express α2,3-linked receptors. However, avian and human influenza viruses can both infect pigs because porcine respiratory epithelial cells express both N-acetylneuraminic acid-α2,3-galactose and N-acetylneuraminic acid-α2,6-galactose. Pigs can therefore function as intermediate “mixing vessel” hosts in establishing new influenza virus lineages by supporting coinfection, replication, and reassortment among human, avian, and swine influenza viruses.

Even though influenza viruses can cross species barriers and infect pigs, it is not known what properties are necessary to allow a virus to form a stable lineage and to spread efficiently within the pig population. In particular, a wholly human H3N2 virus, A/Swine/Ontario/00130/97 (H3N2) (Sw/ONT), initially crossed the species barrier to infect a pig in Canada in 1997, but it did not infect other pigs in the herd. Its disappearance may have been due to characteristics of the virus (i.e., its replication efficiency in pigs) or epidemiological factors (i.e., the availability of susceptible animals). In contrast, triple-reassortant H3N2 viruses containing genes from human, classical swine, and avian influenza viruses have spread throughout the swine population of the United States since 1998. The critical factors that affect replication ability in pigs may include the overall constellation of genes present in the triple-reassortant viruses. However, we have also identified specific differences in the sequences of the HA genes of triple-reassortant viruses that may represent swine adaptation mutations. As an initial step in understanding the pathogenesis of these viruses in pigs, the present study was designed to define the specific characteristics of these viruses, including their infectivities, replication kinetics, and ability to induce pathological lesions under experimental infection conditions.


Influenza virus infection occurs after transfer of respiratory secretions from an infected individual to a person who is immunologically susceptible. If not neutralized by secretory antibodies, the virus invades airway and respiratory tract cells. Once within host cells, cellular dysfunction and degeneration occur, along with viral replication and release of viral progeny. Systemic symptoms result from inflammatory mediators, similar to other viruses.


Please see Flu -Prevention.


Please see Flu -Treatment.


The most common complication of Influenza is Pneumonia. Other complications include Bronchitis, Sinus, Ear infections, Myocarditis, and Pericarditis. Myositis is among the complications but this one rarely occurs.


Provided primary source of information.

Provided information on Signs and Symptoms.

Provided extra information.

Provided extra information.

Provided information on Pathogenesis.

If you find an error, please let us know.

Monday, January 28, 2008

A Drug's unsightly Side Effect leads to a new understanding of how Stem Cells maintain their potency

Like fine china and crystal, which tend to be used sparingly, stem cells divide infrequently. It was thought they did so to protect themselves from unnecessary wear and tear. But now new research from Rockefeller University has unveiled the protein that puts the brakes on stem cell division and shows that stem cells may not need such guarded protection to maintain their potency.

This research, published in the January 25 issue of Cell, raises questions about what stem cells need in order to maintain their ability to regenerate tissue. It may also be key in developing new treatments for thinning hair.

The impetus for the work began five years ago when Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development, and several researchers in her lab discovered that the protein NFATc1 was one of only a few that are highly expressed within the stem cell compartment of the hair follicle. Clinical research, meanwhile, showed that a particular immunosuppressant that inhibits NFATc1, a drug called cyclosporine A, has a rather unsightly side effect: excessive hair growth.

Fuchs and Valerie Horsley, a postdoc in her lab, realized that there was a connection between the drug's side effect and the abundance of NFATc1 within the hair follicle's stem cell compartment -- the bulge. The mice they treated with the drug grew fur at a much faster rate than mice they did not treat. The researchers then showed that this excessive hair growth was due to increased stem cell activity within the bulge, a process that cranked up the production of hair. Specifically, the hair cycle shifted gears from its resting phase, when stem cells slumber, to its growth phase, when stem cells proliferate.

To maintain their multipotent properties, though, it appears that these stem cells hardly needed much "rest" at all. These findings came as a surprise to the researchers, who, like their colleagues, had believed that stem cells proliferating infrequently protected them from depletion or mutations that would lead to hair loss. "It seems like the resting phase isn't as necessary as was once thought," says Horsley. "Even though these stem cells are highly proliferative, they still maintain their stem cell character."

Using genetically engineered mice bred by colleagues at Harvard Medical School, Horsley and Fuchs then further explored what happens when skin stem cells lack NFATc1. They found that these mice looked exactly like the hairy mice that were treated with cyclosporine A: The loss of NFATc1 didn't stop the hair cycle, but rather shortened the resting phase and prompted precocious entry to the growth state.

In probing the underlying mechanisms mediating this process, Horsley and Fuchs discovered that NFATc1, a transcription factor, blocks the expression of a gene that provides the cell cycle with "go ahead" signals at certain checkpoints. By blocking these signals, NFATc1 prevents the stem cells from dividing, preventing unnecessary wear and tear. These same cells, if treated with cyclosporine A, show a rapid loss of the transcription factor, an effect that turns the light green at these checkpoints.

For those with thinning hair, this research may hold promise. As people age, the resting phase of the hair cycle gets longer and longer such that the stem cells proliferate less frequently and hair does not grow at the rate it once did. "If we could use a local and more specific inhibitor of NFATc1 than cyclosporine A to stimulate these stem cells, which are just sitting there during an extended resting phase, we might be able to promote new hair growth," says Fuchs, who is Rebecca C. Lancefield Professor at Rockefeller and an investigator at the Howard Hughes Medical Institute. "In a sense, by blocking NFATc1 activity in our older mice, their hair follicles were brought back to what appeared to be a more youthful state."

So far, these proliferating stem cells lacking NFATc1 have not led to increased tumor formation, which is often a dangerous byproduct of triggering stem cells into action. "This is the first case where we have been able to activate the hair cycle without accompanying signs of tumorigenesis," says Fuchs. "If we can control the activation process of follicle stem cells without promoting tumorigenesis, then this would be a big move in the right direction."

See Full Article

Genetic Role In Development and Disease may be revealed during search for 'On' Switches

A new resource that identifies regions of the human genome that regulate gene expression may help scientists learn about and develop treatments for a number of human diseases, according to researchers at Duke's Institute for Genome Sciences & Policy (IGSP).

"The majority of DNA in our bodies is packaged, or tightly structured," said Gregory Crawford, Ph.D., a researcher in the IGSP and one of the senior investigators on this study. "Our goal was to identify the areas of DNA across the entire genome that are not packaged, because we know those are the regions that are important in regulating gene activity."

The researchers published their findings in the January 25, 2008 issue of the journal Cell. The study was funded by the Duke IGSP and the National Human Genome Research Institute.

They combined two known processes to look at regulatory regions across the whole human genome, Crawford said.

"We used an enzyme called DNase that has been known for decades to preferentially identify unpackaged regions of DNA," he said. "In this study, we identified all unpackaged regions within the entire genome using two extremely efficient methodologies: microarrays and sequencing."

Microarrays are glass slides on which scientists can simultaneously look at millions of short pieces of DNA. New sequencing technologies are able to determine the genetic code of millions of DNA fragments. Together, these tools generated guides to understanding the location of the unpackaged regions, and the researchers compared the results found using each method and found high levels of agreement.

By combining the two methods, the researchers were able to scan the entire genome efficiently.

"Scientists have used similar methods to look at tiny portions of the genome in the past, but ours is the first technology to really allow researchers to look at the whole genome, so we can see all of the areas where gene regulation occurs," said Terrence Furey, Ph.D., a researcher in the IGSP and co-senior investigator on this study. "Identifying these sites may help us understand the biological basis for gene regulation expression patterns in different cell types. We'll also compare patterns within and across species, in response to external stimuli and in diseased tissues."

The researchers said they looked at normal cells for this study because in order to understand anything about disease or the aging processes, it's important to first understand what a normal cell looks like.

"Perhaps in the future, this data resource could help researchers learn to turn a harmful gene off or increase the expression of helpful ones," Furey said.

See Full Article

Saturday, January 26, 2008

Is this the Beginning of Artificial Life?

In what many believe to be a case of creating artificial life, American scientists have found a way of replicating a bacterium's 582,970 base pair genome which should allow for the creation of biofuel-manufacturing bacteria - in other words, building bacteria from scratch that might produce fuel for things like cars. It is the largest man-made DNA structure ever made. The previous largest one contained only 32,000 base pairs.

You can read about this in Science magazine.

Dr. Hamilton Smith, J. Craig Venter Institute, Rockville, USA, and sixteen others built a bacterium's genome by chemically synthesizing DNA blocks. These blocks were then weaved together to create bigger DNA pieces - these can be formed to create a synthetic version of Mycoplasma genitalium. The scientists say these tailor-made micro-organisms can be designed to produce hydrogen, or tweaked to absorb surplus carbon dioxide in the air.

The team is not using the term artificial life; they prefer to call it synthetic life. Dr. Smith, in a BBC interview, said "We like to distinguish synthetic life from artificial life. It sets the stage for what we hope is going to be a new approach to engineering organisms."

The J. Craig Venter Institute (JCVI) says this is the second of three key steps towards the team's aim of creating a fully synthetic organism. They are currently trying to create a living bacterial cell, based completely on the synthetically made genome.

J. Craig Venter, Ph.D., President and Founder of JCVI, said "This extraordinary accomplishment is a technological marvel that was only made possible because of the unique and accomplished JCVI team. Ham Smith, Clyde Hutchison, Dan Gibson, Gwyn Benders, and the others on this team dedicated the last several years to designing and perfecting new methods and techniques that we believe will become widely used to advance the field of synthetic genomics."

The scientists explain that building blocks of DNA - adenine (A), guanine (G), cytosine (C) and thymine (T) are tremendously tricky chemicals to artificially synthesize into chromosomes. The longer the strands become the more brittle they are, making it very hard to work with them. Making the genome of the M. genitalium bacteria with over 580,000 base pairs was an enormous challenge.

Hamilton Smith said "When we started this work several years ago, we knew it was going to be difficult because we were treading into unknown territory. Through dedicated teamwork we have shown that building large genomes is now feasible and scalable so that important applications such as biofuels can be developed."

See Full Article

Thursday, January 24, 2008

Hypertension Patient's Gene Type influences Response to Medication

If you suffer from high blood pressure (hypertension) your genotype may influence how well you respond to certain medications, according to an article in the Journal of the American Medical Association (JAMA), January 23rd issue.

Of the 71 million Americans who are known to suffer from at least one type of CVD (cardiovascular disease), at least 65 million have high blood pressure. Only about two-thirds of all hypertension patients have their blood pressure controlled successfully with current treatments, the authors explain. Even though treatments have improved in recent years, a sizable number of patients are not being treated effectively. Using treatment tailored to a CVD patient's particular genotype has been an area of focus in recent years - however, there have been no effective therapeutic choices for the clinical setting.

Amy I. Lynch, Ph.D., University of Minnesota, Minneapolis, and team carried out a study to find out whether hypertensive patients with minor atrial natruiretic precursor A (NPPA) genotypes (NPPA G664A and NPPA T2238C) randomized to the diuretic chlorthalidone had different outcomes for CVD measures than patients who were randomized to other types of antihypertensive drugs. According to some previous studies, the NPPA gene may have an impact on the effectiveness of hypertensive medications.

The researchers studied data on 38,462 patients with high blood pressure from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized clinical trial which took place at various centers in the USA and Canada. Genotyping was carried out from February 2004 to January 2005. The patients were selected at random to receive a diuretic (chlorthalidone; n = 13,860), a calcium channel blocker (amlodipine; n = 8,174), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril; n = 8,233), or an alpha-blocker (doxazosin; n = 8,195). They were monitored (followed-up) for 4.9 years (average).

They found evidence of a pharmacogenetic* link of the NPPA T2238C variant to coronary heart disease (CHD), stroke, all-cause death, combined CHD, and combined CVD when they compared the chlorthalidone (diuretic) group with the amlodipine (calcium channel blocker) group, and for stroke when they compared the chlorthalidone group with those receiving amlodipine or lisinopril (ACE inhibitor).

* Pharmacogenetics is the study of how people's genetic makeup affects their responses to drugs.

The link was consistent for all outcomes. Patients who had one copy or more of the minor C allele had a reduced risk of disease/death when given chlorthalidone compared to those who were given amlodipine (and the amlodipine group plus the lisinopril group for stroke). Patients in the chlorthalidone group with the TT genotype had an elevated risk of disease/death compared to those receiving amlodipine.

The researchers wrote "We also observed a pharmacogenetic association of NPPA T2238 on change in systolic and diastolic blood pressure 6 months after treatment randomization in a similar direction: generally, minor C allele carriers had greater reductions in blood pressure when randomized to chlorthalidone vs. either lisinopril or doxazosin relative to those with the common TT genotype."

"This study demonstrates the importance (and sometimes paradoxical findings) of pharmacogenetic research; for example, while minor NPPA T2238C allele carriers (as well as the entire study population viewed as a whole) may have had more favorable outcomes when randomized to a diuretic (chlorthalidone), participants with the most common genotype (TT) responded better when assigned to a calcium channel blocker (amlodipine) for some clinical outcomes. Further research is needed to determine the optimal approach for personalizing antihypertensive medication treatment regiments according to genotype information and for achieving the best possible clinical outcomes," they concluded.

See Full Article

Wednesday, January 23, 2008

Localized Prostate Cancer Patients may benefit from Hormone Suppression combined with Radiation Treatment

While a man with localized prostate cancer will live longer if he receives male hormone suppression therapy combined with radiation treatment, the same does not happen for patients with moderate/high levels of other illnesses, says an article in the Journal of the American Medical Association (JAMA), January 23rd issue.

The authors explain that prior studies have shown that patients with unfavorable localized and locally advanced prostate cancer who receive androgen suppression therapy (AST) together with RT (external radiation therapy) survive for longer than those who receive RT alone. However, patients who have co-existing illnesses may have increased negative side-effects to such a degree that their survival advantages are not there.

Anthony V. D'Amico, M.D., Ph.D., Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, and team carried out an analysis of overall survival of 206 patients with localized but unfavorable-risk prostate cancer in subgroups defined by their level of co-existing illnesses at the time of their randomization to AST combined with RT vs. RT alone. 74 of them died during a follow-up period of 7.6 years.

Overall survival estimates were significantly higher for those patients who randomly received RT combined with AST, compared to the men who just received RT, the authors report. "The cumulative incidence estimates of prostate cancer-specific mortality significantly favored the RT and AST group, with an increased risk of prostate cancer-specific mortality (14 vs. 4 deaths) that translated into an increased risk of all-cause mortality (44 vs. 30 deaths) in men randomized to RT compared with RT and AST."

The researchers observed a substantial interaction between co-morbidity score and treatment. For the 157 patients with no or very low co-morbidity scores there was a significantly higher survival rate for those receiving combination treatment compared to those who just received RT (31 vs. 11 deaths). However, among the 49 patients with moderate/severe co-morbidity, those receiving RT alone did not have a higher all-cause mortality rate than those receiving RT combined with AST (13 vs. 19 deaths).

The researchers wrote "The clinical significance of this finding is that pre-existing co-morbid illness may increase the negative effects of specific anti-cancer treatments such as AST," the authors write. In conclusion, the addition of 6 months of AST to RT resulted in increased overall survival in men with localized but unfavorable-risk prostate cancer. This result may pertain only to men without moderate or severe co-morbidity, but this requires further assessment in a clinical trial specifically designed to assess this interaction."

See Full Article

Tuesday, January 22, 2008

New HIV Drug Etravine wins FDA Approval

The US Food and Drug Administration (FDA) gave approval last Friday, 18th January, for etravine to be used as an adjunct anti-HIV therapy for adults who have failed to respond to other antiretroviral treatments. The drug's brand name is Intelence and is distributed by Tibotec Therapeutics, a division of Ortho Biotech Products of New Jersey.

Etravine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), a family of drugs that prevents the viral DNA from being copied and integrated with host cell DNA by blocking an enzyme. This stops the virus from multiplying. Other NNRTI drugs exist, but the virus has developed new mutant strains that have become resistant to them.

The FDA conducted a priority review of the drug, which has been approved for use only in combination with other anti-HIV treatments.

Director of the FDA's Division of Antiviral Products, Dr. Debra B. Birnkrant, said in a prepared statement that:

"This is another significant new product for many HIV-infected patients who are NNRTI resistant and whose infections are not responding to currently available medications."

When taken as prescribed, in conjunction with other anti-HIV drugs, etravine has two beneficial effects. First, it reduces the amount of HIV in the blood, and second it increases the number of CD4 white blood cells which helps the patient to resist and fight off other infections. This in turn reduces the risk of death or infection from having a weakened immune system.

It was the results of two randomized, double blind, placebo controlled trials called DUET-1 and DUET-2 on around 600 adults that provided the evidence to convince the FDA to approve the drug.

After 24 trial weeks, patients on etravine and background therapy had a higher drop in blood levels of HIV than those who only had the placebo plus background therapy. All the participants had extensive treatment and developed resistance to an average of 12 other antiretrovirals.

DUET-1 was conducted in Argentina, Brazil, Chile, France, Mexico, Panama, Puerto Rico, Thailand, and the US. DUET-2 was the same trial in other countries: Australia, Canada, again the US, and several European countries.

Rash and nausea were the most common side effects reported on the trials. Also, in the overall development of the drug, there have been rare cases of serious skin conditions such as Stevens-Johnson syndrome and erythema multiforme.

The FDA suggests that patients who develop a rash while on etravine should go back and tell their doctor. Also, to prevent other side effects that might occur from the drug in combination with other medications, patients should tell their doctor about all other medications they have been taking before starting on etravine.

Patients on etravine may get infections, for example opportunistic infections and other infections that are usually observed in HIV patients.

The agency stressed that it is too early to assess the long term effects of etravine, and it has not been tested in pregnant women or in children aged 16 and under.

The FDA advises women who get pregnant while on anti-HIV drugs talk to their doctor about the use of etravirine during pregnancy and the possibility of registering with the Antiviral Pregnancy Registry.

See Full Article

Caffeine raises Risk of Miscarriage

US researchers found that pregnant women who have large doses of caffeine every day, for example from coffee, tea, hot chocolate or caffeinated soda or fizzy drinks, have an increased risk of losing their baby through miscarriage. The researchers suggest women stop drinking caffeine while pregnant.

The study was conducted in in San Francisco by the Kaiser Permanente Division of Research and is to be published this week in the American Journal of Obstetrics and Gynecology.

The elevated miscarriage risk appears to be due to caffeine and not coffee alone because caffeine from other sources like tea, hot chocolate, and caffeinated soda or fizzy drinks also raised the risk.

Dr. De-Kun Li, who is a Research Scientist at the Division of Research, Kaiser Permanente, Northern California, led the investigation. Kaiser Permanente is the largest insurance group in the US. Li's co-authors were Xiaoping Weng and Roxana Odouli.

Some scientists have suggested caffeine is harmful to the developing fetus because it crosses the placenta and the fetus's metabolic system is not sufficiently developed to cope with caffeine, which can affect cell development directly and indirectly through decreasing blood flow from the placenta.

Others are skeptical of the claim that caffeine increased miscarriage risk, and maintain that the women who do miscarry tend to reduce their caffeine intake anyway because of morning sickness which makes them averse to caffeine, and this leads to a false impression that reducing caffeine intake reduces miscarriage risk.

Li explained that while other studies have shown links between caffeine intake and miscarriage, he and his team were the first to thoroughly control for morning sickness and other factors.

"This study strengthens the association between caffeine and miscarriage risk because it removes speculation that the association was due to reduced caffeine intake by healthy pregnant women," said Li.

See Full Article

Monday, January 21, 2008

Degenerative Diseases such as Cancer may be combatted by consumption of extra Virgin Olive Oil

In the 1960s, Ancer Keys, a US expert on nutrition, studied the health benefits of the Mediterranean diet for the first time. Since then many studies on the benefits of olive oil have been conducted. According to several studies performed in Italy, Spain and Greece (the main olive-oil-producing countries), the incidence of diseases is lower in these countries than in Northern Europe.

The Environmental, Biochemical and Nutritional Analytical-Control Research Group, directed by Professors Alberto Fernández Gutiérrez and Antonio Segura Carretero, used the most advanced analytical techniques for a precise study on the antioxidant properties of olive oil, characterized by its polyphenolic composition and its potential to combat degenerative diseases.

The study was completed with the collaboration of the Institute of Nutrition and Food Technology of the University of Granada and the Nutrition Team of the Hospital Virgen de las Nieves (Granada). Together with the Research Group, they have determined that consumption of olive oil rich in polyphenols (natural antioxidants) improves the lives of people suffering from oxidative stress, and is also highly beneficial for the prevention of cell aging and osteoporosis.

This research has stirred the interest of the Control Board of the Designation of Origin Sierra Segura. After analyzing samples from 15 olive oil mills, researchers have demonstrated that olive oil is very rich in polyphenols. According to Professors Alberto Fernández and Antonio Segura, "as preventive substances, polyphenols help to combat any oxidative disease associated with the degenerative process."

The Environmental, Biochemical and Nutritional Analytical-Control Research Group of the University of Granada has carried out several related studies, such as the creation of a system aimed at guaranteeing the quality of bee honey and determining its geographical origin, or the polyphenolic characterization of food products such as honey, beer and propolis.

See Full Article

Saturday, January 19, 2008

Inadequate Training designed to prevent Pediatric Prescribing Errors

Training today designed to curb the common pitfalls in pediatric drug prescribing is inadequate, according to an article published in Archives of Disease in Childhood.

These finding are a result of a trawl of published research on methods to lessen the numbers of prescribing errors and a survey a survey of relevant healthcare professionals and medicines researchers on training methods.

The authors explain than children present particular prescribing problems, because the absence of formulations designed specifically for them means that dosages have to be individually calculated, raising the chances of error.

The consequences of a mistake have a bigger impact on children than adults.

Prior research also suggests that junior doctors often feel inadequately trained to prescribe confidently, or don't know which drugs to prescribe for conditions, such as chest infections or life threatening allergic reaction (anaphylaxis).

The researchers did not find much published research on either the teaching of prescribing skills or the ways in which competencies are assessed - they report that only two relevant studies were found.

These two studies showed that the error rate dropped after particular techniques were introduced, but it was impossible to tell from the conclusions which had proved most effective.

319 out of a total of 559 questionnaires were returned for the survey, giving a response rate of 57%.

The responses showed that training in how to avoid mistakes in prescribing medicines for children was brief and predominantly in lecture format. There was little practical, hands on training.

Eleven centers taught how to complete a drug chart, while seven discussed common prescribing errors. And one center provided a computer based prescribing course on how to calculate drug doses correctly.

However, in 13 centers training took the form of a presentation by specialist pharmacists, lasting between 30 and 60 minutes, mostly at induction. And 10 centers gave trainees an induction pack containing written information.

Just three centers tested prescribing competency, using workbooks, questions during lectures, or formal testing.

The researchers acknowledge that their research may not reflect a complete picture of prescribing training, but there is currently no validated method of assessment, nor any national standards on the teaching of prescribing medicines for children, they say.

And they suggest that at the very least it is important to find out which teaching methods work best to reduce errors, if indeed any are effective.

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Thursday, January 17, 2008

Cancer Therapy Pioneer Folkman Dies at Age 74

Judah Folkman, who pioneered a groundbreaking cancer treatment known as angiogenesis inhibition, where tumors are starved of their blood supply, died aged 74, on Monday night in Denver, Colorado, USA. His wife, Paula Folkman said on Tuesday that her husband probably died of a heart attack while changing planes en route to a conference in Vancouver, British Columbia, according to a New York Times report this morning, Wednesday.

President and Medical Director of the Angiogenesis Foundation, Dr. William W. Li, said in a statement on the Foundation's website that the news of Dr. Folkman's death "comes as a great shock to all who trained with and were students of this remarkable surgeon, scientist, teacher, and visionary".

Dr. Folkman was "one of the greatest scientific minds of our time", said Li, and he inspired the creation of the Foundation, which was founded 14 years ago and now works to advance the application of angiogenesis to over 70 different diseases.

Folkman started thinking about angiogenesis in relation to cancer tumors while serving as a Navy surgeon in the 1960s. Later, between 1967 and 1981, while he was the hospital surgeon in chief at Children's Hospital Boston, he published a paper in the New England Journal of Medicine putting forward the idea that in order to thrive, tumors relied on angiogenesis, or the growth of new blood cells to feed the swelling mass of tissue.

However, for about two decades he was shunned by his peers who found his ideas too revolutionary. Sources of funds gradually withered, and he was eventually forced to accept a large sum from chemical giant Monsanto to continue his research, according to an article in Scientific American.

The breakthrough came in the mid 1990s when researchers at Folkman's lab showed that endostatin had dramatically shrunk aggressive malignant tumors in mice by sapping their blood supply. The discovery was further enhanced by the fact not only did the method slow down tumor growth, it also stopped the more stable endothelial cells that make blood vessels and not just tumor generated blood vessel making cells.

Folkman became front page news in 1988 when the New York Times reported that two of his experimental drugs had destroyed tumors in laboratory mice. The report quoted Nobel laureate James Watson, co-discoverer of DNA, as saying that "Judah is going to cure cancer in two years".

But as with many breakthroughs at first, the excitement exceeds the reality, and other researchers had problems trying to get the same results reported by Folkman. The experimental drugs did not seem to work as well in humans as in mice, and funding for them again, dried up.

One of Folkman's experimental drugs was successfully taken to market in China, and the ones that eventually made it in the US were not developed by Folkman. But according to the New York Times, experts say none of the drugs would exist if it had not been for Folkman's work.

A long standing colleague of Folkman, and President emeritus of the Dana-Farber Cancer Institute in Boston, Dr. David G. Nathan, told the paper that the controversies are not important, "the point is, he made the field", he said.

Author of a book on Folkman's struggle titled "Dr. Folkman's War: Angiogenesis and the Struggle to Defeat Cancer", Robert Cooke, told the Associated Press that Dr. Folkman did not develop a cure for cancer, but his ideas helped to turn it into a disease that can be managed, like diabetes, which was a huge breakthrough at the time.

There are ten cancer drugs currently helping 1.2 million people worldwide to manage their cancer, including Avastin and Thalomid, and dozens more in development, all inspired by Folkman's work.

However, there is still some controversy about how angiogenesis inhibitors actually work. Some experts suggest they may not be cutting off the blood supply to tumors, but could actually be fixing blood vessels which makes it easier for the chemotherapy drugs to reach the cancer cells in the tumors.

Li said that Folkman:

"Had the good fortune to witness the field he pioneered evolve, on a global scale, into a major force in modern science and medicine."

"He lived to see his ideas from the laboratory become translated into real, practical treatments that are today helping patients afflicted by cancer, age-related macular degeneration, diabetic wounds, and other serious diseases," he added.

See Full Article

Saturday, January 12, 2008

Researchers Report Breakthrough in Lowering Cholesterol, Fatty Acids

Researchers at the University of Alberta, in Edmonton, Canada, have found a way to reduce the amount of bad cholesterol and fatty acids that end up in the blood from food the body metabolizes, a key discovery that could lead to new drugs to treat and reverse the effects of Type 2 diabetes and heart disease related to obesity.

In a series of recently published articles, Dr. Richard Lehner and his colleagues report they successfully decreased the level of LDL (low density lipids) the so called bad cholesterol and triglycerides in the blood of mice and hamsters by manipulating a particular enzyme.

It's well-known that eating too much fat and sugar and too little exercise will make you fat, and that obesity often leads to diabetes and heart disease. Lehner's group studied the mechanisms behind this.

"We established the proof of principle of how these metabolic pathways work," he says. "We discovered the activity of an enzyme that releases fatty acids from fat cells and the liver into the blood and how to inhibit this from happening."

Drugs called statins are used to lower LDL levels in patients, but do not treat obesity. What makes the U of A researchers' findings noteworthy is their discovery of how to inhibit LDL and triglycerides, which are another form of fat in the blood and a leading risk in obesity-related Type 2 diabetes as well as heart disease.

Lehner is director of the Group on Molecular and Cell Biology of Lipids in the U of A's Faculty of Medicine and Dentistry. The research is being supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation.

Lehner is also a senior scholar for the Alberta Heritage Foundation for Medical Research.

"There is a substantial pharmacological interest in the enzymes that control TG (triglycerides fatty acids) and cholesterol metabolism in tissues," he says.

This unique discovery is an important scientific breakthrough, but one that requires further testing, he notes.

He also notes that a pill would not be "a magic bullet." People still need to make the right lifestyle choices by exercising and eating properly, he says.

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'Fingerprinting' Fruit Juices for Authentification

Adulterations or other possible food frauds are a financial problem that affect many foodstuffs. This is why achieving the authentification of food products is of great importance. In the case of fruit juices, the most common type of adulteration is mixing the original juice with juices from other, cheaper fruits (mainly grapefruit, grape or pear); in other words falsifying the juice.

Amongst the chemical methods of authentification, there are two different strategies. On the one hand, the employment of markers - chemical compounds that are ideally specific for or exclusive to each fruit and that can be rapidly, safely and cheaply measured and analyzed. This would be ideal. On many occasions, however, it is not possible to find markers that fulfill these requirements and, so, another approach to authentification methods is to measure and analyze a greater number of chemical compounds that make up the characteristic profile of each fruit or fruit juice. The complexity of this requires the employment of chemical analysis techniques and highly sophisticated statistical tools.

Polyphenolic compounds

In order to confirm the authenticity of the fruit juices, researchers at the Department of Analytical Chemistry of the University of the Basque Country (EHU-UPV) are trying to identify their fingerprints, as it were, using a family of chemical compounds naturally present in all fruit and known as polyphenols. There are thousands of polyphenols amongst the various species in the vegetable kingdom, with differences both in the number of particular polyphenols present in each vegetable species as well as in the quantities found. Thus, different fruits have specific polyphenolic differences.

In order to analyze polyphenols present in each for each fruit, researchers at the EHU-UPV used a high-performance liquid chromatography technique (HPLC), through which they culled information about what particular polyphenols are present in each fruit and in what quantity. This enables the study of the differences in the polyphenols between one fruit and another.

In any case, to be more certain of these polyphenols profiles, the confirmation is needed of the identity of each one of the polyphenols appearing in these profiles. To this end, a mass spectroscopy (MS) analytical technique was employed.

Orange, mandarin, lemon ...

A total of 16 fruits (Orange, mandarin, lemon, grapefruit, etc.), grown in Spain, were studied. In each case a study of the various varieties of each fruit was undertaken - up to 77 varieties, in order to know the common points of all fruits, and their differences.

Beatriz Abad has found, amongst other things in her PhD, a quite exclusive marker for lemon and three for grapefruit. She has also shown that using several markers instead of one increases the probability in detecting the food fraud. Moreover, she observed key differences in various "prints" and, using certain statistical tools, showed that such differences provide a quite reliable degree of accuracy in the detection of some mixtures of juices. For example, detecting the presence of grapefruit in orange juice is very sure and relatively easy; detecting the presence of lemon juice in orange juice is also quite accurate; but detecting the presence of mandarin oranges in orange juice is much more difficult and not very reliable, given that the mandarin and the orange are very similar in their "prints".

To date they have defined the polyphenolic profiles or polyphenolic "fingerprints" of the various juices from genuine fruit. The next step is currently being carried out by researchers at the EHU-UPV - applying these prints to existing commercial juices on the market in order to detect possible adulterations or frauds.

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Friday, January 11, 2008

Simple Checklist of Seven Clinical Signs/Symptoms could identify Sick Newborns in Developing Countries

A checklist of seven clinical signs and symptoms could help identify sick newborns, aged up to one week, with possibly life-threatening illnesses requiring immediate hospitalization. If this checklist were extensively used it could significantly reduce neonatal mortality in developing nations, according to an Article in The Lancet, this week's issue.

Approximately 4 million infants are estimated to die annually during their first month of life, 75% of them do so during their first week of life. The majority of births in low-income developing countries take place in the home, from which sick newborns are taken to health-care workers at first-level health facilities. Hence, perfecting the identification of young babies with life-threatening illnesses who need hospital referrals can have a major impact on public-health.

Developed during the 1990s, IMCI (Integrated Management of Childhood Illness) standardized the management of sick young babies up to the age of two months. However, most mortality occurs during the first week, and the IMCI does not specifically target the first week of life. The original IMCI guidelines tends to lead to too many healthy children being referred to hospital, which in developing countries places an enormous burden on weak health systems in high-mortality settings.

Dr. Martin Weber (WHO, Jakarta, Indonesia) and team from The Young Infants Clinical Signs Study Group wanted to devise a referral checklist for sick newborns during the first week of life. They also aimed to improve the current IMCI guidelines for infants aged 7 to 59 days old. They carried out a multicenter study to assess the performance of 31 simple clinical signs - when alone or in combination. First-line health workers used them to detect infants with severe illness who required hospitalization (excluding jaundice), and compared their accuracy to the judgment made by an expert pediatrician. They studied 3,177 newborns aged 0-6 days and 5,712 infants aged 7-59 days. These babies were brought in with illness to health facilities in South Africa, Pakistan, India, Ghana, Bolivia and Bangladesh.

They found 12 symptoms/signs that predicted severe illness during the first week of a baby's life:

1 - history of difficulty feeding
2 - history of convulsions
3 - lethargy
4 - movement only when stimulated
5 - respiratory rate of 60 breaths per minute or more
6 - grunting
7 - severe chest indrawing
8 - temperature of 37•5°C or more
9 - temperature below 35•5°C
10 - prolonged capillary refill
11 - cyanosis (skin, lips, tongue are bluish due to lack of oxygen)
12 - stiff limbs

According to the researchers, a decision rule which required the presence of any one sign had high sensitivity (87%) and good specificity (74%) among the babies aged 0-6 days, and an overall sensitivity of 78% and specificity of 74% among the babies aged 7-59 days.

They simplified the decision rule more on the basis of low prevalence of specific signs, or when a sign or symptom was left out of the rule which did not have an effect on sensitivity or specificity.

Consequently, the list went down to 7 sign/symptoms:

1 - history of difficulty feeding
2 - history of convulsions
3 - movement only when stimulated
4 - respiratory rate of 60 breaths per minute or more
5 - severe chest indrawing
6 - temperature of 37•5°C or more
7 - temperature below 35•5°C

This simplified decision rule had a sensitivity of 85% and a specificity of 75% in the 0-6 days age-group. For the 7-59 day age group the simplified decision rule had a sensitivity of 74% and a specifity of 79% (reasonable).

"Our findings have important implications for the adaptation and implementation of IMCI guidelines in countries. A single IMCI algorithm for 0-2-month-old infants based on the findings of this study with a short list of signs is much easier to teach and remember by health workers. It would have a substantially higher specificity than the existing algorithm, thus reducing over-referral," the scientists concluded*.

See Full Article

Thursday, January 10, 2008

Sirolimus Shrinks Tumors, Improves Lung Function

The drug sirolimus, normally used to help transplant patients fight organ rejection, may eventually be used as a less invasive treatment for a tumor called angiomyolipomata in patients who would otherwise face surgery. The finding is reported by investigators from Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine in the Jan.10 edition of The New England Journal of Medicine.

One year of treatment with sirolimus significantly reduced the size of angiomyolipomata by nearly 50 percent in patients with tuberous sclerosis complex (TSC), a rare genetic multi-system disease, or lymphangioleiomyomatosis (LAM), a rare cystic lung disease, according to results of the phase I/II proof-of-concept trial. Sirolimus also improved lung function in the LAM patients. Both TSC and LAM are associated with gene mutations that result in inappropriate activation of mTOR (mammalian target of rapamycin), an enzyme that helps control the growth and proliferation of all cells. Sirolimus inhibits mTOR signaling, researchers said.

"Less invasive therapies are clearly needed to treat the angiomyolipomata that people with TSC and LAM develop, and a drug that maintains or shrinks tumor size may reduce the need for procedures such as surgery," said John Bissler, M.D., lead author of the study and a physician/scientist in the Division of Nephrology and Hypertension at Cincinnati Children's. "Our data suggest that mTOR inhibition with sirolimus may hold promise for treating these and other disease manifestations in patients with TSC and LAM."

In the study, tumor volume in 20 patients treated with sirolimus for 12 months had significant reductions of about 50 percent. In 18 patients evaluated 12 months after sirolimus treatment stopped average tumor volume had increased again to about 85 percent of the original size.

Five of the 18 patients evaluated 12 months post treatment had a persistent tumor volume reduction of 30 percent or more. Bissler and his coauthors speculate that regression in angiomyolipoma size might stem from a form of programmed cell death called apoptosis or cell-volume reduction.

In 11 study participants with LAM, 12 months of sirolimus treat resulted in a 10 to 15 percent improvement in expiratory air flow, a standard measurement of lung function. One year after sirolimus treatment ended, the treatment effect waned somewhat, but remained substantially above the level of lung function that would have been expected over two years with no treatment. Researchers said improved pulmonary function was likely caused by a reduction of gas trapping in the lungs and a decrease in airflow obstruction. Lung function for people with LAM often declines to the point that patients require oxygen and eventually a lung transplant.

Sirolimus treatment led to several side effects, including mouth ulcers, diarrhea, upper respiratory infections and joint pain.

Researchers also noted limitations in the study's open-label design, lack of a control group and small number of study participants. However, given the effects of sirolimus in the trial the researchers at Cincinnati Children's are optimistic about its potential.

Support for the phase I/II proof-of-concept study came from the patient advocacy groups, the LAM Foundation and the Tuberous Sclerosis Alliance (made possible in part by a grant from the Kettering Fund), Wyeth, the National Cancer Institute and National Institutes of Health.

Dr. Bissler and his colleagues are pursuing additional trials to further define the relative risks and benefits of mTOR inhibitors in patients with LAM and TSC. Dr. Bissler is leading another trial to see if different dosing of mTOR inhibitors improves the effectiveness of treating angiomyolipomata tumors, and is working to launch a placebo-controlled multinational trial to better understand the effects of this therapy on angiomyolipomata. Frank McCormack, M.D., a physician and researcher at the UC College of Medicine, is leading multi-institutional Phase III trial of sirolimus involving 120 patients with LAM that is randomized, double-blind and placebo-controlled. David Franz, M.D., a physician and researcher at Cincinnati Children's, is conducting a trial to see if mTOR-inhibitor therapy helps the specific TSC-related brain lesion subependymal giant cell astrocytoma, and is working on a second placebo-controlled, multinational trial for this treatment.

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Breast Cancer Metastasis halted by Small RNAs

Howard Hughes Medical Institute researchers have identified small pieces of ribonucleic acid (RNA) that suppress the spread of breast cancer to the lungs and bone. The new research shows that the most invasive and aggressive human breast cancer tumors are missing three critical microRNA molecules. When the researchers put those molecules back into human breast cancer tumors in mice, the tumors lost their ability to spread.

"The tiny RNAs prevent the spread of cancer by interfering with the expression of genes that give cancer cells the ability to proliferate and migrate," said senior author Joan Massagué, a Howard Hughes Medical Institute researcher at Memorial Sloan-Kettering Cancer Center.

The researchers said their new research findings add to the growing number of cellular targets for drugs designed to prevent breast cancer metastasis. The scientists are also optimistic that their work could spur the development of new clinical tests to assess the likelihood that breast tumors will metastasize. Metastasis of breast cancer is the leading cause of death from the disease.

Metastasis occurs when cells from a primary tumor break off and invade another organ. It is the deadliest transformation that a cancer can undergo, and therefore researchers have been looking for specific genes that propel metastasis. If they can identify distinctive metastatic gene programs for different cancers, it may be possible to slow or halt metastases by targeting the proteins produced by those genes.

Massagué, his postdoctoral fellow Sohail Tavazoie, and colleagues at Sloan-Kettering, published their findings in the January 10, 2008, issue of the journal Nature.

In the experiments reported in Nature, the researchers explored the role that microRNAs play in controlling the expression of genes that trigger the spread of breast cancer. MicroRNAs, which are no more than 20-22 nucleotides in length, play an important role in development, cancer, stress responses and viral infections. Unlike the large messenger RNA (mRNA) molecules that code for cellular proteins, the microRNAs regulate gene activity by repressing or enhancing the translation of mRNAs.

Messenger RNA molecules are the genetic templates for proteins. In constructing proteins, the mRNA template is transcribed from DNA genes and transported to the ribosomes - the cell's protein factories that are large complexes of protein and RNA. Given the importance of mRNA as an information-carrying molecule, the machinery that regulates mRNA levels and destroys faulty mRNA is critical in ensuring that errors in the genetic code are not passed on to proteins.

Massagué and his colleagues have focused on identifying the driving forces behind the spread of breast cancer, and have, in previous work, identified distinct genetic signatures associated with metastasis to the bone and the lungs. They decided to explore the role of microRNAs in breast cancer shortly after other researchers published data showing that certain tumors, including breast cancers, had decreased levels of microRNA expression. These observations suggested to Massagué and others that loss of the gene-suppressing molecules might well play a key role in the growth and spread of tumors.

To follow up on that hunch, Tavazoie and others in Massagué's lab set their sights on identifying microRNAs that were suppressed only in aggressive, metastatic human breast cancers. They first analyzed cultured metastatic human breast cancer cells to create a genetic profile of the array of microRNAs produced by the cancerous cells. When they compared this microRNA profile to that from non-metastatic cancer cells, they found that a small subset of microRNAs was greatly reduced only in the metastatic cells.

They next found that when they restored normal levels of three of these microRNAs - miR-335, miR-126 and miR-206 - in the cultured human breast cancer cells, it greatly reduced the cells' ability to spread to the lungs or bones of mice. They also obtained a sample of metastatic cells from a breast cancer patient and found that those cells had lost the same three microRNAs identified in the cell culture experiments.

To study a broader sample of cancers, the researchers measured levels of the microRNAs in cancer cells from 20 patients with breast cancer. They found lower levels of the microRNAs in patients whose breast cancers had metastasized than in those whose cancers had not metastasized.

Additional biological analysis revealed that miR-126 influences the proliferation rate of the metastatic cells, whereas miR-335 and miR-206 influence the cancer cells' ability to migrate into lungs or bone.

The researchers found a particularly strong association between loss of miR-335 and cancer relapse, so they next sought to determine which genes were regulated by that particular microRNA. Their genetic analysis revealed a set of six genes whose activity greatly increased with loss of miR-335 in metastatic cells. Two genes in particular, SOX4 and TNC, were known to regulate cell migration, which is critical for cancer invasion of other tissues. When the scientists knocked down the activity of those two genes, they reduced the cancer cells' ability to spread.

Taking the analysis a step further, Massagué's team sifted through genetic data from 368 patients with breast cancer. Those data showed that tumors with a higher level of expression of the six miR-335-regulated genes were much more likely to metastasize than those tumors with a lower level of expression of the six genes.

According to Massagué, identification of the microRNAs and the metastasis-controlling genes they regulate could prove valuable for both breast cancer prognosis and treatment. "The gene signature we have identified could offer another tool for assessing the likelihood that a cancer will progress," he said. "There are quite a few of these signatures, and the most useful ones are those that consist of genes that are not just markers, but are actually mediators of metastasis. And in this gene signature, we have identified just such a set of mediators.

"Secondly, these findings reveal still more genes that could be targets of drugs to interfere with metastasis," he said. "Researchers in this field are currently accumulating an inventory of clinically significant genes to explore, and the set we identified has shown such significance."

Massagué said his group is now designing experiments to ask whether the breast cancer genes regulated by the microRNAs they identified also control metastasis of other types of cancer. "We have basically opened a window into a major future inquiry into such genes," he said. "And my hope is that this paper will lead to findings that are even more important and useful than the ones contained in this first installment."

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Breast Cancer Risk varies among Gene Carriers

A new American and Danish study has found that the risk of developing cancer among carriers of the BRCA1 and BRCA2 breast cancer gene mutation varies greatly.

The study is the work of Dr. Colin B. Begg, of the Memorial Sloan-Kettering Cancer Center, in New York, and colleagues and is published in the January 9/16 issue of The Journal of the American Medical Association (JAMA).

BRCA1 and BRCA2 are tumor suppressor genes that control cell division and stop cells proliferating too quickly. Certain mutations of these genes cause them to lose control over this process and predispose the carrier to cancer, namely breast, ovarian and prostate.

According to the researchers, while the cancer risk conferred by BRCA1 and BRCA2 has been studied widely, the extent to which it varies among carriers has not. However, size of risk is an important part of decision making in cancer prevention and treatment.

Begg and colleagues genotyped 2,098 women for mutations in BRCA1 and BRCA2 genes. The women were participants in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) study and had cancer either in one breast only (unilateral) or in the second breast after having had it in the first breast (contralateral).

All the women had their initial cancer diagnosed before they reached the age of 55, between January 1985 to December 2000. They were asked if any of their first degree female relatives (mother, sister, daughter) had ever received a diagnosis for breast cancer.

The results showed that:

* 73 (5.2 per cent) of the 1,394 women with unilateral breast cancer carried "faulty" genes: 42 had faulty BRCA1 and 31 had faulty BRCA2 mutations.

* 108 (15.3 per cent) of the women with contralateral breast cancer also carried faulty genes: 67 had BRCA1 had 41 with BRCA2 mutations.

* Risk of breast cancer among first degree relatives was significantly linked to participant's age at diagnosis.

* The risk was higher for relatives of women who had contralateral breast cancer as opposed to unilateral breast cancer (odds ratio 1.4).

* After adjusting for these observed characteristics, there remained a significant variation in risk among carrier families.

Begg and colleagues concluded that:

"There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations."

Genetic testing for BRCA2 and BRCA2 mutations is not currently recommended as part of routine cancer screening, wrote the authors, but in the future, as technology advances and costs come down, it could become part of routine population wide genetic screening and form a cornerstone of tailored risk reduction programs.

For this reason, wrote the authors, it is important that risk estimation is accurate and the sources of risks correctly identified as they will be important factors in the clinical management of women who carry the BRCA1 and BRCA2 mutations.

Breast cancer is the second biggest cause of cancer deaths among American women. In 1997 it killed 44,190 people, of which 290 were men.

Ovarian cancer accounts for fewer deaths but still represents 4 per cent of all female cancers, and in some cases the two cancers are genetically linked.

Scientists have discovered hundreds of variations among BRCA1 and BRCA2 genes.

See Full Article

Saturday, January 5, 2008

Placebo works equally well as Antipsychotics for Aggression in the Intellectually Disabled

A new UK study found that placebo was just as effective at treating aggressive challenging behavior in intellectually disabled patients as antipsychotic drugs and the researchers recommended antipsychotics no longer be regarded as an acceptable routine treatment for this group.

The study is published in the January 5th issue of The Lancet and is the work of Peter Tyrer, professor of Community Psychiatry Division of Neurosciences and Mental Health, at the Department of Psychological Medicine, Imperial College, London, UK, and colleagues.

Antipsychotic drugs are often used to treat adults with intellectual disability (having an IQ below 75) who present with aggressive challenging behavior, wrote the researchers. This is despite there being insufficient convincing evidence to support such practice.

In this study Tyrer and colleagues compared the effectiveness of treating this behavior with flexible doses of a typical first generation antipsychotic, haloperidol, an atypical second generation antipsychotic, risperidone, and a placebo.

The participants were patients from ten centers in England and Wales, and one in Queensland, Australia. All 86 patients were non-psychotic adults showing aggressive challenging behavior. They were enrolled in a trial called the Neuroleptics for Aggressive Challenging Behavior in Intellectual Disability study.

The patients were randomly assigned to one of three drug groups: 28 to the haloperidol, 29 to the risperidone, and 29 to the placebo group.

The researchers took a range of measurements at 4, 12 and 26 weeks after treatment began. The measurements were taken by telephone interview with the patients' carers. They included: clinical assessments of aggression and aberrant behavior, quality of life, adverse effects of the treatment, carer uplift (how the carer felt about the care of their patient), carer burden, and costs.

The change in aggression after 4 weeks of treatment was the main outcome measure, based on a scale called the modified overt aggression scale (MOAS).

The results showed that:

* 80 per cent of the patients stuck to at least 80 per cent of the treatment (drug adherence).

* Aggression, as measured by the MOAS scale went down significantly in all three groups at week 4.

* The largest decrease was in the placebo group which showed a median MOAS decrease of 79 per cent from baseline.

* This compared with 58 per cent for risperidone and 65 per cent for haloperidol.

* There were no important differences among the treatments, including adverse effects.

* Responses for patients in the placebo group were no worse, at any time, than responses for patients in either of the drug groups.

The study concluded that:

"Antipsychotic drugs should no longer be regarded as an acceptable routine treatment for aggressive challenging behavior in people with intellectual disability."

An accompanying editorial supported Tyrer and colleagues' conclusion, that the practice should come to an end, especially in routine giving of the drugs to children. But while it was "a worthy goal", in practice it will not be easy, wrote Johnny L. Matson and Jonathan Wilkins from Louisiana State University.

However, the researchers said there may still be a place for such drugs in particular circumstances and groups. For example they may be appropriate for treating autistic behavior in children or if the drugs are given in an emergency, it may be necessary to continue with them to prevent further aggressive behavior.

See Full Article

Wednesday, January 2, 2008

2-D Invisibility Cloak Technology also used in Superlens Microscopy Technology

Harry Potter may not have talked much about plasmonics in J. K. Rowling's fantasy series, but University of Maryland researchers are using this emerging technology to develop an invisibility cloak that exists beyond the world of bespectacled teenage wizards.

A research team at Maryland's A. James Clark School of Engineering comprised of Professor Christopher Davis, Research Scientist Igor Smolyaninov, and graduate student Yu-Ju Hung, has used plasmon technology to create the world's first invisibility cloak for visible light. The engineers have applied the same technology to build a revolutionary superlens microscope that allows scientists to see details of previously undetectable nanoscale objects.

Generally speaking, when we see an object, we see the visible light that strikes the object and is reflected. The Clark School team's invisibility cloak refracts (or bends) the light that strikes it, so that the light moves around and past the cloak, reflecting nothing, leaving the cloak and its contents "invisible."

The invisibility cloak device is a two-dimensional pattern of concentric rings created in a thin, transparent acrylic plastic layer on a gold film. The plastic and gold each have different refractive properties. The structured plastic on gold in different areas of the cloak creates "negative refraction" effects, which bend plasmons - electron waves generated when light strikes a metallic surface under precise circumstances - around the cloaked region.

This manipulation causes the plasmon waves to appear to have moved in a straight line. In reality they have been guided around the cloak much as water in a stream flows around a rock, and released on the other side, concealing the cloak and the object inside from visible light. The invisibility that this phenomenon creates is not absolutely perfect because of energy loss in the gold film.

The team achieved this invisibility under very specialized conditions. The researchers' cloak is just 10 micrometers in diameter; by comparison, a human hair is between 50 to 100 micrometers wide. Also, the cloak uses a limited range of the visible spectrum, in two dimensions. It would be a significant challenge to extend the cloak to three dimensions because researchers would need to control light waves both magnetically and electronically to steer them around the hidden object. The technology initially may work only for small objects of specific controlled shape.

The team also has used plasmonics to develop superlens microscopy technology, which can be integrated into a conventional optical microscope to view nanoscale details of objects that were previously undetectable.

The superlens microscope could one day image living cells, viruses, proteins, DNA molecules, and other samples, operating much like a point-and-shoot camera. This new technology could revolutionize the capability to view nanoscale objects at a crucial stage of their development. The team believes they can improve the resolution of their microscope images down to about 10 nanometers - one ten thousandth of the width of a human hair.

A large reason for the success of the group's innovations in both invisibility and microscopy is that surface plasmons have very short wave lengths, and can therefore move data around using much smaller-scale guiding structures than in existing devices. These small, rapid waves are generated at optical frequencies, and can transport large amounts of data. The group also has made use of the unique properties of metamaterials, artificially structured composites that help control electromagnetic waves in unusual ways using plasmonic phenomena.

The diverse applications the group has derived from their plasmonics research is an example of the ingenuity of researchers approaching new and dynamic technologies that offer broad and unprecedented capabilities. The research has attracted a great deal of attention within the scientific community, industry and government agencies. Related plasmonics research offers applications for military and computer chip technologies, which could benefit from the higher frequencies and rapid data transfer rates that plasmons offer.

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"Truth, Lies, And Public Health"

Authored By Weill Cornell's Dr. Madelon Finkel

From stem cell research to needle exchanges to medical marijuana and HIV/AIDS prevention, politics is getting in the way of science, according to a new book by a leading authority on health-care policy and women's health issues at Weill Cornell Medical College.

"Truth, Lies, and Public Health: How We Are Affected When Science and Politics Collide" (Praeger Press, 2007) is authored by Dr. Madelon Finkel, professor of clinical public health, director of the Office of Global Health Education and director of Cornell Analytics Consulting Services (CACS) at Weill Cornell Medical College.

"While political activists and the government can bring much-needed attention and money to a public health problem, politics can also poison science," says Dr. Finkel. "Over the last two decades, politics and ideology have increasingly hijacked and distorted science to serve its own purposes - often ignoring incontrovertible evidence and preventing much-needed policies to improve public health."

The new book looks at how ideology affects research funding and explores the evolution of public health policies on contraception, AIDS, stem cell research, medical marijuana, needle exchanges, tuberculosis control, dietary supplements, silicone breast implants, obesity, vaccination and disease prevention.

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