Med-mission

Researchers Identify Gene Mutations Underlying Risk for Most Common Form of Parkinson's Disease

2009-12-01T15:59:00.000+05:30

Two genes containing mutations known to cause rare familial forms of parkinsonism are also associated with the more common, sporadic form of the disease where there is no family history, researchers have found.
The finding came in the largest genome-wide association study (GWAS) reported to date involving Parkinson's disease. GWAS studies look in the DNA on all of the chromosomes in a specific population of individuals for common genetic associations with a disease. To date, such studies have been done on relatively small numbers of samples and have not been able to identify genetic variations of smaller effect in Parkinson's disease. But now, GWAS studies in very large sample sets are able to identify these elusive genetic variations.

Collaborating scientists in the United States and Europe pooled nearly 14,000 DNA samples and data to confirm that mutations in the alpha-synuclein (SNCA) gene and microtubule associated protein tau (MAPT), both present in the general population, are risk factors for sporadic Parkinson's disease.

In an independent study from Japan, researchers also identified a different combination of genetic variants as risk factors in people of Japanese descent, a finding that highlights the power of GWAS in comparing risk factors among different populations.

The findings presented in the Nov. 15, 2009, online issue of were supported in Nature Genetics part by the National Institute on Aging (NIA), National Institute of Neurological Disorders and Stroke, National Cancer Institute, and the National Institute of Environmental Health Sciences, all components of the National Institutes of Health.

Parkinson's disease, which affects about 1.5 million Americans, is a progressive neurologic disorder caused by the degeneration of nerve cells in the portion of the brain that controls movement. The likelihood of developing the disorder increases with age and involves a combination of environmental risk factors and genetic susceptibility. GWAS studies require large numbers of DNA samples — a hurdle the international team of researchers overcame through collaboration.

"Because previous Parkinson's GWAS were too small and lacked power, we worked together to compile and analyze the large data sets needed to identify the elusive genetic variations that play a role in this complex disease," said Andrew B. Singleton, Ph.D., chief of the NIA Laboratory of Neurogenetics, who co-led the study with Thomas Gasser, M.D., of the Hertie Institute for Clinical Brain Research, University of Tubingen, and the German Center for Neurodegenerative Disease, of Tubingen, Germany. "With this better understanding of the underlying genetic variants involved in the progress of this disorder, we have more insight into the causes and underlying biology of this disease. We hope this new understanding will one day provide us with strategies to delay, or even prevent, the development of Parkinson's disease."

The two-phase GWAS first analyzed DNA samples of 1,713 people with the disease and 3,978 free of the disorder, all of whom were Europeans. The findings were then replicated in a similar group of 3,361 people with Parkinson's disease and 4,573 without the disorder. Following the initial findings implicating SNCA and MAPT variants as risk factors for typical Parkinson's disease, the team then compared results with researchers performing a GWAS study in a group of Japanese people (2,816 with Parkinson's disease and 3,401 free of the disorder). This second GWAS also strong association for SNCA but not for MAPT.

Additionally, both GWAS studies found evidence for two additional risk variants; the first, which was strongest in the Japanese population, was namerevealed the d Park16; the second is close to a gene, LRRK2, which Dr. Singleton's and Dr. Gasser's groups previously found contains mutations that cause an inherited form of Parkinson's disease.

"These findings support the notion that the sporadic and rare familial forms of the disease are related and that common genetic variability plays a role in developing the disorder," said NIA Director Richard J. Hodes, M.D. "Future GWAS involving greater numbers of DNA samples will likely reveal additional common genetic risk factors. As we continue to use these and other novel approaches to understand complex diseases, we move closer to a complete understanding of the genetic basis of Parkinson's disease."

Source : National Institutes of Health

Smart phones allow quick diagnosis of acute appendicitis

2009-12-01T01:24:00.002+05:30

Radiologists can accurately diagnose acute appendicitis from a remote location with the use of a handheld device or mobile phone equipped with special software, according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA).

"The goal is to improve the speed and accuracy of medical diagnoses, as well as to improve communications among different consulting physicians," said the study's lead author, Asim F. Choudhri, M.D., fellow physician in the Division of Neuroradiology at Johns Hopkins University in Baltimore. "When we can make these determinations earlier, the appropriate surgical teams and equipment can be assembled before the surgeon even has the chance to examine the patient."

Appendicitis, or inflammation and infection of the appendix, is a medical emergency requiring surgical removal of the organ. Undiagnosed or left untreated, the inflamed appendix will rupture, causing toxins to spill into the abdominal cavity and potentially causing a life-threatening infection.

Appendicitis can occur at any age but is most common in people between the ages of 10 and 30, according to the National Institutes of Health.

Typically, a patient arriving at the emergency room with suspected appendicitis will undergo computed tomography (CT) and a physical examination. If a radiologist is not immediately available to interpret the CT images or if consultation with a specialist is needed, diagnosis is delayed, increasing the risk of rupture. Transmitting the images over a mobile device allows for instant consultation and diagnosis from a remote location. It can also aid in surgical planning.

"This new technology can expedite diagnosis and, therefore, treatment," Dr. Choudhri said.

For the study performed at the University of Virginia in Charlottesville, CT examinations of the abdomen and pelvis of 25 patients with pain in the right lower abdomen were reviewed over an encrypted wireless network by five radiologists using an iPhone G3 equipped with OsiriX Mobile medical image viewing software. All of the patients had surgical confirmation or follow-up evaluations to confirm whether or not they had appendicitis.

"The scans can be read in full resolution with very little panning, and the software allows the reader to zoom and adjust the contrast and brightness of the image," Dr. Choudhri said. "The radiologist is evaluating actual raw image data, not snapshots."

Fifteen of the 25 patients were correctly identified as having acute appendicitis on 74 (99 percent) of 75 interpretations, with one false negative. There were no false positive readings. In eight of the 15 patients who had appendicitis, calcified deposits within the appendix were correctly identified in 88 percent of the interpretations. All 15 patients had signs of inflammation near the appendix that were correctly identified in 96 percent of interpretations, and 10 of the 15 had fluid near the appendix, which was correctly identified in 94 percent of the interpretations. Three abscesses were correctly identified by all five readers.

"The iPhone interpretations of the CT scans were as accurate as the interpretations viewed on dedicated picture archiving and communication system (PACS) workstations," Dr. Choudhri said.

Dr. Choudhri pointed out that patient privacy concerns would have to be addressed before any handheld mobile device could be considered practical for clinical use, but noted that this technique has great potential for improving emergency room care.

"We hope that this will result in improved patient outcomes, as evidenced by decreased rates of ruptured appendicitis, shorter hospital stays and fewer complications," he said.

Source: Radiological Society of North America

New stem cell technology leads to better treatment for complicated bone fractures

2009-12-01T01:11:00.000+05:30

A novel technology involving use of stem cells, developed by Hebrew University of Jerusalem researchers, has been applied to provide better and rapid healing for patients suffering from complicated bone fractures.

The technology, involving isolation of the stem cells from bone marrow, was developed by Dr. Zulma Gazit, Dr. Gadi Pelled, Prof. Dan Gazit and their research team at the Skeletal Biotechnology Laboratory at the Hebrew University Faculty of Dental Medicine and was given public exposure in an article that appeared in the prestigious journal Stem Cells. The technology has now successfully been used to treat complicated fractures in seven patients at the Hadassah University Hospital in Ein Kerem, Jerusalem.

To date, in clinical orthopedics, standard treatment for severe bone loss has involved either amputation or a prolonged period of disability. The use of prosthetic implants tends to fail in the long term. Excessive bone loss may result in non-uniting fractures, which are observed in more than one million new cases per year in the US alone.

In recent years, the use of mesenchymal stem cells (MSCs, or multipotent stem cells that can differentiate into a variety of cell types) has been claimed to be a promising biological therapy that could be used to treat complicated fractures and other disorders in the skeleton. These cells constitute a unique population of adult stem cells that can readily be isolated from various sites in the human body, especially from bone marrow and adipose (fat) tissues. Following isolation, MSCs can be utilized to repair a variety of injured tissues including bone, cartilage, tendon, intervertebral discs and even the heart muscle.

The conventional method of MSC isolation, using prolonged periods of growth in designated incubators, has proved to be laborious, costly and also possibly injurious to the therapeutic quality of the cells. Therefore, an alternative method involving the immediate use of these stem cells was an unmet need in the field of regenerative medicine.

Now, the Hebrew University group has developed a technology called immuno-isolation in which MSCs are sorted out from the other cells residing in a bone marrow sample, using a specific antibody. In the Stem Cell paper it was shown that the immuno-isolated cells could be immediately used to form new bone tissue when implanted in laboratory animals, without having to undergo a prolonged incubator growth period.

Following this breakthrough, a unique and close collaboration was established among clinicians (Prof. Meir Liebergall, head of orthopedics, Hadassah University Hospital), the Good Manufacturing Practice (GMP) facility at Hadassah (Headed by Prof. Eithan Galun) and the Gazit group at the Faculty of Dental Medicine.
Within this collaborative effort, a clinical-grade protocol for the use of immuno-isolated MSCs was established. Subsequently a clinical trial was initiated at Hadassah, aimed at establishing the foundation for the use of immuno-isolated MSCs in orthopedic surgery.

To date, seven patients suffering from complicated fractures have been treated successfully with a combination of their own immuno-isolated MSCs and blood products. The entire procedure lasted a few hours and without any need to grow the cells for weeks in a laboratory.

It is anticipated that future development of the current endeavor will extend to treat other injuries in the skeleton, such as degenerated intervertebral discs or torn tendons. The Gazit group believes that further clinical trials will demonstrate that the immuno-isolation technology is useful in overcoming morbidity in patients suffering from skeletal fractures and diseases, and might restore function and quality of life to sick and injured people.

In this regard, Yissum Research Development Company of the Hebrew University of Jerusalem, the technology transfer arm of the university, licensed the immuno-isolation technology to TheraCell Inc. of California in July 2009. TheraCell aims to further develop and commercialize the technology for advanced regenerative medicine procedures such as spinal fusion.

New genetic cause of cardiac failure discovered

2009-12-01T00:09:00.000+05:30

Over the course of a lifetime, the heart pumps some 250 million liters of blood through the body. In the order to do this, the muscle fibers of the heart have to be extremely durable. The research group headed by Dr. Wolfgang Rottbauer, vice chair of the Department of Medicine III at Heidelberg University Hospital (Germany), has discovered a protein that is responsible for the stability of the smallest muscular unit, the sarcomere.

In cooperation with other researchers within the National Genome Research Network they proved that mutations of this protein are the cause of a new type of heart failure. The results have been published in the November issue of Nature Medicine.
Primary heart muscle disease with decreased cardiac pump function leading to enlargement of the heart chambers (dilated cardiomyopathy) is one of the most frequent causes of chronic heart failure. Six new cases per 100,000 people occur each year; 20 percent of these cases are genetic. The heart disease weakens cardiac cells and the heart can no longer pump efficiently which leads to dilation of the cardiac chambers.

Muscle activity takes place in the smallest unit of muscle fiber, the sarcomere. In the presence of an appropriate stimulus, actin and myosin filaments interact and contract the muscle. These movable elements are anchored in what are known as Z-disks. With every heartbeat, enormous forces act on the Z-disks.
Torn Z disks weaken the heart.

"In our studies of zebrafish, we discovered a protein that is needed to stabilize the Z-disk. If this protein (nexilin) is mutated, the movable muscle elements are no longer anchored firmly enough. The muscles then lose strength and the heart is weakened," explains Dr. Tillman Dahme, resident and co-author of the study. The researchers examined the genetic material of affected patients and verified a mutated Z-disk protein in 9 of 1000 participants. They showed that in these patients, the defective nexilin was the major cause of heart disease. "The nexilin dilated cardiomyopathy allowed us for the first time to describe a new form of heart muscle dilatation and define the mechanism causing it, namely destabilization of the Z-disk," says Dahme.
The studies also showed that the extent of the damage to the Z-disk is directly related to the workload. This insight has an influence on clinical therapy. "Patients with a nexilin mutation might benefit from early treatment with medications that reduce cardiac stress. This could lower the mechanical stress on the Z-disks and prevent progressive damage to the heart," said Dr. Rottbauer.

Genome advances promise personalized medical treatment

2009-11-30T23:47:00.000+05:30

A whirlwind of activity is under way to apply the findings of the $3 billion Human Genome Project to improve health care in the United States and around the world.

Six years after scientists finished decoding the human genome -- the genetic instruction book for life -- they're starting to take their new knowledge from the research laboratory to the doctor's office and the patient's bedside.

"We hope all this knowledge of the genome will lead to more kinds of therapies," said Francis Collins, who ran the federal government's Human Genome Project from 1993 to 2008.

Researchers are seeking ways to tailor treatments to individuals -- they call it "personalized medicine" -- in order to improve patient outcomes and to lower costs in the overburdened U.S. health care system.

The goal is to deliver the right drug at the right time in the right dose to the right person, and eliminate treatments that don't work.

"Already some of these personalized treatments are finding their way into practice," Collins told a recent seminar in Washington. "We want to optimize the way we practice medicine, diagnosis and risk prediction."

For example, instead of a standard therapy to treat breast cancer, personalized medicine allows doctors to employ a treatment precisely designed to fit one woman's specific needs. If a gene test shows that her tumor overproduces a substance called HER-2, she's considered to be a good candidate for the drug Herceptin, which cuts her chance of a recurrence nearly in half. If the test is negative, using the drug could be wasteful.

Advocates say that personalized medicine also can reduce unnecessary suffering and expense by minimizing the chance of adverse drug reactions. According to the Food and Drug Administration, there were 319,741 serious illnesses and 49,958 deaths due to unexpected reactions to drugs last year in the United States alone. A British study estimated the cost of such reactions at $847 million per year in the United Kingdom.

For instance, heart patients who have two tiny mutations in their genomes have an increased risk of serious problems, even death, if they take the popular anti-clotting drug Plavix, according to Rick Hockett, the chief medical officer of Affymetrix, a genetics firm in Santa Clara, Calif.

Experts caution, however, that it's premature to say that an era of individually customized medicine has arrived. Major scientific and policy hurdles remain before patients can benefit widely from the promises of personalized medicine. Issues of insurance coverage, medical training, privacy and safety remain to be resolved.

"It is not ready for moving into the clinic. It is not ready for prime time," Pamela Sankar, a medical ethicist at the University of Pennsylvania, told the seminar.

Nevertheless, advances in genomic medicine are accelerating, thanks to new, high-speed sequencing machines. Unlike the slow, painstaking methods used to decode the first sample genome, second-generation robotic machines can analyze hundreds of thousands of units of DNA in minutes.

Collins said the improvement in speed of sequencing had been "breathtaking." Costs have come down proportionately.

In 2003, it cost an estimated $300 million to decode the first genome of an individual human. By 2007, the cost per person had come down to $100 million, and by 2008, it was $60,000. The current cost is about $20,000, according to Clifford Reid, the chief executive of Complete Genomics Inc., a gene-processing company in Mountain View, Calif.

Radoje Drmanac, the chief scientist at Complete Genomics, predicted that it soon will be possible to sequence a person's genome in one day. "For the first time, this will enable large numbers of patients to be sequenced to get to the bottom of thousands of genetically controlled diseases," Drmanac said.

Collins said the goal was to be able to sequence a complete human genome for $1,000 by five years from now, making it a staple of medical practice. People routinely will have their genomes sequenced to predict their individual risks of disease and responses to drugs, he predicted.

So far, fewer than two dozen complete human genomes have been published in scientific journals, but more are being sequenced rapidly. Larger efforts are also under way.

Last year, an international consortium launched a "1000 Genomes Project" to sequence the genomes of at least a thousand people from around the world by 2012. The goal is to produce a catalog of all the genetic variations that exist in at least 1 percent of the human population. The cost is estimated to be $30 million to $50 million.

"This will change the way we carry out studies of genetic disease," Collins said.

Already, studies of variant genes have provided clues to hundreds of diseases, he said.

Scientists are beginning to apply a new idea to cut the cost dramatically and speed the process of reading a person's genome. It's based on the fact that only about 1 percent of the 3 billion units of DNA in a person's genome contain the genetic code to produce proteins, the chemical building blocks of an organism. The rest used to be called "junk DNA", but some of it's now known to perform important functions, such as turning genes on or off.

So, instead of sifting through a "vast ocean of stuff", as one researcher called the complete genome, only the coding bits, known as the "exome", need to be read. The faster, simpler, cheaper exome process is sometimes called the "One Percent Solution."

Scientists at the University of Washington in Seattle reported in the journal Nature last week that they've sequenced 12 human exomes and have identified the cause of Miller syndrome, a rare disease that causes terrible facial and limb abnormalities in children.

Trying last-ditch lung bypass for worst swine flu

2009-11-30T23:03:00.000+05:30

**A technology originally developed for premature babies may be helping to save some of the sickest swine flu patients by rerouting their blood so their lungs can rest.

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It's a risky approach using equipment that only certain specialized hospitals have. But faced with children and young adults struggling to breathe despite ventilators has intensive-care doctors dusting off these machines, named ECMO, that they often consider last-ditch and almost never use for influenza.**

"It was pretty scary knowing that was his blood flowing through those tubes in and out of his body," says Susie Damm of Omaha, Neb., whose 19-year-old son Ryan survived a life-threatening bout after 10 days on ECMO.

"I was one of the people sick and tired of hearing about the swine flu, thinking people were making a big deal of it," she adds. "Now I've had a different look, and I'm very, very thankful" he survived.

No one knows which patients are most likely to benefit - not everyone does. But ECMO is gaining attention after Australian researchers reported that the machines helped during that country's outbreak of what scientists call the 2009 H1N1 flu strain. A voluntary U.S.-based registry counts 107 critically ill swine flu patients recently treated with ECMO, most from this country.

In Omaha, Dr. Jeff DeMare credits the technique with saving Ryan Damm and 7-year-old Tania Romero-Oropeza after both patients' lungs went from clogged to nearly useless in a stunning matter of hours. Tania's care was complicated by a drug-resistant staph infection.

"You wonder, 'OK, we've got a lot of folks who get this disease and why is it so bad in some cases?' We don't have a real good handle on that," says DeMare, a critical care specialist at Children's Hospital & Medical Center.

Whatever the reason, "your body needs time to fight the infection," he adds, and he gambled that the pricey equipment could buy that time.

Estimates from the federal Centers for Disease Control and Prevention suggest that swine flu has hospitalized 98,000 Americans in the past six months, and killed nearly 4,000. For most, standard treatment works.

But the sickest often need ventilators to pump their lungs, and ventilators damage lung tissue, especially as they're turned up to higher pressures as patients worsen.

Hospitals are "exhausting all measures" on those patients, says Dr. Pauline Park, a University of Michigan ICU co-director who's helping to analyze the ECMO registry in hopes of determining best candidates. "Physicians don't want to give false hope to families, but also don't want to stand by if a life can be saved."

Enter ECMO, decades-old technology that essentially offers a temporary lung bypass. Tubes carry blood out of the body so a filter can remove carbon dioxide and reinfuse oxygen, and then dump the blood back.

It's a twist on the heart-lung machine used for open-heart surgery, modified so that patients can stay on the machine for weeks instead of just hours and, key here, so that blood doesn't have to bypass the heart if only the lungs need a rest.

There are many cautions. It's risky, requiring blood thinners to avoid clots and posing the potential for additional infection. It can double the cost of ICU care. Only about 120 hospitals in the U.S. offer it, most just a few times a year for newborns with respiratory failure, its primary use.

ECMO in adults is hugely controversial because past research couldn't prove that it significantly increased survival.

Here's what's new:

-Australian researchers reported last month that they used ECMO in 68 critically ill swine flu patients who failed standard care, and about 71 percent survived. That research predicted some 800 people might be ECMO candidates if the U.S. experienced similar rates of swine flu.

-Coincidentally, a British study also published last month found that nearly two-thirds of adults randomly assigned to ECMO survived other types of respiratory failure - before swine flu hit - while just 47 percent survived with regular ICU care. It's the most rigorous study of ECMO performed in adults and one that has lung specialists debating wider use.

-Preliminary data from the Michigan-run ECMO registry suggests survival can reach 72 percent if recipients get it within six days of using a ventilator. With longer ventilator use, the survival rate plummets.

Back in Omaha, DeMare agrees ECMO shouldn't be last-ditch, noting his own patients were on ventilators for just hours before getting it. Still, Tania had a monthlong hospital stay, including her eight days on ECMO.

"Thank God the doctor took that decision to use this machine," said Tania's mother, Antonieta Oropeza, speaking in Spanish through an interpreter.

Irritable Bowel Syndrome (IBS)

2009-11-29T12:38:00.000+05:30

What is irritable bowel syndrome (IBS)?

Irritable bowel syndrome (IBS) is one of the most common ailments of the bowel (intestines) and affects an estimated 15% of persons in the US. The term, irritable bowel, is not a particularly accurate one since it implies that the bowel is responding irritably to normal stimuli, and this may or may not be the case. The several names for IBS, including spastic colon, spastic colitis, and mucous colitis, attest to the difficulty of getting a descriptive handle on the ailment.
IBS is best described as a functional disease. The concept of functional disease is particularly useful when discussing diseases of the gastrointestinal tract. The concept applies to the muscular organs of the gastrointestinal tract; the esophagus, stomach, small intestine, gallbladder, and colon. What is meant by the term, functional, is that either the muscles of the organs or the nerves that control the organs are not working normally, and, as a result, the organs do not function normally. The nerves that control the organs include not only the nerves that lie within the muscles of the organs but also the nerves of the spinal cord and brain to which they connect.
Some gastrointestinal diseases can be seen and diagnosed with the naked eye, such as ulcers of the stomach when visualized with certain methods. Thus, ulcers can be seen at surgery, on X-rays, and at endoscopy. Other diseases cannot be seen with the naked eye but can be seen and diagnosed with the microscope. For example,celiac disease and collagenous colitis are diagnosed by microscopic examination of biopsies of the small intestine and colon, respectively. In contrast, gastrointestinal functional diseases cannot be seen with the naked eye or with the microscope. In some instances, the abnormal function can be demonstrated by tests, for example, gastric emptying studies or antro-duodenal motility studies. However, these tests often are complex, are not widely available, and do not reliably detect the functional abnormalities. Accordingly, by default, functional gastrointestinal diseases are those involving the abnormal function of gastrointestinal organs in which abnormalities cannot be seen in the organs with either the naked eye or the microscope.
Occasionally, diseases that are thought to be functional are ultimately found to be associated with abnormalities that can be seen. Then, the disease moves out of the functional category. An example of this would be Helicobacter pylori infection of the stomach. Many patients with mild upper intestinal symptoms who were thought to have functional abnormal function of the stomach or intestines have been found to have an infection of the stomach with Helicobacter pylori. This infection can be diagnosed by seeing the bacterium and the inflammation (gastritis) it causes under the microscope . When the patients are treated with antibiotics, the Helicobacter pylori, gastritis, and symptoms disappear. Thus, recognition of Helicobacter pylori infection removed some patients' diseases from the functional category.
Functional diseases of the stomach and intestines may be shown ultimately to be caused by reduced levels of normal chemicals within the gastrointestinal organs, the spinal cord, or the brain. Should a disease that is demonstrated to be due to a reduced chemical still be considered a functional disease? I think not. In this theoretical situation, we can't see the abnormality with the naked eye or the microscope, but we can measure it. If we can measure an associated or causative abnormality, the disease probably should no longer be considered functional.
While IBS is a major functional disease, it is important to mention a second major functional disease referred to as dyspepsia, or functional dyspepsia. The symptoms of dyspepsia are thought to originate from the upper gastrointestinal tract; the esophagus, stomach, and the first part of the small intestine. The symptoms include upper abdominal discomfort, bloating (the subjective sense of abdominal fullness without objective distension), or objective distension (swelling, or enlargement). The symptoms may or may not be related to meals. There may be nausea with or without vomiting and early satiety (a sense of fullness after eating only a small amount of food).
The study of functional disorders of the gastrointestinal tract often is categorized by the organ of involvement. Thus, there are functional disorders of the esophagus, stomach, small intestine, colon, and gallbladder. The amount of research on functional disorders has been focused mostly on the esophagus and stomach (such as dyspepsia), perhaps because these organs are easiest to reach and study. Research into functional disorders affecting the small intestine and colon (for example, IBS) is more difficult to conduct and there is less agreement among the research studies. This probably is a reflection of the complexity of the activities of the small intestine and colon and the difficulty in studying these activities. Functional diseases of the gallbladder, like those of the small intestine and colon, also are more difficult to study.

What causes IBS?

As described previously, IBS is believed to be due to the abnormal function (dysfunction) of the muscles of the organs of the gastrointestinal tract or the nerves controlling the organs. The nervous control of the gastrointestinal tract, however, is complex. A system of nerves runs the entire length of the gastrointestinal tract from the esophagus to the anus in the muscular walls of the organs. These nerves communicate with other nerves that travel to and from the spinal cord. Nerves within the spinal cord, in turn, travel to and from the brain. Thus, the abnormal function of the nervous system in IBS may occur in a gastrointestinal muscular organ, the spinal cord, or the brain.
The nervous system that controls the gastrointestinal organs, as with most other organs, contains both sensory and motor nerves. The sensory nerves continuously sense what is happening within the organ and relay this information to nerves in the organ's wall. From there, information can be relayed to the spinal cord and brain. The information is received and processed in the organ's wall, the spinal cord, or the brain. Then, based on this sensory input and the way the input is processed, commands (responses) are sent to the organ over the motor nerves. Two of the most common motor responses in the intestine are contraction or relaxation of the muscle of the organ and secretion of fluid and/or mucus into the organ.
As already mentioned, abnormal function of the nerves of the gastrointestinal organs, at least theoretically, might occur in the organ, spinal cord, or brain. Moreover, the abnormalities might occur in the sensory nerves, the motor nerves, or at processing centers in the intestine, spinal cord, or brain. Some researchers argue that the cause of functional diseases is abnormalities in the function of the sensory nerves. For example, normal activities, such as stretching of the small intestine by food, may give rise to abnormal sensory signals that are sent to the spinal cord and brain, where they are perceived as pain.
Other researchers argue that the cause of functional diseases is abnormalities in the function of the motor nerves. For example, abnormal commands through the motor nerves might produce a painful spasm (contraction) of the muscles. Still others argue that abnormally functioning processing centers are responsible for functional diseases because they misinterpret normal sensations or send abnormal commands to the organ. In fact, some functional diseases may be due to sensory dysfunction, motor dysfunction, or both sensory and motor dysfunction. One area that is receiving a great deal of scientific attention is the potential role of gas produced by intestinal bacteria in patients with IBS. Studies have demonstrated that some patients with IBS produce larger amounts of gas than individuals without IBS, and the gas may be retained longer in the small intestine. Among patients with IBS, abdominal size increases over the day, reaching a maximum in the evening and returning to baseline by the following morning. In individuals without IBS, there is no increase in abdominal size during the day.
There has been a great deal of controversy over the role that poor digestion and/or absorption of dietary sugars may play in aggravating the symptoms of IBS. Poor digestion of lactose, the sugar in milk, is very common as is poor absorption of fructose, a sweetener found in many processed foods. Poor digestion or absorption of these sugars could aggravate the symptoms of IBS since unabsorbed sugars often cause increased formation of gas.
Although these abnormalities in production and transport of gas could give rise to some of the symptoms of IBS, much more work will need to be done before the role of intestinal gas in IBS is clear.
Dietary fat in healthy individuals causes food as well as gas to move more slowly through the stomach and small intestine. Some patients with IBS may even respond to dietary fat in an exaggerated fashion with greater slowing. Thus, dietary fat could--and probably does--aggravate the symptoms of IBS.

What are IBS symptoms?

The primary purpose of the gastrointestinal tract is to digest (break down) and absorb (take into the blood stream) food. In order to fulfill this purpose, food must be ground, mixed, and transported through the intestines, where it is digested and absorbed. In addition, undigested and unabsorbed portions of the food must be eliminated from the body.
In functional diseases of the gastrointestinal tract, the grinding, mixing, digestion, and absorption functions are disturbed to only a minor degree. These functions are essentially maintained, perhaps because of a built-in over-capacity of the gastrointestinal tract to perform these functions. The most commonly affected function in these diseases is transportation. In the stomach and small intestine, the symptoms of slowed transportation are nausea, vomiting, abdominal bloating (the sensation of abdominal fullness), and abdominal distention (enlargement). The symptom of rapid transportation usually is diarrhea. The interpretation of symptoms, however, may be more complicated than this. For example, let's say that a person has abnormally rapid emptying of the stomach. The sensing of this rapid emptying by the intestinal sensory nerves normally brings about a motor nerve response to slow emptying of the stomach and transportation through the small intestine. Thus, rapid emptying of the stomach may give rise to symptoms of slowed transportation.
In the colon, abnormally slowed or rapid transportation results in constipation or diarrhea, respectively. In addition, there may be increased amounts of mucus coating the stool or a sense of incomplete evacuation after a bowel movement.
As discussed previously, normal sensations may be abnormally processed and perceived. Such an abnormality could result in abdominal bloating and pain. Abnormally processed sensations from the gastrointestinal organs also might lead to motor responses that cause symptoms of slowed or rapid transportation.
Slowed transportation of digesting food through the small intestine may be complicated, for example, by bacterial overgrowth. In bacterial overgrowth, gas-producing bacteria that are normally restricted to the colon move up into the small intestine. There, they are exposed to greater amounts of undigested food than in the colon, which they turn into gas. This formation of gas can aggravate bloating and/or abdominal distention and result in increased amounts of flatus (passing gas, or flatulence) and diarrhea.
The gastrointestinal tract has only a few ways of responding to diseases. Therefore, the symptoms often are similar regardless of whether the diseases are functional or non-functional. Thus, the symptoms of both functional and non-functional gastrointestinal diseases are nausea, vomiting, bloating, abdominal distention, diarrhea, constipation, and pain. For this reason, when functional disease is being considered as a cause of symptoms, it is important that the presence of non-functional diseases be excluded (ruled out). In fact, the exclusion of non-functional diseases usually is more important in evaluating patients who are suspected of having functional disease. This is so, in large part, because the tests for diagnosing functional disease are complex, not readily available, and often not very reliable. In contrast, the tests for diagnosing non-functional diseases are widely available and sensitive (able to diagnose most cases).

What are the complications of IBS?

The complications of functional diseases of the gastrointestinal tract are relatively limited. Since symptoms are most often provoked by eating, patients who alter their diets and reduce their intake of calories may lose weight. Fortunately, loss of weight is unusual in functional diseases, and it should suggest the presence of a non-functional disease. Symptoms that awaken patients from sleep also are more likely to be due to non-functional than functional diseases.
Most commonly, functional diseases interfere with the patients' comfort and their daily activities. For example, patients who suffer from morning diarrhea may not leave their home until the diarrhea stops. If the diarrhea is constant, they may go only to places where they know that a toilet is readily available. Patients who develop pain after eating may skip lunch. Very commonly, patients associate symptoms with specific foods, such as milk, fat, vegetables, etc. Whether or not these associations are real, these patients will restrict their diets accordingly. Milk is the food that is most commonly eliminated, often unnecessarily and to the detriment of adequate calcium intake. The interference with daily activities also can lead to problems with interpersonal relationships, especially with spouses. However, most patients with functional disease tend to just live with their symptoms and infrequently visit physicians for diagnosis and treatment.

How is IBS diagnosed?

The Rome Criteria

The symptoms of IBS are varied and inconsistent among patients. Moreover, there are no characteristically abnormal tests that can be used to diagnose IBS. All of this has made it difficult to define IBS and identify patients, especially for research studies. In 1999, a group of international investigators met in Rome for a second time (Rome II). There, they developed a set of criteria for symptoms to be used for diagnosing IBS.
The Rome II Criteria state that in order to be diagnosed with IBS, a patient should have suffered abdominal pain or discomfort for 12 weeks or more (not necessarily consecutive weeks) in the previous 12 months. The pain or discomfort should have two out of the three following features:

Relief with defecation
Onset associated with a change in the frequency of stool
Onset associated with a change in the form of stool

Other symptoms that are not essential, but support a diagnosis of IBS, are: (1) abnormal frequency of stools (more than 3/day or less than 3/week); (2) abnormal stool form (lumpy and hard, or loose and watery); (3) abnormal stool passage (straining, urgency, or feeling of incomplete evacuation); (4) passage of mucus; and (5) bloating (feeling of abdominal distention, or enlargement).
The Rome II criteria are rather specific for a diagnosis of IBS. In essence, they require the presence of prolonged abdominal pain or discomfort that is in some way related to an alteration in the pattern of bowel movements. Symptoms of dyspepsia (nausea or abdominal discomfort following meals), abdominal distention, and increased flatus (passing gas, or flatulence) alone do not fall within this definition. Nevertheless, many patients have these symptoms along with the symptoms of IBS. It is not clear if these patients have one problem (IBS) or more than one problem.
In 2006, the group of international investigators met for the third time in Rome and developed the Rome III criteria. A system of classification of gastrointestinal functional disorders came out of this meeting that was much more comprehensive and detailed than prior classifications. The definition of the subcategory, IBS, remained essentially unchanged, however, except for a requirement that the abdominal pain occur at a frequency of at least three times per month. The classification also clearly set apart from IBS three other functional bowel disorders - functional bloating, functional constipation, functional diarrhea, and unspecified functional bowel disorder.

Exclusion of non-functional gastrointestinal disease

As mentioned previously, the exclusion of non-functional disease in patients with suspected IBS is an important concern. There are many tests to exclude non-functional diseases. The primary issue, however, is to decide which tests are reasonable to perform. Since each case is individual, different tests may be reasonable for different patients. Nevertheless, there are some basic tests that are often performed to exclude non-functional gastrointestinal disease. These tests identify anatomic (structural) and histological (microscopic) diseases of the intestines. As always, a detailed history from the patient and a physical examination frequently will suggest the cause of symptoms. Routine screening blood tests often are performed looking for clues to unsuspected diseases. Examinations of stool also are a part of the evaluation since they may reveal infection, signs of inflammation, or blood and direct further diagnostic testing. Sensitive stool testing (antigen/antibody) for Giardia lamblia would be reasonable because this parasitic infection is common and can be acute or chronic. Some physicians do blood testing for celiac disease (sprue), but the value of doing this is unclear. Moreover, if an EGD is planned, biopsies of the duodenum usually will make the diagnosis of celiac disease. Both X-rays and endoscopies can identify anatomic diseases. Only endoscopies, however, can diagnose histological diseases because biopsies (taking samples of tissue) can be taken during the procedure. The X-ray tests include:

The esophagram and video-fluoroscopic swallowing study for examining the esophagus
The upper gastrointestinal series for examining the stomach and duodenum
The small bowel series for examining the small intestine
The barium enema for examining the colon and terminal ileum.

The endoscopic tests include:

Upper gastrointestinal endoscopy (esophago-gastro-duodenoscopy, or EGD) to examine the esophagus, stomach, and duodenum
Colonoscopy to examine the colon and terminal ileum
Endoscopy also is available to examine the small intestine, but this type of endoscopy is complex, not widely available, and of unproven value in suspected IBS.

For examination of the small intestine, there is also a capsule containing a tiny camera that can be swallowed. As the capsule travels through the intestines, it sends pictures of the inside of the intestines to an external recorder for later review. However, the capsule is not widely available and its value in IBS has not yet been proven.
X-rays are easier to perform and are less costly than endoscopies. The skills necessary to perform X-rays, however, are becoming rarer among radiologists because they are doing them less often. Therefore, the quality of the X-rays often is not as high as it used to be. As noted above, endoscopies have an advantage over X-rays because at the time of endoscopies, biopsies can be taken to diagnose or exclude histological diseases, something that X-rays cannot do.

Exclusion of non-intestinal disease

Patients with suspected IBS often undergo abdominal ultrasonography (US), computerized tomography (CT or CAT scans), or magnetic resonance imaging (MRI). These tests are used primarily to diagnose non-intestinal diseases. (Although these tests also may diagnose intestinal diseases, their value for this purpose is limited. As described above, X-ray and endoscopy are better tests.) It also is important to realize that US, CT, and MRI are powerful tests and will uncover abnormalities that are unrelated to IBS. The most common example is the finding of gallstones that, in fact, often cause no symptoms. This finding can cause a problem if the gallstones are assumed to be the source of the IBS symptoms. The problem is that surgical removal of the gallbladder with its gallstones (cholecystectomy) is unlikely to relieve the symptoms of IBS. (Cholecystectomy would be expected to relieve only the characteristic symptoms that gallstones sometimes can cause.) Tests to exclude non-intestinal diseases may be appropriate in specific situations, although certainly not in most patients.

Evaluation of intestinal transportation

If abnormal function of the muscles of the small intestine is suspected, tests to evaluate transportation through the small intestine or the colon (small intestinal and colonic transit studies, respectively) are available. These studies are done with either radioactive compounds or markers that can be seen on X-rays of the abdomen. It also is possible to pass catheters into the stomach and small intestine or the colon to determine if the muscles of these organs are working normally (antro-duodenal and colonic motility studies, respectively). Finally, constipation due to malfunction of the anal muscles can be diagnosed by ano-rectal motility studies.

Psychiatric illness

The possibility of psychiatric (psychosomatic) illness often arises in patients with IBS because the symptoms frequently are subjective, and no objective abnormalities can be identified. Psychiatric illness may complicate IBS, but it is unclear if psychiatric illness causes IBS. If there is a possibility of psychiatric illness, a psychiatric evaluation is appropriate.

How is IBS treated?

The treatment of IBS is a difficult and unsatisfying topic because so few drugs have been studied or have been shown to be effective in treating IBS. Moreover, the drugs that have been shown to be useful have not been substantially effective. This difficult situation exists for many reasons, as follows:

Life-threatening illnesses (for example, cancer, heart disease , and high blood pressure), are the diseases that capture the public's interest and, more importantly, research funding. IBS is not a life-threatening illness and has received little research funding. Because of the lack of research, an understanding of the physiologic processes (mechanisms) that are responsible for IBS has been slow to develop. Effective drugs cannot be developed until there is an understanding of these mechanisms.

Research in IBS is difficult. IBS is defined by subjective symptoms, (such as pain), rather than objective signs (for instance, the presence of an ulcer). Subjective symptoms are more unreliable than objective signs in identifying homogenous groups of patients. As a result, groups of patients with IBS who are undergoing treatment are likely to contain some patients who do not have IBS, and this may negatively affect the results of the treatment. Moreover, the results of treatment must be evaluated on the basis of subjective responses (such as improvement of pain). In addition to being more unreliable, subjective responses are more difficult to measure than objective responses (such as the healing of an ulcer).

Different subtypes of IBS (for example, diarrhea-predominant, constipation-predominant, etc.) are likely to be caused by different physiologic processes (mechanisms). It also is possible, however, that the same subtype may be caused by several different mechanisms in different people. What's more, any drug is likely to affect only one mechanism. Therefore, it is unlikely that any one medication can be effective in all-even most-patients with IBS, even patients with similar symptoms. This inconsistent effectiveness makes the testing of drugs difficult. Indeed, it can easily result in drug trials that demonstrate no efficacy (usefulness) when, in fact, the drug is helping a subgroup of patients.

Subjective symptoms are particularly prone to responding to placebos (inactive drugs, or sugar pills). In fact, in most studies, 20% to 40% of patients with IBS will improve if they receive inactive drugs. Now, all clinical trials of drugs for IBS require a placebo-treated group for comparison with the drug-treated group. So, the placebo response means that these clinical trials must utilize large numbers of patients to detect meaningful (significant) differences in improvement between the placebo and drug groups. Therefore, such trials are expensive to conduct.

The lack of understanding of the physiologic processes (mechanisms) that cause IBS has meant that treatment cannot be directed at these mechanisms. Instead, treatment usually is directed at the symptoms, which are primarily constipation, diarrhea, and abdominal pain. These symptoms are not mutually exclusive since patients may have abdominal pain with either constipation or diarrhea. Moreover, periods of constipation may alternate with periods of diarrhea. This variation in symptoms over time can make the treatment of symptoms complex. The psychotropic drugs (antidepressants) and psychological treatments (for example, cognitive behavioral therapy) treat hypothetical causes of IBS (such as abnormal function of sensory nerves and the psyche) rather than the symptoms.

Constipation

Constipation is due to the slow transport (transit) of intestinal contents through the intestines, primarily the colon. This slow transit may be due to either abnormal function of the muscles of the entire colon or just the muscles of the anus and rectum.
The treatment of constipation in IBS usually begins with a trial of the supplements and medications that are used to treat constipation of any cause. In 2002, the FDA approved tegaserod (Zelnorm), the first drug specifically for the treatment of abdominal pain and constipation in women with IBS. However, in March of 2007, the FDA asked Novartis to suspend sales of tegaserod (Zelnorm) in the United States because a retrospective analysis of data by Novartis from more than 18,000 patients showed a slight difference in the incidence of cardiovascular events (heart attacks, strokes and angina) among patients on Zelnorm compared to placebo. The data showed that cardiovascular events occurred in 13 out of 11,614 patients treated with Zelnorm (.11%), compared to one cardiovascular event in 7,031 (.01%) placebo-treated patients. However, it is unclear whether Zelnorm actually causes heart attacks and strokes. Doctors and scientists will be scrutinizing the data to determine the long-term safety of Zelnorm.
The mechanism whereby tegaserod reduces constipation is interesting. It is the contractions of the intestinal muscles that controls transit of digesting food through the intestine. More contractions speed transit, fewer contractions slow transit. In constipated patients, contractions are fewer. One important factor in the control of the contractions is serotonin. Serotonin is a chemical manufactured by nerves in the intestine. It is released by the nerves and then travels to other nerves where it binds to receptors on the nerves. It is, in scientific terms, a "neurotransmitter" that allows nerves to communicate with each other. When it binds to receptors on nerves that control the contractions of intestinal muscles, serotonin can either promote or prevent contractions depending on the type of receptor it binds to. Binding to some types of receptors causes contractions, and binding to other types of receptors prevents contractions. The serotonin 5-HT4 receptor is a receptor that prevents contractions when serotonin binds to it. Tegaserod blocks the 5-HT4 receptor, prevents serotonin from binding to it, and thereby increases contractions of the intestinal muscles. The increased contractions speed the transit of digesting food. In addition, tegaserod reduces the sensitivity of the intestinal pain-sensing nerves and can thereby reduce the perception of pain.
In a randomized, double blind, placebo-controlled, study involving more than 1000 patients (80% women) with constipation-predominant IBS, tegaserod was found to be more effective than placebo in increasing the frequency of stools, relieving abdominal pain and discomfort, and decreasing the sensations of bloating among women. (There was an insufficient number of men in the study to draw conclusions about the effectiveness of treatment in men.) The beneficial effects of treatment started during the first week of treatment and were sustained throughout the 12-week period of study.
Diarrhea was the only side effect in the tegaserod study. Diarrhea usually occurred early during treatment and resolved quickly even if the treatment was continued. There was no effect of tegaserod on blood counts, liver and kidney tests, electrocardiograms, blood pressure, pulse, and body weight. (A medication similar to tegaserod, called cisapride or Propulsid, which also promoted intestinal muscle contractions, was withdrawn from the market due to rare but potentially fatal effects on the electrical rhythm of the heart. So far, there have been no reports of rhythm disturbances related to tegaserod.) Patients with major liver or kidney disease should not take tegaserod. The safety of tegaserod to the fetus or nursing infants has not been studied and is unknown. Therefore, pregnant or nursing women should avoid tegaserod.

Diarrhea

The most widely studied drug for the treatment of diarrhea in IBS is loperamide (Imodium). Loperamide appears to work by inhibiting (slowing down) the contractions of the muscles of the small intestine and colon. Loperamide is approximately 30% more effective than a placebo in improving symptoms among patients who have diarrhea as the predominant manifestation of their IBS. It is not clear if loperamide reduces abdominal pain. Loperamide can be potent and itself can cause constipation. Therefore, the dose must be carefully adjusted and individualized for each patient. Alosetron (Lotronex) is used to treat diarrhea and abdominal discomfort that occurs in women with severe IBS that does not respond to other simpler treatments.
Alosetron, like tegaserod, affects the serotonin receptors. (See the discussion above of tegaserod.) Alosetron blocks the 5-HT3 receptor, a receptor that causes contractions when serotonin binds to it. Alosetron, by blocking 5-HT3 receptors, prevents serotonin from binding and thereby prevents contractions.
Alosetron was approved by the FDA in February, 2000, but was withdrawn from the market in November, 2000, because of serious, life-threatening, gastrointestinal side effects. In June 2002, it was approved again by the FDA for marketing but in a restricted manner as part of a drug company-sponsored program for managing the risks associated with treatment. Use of alosetron is allowed only among women with severe, diarrhea-predominant, IBS who have failed to respond to conventional treatment for IBS.
The most common side effect with alosetron is constipation. One-quarter to one-third of patients may develop this side effect, but in only 10% (10 out of every 100 patients) will the drug need to be stopped temporarily or permanently.
A rare side effect that has occurred with alosetron is severe intestinal inflammation caused by poor circulation of blood ( ischemic colitis). This complication is life-threatening, may require surgery, and has even caused death in a small number of patients. Therefore, immediate medical attention should be sought if the signs of ischemic colitis (rectal bleeding or a sudden worsening of abdominal pain) occur.

Abdominal pain

The most widely studied drugs for the treatment of abdominal pain are a group of drugs called smooth-muscle relaxants.
The gastrointestinal tract muscle is composed of a type of muscle called smooth muscle. (By contrast, skeletal muscles, such as the biceps, are composed of a type of muscle called striated muscle.) Smooth muscle relaxant drugs reduce the strength of contraction of the smooth muscles but do not affect the contraction of other types of muscles. They are used in IBS with the assumption (not proved) that strong or prolonged contractions of smooth muscles in the intestine-spasms-are the cause of pain in IBS. There are even smooth muscle relaxants that are placed under the tongue, like nitroglycerin for angina, so that they may be absorbed rapidly. Smooth muscle relaxants are approximately 20% more effective than a placebo in reducing abdominal pain. It is not clear if smooth muscle relaxants have a beneficial effect on constipation or diarrhea.
Commonly used smooth muscle relaxants are hyoscyamine (for example, Levsin) and methscopolamine (for example, Pamine). Other drugs combine smooth muscle relaxants with a sedative (for example, Donnatal), but there is no evidence that the addition of sedatives adds to the efficacy (effectiveness) of the treatment.

Psychotropic drugs

Patients with IBS are frequently found to be suffering from depression, but it is unclear if the depression is the cause of IBS, the result of the IBS, or unrelated to the IBS. Several trials have shown that antidepressants are effective in IBS in relieving abdominal pain and, perhaps, diarrhea. The antidepressants work in IBS, however, at relatively low doses that have little or no effect on depression. It is believed therefore, that they are working not by combating depression, but in different ways (through different mechanisms). For example, these drugs have been shown to adjust (modulate) the activity of nerves and to have analgesic (pain-relieving) effects as well. Commonly used psychotropic drugs include the tricyclic antidepressants, amitriptyline (Elavil, Endep), desipramine (Norpramine), and trimipramine (Surmontil). Although studies are encouraging, it is not yet clear whether the newer class of antidepressants, the serotonin-reuptake inhibitors, such as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) are effective.

Psychological treatments

Psychological treatments include cognitive-behavioral therapy, hypnosis, psychodynamic or interpersonal psychotherapy, and relaxation/stress management. They have been used in patients with IBS who are psychologically distressed to the point that their quality of life is being impaired. A few studies have shown that psychological treatments can reduce anxiety and other psychological symptoms in addition to reducing IBS symptoms, particularly pain and diarrhea.

Diet

It is unclear if diet has much effect on the symptoms of IBS. Nevertheless, patients often associate their symptoms with specific foods (such as salads, fats, etc.). Although specific foods might worsen IBS, it is clear that they are not the cause of IBS. The common placebo response in IBS also may explain the improvement of symptoms in some people with the elimination of specific foods.
Dietary fiber often is recommended for patients with IBS. Fiber probably is of benefit to IBS patients with constipation, but it does not reduce abdominal pain. Lactose (milk sugar) intolerance often is blamed for diarrhea-predominant IBS, but it does not cause IBS. Because they are both common, lactose intolerance and IBS may coexist. In this situation, restricting lactose will improve, but not eliminate the symptoms. Lactose intolerance is easily determined by testing the effect of lactose (hydrogen breath testing) or trying a strict lactose elimination diet. Intolerance to sugars other than lactose, specifically, fructose, sucrose, and sorbitol, may cause symptoms that are similar to IBS or make IBS worse. It is unlikely, however, that these sugars cause IBS.

Is there a relationship between IBS and small intestinal bacterial overgrowth?

IBS and small intestinal bacterial overgrowth (SIBO)

There is a striking similarity between the symptoms of IBS and a condition known as small intestinal bacterial overgrowth (SIBO).
The entire gastrointestinal tract, including the small intestine, normally contains bacteria. The number of bacteria is greatest in the colon (at least 1,000,000,000 bacteria per ml of fluid) and much lower in the small intestine (less than 10,000 bacteria per ml of fluid). Moreover, the types of bacteria within the small intestine are different than the types of bacteria within the colon. SIBO refers to a condition in which abnormally large numbers of bacteria (at least 100,000 bacteria per ml of fluid) are present in the small intestine, and the types of bacteria in the small intestine resemble more the bacteria of the colon than the small intestine.
The symptoms of SIBO include excess gas, abdominal bloating and distension, diarrhea, and abdominal pain. A small number of patients with SIBO have chronic constipation rather than diarrhea. When the overgrowth is severe and prolonged, the bacteria may interfere with the digestion and/or absorption of food, and deficiencies of vitamins and minerals may develop. Loss of weight also may occur. The symptoms of SIBO tend to be chronic; a typical patient with SIBO can have symptoms that fluctuate in intensity over months, years, or even decades before the diagnosis is made.
It has been theorized that SIBO may be responsible for the symptoms in at least some patients with IBS. The estimates run as high as 50% of patients with IBS. Support for the SIBO theory of IBS comes from the observation that many patients with IBS are found to have an abnormal hydrogen breath test, a test used for diagnosing SIBO. In addition, some patients with IBS have improvement of their symptoms after treatment with antibiotics, the primary treatment for SIBO. Moreover, small, scientifically sound studies have shown that treatment with probiotics ("good" bacteria) improves the symptoms of IBS. Although there are several ways in which probiotics may be having their beneficial effect, one way is by affecting the existing bacteria in the small intestine. If this is indeed the mechanism of action, it would support the theory that SIBO is a cause of IBS. Nevertheless, it has not been determined if this is the mechanism of action of probiotics in IBS.
Although the theory that SIBO causes IBS is tantalizing and there is much anecdotal information that supports it, the rigorous scientific studies that are necessary to prove or disprove the theory have just begun. Nevertheless, many physicians have already begun to treat patients with IBS for SIBO. In addition, a lack of rigorous scientific studies demonstrating benefit from antibiotics and probiotics has not stopped physicians from using them for treating patients.

Treatment of IBS based on the theory of small intestinal bacterial overgrowth.

The two most common treatments for SIBO among patients with IBS are oral antibiotics and probiotics. Probiotics are live bacteria that when ingested by an individual, result in a health benefit to the individual. The most common probiotic bacteria are lactobacilli (also used in the production of yoghurt) and bifidobacteria, both of which are found in the intestine of normal individuals. There are numerous explanations for how probiotic bacteria might benefit individuals; however, the beneficial mechanism of action has not been identified clearly. It may be that the probiotic bacteria inhibit other bacteria in the intestine that may be causing symptoms, or it may be that the probiotic bacteria act on the host's intestinal immune system to suppress inflammation.
Several antibiotics either alone or in combination are reported to be successful in treating SIBO in patients with IBS. Treatment success, when measured by either improvements in symptoms or by normalization of the hydrogen breath test, ranges from 40-70%. When one antibiotic fails, doctors may add another antibiotic or change to a different antibiotic, but the doses of antibiotic, the duration of treatment, and the need for maintenance treatment to prevent recurrence of SIBO have not been adequately studied. Most physicians use standard doses of antibiotics for one to two weeks. Probiotics may be used alone, in combination with antibiotics, or for prolonged maintenance. When probiotics are used, it probably is best to use one of the several probiotics that have been studied in medical trials and shown to have effects on the small intestine, (though not necessarily in SIBO). The commonly-sold probiotics in health-food stores may not be effective. Moreover, they often do not contain the stated bacteria or the bacteria are dead. Following are some options for treatment:

neomycin orally for 10 days (One observation that has been made is that neomycin eradicates methane-producing bacteria and alleviates constipation.)

levofloxacin (Levaquin) or ciprofloxacin (Cipro) for 7 days

metronidazole (Flagyl) for 7 days

levofloxacin (Levaquin) combined with metronidazole (Flagyl) for 7 days

rifaximin (Xifaxan) for 7 days. Rifaximin is a unique antibiotic that is not absorbed from the intestine, and, therefore, acts only within the intestine. Because very little rifaximin is absorbed into the body, it has few important side effects. Higher-than-normal doses of rifaximin (1200 mg/day for 7 days) were superior to standard lower doses (400 or 800 mg/day) in normalizing the hydrogen breath test in patients with SIBO and IBS; however, it is not yet known whether the larger dose is any better at suppressing symptoms.

Commercially available probiotics such as VSL#3 or Flora-Q which are mixtures of several different bacterial species have been used for treating small intestinal bacterial overgrowth and IBS, but their effectiveness is not known. Bifidobacterium infantis 35624 is the only probiotic that has been demonstrated to be effective for treating patients with IBS.

Treatment with antibiotic versus probiotic.

There are no trials of treatment comparing antibiotics and probiotics; however, antibiotics have certain disadvantages. Specifically, symptoms tend to recur after treatment is discontinued, and prolonged or repeated courses of treatment may be necessary in some patients. Physicians are reluctant to prescribe prolonged or repeated courses of antibiotics because of concern over long-term side effects of the antibiotics and emergence of bacteria that are resistant to the antibiotics. Physicians have less concern over long-term side effects or emergence of resistant bacteria with probiotics and, therefore, are more willing to prescribe probiotics repeatedly and for prolonged periods. One option is to treat initially with a short course of antibiotics and then long-term with probiotics. Long-term studies comparing antibiotics, probiotics, and combinations of antibiotics and probiotics are badly needed.

What is a reasonable approach to IBS?

The initial approach to IBS-treatment or testing--depends on the patient's symptoms and their duration. If the symptoms clearly fit the definition for IBS and have been present for years without change, then there is less need for extensive testing to exclude other intestinal and non-intestinal diseases. Rather, treatment that is directed at specific symptoms, as discussed previously, can begin. The role of antibiotics and/or probiotics is currently being studied.
On the other hand, if the symptoms are of recent onset (such as weeks or months), progressively worsening, severe, or associated with "warning" signs, then early testing is appropriate. Warning signs include loss of weight, nighttime awakening, rectal bleeding, and signs of inflammation, such as fever or abdominal tenderness. Testing also is appropriate if, in addition to symptoms of IBS, there are other prominent symptoms that are not part of IBS (for example, abdominal distention, increased flatus, or vomiting). Finally, testing is warranted if attempts at treating the symptoms of IBS are unsuccessful.
If there are symptoms that suggest non-IBS diseases, tests that are specific for these conditions should be done first. The reason is that if these other tests disclose disease other than IBS, it may not be necessary to do additional testing. Examples of symptoms and possible testing include:

Vomiting: upper gastrointestinal endoscopies to diagnose inflammatory or obstructing diseases; and gastric emptying studies and/or electrogastrography to diagnose impaired emptying of the stomach.

Abdominal distention with or without increased flatulence: upper gastrointestinal and small intestinal X-rays to diagnose obstructing diseases; and hydrogen breath testing to diagnose SIBO.

Constipation without pain: colonoscopy or barium enema to exclude colonic cancer; marker studies to diagnose slow colonic transit; and ano-rectal motility studies to diagnose rectal muscle disorders

For a patient with typical symptoms of IBS who requires testing to exclude other diseases, the testing might reasonably include a standard screening panel of blood tests and stool specimens for examination for parasites, pus, and blood. A plain X-ray of the abdomen might be done during an episode of abdominal pain (to look for intestinal blockage or obstruction). Testing for lactose intolerance or a trial of a strict lactose-free diet should be done. Colonoscopy (and, possibly, esophago-gastro-duodenoscopy, or EGD) would be the next test, probably with multiple biopsies of the colon (and stomach and duodenum if EGD is done). Finally, small intestinal X-rays might be done.
If all of the above appropriate testing reveals no disease that could be causing the symptoms, other tests should be considered. These tests include hydrogen breath testing to diagnose SIBO and antro-duodenal and colonic motility studies to diagnose intestinal muscle or nerve disorders. These studies probably should be done at centers that have experience and expertise in diagnosing and treating these diseases.

Heart Failure : Causes, Types, Symptoms and Medications

2009-11-26T19:37:00.001+05:30

Heart Failure Overview

Heart failure affects about 5 million Americans. Roughly 550,000 people are diagnosed with heart failure each year. It is the leading cause of hospitalization in people older than 65.

What Is Heart Failure?

Heart failure does not mean the heart has stopped working. Rather, it means that the heart's pumping power is weaker than normal. With heart failure, blood moves through the heart and body at a slower rate, and pressure in the heart increases. As a result, the heart cannot pump enough oxygen and nutrients to meet the body's needs. The chambers of the heart respond by stretching to hold more blood to pump through the body or by becoming more stiff and thickened. This helps to keep the blood moving for a short while, but in time, the heart muscle walls weaken and are unable to pump as strongly. As a result, the kidneys often respond by causing the body to retain fluid (water) and sodium. If fluid builds up in the arms, legs, ankles, feet, lungs or other organs, the body becomes congested, and congestive heart failure is the term used to describe the condition.

What Causes Heart Failure?

Heart failure is caused by many conditions that damage the heart muscle, including:

Coronary artery disease. Coronary artery disease (CAD), a disease of the arteries that supply blood and oxygen to the heart, causes decreased blood flow to the heart muscle. If the arteries become blocked or severely narrowed, the heart becomes starved for oxygen and nutrients.
Heart attack. A heart attack may occur when a coronary artery becomes suddenly blocked, stopping the flow of blood to the heart muscle and damaging it. All or part of the heart muscle becomes cut off from its supply of oxygen. A heart attack can damage the heart muscle, resulting in a scarred area that does not function properly.
Cardiomyopathy. Damage to the heart muscle. Causes include artery or blood flow problems, infections, and alcohol and drug abuse.
Conditions that overwork the heart. Conditions including high blood pressure (hypertension), heart valve disease, thyroid disease, kidney disease, diabetes or heart defects present at birth can all cause heart failure. In addition, heart failure can occur when several diseases or conditions are present at once.

What Are the Types of Heart Failure?

Systolic dysfunction (or systolic heart failure) occurs when the heart muscle doesn't contract with enough force, so there is less oxygen-rich blood that is pumped throughout the body.
Diastolic dysfunction (or diastolic heart failure) occurs when the heart contracts normally, but the ventricle – the main pumping chamber -- does not relax properly, reducing the amount of blood that can enter the heart.
A test called the ejection fraction (EF) is used measure how well your heart pumps with each beat to help determine if systolic or diastolic dysfunction is present. The ejection fraction is a measure of the percentage of blood that your heart pumps out with each beat. Your doctor can discuss which condition you have.
In patients with systolic heart failure, the ejection fraction is less than 40%. Imaging studies such as X-ray and an echocardiogram (heart ultrasound) show the heart is enlarged and pumps out less than a normal amount of blood with each beat.
In contrast, patients with diastolic heart failure usually have a normal ejection fraction, normal heart pumping capability, but the imaging studies show that the heart does not fill up with blood properly during the heart relaxation phase that occurs between beats.

Stages of Heart Failure

In 2001, the American Heart Association (AHA) and American College of Cardiology (ACC) developed the "Stages of Heart Failure." These stages, which were updated in 2005, will help you understand that heart failure is often a progressive condition and can worsen over time. They will also help you understand why a new medication was added to your treatment plan and may help you understand why lifestyle changes and other treatments are needed.
The stages classified by the AHA and ACC are different than the New York Heart Association (NYHA) clinical classifications of heart failure that rank patients as class I-II-III-IV, according to the degree of symptoms or functional limits. Ask your doctor what stage of heart failure you are in.

Check the table below to see if your therapy matches what the AHA and ACC recommend. Note that you cannot go backward in stage, only forward.

The table below outlines a basic plan of care that may or may not apply to you, based on the cause of your heart failure and your special needs. Ask your doctor to explain therapies that are listed if you do not understand why you are or are not receiving them.

Stage

Definition of Stage

Usual Treatments

Stage A

People at high risk of developing heart failure (pre-heart failure), including people with:

Hypertension
Diabetes
Coronary artery disease
Metabolic syndrome
History of cardiotoxic drug therapy
History of alcohol abuse
History of rheumatic fever
Family history of cardiomyopathy

Exercise regularly.
Quit smoking.
Treat hypertension.
Treat lipid disorders.
Discontinue alcohol or illegal drug use.
An angiotensin converting enzyme inhibitor (ACE inhibitor) or an angiotensin II receptor blocker (ARB) is prescribed if you've had coronary artery disease or if you have diabetes, high blood pressure, or other vascular or cardiac conditions.
Beta-blockers may be prescribed if you have high blood pressure or if you've had a previous heart attack.

Stage B

People diagnosed with systolic left ventricular dysfunction but who have never had symptoms of heart failure (pre-heart failure), including people with:

Prior heart attack
Valve disease
Cardiomyopathy

The diagnosis is usually made when an ejection fraction of less than 40% is found during an echocardiogram test.

Treatment methods above for Stage A apply.
All patients should take an angiotensin converting enzyme inhibitor (ACE inhibitors) or angiotensin II receptor blocker (ARB).
Beta-blockers and an aldosterone inhibitor should be prescribed for patients after a heart attack.
Surgery options for coronary artery repair and valve repair or replacement (as appropriate) should be discussed.
If appropriate, surgery options should be discussed for patients who have had a heart attack.

Stage C

Patients with known systolic heart failure and current or prior symptoms. Most common symptoms include:

Shortness of breath
Fatigue
Reduced ability to exercise

Treatment methods above for Stage A apply.
All patients should take an angiotensin converting enzyme inhibitor (ACE inhibitors) and beta-blockers.
African-American patients may be prescribed a hydralazine/nitrate combination if symptoms persist.
Diuretics (water pills) and digoxin may be prescribed if symptoms persist.
An aldosterone inhibitor may be prescribed when symptoms remain severe with other therapies.
Restrict dietary sodium (salt)
Monitor weight
Restrict fluids (as appropriate)
Drugs that worsen the condition should be discontinued.
As appropriate, cardiac resynchronization therapy (biventricular pacemaker) may be recommended.
An implantable cardiac defibrillator (ICD) may be recommended.

Stage D

Patients with systolic heart failure and presence of advanced symptoms after receiving optimum medical care.

Treatment methods for Stages A, B ,& C apply.
Patient should be evaluated to determine if the following treatments are available options: heart transplant, ventricular assist devices, surgery options, research therapies, continuous infusion of intravenous inotropic drugs, and end-of-life (palliative or hospice) care.

Heart Failure Symptoms

What Are Heart Failure Symptoms?

You may not have any heart failure symptoms, or the symptoms may be mild to severe. Symptoms can be constant or can come and go. Heart failure symptoms are related to the changes that occur to your heart and body, and the severity depends on how weak your heart is. The symptoms can include:

Congested lungs. A weak heart causes fluid to back up in the lungs. This can cause shortness of breath with exercise or difficulty breathing at rest or when lying flat in bed. Lung congestion can also cause a dry, hacking cough or wheezing.
Fluid and water retention. A weak heart pumps less blood to your kidneys and causes fluid and water retention, resulting in swollen ankles, legs, and abdomen (called edema) and weight gain. This can also cause an increased need to urinate during the night as your body attempts to get rid of this excess fluid. Bloating in your stomach may cause a loss of appetite or nausea.
Dizziness, fatigue, and weakness. Less blood to your major organs and muscles makes you feel tired and weak. Less blood to the brain can cause dizziness or confusion.
Rapid or irregular heartbeats. The heart beats faster to pump enough blood to the body. This can cause a fast or irregular heartbeat.

If you have heart failure, you may have one or all of these symptoms or you may have none of them. In addition, your symptoms may not be related to how weak your heart is; you may have many symptoms but your heart function may be only mildly weakened. Or you may have a more severely damaged heart but have few symptoms.

How Can I Lessen My Symptoms?

To lessen symptoms:

Maintain fluid balance. Your doctor may ask you to keep a record of the amount of fluids you drink or eat and how often you go to the bathroom. Remember, the more fluid you carry in your blood vessels, the harder your heart must work to pump excess fluid through your body. Limiting your fluid intake to less than two liters per day will help decrease the workload of your heart and prevent symptoms from recurring.
Limit how much salt (sodium) you eat.
Monitor your weight and lose weight if needed. Learn what your "dry" or "ideal" weight is. This is your weight without extra water (fluid). Your goal is to keep your weight within four pounds of your dry weight. Weigh yourself at the same time each day, preferably in the morning, in similar clothing, after urinating but before eating, and on the same scale. Record your weight in a diary or calendar. If you gain 2 pounds in one day or 5 pounds in one week, call your doctor. Your doctor may want to adjust your medications.
Monitor your symptoms. Call your doctor if new symptoms occur or if your symptoms worsen. Do not wait for your symptoms to become so severe that you need to seek emergency treatment.
Take your medications as prescribed.Medications are used to improve your heart's ability to pump blood, decrease stress on your heart, decrease the progression of heart failure, and prevent fluid retention. Many heart failure medications are used to decrease the release of harmful hormones. These drugs will cause your blood vessels to dilate or relax (thereby lowering your blood pressure).

Heart Failure - Medications

You probably will need to take a combination of medicines to treat heart failure, even if you do not have symptoms yet. Medicines do not cure heart failure. But they can help you manage your symptoms.

The goals of drug treatment are to relieve or control symptoms of heart failure, improve daily function and quality of life, slow the progression of the disease, and reduce the risk of complications, hospital stays, and premature death.

Medicines are used to treat the problems associated with heart failure, including:

Fluid buildup, swelling, and water retention (edema).
The reduced pumping ability of the heart.
The effects of the body's attempt to compensate for heart failure.
Other conditions that can lead to heart failure, such as coronary artery disease, high blood pressure, or diabetes.
Prevention of complications, such as stroke.

It is extremely important that you take your medicines exactly as recommended by your doctor. If you don't, your heart failure may get worse or you may develop sudden heart failure. For more information, see:

Heart failure: Taking your medicines properly.

Medicine Choices

A combination of medicines is often needed to control symptoms and slow the progression of heart failure. Some medicines are used to treat pumping problems systolic heart failure), and others are used to treat problems with filling (diastolic heart failure). The most commonly used and effective classes of medicines are as follows:

Medicines for pumping problems (systolic heart failure)

These include:

ACE inhibitors (angiotensin-converting enzyme inhibitors). ACE inhibitors allow blood vessels to relax and widen (dilate), making it easier for blood to flow through the vessels.
ARBs (angiotensin II receptor blockers). Like ACE inhibitors, ARBs allow blood vessels to relax and widen (dilate), making it easier for blood to flow through the vessels.
Diuretics. Diuretics stimulate the kidneys to remove more water and salt (sodium) from the body.
Aldosterone receptor antagonists. These medicines cause the kidneys to get rid of extra salt and fluid, and they help hold on to (retain) potassium by inhibiting the action of the hormone aldosterone.
Digoxin. Digoxin slows and strengthens heart contractions, enabling the heart to pump more blood with each beat.
Beta-blockers. Beta-blockers control symptoms of heart failure by either slowing the heart rate or making the blood vessels wider so blood flows more easily.
Vasodilators. Vasodilators lower blood pressure and reduce the workload on the heart. Vasodilators like hydralazine are often used along with nitrates.

Medicines for filling problems (diastolic heart failure)

Beta-blockers
Diuretics
ACE inhibitors
ARBs (angiotensin II receptor blockers)
Calcium channel blockers
Direct renin inhibitors

If your heart failure is related to another condition, such as irregular rapid heartbeats (arrhythmias), impaired blood flow to the heart muscle (ischemia), or high blood pressure, you may take specific drugs for these conditions.

Anticoagulants thin the blood and make it less likely to clot. These drugs may help prevent strokes.
Antiarrhythmics prevent rapid and sometimes irregular heart rhythms.
Antianginals control chest pain (angina) caused by impaired blood flow to the heart muscle.
Antihypertensives lower blood pressure.

My Disclosure Policy

2009-11-25T19:47:00.003+05:30

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25 Top Heart-Healthy Foods

2009-11-22T18:56:00.001+05:30

These 25 foods are loaded with heart-healthy nutrients that help protect your cardiovascular system.

By Jeanie Lerche Davis

Reviewed by Kathleen M. Zelman, MPH, RD, LD

From asparagus to sweet potatoes to a robust cabernet -- every bite (or sip) of heart-healthy foods delivers a powerful dose of phytonutrients that prevent and repair damage to cells. That's the essence of preventing heart disease.

"There really is an abundance of fruits and vegetables in many colors, shapes, sizes that are good for your heart," says Julia Zumpano, RD, LD, a dietitian with the Preventive Cardiology Center at The Cleveland Clinic. "You can definitely reduce your risk of developing cardiovascular disease by eating these foods every day."

Indeed, fresh produce provide the cornerstone for a heart- healthy diet because they help wipe out free radicals in the bloodstream, protecting blood vessels.
It's what Zumpano calls "the whole-foods diet. You want everything to be in its natural form, as it comes from the ground, the less processed the better," she says.
Whole grains, beans and legumes, nuts, fatty fish, and teas are just as important -- offering all sorts of complex heart-protective phytonutrients.
That's why variety is best in selecting heart-healthy foods, says Suzanne Farrell, MS, RD, a spokeswoman for the American Dietetic Association and owner of Cherry Creek Nutrition in Denver.
"Everyone's looking for that one magic food," Farrell tells WebMD. "But heart-healthy is not only about oatmeal and omega-3 fats. You need to look for ways to get all the different nutrients. Plus, you'll stick to a heart-healthy lifestyle longer if you have variety."

Lower Cholesterol: 15 Tips for Avoiding Heart Disease

25 Top Heart-Healthy Foods

With the help of these nutrition experts from The Cleveland Clinic and the American Dietetic Association, we've put together a list of the "best of the best" heart-healthy foods.
The foods listed here are all top-performers in protecting your heart and blood vessels. We've also got menu ideas -- so you can easily bring heart-healthy foods into your daily breakfast, lunch, and dinner.

Salmon

Omega-3 fatty acids.

Grill salmon with a yummy rub or marinade. Save a chunk to chop for a pasta or salad later on.

Flaxseed (ground)

Omega-3 fatty acids; fiber, phytoestrogens.

Ground flaxseed hides easily in all sorts of foods -- yogurt parfaits, morning cereal, homemade muffins, or cookies.

Oatmeal

Omega-3 fatty acids; magnesium; potassium; folate; niacin; calcium; soluble fiber.

Top hot oatmeal with fresh berries. Oatmeal-and-raisin cookies are a hearty treat.

Black or Kidney Beans

B-complex vitamins; niacin; folate; magnesium; omega-3 fatty acids; calcium; soluble fiber.

Give soup or salad a nutrient boost -- stir in some beans.

Almonds

Plant omega-3 fatty acids; vitamin E; magnesium; fiber; heart-favorable mono- and polyunsaturated fats; phytosterols.
Mix a few almonds (and berries) into low-fat yogurt, trail mix, or fruit salads.

Walnuts

Plant omega-3 fatty acids; vitamin E; magnesium; folate; fiber; heart-favorable mono- and polyunsaturated fats; phytosterols.
Walnuts add flavorful crunch to salads, pastas, cookies, muffins, even pancakes.

Red wine

Catechins and reservatrol (flavonoids).

Toast your good health! A glass of red wine could improve "good" HDL cholesterol.

Tuna

Omega-3 fatty acids; folate; niacin.

Here's lunch: Salad greens, fresh fruit, canned tuna. Keep "Salad Spritzer" - a light dressing -- in your office fridge.

Tofu

Niacin; folate; calcium; magnesium; potassium.

Tasty tofu is easy: Thinly slice "firm" tofu, marinate several hours, grill or stir-fry.

Brown rice

B-complex vitamins; fiber; niacin; magnesium, fiber.

Microwavable brown rice makes a quick lunch. Stir in a few chopped veggies (broccoli, carrots, spinach).

Soy milk

Isoflavones (a flavonoid); B-complex vitamins; niacin; folate, calcium; magnesium; potassium; phytoestrogens.

Soy milk is great over oatmeal or whole-grain cereal. Or, make a smoothie with soy milk.

Blueberries

Beta-carotene and lutein (carotenoids); anthocyanin (a flavonoid); ellagic acid (a polyphenol); vitamin C; folate; calcium, magnesium; potassium; fiber.

Cranberries, strawberries, raspberries are potent, too -- for trail mixes, muffins, salads!

Carrots

Alpha-carotene (a carotenoid); fiber.

Baby carrots are sweet for lunch. Sneak shredded carrots into spaghetti sauce or muffin batter.

Spinach

Lutein (a carotenoid); B-complex vitamins; folate; magnesium; potassium; calcium; fiber.

Pick spinach (not lettuce) for nutrient-packed salads and sandwiches.

Broccoli

Beta-carotene (a carotenoid); Vitamins C and E; potassium; folate; calcium; fiber.

Chop fresh broccoli into store-bought soup. For a veggie dip, try hummus (chickpeas).

Sweet potato

Beta-carotene (a carotenoid); vitamins A, C, E; fiber.

Microwave in a zip-lock baggie for lunch. Eat au naturale, or with pineapple bits.

Red bell peppers

Beta-carotene and lutein (carotenoids); B-complex vitamins; folate; potassium; fiber.

Rub with olive oil, and grill or oven-roast until tender. Delicious in wraps, salads, sandwiches.

Asparagus

Beta-carotene and lutein (carotenoids); B-complex vitamins; folate; fiber.
Grill or steam slightly, then dress with olive oil and lemon. It's a pretty side dish.

Oranges

Beta-cryptoxanthin, beta- and alpha-carotene, lutein (carotenoids) and flavones (flavonoids); vitamin C; potassium; folate; fiber.
Got orange juice? Check out the new nutrient-packed blends.

Tomatoes

Beta- and alpha-carotene, lycopene, lutein (carotenoids); vitamin C; potassium; folate; fiber.
For a flavor twist, try oil-packed tomatoes in sandwiches, salads, pastas, pizzas.

Acorn squash

Beta-carotene and lutein (carotenoids); B-complex and C vitamins; folate; calcium; magnesium; potassium; fiber.
Baked squash is comfort food on a chilly day. Serve with sautÃ©ed spinach, pine nuts, raisins.

Cantaloupe

Alpha- and beta-carotene and lutein (carotenoids); B-complex and C vitamins; folate; potassium; fiber.

A fragrant ripe cantaloupe is perfect for breakfast, lunch, potluck dinners. Simply cut and enjoy!

Papaya

Beta-carotene, beta-cryptoxanthin, lutein (carotenoids); Vitamins C and E; folate; calcium; magnesium; potassium.

Serve papaya salsa with salmon: Mix papaya, pineapple, scallions, garlic, fresh lime juice, salt and black pepper.

Dark chocolate

Reservatrol and cocoa phenols (flavonoids).

A truffle a day lowers blood pressure, but choose 70% or higher cocoa content.

Tea

Catechins and flavonols (flavonoids).

Make sun tea: Combine a clear glass jar, several tea bags, and hours of sunshine.

Your Guide to Nutrients in Heart-Healthy Foods

Phytoestrogens are substances in plants (like flaxseed) that have a weak estrogen-like action in the body. Studies suggest that flaxseed lowers the risk of blood clots, stroke, and cardiac arrhythmias. It may also help lower total and LDL "bad" cholesterol and triglycerides, and even blood pressure.

Phytosterols are plant sterols that chemically resemble cholesterol -- and seem to reduce blood cholesterol. All nuts and seeds, including wheat germ, have phytosterols.

Carotenoids are heart-protective antioxidants in many colorful fruits and veggies. Alpha-carotene, beta-carotene, lutein, and lycopene are carotenoids.
Polyphenols are another set of antioxidants that protect blood vessels, lower blood pressure, reduce LDL "bad" cholesterol. Flavonoid polyphenols include catechins, flavonones, flavonols, isoflavones, reservatrol, and anthocyanins. Non-flavonoid polyphenols include ellagic acid (found in all types of berries).
Omega-3 fatty acids (found in fatty fish like salmon) and alpha-linolenic fatty acids (found in plant foods like walnuts) help boost the immune system, reduce blood clots, and protect against heart attacks. They also increase good HDL levels, lower triglyceride levels, protect arteries from plaque buildup, are anti-inflammatory, and lower blood pressure.
B-complex vitamins -- like Vitamin B-12 (folate) and vitamin B-6 -- protect against blood clots and atherosclerosis, or hardening of the arteries. Niacin (vitamin B-3) helps increase HDL "good" cholesterol.
Vitamins C and E are antioxidants that protect cells from free radical damage. Magnesium, potassium, and calcium help lower blood pressure. Fiber-rich foods help lower cholesterol levels.

Reduce Your Risk of Nerve Pain and Damage From Diabetes

2009-11-21T19:57:00.001+05:30

By Rebecca Buffum Taylor

Reviewed by Louise Chang, MD

If you have diabetes, chances are good that you already have some form of nerve pain or nerve damage, called diabetic neuropathy. "People with diabetes have about a 60% chance of getting neuropathy of any kind," says Dace L. Trence, MD, an endocrinologist and director of the Diabetes Care Center at the University of Washington Medical Center in Seattle. "It's probably an equal risk of getting neuropathy with type 1 and type 2 diabetes."

You may have tingling, pain, or numbness in your feet and hands -- common signs of the diabetic nerve damage called peripheral neuropathy. Or you may have damage to the nerves that send signals to your heart, stomach, bladder, or sex organs, called autonomic neuropathy. Nerve damage can also be "silent," meaning you have no symptoms at all.

Sometimes, nerve damage starts even before a person is diagnosed with diabetes, Trance tells WebMD. "Even somebody with prediabetes may have neuropathy," she says. As many as 57 million Americans have prediabetes -- a condition where blood sugar levels are abnormally high, but not high enough to qualify as diabetes -- says the American Diabetes Association (ADA). Add to that the nearly 24 million Americans already coping with full diabetes, and you can see how common nerve pain may be.
The good news? Many of the risk factors for diabetic neuropathy are under your control. So while you may not be able to prevent nerve pain and damage completely, you may be able to help slow it down. You can reduce your risk of nerve damage and other diabetes complications by keeping your blood sugars under tight control, says the National Diabetes Information Clearinghouse (NDIC).
Trence agrees. "The better the blood sugar control," she says, "the less likely neuropathy is to progress." A healthy lifestyle helps lower your risk of heart disease, stroke, and other diabetes complications, as well. So know your risk for complications, and work to control the ones you can control.

How well are you managing your diabetes?

Take WebMD's Diabetes Health Check to find out.

Are You at Risk for Diabetic Neuropathy?

1. You Have High Blood Sugar.

The risk: Who are the people at highest risk of nerve pain and damage from diabetes? Those who have trouble controlling their blood sugar.
What you can do: Sometimes glucose control is about mind over matter: you may simply need a little help staying motivated, sticking to your exercise program, or learning how to prepare more varied, tasty, healthy meals. But if you're "doing everything right" and still have high glucose levels, you may need to change your plan and start or adjust medications to help better manage your blood sugars.

2. You've Had Diabetes for Many Years.

The risk: Nerve pain and damage is more common in people who have had diabetes for more than 25 years.
What you can do: Do your best to monitor your blood sugar at home as often as advised by your doctor. The NDIC also advises having the A1c test, a blood test that measures your average blood glucose control over the previous 2 to 3 months, at least twice a year. Trence advises taking the A1c more often as an extra measure of control. "I think most of us believe it should be done every 3 to 4 months," she says. "It can vary, but we need to keep on top of things, and it's such a powerful piece of information to have to complement the patient's own blood sugars."

3. You're Overweight.

The risk: Being overweight is double trouble for people with diabetes. It puts you at higher risk of diabetic nerve damage -- and higher risk of deadly diabetes complications like heart attack and stroke.
What you can do: Losing weight is hard for everyone, since meals are loaded with emotional meaning, well-being, satisfaction -- or frustration. So if you're overweight, be patient -- but consistent -- with yourself. Losing even a few extra pounds can be a big boost to your health, says the ADA. You really can control this risk with a balanced diet and exercise plan designed for slow, safe weight loss. And losing weight means less pressure on those tender feet if you already have diabetic nerve pain.

4. You're Off-Target With Your Blood Fats.

The risk: The wrong levels of fats in your blood put you at higher risk of diabetic neuropathy. Often, people with diabetes have too-high levels of the blood fat called triglycerides, says the ADA. To make matters worse, an elevated LDL ("bad cholesterol") can increase the risk of a heart attack. A grim truth: 65% of deaths in people with diabetes will be due to a heart attack or stroke, according the ADA.
What you can do: Find out your numbers, if you're not sure. Have your cholesterol checked at least once a year, and aim for these target levels, advises the ADA:

LDL cholesterol:
below 100 mg/dL

HDL cholesterol:
above 40 mg/dL for men

above 50 mg/dL for women

Triglycerides:
below 150 mg/dL

Keep in mind that these are general guidelines; check with your doctor to see if your target levels are different, given your medical condition.

5. You Smoke.

The risk: Smokers are at greater risk of nerve damage from diabetes. And as you no doubt know, smoking has been linked to heart disease for years.
What you can do: You really can quit, even if you've been a longtime smoker. And it's never too late: Even if you've smoked for years, you'll do yourself a world a good if you quit. These days, you'll find smoking cessation classes, groups, and resources everywhere. Set a quit date, commit yourself, and ask your friends, family, colleagues, and your doctor for support.

6. You Drink a Lot of Alcohol.

Risk: Alcohol can seriously affect blood sugar levels. Even more sobering? Alcohol can raise your level of unhealthy blood fats called triglycerides.
What you can do: The ADA and NDIC both advise cutting down on drinking to help prevent -- or at least try to control -- diabetic nerve damage. If you already have nerve pain, ask your doctor whether you should have any alcohol at all. If you're living with diabetes, you may decide to cut out drinking entirely. The ADA suggests no more than 2 drinks a day for men and one drink a day for women.

So, quick review: your blood sugar, weight, blood fats like triglycerides, smoking, and drinking. That's five risk factors for diabetic neuropathy that are under your control. Not bad. Now if medicine can just come up with a "cure" for aging.

The Dangers of High Cholesterol

2009-11-21T19:41:00.001+05:30

High cholesterol is tough on arteries and your health. Here's how to fight back.

By Katherine Kam

Reviewed by Brunilda Nazario, MD

When Ramona Richman's older sister was diagnosed with high cholesterol, Richman wasn't worried about her own risk. The San Francisco Bay Area stay-at-home mom had her weight under control and assumed that her diet was healthy. So when her doctor broke the news that she, too, had high cholesterol, she was shocked. Her reading of 269 mg/dL was well over the desirable level of less than 200 mg/dL. "My sister had high cholesterol and went on medication, so I imagine that it's a genetic thing," Richman, 48, says.

Genes can be a factor in high cholesterol, but so can being overweight, being physically inactive, and eating foods loaded with saturated fat and cholesterol. The liver manufactures all the cholesterol a body needs, but many people get substantial amounts from their diet. Regardless of the cause, high cholesterol poses dangers. It plays a major role in the development of atherosclerosis, or hardening and narrowing of the arteries, which in turn raises the risk of heart attack and stroke.

Related Medications

More information on common Cholesterol drugs from RxList:

Vytorin
Lipitor
Zetia

When doctors talk about high cholesterol, they don't mean the amount of cholesterol a person gets from food, but rather how much of the substance is circulating in the blood. With atherosclerosis, the specific culprit is elevated LDL cholesterol, the "bad" kind associated with "increased risk of heart attacks and dying of heart disease," says Antonio M. Gotto Jr., MD, a professor of medicine at Weill Medical College of Cornell University and an expert on cholesterol and atherosclerosis.
Atherosclerosis is a gradual process. "It can start early in life," Gotto says. Fatty streaks can show up in adolescent arteries, and autopsies on men in their 20s have revealed "significant plaque in coronary arteries," he adds. "It doesn't just occur overnight." Over time, this plaque buildup can turn into a serious health threat, boosting risk of heart attack and stroke -- as people enter their 40s, 50s, and 60s, Gotto says. "Coronary disease shows a sharp increase during the 50s in men, and the late 50s and 60s in women."

How Arteries Harden

How does atherosclerosis begin to happen exactly? In a healthy artery, the inner lining, or endothelium, is smooth and intact. But disease or injury -- including diabetes, high blood pressure, and high cholesterol -- can damage this lining, paving the way for atherosclerosis.
Scientists aren't sure how high cholesterol injures arteries, Gotto says, but he explains one theory: The fatty acids carried by LDL become oxidized and injure blood vessel walls. "The higher the level of LDL circulating in the blood, the more the wall gets injured." An inflammatory reaction ensues, Gotto says. "The blood vessel responds by a reaction to injury. It treats this as if you scratched your finger."
Atherosclerosis begins when white blood cells move into the lining and artery wall. They transform into foam cells, which accumulate fat and cholesterol. Other substances, such as calcium, also collect at the site. Eventually, an atherosclerotic plaque, or atheroma, forms.
These plaques thicken and harden the artery wall and bulge into the bloodstream to reduce or block blood flow. When an atheroma ruptures, it can trigger a blood clot leading to heart attack or stroke. Most commonly, atherosclerosis affects the left anterior descending coronary artery [one of the main arteries of the heart], the carotid arteries in the neck, and the abdominal aorta, Gotto says.

Lowering Your Cholesterol

While LDL is harmful, HDL, a "good" form of cholesterol, helps arteries. Besides quieting down inflammation in damaged arteries, "it blocks the oxidation of LDL," Gotto says, "and we think that HDL has the ability to pull some of the cholesterol out of the cells on the arterial wall and transport it back to the liver, where the body can get rid of it. The higher the level of HDL, the lower the risk of heart attacks and cardiovascular disease."

Know your cholesterol numbers, he adds. "It's better to talk to your doctor about atherosclerosis before you get symptoms, and unfortunately for many people, the first symptom may be the fatal one if they have sudden cardiac death or cardiac arrest."

Gotto suggests people talk to their doctor about risk factors for atherosclerosis while still in their 20s and get a blood test to check cholesterol levels. Before age 40, get a cholesterol test every three years, Gotto says, and after age 40, test annually.
When Richman got her unsettling results, she replaced whole-milk products with low-fat dairy foods. She ate more heart-healthy salmon. She also began walking for 40 minutes, five times each week. The changes have paid off slowly. Her cholesterol readings have dropped a bit, from a high of 269 to 247, and she hopes to get her reading low enough to avoid taking cholesterol medications.
"At the beginning, it was 'Oh, wow, I'm sick,'" she says. "But I was able to start getting my levels down, so that's been very encouraging."

Could You Have Atherosclerosis?

You may be at a higher risk of atherosclerosis if you:

Have high levels of LDL cholesterol in the blood
Have high blood pressure
Have diabetes
Are obese
Are physically inactive
Smoke
Are older
Have a family history of early atherosclerosis
Are male

6 Diet Tips to Help Manage Diabetes Nerve Pain

2009-11-21T19:23:00.001+05:30

Eating right may help protect your nerves from diabetic neuropathy.

By Rebecca Buffum Taylor

Reviewed by Brunilda Nazario, MD

If you have diabetes, you already know the drill. What you eat, when you eat, and how much you eat can send your blood sugar skyrocketing -- or make it plummet. For better or worse, "diet and diabetes" go together like salt and pepper.

So if you need a little motivation to eat better - and who doesn't? - consider this: with diabetes, you're at high risk of the nerve pain and damage called diabetic neuropathy. What can start as a little tingling or numbness in your feet can turn into major problems with walking, working, and leading an active lifestyle. Diabetic neuropathy can also wreak havoc with your digestion, your sexual response, and make it hard to feel normal body sensations - like the signs of plummeting blood sugar or a heart attack.

Fortunately, a balanced diet that helps treat nerve pain is really no different than the standard diet advised by the American Diabetes Association, says Dace L. Trence, MD, an endocrinologist and director of the Diabetes Care Center at the University of Washington Medical Center in Seattle. "The emphasis is really on blood sugar control," she says. "Certainly, if a dietary change might facilitate that, of course, it would be advisable."
Good glucose control can protect the health of your nerves - and may even help prevent diabetic neuropathy, says the National Diabetes Information Clearinghouse (NDIC). You see your doctor only every once in a while, but you eat several times every day. No matter what medications you may be on, your diabetes diet has a constant - and colossal - impact on your health and well-being, with every bite you take.

Tip 1. Eat a Balanced Diet

Why? Remember the good-old food pyramid you learned about back in school? A balanced diet includes a variety of foods: carbohydrates (starches), fruits, vegetables, milk and dairy, meat, poultry, fish, and healthy fats. Eating a balanced diet helps you keep your glucose within target levels, control your weight, and reduce the risk of complications like neuropathy, heart disease, and stroke.
The goal. Step out of any food ruts you're in. Try new foods, and include all of the major food groups in your diabetes diet.
How? The shape of your diet will depend on how active you are, whether you're a man or a woman, and whether you're trying to lose weight. The American Diabetes Association offers these general guidelines, but check with your doctor to fine-tune your specific plan:

Choose a variety of nutrient-dense foods and beverages among the basic food groups.
Balance calories from foods and beverages with physical activity to manage body weight.
Choose fiber-rich fruits, vegetables, and whole grains often.
Eat 2 cups of fruit and 2 1/2 cups of vegetables daily (for someone eating 2,000 calories)
Make at least half the grains you eat whole grains.
Decrease saturated fats and trans fatty acids by choosing lean meats and poultry, and low-fat or non-fat dairy products.
Substitute monounsaturated fats and polyunsaturated fats (from fish, nuts, and vegetable oils) for saturated and trans fat fats.
Choose and prepare foods and beverages with little added sugars or caloric sweeteners.
Eat less than 2,300 mg per day of sodium.
Limit alcohol to no more than 1 drink for women and 2 drinks for men.
Regular physical activity of at least 30 minutes a day for adults and 60 minutes for children.

Tip 2. Spread Your Meals Throughout the Day

Why? Skipping meals and overeating can send your blood sugar plunging - and then through the roof. Since diabetic nerve damage and pain can decrease appetite and make it harder to digest food, several smaller meals may work better for you. Plus, some diabetes medications work their best when you're taking them in concert with regularly scheduled meals.
The goal. Find a workable schedule for meals and snacks that fits your real lifestyle - not one you wish you had. Be realistic about planning your diabetes diet around your work, driving time, feeding kids, and other commitments.
How? Aim for 3 small meals and 3 healthy snacks each day to balance out your blood sugar:

Breakfast
A mid-morning snack
Lunch
A mid-afternoon snack
Dinner
An evening snack

Tip 3. Go for Complex "Carbs"

Why? Carbohydrates digest more slowly and don't "spike" your blood sugar the way sugars do. They also fill you up faster, so you're less likely to overeat, and they give you more vitamins, minerals, and fiber.

The goal. Most of what you eat should be healthy carbohydrates. Include whole-grains, fruits, vegetables and low fat milk. Whole grain breads and cereals, brown rice, beans, lentils, potatoes, and corn tortillas are good choices.

How?

Shop the perimeter of grocery stores, where you'll find the freshest foods. Avoid temptation in the middle aisles, where canned, boxed, and frozen goods are shelved.
Reach for the least-processed version of any food. Try to cut out prepared, pre-mixed foods like stove-top dinners: they're not "helpers" when it comes to diabetes and nerve pain.
Have fun trying a new kind of starchy vegetable, like baked yams, oven-roasted carrots, or cooked lentils, instead of white rice or dinner rolls.

Tip 4. Forget "Supersizing"

Why? Most people are shocked to realize how small "official" serving sizes are. A serving of carbs? Only 1 slice of whole-grain bread or 1/2 cup of cooked oatmeal. A serving of dry cereal? Only 3/4 of a cup - that's smaller than your average cup of coffee. Meat, fish, or poultry? A mere 3 ounces is a serving - that's about the size of a cassette tape - once it's cooked. Go for that 16-ounce porterhouse and you've just eaten nearly 6 dinners-worth of protein.
The goal. Get in the habit of reading food labels to find out the real portion sizes for the foods you enjoy. And do the math. If you double up on a special treat one day, subtract that from your next day's diet planning.

How?

Split entrees or dinner-size salads when you eat out, or have a small salad and appetizer instead of an entree.
Keep a good diabetes diet book on hand to find portion sizes for fresh foods like fruits and vegetables.
Buy a new set of measuring cups and spoons and keep them out on the counter, so you're more motivated to measure servings.

Tip 5. Jump on the Wagon

Why? Alcohol toxic to nerves, says the ADA. Your liver has two main jobs: to clear toxins like alcohol from your body, and to convert carbohydrate into blood glucose your body can use. But drinking sidetracks your liver; it won't start working to level out blood sugar until it "sweeps" the alcohol from your bloodstream, so blood sugar swings can result. And if you have diabetic neuropathy, drinking may spur on pain, tingling, and other symptoms, says the ADA.
The goal. To be safe, the ADA advises people with advanced diabetic neuropathy not to drink at all, since it's possible that nerve damage can be brought on even by light drinking (fewer than 2 drinks a week). If you do drink, they advise no more than 1 drink a day for women and 2 drinks a day for men.

How?

Try a variety of mineral waters with a fresh slice of lemon, lime, or orange for flavor.
Make a "Virgin Mary": spice up tomato juice with a splash of hot pepper sauce, lemon juice, dried herbs, and a stalk of fresh celery - but hold the liquor.
If you do celebrate occasionally, never drink on an empty stomach. Have your drink with or after dinner, to help prevent sugar "lows."

Tip 6. Eat Less Fat

Why? Nearly 9 out of 10 adults with type 2 diabetes are overweight, says the ADA. Losing weight can lower blood glucose, give you more energy, lighten the load on feet already sore from nerve pain, and lower your risk of heart disease and stroke.
The goal? Try to stick to 3 - 5 servings of fat a day (or as advised by your doctor). Remember that 1 serving of fat is only 1 teaspoon of olive oil or margarine.

How?

These days, "low-fat" is everywhere. But read food labels carefully. "Lite" doesn't always mean "low-fat." Find out how many grams of fat are in each serving of the foods you enjoy.
No matter how rushed you feel, avoid grabbing fast foods on the go. A single fast-food meal could cost you a week's worth of fat servings.
Fill up on low-fat soups, salads with low-fat dressing, and raw veggies that satisfy your taste buds with a variety of flavors and textures.

And remember to relax and enjoy your meals. That way, you're less likely to overeat from stress, and more likely to savor the flavor of foods. Your nerves will be glad you did.

Critical Care Services and 2009 H1N1 Influenza

2009-11-17T14:32:00.002+05:30

Background : Planning for the treatment of infection with the2009 pandemic influenza A (H1N1) virus through health care systemsin developed countries during winter in the Northern Hemisphereis hampered by a lack of information from similar health caresystems.
Methods : We conducted an inception-cohort study in all Australianand New Zealand intensive care units (ICUs) during the winterof 2009 in the Southern Hemisphere. We calculated, per millioninhabitants, the numbers of ICU admissions, bed-days, and daysof mechanical ventilation due to infection with the 2009 H1N1virus. We collected data on demographic and clinical characteristicsof the patients and on treatments and outcomes.
Results : From June 1 through August 31, 2009, a total of 722patients with confirmed infection with the 2009 H1N1 virus (28.7cases per million inhabitants; 95% confidence interval [CI],26.5 to 30.8) were admitted to an ICU in Australia or New Zealand.Of the 722 patients, 669 (92.7%) were under 65 years of ageand 66 (9.1%) were pregnant women; of the 601 adults for whomdata were available, 172 (28.6%) had a body-mass index (theweight in kilograms divided by the square of the height in meters)greater than 35. Patients infected with the 2009 H1N1 viruswere in the ICU for a total of 8815 bed-days (350 per millioninhabitants). The median duration of treatment in the ICU was7.0 days (interquartile range, 2.7 to 13.4); 456 of 706 patients(64.6%) with available data underwent mechanical ventilationfor a median of 8 days (interquartile range, 4 to 16). The maximumdaily occupancy of the ICU was 7.4 beds (95% CI, 6.3 to 8.5)per million inhabitants. As of September 7, 2009, a total of103 of the 722 patients (14.3%; 95% CI, 11.7 to 16.9) had died,and 114 (15.8%) remained in the hospital.
Conclusions : The 2009 H1N1 virus had a substantial effect onICUs during the winter in Australia and New Zealand. Our datacan assist planning for the treatment of patients during thewinter in the Northern Hemisphere.

Infection with the 2009 pandemic influenza A (H1N1) virus emergedin Mexico toward the end of the 2008–2009 influenza seasonin the Northern Hemisphere. As of September 6, 2009, the WorldHealth Organization had reported over 277,607 laboratory-confirmedcases of 2009 H1N1 influenza, with at least 3205 deaths.¹ FromJune through August 2009, Australia and New Zealand experiencedthe combined effect of the pandemic and winter in the SouthernHemisphere. The reported incidence of infection with the 2009H1N1 virus during winter in Australia and New Zealand was 8times that reported for the same period in the United States.¹^,² This resulted in a substantial increase in demand for hospitalservices, particularly critical care services. Reports of critical illness caused by 2009 H1N1 influenza duringsummer in the Northern Hemisphere contain insufficient datato provide reliable estimates of the burden of critical illnessto be expected during winter in the Northern Hemisphere.³^,⁴^,⁵^,⁶^,⁷^,⁸^,⁹ Although the successful deployment of a safe and effectivevaccine may modify the burden of disease,¹⁰^,¹¹ population-baseddata from Australia and New Zealand can currently provide areasonable estimate of the likely effect of 2009 H1N1 influenzaduring the Northern Hemisphere winter. In addition, the datacan be used to identify persons who are at high risk of developingsevere disease.
In this report, we describe the incidence of intensive careunit (ICU) admission, demographic characteristics, treatment,use of critical care resources, and outcome for all patientswith laboratory-confirmed infection with the 2009 pandemic influenzaA (H1N1) virus admitted to ICUs in Australia and New Zealandduring the winter of 2009 in the Southern Hemisphere.

Methods

We performed a multicenter inception-cohort study involving187 ICUs in Australia and New Zealand — all the ICUs (adult,pediatric, or adult and pediatric) in the two countries.¹² TheICUs had a total of 1879 beds, of which 1449 were equipped formechanical ventilation. Each center obtained approval from theinstitutional ethics committee. The requirement for writteninformed consent from individual patients was waived at allsites.
From June 1 through August 31, 2009, we identified all patientsadmitted to the ICU with confirmed infection with the 2009 pandemicinfluenza A (H1N1) virus. The 2009 H1N1 influenza was confirmedby means of a polymerase-chain-reaction (PCR) assay or serologicanalysis. The 2009 pandemic influenza A (H1N1) virus and seasonalsubtypes (preexisting H1N1 and H3N2 strains) were confirmedby PCR assay. The PCR assay was conducted initially at referencelaboratories in each region and later, as the pandemic evolved,at local laboratories. The performance of these laboratorieswas accredited by the National Association of Testing Authoritiesin Australia or by International Accreditation New Zealand.In addition, the 2009 H1N1 virus could be confirmed in a singlereference laboratory by means of a hemagglutination-inhibitionassay to detect antibodies specific for the 2009 H1N1 virus.Population data for Australia and New Zealand and their constituentregions were obtained from Australian Bureau of Statistics¹³and Statistics New Zealand.¹⁴
We collected several types of data for the patients: the datesand times of admission to the hospital and the ICU; age; raceor ethnic group, including indigenous group (reported by patientsor their next of kin or, for patients under 18 years of age,by a parent or guardian); sex; pregnancy or childbirth lessthan 28 days previously (for women); coexisting conditions,which for patients 16 years of age or older were any conditionthat is defined within the Chronic Health Evaluation componentof the Acute Physiology, Age, and Chronic Health Evaluation(APACHE III, for which scores can range from 0 to 299, withhigher scores indicating a greater severity of illness),¹⁵ andfor patients under 16 years of age, defined as prematurity,immunodeficiency, cystic fibrosis, congenital heart disease,neuromuscular disorder, or chronic neurological impairment;history of asthma or another chronic pulmonary disease, chronicheart failure, or diabetes; measured or estimated weight andheight (for calculation of the body-mass index [BMI]); dateand time of first symptoms; presence and type of influenza syndrome,including viral pneumonitis or the acute respiratory distresssyndrome, secondary bacterial pneumonia, exacerbation of airflowlimitation due to either asthma or chronic obstructive pulmonarydisease, or intercurrent illness; and airway status at the timeof ICU admission (presence or absence of endotracheal intubation,tracheotomy, sealed face mask, and any artificial airway).
We categorized patients according to the age groups used ina previous report: 0 to 1 year of age, 1 to 4 years, 5 to 24years, 25 to 49 years, 50 to 64 years, and 65 years of age orolder.¹⁶ Data were collected daily on the use of mechanicalventilation and extracorporeal membrane oxygenation. We calculatedthe duration of treatment in the ICU and the hospital, as wellas the rates of occupancy of the ICU, for Australia and NewZealand and their constituent regions. We recorded outcomesof patients in the ICU and whether the patients had been dischargedor were still in the hospital or the ICU as of September 7,2009. To compare data from the current year with those fromprevious years, we obtained the number of patients who had beenadmitted to Australian or New Zealand ICUs with viral pneumonitisduring the winters of 2004 through 2008, from the Australianand New Zealand Intensive Care (ANZIC) Society's Adult PatientDatabase.¹⁷ This source of data does not categorize the causeof viral pneumonitis and may include some patients who had viralpneumonitis due to causes other than influenza A. To determinewhich groups were at increased risk of admission to an ICU with2009 H1N1 influenza, we compared the proportions of patientswith such an admission in each group of interest with the proportionsof the general population of Australia¹³ and New Zealand¹⁴ thatthose admitted patients represented.

Data Management

We collected data by means of electronic case report forms.The study coordinating center was the ANZIC Research Centre,Monash University, Melbourne, Australia.¹⁸ Infection with the2009 H1N1 virus is subject to mandatory reporting in both Australiaand New Zealand, and all diagnoses were confirmed with the relevantstate or territory's Department of Health. In addition, to confirmthe completeness of case ascertainment, we contacted the 83ICUs that had no reported cases at the end of the study period(August 31, 2009). Patients transferred between ICUs were countedas a single ICU admission. We made no assumptions regardingmissing data; all proportions were calculated as percentagesof the patients with available data.

Statistical Analysis

We performed statistical analysis using ,SAS software version9.1 (SAS Institute). We calculated descriptive statistics forall study variables. We report data for continuous variablesas medians (with interquartile ranges) and for categorical variablesas percentages (with 95% confidence intervals, where appropriate).We estimated the age-based population-admission rates.¹³ Weperformed a univariate analysis for in-hospital mortality, usingthe chi-square test, Fisher's exact test, or Wilcoxon rank-sumtest, as appropriate. We performed multivariate logistic-regressionanalysis to identify factors independently associated with in-hospitalmortality, with the multivariate model constructed by usingboth stepwise-selection and backward-elimination techniques.We first included age, as a continuous variable. We then includedin the model, as categorical variables,¹⁶ the presence or absenceof pregnancy, asthma or another chronic pulmonary disease, andchronic heart failure; BMI (the weight in kilograms dividedby the square of the height in meters) greater than 35 versus35 or less; race or ethnic group; and the presence or absenceof any coexisting condition; and the type of influenza syndrome.Goodness of fit was determined with the use of the Hosmer–Lemeshowstatistic. A two-sided P value of less than 0.05 was consideredto indicate statistical significance, except in the multivariatemodel, where a P value of less than 0.01 was considered to indicatestatistical significance.

Results

We identified 856 patients with influenza A infection who wereadmitted to an ICU between June 1 and August 31, 2009. Of these,722 (84.3%) had a confirmed infection with 2009 pandemic influenzaA (H1N1) virus (Figure 1). The 2009 H1N1 virus was diagnosedby means of PCR assay in 717 patients and serologic analysisin 5 patients. Among the 722 patients with 2009 H1N1 influenza,626 were admitted to an ICU in Australia and 96 to an ICU inNew Zealand. The numbers of patients with viral pneumonitisadmitted to Australian or New Zealand ICUs from June 1 throughAugust 31 were 57 in the year 2005, 33 in 2006, 69 in 2007,and 69 in 2008 (mean, 57 patients). During the winter of 2009,37 patients were admitted to an ICU with confirmed seasonalsubtypes of influenza A (H1N1) virus. The combined populationof Australia and New Zealand was estimated at 25,180,770, givingan incidence of ICU admission for 2009 H1N1 influenza duringwinter 2009 of 28.7 (95% confidence interval [CI], 26.5 to 30.8)per million inhabitants.¹³^,¹⁴

Figure 1. Enrollment and Follow-up of Patients with Influenza A Admitted to Intensive Care Units (ICUs) in Australia and New Zealand. Follow-up data are as of September 7, 2009.

The number of admissions and the age-specific incidences variedsubstantially according to the age group (Figure 2). The highestage-specific incidence of ICU admission was among infants (0to 1 year of age) (Figure 2A), whereas the highest number ofICU admissions was among patients 25 to 49 years of age (Figure 2B). Additional demographic data and data on risk factors andtype of critical illness among patients with 2009 H1N1 influenzaare presented in Table 1.

Figure 2. Incidence and Number of Admissions to the Intensive Care Unit (ICU), According to Age Group. The incidence of ICU admission, expressed as the number per million residents, is shown in Panel A, and the number of ICU admissions is shown in Panel B. The age-specific incidence was calculated by dividing the number of admissions in each age group by the estimated number of persons in that age group in the population of Australia and New Zealand (which was 350,346 for 0 to 1 years, 1,324,185 for 1 to 4 years, 6,938,498 for 5 to 24 years, 9,111,600 for 25 to 49 years, 4,563,709 for 50 to 64 years, and 3,377,580 for 65 years or older). I bars indicate the 95% confidence intervals.

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Table 1. Baseline Characteristics of Patients with Confirmed Critical Illness Related to 2009 H1N1 Influenza.

Pregnant women represent approximately 1% of the general populationof Australia and New Zealand.¹³^,¹⁴ A total of 66 of the 722patients (9.1%) admitted to the ICU with 2009 H1N1 influenzawere pregnant women. Of the 601 adults for whom BMI data wereavailable, 172 (28.6%) had a BMI greater than 35. The proportionof a representative adult Australian population with a BMI greaterthan 35 was 5.3% in 2003.¹⁹ We estimate the proportion of patientswith asthma or other chronic pulmonary disease in the generalpopulation to be around 13%.²⁰ Data on premorbid pulmonary diseasewere missing for 15 of the 722 patients with 2009 H1N1 influenzain our study; of the remaining 707 patients, 231 (32.7%) hadasthma or another chronic pulmonary disease. Indigenous groupswere relatively overrepresented in our study: aboriginal andTorres Strait Islanders account for 2.5% of the Australian population¹³ but made up 9.7% of our patients with 2009 H1N1 influenzawho were admitted to Australian ICUs. Maori represent 13.6%of the New Zealand population¹⁴ but accounted for 25.0% of thepatients with 2009 H1N1 influenza who were admitted to New ZealandICUs. Overall, 229 patients (31.7%) had no known predisposingfactor. Almost half of all patients (48.8%) had the acute respiratorydistress syndrome or viral pneumonitis, and 20.3% of patientswere clinically diagnosed with bacterial pneumonia (i.e., hadunilateral or bilateral asymmetric lung infiltrates consistentwith bacterial pneumonia, with bacterial infection proven orsuspected) in association with confirmed infection with the2009 H1N1 virus. Data on the use of mechanical ventilation in the ICU were availablefor 706 patients; of these, 456 (64.6%) underwent mechanicalventilation for a median of 8 days (interquartile range, 4 to16). The total number of days of ventilation was 5249, representing208 days (95% CI, 203 to 214) per million inhabitants. Of the456 patients undergoing mechanical ventilation, 53 (11.6%) weresubsequently treated with extracorporeal membrane oxygenation,representing 2.1 patients (95% CI, 1.5 to 2.7) per million inhabitants.Available data on other cointerventions are given in the Supplementary Appendix (available with the full text of this article at NEJM.org).
As of September 7, 2009, a total of 114 of the 722 patients(15.8%) were still in the hospital, of whom 37 (5.1%) were stillin the ICU. Excluding these 114 patients still in the hospitalor ICU and an additional 33 for whom data were not available(regarding duration of ICU treatment, for 3 patients, and durationof in-hospital treatment, for 30), we calculated the medianduration of treatment in the ICU as 7.4 days (interquartilerange, 3.0 to 16.0) (Figure 3) and the median duration of treatmentin the hospital as 12.3 days (interquartile range, 6.4 to 22.1).

Figure 3. Length of Stay in the Intensive Care Unit (ICU) among Patients with 2009 H1N1 Influenza.

The number of ICU admissions per million inhabitants variedover the study period, for Australia and New Zealand overalland for each of the main regions affected, as did the numberof ICU beds occupied per million inhabitants (Figure 4). Patientswith 2009 H1N1 influenza occupied the ICU for a total of 8815ICU bed-days, representing 350 bed-days (95% CI, 342 to 357)per million inhabitants. Across Australia and New Zealand, themaximum number of ICU beds occupied per million inhabitantswas 7.4 (95% CI, 6.3 to 8.5) during the week ending July 27,2009. The maximum number of beds occupied by region in the Australianstates or New Zealand ranged between 6.3 and 10.6 per millioninhabitants (Figure 4). Over the 3-month study period, 5.2%of ICU bed-days were accounted for by patients with 2009 H1N1influenza. The peak percentage of ICU beds occupied by patientswith 2009 H1N1 influenza in Australian states and New Zealandranged from 8.9 to 19.0%.

Figure 4. Numbers of Patients with 2009 H1N1 Influenza Admitted to an ICU and Numbers of ICU Beds Occupied by Those Patients, According to Study Week and Region. The panels on the left show the numbers of patients admitted to an ICU, and the panels on the right show the numbers of ICU beds occupied by those patients. All data are per million inhabitants. Data are shown for the Australian states of Victoria, New South Wales, and Queensland; for New Zealand; and for all regions of Australia and New Zealand combined.

As of September 7, 2009, a total of 608 patients (84.2%) hadbeen discharged from the hospital: 103 (16.9%) had died in thehospital and 505 (83.1%) had been discharged alive. For thosewho had died or been discharged alive, three factors were found,on multivariate logistic-regression analysis, to be independentlyassociated with death in the hospital: requirement of invasiveventilation at ICU admission (odds ratio for in-hospital death,5.51; 95% CI, 3.05 to 9.94; P<0.001), any coexisting condition(as defined in our study) (odds ratio, 2.56; 95% CI, 1.52 to4.30; P<0.001), and older age (odds ratio per year of age,1.02; 95% CI, 1.01 to 1.04; P=0.002). The data were well fittedby the model (P=0.79 by the Hosmer–Lemeshow test).

Discussion

This cohort study identified all patients with confirmed 2009H1N1 influenza who were admitted to Australian or New ZealandICUs during winter 2009 in the Southern Hemisphere. We identified722 patients with the infection and estimated the winter populationincidence of ICU admission: 28.7 per million inhabitants. Thenumber of ICU admissions due to influenza A in 2009 was 15 timesthe number due to viral pneumonitis in recent years. We wereable to document the use of ICU beds and patients' outcomesand estimate the number of ICU bed-days occupied: 350 per millioninhabitants. We identified infants (0 to 1 year of age) andadults 25 to 64 years of age to be at particular risk. Pregnantwomen, adults with a BMI greater than 35, and indigenous Australianand New Zealand populations also appeared to have an increasedrisk. In-hospital mortality, estimated on the basis of dataavailable at the time of this report, exceeded 16%.
Previously published reports have highlighted cases of severeviral pneumonia affecting patients younger than the expectedage of patients affected during a normal influenza season⁸^,⁹and have noted that pregnant women are at increased risk.²¹Our findings are consistent with these reports. The age-specificincidence rates were highest among infants and adults 25 to64 years of age. Although the incidence of ICU admission variedacross the age groups and was low for patients 65 years of ageor older, the risk of death increased with increasing age. Theproportion of patients who were admitted to an ICU and werepregnant, had chronic lung disease, had a BMI greater than 35,or were indigenous to Australia or New Zealand were all higherthan the corresponding proportions in the general population.Finally, a third of our patients were young or middle-aged adultswho neither were pregnant nor had a known coexisting condition.
Australia and New Zealand have 75 ICU beds per million inhabitants.The number of ICU beds varies greatly among developed countries,²² and the capacity of countries to cope with a surge in demandfor critical care services owing to infection with the 2009pandemic influenza A (H1N1) virus will depend on the currentnumbers of ICU beds and the countries' ability to expand thatcapacity or restrain other demands on it.
Our data indicate that the greatest effect on ICU resourcesin a given region occurs approximately 4 to 6 weeks after thefirst confirmed winter ICU admission and that the extra workloadlasts several weeks. Current recommendations are that patientswith 2009 H1N1 influenza should receive treatment in isolation.²³ The requirement to treat many patients in isolation, combinedwith the need for interhospital transfer for optimal care, mayfurther increase the strain on critical care resources.
The proportion of patients who died in the hospital in our studyis no higher than that previously reported among patients withseasonal influenza A who were admitted to an ICU.²⁴ Patientsadmitted to an ICU with seasonal influenza A predominantly areelderly and have coexisting conditions.²⁴ Among patients admittedto ICU, older age, the presence of coexisting conditions, anda requirement for invasive ventilation were independently associatedwith increased risk of death, but because there were greaternumbers of younger patients in our cohort, the majority of deathsoccurred in younger patients.
The inferences that can be drawn from our data are subject tosome limitations. First, to make this report available in timeto assist planning in the Northern Hemisphere, we censored thehospital-outcome data, which may have introduced bias. Second,our data were gathered early during the pandemic in Australiaand New Zealand. The findings may be different during futurewaves, owing to the timely deployment of an effective vaccine,to viral mutation, and to resistance to antiviral drugs. Third,the data regarding previous winters come not from an inception-cohortstudy but from our Australia–New Zealand database; therefore,they are not directly comparable to the data in the currentstudy for winter 2009. Fourth, ascertainment of patients with2009 H1N1 influenza who were admitted to an ICU may not havebeen complete, and we cannot rule out the possibility that asmall number of cases were not reported to the registry. Finally,false negative diagnostic tests may well have led us to underestimatethe true burden of 2009 H1N1 influenza in our patients. Amongthe patients with confirmed influenza A, there were 97 in whomthe influenza virus was not subtyped, some of whom may havehad false negative tests for the 2009 H1N1 virus. Nonetheless,with these caveats, knowledge of the rate of ICU admission andoccupancy due to 2009 H1N1 influenza during the winter in Australiaand New Zealand can inform the planning and assessment of criticalcare needs in countries yet to face the 2009 winter.

Chronic Myelogenous Leukemia:Causes, Symptoms, and Treatment

2009-11-15T19:51:00.008+05:30

Medical Author: Benjamin C. Wedro, MD, FAAEM
Medical Editor: William C. Shiel, Jr., FACP, FACR

Pro athletes often seem to know their bodies, and notice bodily changes early when something isn't quite right. This intuition may have led Kareem Abdul-Jabbar to seek medical help when he started to get hot flashes and night sweats last fall. Many people may have ignored these symptoms and sloughed them off as unimportant. Hot flashes may be normal for women in menopause, but not for a male basketball legend. Mr. Abdul-Jabbar's symptoms led to an early diagnosis of chronic myelogenous leukemia (CML).

What causes chronic myelogenous leukemia?

Chronic myelogenous leukemia is a rare type of leukemia that tends to affect older males. More than 90% of cases are due to a gene abnormality caused when two chromosomes swap sections with each other. There are 23 chromosomes in humans, and in patients with chronic myelogenous leukemia chromosomes 9 and 22 within blood cells exchange bits of genetic material to form a Philadelphia chromosome, named after the city where it was discovered. The new gene on this chromosome makes a protein called tyrosine kinase that allows white blood cells to grow out of control; moreover, these abnormal white blood cells tend not to become old and die. The bone marrow, where red blood cells, white blood cells, and platelets are made, becomes filled with white blood cells crowding out the normal cells and damaging the bone marrow itself. This can impair the ability of the bone marrow to manufacture normal amounts of blood cells.

Latest on Kareem Abdul-Jabbar & CML

Kareem Abdul-Jabbar and CML:

Kareem Abdul-Jabbar Has CML Form of Leukemia: Abdul-Jabbar, 62, has chronic myelogenous leukemia or CML. Once a fatal disease, oral medications now keep CML under control for 80% to 90% of patients...
Chronic Leukemia: Early in the disease, the leukemia cells can still do some of the work of normal white blood cells. People may not have any symptoms at first. Doctors often find chronic leukemia during a routine checkup - before there are any symptoms...

What are the symptoms of chronic myelogenous leukemia?

Early symptoms of chronic myelogenous leukemia include chills, sweating, fever without infection, and fatigue.
Later symptoms of chronic myelogenous leukemia are due to decreasing function of the bone marrow and include:

Bone and joint pain may occur as the bone marrow pressure increases due to an excess build-up of white blood cells.
Fatigue may be due to anemia because not enough red blood cells are being produced and bleeding can occur if not enough platelets are being manufactured.
In some patients with chronic myelogenous leukemia their bone marrow makes too many platelets and they can develop abnormal blood clotting, which can cause strokes.
In chronic myelogenous leukemia there are too many white blood cells, but these white blood cells tend not to function properly and their ability to fight infection is compromised, which leads to an increased risk of infection.
The increased numbers of white blood cells spill out of the bone marrow and start circulating in the blood stream and eventually become trapped in the spleen, causing it to enlarge.

How is chronic myelogenous leukemia diagnosed?

The diagnosis of chronic myelogenous leukemia is usually via a blood test called a complete blood count(CBC). Complete blood count is a common blood test that measures the number, type, and characteristics of red and white blood cells and platelets. Abnormal numbers of cells being produced are noted on the CBC and chronic myelogenous leukemia is diagnosed by reviewing a smear of the blood under a microscope. A bone marrow sample examines the area where the cells are made, and if the diagnosis of chronic myelogenous leukemia is being considered, this can be tested for the Philadelphia chromosome.

What is the treatment for chronic myelogenous leukemia?

Chronic myelogenous leukemia is a treatable disease with drugs that target the abnormal enzyme responsible for the faulty white blood cells. Imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna) shut down the tyrosine kinase enzyme and can keep chronic myelogenous leukemia in remission, but once the drug is started, the patient will likely need to take the medication throughout their lifetime. If the leukemia reactivates, a next option of treatment is a bone marrow transplant, which has a long-term cure rate of 60%-80%.

What is the outlook (prognosis) for chronic myelogenous leukemia?

The ability listen to your body is an important first step in finding a problem so it can be properly diagnosed and treated. Often, chronic myelogenous leukemia is diagnosed when a patient has a routine screening blood test. It's no different than finding a problem when taking your car in for an oil change; if a problem is found early the car can be fixed. However, if the problem is ignored, issues mount and the car engine cannot be repaired. People are no different. Ignoring warning signs and symptoms can make a treatable condition terminal. For Mr. Abdul-Jabbar and the 5,000 new chronic myelogenous leukemia patients diagnosed each year, the hope is that medication can keep them treatable for years to come.

REFERENCE: : Kasper DL, Fauci AS, etal. Harrison's Principles of Internal Medicine.16th edition Mc Graw Hill. 2005

Last Editorial Review: 11/11/2009 2:29:15 PM

Researchers Identify A Weak Link In Cancer Cell Armor

2009-11-13T19:31:00.004+05:30

Main Category: Cancer / Oncology
Also Included In: Genetics; Biology / Biochemistry
Article Date: 13 Nov 2009

The seeming invincibility of cancerous tumors may be crumbling, thanks to a promising new gene therapy that eliminates the ability of certain cells to repair themselves. Researchers at the Cornell University College of Veterinary Medicine have discovered that inactivation of a DNA repair gene called Hus1 efficiently kills cells lacking p53 -- a gene mutated in the majority of human cancers.

Using a mouse model, senior author Robert Weiss, associate professor of molecular genetics, first author and graduate student Stephanie Yazinski and colleagues explored how cells respond when both genes are inhibited. When they inactivated the Hus1 gene in healthy mammary gland tissues, the researchers report, it caused genome damage and cell death. And when they studied the effects of Hus1 inactivation in p53-deficient cells, which are highly resistant to cell death, they discovered that the ability of Hus1 inactivation to kill cells was even greater.

The study is published in the Nov. 9 issue of the Proceedings of the National Academy of Sciences.

"Our work contributes to an important new understanding of cancer cells and their weaknesses," Weiss said. "The mutations that allow cancer cells to divide uncontrollably also make the cancer cells more dependent on certain cellular processes. We were able to exploit one such dependency of p53-deficient cells and could efficiently kill these cells by inhibiting Hus1."

Weiss and his team have new experiments under way.

"We've proven the power of inhibiting both pathways in normal tissue," said Weiss. "Now we want to extend our knowledge to cancerous tissue and determine if the loss of Hus1 will impact the ability of cancers with to p53 mutation take hold and grow."

Weiss's research was funded by the National Institutes of Health and is now funded through 2013 in part by the American Recovery and Reinvestment Act (ARRA). To date, Cornell has received 124 ARRA grants, totaling more than $99.9 million. Weiss's ARRA funding will support one faculty and two student positions as well as the research activities of several additional lab members.

Written by Stephanie Specchio, communications director for the College of Veterinary Medicine. This article originally appeared in the Cornell Chronicle.

Source: Cornell University

Newly Recognized Structure Of HIV Coat Could Lead To New Drugs

2009-11-13T19:06:00.004+05:30

Main Category: HIV / AIDS
Also Included In: Genetics; Biology / Biochemistry
Article Date: 13 Nov 2009

Structural biologists at the University of Pittsburgh School of Medicine have described the architecture of the complex of protein units that make up the coat surrounding the HIV genome and identified in it a "seam" of functional importance that previously went unrecognized. Those findings, reported in Cell, could point the way to new treatments for blocking HIV infection.

The researchers used a combination of nuclear magnetic resonance and cryoEM, which are standard structural biology tools, to see both the overall shape and the atomic details of capsid protein (CA) assembly. It takes about 1,500 copies of CA to make the coat, or capsid, that surrounds the genome of the AIDS virus.

"This strategy allowed us to see both the forest and the trees," explained study co-author Peijung Zhang Ph.D., assistant professor in the Department of Structural Biology, Pitt School of Medicine. "Knowing what the CA protein looks like and how the capsid is built will allow scientists to rationally design therapeutic compounds that interfere with assembly of the protein and affect its function."

Capsid proteins, and particularly the interfaces or seams where one connects to another, are very important for assembling and disassembling the HIV coat, said senior author Angela Gronenborn, Ph.D., chair,Department of Structural Biology, and director,University of Pittsburgh Center for HIV Protein Interactions. The study indicates that these seams provide the flexibility to dismantle the coat efficiently after viral entry into the host and to put it back together when new viruses emerge from the cell.

"Our lab experiments show that if we replace a few of the pivotal stitches in the seam by mutation, the resulting viruses are less infectious or even non-infectious," Dr. Gronenborn said. "The capsid, and therefore the virus, can no longer function properly."

Study co-authors include In-Ja L. Byeon, Ph.D., Xin Meng, Ph.D., Jinwon Jung, Ph.D., Gongpu Zhao, Ph.D., Jinwoo Ahn, Ph.D., and Jason Concel, all of the Department of Structural Biology, Pitt School of Medicine; and Ruifeng Yang, Ph.D., Jiong Shi, and Christopher Aiken, Ph.D., all of the Department of Microbiology and Immunology, Vanderbilt University School of Medicine.

The research was funded by the National Institutes of Health.

Source: Anita Srikameswaran
University of Pittsburgh Schools of the Health Sciences

Experts To Discuss DNA Barcodes And Their Uses

2009-11-13T18:12:00.007+05:30

Featured Article http://www.medicalnewstoday.com/articles/170276.php
Main Category: Genetics
Also Included In: Regulatory Affairs / Drug Approvals; Veterinary; Biology / Biochemistry

World experts gathered this week to discuss DNA barcodes and their uses, covering a wide range of areas from medicine to agriculture, health to fraud, from smuggling to exploring our planet's prehistoric life.

About 350 experts from 50 countries met for the third International Barcode of Life conference that took place from 9 to 11 November in Mexico City.

DNA barcoding is a new technique that uses a short DNA sequence from the genome of an organism, living or dead, as a molecular way of identifying the species it belongs to. DNA barcode sequences are very short compared to the entire genome and can be obtained quite quickly and cheaply.

The Consortium for the Barcode of Life (CBO) is an international initiative devoted to developing DNA barcoding as a global standard for the identification of biological species.

Through the CBOL initiative, experts are agreeing a standard for DNA barcoding.

The challenge for the initiative is finding an area of DNA that does not vary much down generations, yet varies sufficiently between species to make identification reliable. A number of studies have shown that for higher animals, the variability of the "Folmer region" at the 5' end of the cytochrome c oxidase subunit 1 mitochondrial region (COI) is very low (about 1 to 2 per cent) and even between closely related species it differs by several per cent, making this the ideal region on which to settle as the standard for DNA barcoding.

This section of DNA is 648 nucleotide pairs long for most groups and is surrounded by regions that are reasonably conserved, making it quite easy to isolate and analyze.

In some groups, COI is not an effective barcode region and a different standard region will have to be sought and agreed on. But the idea is that in all cases, DNA barcoding uses a short, standard region that enables cost-effective species identification.

As the standard is being thrashed out and discussed, all manner of professionals are starting to get interested in its application, from medical and agricultural researchers, to police and customs officers.

For instance, using DNA barcoding, palaeontologists hope to be able to sequence ancient plant and animal remains extracted from degraded DNA in northern permafrost cores to reveal Earth's pre-historic life, and how life on Earth responded to global climate change.

And by analyzing the DNA of gut contents, scientists hope to discover secrets of what eats what in the animal world.

One such group is the The International Barcode of Life Project, headquartered in Guelph, Canada, where barcoding was pioneered. They will be telling meeting delegates about their discovery that eight species of bat feed on over 300 types of insect, one of the largest food webs ever found.

Conservationists are now getting very excited about the application of DNA barcoding to help unravel the complexity of the dynamics in the natural world.

Scott Miller, Acting Under Secretary for Science at the Smithsonian Institution and Chair of the Consortium for the Barcode of Life (CBOL), who are co-hosting the meeting with the Instituto Biologia, Universidad Nacional Autonoma de Mexico (UNAM), told the press that:

"DNA barcoding is opening a new window into the relations between hunter and prey in the wild and how diets may be changing due to climate change."

He explained that like gut contents, soils contain a mixture of species that are hard to identify using convetional tools. Tiny soil organisms eat each other, they eat roots, and all sorts of animal and plant debris, so:

"Knowing what eats what is important to many studies, including investigations into how much carbon dioxide and other greenhouse gases are being released from soils into the atmosphere," said Miller.

Another area of application would be producing evidence to prosecute smugglers of wild bushmeat and other products made from endangered species: a trade that last year netted 15 billion dollars worldwide.

When smoked or sundried, only DNA barcoding can differentiate bushmeat from domestic animal meat like beef, goat or pork, so law enforcement agencies are becoming increasingly interested in the DNA barcode library of endangered species that Dr George Amato of the American Museum of Natural History in New York is compiling.

The hope is that the Mexico meeting will bring about a global agreement on how to do the same with plants, which would for instance help to track down illegal timber trading and regulate herbal medicines, among others.

Biodiversity scientists are using DNA technology to unravel mysteries, much like detectives use it to solve crimes. It is having a profound impact on our understanding of organisms in nature and how they interact with the environment.

Following increases in the number of puffer fish poisoning cases in the US due to fradulent food labelling, the US Food and Drug Administration (FDA) will be telling delegates about their interest in DNA barcoding and the challenge posed by trying to differentiate among different species in marketed seafood, an increasing proportion of which is now imported, and which is also processed to "a point where traditional morphologic species determination is not possible".

An FDA representative told the press that:

"New methods that allow accurate and rapid species identifications are critical for both food borne illness investigations and for the prevention of deceptive practices, such as those where species are intentionally mislabeled to circumvent import restrictions or for resale as species of higher value."

The FDA will also be presenting a study that showed DNA barcoding reliably distinguished the seedpods of Star Anise ( Illicium verum, a herb used in teas, herbal remedies and cooking) from otherwise identical seedpods of a sister species, Illicium anisatin, considered to contain neurotoxic compounds and therefore a health risk.

The delegates will also hear of a case from Canada, where students nationwide collected fish samples from stores and analyzed the resulting DNA data, revealing significant market "mislabelling" of seafood.

Another case that will be presented will be the successful apprehension of a Brazilian smuggler last year who was caught trying to smuggle parrot eggs which he said were quails' eggs, but DNA barcoding revealed that they were the eggs of several species of parrots and macaws, many of which where either threatened or vulnerable.

A medical application of DNA barcoding will help to identify black flies in Brazil and other South American countries where they spread river blindness disease. So far 70 species of black flies have been barcoded to date, about 20 per cent of the number known to science, and including three previously unrecognized.

Other medical applications include identification of malaria mosquitoes in India, parasite bearing freshwater snails in the Cameroons, nematode parasites in Mexico that attack crops, humans and livestock.

Mexico is one of the countries that is moving ahead quickly in using DNA barcoding. Under the auspices of CONACYT, Mexico's National Council on Science and Technology, they have established a national barcode network (MexBOL) involving 60 researchers from 15 institutions.

Mexico now has a number of new "barcode factories" at institutions in the north, center and south of the country, including CIBNOR (Centro de Investigaciones Biológicas del Noroeste), IBUNAM (Instituto de Biología, UNAM), and ECOSUR (El Colegio de la Frontera Sur).

Meeting co-host Patricia Escalante, chair of the Zoology Department, Institute of Biology, UNAM, said this work in Mexico and elsewhere was very important.

"Barcoding is a tool to identify species faster, more cheaply, and more precisely than traditional methods," she explained.

MexBOL will produce barcodes for all important taxonomic groups including national campaigns, such as barcoding all trees (ArBOL), fungi, bees, aquatic insects, crayfishes, fishes, birds, mammals and more.

Escalante explained that:

"We need an accurate inventory of global biodiversity to recognize parasites of medical, economic or ecological importance."

"This work will help develop biological control measures, monitor and control of human diseases and potential zoonoses, manage agricultural and aquaculture pathogens, and detect the presence of invasive species," she added.

The largest barcode factory in the world is at the Biodiversity Institute of Ontario at the University of Guelph in Canada, where DNA barcoding was first proposed and developed.

Similar facilities are being set up at the French Museum National d'Histoire Naturelle, as well as in the Netherlands and Poland.

Raising awareness about breast cancer

2009-11-10T15:14:00.006+05:30

In this episode we look at how a disease once considered a close companion of affluent societies has moved to the developing world.

Listen to this episode - duration 00:05:45 [mp3 3.3Mb]

Transcript of the podcast

Veronica Riemer: You're listening to the WHO Podcast and my name is Veronica Riemer. October is Breast cancer awareness month and in this episode we look at how a disease once considered a close companion of affluent societies has moved to the developing world.
According to the latest WHO statistics, cancer causes around 7.9 million deaths worldwide each year. Of these deaths, more than 72% are now occurring in low- and middle-income countries. Among women, breast cancer features as one of the most frequent types of cancer globally. Dr Margaret Chan, Director-General of the World Health Organization talks about the challenges faced by countries where resources are limited and access to care is further constrained by cultural and social factors.
Dr Margaret Chan: We know that the incidence of breast cancer is increasing in developing countries, but we do not fully understand the reasons why. We know that the early detection and management of a disease like breast cancer becomes even more difficult in areas characterized by a shortage of data, a shortage of doctors, a shortage of screening services, a shortage of treatment facilities and, above all, a shortage of awareness. We need to tackle cultural barriers to care, and tackle the stigma and social isolation that frequently compound the misery of women diagnosed with advanced breast cancer.
Veronica Riemer: 30 years ago WHO's Goodwill Ambassador Nancy Brinker lost her only sister to breast cancer. She promised her dying sister, Susan G. Komen, she would do everything in her power to combat this disease. In 1982, she established Susan G. Komen for the Cure and launched a global breast cancer movement. She talks about what needs to be done.
Nancy Brinker: There are strategies in place to diagnose chronic disease, diabetes, heart disease, but with cancer, it is particularly important that it is diagnosed as early as possible and in many countries we have no health care systems with the bottom billion or two billion people with very low resources. We need to provide ways for them to have opportunities to be diagnosed, to have productive lives, to continue in the case of women to be mothers, to be able to carry their families and their communities into lifestyles, and normal life spans. And we need to approach cancer as a disease that can be conquered and managed and that won't happen until governments and NGOs and very powerful people take the leadership role in making it happen.
Veronica Riemer: Today the Susan G. Komen for the Cure Foundation is working to turn millions of breast cancer patients into breast cancer survivors. Patricia Allen, President of the English Speaking Cancer Association is one of those survivors and believes that the more we talk about cancer the more chance we have to save lives.
Patricia Allen: I was actually one of the very lucky ones, my cancer was detected on a routine mammogram in 2002. Because the cancer was detected at such an early stage, I did not need chemotherapy or radiotherapy. I had surgery and that was it. So by all means the quality of my life is much better because it was detected early. Right now I am absolutely 100% healthy. It has been seven years. I still have an MRI every year. As far as I am concerned, I am 100% cured.
Veronica Riemer: Regular mammograms are the best tests doctors have to find breast cancer early. But on a day to day basis, women can help themselves. Patricia tells us how.
Patricia Allen: My message to women today is for all women aged 16 and up, be vigilant about breast awareness, to know their breasts, to know how they look, how they feel and to note any changes and get them checked out. Certainly when you get up into the 20s and 30s, these young women should be doing not only monthly self breast exams but also going once a year to their gynaecologist for a clinical breast exam.
Veronica Riemer: Dr Andreas Ullrich is a WHO Medical Officer in the department for cancer control. He talks about reducing cancer risks.
Dr Andreas Ullrich: My advice to women to reduce cancer risks is to have a healthy lifestyle to choose a healthy diet rich in fruit and vegetables, whole grains and nuts; to keep weight down and to avoid weight gain; to exercise regularly in particular with some brisk physical activity every day; to keep alcohol drinking moderate and certainly please do not smoke.
Veronica Riemer: If you would like more information about WHO's work on cancer, please see the links published on the transcript page of this podcast.
That's all for this episode of the WHO podcast. Thanks for listening. If you have any comments on our podcast or have any suggestions for future health topics drop us a line. Our email address is Podcast@who.int.
For the World Health Organization, this is Veronica Riemer in Geneva.

Experts advise WHO on pandemic vaccine policies and strategies

2009-11-10T15:09:00.065+05:30

009 briefing note

30 OCTOBER 2009 | GENEVA -- The Strategic Advisory Group of Experts (SAGE) on Immunization, which advises WHO on policies and strategies for vaccines and immunization, devoted a session of its 27–29 October meeting to pandemic influenza vaccines. The experts reviewed the current epidemiological situation of the pandemic worldwide and considered issues and options from a public health perspective.
Items on the agenda included the status of vaccine availability, results from clinical trials on vaccine immunogenicity, and early results from safety monitoring in countries where administration of the H1N1 pandemic vaccine is currently under way.
The experts also advised WHO on the number of doses of vaccine needed to confer protection, also in different age groups, the co-administration of seasonal and pandemic vaccines, and vaccines for use in pregnant women. Recommendations on the formulation of seasonal influenza vaccines for the southern hemisphere in 2010 were also provided.

Current situation

elated links

Vaccines for pandemic (H1N1) 2009
Pandemic (H1N1) 2009: What can I do?

Globally, teenagers and young adults continue to account for the majority of cases, with rates of hospitalization highest in very young children. Between 1% to 10% of patients with clinical illness require hospitalization. Of hospitalized patients, from 10% to 25% require admission to an intensive care unit, and from 2% to 9% have a fatal outcome.
Overall, from 7% to 10% of all hospitalized patients are pregnant women in their second or third trimester of pregnancy. Pregnant women are ten times more likely to need care in an intensive care unit when compared with the general population.
Based on these and other current findings, the experts made a number of recommendations.

Dosage

The experts noted that a variety of pandemic vaccines, including live attenuated and both adjuvanted and non-adjuvanted inactivated vaccines, have now been licensed for use by regulatory authorities. SAGE recommended the use of a single dose of vaccine in adults and adolescents, beginning at the age of 10 years, provided such use is consistent with indications from regulatory authorities.
Data on immunogenicity in children older than 6 months and younger than 10 years are limited and more studies are needed. Where national authorities have made children a priority for early vaccination, SAGE recommended that priority be given to the administration of one dose of vaccine to as many children as possible. SAGE further stressed the need for studies to determine dosage regimens effective in immunocompromised persons.

Co-administration of vaccines

Clinical trials investigating the co-administration of seasonal and pandemic vaccines are ongoing, but SAGE US Centers for Disease Control and Prevention, acknowledged the recommendation, from the that live attenuated seasonal and live attenuated pandemic vaccines should not be co-administered.
The experts recommended that seasonal and pandemic vaccines can be administered simultaneously, provided both vaccines are inactivated, or one is inactivated and the other is live attenuated. The experts found no evidence that co-administration of vaccines, as recommended, would increase the risk of adverse events.

Vaccine safety

The experts reviewed early results from the monitoring of people who have received pandemic vaccines and found no indication of unusual adverse reactions. Some adverse events following vaccination have been notified, but these are well within the range of those seen with seasonal vaccines, which have an excellent safety profile. Although early results are reassuring, monitoring for adverse events should continue.

Vaccines for pregnant women

Concerning vaccines for pregnant women, SAGE noted that studies in experimental animals using live attenuated vaccines and non-adjuvanted or adjuvanted inactivated vaccines found no evidence of direct or indirect harmful effects on fertility, pregnancy, development of the embryo or fetus, birthing, or post-natal development.
Based on these data and the substantially elevated risk for a severe outcome in pregnant women infected with the pandemic virus, SAGE recommended that any licensed vaccine can be used in pregnant women, provided no specific contraindication has been identified by the regulatory authority.

Vaccines for the southern hemisphere in 2010

SAGE also considered vaccines for use in the southern hemisphere during the 2010 winter season. Two options were assessed: a trivalent vaccine, effective against the H1N1 pandemic virus, the seasonal H3N2 virus, and influenza B viruses, and a bivalent seasonal vaccine, effective against H3N2 and influenza B viruses, which might need to be supplemented with a separate monovalent H1N1 pandemic vaccine.
The experts concluded that both options should remain available for vaccine formulations in the southern hemisphere, subject to national needs.http://www.who.int/csr/disease/swineflu/notes/briefing_20091030/en/index.html

The Emergency Use Authorization of Peramivir for Treatment of 2009 H1N1 Influenza

2009-11-10T13:09:00.007+05:30

On October 23, 2009, Food and Drug Administration (FDA) CommissionerMargaret Hamburg issued an Emergency Use Authorization (EUA)for peramivir for intravenous injection (BioCryst Pharmaceuticals).Peramivir is an unapproved investigational neuraminidase inhibitorthat may be effective in treating certain hospitalized adultand pediatric patients with suspected or confirmed cases of2009 H1N1 influenza. The EUA allows health care providers touse peramivir, subject to specified conditions. This is thefirst EUA that has been issued for an unapproved drug.The legal standard for the authorization of an EUA during adeclared public health emergency requires a finding that itis "reasonable to believe" that the product "may be effective,"as well as a finding that its known and potential benefits outweighits known and potential risks.¹ There must also be no otheradequate, approved, and available treatment alternatives forthe specific indication. This is a lower evidentiary standardthan that used for marketing approval, which requires a findingof "substantial evidence" of efficacy for the proposed use basedon adequate and well-controlled trials, as well as a robustsafety evaluation.

Childhood Acute Lymphoblastic Leukemia

2009-11-09T19:16:00.004+05:30

Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).

Childhood acute lymphoblastic leukemia (also called acute lymphocytic leukemia or ALL) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of cancer in children.
Normally, the bone marrow makes blood stem cells (immature cells) that develop into mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.
The myeloid stem cell develops into one of three types of mature blood cells:

Red blood cells that carry oxygen and other materials to all tissues of the body.
Platelets that help prevent bleeding by causing blood clots to form.
Granulocytes (white blood cells) that fight infection and disease.

The lymphoid stem cell develops into a lymphoblast cell and then into one of three types of lymphocytes (white blood cells):

B lymphocytes that make antibodies to help fight infection.
T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
Natural killer cells that attack cancer cells and viruses.

Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

In ALL, too many stem cells develop into lymphoblasts or lymphocytes. These cells may also be called leukemic cells. The leukemic cells are not able to fight infection very well. Also, as the number of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may lead to infection, anemia, and easy bleeding.
There are subgroups of childhood ALL.
Four of the subgroups of ALL are based on the type of blood cell that is affected, whether there are certain changes in the chromosomes, and age at diagnosis:

T cell ALL.
Philadelphia chromosome positive ALL.
ALL diagnosed in an infant.
ALL diagnosed in children who are aged 10 and older and adolescents (teenagers).

These subgroups are treated differently from other types of ALL.

Family history and exposure to radiation may affect the risk of developing childhood ALL.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Possible risk factors for ALL include the following:

Having a brother or sister with leukemia.
Being white or Hispanic.
Living in the United States.
Being exposed to x-rays before birth.
Being exposed to radiation.
Past treatment with chemotherapy or other drugs that weaken the immune system.
Having certain genetic disorders, such as Down syndrome.

Possible signs of childhood ALL include fever and bruising.

These and other symptoms may be caused by childhood ALL. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

Fever.
Easy bruising or bleeding.
Petechiae (flat, pinpoint spots under the skin caused by bleeding).
Bone or joint pain.
Painless lumps in the neck, underarm, stomach, or groin.
Pain or feeling of fullness below the ribs.
Weakness or feeling tired.
Loss of appetite.

Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood ALL.

The following tests and procedures may be used:

Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:

The number of red blood cells and platelets.
The number and type of white blood cells.
The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
The portion of the sample made up of red blood cells.

Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.

Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.
Cytogenetic analysis: A laboratory test in which the cells in a sample of blood or bone marrow are viewed under a microscope to look for certain changes in the chromosomes in the lymphocytes. For example, in ALL, part of one chromosome is moved to another chromosome. This is called the “ Philadelphia chromosome.”

Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.

Immunophenotyping: A test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if malignant lymphocytes (cancer) began from the B lymphocytes or the T lymphocytes.
Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on:

Age and white blood cell count at diagnosis.
How quickly and how low the leukemia cell count drops after initial treatment.
Gender and race.
Whether the leukemia cells began from the B lymphocytes or the T lymphocytes.
Whether there are certain changes in the chromosomes of lymphocytes.
Whether the leukemia has spread to the brain and spinal cord.
Whether the child has Down syndrome.

Once childhood ALL has been diagnosed, tests are done to find out if the cancer has spread to the central nervous system (brain and spinal cord), testicles, or to other parts of the body.
The extent or spread of cancer is usually described as stages. For childhood acute lymphoblastic leukemia (ALL), risk groups are used instead of stages. The following tests and procedures may be used to determine the risk group:

Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.
Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
Testicular biopsy: The removal of cells or tissues from the testicles so they can be viewed under a microscope by a pathologist to check for signs of cancer. This procedure is done only if there seems to be anything unusual about the testicles during the physical exam.

There are three ways that cancer spreads in the body.
When cancer cells spread outside the blood, a solid tumor may form. This process is called metastasis. The three ways that cancer cells spread in the body are:

Through the blood. Cancer cells travel through the blood, invade solid tissues in the body, such as the brain or heart, and form a solid tumor.
Through the lymph system. Cancer cells invade the lymph system, travel through the lymph vessels, and form a solid tumor in other parts of the body.
Through solid tissue. Cancer cells that have formed a solid tumor spread to tissues in the surrounding area.

The new (metastatic) tumor is the same type of cancer as the primary cancer. For example, if leukemia cells spread to the brain, the cancer cells in the brain are actually leukemia cells. The disease is metastatic leukemia, not brain cancer.

In childhood ALL, risk groups are used instead of stages.

Risk groups are described as:

Standard (low) risk: Includes children aged 1 to 9 years who have a white blood cell count of less than 50,000/µL at diagnosis.
High risk: Includes children younger than 1 year or older than 9 years and children who have a white blood cell count of 50,000/µL or more at diagnosis.
It is important to know the risk group in order to plan treatment.

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent childhood ALL is cancer that has recurred (come back) after it has been treated. The leukemia may come back in the blood and bone marrow, brain, testicles, spinal cord, or in other parts of the body.

There are different types of treatment for childhood acute lymphoblastic leukemia (ALL).

Different types of treatment are available for children with acute lymphoblastic leukemia (ALL). Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.
Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.
Children with ALL should have their treatment planned by a team of doctors with expertise in treating childhood leukemia.
Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric health professionals who are experts in treating children with leukemia and who specialize in certain areas of medicine. These may include the following specialists:

Hematologist.
Medical oncologist.
Pediatric surgeon.
Radiation oncologist.
Endocrinologist.
Neurologist.
Neuropathologist.
Neuroradiologist.
Pediatric nurse specialist.
Social worker.
Rehabilitation specialist.
Psychologist.

Regular follow-up exams are very important. Side effects can result from treatment long after it ends. These are called late effects. Radiation therapy to the head may affect the child's developing brain and cause changes in mood, feelings, thinking, learning, or memory. Late effects of treatment for ALL also include the risk of second cancers (new types of cancer), especially brain tumors. Early diagnosis and treatment of these secondary brain tumors may help lower the risk from these brain tumors. Children younger than 4 years have a higher risk of side effects from radiation therapy to the brain. It is important to talk with your child's doctors about the possible late effects caused by some treatments. See the PDQ summary on Late Effects of Treatment for Childhood Cancer.
The treatment of childhood ALL usually has 3 phases.
The treatment of childhood ALL is done in phases:

Induction therapy: This is the first phase of treatment. Its purpose is to kill the leukemia cells in the blood and bone marrow. This puts the leukemia into remission. This is also called the remission induction phase.
Consolidation /intensification therapy: This is the second phase of therapy. It begins once the leukemia is in remission. The purpose of consolidation/intensification therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse.
Maintenance therapy: This is the third phase of treatment. Its purpose is to kill any remaining leukemia cells that may regrow and cause a relapse. Often the cancer treatments are given in lower doses than those used for induction and consolidation/intensification therapy. This is also called the continuation therapy phase.

Bone marrow biopsy and aspirates are done throughout all phases to see how well the leukemia is responding to treatment.
Treatment called central nervous system (CNS) sanctuary therapy is usually given during each phase of therapy. Because chemotherapy that is given by mouth or injected into a vein may not reach leukemia cells in the CNS (brain and spinal cord), the cells are able to find “sanctuary” (hide) in the CNS. Intrathecal chemotherapy and radiation therapy are able to reach leukemia cells in the CNS and are given to kill the leukemia cells and prevent the cancer from recurring (coming back). CNS sanctuary therapy is also called CNS prophylaxis.
Three types of standard treatment are used:
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column (intrathecal), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type of the cancer being treated.
Intrathecal chemotherapy may be used to treat childhood ALL that has spread, or may spread, to the brain and spinal cord. When used to prevent cancer from spreading to the brain and spinal cord, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. Intrathecal chemotherapy is given in addition to chemotherapy by mouth or vein.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. External radiation therapy may be used to treat childhood ALL that has spread, or may spread, to the brain and spinal cord. When used this way, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.
Because radiation therapy to the brain can affect growth and brain development in young children, clinical trials are studying new ways of using radiation therapy that may have fewer side effects, including lower doses and fractionation (dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days).

Chemotherapy with stem cell transplant

Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells. A stem cell transplant using stem cells from a donor who is not related to the patient is being studied in
clinical trials.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.
High-dose chemotherapy
High-dose chemotherapy is giving high doses of anticancer drugs to kill cancer cells. This treatment often causes the bone marrow to stop making blood cells and can cause other serious side effects. High-dose chemotherapy is usually followed by stem cell transplant to restore the bone marrow. Clinical trials are studying high-dose chemotherapy for certain patients, including children whose ALL does not go into remission after induction therapy.

Other drug therapy

Imatinib mesylate (Gleevec) is a type of anticancer drug called a tyrosine kinase inhibitor. It blocks the enzyme, tyrosine kinase, that causes stem cells to develop into more white blood cells (granulocytes or blasts) than the body needs.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Childhood Acute Lymphoblastic Leukemia

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Untreated Childhood Acute Lymphoblastic Leukemia

Standard treatment of childhood acute lymphoblastic leukemia (ALL) during the induction, consolidation /intensification, and maintenance phases may include the following:

Combination chemotherapy.
CNS sanctuary therapy with intrathecal chemotherapy and/or radiation therapy to the brain.

Some of the treatments being studied in clinical trials for childhood ALL include the following:

Combination chemotherapy with or without intrathecal chemotherapy. Radiation therapy to brain may also be given.
Combination chemotherapy followed by stem cell transplant using stem cells donated by a brother or sister.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with untreated childhood acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Childhood Acute Lymphoblastic Leukemia Subgroups

Standard treatment of T-cell childhood acute lymphoblastic leukemia (ALL) is usually combination chemotherapy. CNS sanctuary therapy with intrathecal chemotherapy and/or radiation therapy to the brain may also be given. One of the treatments being studied in clinical trials for T-cell childhood ALL is a new kind of anticancer drug.
Treatment of infants with ALL is usually a clinical trial of systemic chemotherapy with intrathecal chemotherapy or chemotherapy followed by a donor stem cell transplant.
Treatment of ALL in older children and adolescents usually involves more aggressive therapy (stronger treatments and higher doses) than that given to children aged 1-9 years.
Standard treatment of Philadelphia chromosome-positive childhood ALL is usually a stem cell transplant using stem cells donated by a brother or sister. One of the treatments being studied in clinical trials for Philadelphia chromosome-positive childhood ALL is imatinib mesylate (Gleevec).
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with T-cell childhood acute lymphoblastic leukemia and Philadelphia chromosome positive childhood precursor acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Recurrent Childhood Acute Lymphoblastic Leukemia

Standard treatment of recurrent childhood acute lymphoblastic leukemia (ALL) may include the following:

Combination chemotherapy.
Systemic chemotherapy and intrathecal chemotherapy with or without radiation therapy to the brain and spinal cord.
Chemotherapy with stem cell transplant, using stem cells from a donor who is related to the patient, with or without total-body irradiation.
Chemotherapy plus radiation therapy for cancer that recurs in the testicles only.

Some of the treatments being studied in clinical trials for recurrent childhood ALL include the following:

A clinical trial of chemotherapy with stem cell transplant, using stem cells from a donor who is not related to the patient, with or without total-body irradiation.
A clinical trial of new anticancer drugs and new combination chemotherapy treatments.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent childhood acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Get More Information From NCI

Call 1-800-4-CANCER
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. A trained Cancer Information Specialist is available to answer your questions.
Chat online
The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
Write to us
For more information from the NCI, please write to this address:

NCI Public Inquiries Office Suite 3036A 6116 Executive Boulevard, MSC8322 Bethesda, MD 20892-8322

SOURCE:

National Cancer Institute, U.S. National Institutes of Health

Schizophrenia

2009-11-09T19:00:00.004+05:30

How is schizophrenia treated?

Because the causes of schizophrenia are still unknown, treatments focus on eliminating the symptoms of the disease. Treatments include antipsychotic medications and various psychosocial treatments.

Antipsychotic medications

Antipsychotic medications have been available since the mid-1950's. The older types are called conventional or "typical" antipsychotics. Some of the more commonly used typical medications include:

Chlorpromazine (Thorazine)
Haloperidol (Haldol)
Perphenazine (Etrafon, Trilafon)
Fluphenazine (Prolixin).

In the 1990's, new antipsychotic medications were developed. These new medications are called second generation, or "atypical" antipsychotics.
One of these medications, clozapine (Clozaril) is an effective medication that treats psychotic symptoms, hallucinations, and breaks with reality. But clozapine can sometimes cause a serious problem called agranulocytosis, which is a loss of the white blood cells that help a person fight infection. People who take clozapine must get their white blood cell counts checked every week or two. This problem and the cost of blood tests make treatment with clozapine difficult for many people. But clozapine is potentially helpful for people who do not respond to other antipsychotic medications.
Other atypical antipsychotics were also developed. None cause agranulocytosis. Examples include:

Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Aripiprazole (Abilify)
Paliperidone (Invega).

What are the side effects?

Some people have side effects when they start taking these medications. Most side effects go away after a few days and often can be managed successfully. People who are taking antipsychotics should not drive until they adjust to their new medication. Side effects of many antipsychotics include:

Drowsiness
Dizziness when changing positions
Blurred vision
Rapid heartbeat
Sensitivity to the sun
Skin rashes
Menstrual problems for women.

Atypical antipsychotic medications can cause major weight gain and changes in a person's metabolism. This may increase a person's risk of getting diabetes and high cholesterol. A person's weight, glucose levels, and lipid levels should be monitored regularly by a doctor while taking an atypical antipsychotic medication.
Typical antipsychotic medications can cause side effects related to physical movement, such as:

Rigidity
Persistent muscle spasms
Tremors
Restlessness.

Long-term use of typical antipsychotic medications may lead to a condition called tardive dyskinesia (TD). TD causes muscle movements a person can't control. The movements commonly happen around the mouth. TD can range from mild to severe, and in some people the problem cannot be cured. Sometimes people with TD recover partially or fully after they stop taking the medication.
TD happens to fewer people who take the atypical antipsychotics, but some people may still get TD. People who think that they might have TD should check with their doctor before stopping their medication.

How are antipsychotics taken and how do people respond to them?

Antipsychotics are usually in pill or liquid form. Some anti-psychotics are shots that are given once or twice a month.
Symptoms of schizophrenia, such as feeling agitated and having hallucinations, usually go away within days. Symptoms like delusions usually go away within a few weeks. After about six weeks, many people will see a lot of improvement.
However, people respond in different ways to antipsychotic medications, and no one can tell beforehand how a person will respond. Sometimes a person needs to try several medications before finding the right one. Doctors and patients can work together to find the best medication or medication combination, as well as the right dose.
Some people may have a relapse -- their symptoms come back or get worse. Usually, relapses happen when people stop taking their medication, or when they only take it sometimes. Some people stop taking the medication because they feel better or they may feel they don't need it anymore. But no one should stop taking an antipsychotic medication without talking to his or her doctor. When a doctor says it is okay to stop taking a medication, it should be gradually tapered off, never stopped suddenly.

How do antipsychotics interact with other medications?

Antipsychotics can produce unpleasant or dangerous side effects when taken with certain medications. For this reason, all doctors treating a patient need to be aware of all the medications that person is taking. Doctors need to know about prescription and over-the-counter medicine, vitamins, minerals, and herbal supplements. People also need to discuss any alcohol or other drug use with their doctor.
To find out more about how antipsychotics work, the National Institute of Mental Health (NIMH) funded a study called CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness). This study compared the effectiveness and side effects of five antipsychotics used to treat people with schizophrenia. In general, the study found that the older typical antipsychotic perphenazine (Trilafon) worked as well as the newer, atypical medications. But because people respond differently to different medications, it is important that treatments be designed carefully for each person. More information about CATIE is on the NIMH website.

Psychosocial treatments

Psychosocial treatments can help people with schizophrenia who are already stabilized on antipsychotic medication. Psychosocial treatments help these patients deal with the everyday challenges of the illness, such as difficulty with communication, self-care, work, and forming and keeping relationships. Learning and using coping mechanisms to address these problems allow people with schizophrenia to socialize and attend school and work.
Patients who receive regular psychosocial treatment also are more likely to keep taking their medication, and they are less likely to have relapses or be hospitalized. A therapist can help patients better understand and adjust to living with schizophrenia. The therapist can provide education about the disorder, common symptoms or problems patients may experience, and the importance of staying on medications. For more information on psychosocial treatments, see the psychotherapies section on the NIMH website.

Illness management skills.

People with schizophrenia can take an active role in managing their own illness. Once patients learn basic facts about schizophrenia and its treatment, they can make informed decisions about their care. If they know how to watch for the early warning signs of relapse and make a plan to respond, patients can learn to prevent relapses. Patients can also use coping skills to deal with persistent symptoms.
Integrated treatment for co-occurring substance abuse. Substance abuse is the most common co-occurring disorder in people with schizophrenia. But ordinary substance abuse treatment programs usually do not address this population's special needs. When schizophrenia treatment programs and drug treatment programs are used together, patients get better results.

Rehabilitation.

Rehabilitation emphasizes social and vocational training to help people with schizophrenia function better in their communities. Because schizophrenia usually develops in people during the critical career-forming years of life (ages 18 to 35), and because the disease makes normal thinking and functioning difficult, most patients do not receive training in the skills needed for a job.
Rehabilitation programs can include job counseling and training, money management counseling, help in learning to use public transportation, and opportunities to practice communication skills. Rehabilitation programs work well when they include both job training and specific therapy designed to improve cognitive or thinking skills. Programs like this help patients hold jobs, remember important details, and improve their functioning.

Family education.

People with schizophrenia are often discharged from the hospital into the care of their families. So it is important that family members know as much as possible about the disease. With the help of a therapist, family members can learn coping strategies and problem-solving skills. In this way the family can help make sure their loved one sticks with treatment and stays on his or her medication. Families should learn where to find outpatient and family services.

Cognitive behavioral therapy.

Cognitive behavioral therapy (CBT) is a type of psychotherapy that focuses on thinking and behavior. CBT helps patients with symptoms that do not go away even when they take medication. The therapist teaches people with schizophrenia how to test the reality of their thoughts and perceptions, how to "not listen" to their voices, and how to manage their symptoms overall. CBT can help reduce the severity of symptoms and reduce the risk of relapse.

Self-help groups.

Self-help groups for people with schizophrenia and their families are becoming more common. Professional therapists usually are not involved, but group members support and comfort each other. People in self-help groups know that others are facing the same problems, which can help everyone feel less isolated. The networking that takes place in self-help groups can also prompt families to work together to advocate for research and more hospital and community treatment programs. Also, groups may be able to draw public attention to the discrimination many people with mental illnesses face.
Once patients learn basic facts about schizophrenia and its treatment, they can make informed decisions about their care.

Pregnant Women Mount Strong Immune Response to One Dose of 2009 H1N1 Flu Vaccine

2009-11-09T18:49:00.003+05:30

Healthy pregnant women mount a robust immune response following just one dose of 2009 H1N1 influenza vaccine, according to initial results from an ongoing clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.

"For pregnant women, who are among the most vulnerable to serious health problems from 2009 H1N1 infection, these initial results are very reassuring," says NIAID Director Anthony S. Fauci, M.D. "The immune responses seen in these healthy pregnant women are comparable to those seen in healthy adults at the same time point after a single vaccination, and the vaccine has been well tolerated."

According to the Centers for Disease Control and Prevention, since the outbreak began last spring, at least 100 pregnant women have been hospitalized in intensive care units in the United States and at the last official count, 28 pregnant women have died.

A preliminary analysis of blood samples taken 21 days post-vaccination from a subgroup of 50 pregnant women participating in the trial shows the following:

In 25 women who received a single 15-microgram dose of the vaccine, the H1N1 flu vaccine elicited an immune response likely to be protective in 92 percent, or 23 of 25, of these women.
In 25 women who received a single 30-microgram dose of the vaccine, the H1N1 flu vaccine elicited an immune response likely to be protective in 96 percent, or 24 of 25, of these women.

The trial began on Sept. 9 and reached its target enrollment of 120 volunteers in mid-October. All participants are between 18 to 39 years old and began the study in their second or third trimester (14 to 34 weeks) of pregnancy. At entry into the study, the participants were divided at random into two groups: half are receiving two doses of a 15-microgram vaccine and the other half are receiving two doses of a 30-microgram vaccine. The two injections of vaccine are spaced three weeks apart.
Safety is being monitored closely in the trial, by the study investigators and by an independent panel of experts known as a safety monitoring committee. To date, the vaccine appears to be well-tolerated, and no safety concerns related to the vaccine have arisen.
The vaccine used in this clinical trial was manufactured by Sanofi Pasteur in its plant in Swiftwater, Pa., in the same manner as the company’s injectable seasonal influenza vaccine. Like the seasonal flu vaccine, the 2009 H1N1 flu vaccine contains a purified portion of the killed virus and therefore cannot cause infection. The vaccine does not contain the preservative thimerosal or an immune boosting substance known as an adjuvant.

NIAID is conducting this trial through five clinical sites affiliated with its longstanding clinical trials network known as the Vaccine and Treatment Evaluation Units. For additional information about the NIAID trial in healthy pregnant women, see the Sept. 9 NIAID news release http://www3.niaid.nih.gov/news/newsreleases/2009/H1N1pregnanttrials.htm and related Q&A http://www3.niaid.nih.gov/news/QA/H1N1pregnanttrials.htm.
For more information on influenza, including pandemic influenza and avian influenza, visit www.flu.gov. Also see NIAID's influenza Web portal at http://www3.niaid.nih.gov/topics/Flu/.
NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Mutations in Genes that Cause Early-Onset Inflammatory Bowel Disease

2009-11-09T18:46:00.003+05:30

Finding Enables Successful Treatment of a Previously Treatment-Resistant Patient

An international team including researchers with the National Institutes of Health has discovered that mutations in either of two related genes cause a severe and rare form of inflammatory bowel disease (IBD) in young children.

Discovery of the genetic mutations allowed the researchers to successfully treat one of the study patients with a bone marrow transplant. The patient, who had not responded to other therapies, showed dramatic improvement following the bone marrow transplant and has remained in remission from IBD for more than a year.

The collaborative study included researchers from the National Center for Biotechnology Information (NCBI) at the National Institutes of Health, Hannover Medical School in Germany, University College London (UCL) in the United Kingdom, and several other institutions.
"This is an excellent example of how discovery of causative genes and mutations can enable clinicians to go from bench to bedside for an informed treatment of patients," said Professor Christoph Klein, Medical School of Hannover, Germany, who led the diagnosis and treatment effort. Professor Klein and his team recently created the "Care for Rare Foundation" (www.care-for-rare.org) to support treatment of children with rare immunological disorders and to speed their treatment based on new discoveries such as genetic mutations.
The IBD research will be published in the Nov. 19, 2009 edition of The New England Journal of Medicine, and will be available on the journal's Web site beginning Nov. 4, at 5 p.m. EST.

The successful treatment of the patient in this study built upon a well established treatment approach: that bone marrow transplants can be curative in genetic disorders where the affected gene is normally active in cells derived from the bone marrow. Because of the risks associated with bone marrow transplants, they are used only in cases of severe diseases, where the potential benefits outweigh the risks. Patients with the IBD caused by the genetic mutations identified in this research have very severe disease that meets this general criterion, though each case must be evaluated individually. In order to perform a bone marrow transplant a matched donor is needed. The study patient’s matched donor was a healthy sibling, which is the preferred approach, but bone marrow transplants also can be done using more distantly related or unrelated matched donors.
The study is the first to show that a single genetic mutation is sufficient to cause IBD. Other research groups focusing primarily on adult-onset IBD have identified dozens of genes and variants that affect the risk for IBD, but none that singly can cause the disease.

The mutated genes identified in the study encode the proteins IL10R1 and IL10R2, which act together to receive signals from the cytokine IL10. IL10 (interleukin 10) plays a crucial role in keeping the body’s inflammatory responses in check. The human body is continuously generating local inflammatory responses to control microbial infections and repair damage from other toxins, but if that inflammatory response is not properly controlled tissues may be excessively damaged. When either IL10R1 or IL10R2 is mutated, the signals from IL10 cannot be received, and the resulting inflammation causes tissue damage, especially in the gastrointestinal system.
"This discovery is a milestone in research on inflammatory bowel disease, and will enable us to gain further insights into the physiology and immunity of the intestine," said Erik Glocker, UCL, who found the first mutation in IL10R2 identified in the study. Analysis of additional patients with early-onset IBD revealed mutations in IL10R1.
The gene identification effort was led by Professor Bodo Grimbacher, UCL Medical School (Royal Free Campus Hampstead), and head of the Marie-Curie Excellence Research Group, who said: "This discovery will lead to future therapeutic options not only in children, but potentially also in adult patients with IL10 signalling problems."
Alejandro Schaffer and his team from the U.S. National Center for Biotechnology Information (NCBI) led the computational analysis to pinpoint the genes. By studying genetic data on a family with two affected siblings and two unaffected siblings, Dr. Schaffer's team provided computational and statistical proof that the mutated gene should be located in one of three small regions in the human genome. One of these regions included the gene encoding IL10R2, which was determined to be the best candidate because of studies showing mice deficient in the corresponding gene had IBD. "NCBI is proud to be a part of this important research, which illustrates how computational biology can facilitate selection of effective treatments," said David Lipman, M.D., director of NCBI.
NCBI creates public databases in molecular biology, conducts research in computational biology, develops software tools for analyzing molecular and genomic data, and disseminates biomedical information, all for the better understanding of processes affecting human health and disease. NCBI (www.ncbi.nlm.nih.gov) is a division of the National Library of Medicine (www.nlm.nih.gov), the world's largest library of the health sciences. The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

LDL cholesterol:	below 100 mg/dL
HDL cholesterol:	above 40 mg/dL for men
	above 50 mg/dL for women
Triglycerides:	below 150 mg/dL

Med-mission

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In this episode we look at how a disease once considered a close companion of affluent societies has moved to the developing world.

Transcript of the podcast

Experts advise WHO on pandemic vaccine policies and strategies

009 briefing note

Current situation

Dosage

Co-administration of vaccines

Vaccine safety

Vaccines for pregnant women

Vaccines for the southern hemisphere in 2010

The Emergency Use Authorization of Peramivir for Treatment of 2009 H1N1 Influenza

Childhood Acute Lymphoblastic Leukemia

Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).

Family history and exposure to radiation may affect the risk of developing childhood ALL.

Possible signs of childhood ALL include fever and bruising.

Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood ALL.

Certain factors affect prognosis (chance of recovery) and treatment options.

In childhood ALL, risk groups are used instead of stages.