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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.

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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.

Diagnosis

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.

Pathogenesis

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.

Pathophysiology

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.

Prevention

Please see Flu -Prevention.

Treatment

Please see Flu -Treatment.

Complications

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.

References

http://www.medterms.com
Provided primary source of information.

http://wrongdiagnosis.com
Provided information on Signs and Symptoms.

http://en.wikipedia.org
Provided extra information.

http://www3.hku.hk
Provided extra information.

http://www.pubmedcentral.nih.gov
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."

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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.

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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."

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