Healthy Information

Seventh case of swine flu is confirmed in Hong Kong

2009-05-24T18:31:00.001+07:00

Hong Kong - A seventh case of swine flu was confirmed in Hong Kong Sunday, involving a 21-year-old female student who flew to the city from New York City.

The student fell ill a day after flying to Hong Kong via Seoul and was Sunday in isolation at the city's Princess Margaret Hospital, a Department of Health spokesman said.

Family members of the student had been tested and her travelling companion had been taken to hospital for tests, the spokesman said. Fellow passengers were being contacted.

The student is the fourth imported case of swine flu to be confirmed in the densely-populated city of 7 million in the past three days.

Two patients were detected as they arrived in Hong Kong on a flight from the United States Friday evening and have been put in isolation in the Princess Margaret Hospital.

A 19-year-old female student who returned to Hong Kong from New York City six days ago, was confirmed as having swine flu on Friday. All cases in Hong Kong so far have been imported.

Hong Kong officials have appealed to students returning to Hong Kong from the US not to travel unless they are healthy and to wear face masks and alert cabin crew if they feel ill while flying.

The first Hong Kong swine flu case was confirmed in a Mexican visitor at the beginning of May, leading to a seven-day quarantine for 300 guests and staff in the hotel where he stayed.

Quarantine measures have since been eased in the city which has had strict anti-virus measures since the 2003 severe acute respiratory syndrome or SARS outbreak that killed 299 and infected 1,799.

Influenza

2009-05-24T17:55:00.004+07:00

Influenza is a viral infection of the respiratory tract. It can occur in epidemic proportions during the winter. Because the structure of the virus may change every two or three years, people will periodically be susceptible to a virus they have never been exposed to before. This creates the possibility of an epidemic outbreak of influenza, or "the flu," every two to three years. Between epidemics, smaller outbreaks may occur as people or young children not exposed in the last outbreak are infected.

Influenza is very contagious and is spread by contact with an infected person. A person is contagious from about two days before symptoms occur until about the fifth day of the illness. Symptoms of influenza include chills, fever, headache, achiness, fatigue, and lack of appetite.

Treatment is generally directed at alleviating symptoms, which can make the sufferer truly miserable. Although the illness generally runs its course in three to four days, complications such as encephalitis, pneumonia, croup, or seizures can occur. If any of these develop, your child will need immediate medical attention.

WHEN TO CALL THE DOCTOR ABOUT INFLUENZA
*If your child develops a very high fever, if she has a seizure, or if you notice any changes in her level of consciousness or mental function, seek medical advice immediately. These may be signs that she is developing encephalitis.

* A child with influenza who has a high fever is at risk for having a seizure. If your child has a seizure, call your physician immediately.

* If your child shows signs of increased respiratory distress, such as an increased respiratory rate, gasping, wheezing, nasal flaring, or a pale or bluish color to the skin, call your doctor. Your child may have developed pneumonia and needs medical attention.

Conventional Treatment
*The cornerstones of treatment for influenza are fever control, rest, and plenty of fluids. Acetaminophen (in Tylenol, Tempra, and other medications) or ibuprofen (Advil, Nuprin, and others) can tee used to reduce fever and alleviate achiness.
Note: In excessive amounts, acetaminophen can cause liver damage. Read package directions carefully so as not to exceed the proper dosage for your child's age and size. Ibuprofen can cause stomach upset in some children. To avoid this problem, try giving this medication with food.

*Do not give aspirin to a child or teenager with the flu. The combination of aspirin and viral infection is associated with Reye's syndrome, a dangerous disease affecting the brain and liver.

*Because influenza is caused by a virus, antibiotics have no effectiveness and are not used. A drug containing amantadine hydrochloride (Symmetrel) is sometimes used in epidemics known to be caused by influenza type A. This drug is effective only if started in the first two days after the onset of symptoms, and it is not used in younger children.

Dietary Guidelines
f your child doesn't feel like eating, it's best not to force food. Suggest juices, applesauce, soups, and herbal teas.

Triglycerides implicated in diabetes nerve loss

2009-05-24T17:46:00.002+07:00

To stall progress of neuropathy, doctors should monitor levels of an easily measured blood fat as closely as they do blood sugar, study suggests

ANN ARBOR, Mich.- A common blood test for triglycerides - a well-known cardiovascular disease risk factor - may also for the first time allow doctors to predict which patients with diabetes are more likely to develop the serious, common complication of neuropathy.

In a study now online in the journal Diabetes, University of Michigan and Wayne State University researchers analyzed data from 427 diabetes patients with neuropathy, a condition in which nerves are damaged or lost with resulting numbness, tingling and pain, often in the hands, arms, legs and feet. The data revealed that if a patient had elevated triglycerides, he or she was significantly more likely to experience worsening neuropathy over a period of one year. Other factors, such as higher levels of other fats in the blood or of blood glucose, did not turn out to be significant. The study will appear in print in the journal’s July issue.

“In our study, elevated serum triglycerides were the most accurate at predicting nerve fiber loss, compared to all other measures,” says Kelli A. Sullivan, Ph.D., co-first author of the study and an assistant research professor in neurology at the U-M Medical School.

“These results set the stage for clinicians to be able to address lowering lipid counts with their diabetes patients with neuropathy as vigilantly as they pursue glucose control,” says Eva L. Feldman, M.D., Ph.D., senior author of the study and the Russell N. DeJong Professor of Neurology at the U-M Medical School.

With a readily available predictor for nerve damage - triglycerides are measured as part of routine blood testing - doctors and patients can take pro-active steps when interventions can do some good, says Feldman.

“Aggressive treatment can be very beneficial to patients in terms of their neuropathy,” says Feldman, who is also director of the A. Alfred Taubman Medical Research Institute and director of the Juvenile Diabetes Research Foundation Center at U-M for the study of complications in diabetes.

People can reduce blood triglyceride levels with the same measures that reduce cholesterol levels: by avoiding harmful fats in the diet and exercising regularly.

Context
Diabetic neuropathy affects around 60 percent of the 23 million people in the United States who have diabetes. It is a complication in both type 1 and type 2 diabetes.

Until now, doctors have lacked an effective way to predict which diabetes patients are at greatest risk of neuropathy. Most often, the condition becomes evident when irreversible nerve damage has already occurred. Neuropathy is the leading cause of diabetes-related hospital admissions and amputations that are not secondary to trauma.

Triglycerides are a type of lipid, or fat, that the body makes from calories it doesn’t need immediately. Triglycerides are stored in fat cells until they are needed to provide energy. When higher-than-normal amounts circulate in the blood, a person is at higher risk of cardiovascular disease.

Research implications
The new finding adds to an emerging picture of the close connections between cardiovascular disease and diabetes. Elevated triglycerides are one of the most common features of the lipid disorders found in patients with type 2 diabetes, by far the most common form of diabetes, says Rodica Pop-Busui, M.D., Ph.D., one of the study’s authors and an assistant professor in the metabolism, endocrinology and diabetes division of the Department of Internal Medicine at the U-M Medical School.

“Cardiovascular disease is the main cause of excess mortality among patients with diabetes. Research also has shown that the presence of neuropathy is an important predictor of these deaths,” says Pop-Busui.

“Our findings in this study reinforce the tight links between cardiovascular disease and peripheral neuropathy in patients with diabetes. We demonstrated that the same lipid particles that contribute to the progression of atherosclerosis are also very important players in peripheral nerve fiber loss.”

In addition, the study confirms a growing belief among some diabetes researchers that elevated blood levels of certain lipids, rather than solely elevated blood sugar, are key in the progression of diabetic neuropathy. The study pinpoints triglycerides as the critical indicator.

Research details
The researchers examined data from a previous clinical trial of a drug that showed promise for relieving neuropathy. They looked at data from 427 participants who had mild to moderate diabetic neuropathy at the beginning of the one-year trial. Among other factors, the trial measured myelinated fiber density in a peripheral nerve in the leg in participants over the course of the year. A decline in this density is a prime indicator that neuropathy is worsening.

The new findings from U-M are an example of how medical science often looks for one thing and doesn’t find it-the drug trial found that a promising agent turned out to be ineffective for treating neuropathy-but the data can yield unexpected, useful knowledge about something else.

Realizing the trial data held potential clues, the U-M team selected trial participants who had similar characteristics regarding nerve function at the beginning of the study but significantly lower myelinated fiber densities at the end. They used microarray technology not available 15 years ago, when the data was collected.

“We then compared all of the other data concerning lipids and blood glucose. We found that out of all the data collected on these patients, elevated triglycerides were the factor that differed the most, when we compared the patients who lost nerve fibers with those who didn''t,” says Sullivan.

Elevated triglycerides correlated with the nerve fiber loss independent of disease duration, age, diabetes control or other variables.

Other U-M authors include Timothy D. Wiggin, M.S., co-first author; non U-M authors are Anders Sima, M.D., professor of pathology and neurology at Wayne State University Medical School, and Antonino Amato, M.D., from Sigma-Tau Research.

Funding: National Institutes of Health, Juvenile Diabetes Research Foundation Center for the Study of Complications in Diabetes, American Diabetes Association, Thomas Foundation, Sigma Tau Research, and the U-M Program for Neurology Research and Discovery.

Homeopathic remedy approved to treat sprains

2009-05-24T17:45:00.001+07:00

Much to the anger of conventional medicine, the homeopathic remedy Arnica has been officially recognised as a successful remedy for treating sprains and bruises in the United Kingdom.

The Medicines and Healthcare Products Regulatory Agency (MHPRA) has registered the product, which means that the manufacturer can now make claims for its effectiveness.

Arnica 30c, manufactured by Nelsons, is the first homeopathic remedy to be recognised without going through clinical trials. Since 1971, homeopathic products have not been allowed to make any health claim without proper evidence.

But new rules, introduced in 2006, allow a manufacturer to make health claims for a product provided there is a tradition for its use in the UK, and it is for the treatment only of minor problems.

Fake journal created to sell Vioxx, court hears

2009-05-24T17:43:00.000+07:00

Ever heard of a medical journal called the Australasian Journal of Bone & Joint Medicine? Thought not – because it was invented by pharmaceutical giant Merck in order to sell its discredited drug Vioxx.

Merck invented the journal and fake research that was published in it to demonstrate the safety and effectiveness of its painkiller, an Australian court has heard.

Merck made a $4.85bn out of court settlement in the US to the 50,000 victims or families who had taken the drug, and had either died or suffered long-lasting heart problems.

While Merck hid vital data from the regulators in America, they took another tack in Australia, a court there has been hearing. There they created the medical journal which was used as a vehicle to publish supposed medical trials, the court was told.

Vioxx was taken off the market in 80 countries in 2004 after a trial, published in an independent medical journal, found the drug increased the risk of stroke and heart attack.

If the current case against Merck is proved, the drug company is expected to make a multi-million dollar payout to around 3,000 Vioxx victims in Australia.

(Source: New York Times)

Do you have insomnia if you have a bad night's sleep?

2009-05-24T17:42:00.001+07:00

Are you suffering from insomnia if you have the occasional night when you don’t sleep well? Latest research reckons the odd night’s bad sleep doesn’t add up to insomnia – that’s reserved for those who have a poor sleeping pattern lasting for one year, and sometimes three.

Researchers were surprised by the extent of poor sleep that a group of 388 insomniacs suffered. For 74 per cent of them, regular poor sleep had lasted for a year, and for 46 per cent of them, for three years.

While more than half – 54 per cent – experienced ‘remissions’ from insomnia when normal sleep was re-established, half of those saw their insomnia come back.

(Source: Archives of Internal Medicine)

Swine flu may have started in laboratory, expert says

2009-05-24T17:29:00.002+07:00

The man who helped develop the Tamiflu flu vaccine believes the swine flu epidemic has been caused by human error. Adrian Gibbs says the H1N1 virus may have been man-made and was passed to humans after a handling mistake at a laboratory.

Gibbs, who has studied germ evolution for 40 years, is to publish a paper about his theory, which he developed after studying the swine flu virus’s genetic blueprint. “One of the simplest explanations is that it’s a laboratory escape,” he told reporters from Bloomberg.

Viruses are developed on eggs, and Gibbs believes the new H1N1 strain may have accidentally evolved before being passed to humans. He has discovered that the strain mutates three times faster than the most closely-related viruses found in pigs, which suggests it had evolved outside of swine.

It would not be the first time a virus has ‘escaped’ from a laboratory. Earlier this year the avian flu virus made its way into a consignment of seasonal flu vaccines, which were destined for around 18 countries in Europe.

Some scientists also suspect that the Russian flu outbreak of 1977 was started when a virus was accidentally released from a laboratory.

Swine flu, pigflu, H1N1 (as WHO now prefers), whatever-you-call-it

2009-05-24T17:09:00.002+07:00

This is fast-breaking story if ever there was one, and it looks impossible from this perch to do any more than sample the coverage randomly. Web sites are updating stories hourly, even minutely. So what the Tracker will focus on in coming days are what might be called the metastories, the sidebars with information that’s a bit more durable.

One alarming sidebar that ought to be its own main story is David Brown’s excellent piece in the Washington Post saying that the outbreak reporting system set up after SARS six years ago didn’t work well this time. Brown says that once the outbreak was first recognized in Mexico City, it took 18 days for the world at large to hear about it. “By the time international authorities became fully aware of the outbreak,” Brown writes, “there were about 800 cases and at least 50 deaths, and the virus was unknowingly being carried into other countries.” It’s a long story and sure to trigger investigations.

Jessica Mintz at the AP has a related story saying that weeks before CDC and WHO issued their warnings a small Seattle startup “already had a hunch something was up.” It’s an Internet-based system that tracks blogs, chat rooms, Twitter feeds and other publicly available Internet forums for signs that people are talking about a disease outbreak. The company, called Veratect, even issued some alerts before the public health agencies did.

Google is trying something similar by compiling search terms it receives from specific locations. Google.org is publishing its findings for Mexico, which appear to have logged a peak of flu-related searches in January and February but at levels below those seen in previous years.

Lost in most of the coverage is any discussion of how bad it is for an individual to get swine…oops, I mean H1N1 flu? After all, ordinary flu kills several hundred thousand people every year, and we live with that. In 1968 the so-called Hong Kong flu killed about a million people. The Tracker, then working at the Detroit Free Press, recalls that pandemic as something we hoped not to catch but didn’t get all that exercised over. Maggie Fox at Reuters makes a good start on explaining these things in the reader-friendly Q&A form. We need more examples of this kind of thing in other outlets.

Tracker fans, if you spot good examples of flu metastories, please send links to the Tracker via the “Suggest Stories” button at the top of this page. Please put only one link in each suggestion because our software is set to reject anything more spamlike.

Australian swine-flu cases reach 16

2009-05-24T16:57:00.002+07:00

Sydney - Sixteen swine-flu cases have been confirmed in Australia, officials said Sunday.

A 15-year-old Melbourne boy became the third in his school to test positive to the H1N1 influenza virus. Authorities ordered the school to be closed for a week.

In the state of Victoria, where 11 of the cases were reported, Health Minister Daniel Andrews reiterated his view that there was no need for Melbourne residents to be alarmed.

"No one that has tested positive so far is exhibiting symptoms that are any more severe than a normal winter flu," Andrews said.

Prime Minister Kevin Rudd apologized to foreign tourists annoyed by the government's response to swine flu. On Saturday a luxury liner visiting Sydney was held for five hours as doctors assessed the condition of its 2,000 passengers and 900 crew.

"I understand people are going to be inconvenienced by a number of these measures, particularly as it relates to schools and certain parts of the tourism industry," he said. "But these are necessary measures ... because we want to prevent a major outbreak and we want to do anything we can to prevent any deaths."

Outbreak of Swine-Origin Influenza A (H1N1) Virus Infection - Mexico, March - April 2009

2009-05-02T19:28:00.003+07:00

In March and early April 2009, Mexico experienced outbreaks of respiratory illness and increased reports of patients with influenza-like illness (ILI) in several areas of the country. On April 12, the General Directorate of Epidemiology (DGE) reported an outbreak of ILI in a small community in the state of Veracruz to the Pan American Health Organization (PAHO) in accordance with International Health Regulations. On April 17, a case of atypical pneumonia in Oaxaca State prompted enhanced surveillance throughout Mexico. On April 23, several cases of severe respiratory illness laboratory confirmed as swine-origin influenza A (H1N1) virus (S-OIV) infection were communicated to the PAHO. Sequence analysis revealed that the patients were infected with the same S-OIV strain detected in two children residing in California (1). This report describes the initial and ongoing investigation of the S-OIV outbreak in Mexico.

Enhanced Surveillance
On April 17, in response to the increase in reports of respiratory illness, DGE issued a national epidemiologic alert to all influenza-monitoring units and hospitals (Table 1). The alert asked hospitals to report all patients with severe respiratory illness and recommended collection of diagnostic respiratory specimens from these patients within 72 hours of illness onset. On April 18, DGE staff visited 21 hospitals throughout the country to confirm the apparent increase in illness incidence.

After laboratory confirmation of S-OIV infection on April 23, DGE developed case definitions. A suspected case was defined as severe respiratory illness with fever, cough, and difficulty breathing. A probable case was defined as a suspected case in a patient from whom a specimen had been collected and tested positive for influenza A. A confirmed case was defined as a probable case that tested positive for S-OIV by real-time reverse--transcription polymerase chain reaction (RT-PCR). Health-care officials were contacted and asked to provide retrospective and ongoing data for persons having illness consistent with these case definitions and seeking care on or after March 1.

During March 1-April 30, a total of 1,918 suspected* cases were reported, including 286 probable and 97 confirmed cases (Figure). A total of 84 deaths were reported. A majority of case-reports were for hospitalized patients, reflecting the concentration of surveillance efforts within hospitals. However, DGE also received reports from sites conducting routine seasonal influenza surveillance of patients with ILI. Of 1,069 patients with suspected and probable cases for whom information was available, 755 were hospitalized, and the remaining 314 were examined in outpatient settings or emergency departments. Suspected or probable cases were reported from all 31 states and from the Federal District of Mexico. The four areas with the most cases were Federal District (213 cases), Guanajuato (141), Aguascalientes (93), and Durango (77). In other states, the number of suspected or probable cases ranged from two to 46. Suspected and probable cases were identified in all age groups. Mexico routinely monitors seasonal influenza in a network of outpatient facilities throughout the country. Fifty-one influenza A positive specimens from six states were collected during January 4--March 11 in this surveillance network. All of these specimens tested negative for S-OIV at CDC.

Confirmed Cases of S-OIV Infection
As of April 30, DGE surveillance activities, focusing on patients with severe respiratory disease, had identified 97 patients with laboratory-confirmed S-OIV infection, including seven persons who had died. The first of the 97 patients reported onset of illness (any symptom) on March 17, and the most recent patients reported onset on April 26. Laboratory confirmation of S-OIV infection for the most recent 73 of these 97 cases was reported on the evening of April 29. Collection of additional information on these 73 cases is ongoing. Of the 24 patients for whom demographic and clinical information is available, 20 (83%) were hospitalized, three were examined in outpatient settings, and one had illness that was not medically attended. Patients ranged in age from <1 style="font-weight: bold;">Reported by: General Directorate of Epidemiology, Ministry of Health, Mexico; Pan American Health Organization; World Health Organization; Public Health Agency of Canada; CDC (United States).

Editorial Note:
Understanding the epidemiology and clinical profiles of recent cases of S-OIV infection in Mexico can help inform regional, national, and global control measures in response to the emergence of S-OIV infection. Important areas for investigation worldwide include evidence of person-to-person transmission, the geographic distribution of disease, the clinical spectrum of disease, and the effectiveness of mitigation strategies.

Previous instances of human-to-human transmission of other swine viruses have been reported to result in small clusters of disease and limited generations of disease transmission (2,3). Several findings indicate that transmission in Mexico involves person-to-person spread with multiple generations of transmission. Patients with probable and laboratory-confirmed disease have presented over a period of 4 weeks. Limited contact tracing of patients with laboratory-confirmed disease also has identified secondary cases of ILI.

The clinical spectrum of S-OIV illness is not yet well characterized in Mexico. However, evidence suggests that S-OIV transmission is widespread and that less severe (uncomplicated) illness is common. Patients with confirmed disease have been identified in several states, and suspected cases have been identified in all states, which suggests that S-OIV transmission is widespread. In addition, several countries are reporting S-OIV infection among persons who have travel histories involving different parts of Mexico in the 7 days before illness onset. To date, case-finding in Mexico has focused on patients seeking care in hospitals, and the selection of cases for laboratory testing has focused on patients with more severe disease. Therefore, a large number of undetected cases of illness might exist in persons seeking care in primary-care settings or not seeking care at all. Additional investigations are needed urgently to evaluate the full clinical spectrum of disease in Mexico, the proportion of patients who have severe illness, and the extent of disease transmission.

To expedite confirmation of disease in additional patients, the World Health Organization (WHO) Influenza Collaborating Center in Atlanta, Georgia, has placed the genetic sequence of S-OIV from California in GenBank.† Specific primers for S-OIV have been developed and will be distributed through the WHO Global Influenza Surveillance Network to reference laboratories throughout the world. As of April 26, the National Laboratory for Public Health in Mexico has capacity to perform PCR for S-OIV.

The epidemiologic characteristics of this outbreak underscore the importance of monitoring the effectiveness of community mitigation efforts, nonpharmaceutical interventions, and clinical management practices in anticipation of a possible pandemic.

Influenza A(H1NI) - (Mexican swine influenza)

2009-05-02T19:12:00.003+07:00

Information about Influenza A(H1NI) will be added to this page as it becomes available:

Influenza A(H1NI) bulletin - 1 May 2009
The University is closely monitoring the possible epidemic of Influenza A(H1NI) - (Mexican Swine Influenza). While there is as yet no cause for alarm nor any evidence that the University will be affected, we are reviewing the detailed pandemic planning carried in response to the threat of avian flu. Faculties and service divisions have been instructed to take planned precautionary steps appropriate for their area (Halls of Residence for example).

Influenza viruses are transmitted by aerosol droplets being sneezed or coughed directly over other people. Or touching contaminated surfaces and then touching their eyes, mouth or nose. Therefore the University reminds everyone to ensure they follow the very basic hygiene precautions of good sneeze and cough etiquette to prevent the spread of germs. Simply cover your mouth and nose with a tissue if coughing or sneezing, dispose of the soiled tissue in a lined bin and thoroughly wash and dry your hands or use a alcohol base hand gel (sanitiser).

Travel
The University has issued an instruction that no staff are to undertake University business travel to Mexico forthwith. This also applies to any student whose travel is paid for, or funded by or through the University. The University is not to pay for or fund or arrange or permit a student for whom it is therefore responsible to travel to Mexico.

Symptoms
If you have returned from the US or Mexico within the last ten days and think you are suffering influenza symptom it is important that you seek medical attention immediately and contact the following Healthline number (0800 611 116). The Influenza A(H1NI) symptoms are similar to seasonal influenza (flu) which include headache, chills and cough followed by fever, loss of appetite, muscle aches and fatigue, runny nose, sneezing, watery eyes and throat irritation. Nausea, vomiting and diarrhoea may occur in adults as well as in children.

Prior to visiting your doctor please inform them that you have recently returned from these countries so they can prepare their clinics. Please do not re-enter the workplace if you have symptoms.

Key Facts about Swine Influenza (Swine Flu)

2009-04-30T18:58:00.003+07:00

Swine Flu
What is Swine Influenza?
Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus that regularly causes outbreaks of influenza in pigs. Swine flu viruses cause high levels of illness and low death rates in pigs. Swine influenza viruses may circulate among swine throughout the year, but most outbreaks occur during the late fall and winter months similar to outbreaks in humans. The classical swine flu virus (an influenza type A H1N1 virus) was first isolated from a pig in 1930.

How many swine flu viruses are there?
Like all influenza viruses, swine flu viruses change constantly. Pigs can be infected by avian influenza and human influenza viruses as well as swine influenza viruses. When influenza viruses from different species infect pigs, the viruses can reassort (i.e. swap genes) and new viruses that are a mix of swine, human and/or avian influenza viruses can emerge. Over the years, different variations of swine flu viruses have emerged. At this time, there are four main influenza type A virus subtypes that have been isolated in pigs: H1N1, H1N2, H3N2, and H3N1. However, most of the recently isolated influenza viruses from pigs have been H1N1 viruses.

Swine Flu in Humans

Can humans catch swine flu?
Swine flu viruses do not normally infect humans. However, sporadic human infections with swine flu have occurred. Most commonly, these cases occur in persons with direct exposure to pigs (e.g. children near pigs at a fair or workers in the swine industry). In addition, there have been documented cases of one person spreading swine flu to others. For example, an outbreak of apparent swine flu infection in pigs in Wisconsin in 1988 resulted in multiple human infections, and, although no community outbreak resulted, there was antibody evidence of virus transmission from the patient to health care workers who had close contact with the patient.

How common is swine flu infection in humans?
In the past, CDC received reports of approximately one human swine influenza virus infection every one to two years in the U.S., but from December 2005 through February 2009, 12 cases of human infection with swine influenza have been reported.

What are the symptoms of swine flu in humans?
The symptoms of swine flu in people are expected to be similar to the symptoms of regular human seasonal influenza and include fever, lethargy, lack of appetite and coughing. Some people with swine flu also have reported runny nose, sore throat, nausea, vomiting and diarrhea.

Can people catch swine flu from eating pork?
No. Swine influenza viruses are not transmitted by food. You can not get swine influenza from eating pork or pork products. Eating properly handled and cooked pork and pork products is safe. Cooking pork to an internal temperature of 160°F kills the swine flu virus as it does other bacteria and viruses.

How does swine flu spread?
Influenza viruses can be directly transmitted from pigs to people and from people to pigs. Human infection with flu viruses from pigs are most likely to occur when people are in close proximity to infected pigs, such as in pig barns and livestock exhibits housing pigs at fairs. Human-to-human transmission of swine flu can also occur. This is thought to occur in the same way as seasonal flu occurs in people, which is mainly person-to-person transmission through coughing or sneezing of people infected with the influenza virus. People may become infected by touching something with flu viruses on it and then touching their mouth or nose.

What do we know about human-to-human spread of swine flu?
In September 1988, a previously healthy 32-year-old pregnant woman was hospitalized for pneumonia and died 8 days later. A swine H1N1 flu virus was detected. Four days before getting sick, the patient visited a county fair swine exhibition where there was widespread influenza-like illness among the swine.

In follow-up studies, 76% of swine exhibitors tested had antibody evidence of swine flu infection but no serious illnesses were detected among this group. Additional studies suggest that one to three health care personnel who had contact with the patient developed mild influenza-like illnesses with antibody evidence of swine flu infection.

How can human infections with swine influenza be diagnosed?
To diagnose swine influenza A infection, a respiratory specimen would generally need to be collected within the first 4 to 5 days of illness (when an infected person is most likely to be shedding virus). However, some persons, especially children, may shed virus for 10 days or longer. Identification as a swine flu influenza A virus requires sending the specimen to CDC for laboratory testing.

What medications are available to treat swine flu infections in humans?
There are four different antiviral drugs that are licensed for use in the US for the treatment of influenza: amantadine, rimantadine, oseltamivir and zanamivir. While most swine influenza viruses have been susceptible to all four drugs, the most recent swine influenza viruses isolated from humans are resistant to amantadine and rimantadine. At this time, CDC recommends the use of oseltamivir or zanamivir for the treatment and/or prevention of infection with swine influenza viruses.

What other examples of swine flu outbreaks are there?
Probably the most well known is an outbreak of swine flu among soldiers in Fort Dix, New Jersey in 1976. The virus caused disease with x-ray evidence of pneumonia in at least 4 soldiers and 1 death; all of these patients had previously been healthy. The virus was transmitted to close contacts in a basic training environment, with limited transmission outside the basic training group. The virus is thought to have circulated for a month and disappeared. The source of the virus, the exact time of its introduction into Fort Dix, and factors limiting its spread and duration are unknown. The Fort Dix outbreak may have been caused by introduction of an animal virus into a stressed human population in close contact in crowded facilities during the winter. The swine influenza A virus collected from a Fort Dix soldier was named A/New Jersey/76 (Hsw1N1).

Is the H1N1 swine flu virus the same as human H1N1 viruses?
No. The H1N1 swine flu viruses are antigenically very different from human H1N1 viruses and, therefore, vaccines for human seasonal flu would not provide protection from H1N1 swine flu viruses.

Swine Flu in Pigs
How does swine flu spread among pigs?
Swine flu viruses are thought to be spread mostly through close contact among pigs and possibly from contaminated objects moving between infected and uninfected pigs. Herds with continuous swine flu infections and herds that are vaccinated against swine flu may have sporadic disease, or may show only mild or no symptoms of infection.

What are signs of swine flu in pigs?
Signs of swine flu in pigs can include sudden onset of fever, depression, coughing (barking), discharge from the nose or eyes, sneezing, breathing difficulties, eye redness or inflammation, and going off feed.

How common is swine flu among pigs?
H1N1 and H3N2 swine flu viruses are endemic among pig populations in the United States and something that the industry deals with routinely. Outbreaks among pigs normally occur in colder weather months (late fall and winter) and sometimes with the introduction of new pigs into susceptible herds. Studies have shown that the swine flu H1N1 is common throughout pig populations worldwide, with 25 percent of animals showing antibody evidence of infection. In the U.S. studies have shown that 30 percent of the pig population has antibody evidence of having had H1N1 infection. More specifically, 51 percent of pigs in the north-central U.S. have been shown to have antibody evidence of infection with swine H1N1. Human infections with swine flu H1N1 viruses are rare. There is currently no way to differentiate antibody produced in response to flu vaccination in pigs from antibody made in response to pig infections with swine H1N1 influenza.

While H1N1 swine viruses have been known to circulate among pig populations since at least 1930, H3N2 influenza viruses did not begin circulating among US pigs until 1998. The H3N2 viruses initially were introduced into the pig population from humans. The current swine flu H3N2 viruses are closely related to human H3N2 viruses.

Is there a vaccine for swine flu?
Vaccines are available to be given to pigs to prevent swine influenza. There is no vaccine to protect humans from swine flu. The seasonal influenza vaccine will likely help provide partial protection against swine H3N2, but not swine H1N1 viruses.

Influenza-associated Deaths in Tropical Singapore

2009-04-19T19:12:00.002+07:00

We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996–2003. Influenza A (H3N2) was the predominant circulating influenza virus subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8–19.8), 2.9 (1.0–5.0), and 11.9 (8.3–15.7) per 100,000 person-years, respectively. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries.

Influenza virus infections cause excess illness and deaths in temperate countries. In the United States, influenza is responsible for 50 million illnesses and up to 47,200 deaths annually.

However, little is known about the impact of influenza on death rates in tropical regions, where the effect of influenza is thought to be less. In subtropical Hong Kong, deaths from underlying pneumonia and influenza attributable to influenza were estimated to be 4.1/100,000 population per year, higher than the rate (3.1/100,000) reported in the United States.

In tropical Singapore, influenza viruses circulate year round, with a bimodal increase in influenza incidence observed in April–July and November–January. Respiratory syncytial virus (RSV) is also associated with excess deaths. Methods
National Influenza Viral Surveillance

Influenza virus surveillance is carried out throughout the year and has been instituted in Singapore since 1973. We obtained monthly data on influenza A and B viruses and RSV from the WHO-designated National Influenza Centre in Singapore from January 1996 to December 2003. RSV was detected by immunofluorescence tests and virus isolation. Influenza viruses were identified by direct antigen detection with immunofluorescence techniques, serologic tests with complement fixation, and virus isolation. The National Influenza Center provided aggregated data for this study, i.e., monthly numbers of total respiratory specimens tested for influenza virus, positive influenza test results, and influenza virus isolates by subtype, as well as monthly RSV data.

Mortality Data
Three death outcomes were analyzed: underlying pneumonia and influenza (P&I) deaths (ICD-9: 480–487), underlying circulatory and respiratory (C&R) deaths (ICD-9: 390–519), and all-cause deaths (ICD-9: 000–999).
We first applied 6 negative binomial regression models to the monthly number of deaths and monthly proportions of positive influenza virus and RSV tests, to examine the relationships between mortality and the respiratory viruses (namely, models. We also attempted to estimate the excess number of deaths from the viruses.

We estimated the influenza-associated mortality fraction by dividing the number of excess deaths (the difference between observed and expected deaths) by the number of observed deaths, when the proportion of positive influenza results was set to 0 in model 6. The number of excess deaths attributable to influenza was then derived by multiplying the total number of deaths in each mortality category by the respective influenza-associated mortality fraction.

Results
From January 1996 to December 2003, 57,060 specimens were tested for influenza virus, and 51,370 were tested for RSV. There were 9,103 positive results for RSV and 3,829 positive results for influenza. The annual mean number of tests positive for influenza A was 5.8% (range 2.6%–9.5%) and for influenza B, 0.9% (range 0.4%–1.6%). Annually, influenza A (H3N2) was the predominant influenza virus subtype in circulation. During the 8-year period, an annual mean of 15,616 deaths (range 15,301–16,024) occurred in Singapore. An average of 1,798 (range 1,545–2,340) underlying P&I deaths and 8,237 (range 7,833–8,715) underlying C&R deaths occurred each year.

The Figure shows the temporal trends for death outcomes as well as influenza virus and RSV activities. Peaks in monthly influenza A viruses corresponded very well with peaks in monthly all-cause deaths, underlying P&I deaths, and underlying C&R deaths.

We tested the Spearman rank correlations between influenza and RSV, and meteorologic variables. Influenza A positivity (Spearman correlation [r] = 0.25) was weakly correlated with relative humidity. The influenza A (H3N2) subtype had a high correlation with influenza A (r = 0.75) (data not shown).

The relationship between deaths and each respiratory virus (influenza A, influenza B, and RSV) was examined by using a stepwise sequential approach, i.e., first fitting each of the viruses into separate models, then adjusting for 1 of the other 2 viruses (models 4, 5), and finally, adjusting for all viruses in a single model (model 6). Influenza A had significant and robust effects on monthly all-cause deaths (RR 1.05 for each 10% change in positive test results, without adjusting for influenza B virus, RSV, and other potential confounding factors; vs. RR 1.05, after adjusting for influenza B, RSV, and other confounding factors), underlying P&I (RR 1.12 vs. RR 1.13), and underlying C&R (1.08 vs. 1.09) deaths.

In Table 4, we used model 6 (as described in Table 3) to further explore the association between influenza A virus subtypes and the 3 death outcomes. We replaced influenza A variable with influenza A subtypes and adjusted for influenza B virus, RSV, and other confounding factors. Only influenza A (H3N2) had significant (all p values <0.001) effects on all-cause deaths (RR 1.04 for each 10% change in positive test results, 95% CI 1.02–1.05), underlying C&R deaths (1.05, 1.04–1.07), and underlying P&I deaths (1.08, 1.04–1.12).

Influenza B also had a significant effect on underlying C&R deaths (RR 1.01 for each 1% change in positive test results, 95% CI 1.00–1.03, p = 0.037) and all-cause deaths (1.01, 1.00–1.02, p = 0.008), but not on underlying P&I deaths (p = 0.878). Next, we used the full model to quantify the excess deaths attributable to influenza throughout the year. For deaths from all causes, we estimated an annual mean of 588 influenza-associated deaths, representing 3.8% of total deaths. The mean annual estimates of deaths from underlying P&I and C&R associated with influenza were 116 and 475, respectively, representing 6.5% and 5.8% of such deaths.

We observed that the proportion of influenza-associated deaths was higher among the elderly. The annual influenza-associated proportion of deaths from all causes was 11.3 times higher in persons age >65 years (167.8/100,000 person-years) than in the general population (14.8/100,000). For influenza-associated underlying P&I deaths, the annual death rate in those >65 years (46.9/100,000) was 16.2 times higher than those in the general population (2.9/100,000).

Table 6 compares the excess deaths observed in our study with that derived from studies in a subtropical and temperate country. Our estimates of annual influenza-associated all-cause deaths, underlying P&I deaths, and underlying C&R deaths in Singapore were 14.8, 2.9, and 11.9 per 100,000 person-years, respectively. This finding would translate to an estimated 588 deaths (3.8% of total deaths) due to influenza annually, which is comparable to the proportion of deaths observed in subtropical Hong Kong and in the United States, a temperate country.

This figure far exceeds our estimate of 6.5% of underlying P&I deaths attributable to influenza. In Hong Kong and the United States, influenza-associated deaths represented 7.4% and 9.8% of underlying P&I deaths, respectively.

In Singapore, we observed that the influenza-associated proportion of deaths was highest in persons >65 years. Again, this finding is consistent with those in the United States where 90% of influenza-associated deaths occurred among the elderly. In this population, we estimated an annual number of excess deaths per 100,000 population of 167.8 of all-cause deaths, 46.9 deaths from underlying P&I, and 155.4 deaths from underlying C&R attributable to influenza.

In fact, our estimates for influenza-associated deaths in persons age >65 years were consistently higher than those in Hong Kong and United States, for all 3 mortality outcomes. Annual influenza vaccination for persons age >65 years has been recommended since September 2003 in Singapore by the National Expert Committee on Immunization. Influenza vaccine efficacy for preventing death among people >65 years was estimated to be 68%. We recommend a follow-up study to estimate the impact of vaccination on influenza-associated deaths in this age group in Singapore.

With regard to influenza subtypes, we note that most seasons in the United States were dominated by influenza A (H3N2) virus; the greatest number of influenza-associated deaths were associated with influenza A (H3N2), followed by RSV, influenza B, and influenza A (H1N1) virus. Influenza A (H3N2) virus accounted for 60% and 77% of positive influenza isolates in the United States and Hong Kong, respectively. Influenza A (H3N2) was the predominant virus subtype during our study period and had a consistently significant impact on all 3 categories of deaths. Although influenza B was noted to have significant effects on all-cause deaths and underlying C&R deaths, the magnitudes of RRs were relatively small (RR 1.00–1.01, for each 1% change in positive test results). In addition, influenza B virus did not have any significant and observable impact on underlying P&I deaths. We did not observe any significant impact from influenza A (H1N1) virus and RSV on all 3 outcomes.

The prevalence of influenza in Singapore illustrates the importance of improving worldwide coverage and quality of virologic and epidemiologic surveillance for influenza, as described in WHO's Global Agenda for Influenza Surveillance and Control.

Second, the finding that influenza infections account for substantial disease supports our continued investment in strengthening influenza surveillance in our country. An influenza pandemic can be expected to result in far higher attack and death rates than currently observed. Influenza, in contrast, has caused an average of 588 excess deaths in Singapore annually. Influenza continues to cause an increasing amount of disease in Singapore, particularly in our rapidly aging population. Our study is the first to show unequivocally that influenza has a significant impact on proportion of deaths in a tropical country like Singapore.

Major depressive disorder

2009-04-18T18:16:00.003+07:00

Major depressive disorder
Major depressive disorder (also known as clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities. The term "major depressive disorder" was selected by the American Psychiatric Association to designate this symptom cluster as a mood disorder in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) classification, and has become widely used since. The general term depression is often used to describe the disorder, but as it is also used to describe a more temporarily depressed state of mind, more precise terminology is preferred for the disorder in clinical and research use. Major depression is a disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, approximately 3.4% of people with major depression commit suicide, and up to 60% of all people who commit suicide have depression or another mood disorder.

The diagnosis of major depressive disorder is based on the patient's self-reported experiences, behavior reported by relatives or friends, and a mental status exam. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. Major depression is reported about twice as frequently in women as in men, although men are at higher risk for suicide.

The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent major depressive episodes. Depressed individuals have shorter life expectancies than those without depression, in part because of greater susceptibility to medical illnesses. The understanding of the nature and causes of depression has evolved over the centuries, though many aspects of depression remain incompletely understood and are the subject of discussion and research. Psychological treatments are based on theories of personality, interpersonal communication, and learning theory. Monoamines have been implicated in depression, and most antidepressants work to increase the active levels of at least one.

Symptoms and signs
Major depression is a serious illness that affects a person's family, work or school life, sleeping and eating habits, and general health. Its impact on functioning and well-being has been equated to that of chronic medical conditions such as diabetes.

Depressed people may be preoccupied with, or ruminate over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self hatred. Other symptoms include poor concentration and memory, withdrawal from social situations and activities, reduced sex drive, and thoughts of death or suicide. Depressed children often display an irritable rather than a depressed mood, and show varying symptoms depending on age and situation. Most exhibit a loss of interest in school and a decline in academic performance. The biopsychosocial model proposes that biological, psychological, and social factors all play a role to varying degrees in causing depression. The diathesis–stress model posits that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. For example, a prospective, longitudinal study uncovered a moderating effect of the serotonin transporter (5-HTT) gene on stressful life events in predicting depression. A Swedish study estimated the heritability of depression-the degree to which individual differences in occurrence are associated with genetic differences- to be approximately 40 percent for women and 30 percent for men, and evolutionary psychologists have proposed that the genetic basis for depression lies deep in the history of naturally-selected adaptations. A substance-induced mood disorder resembling major depression has been causally linked to long-term drug use or abuse or withdrawal from certain sedative and hypnotic drugs.

Monoamine hypothesis
Most antidepressants increase synaptic levels of serotonin, one of a group of neurotransmitters known as monoamines. Serotonin is hypothesized to help regulate other neurotransmitter systems; decreased serotonin activity may allow these systems to act in unusual and erratic ways. According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter. Some antidepressants enhance the levels of norepinephrine directly, whereas others raise the levels of dopamine, a third monoamine neurotransmitter. These observations gave rise to the monoamine hypothesis of depression. Experiments with pharmacological agents that cause depletion of monoamines have shown that this depletion does not cause depression in healthy people nor does it worsen symptoms in depressed patients - although an intact monoamine system is necessary for antidepressants to achieve therapeutic effectiveness.According to an essay published by the Public Library of Science (PLoS), the monoamine hypothesis, already limited, has been further oversimplified when presented to the general public.

Other theories
MRI scans of patients with depression have reported a number of differences in brain structure compared to those without the illness. There may be a link between depression and neurogenesis of the hippocampus, a center for both mood and memory. Drugs may increase serotonin levels in the brain, stimulating neurogenesis and thus increasing the total mass of the hippocampus. Antidepressant treatment increases the blood level of BDNF. Although decreased plasma BDNF levels have been found in many other disorders, there is some evidence that BDNF is involved in the cause of depression and the mechanism of action of antidepressants.

Investigations reveal increased levels of the hormone cortisol and enlarged pituitary and adrenal glands, suggesting disturbances of the endocrine system may play a role in some psychiatric disorders, including major depression. Depression may be related to abnormalities in the circadian rhythm, or biological clock. REM sleep depends on decreased serotonin levels in the brain stem, and is impaired by compounds, such as antidepressants, that increase serotoninergic tone in brain stem structures. Overall, the serotonergic system is least active during sleep and most active during wakefulness. Depressed individuals can exhibit a significant lift in mood after a night of sleep deprivation. Research on the effects of light therapy on treating seasonal affective disorder suggests that light deprivation is related to decreased activity in the serotonergic system and to abnormalities in the sleep cycle, particularly insomnia. Exposure to light also targets the serotonergic system, providing more support for the important role this system may play in depression. Sleep deprivation and light therapy both target the same brain neurotransmitter system and brain areas as antidepressant drugs, and are now used clinically to treat depression. Light therapy, sleep deprivation and sleep time displacement (sleep phase advance therapy) are being used in combination quickly to interrupt a deep depression in hospitalized patients.

The hormone estrogen has been implicated in depressive disorders due to the increase in risk of depressive episodes after puberty, the antenatal period, and reduced rates after menopause. Conversely, the premenstrual and postpartum periods of low estrogen levels are also associated with increased risk. The use of estrogen has been under-researched, and although some small trials show promise in its use to prevent or treat depression, the evidence for its effectiveness is not strong. Estrogen replacement therapy has been shown to be beneficial in improving mood in perimenopause, but it is unclear if it is merely the menopausal symptoms that are being reversed.

Psychological
Various aspects of personality and its development appear to be integral to the occurrence and persistence of depression. Although depressive episodes are strongly correlated with adverse events, a person's characteristic style of coping may be correlated with their resilience. Additionally, low self-esteem and self-defeating or distorted thinking are related to depression. Depression may be less likely to occur, as well as quicker to remit, among those who are religious. It is not always clear which factors are causes or which are effects of depression; however, depressed persons who are able to make corrections in their thinking patterns often show improved mood and self-esteem.

American psychiatrist Aaron T. Beck developed what is now known as a cognitive model of depression in the early 1960s. Depressed individuals often blame themselves for negative events. In a study of hospitalized adolescents with self-reported depression, those who felt responsible for negative events did not take credit for positive outcomes. This tendency is characteristic of a depressive attributional, or pessimistic explanatory style. According to Albert Bandura, a Canadian social psychologist associated with social cognitive theory, depressed individuals have negative beliefs about themselves, based on experiences of failure, observing the failure of social models, a lack of social persuasion that they can succeed, and their own somatic and emotional states including tension and stress. From the classical psychoanalytic perspective of Austrian psychiatrist Sigmund Freud, depression, or melancholia, may be related to interpersonal loss and early life experiences. Existential psychologists have connected depression to the lack of both meaning in the present and a vision of the future. The founder of humanistic psychology, American psychologist Abraham Maslow, suggested that depression could arise when people are unable to self-actualize, or to realize their full potential.

Social
Poverty and social isolation are associated with increased risk of psychiatric problems in general. Child abuse (physical, emotional, sexual, or neglect) is also associated with increased risk of developing depressive disorders later in life. Disturbances in family functioning, such as parental (particularly maternal) depression, severe marital conflict or divorce, death of a parent, or other disturbances in parenting are additional risk factors. In adulthood, stressful life events are strongly associated with the onset of major depressive episodes; a first episode is more likely to be immediately preceded by stressful life events than are recurrent ones.

The relationship between stressful life events and social support has been a matter of some debate; the lack of social support may increase the likelihood that life stress will lead to depression, or the absence of social support may constitute a form of strain that leads to depression directly. There is evidence that neighborhood social disorder, for example, due to crime or illicit drugs, is a risk factor, and that a high neighborhood socioeconomic status, with better amenities, is a protective factor. Adverse conditions at work, particularly demanding jobs with little scope for decision-making, are associated with depression, although diversity and confounding factors make it difficult to confirm that the relationship is causal.

Evolutionary
From the standpoint of evolutionary theory, major depression is hypothesized, in some instances, to increase an individual's ability to reproduce. Evolutionary approaches to depression and evolutionary psychology posit specific mechanisms by which depression may have been genetically incorporated into the human gene pool, accounting for the high heritability and prevalence of depression by proposing that certain components of depression are adaptations, such as the behaviors relating to attachment and social rank. Current behaviors can be explained as adaptations to regulate relationships or resources, although the result may be maladaptive in modern environments.

Drug use
This increased risk may be due in part to the effects of drugs on neurochemistry, such as decreased levels of serotonin and norepinephrine. Alcoholism or excessive alcohol consumption significantly increases the risk of developing this syndrome. Chronic use of benzodiazepines, a class of medication which are commonly used to treat insomnia, anxiety and muscular spasms, also increase the risk. Chronic, severe depression can develop as a result of chronic use of benzodiazepines or as part of a protracted withdrawal syndrome.

Diagnosis
Clinical assessment
Before diagnosing a major depressive disorder, a doctor generally performs a medical examination and selected investigations to rule out other causes of symptoms. Testosterone levels may be evaluated to diagnose hypogonadism, a cause of depression in men. Depression is also a common initial symptom of dementia. Conducted in older depressed people, additional tests such as cognitive testing and brain imaging, can help distinguish depression from dementia. A CT scan can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms. No biological tests confirm major depression. Investigations are not generally repeated for a subsequent episode unless there is a medical indication.

Breast Cancer

2009-04-18T17:50:00.002+07:00

Breast cancer
Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted) and the fifth most common cause of cancer death. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).

A well-differentiated (low grade) tumor resembles normal tissue. Protein & gene expression status - Currently, all breast cancers should be tested for expression, or detectable effect, of the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins. Stage of a tumor - The currently accepted staging scheme for breast cancer is the TNM classification. Breast cancer is usually, but not always, primarily classified by its histological appearance. For example, inflammatory breast cancer (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other carcinomas by the inflamed appearance of the affected breast. In the future, some pathologic classifications may be changed. The first symptom, or subjective sign, of breast cancer is typically a lump that feels different from the surrounding breast tissue. According to the The Merck Manual, more than 80% of breast cancer cases are discovered when the woman feels a lump.[According to the American Cancer Society, the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram. Lumps found in lymph nodes located in the armpits and/or collarbone can also indicate breast cancer.

Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues such as mastodynia.

When breast cancer cells invade the dermal lymphatics - small lymph vessels in the skin of the breast-its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.

Another reported symptom complex of breast cancer is Paget's disease of the breast. Approximately half of women diagnosed with Paget's also have a lump in the breast.

Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. There is no cure for breast cancer.

The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.

Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors. 3. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth. For example, tumors can induce blood vessel growth (angiogenesis) by secreting various growth factors further facilitating cancer growth.

Experts believe that 95 percent of inherited breast cancer can be traced to one of two genes, which they call Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2). Hereditary breast cancers can take the form of a site-specific hereditary breast cancer- cancers affecting the breast only- or breast- ovarian and other cancer syndromes. Breast cancer can be inherited both from female and male relatives.

Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is often unknowable. In other words, epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. Due to breast cancer is vary in different racial and ethnic group. No etiology is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes. In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occurs.

Worldwide, breast cancer is by far the most common cancer amongst women, with an incidence rate more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer. However breast cancer mortality worldwide is just 25% greater than that of lung cancer in women. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). The incidence of breast cancer varies greatly around the world, being lower in less-developed countries and greatest in the more-developed countries. Women in the United States have the highest incidence rates of breast cancer in the world; 141 among white women and 122 among African American women.Among women in the US, breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer). Women in the US have a 1 in 8 (12.5%) lifetime chance of developing invasive breast cancer and a 1 in 35 (3%) chance of breast cancer causing their death. In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths).

Many doctors say that women exaggerate their risk of breast cancer.

Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences. Breast cancer screening is an attempt to find unsuspected cancers. The most common screening methods are self and clinical breast exams, x-ray mammography, and breast Magnetic Resonance Imaging (MRI). Breast self-examination involves examining one's own breasts using a specific palpation technique to detect any lumps in the breast tissue, which may be cancerous. A recent study involving 160,921 women recruited at age 39-41 showed that annual screening mammograms up to age 48 did decrease breast cancer mortality over an average of 10.7 years. According to these findings, about 2,500 women would need to be screened to prevent one breast cancer death during this time period.

The most recent technology for breast cancer screening is ultrasound computed tomography, which uses sound waves to create a three-dimensional image and detect breast cancer without the use of dangerous radiation used in x-ray mammography. Genetic testing for breast cancer typically involves testing for mutations in the BRCA genes. This is not generally a recommended technique except for those at elevated risk for breast cancer.

Diagnosis
Staging
Breast cancer is staged according to the TNM system, updated in the AJCC Staging Manual, now on its sixth edition. For a more detailed discussion on staging of breast cancer, see here.

Hormone receptors
Breast lesions are examined for certain markers, notably sex steroid hormone receptors. About two thirds of postmenopausal breast cancers are estrogen receptor positive (ER+) and progesterone receptor positive (PR+). Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal therapy.

HER2
In normal cells, HER2 controls aspects of cell growth and division. When activated in cancer cells, HER2 accelerates tumor formation. About 20-30% of breast cancers overexpress HER2. Treatment
The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor), chemotherapy, and/or radiotherapy. In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests like MammaPrint that predict breast cancer recurrence risk based on gene expression. Radiation treatment is also used to help destroy cancer cells that may linger after surgery. Prognosis
The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer invasive. Ductal Carcinoma in situ throughout the entire breast is stage zero.

The closer to normal cancer cells are, the slower their growth and the better the prognosis. The presence of estrogen and progesterone receptors in the cancer cell, while not prognostic, is important in guiding treatment. Elevated CA15-3, in conjunction with alkaline phosphatase, was shown to increase chances of early recurrence in breast cancer.

The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.
As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.

Metastasis
Most people understand breast cancer as something that happens in the breast. Breast cancer can also spread to other parts of the body via blood vessels or the lymphatic system. When breast cancer is found in bones, it has usually spread to more than one site. Like normal breast cells, these tumors in the bone often thrive on female hormones, especially estrogen. This important finding could potentially alter the way in which breast cancer is treated.

Breast cancer may be one of the oldest known forms of cancerous tumors in humans. In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease. The patron saint of breast cancer is Saint Agatha of Sicily.

Arthritis Types

2009-04-15T18:16:00.007+07:00

Arthritis is the knee's biggest enemy. Caused by injury, disease, or just the passing of time, arthritis causes the pain and joint damage that can lead to hip and knee replacement.

The following offers a summary of information about arthritis.

What is arthritis?
Arthritis is the number one cause of chronic disability. Affecting nearly 1 in 5 people in UK, it refers to more than 100 diseases that cause pain, stiffness and swelling from the inflammation of a joint or the area around joints.

The three basic types of arthritis that may cause hip and knee pain: osteoarthritis and inflammatory arthritis (most commonly rheumatoid arthritis), and traumatic arthritis.

	Osteoarthritis	Rheumatoid arthritis	Traumatic arthritis
Number affected in the UK	about 3 million (most common type of arthritis)	over 400,000 (most common type of inflammatory arthritis)	not known
Who is likely to get condition	usually middle-aged and older people	75 percent are women; most often begins between 30 and 60, but can develop at any age	people who have experienced a hip injury or fracture
Definition	joint disease that gets worse over time; does not cause swelling in joints (not inflammatory)	inflammatory condition (causes joint swelling) in which the immune system mistakenly attacks the tissue that lines and cushions the joints	from an injury which leads to a condition called avascular necrosis: blood supply to the ball portion (the femoral head) of the thighbone is cut off
Why it causes pain	cartilage that cushions the bones of the hip starts to erode, eventually allows the bones of the joint to grind or rub together	cartilage wears away and the cushioning fluid in the joint (the synovium) becomes inflamed (swollen) inflammation causes chemicals to be released that damage the cartilage and bone of the affected joint	lack of blood supply causes the ball portion (the femoral head) of the thighbone to wither and surrounding cartilage deteriorates and bones grind or rub together
Symptoms	pain and stiffness	pain and swelling	pain and other symptoms

What is osteoarthritis?
Osteoarthritis is the most common type of arthritis affecting about 3 million Britons, usually middle-aged and older people. This is a noninflammatory degenerative joint disease characterised by the breakdown of the joint's cartilage. Cartilage that cushions the bones of the hip starts to erode, eventually allowing the bones to grind or rub together and causing hip pain and stiffness.The exact cause of osteoarthritis is unknown.

What is rheumatoid arthritis?
In some types of arthritis, such as rheumatoid arthritis, the synovium becomes inflamed. This inflammation causes chemicals to be released that thicken the synovium and damage the cartilage and bone of the affected joint. This leads to inflammation of the synovium causing pain and swelling.

What is inflammatory arthritis?
This chronic disease results when, for unknown reasons, the immune system mistakenly attacks the tissue that lines and cushions the joints. As cartilage wears away, the knee often becomes stiff and swollen. A well-known example is rheumatoid arthritis.

What is traumatic arthritis?
The culprit here is a serious hip injury or fracture that can lead to a condition called avascular necrosis. In avascular necrosis, the blood supply to the ball portion (the femoral head) of the thighbone is cut off and the bone begins to wither. As a result, the surrounding cartilage begins to deteriorate, producing pain and other symptoms.

What is fibromyalgia?
Fibromyalgia is the second most common type of arthritis affecting 750,000 people in UK, mostly women; 70 to 90 percent of people who develop this disease are women aged 20 to 50. Fibromyalgia is a disease involving pain in muscles or joints with no clinical signs of infection. It is often misdiagnosed as chronic fatigue syndrome, and usually does not require surgery.

What causes arthritis?
The causes of the 100 types of arthritis are unknown. Because there are so many different forms of arthritis, the causes are likely to vary. Scientists are currently examining how the roles of major factors including genetics and lifestyles affect the development of arthritis.

What changes occur in the cartilage of an arthritic hip?
In a healthy hip, cartilage cushions the area surrounding the hip ball and socket to allow easy movement without pain. In an unhealthy hip, the cartilage is damaged or worn away causing pain from bones rubbing and grinding together.

What changes occur in the cartilage of an arthritic knee?
In a healthy knee, cartilage protects and cushions bone surfaces that come together at the joint allowing bones to move without friction. In an unhealthy knee, cartilage is damaged or worn away causing pain from bones rubbing together.

What are some of the symptoms of arthritis?
The type of pain caused by arthritis depends on the type you have. Pain from arthritis can be continuous or intermittent. Pain may occur after activity or exercise but it may also happen even if you have been resting and still for a period of time. Pain may be concentrated in one spot or you may feel it all over your body. Joints may feel stiff and difficult to move. Daily chores such as climbing stairs and opening cans may become a challenge. You may notice that pain is more severe during certain times of the day or after performing certain tasks.

Some kinds of arthritis cause swelling or inflammation. The skin over the joint may appear swollen and red, and feel hot when touched. Arthritis may also cause fatigue or weariness. Read Easing the Pain to learn more about pain management.

How can I know if I have arthritis?
Early diagnosis and treatment tailored to an individual's needs are crucial in slowing or preventing damage to joints. Only a physician can determine if you have arthritis and what type it is. Arthritis is diagnosed based on the overall pattern of symptoms, medical history, physical exam, x-rays and lab tests.

Your doctor will start by taking your history and doing a complete physical examination. Your doctor may observe you while standing, sitting, lying down, etc. and watch how well you walk around the room. He or she will also examine your hip and knee carefully, looking and feeling for details that offer clues about your condition. He or she will ask you where it hurts and how long you’ve had the pain. He or she will want to know if you fell or suffered any other trauma to the hip.

The location of the pain is often a tip-off of the condition you have. The source is not always what you would think. Pain that truly comes from a hip problem is often located in the thigh or groin area. In other cases, hip pain may be a signal of a problem elsewhere in the body. If the pain is more in the buttocks than the hip, for example, it may actually be the result of a problem in the back. And, while hip pain that travels down the leg may be the result of infammation in the hip joint, it can also be a sign of sciatica (a condition usually caused by a pinched nerve in the back). If the pain travels below the knee, it could be a sign of disease in the nerves or blood vessels. In women, pain in the hip or upper leg may stem from several other causes, including tumors of the uterus or ovaries, endometriosis (the presence of uterine tissue elsewhere in the body), or pelvic inflammatory disease (infection in the reproductive organs).

Your doctor will also observe your posture while standing, sitting, and lying down, and watch how well you walk around the room. He’ll check for bruises, discouloration, areas of muscle wasting, and any curvature of the back. These observations all offer clues about your condition.

He may order x-rays to rule out a fracture or detect osteoarthritis. A magnetic resonance imaging (MRI) scan can confirm the presence of avascular necrosis or soft tissue damage. If he thinks you have an inflammatory condition or infection, he may order blood tests.

What are the treatment options for arthritis?
Because there are so many types of arthritis, each type of arthritis has different symptoms and treatments. The good news is there are many ways to help control arthritis. Care for arthritis often involves more than one type of treatment. Treatment may vary over time and may be different depending on the kind of arthritis. Consult your doctor to discuss the best treatment options for you.

There are three basic categories of treatments, and your plan may involve one, two, or all three. Brief details are provided here and you can also go to individual sections for each option. Click the links to these sections for detailed information that may help.

Lifestyle Changes
It's hard to make changes in your life, but altering some small daily habits can make a big difference to the way your feel every day. Think about:

Medication : Many drugs, both prescriptions and over-the-counter medications, are used to treat arthritis. Common medications are aspirin-free pain relievers, anti-inflammatory drugs, corticosteroids, disease modifiers, and sleep medications.

Exercise: Regular exercise is important to keep the body moving and flexible. It may lessen pain, increase movement, reduce fatigue, and helps you look and feel better.

Heat or Cold: Use of heat or cold over joints may provide short- term relief from pain and stiffness.

Pacing Activities: Pacing helps protect your joints by alternating periods of activity with periods of rest so that your joints don't tire from the stress of repeated tasks.

Joint Protection: Joints can be protected by learning to use them in ways that avoid excess stress. One way of doing this is to avoid using sore and weak joints. Unless larger joints are sore, for example, it is best to use them when carrying heavy items. The second method is walking with assistive devices like a cane. Lastly, weight control helps ease pain by reducing stress on your joints.

Self-Help Skills: You can learn ways to better manage how arthritis affects you emotionally by talking about your feelings with family members and friends, doing mental exercises, and by joining your local arthritis support group.

Surgery: Most people will not need surgery, but in many cases surgery may be effective in minimising or eliminating pain when other treatment methods have failed.

Not all surgical procedures are alike. In fact, many advances have been made recently allowing surgical procedures that are much less invasive. Such minimally invasive procedures are revolutionising the way patients experience and recover from surgery. New procedures may allow for: less postoperative pain, a faster recovery period, and a shorter hospital stay.

source:zimmer.co.uk

Anxiety

2009-04-15T17:28:00.003+07:00

Anxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear, or worry.

Anxiety is a generalized mood state that occurs without an identifiable triggering stimulus. As such, it is distinguished from fear, which occurs in the presence of an external threat. Additionally, fear is related to the specific behaviors of escape and avoidance, whereas anxiety is the result of threats that are perceived to be uncontrollable or unavoidable.

Anxiety is a normal reaction to stress. It may help a person to deal with a difficult situation, for example at work or at school, by prompting one to cope with it. When anxiety becomes excessive, it may fall under the classification of an anxiety disorder.

Symptoms
Anxiety can be accompanied by physical effects such as heart palpitations, fatigue, nausea, chest pain, shortness of breath, stomach aches, or headaches. Physically, the body prepares the organism to deal with a threat. Blood pressure and heart rate are increased, sweating is increased, bloodflow to the major muscle groups is increased, and immune and digestive system functions are inhibited (the fight or flight response). External signs of anxiety may include pale skin, sweating, trembling, and pupillary dilation. Someone suffering from anxiety might also experience it as a sense of dread or panic.

Although panic attacks are not experienced by every anxiety sufferer, they are a common symptom. Panic attacks usually come without warning, and although the fear is generally irrational, the perception of danger is very real. A person experiencing a panic attack will often feel as if he or she is about to die or pass out. Panic attacks may be confused with heart attacks.

Anxiety does not only consist of physical symptoms. There are many emotional symptoms involved as well. Some of them include: "Feelings of apprehension or dread, trouble concentrating, feeling tense or jumpy, anticipating the worst, irritability, restlessness, watching (and waiting) for signs (and occurences) or danger, and, feeling like your mind's gone blank."There's also, "nightmares/bad dreams, obsessions about sensations, deja vu, a trapped in your mind feeling, and feeling like everything is scary."

One of the most common symptoms of anxiety is fear, which includes the fear of dying. "You may...fear that the chest pains [a physical symptom of anxiety] are a deadly heart attack or that the shooting pains in your head another physical symptom of anxiety are the result of a tumor or aneurysm. You feel an intense fear when you think of dying, or you may think of it more often than normal, or can’t get it out of your mind."

Biological basis
Neural circuitry involving the amygdala and hippocampus is thought to underlie anxiety. When confronted with unpleasant and potentially harmful stimuli such as foul odors or tastes, PET-scans show increased bloodflow in the amygdala. In these studies, the participants also reported moderate anxiety. This might indicate that anxiety is a protective mechanism designed to prevent the organism from engaging in potentially harmful behaviors.

Varieties
Existential anxiety
Theologian Paul Tillich characterized existential anxiety as "the state in which a being is aware of its possible nonbeing" and he listed three categories for the nonbeing and resulting anxiety: ontic (fate and death), moral (guilt and condemnation), and spiritual (emptiness and meaninglessness). According to Tillich, the last of these three types of existential anxiety is predominant in modern times while the others were predominant in earlier periods. Tillich argues that this anxiety can be accepted as part of the human condition or it can be resisted but with negative consequences. In its pathological form, spiritual anxiety may tend to "drive the person toward the creation of certitude in systems of meaning which are supported by tradition and authority" even though such "undoubted certitude is not built on the rock of reality".

According to Viktor Frankl, author of Man's Search for Meaning, when faced with extreme mortal dangers the very basic of all human wishes is to find a meaning of life to combat this "trauma of nonbeing" as death is near and succumbing to it (even by suicide) seems attractive. The "father" of existentialism, Søren Kierkegaard, regarded all humans to be born into despair by default (in The Sickness Unto Death). Such despair was created by having a false conception of the self. He regarded the mortal self which can exist relatively, and therefore be born or die, as the false self. The true self was the relationship of self to God, rather than to any relative object. For more information see angst and existential crisis.

Test anxiety
Test anxiety is the uneasiness, apprehension, or nervousness felt by students who have a fear of failing an exam. Students suffering from test anxiety may experience any of the following: the association of grades with personal worth, fear of embarrassment by a teacher, fear of alienation from parents or friends, time pressures, or feeling a loss of control. Emotional, cognitive, behavioral, and physical components can all be present in test anxiety. Sweating, dizziness, headaches, racing heartbeats, nausea, fidgeting, and drumming on a desk are all common. An optimal level of arousal is necessary to best complete a task such as an exam; however, when the anxiety or level of arousal exceeds that optimum, it results in a decline in performance. Because test anxiety hinges on fear of negative evaluation, debate exists as to whether test anxiety is itself a unique anxiety disorder or whether it is a specific type of social phobia. In 2006, approximately 49% of high school students were reportedly experiencing this condition. While the term "test anxiety" refers specifically to students, many adults share the same experience with regard to their career or profession. The fear of failing a task and being negatively evaluated for it can have a similarly negative effect on the adult.

Stranger and social anxiety
Anxiety when meeting or interacting with unknown people is a common stage of development in young people. For others, it may persist into adulthood and become social anxiety or social phobia. "Stranger anxiety" in small children is not a phobia. Rather it is a developmentally appropriate fear by toddlers and preschool children of those who are not parents or family members. In adults, an excessive fear of other people is not a developmentally common stage; it is called social anxiety.

Trait anxiety
Anxiety can be either a short term "state" or a long term "trait." Trait anxiety reflects a stable tendency to respond with state anxiety in the anticipation of threatening situations. It is closely related to the personality trait of neuroticism.

Genes associated with anxiety
Although single genes have little effect on complex traits and interact heavily both between themselves and with the external factors, the research is ongoing to unravel possible molecular mechanisms of anxiety and comorbid conditions.

Clinical Scales
The HAM-A (Hamilton Anxiety Scale) is a widely used interview scale that measures the severity of a patient's anxiety, based on 14 parameters, including anxious mood, tension, fears, insomnia, somatic complaints and behavior at the interview. Developed by M. Hamilton in 1959, the scale predates the current definition of generalized anxiety disorder (GAD). However, it covers many of the features of GAD and can be helpful in assessing its severity.

What are allergy shots?

2009-04-15T17:00:00.002+07:00

When medications fail to adequately control allergy symptoms and avoidance of the trigger is not easy or possible, an allergist may recommend immunotherapy or “allergy shots”. This treatment consists of a series of injections containing small amounts of the substances to which a person is allergic. After a course of allergy shots, 80 to 90 percent of patients have less allergy symptoms, and in many cases their allergies have completely resolved. Allergy shots can be given for allergic rhino-conjunctivitis (nose and eyes), allergic asthma and insect sting allergies.

Are allergy shots experimental therapies?
No. Allergy shots have been given for nearly 100 years and are FDA approved therapies. Numerous well-designed medical studies show the efficacy of allergy shots. And allergy shots do not contain steroids, which can have adverse long-term side effects.

How do allergy shots work?
Unlike allergy medicines, which act only to “cover up” allergic symptoms or prevent them temporarily, allergy shots fix the underlying problem of allergies. This occurs because the body treats the injection much like a vaccine, resulting in the production of infection-fighting antibodies against the pollen, dust, mold or pet dander. The body then stops producing as much allergic antibodies against the triggers, and therefore won’t have as much, or any, allergic response when exposed to the allergens. These changes can last for many years even after stopping allergy shots. Recent studies show that allergy shots can also prevent people from developing new allergies, and reduce the risk of developing asthma in children with nasal allergies.

How are allergy shots given?
The method of immunotherapy consists of starting at a small dose that will not cause an allergic reaction, with slowly advancing the dosage until the person becomes tolerant to large amounts of the extract. These injections are initially given once to twice a week until a maintenance, or constant dose, is achieved. This usually takes approximately 3 to 6 months. Once the maintenance dosage is reached, the allergic symptoms are largely resolved in most patients. Thereafter, the injections are given every two to four weeks.

How long must I take allergy shots?
Therapy is continued for 3 to 5 years total, after which the patient continues to get benefit for another 5 to 10 years or longer, even after the shots are stopped. If the shots are stopped prior to a total of 3 years, the allergic symptoms typically return more quickly.

What are the risks of allergy shots?
The risks of immunotherapy consist of the possibility of experiencing an allergic reaction to the allergy shot. Most allergic reactions consist of mild to moderate swelling and itching at the site of the injection. These reactions occur frequently, but rarely require any change in treatment. A large swelling may require an adjustment of the immunotherapy dosage or a change in the frequency and amount of the shots.

Less commonly patients experience whole-body allergic reactions, sometimes called “anaphylaxis”. Most of these reactions are mild and consist of itching of the skin, hives, or runny nose. Others are more severe and can present as cough, chest tightness, wheezing, throat tightness, shock and rarely can be life-threatening.

For this reason, it is normally required that patients remain in the physician’s office for 20 to 30 minutes after the injection since most reactions occur during this time. These reactions are typically easily reversed with medicines such as injectable epinephrine and anti-histamines.

Should I take allergy shots?
Obviously, this is a question that only you and your doctor can answer. There are many reasons to consider allergy shots:

* Medicines don't work: Many patients go to the allergist because they still have symptoms despite having tried numerous allergy medications, with little to no relief of their symptoms. Sometimes allergy shots are the only therapy left for these patients.
* Go for the cure: Other patients like the idea of a “cure”, and opt for allergy shots for that reason. Remember, immunotherapy is the only treatment for allergies that fixes the underlying problem of the immune system, much like a vaccine.
* Don't like medicines: Some patients experience severe side effects from medications, or don’t like taking medications on a daily basis – the idea of a “once a month shot” is a better option for them.
* Cost of medicines: Medications can be expensive, and since allergy symptoms typically return soon after medications are stopped, patients may require medications for many, many years. Allergy shots can alleviate much of the need for medications and can be a significant cost savings measure in the long run.

Medical Library

2009-04-12T17:59:00.003+07:00

Acute Renal Failure

Renal failure occurs when the kidneys are unable to do their job: to filter wastes from the blood, help regulate blood pressure, and regulate salt and water balances in the body. As blood flows through the kidneys, it is filtered, and wastes are removed and sent to the bladder as urine. If kidney function becomes impaired, acute (rapid) or chronic (gradually developing) renal failure may occur. With acute renal failure, kidney function can return to normal if the underlying cause of the failure is discovered and successfully treated.

Symptoms of Acute Renal Failure
The symptoms of the underlying cause of acute renal failure may be more prominent, but the following symptoms of acute renal failure may occur:

* Little or no urine output (in some cases, urine output may continue)
* Foot, ankle and leg swelling
* Drowsiness
* Shortness of breath

Acute renal failure is usually diagnosed by blood tests that indicate impaired kidney function. Treating the cause of acute renal failure can help restore kidney function rapidly. Abnormalities in blood pressure, amount of body fluid, and electrolytes (minerals in the blood) also need to be evaluated and treated. In some cases, dialysis (filtering of the blood outside the body using a machine) may be necessary to replace kidney function.

For More Information
National Institute of Diabetes & Digestive & Kidney Diseases
(800) 891-5390

National Kidney Foundation
(800) 622-9010

Kidney & Urology Foundation of America
(800) 633-6628

American Association of Kidney Patients
(800) 749-2257

American Kidney Fund
(800) 638-8299

Sources: Kidney & Urology Foundation of America, National Kidney Foundation, National Institute of Diabetes & Digestive & Kidney Diseases

Sharon Parmet, M.S., Writer
Cassio Lynm, M.A., Illustrator
Richard M. Glass, M.D., Editor

The JAMA Patient Page is a public service of JAMA. The information and recommendations appearing on this page are appropriate in most instances, but they are not a substitute for medical diagnosis. For specific information concerning your personal medical condition, JAMA suggests that you consult your physician. This page may be reproduced noncommercially by physicians and other health care professionals to share with patients. Any other reproduction is subject to AMA approval. To purchase bulk reprints, call (718) 946-7424.

Research Studies on Alcohol Abuse and Domestic Violence

2009-04-12T17:28:00.005+07:00

Current alcoholism research studies demonstrate a strong correlation between the abuse of alcohol and domestic violence.

Research Studies on Alcohol Abuse and Domestic Violence

Many studies demonstrate a strong relationship between alcohol abuse and domestic violence. More specifically, various research studies have found a high rate of alcohol abuse among men who batter their female partners.

Since, however, the evidence does not support a cause-and-effect relationship between the two problems, it is unlikely that a causal link exists between alcohol abuse and domestic violence.

In a word, the relatively high occurrence of alcohol abuse by men who batter women, though correlated, must be seen as the overlap of two separate but frequently occurring social problems.

Battering is a socially learned behavior that is not necessarily the result mental illness or substance abuse. Men who batter women often use excessive drinking as an excuse for their violence. That is, they attempt to shirk personal responsibility for the problem by blaming physical violence on the effects of alcohol.

It is important to point out, however, that many male alcoholics do not batter their female partners and numerous men who beat their female partners do not drink excessively. Some men with alcohol problems batter their female partners when they are drunk, others beat their female partners when they are sober, and some men with alcohol problems never batter their female partners.

Men who have a predisposition for physical violence toward their female partners and who drink alcohol are more likely to be violent on the days they drink alcohol. This study was undertaken by the University of Buffalo's Research Institute on Addictions (RIA) and reported in the February 2003 issue of the American Psychological Association's Journal of Consulting and Clinical Psychology.

It is important to note that the participants in this study were men who had exhibited domestic violence and who had entered an outpatient treatment facility for alcoholism or for battering their partner. It is not clear, however, how these results would generalize to the general population. In fact, according to research, heavy alcoholic drinking by men in the general population does not necessarily lead to domestic violence.

Similarities Between Alcoholism and Wife Battering
Alcoholism and battering, however, do share some similarities, including the following:

* Both may be centered around control and power.
* Both can be transmitted from generation to generation.
* Both involve denial or the attempt to down play the problem.
* Both can involve the isolation of the family, the perpetrator, or the victim.
* A battering incident that is coupled with alcohol abuse may be more severe and result in greater injury.
* Alcoholism treatment does not "cure" battering behavior; both problems must be addressed separately.

Alcohol abuse and violence in a relationship can exist before a couple gets married. Indeed, alcohol abuse and physical or verbal abuse often develop before a relationship begins. In abusive relationships where alcohol abuse also exists, the key issue frequently is the need of one partner to exercise power and control over the other. This need to control the partner, however, is also found in abusive relationships in which there is no alcohol abuse.

A woman's substance abuse problems do not necessarily relate to the cause of her physical abuse, although some women may resort to alcohol and other drugs in response to the physical abuse.

Interestingly, men who abuse their partners at home do not typically get into fights outside the home. Abusive men who need power and control usually abuse individuals who are seen as weaker, more submissive, or more vulnerable.

Not surprisingly, the target of abusive men frequently is their female partner or their children. Men who experience relationship problems often engage in drinking excessive alcohol in an attempt to maintain control. Ironically, alcohol abuse has the reverse effect: The more the man drinks, the more he loses control.

Physical addiction takes place when a person's body becomes dependent on a particular substance such as drug or alcohol. It also means that a person develops a tolerance to that particular substance, meaning that the user requires a larger dose than before to get the same "buzz" or "high."

It appears that many if not most people see women on the receiving end of physical abuse due to the alcohol abuse of their husbands. There is another viewpoint: that women who are battered resort to alcohol and eventually abuse alcohol as a response to the physical battering. That is, women who become a victim of battering are at risk of abusing alcohol and other drugs as an attempt to cope with their pain and shame.

Research has shown that people who start drinking at an early age, for instance at 13 years old or younger, significantly increases the likelihood that they will experience alcohol problems
later in life.

Women of all ages can become victims of sexual, economic, physical, and emotional abuse. Some abusive male partners force women to take drugs or to drink alcohol under the threat of further physical violence if the women refuse. Some women do not understand that alcohol and drugs put them at risk for physical, sexual, or psychological abuse.

The following represents severe withdrawal symptoms that usually occur within 48 to 96 hours after the last alcoholic drink: high fever, visual hallucinations, seizures, black outs,
severe autonomic nervous system
over activity, extreme confusion, convulsions, delirium tremens
(DTs), agitation, and
muscle tremors.

Domestic Violence and Alcohol Abuse in Women

Women who have experienced domestic violence and alcohol abuse have reported the following:

Repeated episodes of substance abuse or returning to a relationship involving battering before making lasting change
Isolation, guilt, and shame
Behaviors and actions that others describe as dysfunctional or weird
Experiences of trauma
Initial denial or rejection of the problem
Loss of personal support systems
Fear of losing their children as a consequence of disclosing their problem
Low self esteem
A belief or conviction that the problem will simply disappear or go away
Diminished logical decision-making capabilities
Involvement in the criminal justice system, either as an offender or as a victim.
A propensity to seek professional help only when facing a crisis

Since some women remain unaware of their pregnancy, sometimes for 2 or more months, women who are pregnant or those who are trying to become pregnant should abstain from all alcoholic beverages, according to the
March of Dimes.

Why Women Stay in Abusive Relationships

Women stay in abusive relationships for numerous reasons, including the following:

She might be fearful of what her male partner may do to her, to their children, or to their animals if she leaves
She might be pregnant
She may not have experienced another relationship, so she might think abuse is normal for all relationships
She might feel pressured to stay in the marital relationship because of her family or religious beliefs
She believes that she is at fault for the abuse
She loves the abuser and believes that he will change
She might have a substance abuse problem and ironically, her partner may be her drug supplier
She might believe that her partner's jealousy and abuse are indications of his love for her
She might not have a place to stay if she leaves
She might be afraid to tell her family, especially her parents, because they might make her break up with her male partner
She feels guilt, shame, or embarrassment about the abuse
She is unaware of the community resources that are available for getting help
She might not have the financial resources to support herself or her children without her male partner

Problem drinkers are mostly found in young adults between the ages of 18 and 29. Conversely, the age group with the fewest alcohol problems is adults who
are 65 years old or older.

Alcohol-Related Violence Statistics

The following represents some the statistical findings of alcohol-related violence:

A national survey of female college students found that 15 percent of them had been raped at some time since the age of 14. In 53% of these cases, the victim was drinking and in 64% of these cases, the offender was drinking.
A woman involved in alcohol abuse is at risk for becoming the victim of sexual assault due to the fact that many perpetrators see a woman's drinking as sexual consent.
Drinking by both victims and offenders has been correlated with assaults taking place in unplanned social situations such as at wedding receptions or bars in which the victim did not know the offender before the assault.
Abused women of all races report less support from their partners, more substance abuse, higher levels of stress, lower self-esteem, and less support from others than women who are not abused.
Men who abuse alcohol and who commit sexual assault frequently commit more severe sexual assaults than men who do not drink excessively but who commit sexual assault.
Continued alcohol abuse is one of the major risk factors for violence in intimate relationships.
The correlation between the battering of women and alcohol abuse is the highest for men who believe that male control and power over women are acceptable in certain situations.

In many instances, people abuse drugs or alcohol in order to have "fun" or to get a "buzz." Many people, in fact, report that having a few drinks makes them feel more comfortable in social situations. The danger, however, is this: repeated alcohol or drug abuse can result in addiction.

Alcohol Abuse and Abusive Men

The following represents the relationship between abusive men and alcohol abuse:

* Alcohol abuse in men increases the chance of partner abuse eightfold. It also doubles the risk that they will kill or attempt to kill their female partners.
* Among men who batter their partners and who abuse drugs, a third of the violence happens when the men are sober.
* Being physically abused as a child is a risk factor for substance abuse as an adult.
* Alcohol or drug abuse remains a major risk factor for men who become violent.
* Men who have been a victim of violence or who have seen violence in the home may imitate the violence they have seen or experienced.
* Men who tend to resort to violence when they are frustrated or angry may not have learned the nonviolent ways of expressing these emotions.
* Approximately 46% of men who commit acts of violence with their partners also have substance abuse problems.
* Not all men who are dependent on drugs or alcohol resort to violence. In a similar manner, not all violent men abuse drugs or alcohol.
* Men living with women who have alcohol abuse problems often try to justify their violence as a way to control their female partners when they are drunk.

Alcohol Abuse and Domestic Violence: Conclusion
Numerous research studies demonstrate a relatively strong relationship between alcohol abuse and domestic violence. Since the evidence does not support a cause-and-effect relationship between the two problems, however, it is unlikely whether a causal link between alcohol abuse and domestic violence exists.

Stated differently, the relatively high occurrence of alcohol abuse by men who batter women, though correlated, must be seen as the overlap of two separate but frequently occurring social problems.

About 10 to 20 % of the people who drink heavily eventually develop cirrhosis of the liver (i.e., a scarring of the liver). Alcoholic cirrhosis can be fatal if the individual continues to drink. Even though cirrhosis is irreversible, if the affected person stops drinking, his or her chances of survival can improve significantly. Even though some people may eventually need a liver transplant as a last resort, many people with cirrhosis who stop drinking alcoholic beverages can receive treatment and may never require
liver transplantation.

What is acute kidney failure?

2009-04-12T17:17:00.003+07:00

What is acute kidney failure?
Acute kidney (renal) failure is the sudden shutdown of your kidneys. This problem is also called acute renal failure or acute renal insufficiency.

Your kidneys are located on each side of your spine above your waist. They make urine by filtering waste products from your blood, control the balance of salt and water in your body, and help regulate your blood pressure. As long as you have at least one kidney that is working, your body can get by.

When you have kidney failure, the kidneys are no longer able to make urine, rid your body of wastes, or keep a healthy balance of chemicals such as sodium and potassium.

How does it occur?
Tiny blood vessels in the kidneys filter the blood that flows through them. The kidneys need good blood flow to work properly. Acute kidney failure can happen when the kidneys are not getting enough blood flow. It can also happen when they are injured by disease, drugs, or poisons.

People who have been badly burned, have had a heart attack, have lost a lot of blood, are dehydrated, or are very ill may go into shock. Shock decreases blood flow to the kidneys and may injure them.

Problems in the kidneys that can cause failure are:
* kidney stones
* cysts
* tumors
* infection
* nephritis (inflammation of one or both kidneys)
* injury from drugs, solvents, insecticides, or other poisons.

Sometimes blockage of urine flow causes or contributes to acute kidney failure. This can happen, for example, when the prostate gland is enlarged.

What are the symptoms?
Symptoms of acute kidney failure may include:

* confusion
* drowsiness and fatigue
* itchy skin or skin darkening
* loss of appetite
* muscle cramps or weakness
* nausea and vomiting
* urinating less
* seizures
* swelling of feet and ankles
* skin or breath that smells like urine.

How is it diagnosed?
Your healthcare provider will ask about your symptoms and examine you. You will have urine and blood tests to see how well your kidneys are working. A catheter (tube) may be placed in your bladder to keep track of the amount of urine being made.

Your healthcare provider will look for the cause of the kidney failure. You may have special X-rays and ultrasound scans to show the size of your kidneys and to look for blockages. You may need to have a biopsy, a test in which tissue or cell samples are taken from the kidney and examined.

How is it treated?
Your kidneys may work normally again when the cause is treated. However, if your kidneys do not begin to function soon, you may need kidney dialysis.

Dialysis is a mechanical way to do the work your kidneys normally do. It removes waste products and extra water from the blood and can be life-saving. After several weeks the kidneys may begin to function again and dialysis can be stopped. Sometimes chronic (long-lasting) kidney failure develops, which could require long-term dialysis or a kidney transplant.

You may need to change your diet. Follow your healthcare provider's guidelines for the amount of salt in your diet. Also, the amounts of liquids you drink must be balanced against how much you urinate. You may need to have less protein to prevent further damage to your kidneys. You may also need to limit the potassium in your diet because it may be hard for your body to get rid of extra potassium. (Too much potassium can cause heart rhythm problems.) With the right diet, you can reduce the work your kidneys must do.

How long will the effects last?
The kidneys usually start working normally again when the condition causing the kidney failure is treated. Acute kidney failure can last for days or weeks. It may take the kidneys many months to regain full function. There is a risk your kidneys could be permanently damaged.

In some cases acute kidney failure can lead to chronic kidney failure or even death.

How can I take care of myself?
* Carefully follow your healthcare provider's instructions for treating your kidney failure.
* Follow your provider's instructions for balancing your fluids through the day.
* Make changes in your diet as recommended by your healthcare provider. Ask your provider for written diet instructions or for a referral to a dietitian.

source:kidney.org

Acute Kidney Failure Causes

2009-04-12T17:04:00.002+07:00

Causes of acute kidney failure fall into one of the following categories:
* Prerenal: Problems affecting the flow of blood before it reaches the kidneys
* Postrenal: Problems affecting the movement of urine out of the kidneys
* Renal: Problems with the kidney itself that prevent proper filtration of blood or production of urine

Prerenal failure
Prerenal failure is the most common type of acute renal failure (60%-70% of all cases). The kidneys do not receive enough blood to filter. Prerenal failure can be caused by the following conditions:
* Dehydration: - From vomiting, diarrhea, water pills, or blood loss
* Disruption of blood flow to the kidneys from a variety of causes:

o Drastic drop in blood pressure from major surgery with blood loss, severe injury or burns, or infection in the bloodstream (sepsis) causing blood vessels to inappropriately relax

o Blockage or narrowing of a blood vessel carrying blood to the kidneys

o Heart failure or heart attacks causing low blood flow

o Liver failure causing changes in hormones that affect blood flow and pressure to the kidney

There is no actual damage to the kidneys early in the process with prerenal failure. With appropriate treatment, the dysfunction usually can be reversed. Prolonged decrease in the blood flow to the kidneys, for whatever reason, can however cause permanent damage to the kidney tissues.

Postrenal failure
Postrenal failure is sometimes referred to as obstructive renal failure, since it is often caused by something blocking elimination of urine produced by the kidneys. It is the rarest cause of acute kidney failure (5%-10% of all cases). This problem can be reversed, unless the obstruction is present long enough to cause damage to kidney tissue.

Obstruction of one or both ureters can be caused by the following:
* Kidney stone: usually only on one side
* Cancer of the urinary tract organs or structures near the urinary tract that may obstruct the outflow of urine
* Medications
Obstruction at the bladder level can be caused by the following:
* Bladder stone
* Enlarged prostate (the most common cause in men)
* Blood clot
* Bladder cancer
* Neurologic disorders of the bladder impairing its ability to contract

Treatment consists of relieving the obstruction. Once the blockage is removed, the kidneys usually recover in one to two weeks if there is no infection or other problem.

Renal damage
Primary renal damage is the most complicated cause of renal failure (accounts for 25%-40% of cases). Renal causes of acute kidney failure include those affecting the filtering function of the kidney, those affecting the blood supply within the kidney, and those affecting the kidney tissue that handles salt and water processing.

Some kidney problems that can cause kidney failure include:
* Blood vessel diseases
* Blood clot in a vessel in the kidneys
* Injury to kidney tissue and cells
* Glomerulonephritis
* Acute interstitial nephritis
* Acute tubular necrosis

Glomerulonephritis: The glomeruli, the initial filtration system in the kidney, can be damaged by a variety of diseases, including infections. The resulting inflammation impairs kidney function.
* A common example is strep throat. Streptococcal bacterial infections may damage the glomeruli.
* Glomerular disorder symptoms may include dark-colored urine (like cola or tea) and back pain.
* Other symptoms include producing less urine than usual, blood in the urine, high blood pressure, and body swelling (retaining water).
* Treatment usually consists of medications and, if kidney function fails significantly, dialysis may be needed to remove life-threatening waste products that cannot be excreted.

Acute interstitial nephritis: This is a sudden decline in kidney function caused by inflammation of interstitial kidney tissue which primarily handles salt and water balance rather than the filtering of wastes.

* Medications such as antibiotics, anti-inflammatory medicines (for example, aspirin, ibuprofen), and water pills (diuretics) are the most common causes.
* Other causes include infections and immune-related diseases such as lupus, leukemia, lymphoma, and sarcoidosis.
* It is usually reversible if the kidney damage is not severe.
* Treatment consists of withdrawal of offending drugs, treatment of infection, and dialysis in cases of very low kidney function.

Acute tubular necrosis: The kidney tubules are damaged and do not function normally. Tubular necrosis is usually the end result from the other causes of acute renal failure. The tubules are delicate structures that handle much of the kidney's filtration function. When there is necrosis, the cells that form the tubules become dysfunctional and "die".

* This condition accounts for 90% of cases of primary acute kidney failure.
* Causes include shock (decreased blood supply to the kidneys), drugs (especially antibiotics) and chemotherapy agents, toxins and poisons, and dyes used in certain kinds of x-rays.

* Some people produce much less urine than usual. Other symptoms of acute tubular necrosis include tiredness, swelling, lethargy, nausea, vomiting, abdominal pain, loss of appetite, and rash. Sometimes there are no symptoms.

* Treatment depends on the cause of the damage and may consist of discontinuing problem medications, replenishing body fluids, and improving blood flow to the kidney. A diuretic may be given to increase urine production if the total body water level is too high. Medications may be given to correct blood chemistry imbalances.

* If there is no recovery of the patient's kidneys and these treatments do not sufficiently substitute for the lost kidney function, the patient will need regular dialysis or may be a candidate for kidney transplantation.

source:emedicinehealth

Syndrome

2009-04-10T18:13:00.004+07:00

Introduction
This article is a very brief overview of Turner syndrome (TS), which is a chromosomal condition. The information presented is based on the resources listed and the reader is encouraged to go to these sites to learn more about this condition.

"Marissa’s Story" as told by her Mother"
Marissa was born with lymphedema. Her hands and feet were as thick as they were long. Everyone in the delivery room knew that she had edema, but no one know why. The doctor asked if it was OK to do some blood work. Of course I said it would be fine. We left the hospital and two weeks later the test results were back: she had Turner Syndrome.

My husband and I did what the doctors told us to do. It worked for the most part and everything was fine. Marissa was not aware that anything was going on, until right after her second birthday. She look up at me and said, "Why my foot big?" It broke my heart. How do you explain lymphedema to a two year old? She will be three in December and the questions have not stopped. I just tell her she is a little different; like some people have short hair and some have long hair.

Marissa is a bright and happy little girl and she is dealing with her difference very well. My hope is that she will grow up to be a wonderful young lady who may one day help other people with differences, whatever they may be.

Turner Syndrome is a Chromosal Condition
TS is a chromosomal condition that affects approximately 1 out of every 2,500 female live births worldwide. Normally a female has two X chromosomes. In females with TS, only one normal X chromosome is present. TS results when all or part of the other X chromosomes is lost or damaged before or soon after the time of conception.

TS is a highly variable condition that affects only females. Every girl with TS is unique and most of them are healthy and well-adjusted; however, some face special physical, emotional, social, or learning challenges.

Turner Syndrome Facts
* One in 3,000 live female births have Turner Syndrome.
* The average adult height for a woman with Turner Syndrome is 4 ft 8in.
* At least 60,000 American girls and women have Turner Syndrome.
* Approximately 800 new cases of Turner's are reported yearly in the US.

What causes Turner Syndrome?
No known causes of TS have been found. There is nothing that parents do to cause, or increase, the risk of TS in their daughters. Unfortunately there is also nothing they can do to prevent it. Based on current knowledge, TS appears to be a random event that could happen to anyone.

What are the characteristics of Turner Syndrome?
Short stature and lack of ovarian development are the two most common features of TS. At the appropriate ages, these are treated with growth hormone and estrogen replacement therapy to stimulate a more normal growth pattern.

Other characteristics of TS vary greatly in their presence and their severity. These include heart and kidney abnormalities, physical characteristics such as a short neck, a low hairline at the back of the neck, and low-set ears.

Are girls with TS mentally retarded?
No! There is no connection between TS and mental retardation. The intelligence of girls with TS varies just as it does in the general population. Girls with TS are usually in the normal intelligence range; however, some may have nonverbal learning disabilities.

Where does lymphedema come into this?
Lymphedema is present in about 70% of those with TS and the hands and feet are most commonly affected. This form of lymphedema is the result of the underdevelopment of the lymphatic system before birth. As the child matures, this swelling is managed using with the same treatment methods that are used to control other types of lymphedema.

How is Turner Syndrome diagnosed?
A prenatal ultrasound may indicate that the fetus has a physical condition common to TS. However the ultrasound alone, does not provide a definitive diagnosis.

After birth a diagnosis of TS is made on the basis of a karyotype. This chromosome profile, which is based on a study of cells obtained from a blood test, is performed to confirm a missing or damaged X chromosome that is characteristic of TS.

What does the future look like for girls with Turner Syndrome?
With good medical and psychological care and the emotional support of friends and family, a girl with TS should look forward to a healthy and satisfying life.

References and Resources
The Turner Syndrome Society is web site of the National Turner Syndrome organization. It contains information and helpful links.

C.A. Bondy for The Turner Syndrome Consensus Study Group “A Guideline of the Turner Syndrome Study Group”

Living with Turner Syndrome is an excellent informative site that fulfills the promise of its name by presenting helpful information on “Living with Turner Syndrome.”

Complications of Turner Syndrome is part of the Turner Syndrome web site that provides details on possible complications and includes information on TS clinical trials.

Sick building syndrome (SBS)

2009-04-10T17:59:00.003+07:00

Sick building syndrome (SBS) is a combination of ailments (a syndrome) associated with an individual's place of work (office building) or residence. A 1984 World Health Organization report into the syndrome suggested up to 30% of new and remodelled buildings worldwide may be linked to symptoms of SBS. Most of the sick building syndrome is related to poor indoor air quality.

Sick building causes are frequently pinned down to flaws in the heating, ventilation, and air conditioning (HVAC) systems. Other causes have been attributed to contaminants produced by outgassing of some types of building materials, volatile organic compounds, molds (see mold health issues), improper exhaust ventilation of light industrial chemicals used within, or fresh-air intake location / lack of adequate air filtration (see Minimum Efficiency Reporting Value).

Symptoms are often dealt with after-the-fact by boosting the overall turn-over rate of fresh air exchange with the outside air, but the new green building design goal should be to avoid most of the SBS problem sources in the first place, minimize the ongoing use of VOC cleaning compounds, and eliminate conditions that encourage allergenic, potentially-deadly mold growth.

Many published studies have consistently found that women tend to be more prone to SBS than men.

Symptoms
Building occupants complain of symptoms such as:

* Headache
* Eye, nose, or throat irritation
* Dry cough; dry or itchy skin
* Dizziness and nausea
* Difficulty in concentrating
* Fatigue
* Sensitivity to odors
* Increased incidence of asthma attacks/appearance of asthma in non-asthmatics
* Personality changes such as rage/weeping/paranoia/depression
* Putative cases of bronchitis or pneumonia which do not respond to antibiotic treatment
* Symptoms resembling irritable bowel syndrome (IBS)

This is a shortened list, as over 50 possible symptoms are known. It is possible for a dozen sick occupants to report a surprising array of individual symptoms which may be dismissed as unconnected. The key to discovery is the increased incidence of illnesses in general with onset or exacerbation within a fairly close time frame - usually within a period of weeks. Some sources will insist that for SBS to exist, these symptoms must disappear soon after the occupants go outside. However, this view discounts the lingering effects of various neurotoxins, which may not clear up when the occupant leaves the building. In particularly sensitive individuals, the potential for long-term health effects cannot be overlooked.

Causes
The contributing factors often relate to the design of the built environment, and may include combinations of some or all of the following:
* Indoor air quality (including smoking where not prohibited)
* Toxic mold
* Artificial fragrance, such as dryer sheets
* Poor or inappropriate lighting (including absence of or only limited access to natural sunlight)
* Poor heating or ventilation
* Microbial or mite contamination of HVAC systems.
* Bad acoustics or infrasound.
* Poorly designed furnishings, furniture and equipment (e.g. computer monitors, photocopiers, etc.).
* Poor ergonomics.
* Chemical contamination.
* Biological contamination.

To the owner or operator of a "sick building", the symptoms may include high levels of employee sickness or absenteeism, lower productivity, low job satisfaction and high employee turnover.

Prevention
* Pollutant source removal or modification to storage of sources.
* Replacement of water-stained ceiling tiles and carpeting.
* Institution of smoking restrictions.
* Use paints, adhesives, solvents, and pesticides in well-ventilated areas, and use of these pollutant sources during periods of non-occupancy.
* Increase the number of air exchanges, The American Society of Heating, Refrigeration & Air Conditioning Engineers recommend a minimum of 8.4 air exchanges per 24 hour period.
* Proper and frequent maintenance of HVAC systems
* Fitting easy to clean air supply diffusers and ductwork like a textile diffuser.

wikipedia.

Marfan Syndrome

2009-04-10T17:48:00.004+07:00

Introduction
Marfan Syndrome is a hereditary disorder of the connective tissue affecting many organ systems, including the skeleton, lungs, eyes, heart, and blood vessels.

The syndrome affects men, women, and children, and has been found among people of all races and ethnic backgrounds.

Causes
Marfan Syndrome is caused by a defect in the gene that determines the structure of fibrillin, a protein that is an important part of connective tissue. The defective gene can be inherited.

External Signs
Marfan Syndrome affects people in many different ways. While some people have only mild symptoms, others are more severely affected. In most cases, the disorder becomes more serious as the person ages.

People with Marfan syndrome are typically very tall, slender, and loose jointed. The long bones of the skeleton, arms, legs, fingers, and toes may be noticeably long in relation to the rest of the body.

Other characteristics include a long, narrow face, and the roof of the mouth may be arched causing teeth to be crowded. Other skeletal abnormalities may include a protruding or indented breastbone, curvature of the spine, and/or flat feet.

Internal Signs
Marfan syndrome may also affect eyes. More than half of all people with the condition experience dislocation of one or both lenses. Great care must be taken in the health of the eyes as retinal detachment is a possible complication of the syndrome.

Heart and blood vessel abnormalities are also common. The valve between the left chambers of the heart may be large and soft, resulting in an abnormal valve motion when the heart beats. In some cases, the valve may leak creating a heart murmur. Small leaks may not cause any symptoms, but larger ones may cause shortness of breath, fatigue, and a very fast or irregular heart rate. Other symptoms include stretch marks. People with Marfan syndrome are also at increased risk for developing an abdominal hernia where a bulge containing part of the intestines develops.

Treatment
Although there is no cure for Marfan syndrome, there are many options for managing the symptoms the condition.

Because Marfan syndrome is rare, it is important to find a physician who is knowledgeable about the condition. During the initial physical examination, a detailed medical and family history will be taken along with height measurement, eye exam and an electrocardiogram.

An annual skeletal evaluation to detect any changes in the spine or sternum is typically conducted. This evaluation is particularly important during the high-growth period of adolescence. A serious abnormality is not only disfiguring but it can also prevent the heart and lungs from functioning properly. In some cases, an orthopedic brace or surgery may be recommended to limit the damage.

Regular eye examinations are vital in uncovering and correcting any vision problems. In most cases glasses or contact lenses can correct the problem. However, surgery may be necessary in some cases.

Regular checkups and echocardiograms help in evaluating the size of the aorta and the way the heart is working. The earlier a potential problem is identified and treated, the lower the risk of life-threatening complications. Those with heart problems should wear a medical alert bracelet and to go to the emergency room if they experience chest, back, or abdominal pain. Some heart valve problems can be managed with drugs, such as beta-blocker, that may help decrease stress on the aorta. However, surgery to replace a valve or repair the aorta may be necessary.

CYTOKINE STORM and the INFLUENZA PANDEMIC

2009-04-10T16:48:00.004+07:00

Angela L. Petrosino, MPH, CHES (Northwest Ohio Consortium for Public Health)

A cytokine storm is the systemic expression of a healthy and vigorous immune system resulting in the release of more than 150 inflammatory mediators (cytokines, oxygen free radicals, and coagulation factors). Both pro-inflammatory cytokines (such as Tumor Necrosis Factor-alpha, InterLeukin-1, and InterLeukin-6) and anti-inflammatory cytokines (such as interleukin 10, and interleukin 1 receptor antagonist) are elevated in the serum, and the fierce and often lethal interplay of these cytokines is referred to as a "Cytokine Storm". The primary contributors to the cytokine storm are TNF-a (Tumor Necrosis Factor-alpha) and IL-6 (Interleukin-6). The cytokine storm is an inappropriate (exaggerated) immune response that is caused by rapidly proliferating and highly activated T-cells or natural killer (NK) cells. These cells are themselves activated by infected macrophages. The cytokine storm must be treated and suppressed or lethality can result.

Treating the Cytokine Storm of Avian Influenza, the Premise of this Website:
1. Bird flu patients die from acute respiratory distress syndrome (ARDS) caused by the cytokine storm, and not directly from the virus. Historic survival in ARDS is 60%-85%; with bird flu-associated ARDS it is 43%.
2. Neuraminidase inhibitors (i.e. Tamiflu, Relenza) are not clinically proven effective for bird flu patients and cannot address the lethal cytokine storm associated with the infection.
3. The treatment to prevent or stop the autoimmune reaction (cytokine storm) is commercially available by prescription, but is not currently being recommended by the World Health Organization to treat these patients.

Acute respiratory viral infection (especially from the H5N1 subtype influenza virus) results in a cytokine storm effecting the lungs, and subsequent damage to alveoli and lung tissue results in the lethality seen in more severe flu viral infections, especially those fatalities among young healthy adults.
H5N1 Virus

In the absence of prompt medical intervention to stop the "cytokine storm", the lung will suffer permanent damage. Many of these patients will develop acute respiratory distress syndrome (ARDS), i.e. will present with pulmonary edema that is not caused by volume overload, or a depressed left ventricular function. Deaths will usually result from multisystem organ failure, and not from lung failure.

Proposed Mechanism of the Cytokine Storm Evoked by Influenza virus.
Osterholm. New England Journal of Medicine, 352 (18): 1839, Figure 3. May 5, 2005
Animation of chart above on NEJM.org

Sepsis and cytokine storm
Sepsis is a severe systemic inflammatory response and is one example of a pathologic condition associated with "cytokine storm". Sepsis is an often lethal hemodynamic collapse which is usually the result of a super infection by gram-negative bacterial endotoxins. Sepsis is also classified as septic shock syndrome (SSS).

Cytokine storm can also result from viral infections such as influenza, and an exaggerated systemic immune response to that particular viral infection (designated a type A, subtype "H1N1" virus) may have been the cause of high lethality seen in the influenza pandemic of 1918 to 1919. The great influenza pandemic was the most destructive pandemic in recorded world history, and killed more people (estimated between 20 to 50 million) than all casualties resulting from the first World War. Although the Spanish Flu pandemic affected an enormous percentage of the world wide population (up to 20% of the world population according to some sources), and killed between 20 and 50 million persons, no more than 5% of the people who contracted the Spanish Flu died (Brown et. al reported the highest death rate in India at 50 deaths per 1000 persons contracting the disease, or a five percent fatality rate). After 218 human cases of bird flu have been confirmed world-wide (as of May, 2006) the lethality rate stands at 57%. Should this strain develop into a pandemic, and should it keep its current mortality rate, it has the potential to be 10 times more lethal than the 1918 pandemic.

Influenza A, The most lethal influenza and the precursor of all Pandemic Viruses

Influenza viruses responsible for causing pandemics are influenza type A viruses which emerge as a result of a process called "antigenic shift”. Antigenic shift causes an abrupt or sudden, major change in certain proteins on the surface of the influenza A virus (specifically the hemagglutinin or “HA” protein and the neuraminidase or the “NA” protein).Certain antigenic shifts may allow the virus to become more easily transmissible, more "contagious". Once this type of shift occurs, wide-spread infection usually follows quickly. Antigenic shift is most dangerous when it occurs in a virus that has demonstrated high lethality, such as the H5N1 bird flu.

Electron Micrograph of the H5N1 Bird Flu Virus

History has recorded 10 pandemics of influenza A in the past 300 years. The sudden appearance of new influenza A virus subtypes during the 20th century has caused three pandemics, all of which spread world-wide within 1 year of first being detected.

Tamiflu and Relenza have not been effective in patients with cytokine storm, and have not been tested in patients with bird flu. Prescription Angiotension Blockers may be beneficial in treating Bird Flu, and the cytokine storm which has proven lethal in over half of the patients who have contracted the avian flu to date. This book is a must read for those wanting to be prepared to treat a patient with avian influenza: Prescription Angiotension Blockers and their use in treating Bird Flu.

1918-19, "Spanish flu," [Type A, subtype (H1N1)], caused the highest number of known influenza deaths: more than one-half million people died within the United States (nearly half of the deaths were young healthy adults aged 20-40), and between 50 and 100 million people may have died worldwide. Most deaths occurred within the first few days after infection, some deaths within hours of symptom onset, and other deaths occurred later as a result of complications. Influenza A (H1N1) viruses still circulate today after having been reintroduced in the 1970s. Although called the "Spanish Flu" because the first widely reported deaths were in Spain, it probably originated in China.

1957-58, "Asian flu," [Type A, subtype (H2N2)], caused about 70,000 deaths in the United States. The "asian flu" was initially identified in China in late February 1957. Three months later, it spread to the United States with early reports of infection as early as June 1957.
1968-69, " Hong Kong flu," [Type A subtype (H3N2)], was responsible for about 34,000 deaths in the United States. The "Hong Kong flu" virus was first detected in Hong Kong in early 1968 and spread to the United States within a few months. Influenza A (H3N2) viruses still circulate today.

The Bird Flu
Both the 1957-58 and 1968-69 pandemics were caused by viruses containing a combination of genes from a human influenza virus and an avian influenza virus. The origin of the 1918-19 pandemic virus is not clear, but if its origin was in China as suspected, it could have similarly been caused by a genetic recombination of human and avian influenza viruses. This can more easily occur if humans are in close proximity to both live birds and pigs, as can occur in public markets in Asia. Osterholm reports the last influenza pandemic (1968) occurred 37 years ago, emerging in China. At that time China's human population was 790 million, its pig population was 5.2 million, and its poultry population was 12.3 million. Today, these populations number 1.3 billion, 508 million, and 13 billion, respectively. The human and animal populations of other Asian countries have similarly increased exponentially, which has increased the chances for close contact between birds, pigs and humans in these countries, creating optimal conditions for the emergence of new viruses, such as the H5N1 subtype.

On August 12, 2004, the Vietnamese Ministry of Health reported three confirmed human deaths to the World Health Organization (WHO) from confirmed avian influenza H5 infection. If the virus is confirmed to belong to the same H5N1 strain that caused 22 cases (15 deaths) in Vietnam and 12 cases (8 deaths) in Thailand earlier this year, and human-to-human contact versus human to bird or human-to-swine contact is suspected, this may indicate that H5N1 has adapted to the point that it is transmissible and has the potential to cause the next pandemic.

How do physicians rate our preparedness to handle the potential H5N1 pandemic? This MDLinx survey is telling.

SYMPTOMS OF BIRD FLU (H5N1):
Initial Presentaion of Influenza A (H5N1) Avian Influenza:
* Pulmonary: Radiographically confirmed pneumonia, acute respiratory distress syndrome (ARDS), or other severe respiratory illness for which an alternate diagnosis cannot be established
* One or more of the following: cough and/or sore throat and/or shortness of breath, AND a history of contact with poultry (e.g., visited a poultry farm, a household raising poultry, or a bird market) or contact with a known or suspected human case of influenza A (H5N1) in an H5N1-affected country within 10 days of symptom onset.
* Dyspnea
* Fever (temperature of >38°C or >100.4°F)

SYMPTOMS OF THE CYTOKINE STORM:
The end stage, or final result, of cytokine storm (SIRS) or sepsis is multiple organ dysfunction syndrome (MODS). The end-stage symptoms of the bird flu, or other infection precipitating the cytokine storm may include:

* hypotension
* tachycardia
* dyspnea
* fever (temperature of >38°C or >100.4°F)
* Ischemia, or insufficient tissue perfusion (especially involving the major organs)
* uncontrollable hemorrhage
* and multisystem organ failure (caused primarily by hypoxia, tissue acidosis, and severe metabolism dysregulation

Oxygen free radicals, histamine, complement factor C5a, Beta-endorphin, thromboxane B2, and platelet activating factor are implicated in SSS. The major pro-inflammatory cytokines which are implicated in SSS are TNF-alpha, IL1, IL6 and IL8. Serum TNF alpha concentrations in excess of 1 ng/mL are frequently predictive of a lethal outcome, however serum concentrations of other inflammatory cytokines involved in the pathophysiology of Septic shock are usually not reliable predictors of the severity of the shock state or clinical outcome. These cytokines are released by macrophages following activation by bacterial endotoxins.

Preventing and/or treating the cytokine storm associated with influenza with antiviral medications, prescription medications and vaccines that are approved (or may soon be approved) by the U.S. Food and Drug Administration (FDA):

* Acambis Biotechnology Vaccine: Acambis announced on August 4, 2005 that it has entered into collaboration with a Belgian research centre to develop a single-dose flu vaccine that could offer permanent protection against all strains of both influenza A and influenza B, potentially offering protection against future influenza pandemics.
* ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) have proven to be beneficial in treating the cytokine storm (the major cause of lethality in Bird Flu). PUBMED: The cytomine storm and the renin-angiotensin-aldosterone system. More information is found on ACE inhibitors and the Bird Flu in this e-book.
* Amantadine (Brand name Symmetrel: Treatment of influenza type A-2, but not type B). This drug cannot treat the cytokine storm associated with avian influenza, and has not been tested in patients with the bird flu.
* Aventis Vaccine: Preliminary research suggests the influenza A vaccine developed by Sanofi-Aventis is effective against H5N1 avian flu virus. The NIH (US National Institutes of Health) reported on August 5, 2005 (New York Times) that preliminary tests have confirmed that an experimental vaccine in development by Sanofi-Aventis Pharmaceutical Company appears to be effective in preventing infection with the bird flu (avian influenza virus). Researchers believe that the avian influenza virus, an influenza type-A, subtype H5N1, could trigger the next worldwide flu pandemic.
* Oseltamivir (Brand name Tamiflu: a neuraminidase inhibitor for treatment or prevention of both influenza type A and B, indicated for use within 2 days of symptoms). This drug cannot treat the cytokine storm associated with avian influenza, and has not been tested in patients with the bird flu. Most of the avian flu victims in SE Asia and Turkey received Tamiflu, and still suffered mortality rates exceeding 50%. Tamiflu has been declared "ineffective" against the bird flu by a physician who has personally used the drug to treat 41 bird flu patients (19% of all reported cases to date).
* Prednisone and corticosteroids: Treatment of active disease may involve the use of corticosteroids .
* Rimantadine (Brand name Flumadine: Treatment of influenza type A, but not B). This drug cannot treat the cytokine storm associated with avian influenza, and has not been tested in patients with the bird flu.
*Zanamivir (Brand name Relenza: a neuraminidase inhibitor for treatment of both influenza type A and type B, indicated for use within 2 days of symptoms). This drug cannot treat the cytokine storm associated with avian influenza, and has not been tested in patients with the bird flu. Most of the avian flu victims in SE Asia and Turkey received Tamiflu (a drug similar to Relenza), and still suffered mortality rates exceeding 50%.

Drug-resistance may occur in about one-third of patients taking amantadine or rimantadine. Additionally influenza A and B viruses could develop resistance to zanamivir and oseltamivir based on laboratory studies of the drugs.

Influenza A virus subtype H5N1

2009-04-10T16:05:00.006+07:00

Influenza A virus subtype H5N1, also known as "bird flu," A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu, commonly known as "avian influenza" or "bird flu". It is enzootic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic (an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Most references to "bird flu" and H5N1 in the popular media refer to this strain.

According to the FAO Avian Influenza Disease Emergency Situation Update, H5N1 pathogenicity is continuing to gradually rise in wild birds in endemic areas but the avian influenza disease situation in farmed birds is being held in check by vaccination. Eleven outbreaks of H5N1 were reported worldwide in June 2008 in five countries (China, Egypt, Indonesia, Pakistan and Vietnam) compared to 65 outbreaks in June 2006 and 55 in June 2007. The "global HPAI situation can be said to have improved markedly in the first half of 2008 cases of HPAI are still underestimated and underreported in many countries because of limitations in country disease surveillance systems".

Overview
HPAI A(H5N1) is an avian disease. There is some evidence of limited human-to-human transmission of the virus. A risk factor for contracting the virus is handling of infected poultry, but transmission of the virus from infected birds to humans is inefficient. Still, around 60% of humans known to have been infected with the current Asian strain of HPAI A(H5N1) have died from it, and H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. In 2003, world-renowned virologist Robert Webster published an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in American Scientist. He called for adequate resources to fight what he sees as a major world threat to possibly billions of lives. On September 29, 2005, David Nabarro, the newly-appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill anywhere between 5 million and 150 million people. Experts have identified key events (creating new clades, infecting new species, spreading to new areas) marking the progression of an avian flu virus towards becoming pandemic, and many of those key events have occurred more rapidly than expected.

Due to the high lethality and virulence of HPAI A(H5N1), its endemic presence, its increasingly large host reservoir, and its significant ongoing mutations, the H5N1 virus is the world's largest current pandemic threat, and billions of dollars are being spent researching H5N1 and preparing for a potential influenza pandemic. At least 12 companies and 17 governments are developing pre-pandemic influenza vaccines in 28 different clinical trials that, if successful, could turn a deadly pandemic infection into a nondeadly one. Full-scale production of a vaccine that could prevent any illness at all from the strain would require at least three months after the virus's emergence to begin, but it is hoped that vaccine production could increase until one billion doses were produced by one year after the initial identification of the virus.

H5N1 may cause more than one influenza pandemic as it is expected to continue mutating in birds regardless of whether humans develop herd immunity to a future pandemic strain. Influenza pandemics from its genetic offspring may include influenza A virus subtypes other than H5N1. While genetic analysis of the H5N1 virus shows that influenza pandemics from its genetic offspring can easily be far more lethal than the Spanish Flu pandemic, planning for a future influenza pandemic is based on what can be done and there is no higher Pandemic Severity Index level than a Category 5 pandemic which, roughly speaking, is any pandemic as bad as the Spanish flu or worse; and for which all intervention measures are to be used.

Genetics
The first known strain of HPAI A(H5N1) (called A/chicken/Scotland/59) killed two flocks of chickens in Scotland in 1959; but that strain was very different from the current highly pathogenic strain of H5N1. The dominant strain of HPAI A(H5N1) in 2004 evolved from 1999 to 2002 creating the Z genotype. It has also been called "Asian lineage HPAI A(H5N1)".

Asian lineage HPAI A(H5N1) is divided into two antigenic clades. "Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections:

* Subclade 1, Indonesia
* Subclade 2, Europe, Middle East, and Africa (called EMA)
* Subclade 3, China"

A 2007 study focused on the EMA subclade has shed further light on the EMA mutations. "The 36 new isolates reported here greatly expand the amount of whole-genome sequence data available from recent avian influenza (H5N1) isolates. Before our project, GenBank contained only 5 other complete genomes from Europe for the 2004–2006 period, and it contained no whole genomes from the Middle East or northern Africa. Our analysis showed several new findings. First, all European, Middle Eastern, and African samples fall into a clade that is distinct from other contemporary Asian clades, all of which share common ancestry with the original 1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show a consistent picture of 3 lineages, as illustrated by the HA tree shown in Figure 1. Two of the clades contain exclusively Vietnamese isolates; the smaller of these, with 5 isolates, we label V1; the larger clade, with 9 isolates, is V2. The remaining 22 isolates all fall into a third, clearly distinct clade, labeled EMA, which comprises samples from Europe, the Middle East, and Africa. Trees for the other 7 segments display a similar topology, with clades V1, V2, and EMA clearly separated in each case. Analyses of all available complete influenza (H5N1) genomes and of 589 HA sequences placed the EMA clade as distinct from the major clades circulating in People's Republic of China, Indonesia, and Southeast Asia.

Terminology
H5N1 isolates are identified like this actual HPAI A(H5N1) example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1):

* A stands for the species of influenza (A, B or C).
* chicken is the species the isolate was found in
* Nakorn-Patom/Thailand is the place this specific virus was isolated
* CU-K2 identifies it from other influenza viruses isolated at the same place
* 04 represents the year 2004
* H5 stands for the fifth of several known types of the protein hemagglutinin.
* N1 stands for the first of several known types of the protein neuraminidase.

(Other examples: A/duck/Hong Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and A/shoveler/Egypt/03(H5N2)).

As with other avian flu viruses, H5N1 has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent, and mortality rates in infected flocks often approach 100%. LPAI viruses have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. The current strain of H5N1 responsible for the deaths of birds across the world is an HPAI strain; all other current strains of H5N1, including a North American strain that causes no disease at all in any species, are LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally a highly pathogenic avian virus is not highly pathogenic to either humans or non-poultry birds. This current deadly strain of H5N1 is unusual in being deadly to so many species, including some, like domestic cats, never previously susceptible to any influenza virus.

Genetic structure and related subtypes

H5N1 is a subtype of the species Influenza A virus of the Influenzavirus A genus of the Orthomyxoviridae family. Like all other influenza A subtypes, the H5N1 subtype is an RNA virus. It has a segmented genome of eight negative sense, single-strands of RNA, abbreviated as PB2, PB1, PA, HA, NP, NA, MP and NS.

HA codes for hemagglutinin, an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. NA codes for neuraminidase, an antigenic glycosylated enzyme found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells. The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies. HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the H and N come from in H5N1.

Influenza A viruses are significant for their potential for disease and death in humans and other animals. Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include:

* H1N1, which caused "Spanish flu" and currently causes seasonal human flu
* H2N2, which caused "Asian flu"
* H3N2, which caused "Hong Kong flu" and currently causes seasonal human flu
* H5N1, the world's major current pandemic threat
* H7N7, which has unusual zoonotic potential and killed one person
* H1N2, which is currently endemic in humans and pigs and causes seasonal human flu
* H9N2, which has infected three people
* H7N2, which has infected two people
* H7N3, which has infected two people
* H10N7, which has infected two people

Low pathogenic H5N1
Low pathogenic avian influenza H5N1 (LPAI H5N1) also called "North American" H5N1 commonly occurs in wild birds. In most cases, it causes minor sickness or no noticeable signs of disease in birds. It is not known to affect humans at all. The only concern about it is that it is possible for it to be transmitted to poultry and in poultry mutate into a highly pathogenic strain.

* 1975 – LPAI H5N1 was detected in a wild mallard duck and a wild blue goose in Wisconsin.
* 1981 and 1985 – LPAI H5N1 was detected in ducks by the University of Minnesota conducting a sampling procedure in which sentinel ducks were monitored in cages placed in the wild for a short period of time.
* 1983 – LPAI H5N1 was detected in ring-billed gulls in Pennsylvania.
* 1986 - LPAI H5N1 was detected in a wild mallard duck in Ohio.
* 2005 - LPAI H5N1 was detected in ducks in Manitoba, Canada.
* 2008 - LPAI H5N1 was detected in ducks in New Zealand.
* 2009 - LPAI H5N1 was detected in commercial poultry in British Columbia.

"In the past, there was no requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so states and universities tested wild bird samples independently of USDA. Because of this, the above list of previous detections might not be all inclusive of past LPAI H5N1 detections. However, the World Organization for Animal Health (OIE) recently changed its requirement of reporting detections of avian influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be reported to the OIE because of their potential to mutate into highly pathogenic strains. Therefore, USDA now tracks these detections in wild birds, backyard flocks, commercial flocks and live bird markets.

Properties of H5N1
Infectivity
H5N1 is easily transmissible between birds facilitating a potential global spread of H5N1. While H5N1 undergoes mutation and reassortment, creating variations which can infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1 as an avian virus preferentially binds to a type of galactose receptors that populate the avian respiratory tract from the nose to the lungs and are virtually absent in humans, occurring only in and around the alveoli, structures deep in the lungs where oxygen is passed to the blood. Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission.

H5N1 is mainly spread by domestic poultry, both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migrating waterfowl (wild ducks, geese and swans) carry H5N1, often without becoming sick. Many species of birds and mammals can be infected with HPAI A(H5N1), but the role of animals other than poultry and waterfowl as disease-spreading hosts is unknown.

According to a report by the World Health Organization, H5N1 may be spread indirectly. The report stated that the virus may sometimes stick to surfaces or get kicked up in fertilizer dust to infect people.

Virulence
H5N1 has mutated into a variety of strains with differing pathogenic profiles, some pathogenic to one species but not others, some pathogenic to multiple species. Each specific known genetic variation is traceable to a virus isolate of a specific case of infection. Through antigenic drift, H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all currently belonging to genotype Z of avian influenza virus H5N1, now the dominant genotype. H5N1 isolates found in Hong Kong in 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002 new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death in ducks. This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961. Genotype Z emerged in 2002 through reassortment from earlier highly pathogenic genotypes of H5N1 that first infected birds in China in 1996, and first infected humans in Hong Kong in 1997. Genotype Z is endemic in birds in Southeast Asia, has created at least two clades that can infect humans, and is spreading across the globe in bird populations. Mutations are occurring within this genotype that are increasing their pathogenicity. Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.

Transmission and host range

Infected birds transmit H5N1 through their saliva, nasal secretions, feces and blood. Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. H5N1 remains infectious after over 30 days at 0 °C ( 32.0 °F) (over one month at freezing temperature) or 6 days at 37 °C ( 98.6 °F) (one week at human body temperature) so at ordinary temperatures it lasts in the environment for weeks. In Arctic temperatures, it doesn't degrade at all.

Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry.

In October 2004, researchers discovered that H5N1 is far more dangerous than was previously believed. Waterfowl were revealed to be directly spreading the highly pathogenic strain of H5N1 to chickens, crows, pigeons, and other birds, and the virus was increasing its ability to infect mammals as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic.

"Since 1997, studies of influenza A (H5N1) indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability."

The New York Times, in an article on transmission of H5N1 through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important".

The H5N1 bird flu virus can also pass through a pregnant woman's placenta to infect the fetus, researchers reported on Thursday 27 September 2007. They also found evidence of what doctors had long suspected that the virus not only affects the lungs, but also passes throughout the body into the gastrointestinal tract, the brain, liver, and blood cells.

High mutation rate
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different influenza viruses at the same time. A previously uncontagious strain may then be able to pass between humans, one of several possible paths to a pandemic.

The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. This doesn't mean that one amino acid substitution can cause a pandemic, but it does mean that one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans.

H3N2 ("swine flu") is endemic in pigs in China, and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. The dominant strain of annual flu virus in January 2006 was H3N2, which is now resistant to the standard antiviral drugs amantadine and rimantadine. The possibility of H5N1 and H3N2 exchanging genes through reassortment is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of H3N2.

Both the H2N2 and H3N2 pandemic strains contained avian influenza virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source".

Symptoms in humans
Avian influenza hemagglutinin bind alpha 2-3 sialic acid receptors while human influenza hemagglutinin bind alpha 2-6 sialic acid receptors. Usually other differences also exist. There is as yet no human form of H5N1, so all humans who have caught it so far have caught avian H5N1.

In general, humans who catch a humanized Influenza A virus (a human flu virus of type A) usually have symptoms that include fever, cough, sore throat, muscle aches, conjunctivitis, and, in severe cases, breathing problems and pneumonia that may be fatal. The severity of the infection depends to a large part on the state of the infected person's immune system and whether the victim has been exposed to the strain before (in which case they would be partially immune). No one knows if these or other symptoms will be the symptoms of a humanized H5N1 flu.

The reported mortality rate of highly pathogenic H5N1 avian influenza in a human is high; WHO data indicates that 60% of cases classified as H5N1 resulted in death. However, there is some evidence that the actual mortality rate of avian flu could be much lower, as there may be many people with a milder symptoms who do not seek treatment and are not counted.

In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. There have been studies of the levels of cytokines in humans infected by the H5N1 flu virus. Of particular concern is elevated levels of tumor necrosis factor-alpha, a protein that is associated with tissue destruction at sites of infection and increased production of other cytokines. Flu virus-induced increases in the level of cytokines is also associated with flu symptoms including fever, chills, vomiting and headache. Tissue damage associated with pathogenic flu virus infection can ultimately result in death. The inflammatory cascade triggered by H5N1 has been called a 'cytokine storm' by some, because of what seems to be a positive feedback process of damage to the body resulting from immune system stimulation. H5N1 induces higher levels of cytokines than the more common flu virus types.

Treatment and prevention for humans
There is no highly effective treatment for H5N1 flu, but oseltamivir (commercially marketed by Roche as Tamiflu), can sometimes inhibit the influenza virus from spreading inside the user's body. This drug has become a focus for some governments and organizations trying to prepare for a possible H5N1 pandemic. On April 20, 2006, Roche AG announced that a stockpile of three million treatment courses of Tamiflu is waiting at the disposal of the World Health Organization to be used in case of a flu pandemic; separately Roche donated two million courses to the WHO for use in developing nations that may be affected by such a pandemic but lack the ability to purchase large quantities of the drug.

However, WHO expert Hassan al-Bushra has said:

"Even now, we remain unsure about Tamiflu's real effectiveness. As for a vaccine, work cannot start on it until the emergence of a new virus, and we predict it would take six to nine months to develop it. For the moment, we cannot by any means count on a potential vaccine to prevent the spread of a contagious influenza virus, whose various precedents in the past 90 years have been highly pathogenic".

There are several H5N1 vaccines for several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use to date: while vaccines can sometimes provide cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Dr. Daniel Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine". However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.

Animal and lab studies suggest that Relenza (zanamivir), which is in the same class of drugs as Tamiflu, may also be effective against H5N1. In a study performed on mice in 2000, "zanamivir was shown to be efficacious in treating avian influenza viruses H9N2, H6N1, and H5N1 transmissible to mammals".[49] While no one knows if zanamivir will be useful or not on a yet to exist pandemic strain of H5N1, it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic. Neither oseltamivir nor zanamivir can currently be manufactured in quantities that would be meaningful once efficient human transmission starts.

In September, 2006, a WHO scientist announced that studies had confirmed cases of H5N1 strains resistant to Tamiflu and Amantadine. Tamiflu-resistant strains have also appeared in the EU, which remain sensitive to Relenza.

wikipedia

Pandemic Flu

2009-04-07T15:03:00.001+07:00

The 1918 Spanish flu epidemic was caused by an influenza A (H1N1) virus, killing more than 500,000 people in the United States, and up to 50 million worldwide. The possible source was a newly emerged virus from a swine or an avian host of a mutated H1N1 virus. Many people died within the first few days after infection, and others died of complications later. Nearly half of those who died were young, healthy adults. Photo courtesy of the National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, D.C., Image NCP 1603

Pandemic Flu
Pandemic flu is a global outbreak of disease that occurs when a new influenza A virus appears or “emerges” in the human population, causes serious illness and then spreads easily from person to person worldwide. Past influenza pandemics have led to high levels of illness, death, social disruptions and economic loss.

For a flu pandemic to occur, three conditions must be met:

1. An new influenza A virus appears or “emerges” in the human population
2. The new virus must cause serious illness in people
3. The new virus is spread easily from person to person worldwide

Many scientists believe that avian influenza will develop into the next pandemic. Currently, avian influenza meets the first two criteria for being a pandemic. Avian influenza does not spread easily from person to person.

However, with every new case of avian influenza in humans it becomes more likely that avian influenza will change into a virus that is easily spread between humans and would then be considered a pandemic.

source:vaccine4me.com

Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States

2009-04-07T14:58:00.001+07:00

Nila J. Dharan, MD; Larisa V. Gubareva, PhD; John J. Meyer, MPH; Margaret Okomo-Adhiambo, PhD; Reginald C. McClinton, MPH; Steven A. Marshall, MS; Kirsten St. George, MAppSc, PhD; Scott Epperson, MPH; Lynnette Brammer, MPH; Alexander I. Klimov, PhD; Joseph S. Bresee, MD; Alicia M. Fry, MD, MPH; for the Oseltamivir-Resistance Working Group.

Context During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season.

Objectives To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes.

Design, Setting, and Patients Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008.

Main Outcome Measures Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes.

Results During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested.

Conclusions Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.

Author Affiliations: Epidemic Intelligence Service, Office of Workforce and Career Development Assigned to Influenza Division (Dr Dharan), and Influenza Division (Drs Gubareva, Okomo-Adhiambo, Klimov, Bresee, and Fry and Ms Brammer and Mr Epperson), Centers for Disease Control and Prevention, Atlanta, Georgia; Arizona Department of Health Services, Phoenix (Mr Meyer); Wyoming Department of Health, Cheyenne (Mr McClinton); Wisconsin State Laboratory of Hygiene, Madison (Mr Marshall); and Wadsworth Center, New York State Department of Health, Albany (Dr St. George).

source:jama.ama-assn.org

H1N1 influenza as Lazarus: Genomic resurrection from the tomb of an unknown

2009-04-07T14:44:00.001+07:00

Figure 1 Diagram of an influenza-virus particle. The surface of each influenza virion consists of a lipid envelope in which two major viral surface antigens, the hemagglutinin (HA) and the neuraminidase (NA), are found. Within the particle are the eight negative-sense viral RNA segments encoding the viral proteins. The smallest viral segment, the NS segment, encodes two proteins: the NS1, an antagonist of the cellular type I interferon system, and the nuclear export protein (NEP), which functions in viral assembly.

The 1918–1919 pandemic of H1N1 virus influenza was the greatest acute plague of the 20th century. Incurring over 20 million human fatalities, however, was not a good strategy for sustaining the evolutionary fitness of the virus, because it is no longer extant; whereas, say, measles and chickenpox remain with us with no evidence of remarkable genetic change, although this may become more evident if they were to face total or near eradication through vaccination programs. The folly of flu virulence remains our chagrin, because the threat always looms over us that this family of viruses, endemic in birds, again may generate human-lethal gene reassortments. We had valid scares about that contingency with the appearance of H5N1 variant flu in Hong Kong just 3 years ago. Influenza can be regarded as a zoonosis prevalent in birds, many of them world travelers, with occasional outbreaks in humans and other animals mainly rooted in nature's own experiments in genetic engineering. Special importance is attached to reassortments between bird- and human-adapted strains most likely to occur in habitats with close contact between birds, e.g., ducks, humans, and swine (as a mixing reservoir; ref. 1). For these reasons, high urgency attaches to efforts to resurrect genetic information about the singularities of H1N1–1918. The intact virus is nowhere to be found, but genomic fragments can still be detected sensitively and diagnosed. Exemplifying the latest technical advances in the use of DNA amplification, reverse-transcriptase–PCR (RT-PCR), Jeffery Taubenberger and his associates at the Armed Forces Institute of Pathology initiated the tour de force of recovering sequences of flu from paraffin-embedded pathological specimens preserved since 1918 in the AFIP collections (2). These sources then were augmented by samples from frozen remains of an Inuit woman who succumbed to the flu in 1918 and was buried in permafrost at Brevig Mission on the Seward Peninsula of Alaska's western coast, not far from the Bering Strait. This nameless woman has left an indelible mark on world medical history (3). Now, as reported in this issue, the AFIP team has joined forces with teams from the U.S. Department of Agriculture and the Peter Palese/Adolfo García-Sastre groups at Mt. Sinai Medical School in a further quest for the RNA sequences of H1N1–1918 that might account for its historic human virulence (4).

The flu genome comprises about 13,500 bases of single-stranded RNA, disposed in eight segments varying from approximately 900 to 2,341 each. This genome is only a few millionths of the complexity of the human genome, but it is organized with great efficiency, lacks “junk R/DNA,” and encodes for a short dozen of identified gene products (Fig. 1). Many strains of flu have been sequenced fully; this feat will be achieved for H1N1–1918 with arduous labor, because the RNA, although frozen, is fragmented into snippets no larger than approximately 120 bases each. The practical way now available is to devise probes by using segments from extant flu strains, guessing at possible homologous strings, or synthesizing probes with calculated degeneracy. Until a complete genomic sequence is achieved, and it is hard to see how that will be authenticated, it is possible even that H1N1–1918 contains extraneous inserted sequences quite foreign to the canonical flu strains. Very reasonably, initial efforts focus on flu genes already identified in viruses recovered from recent outbreaks in humans, birds, swine, and other animals.

Previous work has focused on two well studied gene products: hemagglutinin (HA) and neuraminidase (NA), which dominate the surface specificities of the virus and underlie most of its taxonomy (e.g., H1N1 refers to type 1 hemagglutinin, type 1 neuraminidase). These gene products are also the chief determinants of specificity in vaccine prophylaxis for flu strains circulating at any given time. HA variation can account for fluctuations of virulence and host specificity of extant flu viruses. However, nothing remarkable was seen in the HA or the NA of H1N1–1918. The next gene to be scrutinized now is NS1 (nonstructural protein 1), which the Palese/García-Sastre groups have fingered recently as an interferon antagonist and as gene essential for flu virulence in a mouse model. A reasonable conjecture was that the hypervirulence of H1N1–1918 might be lodged in its NS1, and this might be revealed in reinsertions of the 1918-NS1 segment into mouse-adapted flu strains. This challenging construct was generated in the laboratory—one hastens to footnote, under BL-3+ conditions, and under the USDA's stern regulatory scrutiny—and tested in mice. The unexpected and perhaps disappointing result was the mitigation not enhancement of virulence in this species. The incapacitation of the NS1-virulence function in the mouse was ascribed to interaction with its host factors; the other variable would be other elements of the genome of the mouse-adapted flu strain. NS1 singularity for the human virulence of H1N1–1918 is neither falsified nor corroborated by these findings.

There still remain a handful of gene candidates, including the polymerases essential for the replication of the virus. This label does not preclude any of them from also functioning in networks and pathways that are expressed as virulence. It should caution us about the nominalist fallacy to recall that the δ crystallin of the bird's lens does double duty as argininosuccinate lyase, an enzyme in the urea cycle.

In principle, the NS1 hypothesis (and its alternatives) might be tested by using similar gene constructs based on flu viruses adapted to other animal species, including primates, and challenging the corresponding hosts. Negative results would be as inconclusive as those with the mouse. Positive results, namely the association of hypervirulence with a gene sequence borrowed from N1H1–1918, would be a great advance in medical science and would offer constructive models for the development of prophylactic and therapeutic measures. They would also induce great alarm about the potential hazards to human health, if humans were also susceptible, and the virus might escape. Any such experiments should be done with strains for which current vaccines are disseminated widely and have proven effectiveness.

To conduct such experiments with human-adapted strains and challenge to human subjects as the probative step, is well nigh unthinkable. But nature is under no such restraint! The current results are a caution to look closely at the involvement of NS1 (as well as HA and NA) variation in natural outbreaks in many species and to look out for their reassortment into human strains. In addition, it might be well to undertake a special search for close homologues to 1918-NS1 in viruses circulating in avian and other species, in which they may appear to be benign in their current hosts (as in the present mouse experiments). That would be nature's inverse of the current report.

The publication by Basler et al. (4) will attract great admiration for its technical finesse and will serve as an example of the fruits from convergence of natural history, field exploration, clinical insight, and sophisticated molecular wizardry. It also will awaken anxieties about the obvious opportunities for abuse. The really fateful step was taken with the very first cultivation of pathogenic bacteria and viruses a century ago—perhaps most importantly with the discovery of the concepts of germs and communicable diseases. The notion of using ever more sophisticated technology for intentionally constructing or reconstructing ever more pathogenic variants lends further weight to that anxiety. The great debate of the mid-1970s led to sensible measures for the regulation of recombinant DNA research. There has been increasing understanding that some of nature's pathogens deserve equal or greater respect. We should be sure that we continue to devote as much reasoned ingenuity to the design of safeguards and to informed and transparent third-party scrutiny of potential hazards as we do generally to the authentication of scientific claims. We cannot afford to forego the deepest research into the plagues that beset humankind. Nor can we afford to blunder into mistakes that will do primary injury to bystanders and incur incommensurate social sanctions.

My deepest anxieties pertain to the smoldering technology and arms race that attends the power struggles in the Middle East and the economic instabilities of the former Soviet Union. Although the 1975 Biological Weapons Convention (BWC) has demilitarized the main drivers of bioweaponry technical advance, in the U.S. and in the overt activities of other formidable powers, the BWC has not been enforced successfully against Iraq and is more or less openly flouted in a handful of other countries. The United Nations (UN) Security Council is too splintered on other issues to take a firm stand on the defiance by Iraq of the UN-mandated inspections. It would not be child's play for defiant small countries to adopt advanced biotechnology into their weapons programs. But we have seen that the climactic high-science successes in one decade become fodder for high-school projects in the next. Influenza is an unlikely candidate for rational weapons development, because new strains promptly embrace the world. But that logic is insufficient reason to neglect the contingency. More likely similar principles would be applied to more governable bioagents, but any bioagents in warfare are an affront and a threat to the entire human species. Informed professionals throughout the world should be leading campaigns to insist on universal compliance with the BWC as a major bulwark of human health and associating that with the most positive measures to apply advanced biotechnology in a constructive way for dealing with nature's continued scourges.

source:Joshua Lederberg

1918 Influenza A (H1N1) Fact Sheet

2009-04-07T14:36:00.001+07:00

Quick Facts
Agent Type: Virus
Lethality: Low
Transmission: Highly contagious
Treatment: Oseltamivir (Tamiflu), zanamivir (Relenza), amantadine, and rimantadine antivirals, vaccine
Status: Select Agent
Delivery: Inhalation

The Influenza Ward of the U.S. Army Camp Hospital in France, circa 1918 (Source: Armed Forces Institute of Pathology)

The "Spanish" flu pandemic of 1918 and 1919 caused the deaths of 20-50 million people worldwide including up to 675,000 in the U.S. While only about 1% of those infected with the virus died, it became one of the deadliest viruses ever known to man. The 1918 flu has been described as capable of sickening and killing a person on the same day. The virus is an H1N1 type A influenza. Symptoms of infection were similar to, but more severe than typical, seasonal flu. Viral pneumonia leading to acute respiratory distress was the primary cause of death. Recently, the virus was reconstituted from frozen tissue samples from a woman who died from the virus.

History: Unlike seasonal flu, where most deaths are seen in the elderly and children under 2-years-old, almost half of the deaths associated with the 1918 pandemic were in adults between 20 and 40-years-old. Scientists theorize that this could be because people over the age of 40 had previously been exposed to a similar flu that gave them some immunity. As the 1918 flu spread through the United States, public gatherings were reduced to prevent infections since doctors had no way to fight the infections.

However, the virus was able to cross the ocean with troops arriving to fight in Europe during World War I. Foreign troops soon became exposed to the virus and carried it back to their home countries starting new waves of infection.

Spanish Flu?: Although it is not known where the 1918 flu virus began infecting humans and transmitting from person-to-person, the U.S. experienced its first wave of illness in the spring of 1918. It was dubbed the “Spanish” flu because Spanish newspapers published many reports of the pandemic while publications from nations involved in the World War I refrained. Some scientists think the “Spanish” flu designation might have been in error because of reports of it cropping up outside of the region before it affected the Spanish population. It is still unclear where the virus and the pandemic originated.

Reconstituted Virus: When the 1918 flu disappeared, no samples of the virus were retained for scientific study. In 1997, however, scientists recovered fragments of the virus’s RNA genome from the preserved remains of infected people. The genome of the flu virus is composed of 8 RNA segments. Recently, scientists were able to remake 1918 flu using a technique called reverse genetics. They started by making DNA copies of the virus genome segments because DNA is easier to manipulate in the lab than RNA. Each of those copies was then placed into a larger piece of circular DNA called a plasmid. Those eight DNA circles are then put into an animal cell. The animal cell produces the proteins that correspond to the 8 segments which then form the flu virus. The technique also allows scientists to selectively manipulate individual parts of the virus when doing experiments.

Mechanism: Flu strains are named for the H and N proteins, hemagglutinin and neuraminidase, which stick out from the surface of the virus like spikes. These protein spikes allow influenza to infect and damage cells and are what the immune system recognizes. The hemagglutinin spike allows the virus to bind to and enter cells. After co-opting the cells molecular machinery to produce more viruses, the neuraminidase spike is used to escape the cell, destroying it in the process. The 1918 influenza is an H1N1 strain and research on the reconstituted virus shows that it was particularly infective and had the unusual property of being able to infect mice, which typical human influenza strains cannot.

Treatment: During the 1918 pandemic doctors did not have vaccines, antivirals, or antibiotics to treat or prevent infections and associated complications. Since then, four drugs have been developed to fight influenza infections; amantadine, rimantadine, oseltamivir (Tamiflu) and zanamivir (Relenza). Tamiflu and amantadine have both been shown to be effective against engineered viruses containing the parts of the 1918 flu and vaccines have also protected mice against viruses with some of the 1918 influenza components. However, it is still unclear whether drugs or vaccines would be effective against the fully reconstituted 1918 influenza virus. Currently, the U.S. only has 2.5 million doses of Tamiflu in its stockpile, raising concerns that we have not adequately prepared for a potential pandemic caused by avian H5N1 influenza.

How does AIDS effect the immune system?

2009-03-31T16:09:00.001+07:00

Have you ever wondered what the immune system actually is? This explains the main features of the immune system and what AIDS does to destroy it.

AIDS gets a lot of press. Most of us know that it affects the immune system, and that the name is short for Acquired Immune Deficiency Syndrome. Most of us probably also know that the immune system helps protect us from infection. But how many of us know what the immune system actually is, or how it works?

The fact is, the immune system is no one thing. You can't pinpoint any specific part of the body and say "That's the immune system." It is so complex, that no body of science yet fully understands exactly how it all works. So let's go through the key points of what we do know, in order to gain a better understanding of this strange condition called AIDS.

The biggest organ of your immune system is your skin. Does that surprise you? Remember that the microbes that cause infection, whether they are bacteria, viruses or fungi, are all invisible to the human eye. So although we are surrounded by millions of them every day, we can't see them. Your skin helps prevent all those microbes from gaining access to your body. Think of it as fortress walls with electric fencing – that's the immune function of your skin. Your mucous membranes also form part of this fortress that keeps the microbes out.

Of course, no fortress is impenetrable. You may have a cut on your skin, or a wound. And of course, there are doorways into your body through your nose and mouth. Fortunately, these have little burglar alarms that alert the immune system when an intruder tries to make an uninvited entry.

The immune system, of course, has to be very smart. It has to know which cells belong to the body, and which don't. It does this by looking for little markers called antigens. Think of antigens as being little uniforms. All the cells in your body wear the same uniform, even though they may have different functions. Microbes coming into the body have their own uniforms, which are usually very different. Maybe they're even dressed in civvies, who knows.

Guard cells patrol the body all the time. There are small, quick-footed, lightly armed guards called microphages ("little eaters") which patrol the bloodstream. There are also bigger, slower, better-armed guards called macrophages ("big eaters") which hang around the spleen and lymph nodes, waiting to be called. They also patrol the body tissues.

Microphages are cells with powerful digestive enzymes and antibacterial substances. When a microphage sees a foreign uniform, it rushes over with a baton, bangs the microbe over the head and then gobbles it up to get rid of it. They are always first at the scene of the crime, and call for reinforcements from more powerful immune cells. It's quite possible that the microbes may be more powerful than the microphages, in which case it's the microphage that gets shot before it can wield the baton. The macrophages arrive afterwards, to collect the evidence and destroy any microbes that may have escaped the microphage guards.

Both microphages and macrophages come from the bone marrow. But the bone marrow also makes stem cells, which move to different parts of the body. These include other important immune organs like the thymus gland, spleen, lymph nodes, tonsils, appendix and Peyer's patches in the intestinal wall. Once settled into the organ, the stem cells produce white blood cells called lymphocytes.

Cells produce more cells by dividing into two cells. The daughter cells divide again, and so the process continues. The stem cells that go into the thymus gland divide very quickly, to produce a large number of daughter cells, most of which don't survive. Those that do, then leave the thymus gland and travel between the other immune organs at will. But they never return to the thymus.

These particular cells, formed in the thymus gland, are called T-lymphocytes or T-cells. And they learn special skills in the thymus gland which are very useful in fighting off foreign microbes.

When a T-cell reaches the scene of a crime, three things can happen. The foreign microbe can either inactivate or kill the T-cell. If it kills all the T-cells, the body can't see the foreign uniform any more and the microbe can go where it likes.

The T-cells can also start dividing. This means there are more cells that recognise the foreign uniform, which in turn means that if any more of these uniforms try and get into the body, the body can respond quicker and better.

The third thing the T-cell can do is release cytokines. This is a bit like casting a magic spell which makes the macrophages in the area stronger and more powerful, so that they can hit the microbes faster and have more chance of devouring them.

T-cells make up about 70% of the lymphocytes in the body. The rest are B-lymphocytes, which never go to the thymus gland. They don't travel as easily as T-cells, and they have different skills, including the ability to make antibodies which inactivate foreign particles.

HIV targets mainly the T-cells, specifically those which have a special receptor called a CD4 receptor. The virus attaches onto that receptor so that it can take over the inside of the cell. So we have a virus which looks – and acts like – a CD4 T-cell.

During the first stage of infection with HIV, the virus will kill a number of T-cells as it infects them. The immune system will react to the infection, and the body will display all the symptoms of an immune response such as fever, headache, tender lymph nodes, and generally feeling unwell.

However, once the B-cells have formed antibodies, the spread of infection stabilises. The symptoms disappear, and nothing seems to happen for a few months to several years.

But think what happens in the meantime. The virus has not been destroyed, just stabilised. There are antibodies, but not enough. The virus can continue to spread, although at a much slower rate.

Now think what happens when a microbe breaches the skin and enters the bloodstream. The immune systems sends the T-cells to fight the new microbe. But some of these T-cells are infected with HIV. They've lost their magic spells, and can either die from a microbe attack, or start dividing to make more T-cells. Except that they start making more virus-infected T-cells, which will eventually succumb to the virus. As more and more T-cells die, the body is less able to recognise foreign uniforms.

As time passes, the number of CD4 T-cells slowly drops, and the amount of virus slowly increases until a critical level is reached. Then the number of CD4 T-cells plummets, and the amount of virus in the bloodstream shoots up. Without the T-cells, the immune system becomes virtually useless. The foreign uniforms can march in unchallenged. Even an army of 98 lb. weaklings can come in and create havoc. These diseases – caused by everyday, normally harmless microbes – are the ones that usually define the beginning of AIDS.

Scientists have now developed tests to measure the amount of CD4 T-cells and the amount of virus in the body. When the T-cells get too low, or the virus gets too high, they can adjust the HIV treatment to restore a measure of law and order in the body. When pharmaceutical companies test their new anti-HIV drugs, they measure the T-cells and amount of virus in order to measure exactly how effective their drug is.

As a result of understanding the immune system better, people infected with HIV are able to live longer, healthier, productive lives. New research is leading scientists to consider the possibilities of cell transplants. Perhaps one day, our understanding will grow to the point that we know how to rebuild a defective immune system completely.

HIV/AIDS

2009-03-31T15:52:00.001+07:00

AIDS (Acquired Immune Deficiency Syndrome) is caused by the Human Immunodeficiency Virus (HIV). In order for the virus to attack a person's immune system, it has to enter the bloodstream and there are three ways in which this may occur:

Through sexual intercourse - this includes both heterosexual and homosexual intercourse, although most infections in the developing world are transmitted heterosexually.
Directly into the bloodstream through use of contaminated blood or blood products, or sharing of intravenous drug-injecting equipment.
From mother to child - it is estimated that about one third of infants born to infected mothers will be infected. This may occur prior to birth across the placenta, during birth, or via breast milk.

The possible responses to the epidemic are well documented. Risk of sexual transmission can be reduced by use of condoms and/or cutting down on numbers of partners and treating other sexually transmitted infections. Blood and blood products can be made safer through screening of donors and their blood. Drug users can be encouraged to sterilise or exchange needles. Work on developing means of reducing mother to child infection is underway.

One of the crucial points that has to be made about the HIV/AIDS epidemic is that it is different from most other epidemics and diseases, and consequently requires a different and much broader response - one which must encompass far more than the health sector. The factors that make it unique are:

It is a new epidemic. AIDS was first recognised as a specific condition only in 1981 and it was not until 1984 that the cause (and a test to detect it) was identified.
It has a long incubation period. Persons who are infected by the virus may have many years of productive normal life, although they can infect others during this period. It is not certain how long this latent period is; estimates range from five to fifteen years, with the shorter period being found in the developing world, where people are less healthy and well nourished. It is known that good health and nutrition, and early treatment of opportunistic infections, will extend the period of healthy and productive life. Unfortunately infected children will, for the most part, die before their fifth birthdays.
The prognosis for people infected with HIV is bleak. At the end of the incubation period, a person will usually experience periods of sickness increasing in severity, duration and frequency, until he/she dies.
The disease is found mainly in two specific age groups: children under five, and adults aged between 20-40 years. For various reasons there seem, in the developing world, to be slightly more females than males infected, and women develop the disease at a younger age.
The scale of the epidemic is also different from most other diseases. As Table 1 shows, in some settings, up to 30 per cent of ante-natal clinic attendees are infected. This means that between 20-25 per cent of sexually active adults may be infected.
HIV is mainly sexually transmitted, which means it is passed on through one of the most fundamental human activities, but one with which we are neither open nor comfortable.
There are links between HIV and other diseases, most notably tuberculosis, which has further implications for public health.
In general, the epidemic is still spreading in the developing world, although there are signs that the level of infection may have peaked in some areas.

Table 1. HIV Prevalence, Selected Sites and Countries, Ante-natal Clinic Attenders (% HIV+)

	1991	1992	1993	1994	1995
Gwanda, Zimbabwe ^[1]	16	21	NA	25	NA
Nsambya, Uganda ^[2]	27.8	29.5	26.6	21.8	NA
Francistown, Botswana ^[3]	NA	23.7	34.2	29.7	39.6
KwaZulu-Natal, South Africa ^[4]	2.9	4.8	9.6	14.35	18.23

Sources:

[1] Gwanda Hospital, ZIANet AIDS News, Vol. 2, No. 1 March 1994.

[2] Nsambya, HIV/AIDS Surveillance Report, Ministry of Health, Kampala, March 1995.

[3] AIDS Analysis Africa (Southern African Edition) 6(3), Oct/Nov. 1995.

[4] AIDS Analysis Africa (Southern African Edition) 6(3). Oct/Nov. 1995.

The result of infection is an increase in morbidity (sickness) and mortality (death). There are few data on increased morbidity but the effect on mortality has been predicted (see Figure 1).

Attempts to predict and plan for the impact of the epidemic have foundered, firstly on the fact that nowhere has it run its course, thus we do not have examples of what might happen. Secondly, there is a paucity of good primary fieldwork and data; and thirdly, like the epidemic, the response is dynamic, thus people evolve coping mechanisms and strategies. Nonetheless, some results have been observed and predictions can be made.

The effect of an infection is felt first and most immediately by the person who falls ill and their family. It then spreads like a ripple out through the household, community, and then through the country as a whole. This interaction is illustrated in Figure 2. It should be remembered that while an individual may not be a producer, he or she will always be a consumer and have social roles. Broad areas of concern for development assistance, where we expect the epidemic to have an impact, are demographic, economic and developmental.

Demographic Consequences
AIDS will not stop population growth, nor cause populations to fall, thus any idea that “AIDS is the solution to the population problem” is unfounded. What it will do, in some regions, is to slow the rate of population growth and alter the structure of the population. Of particular concern is the increased mortality in the 20-40 year age group. This has the effect of reducing the working age population and increasing the dependency ratio. Most women will complete their child-bearing before falling ill so the number of orphans will rise.

Economic Effect

AIDS will have an effect on economies at various levels. The most obvious is at the household level. A household with a infected member will find that expenditure increases as the person requires medical care, a special diet and so on. If the infected person is an adult then their labour will be lost, which may affect income if the person was in paid employment or producing goods for sale, and will reduce household welfare.

At the sectoral and firm level the impact AIDS has will depend very much on how the sector or firm uses labour, what level of labour is employed, how the workers are treated in terms of benefits, and the importance of experience. In some instances the epidemic may have a significant effect on efficiency and cost, while in others the effect will be minimal.

The macro-economic impact is also uncertain. It is believed that AIDS will affect national economic growth through diversion of savings to care and consumption (thus reducing investment), and through the illness and death of productive members of the society.

There have been attempts to model the economic impact for specific countries. These models show that HIV will probably reduce the rate of economic growth; and, over a period of 20 years, this may be significant (up to 25 per cent lower than it would otherwise have been).

The Effect on Development

It is increasingly argued that development is about more than economic growth and increases in GDP per capita. It is on the development indicators that the impact of the epidemic will be felt first and worst.

Particularly vulnerable are the indicators of life expectancy; infant mortality rates; child mortality rates and the crude death rate. Infant mortality rates may nearly double in Zambia and Zimbabwe and increase by 50 per cent in Kenya and Uganda. Child mortality rates will increase even more, as many children survive beyond their first birthday. Life expectancy is predicted to fall by an estimated 9 years in Zaire to more than 25 years in the worst affected countries by the year 2010 (Way and Stanecki, 1994).

The effect of AIDS will be to reverse hard-won development gains and to make people and nations worse off. It is possible that these effects may last for decades. The people who fall ill and die are the parents and leaders in society, which means that a generation of children may grow up without the care and role models they would normally have.

Conclusion

It is clear that HIV/AIDS presents a major challenge to developing countries. The question remains as to what can be done about it. The obvious response is to reduce the number of infections. This includes 'technical solutions', such as making the blood supply safe, treating STIs, and providing condoms, but these interventions will not be successful if they are imposed without an understanding of the social and economic factors that determine both behaviour and the response to the epidemic.

The sad reality is that in many countries a significant number of people are already infected. While prevention must remain a priority: - there are those who are as yet uninfected and other who are becoming sexually active - there is a need to plan for the impact of the epidemic. The number of people falling ill and requiring care will increase. The rise in mortality and its consequences will have to be accommodated.

Thus while the first response is prevention, the second is to plan for and mitigate the impact of the epidemic. This is hard to do because: in most settings the impact is not visible; it is incremental rather than catastrophic; AIDS is only one of a number of problems facing policy makers; and there have been only a limited number of ideas as to what can be done.

References:

Lieve Fransen and Alan Whiteside, (eds.), HIV/AIDS and Development Assistance, Workshop Proceedings, Brussels, 13 June 1996.
Peter O Way and Karen A Stanecki, The Impact of HIV/AIDS on World Population, US Bureau of the Census, Washington DC, 1994.
World Bank, AIDS Prevention and Mitigation in Sub-Saharan Africa, An Updated World Bank Strategy, Report No. 15569-AFR, Human Resources and Poverty Division, Technical Department, Africa Region, Washington DC, April 20, 1996.

insomnia

2009-03-24T08:02:00.001+07:00

This article is about the sleeping disorder. For other uses, see Insomnia (disambiguation).
Insomnia is a symptom of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both" and it may be due to inadequate quality or quantity of sleep. It is typically followed by functional impairment while awake. Insomniacs have been known to complain about being unable to close their eyes or "rest their mind" for more than a few minutes at a time. Both organic and non-organic insomnia constitute a sleep disorder.

According to the U.S. Department of Health and Human Services in year 2007, approximately 64 million Americans suffer from insomnia on a regular basis each year. Insomnia is 1.4 times more common in women than in men.

Types of insomnia
Although there are several different degrees of insomnia, three types of insomnia have been clearly identified: transient, acute, and chronic.

1. Transient insomnia lasts from days to weeks. It can be caused by another disorder, by changes in the sleep environment, by the timing of sleep, severe depression, or by stress. Its consequences - sleepiness and impaired psychomotor performance - are similar to those of sleep deprivation.
2. Acute insomnia is the inability to consistently sleep well for a period of between three weeks to six months.
3. Chronic insomnia lasts for years at a time. It can be caused by another disorder, or it can be a primary disorder. Its effects can vary according to its causes. They might include sleepiness, muscular fatigue, hallucinations, and/or mental fatigue; but people with chronic insomnia often show increased alertness. Some people that live with this disorder see things as though they were happening in slow motion, whereas moving objects seem to blend together. Can cause double vision.

Patterns of insomnia
The pattern of insomnia often is related to the etiology.

1. Onset insomnia - difficulty falling asleep at the beginning of the night, often associated with anxiety disorders.
2. Middle-of-the-Night Insomnia - Insomnia characterized by difficulty returning to sleep after awakening in the middle of the night or waking too early in the morning. Also referred to as nocturnal awakenings. Encompasses middle and terminal insomnia.
3. Middle insomnia - waking during the middle of the night, difficulty maintaining sleep. Often associated with pain disorders or medical illness.
4. Terminal (or late) insomnia - early morning waking. Characteristic of clinical depression.

Causes
Insomnia can be caused by:
* Psychoactive drugs or stimulants, including certain medications, herbs, caffeine, cocaine, ephedrine, amphetamines, methylphenidate, MDMA, methamphetamine and modafinil
* Fluoroquinolone antibiotic drugs, see Fluoroquinolone toxicity, associated with more severe and chronic types of insomnia
* Hormone shifts such as those that precede menstruation and those during menopause
* Life problems like fear, stress, anxiety, emotional or mental tension, work problems, financial stress, unsatisfactory sex life
* Mental disorders such as bipolar disorder, clinical depression, general anxiety disorder, post traumatic stress disorder, schizophrenia, or obsessive compulsive disorder.
* Disturbances of the circadian rhythm, such as shift work and jet lag, can cause an inability to sleep at some times of the day and excessive sleepiness at other times of the day. Jet lag is seen in people who travel through multiple time zones, as the time relative to the rising and setting of the sun no longer coincides with the body's internal concept of it. The insomnia experienced by shift workers is also a circadian rhythm sleep disorder.
* Estrogen is considered to play a significant role in women’s mental health (including insomnia). A conceptual model of how estrogen affects mood was suggested by Douma et al 2005 based on their extensive literature review relating activity of endogenous, bio-identical and synthetic estrogen with mood and well-being. They concluded the sudden estrogen withdrawal, fluctuating estrogen, and periods of sustained estrogen low levels correlated with significant mood lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized and/or restored.
* Certain neurological disorders, brain lesions, or a history of traumatic brain injury
* Medical conditions such as hyperthyroidism
* Abuse of over-the counter or prescription sleep aids can produce rebound insomnia
* Poor sleep hygiene, e.g., noise
* Parasomnia, which includes a number of disruptive sleep events including nightmares, sleepwalking, violent behavior while sleeping, and REM behavior disorder, in which a person moves his/her physical body in response to events within his/her dreams
* A rare genetic condition can cause a prion-based, permanent and eventually fatal form of insomnia called fatal familial insomnia
* Parasites can cause intestinal disturbances while sleeping.

A common misperception is that the amount of sleep a person requires decreases as he or she ages. The ability to sleep for long periods, rather than the need for sleep, appears to be lost as people get older. Some elderly insomniacs toss and turn in bed and occasionally fall off the bed at night, diminishing the amount of sleep they receive.

An overactive mind or physical pain may also be causes. Finding the underlying cause of insomnia is usually necessary to cure it. Insomnia can be common after the loss of a loved one, even years or decades after the death, if they have not gone through the grieving process. Overall, symptoms and the degree of their severity affect each individual differently depending on their mental health, physical condition, and attitude or personality.

Epidemiology
The National Sleep Foundation's 2002 Sleep in America poll showed that 58% of adults in the U.S. experienced symptoms of insomnia a few nights a week or more. Although insomnia was the most common sleep problem among about one half of older adults (48%), they were less likely to experience frequent symptoms of insomnia than their younger counterparts (45% vs. 62%), and their symptoms were more likely to be associated with medical conditions, according to the 2003 poll of adults between the ages of 55 and 84.

Diagnosis
Specialists in sleep medicine are qualified to diagnose the many different sleep disorders. Patients with various disorders including delayed sleep phase syndrome are often mis-diagnosed with insomnia. If a patient has trouble getting to sleep, but has normal sleep architecture once asleep, a circadian rhythm disorder is a likely cause.

Insomnia versus poor sleep quality
Poor sleep quality can occur as a result of sleep apnea or clinical depression. Poor sleep quality is caused by the individual not reaching stage 4 or delta sleep which has restorative properties. There are, however, people who are unable to achieve stage 4 sleep due to brain damage who lead perfectly normal lives.

Sleep apnea is a condition that occurs when a sleeping person's breathing is interrupted, thus interrupting the normal sleep cycle. With the obstructive form of the condition, some part of the sleeper's respiratory tract loses muscle tone and partially collapses. People with obstructive sleep apnea often do not remember awakening or having difficulty breathing, but they complain of excessive sleepiness during the day. Central sleep apnea interrupts the normal breathing stimulus of the central nervous system, and the individual must actually wake up to resume breathing. This form of apnea is often related to a cerebral vascular condition, congestive heart failure, and premature aging.

Major depression leads to alterations in the function of the hypothalamic-pituitary-adrenal axis, causing excessive release of cortisol which can lead to poor sleep quality.

Nocturnal polyuria, excessive nighttime urination, can be very disturbing to sleep.

Treatment for insomnia
In many cases, insomnia is caused by another disease, side effects from medications or a psychological problem. It is important to identify or rule out medical and psychological before deciding on the treatment for the insomnia. Attention to sleep hygiene is an important first line treatment strategy and should be tried before any pharmacological approach is considered.

Non-pharmacological strategies
Non-pharmacological strategies are superior to hypnotic medication for insomnia because tolerance develops to the hypnotic effects as well as dependence can develop with rebound withdrawal effects developing upon discontinuation. Hypnotic medication is therefore only recommended for short term use. Non pharmacological strategies however, have long lasting improvements to insomnia and are recommended as a first line and long term strategie of managing insomnia. The strategies include attention to sleep hygiene, stimulus control, behavioral interventions, sleep-restriction therapy, patient education and relaxation therapy.

Cognitive behavior therapy
A recent study found that cognitive behavior therapy is more effective than hypnotic medications in controlling insomnia. In this therapy, patients are taught improved sleep habits and relieved of counter-productive assumptions about sleep. Hypnotic medications are equally effective in the short term treatment of insomnia but their effects wear off over time due to tolerance. The effects of cognitive behavior therapy have sustained and lasting effects on treating insomnia long after therapy has been discontinued. The addition of hypnotic medications with CBT adds no benefit in insomnia. The long lasting benefits of a course of CBT shows superiority over pharmacological hypnotic drugs. Even in the short term when compared to short term hypnotic medication such as zolpidem (Ambien), CBT still shows significant superiority. Thus CBT is recommended as a first line treatment for insomnia.

Medications
Many insomniacs rely on sleeping tablets and other sedatives to get rest. All sedative drugs have the potential of causing psychological dependence where the individual cannot psychologically accept that they can sleep without drugs. Certain classes of sedatives such as benzodiazepines and newer nonbenzodiazepine drugs can also cause physical dependence which manifests in withdrawal symptoms if the drug is not carefully titrated down. The benzodiazepine and nonbenzodiazepine hypnotic medications also have a number of side effects such as day time fatigue, motor vehicle crashes, cognitive impairments and falls and fractures. Elderly people are more sensitive to these side effects.

In comparing the options, a systematic review found that benzodiazepines and nonbenzodiazepines have similar efficacy which was not significantly more than for antidepressants. Benzodiazepines did not have a significant tendency for more adverse drug reactions. Chronic users of hypnotic medications for insomnia do not have better sleep than chronic insomniacs who do not take medications. In fact, chronic users of hypnotic medications actually have more regular nighttime awakenings than insomniacs who do not take hypnotic medications. Thus short term or occasional use of hypnotics can be benefitial but long term use may be detrimental to sleep.

Benzodiazepines
The most commonly used class of hypnotics prescribed for insomnia are the benzodiazepines. Benzodiazepines bind unselectively to the GABAA receptor. These include drugs such as temazepam, flunitrazepam, triazolam, flurazepam, midazolam, nitrazepam and quazepam. These drugs can lead to tolerance, physical dependence and the benzodiazepine withdrawal syndrome upon discontinuation, especially after consistent usage over long periods of time. Benzodiazepines while inducing unconsciousness, actually worsen sleep as they promote light sleep whilst decreasing time spent in deep sleep such as REM sleep. A further problem is with regular use of short acting sleep aids for insomnia, day time rebound anxiety can emerge.

Non-benzodiazepines
Nonbenzodiazepine sedative-hypnotic drugs, such as Ambien (zolpidem), Sonata (zaleplon), Imovane (zopiclone) and Lunesta (eszopiclone), are a newer classification of hypnotic medications. They work on the benzodiazepine site on the GABAA receptor complex similarly to the benzodiazepine class of drugs. Some but not all of the nonbenzodiazepines are selective for the α1 subunit on GABAA receptors which is responsible for inducing sleep and may therefore have a cleaner side effect profile than the older benzodiazepines. Zopiclone and eszopiclone like benzodiazepine drugs bind unselectively to α1, α2, α3 and α5 GABAA benzodiazepine receptors. Zolpidem is more selective and zaleplon is highly selective for the α1 subunit thus giving them an advantage over benzodiazepines in terms of sleep architecture and a reduction in side effects. However, there are controversies over whether these non-benzodiazepine drugs are superior to benzodiazepines. These drugs appear to cause both psychological dependence and physical dependence though less than traditional benzodiazepines and can also cause the same memory and cognitive disturbances along with morning sedation.

Antidepressants
Some antidepressants such as amitriptyline, doxepin, mirtazapine, and trazodone can often have a very strong sedative effect, and are prescribed off label to treat insomnia. [28] The major drawback of these drugs is that they have antihistaminergic, anticholinergic and antiadrenergic properties which can lead to many side effects. Some also alter sleep architecture. As with many benzodiazepines, the use of antidepressants in the treatment of insomnia can lead to physical dependence; withdrawal may induce rebound insomnia and actually further complicate matters in the long-term.

Mirtazapine is known to decrease sleep latency, promoting sleep effiency and increasing the total amount of sleeping time in patients suffering from both depression and insomnia

Melatonin
The hormone and supplement melatonin is effective in several types of insomnia. Melatonin has demonstrated effectiveness equivalent to the prescription sleeping tablet zopiclone in inducing sleep and regulating the sleep/waking cycle. One particular benefit of melatonin is that it can treat insomnia without altering the sleep architecture which is altered by many prescription sleeping tablets. Another benefit is it does not impair performance related skills. Melatonin agonists, including Ramelteon (Rozerem), seem to lack the potential for abuse and dependence. This class of drugs has a relatively mild side effect profile and lower likelihood of causing morning sedation. Natural substances such as 5-HTP and L-Tryptophan have been said to fortify the serotonin-melatonin pathway and aid people with various sleep disorders including insomnia.

Antihistamines
The antihistamine Benadryl (diphenhydramine) is widely used in nonprescription sleep aids such as Tylenol PM, with a 50 mg recommended dose mandated by the FDA. In the United Kingdom, Australia, New Zealand, South Africa, and other countries, a 25mg to 50mg recommended dose is permitted. While it is available over the counter, the effectiveness of these agents may decrease over time and the incidence of next-day sedation is higher than for most of the newer prescription drugs. Dependence does not seem to be an issue with this class of drugs.

Periactin (Cyproheptadine) is a useful alternative to benzodiazepine hypnotics in the treatment of insomnia. Cyproheptadine may be superior to benzodiazepines in the treatment of insomnia because cyproheptadine enhances sleep quality and quantity whereas benzodiazepines tend to decrease sleep quality.

Atypical Antipsychotics
Low doses of certain atypical antipsychotics such as quetiapine (Seroquel) are also prescribed for their sedative effect but the danger of neurological and cognitive side effects make these drugs a poor choice to treat insomnia. Over time, Seroquel may lose its effectiveness as a sedative. The ability of Seroquel to produce sedation is determined by the dosage. Higher doses (300 mg - 900 mg) are usually taken for its use as an antipsychotic, while lower doses (25 mg - 200 mg) have a marked sedative effect, e.g. if a patient takes 300 mg, he/she will more likely benefit from the drug's antipsychotic effects, but if the dose is brought down to 100 mg, it will leave the patient feeling more sedated than at 300 mg, because it primarily works as a sedative at lower doses.

Other Substances
Some insomniacs use herbs such as valerian, chamomile, lavender, hops, and passion-flower. Valerian has undergone multiple studies and appears to be modestly effective. Cannabis has also been proven as an effective treatment for insomnia.

Middle-of-the-night awakenings due to polyuria or other effects from alcohol consumption are common, and hangovers can also lead to morning grogginess.

Insomnia may be a symptom of magnesium deficiency, or low magnesium levels, but this has not yet been proven. A healthy diet containing magnesium, can help to improve sleep in individuals without an adequate intake of magnesium.

Other reports cite the use of an elixir of cider vinegar and honey but the evidence for this is only anecdotal.

Sexual Activity
In several cases, sexual intercourse has been found to heavily reduce stress patterns. Although in many cases stress is not the cause of insomnia.

Complementary and alternative medicine
Some traditional and anecdotal remedies for insomnia include: drinking warm milk before bedtime, taking a warm bath, exercising vigorously for half an hour in the afternoon, eating a large lunch and then having only a light evening meal at least three hours before bed, avoiding mentally stimulating activities in the evening hours, going to bed at a reasonable hour and getting up early, and avoiding exposing the eyes to too much light, especially blue light, a few hours before bedtime. Initial treatment of insomnia may include the rules of sleep hygiene.

The herb valerian can be effective and a useful alternative to benzodiazepines in alleviating insomnia due to its pharmacological activity on the GABAA receptor complex.

Using aromatherapy, including jasmine oil, lavender oil, Mahabhringaraj and other relaxing essential oils, may also help induce a state of restfulness. Many believe that listening to slow paced music will help insomniacs fall asleep.

The more relaxed a person is, the greater the likelihood of getting a good night's sleep. Relaxation techniques such as meditation have been shown to help people sleep. One deep breathing technique involves synchronizing breath to a blue light.

Tai Chi helps improve sleep. At UCLA a controlled study found that the Tai Chi group, practicing two hours of Tai Chi per week, left 63% of the Tai Chi group with improved quality of sleep. The control group practicing only healthy habits, but no Tai Chi practice, left only 32% with improved quality of sleep. Tai chi alone doubled people's chances of improved sleep patterns, over simply adopting healthy habits.

In another study, reported in The Journal of the American Geriatric Society, 5, 892-900, Tai chi participants reported sleep-onset latency of about 18 minutes less per night and sleep duration of about 48 minutes more per night than low-impact exercise participants.

Traditional Chinese medicine has included treatment for insomnia. A typical approach may utilize acupuncture, dietary and lifestyle analysis, herbology and other techniques, with the goal of resolving the problem at a subtle level.

In the Buddhist tradition, people suffering from insomnia or nightmares may be advised to meditate on "loving-kindness", or metta. This practice of generating a feeling of love and goodwill is claimed to have a soothing and calming effect on the mind and body. This is claimed to stem partly from the creation of relaxing positive thoughts and feelings, and partly from the pacification of negative ones. In the Mettā (Mettanisamsa) Sutta, Siddhartha Gautama, the Buddha, tells the gathered monks that easeful sleep is one benefit of this form of meditation.

Hypnotherapy, self hypnosis and guided imagery can be effective in not only falling asleep and staying asleep; they can also help to develop good sleeping habits over time.[citation needed] Visualizing can be effective in taking the mind away from present day anxieties and towards a more relaxing place. Binaural beats can help people fall asleep faster using special sounds.

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