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Safety Steps: Running in the Dark

FitSugar — Wed, 04 Nov 2009 04:30:53 -0800

The end of daylight saving time means that many of us will be running in the dark. For safety reasons, try going on a morning run instead. Wake up at the same time you did during DST and use that "extra" hour for an outdoor run.

If running at night is unavoidable, make sure to follow these tips to protect yourself in the dark:

Make sure others can see you. Make yourself visible to drivers, cyclists, pedestrians, and other runners by wearing bright colors and reflective gear. For extra caution, wear a headlamp or attach blinking bike lights to your clothing.
Run in familiar, well-lit areas. Running a familiar route may protect you from unseen bumps or potholes. To ensure a clear running path, find an area that is lit by streetlamps or hit up an outdoor track.
Be aware. Because running at night cuts down on your line of sight, you want to make sure you can hear clearly - run without an iPod, MP3 player, or Walkman. Make eye contact to alert those around you of your presence. This is especially important to do with drivers when you're crossing the street.

For more safety tips, read more.

Carry a cell phone and ID. Keep a cell phone with you in the event of an emergency, and always carry identification in case you sustain an injury.
Run with a buddy. There's safety in numbers, so always try and run with a buddy. You'll be more visible and can rely on one another if something goes wrong. If you do run alone, make sure to tell someone the route you're running and around what time you'll be back.
Run against traffic. You have a better chance of seeing cars and drivers have a better chance of seeing you.
Change up your routine. Run a few different routes and at different times through the week. Potential attackers may catch on to routines.

Do you have any running tips to share? Join our RunningSugar community and be part of the conversation.

Sickle cell disease

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Screening for Sickle Cell Disease

The United States Preventive Services Task Force’s 2007 guidelines recommend that all newborn infants be screened for sickle cell disease. (In the United States, most states require hospitals to perform this test.) Early detection of sickle cell disease ensures that babies will be given treatment to prevent infections. Sickle cell disease is an inherited condition. About 1 in 375 African-American babies are born with sickle cell disease, but children of other ethnicities are also at risk.

Infections and Sickle Cell Disease

Children with sickle cell disease are highly susceptible to many life-threatening infections, including those caused by the pneumococcus bacterium. Pneumococcal vaccinations are an important protection against this bacterium. Research published in 2007 in Clinical Infectious Diseases indicates that the introduction of the pneumococcal conjugate vaccine has helped reduce by 90% the rate of pneumococcal infections in children with sickle cell disease. Four doses of this vaccine are given from age 2 - 15 months. A second type of pneumococcal vaccine, pneumococcal saccharide, is given when the child reaches 2 years of age.
Daily antibiotics given from age 2 months through 5 years can help prevent many other types of bacterial infections, such as meningitis and blood infections.

Introduction

Blood has two major components:

Plasma is a clear yellow liquid that contains proteins, nutrients, hormones, electrolytes, and other substances. It constitutes about 55% of blood.
White and red blood cells and platelets make up the balance of blood. The white cells are the infection fighters for the body, and platelets are necessary for blood clotting. The important factors in anemia, however, are red blood cells.

Red blood cells (RBCs), also known as erythrocytes, carry oxygen throughout the body to nourish tissues and sustain life. Red blood cells are the most abundant cells in our bodies. Men have about 5.2 million red blood cells per cubic millimeter of blood, and women have about 4.7 million red blood cells per cubic millimeter of blood. To understand red blood cells and their role in anemia, it is useful to know certain facts about them.

Hemoglobin and Iron. Each red blood cell contains about 280 million hemoglobin molecules. Hemoglobin is a complex molecule and the most important component of red blood cells. It is composed of protein (globulin) and a molecule (heme), which binds to iron.

In the lungs, the heme component binds to oxygen in exchange for carbon dioxide. The red blood cells carry the oxygen to the body's tissues, where the hemoglobin releases the oxygen in exchange for carbon dioxide, and the cycle repeats. The oxygen is used in the mitochondria, the power source within all cells.

Structure and Shape. Red blood cells are extremely small and look something like tiny, flexible inner tubes. This unique shape offers many advantages:

It provides a large surface area to absorb oxygen and carbon dioxide.
Its flexibility allows it to squeeze through capillaries, the tiny blood vessels that join the arteries and veins.
Abnormally shaped or sized erythrocytes are typically destroyed and eliminated.

Blood Cell Production (Erythropoiesis). The actual process of making red blood cells is called erythropoiesis. (In Greek, erythro means "red" and poiesis means "the making of things.") The process of manufacturing, recycling, and regulating the number of red blood cells is complex and involves many parts of the body:

The body carefully regulates its production of red blood cells so that enough are manufactured to carry oxygen but not so many that the blood becomes thick or sticky (viscous).
Most of the work of erythropoiesis occurs in the bone marrow.
If the body needs more oxygen (at high altitudes, for instance), the kidney triggers the release of erythropoietin (EPO), a hormone that increases production of red blood cells in the bone marrow.
The lifespan of a red blood cell is 90 - 120 days. The liver and spleen remove old red blood cells from the blood.
When old red blood cells are broken down for removal, iron is returned to the bone marrow to make new cells.

Sickle cell disease occurs from genetic changes which causes a portion of the hemoglobin molecules to be abnormal:

Hemoglobin A (HbA). HbA is the hemoglobin molecule found in normal red blood cells during childhood and adulthood. People without sickle cell anemia have primarily this type of hemoglobin in their blood cells.
Hemoglobin S (HbS). HbS (S is for sickle) is the abnormal variant of hemoglobin A, which occurs in sickle-red blood cells and is the primary characteristic of the disease. The difference between hemoglobin A (HbA) and hemoglobin S (HbS) lies in only one protein out of about 300 that are common to both. This protein lies along an amino-acid chain called beta-globin, where even a tiny abnormality has disastrous results.

Hemoglobin is the most important component of red blood cells. It is composed of a protein called heme, which binds oxygen. In the lungs, oxygen is exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in red blood cell balance. Both low and high values can indicate disease states.

Hemoglobin F (HbF) is a form of hemoglobin that is produced during fetal development in the womb. (The F in HbF stands for fetal.) It is usually present for only a short time after birth. Normally, most HbF is later replaced by HbA, although some HbF may persist throughout life. Importantly, HbF is able to block the sickling action of red blood cells. Infants who have inherited sickle cell disease do not develop symptoms of the illness while they still have HbF present in their blood. People with the sickle cell gene who continue to carry some fetal hemoglobin are better protected, therefore, from severe forms of the disease. This knowledge is being used as the basis for therapies used in treating sickle cell disease.

The symptoms and problems of sickle cell disease are a result of the hemoglobin S (HbS) molecule:

When the sickle hemoglobin molecule loses its oxygen, it forms rigid rods called polymers that change the red blood cells into a sickle or crescent shape.
These abnormally sickle-shaped cells are both rigid and sticky. They stick to the walls and cannot squeeze through the capillaries. Blood flow through tiny blood vessels becomes slowed or stopped throughout the body. This deprives tissues and organs of oxygen.
In the immediate setting, oxygen deprivation (hypoxia) can cause severe pain (the sickle cell crisis). Over time, it leads to gradual destruction in organs and tissues throughout the body.

Click the icon to see an image of sickle cells.

In a vicious cycle, oxygen deprivation in cells leads to more polymerization and increased production of sickle cells. The higher the concentration of sickle hemoglobin and the more acidic the environment, the faster the sickle cell process.
Cell dehydration (not enough water molecules) is another major destructive factor in the sickling process of red blood cells. Dehydration increases the density of hemoglobin S within the cell, thereby speeding up the sickling process.
Sickle cells also have a shorter life span (10 - 20 days) than that of normal red blood cells (90 - 120 days). Every day the body produces new red blood cells to replace old ones, but sickle cells become destroyed so fast that the body cannot keep up. The red blood cell count drops, which results in anemia. This gives sickle cell disease its more common name, sickle cell anemia.

The severity of sickle cell disease generally depends on a number of factors:

The extent of oxygen loss. Prolonged oxygen deprivation contributes to the severe pain experienced as a sickle cell crisis. It also produces both short- and long-term organ damage. The lungs are specifically critical targets of the disease process. Because they supply oxygen, they can restore the sickle molecules to a normal form. Unfortunately, once the process occurs, the lungs become major sites for sickle cell damage, particularly for dangerous acute episodes of chest pain.
The acidity of the environment. The lower the better. The organs most seriously affected are those with an acidic environment (such as the spleen and bone marrow).
The concentration of hemoglobin S within the cell. The lower the better.
The amount of a protective hemoglobin F (for fetal). The more the better.

Risk Factors

Sickle cell disease is inherited. People at risk for inheriting the gene for sickle cell descend from people who are or were originally from Africa and parts of India and the Mediterranean. The sickle cell gene also occurs in people from South and Central America, the Caribbean, and the Middle East. The high incidence of the sickle cell gene in these regions of the world is due to the sickle cell's ability to make red blood cells resistant to the malaria parasite:

People who inherit just a single gene are referred to as having the sickle trait. These people are protected against malaria and do not develop sickle cell disease. About 40% of people in certain parts of Africa and about 9% of African-Americans have the trait.
Those who inherit both copies of the HbS gene develop sickle cell disease. They are not protected from malaria, however. In fact, malaria is more serious in these individuals. An estimated 1 in 500 African-Americans and 1 in 1,000 - 1,400 Hispanic Americans are born with sickle cell disease.

The sickle cell gene for hemoglobin S (HbS) is the most common inherited blood condition in America. About 72,000 Americans -- mostly African-Americans -- have sickle cell disease. The risk for inheriting sickle cell disease from parents with the sickle cell gene is as follows:

One parent has only one copy of the sickle cell gene and the other parent has two normal hemoglobin genes, and the child inherits a healthy gene from each parent. The child will not inherit either the disease or the trait.
The child inherits one copy of the sickle cell gene. The child has the trait (HbS) only. The other, healthy hemoglobin gene overrides HbS and blocks the development of sickle cell disease. Such people lead normal lives.
The child inherits the hemoglobin S gene from both parents (HbSS). The child develops the full-blown disease. (If each parent has one copy of the gene, the child has a 25% chance of acquiring the disease.)
The child inherits one hemoglobin S gene and one abnormal hemoglobin gene from other causes (such as one form called HbSC). Such children may develop a form of sickle cell disease. It is often a milder variant, but children can experience severe symptoms. They are also at risk for some of the complications of sickle cell disease, although their risks for serious problems are lower than in children with the full-blown disease.

Symptoms

General Symptoms in Infants. In infants, symptoms do not usually appear until late in the baby's first year. Most commonly, they include:

Fever
Swelling of the hands and feet
Pain in the chest, abdomen, limbs, and joints
Nosebleeds and frequent upper respiratory infections

General Symptoms in Childhood. Pain is the most common complaint. It can be acute and severe or chronic, usually from orthopedic problems in the legs and low back. Other symptoms include:

Anemia
Fatigue
Irritability
Jaundice (yellowish discoloration of the skin and eyes)
Bedwetting

Additional Symptoms in Adolescence or Adulthood. Symptoms of childhood continue in adolescence and adulthood. In addition, patients may experience:

Delayed puberty (in young teenagers)
Severe joint pain
Progressive anemia
Leg sores
Gum disease

The hallmark of sickle cell anemia is a group of devastating symptoms known collectively as a sickle cell crisis (also sometimes known as a vaso-occlusive crisis). Sickle cell crises are episodes of pain that occur with varying frequency and severity in different patients and are usually followed by periods of remission. Severe sickle cell pain has been described as being equivalent to cancer pain and more severe than postsurgical pain. It most commonly occurs in the lower back, leg, abdomen, and chest, usually in two or more locations. Episodes usually recur in the same areas.

The risk for a sickle cell crisis is increased by any activity that boosts the body's requirement for oxygen, such as illness, physical stress, or being at high altitudes. In more than half the cases, however, the trigger is unknown. Acute chest syndrome is a particularly serious complication of sickle cell crisis. It occurs in the lungs and can be extremely serious and even life threatening.

Diagnosis

Prenatal diagnosis of sickle cell disease is now possible for women who may be at risk for having a child with the disease. A positive result for sickle cell disease, however, poses extremely difficult questions even for parents who are not opposed to abortion.

A genetic test known as preimplantation genetic diagnosis (PGD) may prove to determine the presence or absence of the sickle cell mutation in embryos (fertilized eggs) before they are implanted in the mother during assisted fertilization techniques. This genetic tool may eventually help avoid the often emotionally devastating effects of abortion.

In the United States, most hospitals screen newborn babies for sickle cell disease. To perform the test, a blood sample is taken from the baby's heel using a simple needle prick. Early detection of sickle cell disease can help reduce the risk for life-threatening infections and increase the odds for survival. Babies who are diagnosed with sickle cell disease are given daily antibiotics to help prevent infections.

Unfortunately, no tests can definitely determine which children are at highest risk for a stroke and, therefore, would be candidates for ongoing blood transfusions. The following are diagnostic tools currently used or under investigation:

Transcranial Doppler (TCD) ultrasonography measures the speed of blood flow in the brain and is the most sensitive method to date for identifying children at risk for stroke. However, high-risk children are still vulnerable to stroke even if the TCD screening diagnosed normal blood flow velocities.
The use of follow-up magnetic resonance imaging (MRI) to detect small blockages in blood vessels may help confirm high risk in patients identified by TCD ultrasound.
Some patients may need to undergo angiography, an invasive diagnostic technique useful for detecting aneurysms.
Researchers are also beginning to uncover possible genetic markers that may eventually be used to help identify sickle cell patients at higher risk for stroke.

Outlook

New and aggressive treatments for sickle cell disease are prolonging life and improving its quality. As recently as 1973, the average lifespan for people with sickle cell disease was only 14 years. Currently, life expectancy for these patients can reach 50 years and over. Early studies showed that women had a greater risk for death from sickle cell disease than men, but experts now believe this was due to high mortality during pregnancies before the mid-1970s. Women with sickle cell disease now actually live longer than their male counterparts.

The damage and durability of sickle cell disease occurs because the logjam that sickle cells cause in the capillaries slows the flow of blood and reduces the supply of oxygen to various tissues. Not only does pain occur when body tissues are damaged by lack of oxygen, but serious and even life-threatening complications can result from severe or prolonged oxygen deprivation. Sickle cell disease is referred to in some African languages as "a state of suffering," but the disease has a wide spectrum of effects, which vary from patient to patient. In some people, the disease may trigger frequent and very painful sickle cell crises that require hospitalization. In others, it may cause less frequent and milder attacks.

Children with sickle cell disease are very susceptible to infections, usually because their damaged spleens are unable to protect the body from bacteria. A recent study suggested that signs of impaired lung function occur even in very early years. As medical progress has increased the lifespan of children with sickle cell disease, older patients are now facing medical problems related to the long-term adverse effects of the disease process. The most serious dangers are acute chest syndrome, long-term damage to major organs, stroke, and complications during pregnancy such as high blood pressure in the mother and low birth weight.

Complications

There is still no cure for sickle cell disease other than experimental transplantation procedures, but treatments for complications of sickle cell have prolonged the lives of many patients who are now living into adulthood.

The hallmark of sickle cell disease is the sickle cell crisis (also sometimes known as a vaso-occlusive crisis), which is an episode of pain. It is the most common reason for hospitalization in sickle cell disease. The pattern may occur as follows:

In general, the risk for a sickle cell crisis is increased by any activity that boosts the body's requirement for oxygen, such as illness, physical stress, or being at high altitudes. In more than half of episodes, however, the trigger is unknown.
Episodes typically begin at night and last 3 - 14 days, accelerating to a peak over several days and then declining.
The pain is typically described as sharp, intense, and throbbing. Severe sickle cell pain has been described as being equivalent to cancer pain and more severe than postsurgical pain. Shortness of breath is common.
Pain most commonly occurs in the lower back, leg, hip, abdomen, or chest, usually in two or more locations. Episodes usually recur in the same areas. Pain in the bones (usually occurring symmetrically on both sides) is common because blood obstruction can directly damage bone and because bone marrow is where red blood cells are manufactured.
The liver or spleen may become enlarged, causing pain in the upper right or upper left sides of the abdomen. Liver involvement may also cause nausea, low-grade fever, and increasing jaundice.
Males of any age may experience prolonged, often painful erections, a condition called priapism.

Episodes cannot be predicted, and they vary widely among different individuals. In one study, nearly 40% of patients reported no painful episodes over a 5-year period. About 5% of patients experienced severe and frequent episodes (more than three a year). They sometimes become less frequent with increasing age. Generally, people can resume a relatively normal life between crises. Most patients are pain-free between episodes although pain can be chronic in some cases.

Acute chest syndrome (ACS) occurs when the lungs are deprived of oxygen during a crisis. It can be very painful, dangerous, and even life threatening. It is a leading cause of illness among sickle cell patients and is the most common condition at the time of death. At least one whole segment of a lung is involved, and the following symptoms may be present:

Fever of 101.3°F degrees (38.5°C) or above
Rapid or labored breathing
Wheezing or cough
Acute chest pain

Pain often lasts for several days. In about half of patients, severe pain develops about 2 - 3 days before there are any signs of lung or chest abnormalities. Acute chest syndrome is often accompanied by infections in the lungs, which can be caused by viruses, bacteria, or fungi. Pneumonia is often present. A dull, aching pain usually follows, which most often ends after several weeks, although it may persist between crises.

Air is breathed in (inhaled) through the nasal passageways, and travels through the trachea and bronchi to the lungs.

Causes of Acute Chest Syndrome. Primary causes of acute chest syndrome include:

Infection. Infection from viruses or small atypical organisms (Chlamydia and Mycoplasma) is the most common cause of the oxygen deprivation that leads to acute chest syndrome.
Blockage of blood vessels. Blockage in the blood vessels (called infarction) that cuts off oxygen in the lungs is another important cause of acute chest syndrome. Blockage may be produced by blood clots or fat embolisms. (Fat embolisms are particles formed from fatty tissue in the bone marrow that enter and travel through the blood vessels.)
Asthma. Asthma can increase the frequency and pain of acute chest syndrome episodes in children, according to an important 2006 study. The researchers recommended that all children with sickle-cell disease who have frequent acute chest syndrome attacks should be evaluated for asthma.

In about 45% cases, the cause cannot be established. Some cases of acute chest syndrome may result from treatments of the crisis, including from administration of opioids (which reduce oxygen) or excessive use of intravenous fluids. Other lung diseases may also trigger ACS.

Severity of Acute Chest Syndrome. The mortality rates for ACS are around 2% in children and 4% in adults. The syndrome and its long-term complications are the major causes of death in older patients. The condition is four times more deadly in adults than in children. The longer a patient survives, the greater is the damage done by repetitive sickle cell crises in the chest and lungs.

The following destructive effects can occur:

Damage in the chest area from recurrent episodes increases susceptibility to invading infections, even those that are ordinarily not harmful. Infections frequently clear up if they are limited to small areas of the lung, but if they spread, they can progress very quickly and become life threatening.
Lung damage over time can lead to obstruction in the airways in lungs, causing asthma-like conditions.

Infections are common and an important cause of severe complications in sickle cell patients. Before early screening for sickle cell disease and the use of preventive antibiotics in children, 35% of infants with sickle cell died from infections. Fortunately, with screening tests for sickle cell now required for newborns in most states, and with the use of preventive antibiotics in babies who are born with the disease, this terrible mortality rate has dropped significantly.

Infections in Infants and Toddlers with Sickle Cell Disease. The most common organisms causing infection in children with sickle cell disease include:

Streptococcus pneumoniae (can cause blood infections or meningitis)
Haemophilus influenza (a cause of meningitis)

Such infections pose a grave threat to infants and very young children with sickle cell disease. They can progress to fatal pneumonia with devastating speed in infants, and death can occur only a few hours after onset of fever. The risk for pneumococcal meningitis, a dangerous infection of the central nervous system, is also significant.

Infections in Children and Adults. Infections are also common in older children and adults with sickle cell disease, particularly respiratory infections such as pneumonia, kidney infections, and osteomyelitis, a serious infection in the bone. (The organisms causing them, however, tend to differ from those in young children.) Infection-causing organisms include:

Chlamydia and Mycoplasma pneumoniae. These are the important infections in acute chest syndrome (see above).
Gram-negative bacteria. This group of bacteria mostly infects hospitalized patients and can cause serious pneumonias and other infections.

About 30% of patients with sickle cell disease have pulmonary hypertension. Pulmonary hypertension is a serious and potentially deadly condition that develops when pressure in the arteries of the lungs increases. It is an often unrecognized complication and cause of death in sickle cell disease. Many doctors recommend that all adults with sickle cell disease undergo echocardiographic testing to identify if they are at risk for pulmonary hypertension and require treatment.

Researchers are developing new types of tests that may help with early identification of pulmonary hypertension. For example, some studies indicate that a simple blood test for the hormone brain natriuretic peptide (BNP) could help identify patients with sickle cell pulmonary hypertension. Higher levels of BNP are associated with increased pressure in the pulmonary (lung) arteries. A blood test measuring levels of the enzyme lactate dehydrogenase (LDH) may also help identify patients at risk for pulmonary hypertension, as well as leg ulcerations and priapism (persistent and painful erection of the penis). Echocardiography or other tests would still need to be performed to confirm results from these blood tests.

The primary symptom of pulmonary hypertension is shortness of breath, which is often severe. Pulmonary hypertension can be very serious and life threatening in the short- and long-term. If pulmonary hypertension develops suddenly it can cause respiratory failure, which is life threatening. Over time, pulmonary hypertension may cause a condition called cor pulmonale, in which the right side of the heart increases in size. In some cases, this enlargement can lead to heart failure.

Click the icon to see an image of cor pulmonale.

After acute chest syndrome, stroke is the most common killer of patients with sickle cell disease who are older than 3 years old. Between 8 - 10% of patients suffer strokes, typically at about age 7. Patients may also suffer small strokes that may not be immediately noticeable. However, patients who have many of these small strokes may over time start behaving differently or have worsening mental functioning.

Strokes are usually caused by blockages of vessels carrying oxygen to the brain. Patients with sickle cell disease are also at high risk for stokes caused by aneurysm, a weakened blood vessel wall that can rupture and hemorrhage. Multiple aneurysms are common in sickle cell patients, but they are often located where they cannot be treated surgically.

Click the icon to see an image of stroke.

Anemia is a significant characteristic in sickle cell disease (which is why the disease is commonly referred to as sickle cell anemia).

Severe worsening of anemia. Children, adolescents, and possibly young adults may experience what is called splenic sequestration. This happens when a large amount of the sickled red blood cells collect in the patient's spleen. Symptoms may include pain in the right abdomen below the ribs and a large mass (the swollen spleen) may be felt.

Chronic Anemia. Because of the short lifespan of the sickle red blood cells, the body is often unable to replace red blood cells as quickly as they are destroyed. This causes a particular form of anemia called hemolytic anemia. Most patients with sickle cell disease have a hemoglobin levels of 8 g/dL, much lower than people without sickle cell anemia. Chronic anemia reduces oxygen and increases the demand on the heart to pump more oxygen-bearing blood through the body. Eventually, this can cause the heart to become dangerously enlarged, with an increased risk for heart attack and heart failure.

On occasion, patients may experience what is called an aplastic crisis. This happens when the cells in the bone marrow that are normally trying to make new red blood cells suddenly stop working. This sudden stopping is often triggered by a virus called human parvovirus B19.

The kidneys are particularly susceptible to damage from the sickling process. Persistent injury can cause a number of kidney disorders, including infection. Problems with urination are very common, particularly uncontrolled urination during sleep. Patients may have blood in the urine, although this is usually mild and painless and resolves without damaging consequences. Kidney failure is a major danger in older patients and accounts for 10 - 15% of deaths in sickle cell patients. Renal medullary carcinoma is an aggressive, rapidly destructive tumor in the kidney that is rare but can occur as a result of sickle cell disease.

Click the icon to see an image of kidney anatomy.

A reported 38 - 42% of males, including children, with sickle cell disease suffer from priapism. Priapism causes prolonged and painful erections that can last from several hours to days. Experts think that priapism in sickle cell disease may be caused by the destruction of red blood cells and subsequent reduction of nitric oxide. If priapism is not treated, partial or complete impotence can occur in 80% of cases.

Click the icon to see an image of the male reproductive anatomy.

Enlargement of the liver occurs in over half of sickle cell patients, and acute liver damage occurs in up to 10% of hospitalized patients. Because sickle cell patients often need transfusions, they have been at higher risk for viral hepatitis, an infection of the liver. This risk, however, has decreased since screening procedures for donated blood have been implemented.

About 30% of children with sickle cell disease have gallstones, and by age 30, 70% of patients have them. In most cases, gallstones do not cause symptoms for years. When symptoms develop, patients may feel overly full after meals, have pain in the upper right quadrant of the abdomen, or have nausea and vomiting. Acute attacks can be confused with a sickle cell crisis in the liver. Ultrasound is usually used to confirm a diagnosis of gallstones. If the patient does not have symptoms, no treatment is usually necessary. If there is recurrent or severe pain from gallstones, the gallbladder may need to be removed. Minimally invasive procedures (using laparoscopy) reduce possible complications. [For more information, see In-Depth Report #10: Gallstones.]

Click the icon to see an image of cholithiasis.

The spleen of most adults with sickle cell anemia is nonfunctional due to recurrent episodes of oxygen deprivation that eventually destroy it. Injury to spleen causes problems in immune function and increases the risk for serious infection. A very serious anemic condition called acute splenic sequestration crisis (sudden spleen enlargement) can occur if the damaged spleen suddenly becomes enlarged from trapped blood.

Click the icon to see an image of an enlarged spleen.

In some children with sickle cell disease, excessive production of blood cells in the bone marrow causes bones to grow abnormally, resulting in long legs and arms or misshapen skulls. Sickling that blocks oxygen to the bone can also cause bone loss and pain. Sickling that affects the hands and feet of children causes a painful condition called hand-foot syndrome. A condition called avascular necrosis of the hip occurs in about half of adult sickle cell patients when oxygen deprivation causes tissue death in the bone. Eventually adult patients may require surgery to remove diseased and dead bone tissue. Joint replacement may be required in severe cases. X-rays are not very useful for detecting early disease in the bones. MRI may be important.

Click the icon to see an image of the blood supply to bone.

Leg sores and ulcers occur in up to 10% of sickle cell patients and usually affect patients older than 10 years.

Women with sickle cell disease who become pregnant are at higher risk for complications, but serious problems have dropped significantly over the past decades. One study reported a higher risk for premature birth and low birth weight in the baby, and a higher risk for infections and hospital visits in the mother after delivery. Pain crises occurred in nearly half of the women, and nearly 60% required transfusions. The study also reported, however, that, in general, the outcome for pregnancy is favorable. Still, pregnancy during sickle cell is high-risk and carries a mortality rate of about 1%.

Older children and adult patients with sickle cell are subject to other medical problems, including impaired physical development, gum disease, and scarring and detachment of the retina.

Treatment

Research is ongoing toward identifying the biologic and chemical activities that promote or protect against the sickle cell process. Currently, experimental treatments focus on the basic processes that cause the red blood cells to sickle in the first place. There are three basic modes of treatment:

Stimulation of production of healthy fetal hemoglobin in order to inhibit the sickling process
Blocking dehydration in the cells
Transplantation of bone marrow or stem cells from healthy donors so that normal hemoglobin is produced rather than hemoglobin S

Hemoglobin F (HbF), also called fetal hemoglobin, is the form of hemoglobin in the fetus and small infants. Most HbF is later replaced by the hemoglobin that is present in the growing child and adult, although some HbF may persist. Fetal hemoglobin is able to block the sickling action of red blood cells so that infants with sickle cell disease do not develop symptoms of the illness while they still have hemoglobin F. Adults who have sickle cell disease but still retain high levels of hemoglobin F generally have mild disease.

Studies now suggest that the severity of sickle cell disease can be reduced by using drugs that stimulate production of HbF. Even increases as modest as 4% may have significant benefits for these patients.

Hydroxyurea. Hydroxyurea (Droxia, Hydrea) destroys cells in the bone marrow, which results in an increase in special cells that can produce HbF. It is currently the only drug in general use to prevent acute sickle cell crises.

Hydroxyurea is used to treat adults and adolescents with moderate-to-severe recurrent pain (occurring three or more times a year). Hydroxyurea reduces sickling crises and pain, priapism, the number of transfusions, and life-threatening complications in this group. The benefits appear to be long-lasting. Hydroxyurea is not a cure-all. Not all patients respond to hydroxyurea, and the best candidates for the treatment are not yet clear. Small studies have reported no protection from damage in the spleen or bones and joints. Effects on stroke and complications in the eye or kidney are not yet known.

Hydroxyurea is still being investigated in young people. To date, the response to the drug in children and teenagers with sickle cell disease is similar to the response in adults, and few severe adverse effects are being reported. Recent research also suggests that hydroxyurea is safe and beneficial for infants. A 2005 study indicated that long-term hydroxyurea treatment can improve height, weight, and spleen function, and reduce episodes of acute chest syndrome. Patients in the study started the treatment as babies, and most patients took the drug for at least 4 years. The drug was given by mouth in a flavored liquid form.

Side effects include gastrointestinal problems, headache, drowsiness, and skin and nail changes. In rare cases, there have been reports of hallucinations and seizures. The drug may also cause leg ulcers and gangrene in some patients. Patients should handle hydroxyurea with care and wash their hands before and after touching the bottle or capsules. Household members who are not taking hydroxyurea (such as caregivers) should wear disposable gloves when handling the medicine or its bottle.

Cytidine Analogues. Cytidine analogues increase HbF production by affecting the genes that regulate it. Decitabine is one such drug that was developed to treat leukemia and other blood malignancies. Early studies are suggesting that it significantly increases HbF production, even in patients in whom treatment with hydroxyurea failed. Only minor toxic side effects have been reported to date.

Butyrates. Butyrates are natural fatty acids, the end-products of fermented carbohydrates in the intestinal tract that are also metabolized from fiber. One derivative, arginine butyrate, has been under investigation for some time in sickle cell for its role in stimulating production of HbF. Because its actions are different from hydroxyurea, experts hope the two drugs may eventually be used in combination. However, arginine butyrate is difficult to administer, and different forms that might make it simpler to use are needed.

General Guidelines for Managing a Sickle Cell Crisis. The basic objectives for managing a sickle cell crisis are control of pain and rehydration by administration of fluids. Oxygen is typically given for acute chest syndrome. Effective pain medications are available to help reduce the severe pain of sickle cell crises.

Accurate and continually updated assessment of pain determined by patient input and participation is at the crux of effective care for children with sickle cell disease. Often, however, patients are not given the treatment they require.

Many patients, their families, and even doctors are hesitant to use opioids aggressively because of fear of addiction. This fear, however, is nearly always unwarranted. Addiction occurs in only about 1 - 3% of patients with sickle cell disease who are taking opioids.
Many patients use emergency rooms of large hospitals for treating acute pain. Waiting times are long, and there is no single health care provider who knows the patient and can offer consistent assessment and management of pain.
Many doctors do not understand the nature of sickle cell pain. For example, early phases of sickle cell crisis can cause severe pain before test results confirm a diagnosis of a crisis. In such cases, health professionals may question the patient's self-reporting and withhold appropriate pain medication.
Patients may behave normally (talking on the phone, sleeping) and not appear to be in pain, but have actually developed coping behaviors to allow them to function in spite of severe pain.
Children and adults report pain differently, with children tending to report less pain than they actually feel. (One way of determining the severity of pain that a child feels is to show pictures of faces demonstrating degrees of pain and asking the child to point to the one that best expresses his or her experience.)

Adult patients and parents of children with the disease should insist on aggressive pain-relief treatment. If doctors show any reluctance to administer medications after the onset of pain, patients or caregivers should not hesitate to seek a more responsive health care professional.

All patients should have a treatment plan that helps guide them and their families during a pain episode. Plans should outline which medicines to take and when to seek medical help. Patients and families should learn to recognize symptoms early and begin managing with an appropriate amount of pain medication.

Opioids. Severe pain should be treated with strong painkillers, usually opioids. Opioids are generally given orally to adults and adolescents and intravenously to children. Nevertheless, there are exceptions. Studies indicate that oral medications are also effective in children.

Morphine is often used for frequent or prolonged episodes of pain. Unfortunately, its effectiveness is not as long-lasting in sickle cell patients as it is in other patients with severe pain, such as those with cancer.
The opioid meperidine (Demerol) is also used for sickle cell crises. Meperidine is not as powerful as morphine, however, and, if used for prolonged periods, may cause twitches, tremors, and disturbed mental states including seizures.
Some newer synthetic opioids such as fentanyl (Duragesic) or hydromorphone(Dilaudid) have a rapid onset and possibly fewer side effects than morphine. Fentanyl can be applied using a patch, which may help some patients who have difficult receiving intravenous drugs. It takes 12 hours to be effective, however.
Oral drugs, such as methadone, oral morphine, codeine, and oxycodone, are useful for home management of chronic pain and for transitional treatments between the hospital and home. Tramadol (Ultram) is a potent oral painkiller that has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It may be very useful for sickle cell patients who need painkillers outside the hospital. It has minimal effects on respiratory function and has a low potential for addiction.

Possible side effects of opioids are vomiting and nausea, itching, constipation, itching, skin rashes, and problems urinating. If the patient vomits or becomes nauseated, the doctor may prescribe prochlorperazine (Compazine). Devices have been developed to allow patients to administer their own painkillers as needed.

Anti-Inflammatory Drugs. Because of the potentially serious side effects of opioids, doctors are constantly searching for safer and easier ways of reducing the severity of pain of sickle cell crises. Because experts believe that inflammation is a major contributor to the pain of sickle cell disease, drugs that reduce inflammation are being studied:

Prescription-strength NSAIDs include diflunisal (Dolobid) and ketorolac (Toradol). Ketorolac may be particularly helpful in relieving bone pain, and may be effective for individuals who cannot tolerate opioids. In one study, it was superior to meperidine and had fewer side effects. Studies have suggested, however, that when used as first-line therapy in an acute crisis, ketorolac is effective only in about half of episodes.
Corticosteroids are powerful anti-inflammatory drugs that are commonly used to treat pain caused by inflamed muscles and joints. Such drugs include methylprednisolone (Medrol) and dexamethasone (Decadron, Hexadrol). Studies suggest that using these drugs along with opioids may help some sickle cell patients. Because steroids can suppress the body's infection fighters, they should not be given to patients with bacterial infections or any serious medical complication.

Epidural Anesthesia. An epidural analgesia (injection of an anesthetic into the spinal fluid) may be very effective for pain that is unresponsive to the usual therapies.

Initial Management. Acute chest syndrome can be fatal and must be treated immediately. Basic treatments include the following:

Supplementary oxygen -- this is critical and life saving.
Administration of fluids -- overhydration should be avoided to reduce the risk of fluid in the lungs.
Pain relievers
Bronchoscopy (a diagnostic procedure involving insertion of a tube into the lower airways) may be needed to identify infection.

Other Treatments. Other treatments include:

High-dose intravenous corticosteroids (usually dexamethasone) may hasten recovery from acute chest syndrome and reduce the duration of hospitalization. They are also important if fat embolisms develop.
Antibiotics that specifically target the organisms ( Chlamydia, Mycoplasma) that commonly trigger acute chest syndrome. Such antibiotics include erythromycin, azithromycin, clarithromycin, and various tetracyclines.
Transfusions are important early on for rapid improvement in severe cases, especially if fat embolisms have developed.

To increase oxygen levels in children hospitalized for acute chest syndrome, a simple breathing technique known as incentive spirometry may also be beneficial. A spirometer is a hand-held plastic device commonly used by asthma patients to measure their lung capacity and by patients after surgery to increase intake of oxygen. Patients with sickle cell disease are asked to inhale and exhale into this device every 2 hours during the day and when wake at night until their chest pain subsided. This device forces more air into the lungs, and may help prevent the serious drop in oxygen levels and the risk for infection caused by acute chest syndrome. Spirometry leads to slower rates of collapsed lung tissue and infections. This very inexpensive and simple treatment might have beneficial long-term effects.

General Approach to Treating Infections. Fever in any sickle cell patient should be considered an indication of infection. Temperatures over 101°F in children warrant a call to the doctor. Adults with sickle cell should call the doctor if they have a have fever over 100°F and any signs of infection, including chest pain, productive cough, urinary problems, or any other symptoms. Some approaches for treating infections include:

Hospitalization for infections. When sickle cell patients develop infections, they are nearly always hospitalized immediately and treated with intravenous or high-dose injections of antibiotics in order to prevent septicemia, the dangerous spread of the infection throughout the body. Antibiotics called cephalosporins [cefotaxime (Claforan), ceftriaxone (Rocephin), or cefuroxime (Ceftin)] are typically used. Repeated hospitalizations are very disruptive for both children and adults. Studies have found that older children whose fever is below 38.5°C (101°F) and who have no serious infection or other complications may not need hospitalization. Children who have indications of serious complications of infection (higher fevers, pain, a history of pneumonia, and signs of dehydration) should remain in the hospital.
Treatment of osteomyelitis. If osteomyelitis, an infection in the bone, occurs, a 6-week antibiotic course is needed, most of it intravenous. An accurate diagnosis of osteomyelitis is sometimes difficult to make, because bone damage from sickling can cause similar symptoms. It should be strongly considered in children with signs of pain and swelling in the legs, a high white blood cell count, high fever, and high levels of a test that measures so-called sedimentation rates. It is important, however, to confirm the presence of an actual infection before administering antibiotics, because the antibiotic treatment required for osteomyelitis is so intensive and prolonged. The most common cause of osteomyelitis in children is Salmonella.
Treatment of urinary tract infections. Urinary tract infections may be difficult to manage and can be a serious problem for pregnant women with sickle cell disease. Doctors should take a urine culture before beginning antibiotic treatment and another culture 1 - 2 weeks after treatment to be sure the infection has cleared up.

Bosentan (an endothelin receptor antagonist) and other drugs are used to treat this condition. Investigational therapies include nitric oxide, L-arginine (which converts to nitric oxide), blood transfusions, warfarin, vasodilators, and sildenafil (Viagra). Hydroxyurea does not appear to help.

Folic acid and possibly iron supplements are often given to help treat the anemia that occurs in patients with sickle cell disease. (Patients who are given multiple transfusions may experience iron overload, and iron supplements should be avoided in such cases. Also, folic acid can mask pernicious anemia, which is caused by deficiency of vitamin B12 and is more common in African-Americans than other populations.)

Kidney damage in patients with sickle cell disease can cause bleeding into the urine. Mild episodes can usually be treated with bed rest and fluids. Severe bleeding may require transfusions. ACE inhibitors are drugs commonly used to control high blood pressure and are proving to be important for preventing hypertension and kidney failure in sickle cell patients. Such drugs include captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), and lisinopril (Prinivil, Zestril).

Priapism causes prolonged and painful erections that can last from several hours to days. It is best to relieve this problem within 12 hours. Relief within 36 hours is important to avoid permanent impotence. Pain relief and intravenous fluids are the initial steps. Exchange transfusions may be used to reduce the hemoglobin S and sickling that cause this condition. Drugs used to prevent priapism include terbutaline and phenylephrine, which help restrict blood flow to the penis. Hormonal treatments such as leuprolide (Lupron) and diethylstilbestrol may prevent repetitive and prolonged episodes of priapism in severely affected teenage boys with sickle cell disease. A surgical procedure that implants a shunt to redirect blood flow is sometimes performed. Inflatable penile implants may help maintain potency without causing priapism. Researchers are also investigating other treatments including inhaled nitric oxide, arginine, and sildenafil (Viagra).

The spleen is often removed (splenectomy) in children who have one or two acute splenic sequestration crises. Transfusion therapy is an alternative for preventing acute splenic sequestration in high-risk patients. At this time there are no studies comparing overall survival and benefits between the two approaches.

Leg ulcers are difficult to treat. Simple treatment with a moist dressing usually provides the best results. To treat mild ulcers, the leg should be gently washed with cotton gauze soaked in mild soap or a solution of one tablespoon of household bleach to one gallon of water. A dressing soaked in diluted white vinegar may be applied every 3 - 4 hours.

More severe ulcers require debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means. Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing. Topical antibiotics, saline or zinc oxide dressings, or cocoa butter or oil are also used depending on severity. The leg should be elevated. Bed rest for a week or more is sometimes required for severe ulcers.

Skin grafts and transfusions have been helpful in some extreme cases. In one promising study administering arginine butyrate for many weeks improved ulcer healing by 10-fold. (This drug is also under investigation for other beneficial effects in patients with sickle cell disease.)

Women who are pregnant should be treated at a high-risk clinic. They should take folic acid in addition to multivitamins and iron. Standard treatment is given for sickle cell crises, which may occur more frequently during pregnancy. The benefits of transfusions to prevent crises during pregnancy are not yet clear and experts recommend them only for women who experience frequent complications during pregnancy.

Women with sickle cell disease should talk to their doctors before becoming pregnant. Sexually active women should use contraception at all times.

At this time, the only true cure for sickle cell disease is bone marrow or stem cell transplantation. The bone marrow nurtures stem cells, which are early cells that mature into red and white blood cells and platelets. By destroying the sickle cell patient's diseased bone marrow and stem cells and transplanting healthy bone marrow from a genetically-matched donor, normal hemoglobin may be produced. Clinical studies using a few carefully selected patients have reported very successful results.

Up to 80 - 85% of patients who meet criteria for receiving a transplant receive remain disease free. Unfortunately, only about 7% meet the criteria for transplantation, including those who:

Are age 16 or younger (generally considered the better candidates, but patients in their 20s have had successful transplants)
Have severe symptoms but no long-term organ or neurologic damage
Have a genetically matched brother or sister who will donate their marrow

Complications. Bone marrow transplant carries its own dangers and limitations. About 10% of those who have bone marrow transplants die from the treatment. Some complications include:

In patients who do not receive a bone marrow donation from a matched sibling, the transplanted cells from a donor (called allogeneic grafts) may attack the patient's own tissues, a potentially fatal condition called graft-versus-host disease (GVHD). Drugs that destroy bone marrow and suppress immunity must be administered before the procedure so that the body's immune system does not attack the transplanted tissue. Still, this does not always prevent the problem.
Other very serious complications include bleeding, pneumonia, and severe infection.
Those who live but are not cured face long-term problems caused by the drugs used in transplantation and by the disease itself.
Even in those who are cured, long-term consequences may include a higher risk for cancer and infertility.

The use of umbilical cord blood and cells from placentas is showing promise for providing healthy stem cells to patients who do not have genetically matched donors for bone marrow transplant. Cord blood has certain advantages over stem cell transplantation, including the capacity to produce more cells quickly. Because immune factors in cord blood are immature, the risk and severity of graft-versus-host disease may be reduced.

Early clinical trials are also reporting some success with a process called partial chimerism, in which a mixture of the patient's and a donor's bone marrow is used. The procedure has far fewer side effects because all the bone marrow is not destroyed. Although some sickle blood cells remain, small studies indicate that the patients are still free of the typical infections and pain of the disease.

Transfusions are often critical for treating sickle cell disease. In some cases, they may be given on a regular basis to prevent stroke or other life-threatening complications of the disease. Ongoing transfusions can reduce episodes of pain and acute chest syndrome. They can also help improve height and weight in children with sickle cell disease. Regular transfusions, however, can have severe side effects. Normal hemoglobin levels for patients with sickle cell disease are around 8 g/dL. Doctors will try to keep the hemoglobin level no higher than 10 g/DL after transfusion.

Transfusions may be required by sickle cell patients either for specific episodes (used only for specific events) or as chronic transfusions (ongoing transfusions).

Episodic Transfusions. Episodic transfusions are needed in the following situations:

To manage sudden severe events, including acute chest syndrome, stroke, widespread infection (septicemia), and multi-organ failure.
To manage severe anemia, usually caused by splenic sequestration (dangerously enlarged spleen) or aplasia (halting of red blood cell production, most often caused by parvovirus). Transfusions are generally not required for mild or moderate anemia.
Before major surgeries. Some evidence suggests that a conservative transfusion regime is as effective as aggressive transfusions in these cases, but more research is needed. Transfusions are generally not required for minor surgeries.

Chronic Transfusions. Chronic (on-going) transfusions are used for:

Stroke Prevention. Chronic transfusions are also used to prevent first or recurrent strokes. Evidence shows that regular (every 3 - 4 weeks) blood transfusions can reduce the risk of a first stroke by 90% in high-risk children. The objective of such transfusions is to reduce hemoglobin S concentrations to less than 30% of total hemoglobin. In addition, studies indicate that as many as 90% of patients who have experienced a stroke do not experience another stroke after 5 years of transfusions. In 2004, the National Heart, Lung, and Blood Institute (NHLBI) issued a clinical alert strongly advising doctors against terminating regular transfusions for high-risk children.
Pulmonary hypertension and chronic lung disease
Heart failure
Chronic kidney failure and severe anemia
Unusually severe and protracted episodes of pain

Chronic blood transfusions carry their own risks, including iron overload, alloimmunization (an immune response reaction), and exposure to bloodborne pathogens. Still, data from large-scale trials suggest that the risks for stroke outweigh the risks associated with transfusions. Researchers are working on ways to reduce the side effects associated with transfusion treatment.

Kinds of Transfusions. Transfusions may be either simple or exchange.

Simple Transfusion. Simple transfusions involve the infusion of one or two units of donor blood to restore blood volume levels and oxygen flow. It is used for moderately severe anemia, severe fatigue, and nonemergency situations when there is a need for increased oxygen. It is also used for acute chest syndrome.
Exchange Transfusion. Exchange transfusion involves drawing out the patient's blood while exchanging it for donor red blood cells. It can be done as manual procedure or as automatic one called erythrocytapheresis. Exchange transfusions should be used promptly if there is any evidence that the patient's condition is deteriorating. It prevents stroke and also may be used in patients with severe acute chest syndrome and to reduce the risk of iron overload in patients who require chronic transfusion therapy. Studies suggest that it may improve oxygenation and reduce hemoglobin S levels. Exchange transfusion may also reduce the risk of heart failure and help prevent fat embolism, a life-threatening condition in which fatty tissue from the bone marrow travels to blood vessels in the lungs and cuts off oxygen.

Iron Overload and Chelation Therapy. Iron overload increases risk for complications, including liver cancer and heart failure. A liver biopsy accurately determines whether excess iron levels are present. A non-invasive test called a superconducting quantum interference device (SQUID) should be used if available.

Chelation therapy is used to remove excess iron stores in the body that can harm the liver, heart, and other organs. The drug deferoxamine (Desferal) is commonly used during such therapy. Unfortunately, deferoxamine has some severe side effects and must be used with a pump for about 12 hours each day. Many patients do not continue treatment. In 2005, the drug deferasirox (Exjade) was approved for the treatment of transfusion-related iron overload in patients ages 2 and older. It is taken once a day by mouth. Patients mix the pills in liquid and drink the mixture. This new treatment may make chelation therapy much easier and less painful for patients.

Other Complications of Transfusion Therapy.

Immune reactions. An immune reaction may occur in response to donor blood. In such cases, the patient develops antibodies that target and destroy the transfused cells. This reaction, which can occur 5 - 20 days after transfusion, can result in severe anemia and may be life-threatening in some cases. It can be generally prevented with careful screening and matching of donor blood groups before the transfusion.
Hyperviscosity. With this condition, a mixture of hemoglobin S and normal hemoglobin causes the blood to become sticky. The patient is at risk for high blood pressure, altered mental status, and seizures. Careful monitoring can prevent this condition.
Transmission of viral illness. Before widespread blood screening, transfusions were highly associated with a risk for hepatitis and HIV. This complication has decreased considerably.

Nitric oxide, a soluble gas, is a natural chemical in the body that relaxes smooth muscles and expands blood vessels. Hemoglobin removes nitric oxide. Because sickle cells release hemoglobin, patients with the disease are deficient in nitric oxide. This lack of nitric oxide constricts blood vessels and causes pain in sickle cell diseases. In adult patients, men may be more susceptible to this effect than women. Some studies indicate that inhaling nitric oxide may slow the disease process and improve symptoms in acute sickle cell crises. It is difficult to administer, however. More studies are needed. (Nitric oxide is not the same substance as nitrous oxide, the so-called laughing gas used in dentistry.)

Sickle cell disease can cause red blood cells to break apart. This process is called hemolysis. Hemolysis causes a lack of the amino acid arginine. Arginine is involved in producing nitric oxide. Recent research suggests that a lack of arginine may contribute to the development of pulmonary hypertension, a leading cause of death in patients with sickle cell disease. Pulmonary hypertension causes high blood pressure in the arteries that carry blood to the lungs.

A 2005 study found that patients with sickle cell who had low levels of arginine were 3.6 times more likely to die than patients with high arginine levels. Most patients in the study died from pulmonary hypertension. Scientists are working on developing a blood test that could measure amino acid levels and help identify patients at greatest risk of death. They are also working on developing drugs that could block arginase, a protein in cells that is released during hemolysis, which consumes arginine. There is no evidence indicating that arginine nutritional supplements are helpful or harmful for patients with sickle cell disease. Patients should talk to their doctor before taking these or other supplements.

Researchers are studying the mechanisms behind cell membrane damage, dehydration, and potassium loss in order to develop drugs that will inhibit these processes. Drugs under investigation include those that specifically block the Gardos channel, which is an important route for potassium loss and dehydration. Researchers are also studying specific types of mineral supplements, such as magnesium pidolate and zinc sulfate. Initial studies have shown promising results for zinc’s efficacy in preventing red blood cell dehydration, but more research is needed.

Prevention and Lifestyle Changes

No o proven methods prevent either sickle cell crises or long-term complications of sickle cell disease. By taking precautions and aggressively managing problems that occur, however, patients are now living longer, with a better quality of life.

To prevent or reduce the severity of long-term complications, a number of precautions may be helpful:

Have regular physical examinations every 3 - 6 months.
Have periodic and careful eye examinations.
Have sufficient rest, warmth, and increased fluid intake. (These are critical precautions for reducing oxygen loss and the risk for dehydration.)
Avoid conditions, such as crowds, that increase risk for infections.
Avoid excessive demands on the body that would increase oxygen needs (physical overexertion, stress). Low impact exercise (leg lifts, light weights) may be useful and safe for maintaining strength, particularly in the legs and hips, but patients should consult their doctor about any exercise program.
Avoid high altitudes if possible. If flying is necessary, be sure that the airline can provide oxygen.
Do not smoke, and avoid exposure to second-hand smoke. Both active and passive smoking may promote acute chest syndrome in patients with sickle cell disease.

Vaccinations. Everyone with sickle cell disease should have complete regular immunizations against all common infections. Children should have all routine childhood vaccinations. The following are important vaccinations for everyone with sickle cell disease:

Pneumococcal vaccines. All sickle cell patients should be vaccinated with the pneumococcal vaccine. There are two types of pneumococcal vaccines; the choice between them depends on the age of the patient. Infants and children less than 2 years of age should receive 4 doses of the pneumococcal conjugated vaccine (Prevnar) between 2 - 15 months of age. (This vaccine has helped reduce the rate of serious pneumococcal disease by more than 90%.) The pneumococcal polysaccharide vaccine should be administered at age 2 years or older, repeated after 3 - 5 years for patients younger than age 10, or in 5 years for patients older than age 10.
Vaccination against Haemophilus influenza, the major cause of childhood meningitis, starting at age 2 months.
Influenza vaccines should be given every winter, starting at age 6 months.
Meningococcal vaccination for patients age 5 and older.
Hepatitis B vaccine. Anyone starting transfusion therapy should receive this vaccine.

Tuberculosis skin testing should be performed every year.

Antibiotics. In addition to regular immunizations, preventive (prophylactic) antibiotics are the best approach for protection against pneumonia and other serious infections among children with sickle cell disease. Babies diagnosed with sickle cell are given daily antibiotics, starting at 2 months of age and continuing through 5 years of age. Penicillin is usually the antibiotic given, unless a child is allergic to it.

Many patients stop taking their antibiotics or the parents stop giving them to their children. Doctors are concerned about developing bacterial resistance to common antibiotics and researchers warn that patients might experience breakthrough infections as resistance becomes more frequent.

Foods. Good nutrition, while essential for anyone, is critical for patients with sickle cell disease. Some dietary recommendations include:

Fluids are number one in importance. The patient should drink as much water as possible each day to prevent dehydration.
Diet should provide adequate calories, protein, fats, and vitamins and minerals. Patients and families should discuss vitamin and mineral supplements with their doctors and nurses.
Studies on omega-three fatty acids, found in fish and soybean oil, suggest that they might make red blood cell membranes less fragile, and possibly less likely to sickle, although no studies have proven this definitively. Fish and soy products have health benefits in any case. In one small study, fish oil supplements reduced the frequency of painful episodes over the course of a year.

Vitamins. Patients should take daily folic acid and vitamin B12 and B6 supplements. Vitamin B6 may have specific anti-sickling properties. Some experts recommend 1 mg folic acid, 6 microgram vitamin B12, and 6 mg vitamin B6. Foods containing one or all of these vitamins include meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast. Of note, folic acid can mask pernicious anemia, which is caused by deficiency of vitamin B12 and is more common in African-Americans than other populations.

Click the icon to see an image of vitamin B6 sources.

Note on Iron. Although sickle cell disease is often referred to as anemia, patients should avoid iron supplements or iron rich foods when receiving multiple transfusions, which increase the risk for iron-overload.

In assessing the seriousness of this disease, no one should underestimate its emotional and social impact. For the family, nothing is more heartbreaking than watching their child endure extreme pain and life-threatening medical conditions. The patient endures not only the pain itself but also the emotional strain from unpredictable bouts of pain, fear of death, and lost time and social isolation at school and work. Academic grades among patients average less than C, even in children with a low frequency of hospitalization (averaging 17 days a year).

These problems continue over the years, and both children and adults with sickle cell disease often suffer from depression. The financial costs of medical treatments combined with lost work can be very burdensome.

Any chronic illness places stress on the patient and family, but sickle cell patients and caregivers often face great obstacles in finding psychological support for the disease. Communities in which many sickle cell patients live generally lack services that can meet their needs, and professionals who work in their medical facilities are often overworked. In a study comparing patients with different kinds of long-term illnesses, those with sickle cell disease gave the lowest scores to their doctors and other professional caregivers for compassion, and were least satisfied with their medical care.

It is very important for patients and their caregivers to find emotional and psychological support. No one should or can endure this life-long disease alone. Unfortunately, studies indicate that most patients do not receive even basic supportive care that could help reduce the anxiety and intensity of pain that occurs when a sickle cell crisis erupts.

The following are some measures that some people find helpful in dealing with this disease:

Stress Reduction. Stress reduction techniques and relaxation methods appear to be helpful. Breathing and mediation techniques may be very helpful.
Cognitive-Behavioral Therapy. Studies suggest that cognitive behavioral therapies that teach coping skills can result in less negative thinking and even less pain. Coping skills refer to the patient's ability to respond to symptoms, such as pain.
On-Line Support Help. Computer on-line services are now valuable sources of support groups and access to research. They are particularly valuable for patients who cannot easily leave home or for patients who are ill.
Support Associations. Parent and professional support associations still offer the best and least expensive sources of help.

Other important factors are those that help maintain positive attitudes including spirituality, humor, or having important life goals (such as having children or pursuing a career).

Resources

www.sicklecelldisease.org -- Sickle Cell Disease Association of America
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute (NHLBI)
www.scinfo.org -- Sickle Cell Information Center
www.sicklecellsociety.org -- Sickle Cell Society (UK)
www.sicklecell-info.org -- NHLBI Comprehensive Sickle Cell Centers
www.clinicaltrials.gov -- Find clinical trials

References

Adams RJ, Brambilla D; Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) Trial Investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005 Dec 29;353(26):2769-78.

Al Hajeri AA, Fedorowicz Z, Omran A, Tadmouri GO. Piracetam for reducing the incidence of painful sickle cell disease crises. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD006111.

Bernaudin F, Socie G, Kuentz M, et al Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007 Oct 1;110(7):2749-56. Epub 2007 Jul 2.

Dunlop RJ, Bennett KC. Pain management for sickle cell disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003350.

Fathallah H, Atweh GF. Induction of fetal hemoglobin in the treatment of sickle cell disease. Hematology Am Soc Hematol Educ Program. 2006:58-62.

Halasa NB, Shankar SM, Talbot TR, et al. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis. 2007 Jun 1;44(11):1428-33. Epub 2007 Apr 18.

Hankins JS, Wynn LW, Brugnara C, Hillery CA, Li CS, Wang WC. Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anemia. Br J Haematol. 2008 Jan;140(1):80-5. Epub 2007 Nov 7.

Lee MT, Piomelli S, Granger S, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood. 2006 Aug 1;108(3):847-52.

Mehta SR, Afenyi-Annan A, Byrns PJ, Lottenberg R. Opportunities to improve outcomes in sickle cell disease. Am Fam Physician. 2006 Jul 15;74(2):303-10.

Singh PC, Ballas SK. Drugs for preventing red blood cell dehydration in people with sickle cell disease. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003426.

Tanabe P, Myers R, Zosel A, et al. Emergency department management of acute pain episodes in sickle cell disease. Acad Emerg Med. 2007 May;14(5):419-25. Epub 2007 Mar 26.

U.S. Preventive Services Task Force. Screening for Sickle Cell Disease in Newborns: U.S. Preventive Services Task Force Recommendation Statement. AHRQ Publication No. 07-05104-EF-2, September 2007. Agency for Healthcare Research and Quality, Rockville, MD.

Review Date:
3/11/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (1/1/2008).

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

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Acute lymphocytic leukemia

FitSugar — Wed, 08 Oct 2008 17:35:07 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Risk Factors
Diagnosis
Outlook
Treatment
Home Management
Treatment to Achieve Remiss...
Treatment During Remission...
Treatment After Relapse
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Acute Lymphocytic Leukemia (ALL)

There are four major types of leukemia. ALL is the most common type of leukemia diagnosed in children, and the least common type diagnosed in adults. About 5,200 people are diagnosed with ALL each year. Children account for two-thirds of these cases. In general, children with ALL have a better prognosis than adults. Most children with ALL can be cured of this cancer.

Symptoms and Diagnosis

Symptoms of ALL include fatigue, pale skin, recurrent infections, bone pain, bruising, and small red spots under the skin. Doctors use various tests, including blood counts and bone marrow biopsies, to diagnose ALL.

Treatment

ALL is treated with chemotherapy and, sometimes, radiation. Children receive different types of chemotherapy regimens than adults. Patients with advanced cancer that has not responded to these treatments may need a stem cell transplant.

Infection Prevention

Both chemotherapy and transplantation increase the risk for infection. Patients must take serious precautions to avoid exposure to germs. Ways to prevent infection include:

Practice good hygiene including regular handwashing and dental care (brushing, flossing)
Avoid crowds, especially during cold and flu season
Eat only well-cooked foods (no raw fruits or vegetables)
Boil tap water before drinking it
Do not keep fresh flowers or plants in your house as they may carry mold

Introduction

The word leukemia literally means "white blood" and is used to describe a variety of cancers that begin in the blood-forming cells of the bone marrow.

White blood cells (leukocytes) evolve from immature cells referred to as blasts. Malignancy in these blasts is the source of leukemias, which generally progresses as follows:

Normally, blasts constitute 5% or less of healthy bone marrow. In leukemia, however, these blasts remain abnormally immature and multiply continuously, eventually constituting between 30 - 100% of the bone marrow.
Eventually these malignant blast cells fill up the bone marrow and prevent production of healthy red cells, platelets, and mature white cells (leukocytes).

They spill out of the marrow into the bloodstream and lymph system and can travel to the brain and spinal cord (the central nervous system). As the number of normal cells decline, dangerous symptoms develop, which, if untreated, become lethal.

Leukemias are divided into two major types:

Acute (which progresses quickly with many immature white cells)
Chronic (which progresses more slowly and has more mature white cells)

Some blasts are called lymphoblasts (which become mature cells called lymphocytes) and others are called myeloblasts (which mature to myeloid cells). Acute leukemias are in turn subdivided into two classifications according to whether the malignant blasts are lymphocytes or myeloid:

Acute lymphocytic leukemia (ALL), which is the subject of this report
Acute myeloid leukemia (AML), which is not covered in this report

Acute lymphocytic leukemia (ALL) is also known as acute lymphoid leukemia or acute lymphoblastic leukemia. The majority of childhood leukemias are of the ALL type. Malignancies in this disease can arise either in T-cell or B-cell lymphocytes.

T cell ALL is diagnosed in 15% of children and adults with ALL.
About 85% of ALL cases are of the B-cell lymphocyte lineage (often referred to as "early" or "pre" B-cell lineage).

Blood Cell Lines

In adults, blood cells are produced by the bone marrow, the spongy material filling the body's bones. The bone marrow produces two blood cell groups, myeloid and lymphoid.

Myeloid Cell Line. The myeloid cell line includes the following:

Immature cells called erythrocytes that later develop into red blood cells
Blood clotting cells (platelets)
Some white blood cells, including macrophages (which act as scavengers for foreign particles), eosinophils (which trigger allergies and also defend against parasites), and neutrophils (the main defenders against bacterial infections)

Lymphoid Cell Line. The lymphoid cell line includes the lymphocytes, which are the body's primary infection fighters. Among other vital functions, certain lymphocytes are responsible for producing antibodies, factors that can target and attack specific foreign substances (antigens).

Lymphocytes develop in the thymus gland or bone marrow and are therefore categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).

Lymphocytes and the Lymph System

Understanding how acute lymphocytic leukemia (ALL) arises requires knowledge of lymphocytic development and function:

B cells develop and mature in their final form (known as differentiation) in the bone marrow.
T cells also start out in the bone marrow but differentiate and mature in the thymus gland, located beneath the breastbone. This small gland is active mostly in the fetal stage through the first 10 years of life, after which it atrophies (shrinks).
B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
Once they leave the capillaries, some lymphocytes migrate into the surrounding tissues. Some of these lymphocytes (along with fluid, proteins, and other substances) then enter the lymphatic vessels.
Lymphatic vessels begin as tiny, blind-ended tubes and lead to larger lymphatic ducts and branches. They drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Along the way, the fluid passes through lymph nodes, which are oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or are added to the contents of the node.

Symptoms

The symptoms of ALL may be difficult to recognize. ALL usually begins abruptly and intensely, but in some cases symptoms may develop slowly. They may be present one day, and absent the next, particularly in children. Symptoms develop when:

There are not enough healthy mature white blood cells (leukocytes) to mount a defense against infection.
There are not enough healthy platelets to prevent bleeding.
The depleted oxygen-bearing red blood cells can't provide enough oxygen to organs.

Symptoms include:

Fatigue
Paleness -- patients may have poor coloring from anemia caused by insufficient red blood cells
Recurrent minor infections
Fevers
Bone pain
Bruising -- may result from only slight injury
Poor healing of minor cuts
Uncontrolled bleeding -- bleeding events increase as the bone marrow fails to produce enough platelets to make a normal blood clot, a condition called thrombocytopenia.
Small, red spots on the skin (petechiae)
Vision changes (rare)

Causes

Between 1973 - 1990, the number of acute lymphocytic leukemia cases in children under age 15 rose by 27%. The causes of the disease are not known, but experts believe that ALL develops from a combination of genetic, biologic, and environmental factors.

Advances in genetic technologies have allowed identification of a number of mutations associated with ALL. Missing or defective genes that suppress tumors are responsible for some of these cases. Identifying specific genetic allows doctors to determine how aggressive a specific case is and eventually could provide targets for developing highly specific treatments.

Translocations. Up to 65% of leukemias contain genetic rearrangements, called translocations, in which some of the genetic material (genes) on a chromosome may be altered, or shuffled, between a pair of chromosomes.

The most common genetic injury in ALL is t(12;21), which means a translocation with a genetic shift occurred between chromosome 12 and 21. This translocation is also referred to as TEL-AML1 fusion. It occurs in about 20% of patients with ALL. Researchers believe that this translocation may occur during fetal development in some patients.
About 20% of adults and about 5% of children with ALL have a genetic abnormality called the Philadelphia (Ph) chromosome [t(9;22)].
Another important chromosome translocation is t(4;11) involving the MLL gene, also called HRX or ALL-1.

Ikaros. A defective gene known as Ikaros, which regulates lymphocyte development, may play a major role in childhood ALL.

MTHFR. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism. Children with certain variations in the gene for MTHRF have a reduced risk of developing ALL. Variations in the MTHRF gene may also influence response to antifolate chemotherapy.

Risk Factors

ALL in Children. ALL is the most common type of cancer diagnosed in children. ALL accounts for about 75% of cases of childhood leukemia. Each year, about 2,400 American children and adolescents are diagnosed with ALL. ALL can strike children of all ages, but is most likely to occur when children are 2 - 3 years of age.

ALL in Adults. ALL is the least common type of leukemia among adults. About 1 in 3 cases of ALL occur in adults.

Caucasian and Hispanic children have a much higher risk for ALL than African-American children.

Certain inherited disorders can increase the risk for leukemia. For example, children with Down syndrome have a 20-times greater risk of developing ALL than the general population. Other rare genetic disorders associated with increased risk include Bloom syndrome, Fanconi's anemia, ataxia-telangiectasia, neurofibromatosis, Shwachman syndrome, IgA deficiency, and congenital X-linked agammaglobulinemia.

Previous cancer treatment with high doses of radiation or chemotherapy can increase the risk for developing ALL. Prenatal exposure to x-rays also appears to increase risk in children. Lower levels of radiation (living near power lines, video screen emissions, small appliances, cell phones) are unlikely to pose any cancer risk.

Diagnosis

Laboratory tests provide the basis for diagnosing ALL.

Flow cytometry uses light to count blood cells in a stream of fluid. It is an important tool used to diagnose leukemia, determine its progress, and tell if any disease remains after treatment. It can also determine the components and structural features of individual cells. Flow cytometry can process thousands of cells in seconds.

A complete blood cell count (CBC) is the first step in diagnosing ALL. However, blood tests do not always detect leukemia. About 10% of patients with ALL have a normal blood cell count. A CBC may show various findings, including:

Presence of circulatory leukemic blast cells (may miss the cells on occasion)
Presence and severity of anemia
Count of a variety of blood cell types (a high white blood cell count indicates a more severe disease)

Click the icon to see an illustrated series detailing a complete blood cell count test.

If blood test results are abnormal or the doctor suspects leukemia despite normal cell counts, a bone marrow aspiration and biopsy are the next steps. These are very common and safe procedures. However, because this test can produce considerable anxiety, particularly in children, parents may want to ask the doctor if sedation is appropriate for their child.

A local anesthetic is given.
A needle is inserted into the bone, usually the rear hipbone. There may be brief pressure or pain. A small amount of marrow is withdrawn. Marrow looks like blood.
A larger needle is then inserted into the same place and pushed down to the bone. The health professional will wiggle the needle from side to side to loosen a larger specimen for the biopsy. The patient will feel some pressure.
The sample is then taken to the lab to be analyzed. All the results are completed within a couple of days.

Click the icon to see an image of bone marrow removal.

Normal bone marrow contains 5% or less of blast cells (the immature cells that ordinarily develop into healthy blood cells). In leukemia, abnormal blasts constitute between 30 - 100% of the marrow.

If bone marrow examination confirms ALL, a spinal tap may be performed, which uses a needle inserted into the spinal canal. The patient feels some pressure and usually must lie flat for about an hour afterward to prevent severe headache. This can be difficult, particularly for children, so parents should plan reading or other quiet activities that will divert the child during that time. Parents should also be certain that the professional administering this test is highly experienced.

Click the icon to see an image of a spinal tap.

A sample of cerebrospinal fluid with leukemia cells is a sign that the disease has spread to the central nervous system. In most cases of childhood ALL, leukemia cells are not found in the cerebrospinal fluid.

Once a diagnosis of leukemia has been made, further tests are performed to check:

Whether the cells are myeloid or lymphocytic
Stage of maturity of the ALL B cell
Specific markers, or immunologic features, on the surface of the cancer cell
The genetic makeup of the cells ( cytogenetics)
The physical characteristics of the cells ( morphology)

First, the doctors must determine the cell of origin. In other words, they want to determine if the cell is myeloid or lymphocytic. One method is to measure an enzyme called terminal deoxynucleotidyl transferase (TdT).

About 95% of all ALL types (except the subtype B cell) have elevated TdT.
Only about 20% of cases of acute myeloid leukemia (AML) express TdT, however, so its use in determining the cell line is limited.

The stage of maturity of the leukemic B cell helps determine prognosis. There are three stages:

Early precursor-B. About 80% of patients with ALL have the early precursor-B subtype, which is the least mature. It also offers the best prognosis.
Precursor-B. This is the intermediate stage.
B cell. This is the mature cell and ALL in this stage is identical to Burkitt's non-Hodgkin's lymphoma. It is therefore treated differently from other ALL cases.

A series of tests are used to determine the immunologic pattern of the leukemia cell (how it can be expected to interact with the immune system).

On the surface of malignant ALL cells are markers for certain antigens (molecules that set off a targeted attack by the immune system using antibodies). Such antigens are proving to be very helpful in predicting outcome.

An antigen is a substance that can provoke an immune response. Typically, antigens are substances not usually found in the body.

Important antigens associated with ALL include:

CD10, more frequently referred to as cALLa (common ALL antigen). This antigen occurs in about half of all ALL cases and in about 80% of ALL B-precursor patients. It is associated with a good prognosis.
CD95 (associated with a good prognosis)
CR19
DR

The surfaces of T-cell ALL cancer cells express several antigens as well. For example, the presence of one of these, CD2, suggests a favorable prognosis.

Genetic tests are useful for a number of important criteria:

Diagnosing a specific ALL subtype
Designing appropriate treatment
Deciding prognosis
Monitoring patients throughout treatment and beyond

Cytogenetics is a technique that researchers use to determine specific genetic abnormalities, which are found in nearly 65% of all leukemias. Detecting these genetic defects is helpful in making a full diagnosis of ALL and in planning the most appropriate therapy. Specific technologies called microarray chips are capable of checking up to 48,000 different genes in a single test, which holds promise for assessing prognosis and developing very targeted therapies in the future. Research on DNA microarray analysis continues to reveal different prognostic subgroups of ALL. As the precision, logistics, and cost effectiveness of DNA microarray assays improve, they may be used more commonly in the clinical setting.

MTHFR Variants. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism. Variations in the MTHRF gene may also influence response to antifolate chemotherapy. A 2004 study showed that patients with one of two specific variations of the MTHFR gene had a lower probability of survival following treatment with methotrexate.

Translocations. Genetic translocations (swapping of genes on chromosomes) may affect outlook. Examples include:

Patients with the t(12;21) genetic translocation (also referred to as TEL-AML1 fusion) have an excellent prognosis.
Patients who carry the defective gene called ETV6 often respond well to chemotherapy.
The t(4;11), sometimes referred to as MLL, is the most common translocation in children under age 1 year. Unfortunately, anyone with t(4;11) has a poor outlook. One study suggested that this genetic variant may actually be a unique leukemia and require treatments that differ from standard ALL.
The Philadelphia translocation t(9;22) also indicates a poor outlook. It represents about 20% of adult cases and about only 5% of childhood cases.
The t(1;19) location occurs in about 5% of ALL childhood cases and requires aggressive treatment.

Ploidy. Ploidy refers to the number of chromosomes. Additional copies (hyperdiploidy) or absence of copies (hypodiploidy) of chromosomes affect prognosis. For example, in children hyperdiploidy is associated with a more favorable outcome and hypodiploidy with a poorer outcome. (Hypodiploidy occurs in only 1% of children with ALL.)

The morphology of a cell includes its physical characteristics, such as shape and structure. To determine the morphology of the leukemia cells, samples of the bone marrow are taken and particular contents of the cells are stained with a dye. They are then examined under a microscope.

Acute lymphocytic leukemia cells are grouped, according to the French-American-British (FAB) classification system, into three ALL morphologic types. (It should be noted that this system is subjective and is now used to complement other diagnostic tests mentioned above):

L1 cells. These are small blasts with scant amounts of cytoplasm (the substance in a cell between its membrane and nucleus). L1 cells usually contain a round nucleus and there is little variation among them. L1 represents the most common ALL morphology and offers the best prognosis. It occurs in about 85% of children and 30% of adults with ALL.
L2 cells. These cells are larger than L1 and have more abundant cytoplasm. They vary significantly among each other and have an irregularly shaped nucleus. L2 morphology conveys a poorer prognosis than L1, although the two cells' types are treated similarly. Subtype L2 is the most common morphologic type in ALL adults; 64% of adults with ALL have this subtype compared with only 15% of children.
L3 cells. These are uncommon. They resemble another malignancy called Burkitt's lymphoma, and their treatments are now the same.

Assays that test for cancerous cells are improving, allowing doctors to detect smaller and smaller amounts of hidden disease. For example, flow cytometry assays can detect 0.01% leukemic cells, and PCR assays can detect 0.001% leukemic cells. A new concept called minimal residual disease (MRD) is becoming an important prognostic factor in ALL. A more precise measure of disease response, MRD may soon replace existing measures such as "complete response" and "partial response" when assessing the effectiveness of ALL treatment. Ongoing studies of MRD in ALL may help identify patients in remission who are at risk of relapse. In addition, early therapeutic intervention based on the presence of MRD may improve outcome and prolong survival.

Using the results of the tests described above, patients are classified into low-, average-, and high-risk groups. This information allows the doctor to diagnosis the type of leukemia and plan the best treatment. Each classification requires unique therapies.

Doctors attempt to make a prognosis and determine an optimal treatment plan by assessing all the cell characteristics plus the white blood cell count. As examples:

Patients who have an L1 or L2 morphology, a white blood cell count of less than 15,000 mm3, a t(12;21) genetic translocation, and a cALLa-positive antigen marker have an excellent outlook.
On the other hand, patients who have an L2 morphology, a white blood cell count greater than 30,000 mm3, and who lack the cALLa marker have a poorer prognosis and require more aggressive treatment

Outlook

Acute lymphocytic leukemia is responsible for about 1,400 deaths a year in the U.S., and it can progress quickly if untreated. However, ALL is one of the most curable cancers and survival rates are now at an all-time high. People who have Philadelphia chromosome-positive ALL tend to have a poorer prognosis, although new treatments are helping many of these patients achieve remission.

Outlook in Children with ALL. More than 95% of children with ALL attain remission.

Certain children are at higher risk for a poor outcome than others:

Infants and children age 10 years and older tend to have a poorer outcome than young children (ages 1 - 9 years).
Some studies indicate a better prognosis for girls than boys. This may be partly due to boys’ risks for testicular cancer.
Survival rates for African-American and Hispanic children are lower than Caucasian and Asian children, but this may be due to poorer access to treatment.

Responding well to early treatment is a good sign regardless of the risk category. Other positive predictors include:

Less than 5% of cells being blasts after 7 - 14 days of treatment
Less than 1,000 blasts per microliter on peripheral smear after 7 days

Outlook in Adults with ALL. Adults tend to have a more severe condition than children, even if they are carrying the same ALL genes. Still, 60 - 80% of adults with ALL can expect to achieve full remission with standard treatments, and 35 - 40% survive beyond 2 years with aggressive treatments. Younger adults with ALL have better long-term survival rates than older adults with the disease.

Treatment

The aim of initial treatment is to get rid of the leukemia cells in the body (achieve complete remission) and have 5% of lower levels of blasts in the bone marrow.

There are typically four treatment stages for the average-risk patient with ALL:

Induction therapy in order to achieve a first remission
Central nervous system prophylaxis (preventive treatment), usually given along with induction therapy
Consolidation, intensive therapy to prevent relapse after remission has been achieved
Maintenance treatment, lower intensity therapy given for several years to prevent relapse after remission

The following are specific treatments used for ALL:

Chemotherapy is the primary treatment for each stage.
Radiation to the brain and spinal cord is also administered in some cases.
A bone marrow transplant is often recommended for relapsed ALL or in cases that cannot be induced into remission (refractory disease). It is also sometimes considered after remission is achieved for certain high-risk ALL types. The timing of bone marrow transplantation can be controversial, particularly after a first remission, although it has produced excellent long-term survival rates in appropriate patients.
New drugs known as biological therapies are also being used.

Drugs Used to Prevent Infections During Treatment. Half of all patients with ALL develop fever in the early stages, especially if patients also have low levels of the white blood cells called neutrophils (a condition called neutropenia).

Blood is made of red blood cells, platelets, and various white blood cells.

Neutropenia, common in ALL, is a significant risk factor for serious infection. Doctors are increasingly concerned about fungal infections, which are becoming more common in these patients, particularly after transplant procedures.

Antibiotics and Antifungal Medications. The use and timing of antibiotics and antifungal medications depend on the particular organisms and severity of the infection. In some cases of neutropenia, patients may need preventive antibiotics.
Granulocyte Colony-Stimulating Factor. Granulocyte colony-stimulating factor (lenograstim, filgrastim) is often given to patients who receive chemotherapy in order to stimulate the growth of infection-fighting white blood cells. This helps prevent neutropenia.

Intravenous Fluids. Patients may also need to receive intravenous fluids and be treated for fluid imbalances, which can cause abnormal levels of sodium, potassium, calcium, and uric acid. Such treatments might include sodium bicarbonate, allopurinol, and aluminum hydroxide or calcium carbonate.

Transfusions. Red blood cell or platelet transfusions may be needed. (Patients who may need allogeneic transplantations should not receive transfusions from potential donors.)

Home Management

A parent should call the doctor if the child has any symptoms that are out of the ordinary, including (but not limited) to:

Any fever of 101°F or higher
Any signs of a flu or cold
Shortness of breath
Severe diarrhea
Blood in the urine or stools
Trouble urinating

Tracking Neutrophils. Parents should track their child's absolute neutrophil count. This measurement for the amount of white blood cells is an important gauge of a child's ability to fight infection.

Counts over 1,000 usually provide sufficient protection so that children can engage in normal activities, including school and other functions where they are exposed to other children.
If the count is between 500 - 1,000, the child should avoid large groups.
If it falls between 200 - 500, the child should stay at home and should see only healthy visitors who have washed their hands vigorously.
Neutrophil counts below 200 indicate that the child is at high risk for infection and should have no visitors.

Maintaining Strict Hygiene. Children with ALL and anyone exposed to them, not only friends and family members but also doctors and nurses, should maintain strict hygiene:

Frequent hand washing with antibacterial soap is particularly essential.
Everyone should wash their hands before and after meals, after being outside, before preparing food, and after going to the bathroom.
When visiting the doctor, a parent should ask about a side entrance or areas where the patient will not be exposed to other sick children.

Vaccinations. Studies now suggest that young survivors of leukemia have an increased risk for measles, mumps, and rubella (MMR), even if they have been previously vaccinated. Children may need reimmunization. Siblings of patients with ALL who require polio vaccinations should be given the killed virus (IPV), not the live polio vaccination (OPV).

Use a soft toothbrush when counts are low to prevent gum bleeding.
Avoid common pain relievers known as nonsteroidal anti-inflammatory drugs (NSAIDs). They increase the risk for bleeding and include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), and ketoprofen (Actron, Orudis KT).

Some of the drugs used for leukemia cause extreme sun sensitivity. Children should wear sunblock and be covered with sun-protective clothing when going outside to avoid sunburn, which can cause skin infection.

Treatment to Achieve Remission

The aim of induction therapy, the first treatment phase, is to reduce the number of leukemia cells to undetectable levels. The general guidelines for induction therapy are as follows:

Patients are given intensive chemotherapy that uses powerful multi-drug regimens. (Infants require special regimens not discussed here.)
For both children and adults, some of these therapies are administered orally, others intravenously.
Hospitalization is usually necessary at some point to help prevent infection and to administer blood products. However, much of this therapy can be given on an outpatient basis.
After the first cycle of induction, bone marrow tests are done to determine if the patient is in remission.
Another bone marrow test is sometimes done about a week later to confirm the first results.
A bone marrow transplant is considered for patients who do not respond at all to induction treatment.

Both children and adults typically start with a 3-drug regimen. Imatinib (Gleevec) or dasatanib (Sprycel) may be added for patients with Philadelphia chromosome-positive ALL.

For children, the standard drugs are:

Vincristine (Oncovin), a vinca alkaloid drug
Prednisone or dexamethasone. These drugs are corticosteroids. Dexamethasone may be more effective than prednisone, but it increases the risk for infections and other serious side effects.
Asparaginase. Generally provided as pegaspargase (Oncaspar) in place of L-asparaginase (Elspar) for treating newly diagnosed ALL in children. With pegaspargase, patients need only 3 injections over a 20-week period instead of the 21 injections required for L-asparaginase.

For adults, the standard drugs are:

Vincristine
Prednisone
Anthracycline drug, such as such as doxorubicin, daunorubicin, or epirubicin. Some adult chemotherapy regimens also add on an asparaginase drug or cyclophosphamide (Cytoxan).

The induction chemotherapy described above does not penetrate the blood-brain barrier sufficiently to destroy leukemic cells in the brain. CNS prophylaxis is critical for preventing disease that has spread to the brain, spine, and testes (called sanctuary disease sites). Although only 3% of children with ALL have evidence of leukemia in the central nervous system (CNS) at the time of diagnosis, leukemia will spread to this region in 50 - 70% of children who don't receive preventive (prophylactic) treatment. The brain is one of the first sites for relapsing leukemia.

For children, CNS prophylaxis uses intrathecal chemotherapy, in which a drug is injected directly into the spinal fluid. Intrathecal chemotherapy is given with methotrexate alone or a combination of methotrexate, cytarabine, and hydrocortisone.

Some high-risk children also receive radiation to the skull (cranial irradiation), radiation to the spine, or both at the same time. This combination can be very toxic and can cause later learning problems. It is generally used only in children who have evidence of the disease in the central nervous system at the time of diagnosis. Later complications can include learning and neurologic problems. Using lower-dose units of radiation, however, may significantly reduce the risk for mental impairment. Cranial radiation is also associated with increased risks for stroke and secondary cancers.

Adult CNS prophylaxis is performed in one of three ways:

Cranial radiation plus intrathecal chemotherapy with methotrexate
High-dose systemic infusion of methotrexate plus intrathecal methotrexate without cranial radiation
Intrathecal methotrexate chemotherapy alone

Survival in acute leukemia depends on complete remission. Although not always clear-cut, remission is indicated by the following:

All signs and symptoms of leukemia disappear.
There are no abnormal cells in the blood, bone marrow, and cerebrospinal fluid.
The percentage of blast cells in the bone marrow is less than 5%.
Blood platelet count returns to normal.

Induction can produce extremely rapid results, and the faster the time to remission the better the outlook:

A complete remission usually occurs within the first 4 weeks. Patients who show low disease levels within 7 - 14 days have an excellent outlook, particularly if they have favorable genetic factors, and may need less-intensive treatments afterward.
Patients with high disease levels at 14 days or who require more than 4 weeks to achieve remission are at higher risk for relapse and most likely need more aggressive treatment.

Side effects and complications of any chemotherapeutic regimen and radiation therapy are common, are more severe with higher doses, and increase over the course of treatment. Administering drugs for shorter duration can sometimes reduce toxicities without affecting the drugs' cancer-killing effects.

Common Side Effects. Typical side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs, and most patients who take more powerful drugs. In one study, nearly all patients who took a combination of dexamethasone (a steroid) in combination with ondansetron within 24 hours of chemotherapy experienced either a significant or complete reduction in nausea and vomiting.
Diarrhea
Hair loss
Weight loss
Depression

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used.

Infection from suppression of the immune system or from severe drops in white blood cells is a common and serious side effect. Patients should make all efforts to prevent infection. The patient at high risk for infection may need very potent antibiotics and antifungal medications as well as granulocyte colony-stimulating factors or G-CSF (lenograstim, filgrastim) to stimulate the growth of infection-fighting white blood cells. Patients should make all efforts to minimize exposure to bacteria and viruses. (See “Infection Prevention” in the Transplant section of this report.)

Other serious side effects include:

Liver and kidney damage
Immediate and short-term risks of radiation therapy may include seizures, stroke, and paralysis
Very high levels of uric acid in the blood, which can damage the kidneys
Very high levels of calcium in the blood
Abnormal blood clotting
Allergic reaction
Low blood sugar (hypoglycemia) -- a rare complication in young, thin children who are taking purine analogues such as mercaptopurine and thioguanine
Suppression of adrenal glands in children who take short-term, high-dose corticosteroids such as prednisolone

Long-Term Complications.

Fatigue is very common after chemotherapy and can be significant and long-lasting.
Combinations of intrathecal chemotherapy plus brain radiation in children can cause some serious complications, including seizures and problems in learning and concentration. Methotrexate is particularly toxic. (The effects of intrathecal chemotherapy alone on mental functioning, however, did not seem significant.) Seizures can often be treated successfully with anti-epilepsy medications.
Delayed puberty. The effects of treatment in the brain can affect regions that regulate reproductive hormones, which may affect fertility later on. Chemotherapy, cranial radiation, or both can impair fertility in male and female patients. Cranial radiation can also result in impaired growth.
Bone loss can occur after chemotherapy, particularly with corticosteroids and after bone marrow transplantation. Drugs are available, particularly bisphosphonates, which may help reduce this risk.
Pancreatic beta-cell damage. A 2004 study reported that children who have been off treatment for at least 1 year have a higher risk of impaired insulin response. This suggests that chemotherapy-induced beta cell damage persists after therapy has been stopped.
Heart damage. Some of the treatments increase risk factors for future heart disease, including unhealthy cholesterol levels and high blood pressure. Anthracyclines (doxorubicin, daunorubicin, epirubicin) have been associated with later development of heart failure. Lower doses used for many ALL children may not pose a high risk to the heart. Some anthracyclines (DaunoXome, Myocet, Doxil) now come in tiny protective capsules that may reduce toxic effects. Patients with ALL should be sure to maintain a healthy lifestyle and be regularly monitored for heart risks to help reduce these effects.
Stroke. Survivors of childhood leukemia are at increased risk of later stroke, especially if they received treatment with cranial radiation.
Obesity. Children treated for ALL are at higher risk for obesity, possibly because the treatments trigger an earlier than normal occurrence in childhood weight gain. Corticosteroid drugs used in treatments also increase appetite, which contributes to the problem.
Central nervous system. Radiation and intrathecal MTX therapy may be associated with an increased risk of mood disturbances (such as depression) among adult survivors of childhood ALL. Patients with depression may benefit from psychosocial support. Cranial radiation and drugs used in chemotherapy, especially specific corticosteroids and spinal injection treatments, may also impair mental functioning and cause neurologic problems, such as movement problems.
Infections. Some children may be more vulnerable to infections after completing chemotherapy, although the immune system tends to improve over time. Patients who have had a bone marrow transplantation or lung damage from the treatments may be particularly vulnerable. Studies suggest that young survivors of leukemia have an increased risk for measles, mumps, and rubella (MMR), even if they have been previously vaccinated. Children, then, may need reimmunization.
Secondary Cancers. Studies indicate that survivors of childhood ALL are at increased risk of later developing other types of cancers, including brain and spinal cord tumors, basal cell skin carcinoma, and myeloid (bone marrow) malignancies. Radiation and older types of chemotherapy are mainly responsible for this risk. Newer types of ALL treatment may be less likely to cause secondary cancers.

Treatment During Remission

Consolidation and maintenance therapies follow induction and first remission. The goal of consolidation and maintenance therapies is to prevent a relapse. The specific treatment choices and degree of aggressiveness after induction therapy depend on a number of factors, particularly the risk factors for relapse.

Consolidation therapy is additional treatment that is administered after induction therapy and before maintenance therapy. This is an intense regimen that is designed to prevent the high relapse rates that occur with induction therapy alone. (The benefits of this therapy are clearer in children than in older adults, who may just be given maintenance.)

Consolidation therapy usually continues for about 6 months and uses 1 - 6 courses of chemotherapy, depending on risk factors for relapse.

Examples of consolidation regimens for children at standard risk:

A limited number of courses of intermediate- or high-dose methotrexate, one of the oldest drugs used for leukemia.
An anthracycline drug, such as daunorubicin (Cerubidine), used for reinduction followed by cyclophosphamide (Cytoxan, Neosar) 3 months after remission. These are very powerful drugs, but when used in this way toxicity is limited.
Extended use of an asparaginase drug.

More intense regimens are used for children at high-risk for relapse.

Instead of chemotherapy alone as consolidation therapy, some high-risk patients in first remission who are unlikely to be cured by standard chemotherapy alone may undergo allogeneic stem cell or autologous stem cell bone marrow transplant after the intensive chemotherapy regimens. Many adult patients may fall into this category. Studies on high-risk children have been conflicting about the value of transplants during a first remission.

Allogeneic transplantation is an option when a well-matched donor is available. Although this treatment can be effective in keeping the leukemia away, significant complications -- such as graft versus host disease, blood clots, liver problems, and lung damage -- can occur and may be a cause of death even without a return of cancer.
Autologous stem cell bone marrow transplant (using the patient's own bone marrow cells) seems to be helpful also and may be as effective as allogeneic transplantation.

The last phase of treatment is maintenance, or continuation therapy:

Maintenance therapy typically uses weekly administration of methotrexate (usually in oral form) and daily doses of mercaptopurine. (Mercaptopurine should be given in the evening.)
Treatment continues for 2 - 3 years for most children with ALL (with the exception of those with mature B-cell leukemia). It is not yet clear if prolonged maintenance therapy benefits adults with ALL.
If children were not given CNS prophylaxis before, it may be given now.
Vincristine and a corticosteroid drug (generally dexamethasone) are often added to standard maintenance therapy, although some studies indicate that they do not provide additional benefit.

A maintenance regimen is usually less toxic and easier to tolerate than induction and consolidation. Some studies, however, indicate that overall survival could further be improved with more-aggressive maintenance therapies, including:

Vincristine and a corticosteroid added to the standard maintenance regimen
Longer term low-dose maintenance
Intense regimens similar to induction (called reinduction)

Maintenance is typically ongoing until complete remission has lasted 2 - 3 years.

Investigation is ongoing to determine the best drugs and schedules to use. For example, doctors have debated whether thioguanine is a better choice than mercaptopurine (a 2006 study recommended that mercaptopurine remain the standard thiopurine drug for treating childhood ALL). Researchers are also trying to pinpoint patients who would best benefit from aggressive maintenance treatments.

The following are factors that increase the risk for relapse after initial treatments:

Microscopic evidence of leukemia after 20 weeks of therapy (minimal disease)
Age over 30
A high white blood cell count at the time of diagnosis
Disease that has spread beyond the bone marrow to other organs
Certain genetic abnormalities, such as the presence of the Philadelphia chromosome or MLL gene translocations
Patients with high disease levels after 7 - 14 days of induction therapy
The need for 4 or more weeks of induction chemotherapy in order to achieve a first complete remission

Patients with one or more of these risk factors may be candidates for bone marrow transplantation once they are in first remission.

Treatment After Relapse

Between 50 - 70% of children and 40 - 50% of adults who achieve complete remission after initial therapy but then suffer a relapse may be able to go into a second complete remission.

Treatment for relapse after a first remission may be standard chemotherapy or experimental drugs, or more aggressive treatments such as stem cell transplants.

The decision depends on a number of factors:

Children who relapse 3 or more years after achieving a first complete remission have an excellent chance for a second remission without aggressive treatments.
Those who relapse fewer than 6 months following initial treatment, especially while on chemotherapy, have about a 20% chance of long-term freedom from disease. In such cases, remission is possible following another course of standard chemotherapy but the duration of remission is usually fewer than 6 months.

Treatment decisions also rely on prior treatments and where the relapse has occurred. Relapse can occur in the bone marrow, central nervous system, or sanctuary disease sites (brain, spine, or testicles). The incidence of relapse in sanctuary sites is about 10%.

Candidates for transplantation include:

Patients who relapse following initial remission with standard chemotherapy.
High-risk patients in first remission who are unlikely to be cured by standard chemotherapy alone. Many adult patients may fall into this category. Studies on high-risk children have been conflicting about the value of transplants during a first remission.
Patients who fail to achieve a complete remission during initial chemotherapy.

Transplantation procedures do not appear to offer any additional advantages for patients at low or standard risk.

Many different drugs are used to treat ALL relapses. These drugs include vincristine, asparaginase, anthracyclines (doxorubicin, daunorubicin), cyclophosphamide, cytarabine (ara-C), and epipodophyllotoxins (etoposide, teniposide). Corticosteroids, such as prednisone or dexamethasone, may also be used.

In 2004, the Food and Drug Administration (FDA) approved clofarabine (Clolar) for treatment of relapsed or refractory ALL in children. This drug was the first new leukemia treatment approved specifically for young patients in more than a decade. In 2005, nelarabine (Arranon) was approved to treat adults and children with relapsed or refractory T-cell acute lymphocytic leukemia (T-ALL). In 2006, the FDA approved imatinib (Gleevec) for treating patients with Philadelphia chromosome-positive ALL that has not responded to or has returned after treatment. Also in 2006, the FDA approved dasatinib (Sprycel) for patients who are not helped by imatinib.

Tyrosine kinase inhibitors. Tyrosine kinase is a growth-stimulating protein. Tyrosine kinase inhibitor drugs block the cell signals that trigger cancer growth. Several tyrosine kinase inhibitors, including imatinib (Gleevec) and dastinib (Sprycel), have recently been approved for treating Philadelphia chromosome-positive ALL. In 2006 clinical trials, Nilotinib (AMN-107) produced excellent results in patients with Philadelphia chromosome positive ALL who are resistant to imatinib.

Monoclonal antibodies (MAbs). Used alone or in combination with chemotherapy, MAbs target specific antigens on ALL blast cells. Although MAbs have been studied primarily in the treatment of B-cell non-Hodgkin's lymphoma, drugs demonstrating benefit in preliminary trials of ALL include anti-CD20 (rituximab) and anti-CD22 (epratuzumab). Alemtuzumab (MabCampath) is also showing promise in treating relapsed or refractory T-ALL. More studies are needed to determine the best MAb regimens in ALL.

In order to administer high-dose chemotherapy for advanced cancer cases, stem cell transplantation procedures may be used. These procedures are based on removal and replacement of stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them from the donor into the patient.

Sources of Cells. Stem cells must first be collected either from:

Bone marrow (bone marrow transplantation)
Blood (peripheral blood stem cell transplantation). Evidence suggests that peripheral blood stem cell transplantation may be the superior approach. Studies report survival rates of 45% in bone marrow transplant patients compared to 65 - 70% in stem cell transplant patients, with benefits being significant in those with more severe disease.
Fetal umbilical cord or placentas. This procedure uses donor cells but has a lower risk for immune system rejection of the cells than with a standard donor transplant. It takes longer to restore blood cells with this process, however, so at this time its use is limited to children and sometimes adults with low weight. (Some studies indicate success for adults with normal weights.)

Donor or Patient Cells. The sources of marrow or blood cells can be taken from the patient or a donor:

If the bone marrow or stem cells are taken from a donor, the transplant is referred to as allogeneic. Allogeneic transplants from genetically matched sibling donors offer the best results in ALL. With new techniques, donor bone marrow from unrelated but immunologically similar donors is proving to work as well as those from matched siblings. This approach is still reserved for patients in second remission or beyond. A 2006 study indicated that allogeneic transplant is also a good treatment option for patients with Philadelphia chromosome-positive ALL who are resistant to imatinib (Gleevec).
If the marrow or blood cells used are the patient's own, the transplant is called autologous. Autologous transplants in patients with ALL are generally not beneficial, since there is some danger that the cells used may contain tumor cells and the cancer can regrow. Treatment advances that reduce this risk, however, may make autologous transplantation feasible in patients without family donors.

The donor is usually given a drug called granulocyte colony-stimulating factor, or G-CSF (filgrastim, lenograstim) to stimulate stem cell growth.
The donor (or patient in an autologous procedure) then undergoes apheresis. With this process, the blood is withdrawn from one of the patient's veins and passed through a machine that filters out the white cells and platelets, which contain the stem cells. The blood is returned through another vein. The entire procedure takes 3 - 4 hours but needs to be repeated several times.
The stem cells are then frozen.

The patient is given high-dose chemotherapy with or without radiation -- a treatment known as conditioning. The point is to inactivate the immune system and to kill any residual malignant cells. Drugs used are typically cyclophosphamide, carmustine, and etoposide. Alternative conditioning includes radiation with drugs.
A few days after treatment, the patient is rescued using the stored stem cells, which are administered through a vein. This may take several hours. Patients may experience fever, chills, hives, shortness of breath, or a fall in blood pressure during the procedure.
The patient is kept in a protected environment to minimize infection, and the patient usually needs blood cell replacement and nutritional support.

Two- to 5-year survival rates after transplantation plus chemotherapy range from 40 - 80%. Certain patients with the Philadelphia chromosome, which carries a poor prognosis, may achieve significant success with an allogeneic bone marrow transplant from a closely matched related donor.

Common side effects include nausea, vomiting, fatigue, mouth sores, and loss of appetite.

Blood stem cell transplantation itself is fairly dangerous and has a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now, mortality rates are below 5%. Potentially serious complications include:

Infection resulting from a weakened immune system is the most common side effect. Because the stem cell procedure is done more swiftly, the risk period is shorter than with bone marrow transplantation. The risk for infection is most critical during the first 6 weeks following the transplant, but it takes 6 - 12 months post-transplant for a patient’s immune system to fully recover. Immune systems of patients with graft-versus-host disease can take even longer to function normally

Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis carinii (a protozoan) are among the most important life-threatening infections.

It is very important that patients take precautions to avoid infections. Guidelines for post-transplant infection prevention include:

Discuss with your doctor what vaccinations you need and when you should get them.
Avoid crowds, especially during cold and flu season.
Be diligent about hand washing and make sure that visitors wash their hands.
Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
Boil tap water before drinking it.
Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
Do not sleep with pets. Avoid contact with pets’ excrement.
Avoid fresh flowers and plants as they may carry mold. Do not garden.
Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection. Some of these symptoms can also indicate graft-versus-host disease.
Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.

Graft-versus-host disease (GVHD) is a serious attack by the patient's immune system triggered by the donated new marrow in allogeneic transplants. To reduce the risk for GVHD, doctors remove some immune T cells from the donor’s stem cells before the transplant. Researchers are investigating new techniques to refine this process of T cell depletion.

Acute GVHD occurs in 30 - 50% of allogeneic transplants, usually within 25 days. Its severity ranges from very mild symptoms to a life-threatening condition (more often in older patients). The first sign of acute GVHD is a rash, which typically develops on the palms of hands and soles of feet and can then spread to the rest of the body. Other symptoms may include nausea, vomiting, stomach cramps, diarrhea, loss of appetite and jaundice (yellowing of skin and eyes). To prevent acute GVHD, doctors give patients immune-suppressing drugs such as steroids, methotrexate, cyclosporine, tacrolimus, and monoclonal antibodies.

Chronic GVHD can develop 70 - 400 days after the allogeneic transplant. Initial symptoms include those of acute GVHD. Skin, eyes, and mouth can become dry and irritated, and mouth sores may develop. Chronic GVHD can also sometimes affect the esophagus, gastrointestinal tract and liver. Bacterial infections and chronic low-grade fever are common. Chronic GVHD is treated with similar medicines as acute GVHD.

Too much sun exposure can trigger GVHD. Be sure to always wear sunscreen (SPF 15 or higher) on areas of the skin that are exposed to the sun. Stay in the shade when you go outside.

Other potentially serious complications include:

Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
Infertility
Organ complications to the liver, heart, kidney, or lungs
Failure of the transplant
Muscle problems, including stiffness, cramps, and joint pain
Frequent urination and bladder control problems
Older patients should be screened for osteoporosis (thinning of bones) and hypothyroidism (underactive thyroid)

Resources

www.leukemia-lymphoma.org -- Leukemia and Lymphoma Society
www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.bmtnews.org -- Blood and Marrow Transplant Information Network
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.aspho.org -- American Society of Pediatric Hematology/Oncology
www.candlelighters.org -- Candlelighters Childhood Cancer Foundation
www.clf4kids.com -- Childhood Leukemia Foundation

References

Belson M, Kingsley B, Holmes A. Risk factors for acute leukemia in children: a review. Environ Health Perspect. 2007 Jan;115(1):138-45. Campbell LK, Scaduto M, Sharp W, et al. A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer. 2007 Jul;49(1):65-73.

Hijiya N, Hudson MM, Lensing S, et al. Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA. 2007 Mar 21;297(11):1207-15.

Ribera JM, Ortega JJ, Oriol A, et al. Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as postremission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 Trial. J Clin Oncol. 2007 Jan 1;25(1):16-24.

Waber DP, Turek J, Catania L, et al. Neuropsychological outcomes from a randomized trial of triple intrathecal chemotherapy compared with 18 Gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. J Clin Oncol. 2007 Nov 1;25(31):4914-21.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Tech Dating 101: He's Got a Ton of Female Contacts

GeekSugar — Mon, 31 Aug 2009 05:48:17 -0700

So we'll say that your date left his phone on the dinner table as he ran to the bathroom before the check came, and the snooper that you are couldn't keep from getting your eyeballs on his contact list. And guess what? He's got a large number of female numbers stashed in his cell. Should you be worried? That's what we'll figure out on this edition of Tech Dating 101.

First of all, what are you doing pilfering through your date's cell phone? Snoopers never win my friends. But if you are legitimately worried about whether or not he's a player, I've got a few options on how to figure the situation out without looking like the jealous type. Find out more when you read more.

Ask yourself: What does he do for a living? If your date is in PR, marketing, or any type or advertising, he's going to have a lot of entries, female and male. Don't judge the contact list by its cover.
Watch a wandering eye: If your guy is on a date with you and is constantly checking out other scenery, he's probably just not that into you.
Go with your gut: If you have a gut reaction after seeing the male-to-female ratio that says this dude is a player, then go with it. Sometimes, listening to the little voice inside that's telling you to run away is the one you should obey. Never mind the fact that he's drop-dead gorgeous, just run.
Wait it out: If you're having a good time and aren't looking to marry the guy (well, not yet anyway), then maybe you should go on a couple more dates before you start worrying about how many contacts he has on his email list. Just sayin.

Brain tumors - primary

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Causes
Prognosis
Diagnosis
Common Brain Tumors
Treatment
Surgery
Radiotherapy
Chemotherapy
Other Treatments
Treatment of Complications...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Radiation Therapy Complications

Radiation therapy in children with cancer increases the risk of new brain and spinal cord tumors, suggests a study in the Journal of the National Cancer Institute. The risk appears to increase along with the radiation dosage. Children who receive radiotherapy before age 5 are especially at risk for second primary tumors.
Survivors of childhood brain tumors who received cranial radiotherapy as part of their treatment are at risk for later having a stroke, indicates a study in the Journal of Clinical Oncology. The average length of time from brain tumor diagnosis to post-treatment stroke was 14 years.

Radiation Therapy for Elderly Patients

Radiotherapy provides modest improvement in survival for elderly patients (age 70 years and older) with glioblastoma, with no detriment to quality of life or cognition function, according to a 2007 study in the Journal of the American Medical Association.

Temozolomide (Temodar)

The chemotherapy drug temozolomide (Temodar) has become an important and effective treatment for patients newly diagnosed with glioblastoma. However, not all patients respond equally well to this drug. A 2007 study in the journal Neurology suggests that a patient’s genotype may explain differences in response. Though genetic testing, researchers found that temozolomide works best in people who are missing a particular gene.

Investigational Treatments

Vorinostat (Zolinza), a cancer drug used for T-cell lymphoma, may help patients with recurrent glioblastoma multiforme, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin), a targeted therapy drug used for lung and colorectal cancers, may help prolong survival in patients with advanced glioma, indicates a 2007 study in Clinical Cancer Research. Another anti-angiogenesis drug, cediranib (Recentin), may help make glioblastomas more responsive to chemotherapy and radiotherapy, according to recent interim trial results.
Vitespen (Oncophage), an experimental vaccine for glioma, is showing promise in early clinical trials, suggests research presented at the 2007 meeting of the American Association of Neurological Surgeons.

Introduction

Brain tumors are composed of cells that exhibit unrestrained growth in the brain.

The major areas of the brain have one or more specific functions.

They can be benign (noncancerous, meaning that they do not spread elsewhere or invade surrounding tissue) or malignant (cancerous).

Cancerous brain tumors are further classified as either primary or secondary tumors. Primary tumors start in the brain, whereas secondary tumors spread to the brain from another site such as the breast or lung. (In this report, the term "brain tumor" will refer mainly to primary malignant tumors, unless otherwise specified.)

Benign tumors represent half of all primary brain tumors. Their cells look relatively normal, grow slowly, and do not spread (metastasize) to other sites in the body. Benign tumors can still be serious and even life-threatening if they are in vital areas in the brain where they exert pressure on sensitive nerve tissue or if they increase pressure within the brain. While some benign brain tumors may pose a health risk, including risk of disability and death, most are usually successfully treated with techniques such as surgery.

Click the icon to see an image of a primary brain tumor.

A secondary (metastatic) brain tumor occurs when cancer cells spread to the brain from a primary cancer in another part of the body. Secondary tumors are about three times more common than primary tumors of the brain. Usually, multiple tumors develop. Solitary metastasized brain cancers may occur but are less common. Most often, cancers that spread to the brain to cause secondary brain tumors originate in the lung, breast, kidney, or from melanomas in the skin.

A primary malignant brain tumor is one that originates in the brain itself. Although primary brain tumors often shed cancerous cells to other sites in the central nervous system (the brain or spine), they rarely spread to other parts of the body.

Brain tumors are generally named and classified according to the following:

The normal brain cells from which they originate, or
The location in which the cancer develops

The biologic diversity of these tumors, however, makes classification difficult, and some experts believe that more specific categories are needed.

About half of all primary brain tumors are known collectively as gliomas. They are cancerous forms of glial cells, the building-block cells of the connective, or supportive, tissue in the central nervous system. There are several glial cells types from which gliomas form. Their names are:

Astrocytomas are primary brain tumors derived from astrocytes, which are star-shaped glial cells. Normal astrocytes provide nutrients, support, and insulation for nerve cells and are one of the primary neurologic cells in the body. The malignant astrocytomas called glioblastomas account for 23% of brain tumors and are the most common ones.
Oligodendrogliomas develop from oligodendrocyte glial cells, which form the protective coatings around nerve cells. Although oligodendrogliomas were thought to represent about 5% of all gliomas, more recent evidence suggests they may comprise about 20% of gliomas. Pure oligodendrogliomas, however, are rare. In most cases they occur in mixed gliomas.
Ependymomas are derived from ependymal cells, which line the ventricles (fluid-filled cavities) in the lower part of the brain and the central canal of the spinal cord. They constitute about 6% of all primary tumors in the central nervous system. About 30% of these tumors occur in the spinal cord.
Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

It should be noted that gliomas may also contain cancer cells derived from brain cells other than glial cells.

Some brain tumors are categorized by their location in the brain. Such tumors often contain gliomas but are also frequently a mixture of different cell types.

Meningiomas. Meningiomas are usually benign tumors that develop in the membranes that cover the brain and spinal cord (the meninges).

Click the icon to see an image of the meninges.

They are not technically classified as brain tumors, but they have similar symptoms and develop within the brain. So in practical terms, they are considered brain tumors. In fact, meningiomas comprise 20% of all primary brain tumors. They occur more often in women than in men. Most grow very slowly, and the majority of people who have them never know they are present. Malignant forms called anaplastic meningiomas and hemangiopericytomas are less common and are difficult to remove surgically.

Cerebral Astrocytomas. Gliomas that develop inside the brain often occur in the cerebral hemispheres (the right and left sides of the brain). In such cases, they are referred to as cerebral astrocytomas. Gliomas sometimes occur in another part of the brain, called the cerebellum. The cerebellum is responsible for balance and coordination. In such cases, the term cerebellar astrocytoma is used.

Click the icon to see an image of the function of the left cerebral hemisphere.

Click the icon to see an image of the function of the right cerebral hemisphere.

Brain Stem Gliomas. Brain stem gliomas develop in the lowest portion of the brain. The brain stem connects the cerebrum (the higher centers of the brain) to the spinal cord. The brain stem is thought to be the primitive brain because it controls the most basic functions.

Click the icon to see an image of the function of the brainstem.

The brain stem consists of three primary parts:

The medulla regulates breathing, swallowing, blood pressure, and heart rate.
The pons links the cerebellum to the cerebrum.
The midbrain helps control vision and hearing.

Click the icon to see an image of the structures of the brain.

Medulloblastomas. Medulloblastomas are always located in the cerebellum, which is at the base and toward the back of the brain. They represent about 3% of all brain tumors.

Click the icon to see an image of the function of the cerebellum.

Pituitary Tumors. Pituitary tumors comprise about 10% of primary brain tumors and are often benign, slow-growing masses in the pituitary gland.

Click the icon to see an image of the pituitary gland.

Other Brain Tumor Locations. Optic nerve gliomas occur in the optic nerve, which is located behind the eye. Acoustic neuromas make up 7.5% of brain tumors.

Click the icon to see an image of the optic nerve.

Symptoms

Brain tumors produce a variety of symptoms, ranging from headache to stroke. They are great mimics of other neurologic disorders. Symptoms occur if the tumor directly damages the nerves in the brain or central nervous system or if its growth imposes pressure on the brain. Some gliomas develop gradually, and symptoms may be subtle for a long time, making an early diagnosis difficult.

Headache is probably the most common symptom of a brain tumor. It should be strongly emphasized, however, that everyone has headaches, and they rarely represent an underlying brain tumor. Headaches caused by brain tumors may vary depending on the location, and many different features.

Steady and worse upon waking in the morning and clears up within a few hours
Persistent non-migraine headache that occurs while sleeping and is also accompanied by at least one other symptom (such as vomiting or confusion)
May or may not be throbbing, depending on location of the tumor
Accompanied by double vision, weakness, or numbness
May worsen with coughing or exercise or with a change in body position
Sometimes accompanied by neck pain

Gastrointestinal symptoms, including nausea, are also common. Nausea and vomiting, in fact, often occur in children with brain tumors and in all people with brain stem cell tumors.

Seizures occur in between 15 - 95% of patients, depending on the location of the tumor.

Tumors are more likely to be localized and affect one area of the brain. In such cases they can cause partial seizures. In this case, a person does not lose consciousness but may experience confusion, jerking movements, tingling, or odd mental and emotional events.
Generalized seizures, which can cause loss of consciousness, are less common, since they are caused by disturbances of nerve cells in diffuse areas of the brain.

Sometimes the only symptoms are mental changes, which may include the following:

Memory loss
Impaired concentration
Problems with speech and reasoning
Increased sleep

Gradual loss of movement or sensation in an arm or leg
Unsteadiness
Unexpected visual disturbance (especially if it is associated with headache), including vision loss (usually of peripheral vision) in one or both eyes or double vision
Hearing loss with or without dizziness
Speech difficulty

Specific symptom syndromes may help identify the tumor. The following are some examples.

Symptoms of Brain Stem Gliomas. Sudden onset of symptoms that include vomiting (usually just after waking), a clumsy walk, muscle weakness on one side of the face, difficulty in swallowing, slurred or nasal speech, as well as impaired hearing or vision.

Symptoms of Glioblastoma Multiforme. Rapid onset and worsening of symptoms that include headaches, seizures, memory loss, and changes in behavior.

The below symptoms indicate an emergency condition and require immediate medical attention:

Pupil dilation
A fixed gaze
Paralysis on one or both sides of the body
Blindness or defective vision in one eye

Risk Factors

Nearly 360,000 people in the U.S. are living with brain cancer. Men are at higher risk than women for most brain tumors. Primary malignant brain tumors are still uncommon and represent only 1.3% of all cancers diagnosed in the United States and 2.4% of all deaths due to cancer.

Primary brain cancers are rare, occurring in slightly more than 11 people per 100,000 per year. There has been some evidence of a growing incidence of brain cancer among the elderly since the 1980s. The increase, however, is most likely due to the rise in incidence of non-Hodgkin's lymphomas -- which can occur in the brain. When this malignancy is eliminated, any increase in other tumors is not significant.

The average age of diagnosis for brain tumors is 57, and about 90% of primary brain tumors occur in adults. These tumors can develop at all ages, usually peaking in two age groups.

In adults, ages 55 - 65
In children, ages 3 - 12

Risk Factors in Children. Tumors in the central nervous system are now the most common primary cancers in children, but they are still rare. An estimated 3,110 benign or malignant brain tumors are expected to be diagnosed in children each year. Brain tumors in children are more likely to occur in the cerebellum, the midbrain, or the optic nerve.

The incidence has increased over the past years, but there is some evidence that this increase is only due to better diagnostic procedures. The mortality rate has actually decreased. Researchers have attempted to uncover risk factors for childhood brain cancer. There may be some association between a higher risk and the following conditions:

Children treated with radiation to the head for leukemia and who have a specific genetic defect may face a high risk for brain cancer. (It should be noted that for children without this defect, the risk is very small.)
Having parents with specific cancers. (According to one study, having parents with nervous system cancers, colon cancer, or cancer in the salivary glands increased the risk of specific brain tumors in their children.)

Click the icon to see an illustrated series detailing colon cancer surgery.

The risk for primary brain tumors in Caucasians is higher -- as much as twofold depending on type -- than in African-Americans.

Radiation Exposure. People who receive radiation therapy to the head during cancer treatment have an increased risk of developing brain tumors 10 - 15 years later. Workers in the nuclear industry are also at increased risk.

There is no evidence that electromagnetic field exposure from power lines or household appliances poses any risk. Several recent epidemiological studies, including a 2006 study in the British Medical Journal, found that cell phones, cordless phones, and wireless devices are also safe and do not increase the risk for gliomas.

Chemical and Metals in Brain Tumors. High exposure to numerous metals and chemicals have been associated with brain tumors:

Industrial chemicals, including vinyl chloride and petroleum products
Lead, arsenic, or mercury exposure
Exposure to pesticides. A major study of pesticides is underway, but results are not in yet. A 2003 study indicated that parental exposure to pesticides or herbicides did not appear to be important in increasing risk for brain cancer in their children.

Brain cancer is uncommon, and, over the course of their lifetime, many people are exposed to these chemicals, many of which are very common. To date, there has been no clear evidence that implicates any specific industrial chemical or metal.

One study reported a higher risk for brain cancers in patients who had undergone organ transplantations. Researchers believed that the drugs used to suppress the immune response after the procedures may increase the risk.

One study reported lower risks for brain cancers in individuals with allergies and autoimmune diseases (such as type 1 diabetes). Autoimmune diseases were also associated with a lower risk for meningiomas. The cause of this possible association remains unknown.

Studies have also found an association between lower risk for gliomas and a history of infection with varicella zoster, the virus that causes chicken pox and shingles.

Click the icon to see an image of the chicken pox.

Causes

Only 5 - 10% of primary brain tumors are associated with genetic disorders. These inherited conditions and associated genes include:

Von Recklinghausen disease, also called neurofibromatosis 1 (NF1 gene) and neurofibromatosis 2 (NF2 gene)
Turcot's syndrome (APC gene)
Gorlin syndrome, also called basal cell naevus syndrome (PTCH gene)
Tuberous sclerosis (TSC1 and TSC2 genes)
Li-Fraumeni syndrome (TP53 gene)

Certain types of brain tumors are specifically linked with these genetic conditions. For example, neurofibromatosis 1 is associated with about 15% of cases of pilocytic astrocytomas, the most common type of childhood glioma. Neurofibromatosis results from defects in the tumor suppressor genes NF1 and NF2. Li-Fraumeni syndrome results from mutations in the tumor suppressor gene TP53. These mutations affect the production of tumor suppressor protein p53.

Tumor suppressor genes regulate cell division and help repair DNA damage. When mutations that affect protein encoding occur, unregulated cell division and growth can lead to the development of a tumor. Tumor suppressor genes are sometimes described as being in a tug-of-war with cancer-causing genes called oncogenes. Oncogenes derive from mutations or overexpressions of proto-oncogenes. Proto-oncogenes encode for proteins that regulate cell growth and differentiation. When proto-oncogenes become oncogenes, normal cells start to grow uncontrollably. Cancer can occur when tumor suppressor genes are turned off, or when oncogenes are turned on.

Many different oncogenes are involved in cancer. Growth factors are a particularly important type of oncogene associated with brain tumors. Growth factors attach to receptors (connectors) that stimulate cell growth. Epidermal growth factor receptor (EGFR) has been shown to play a role in high-grade brain tumors such as glioblastoma multiforme. In 2007, scientists identified insulin-like growth factor binding protein (IGFBP2) with an oncogene that may be associated with the development of astrocytoma and oligodendroglioma.

Knowing the molecular origin of a brain tumor may help determine the treatment course, both for standard chemotherapy and "targeted therapy" biologic drugs. For example, patients with tumors marked by high EGFR proliferation may benefit from treatment with the EGFR kinase inhibitor drugs gefitinib (Iressa) or erlotinib (Tarceva).

Most genetic abnormalities that cause brain tumors are not inherited but occur as a result of environmental or other factors that affect genetic materials (DNA) in the cells. Researchers are studying various environmental factors (viruses, hormones, chemicals, radiation) that may trigger the genetic disruptions that lead to brain tumors in susceptible individuals. They are also working to identify the specific genes that are affected by these environmental triggers. For example, in a 2007 study, scientists proposed that genetic susceptibility may explain why some people develop meningioma, a rare type of brain tumor, following exposure to ionizing radiation. Future investigations will hopefully identify the specific genes involved and help determine which people would potentially be most at risk.

Prognosis

About 13,100 people die from cancerous brain tumors each year. Recent advances in surgical and radiation treatments have significantly extended average survival times and can reduce the size and progression of malignant gliomas. In general, survival rates are highest in younger people and lowest in the elderly.


Age	Survival Rates
0 - 19 years	63.1%
20 - 44 years	50.4%
45 - 64 years	14.2%
Over 65	4.9%
Data From: 2002 - 2003 Primary Brain Tumors in the United States Statistical Report. Fact Sheet (1973- 1999 data). Brain Tumor Registry of the United States www.cbtrus.org/factsheet/factsheet.html.

In general, studies are reporting that patients who survive the first 2 years after a diagnosis of a brain tumor have at least a 70% chance of surviving for at least 5 years. The best recent progress has been made for:

Medulloblastomas in both children and adults. Long-term survival rates are now about 60% in children after treatment for medulloblastomas, the most common malignant brain tumor in this age group. (New treatments, however, may significantly improve these rates.)
Nonmalignant astrocytomas and oligodendrogliomas in adults.

Unfortunately, the majority of primary brain tumors, notably anaplastic astrocytomas and glioblastoma multiforme, are only rarely curable.

The specific effects of tumors on the brain can cause seizures, mental changes, and mood, personality, and emotional changes. Such effects can be devastating to the patient and the caregivers. Numerous treatments are available that help alleviate these complications, and patients and family members should discuss these with their doctors.

Diagnosis

A neurological exam is usually the first test given when a patient complains of symptoms that suggest a brain tumor. The exam includes checking eye movements, hearing, sensation, muscle movement, sense of smell, and balance and coordination. The doctor will also test mental state and memory.

X-rays of the skull were once standard diagnostic tools but are now performed only when more advanced procedures are not available. Advanced imaging techniques have dramatically improved the diagnosis of brain tumors in recent years.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is the gold standard for diagnosing a brain tumor. It does not use radiation and provides pictures from various angles that can enable doctors to construct a three-dimensional image of the tumor. It gives a clear picture of tumors near bones, smaller tumors, brainstem tumors, and low-grade tumors. MRI is also useful during surgery to show tumor bulk, for accurately mapping the brain and for detecting response to therapy.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI creates a three-dimensional picture of the brain, which allows doctors to more precisely locate problems such as tumors or aneurysms.

A variant called magnetic resonance spectroscopy (MRS) is capable of providing information on the activity of the brain using magnetic resonance imaging. MRS is proving to be accurate for distinguishing dead (necrotic) tissue caused by previous radiation treatments from recurring tumor cells in the brain, a difficult diagnostic issue.

Computed Tomography. Computed tomography (CT) uses a sophisticated x-ray machine and a computer to create a detailed picture of the body's tissues and structures. It is not as accurate as an MRI and does not detect about half of low-grade gliomas. It is useful in certain situations, however. Often, doctors will inject the patient with an iodine dye, called contrast material, to make it easier to see abnormal tissues. A CT scan helps locate the tumor and can sometimes help determine its type. It can also help detect swelling, bleeding, and associated conditions. In addition, computed tomography is used to check the effectiveness of treatments and watch for tumor recurrence.

Click the icon to see an image of a CT scan of the brain.

Positron Emission Tomography. Positron emission tomography (PET) provides a picture of the brain's activity rather than its structure by tracking substances that have been labeled with a radioactive tracer. As with magnetic resonance spectroscopy (MRS), it is also able to distinguish between recurrent tumor cells from dead cells or scar tissue, although MRS is more widely available. PET is not routinely used for diagnosis, but it may supplement MRIs to help determine tumor grade after a diagnosis. Data from PET may also help improve the accuracy of newer radiosurgery techniques.

Other Imaging Techniques. Numerous other advanced imaging techniques may be used for specific purposes, if available or under investigation.

Single photon emission tomography (SPECT) is similar to PET but is not as effective in distinguishing tumor cells from destroyed tissue after treatments.
Magnetoencephalography (MEG) scans measure the magnetic fields created by nerve cells as they produce electrical currents.
Cerebral angiography involves x-rays of blood vessels in the brain. A long, thin tube (catheter) is threaded through blood vessels from a distant site to the brain, and a radiopaque substance (a substance that is impenetrable to x-rays) is injected through it. The role of angiography in glioma is usually limited to planning surgical removal of a tumor suspected of having a large blood supply.
Radionuclide brain scintigraphy uses a radioactive substance that is administered and absorbed by capillaries in the tumor, which are then viewed using imaging techniques.
Digital holography, a new technique that provides full three-dimensional mapping, is under investigation.

A lumbar puncture is used to obtain a sample of spinal fluid, which is examined for the presence of tumor cells. A computed tomography (CT) scan or magnetic resonance imaging (MRI) should generally be performed before a lumbar procedure to be sure that the procedure will be safe.

Click the icon to see an image of a lumbar puncture.

A biopsy is a surgical procedure in which a small sample of tissue is taken from the suspected tumor and examined under a microscope for malignancy. The results of the biopsy also provide information on the cancer cell type.

In some cases, such as brain stem gliomas, a biopsy might be too hazardous because removing any healthy tissue from this area can affect vital functions. In such cases, diagnosis must rely on less invasive and possibly less accurate measures. Of promise is the stereotactic technique (also called stereotaxy), which uses computers to provide three-dimensional views of very small areas. This may allow precise biopsies of cancer cells without affecting healthy brain tissue. Expertise in this technique is extremely important, however, and the technique is not widely available.

The survival rates in people with brain tumors depend on many different variables:

Whether the tumor is malignant or benign
Cancer cell type and location (location affects whether the tumor can be removed surgically or not)
The tendency to spread and the growth rate (tumor grade)
Patient's age
Patient's ability to function
Duration of symptoms

The outlook is poorer in the very youngest and very oldest patients, although younger patients who survive 2 years after diagnosis have a much better outlook than older patients.

Grading Tumors. Malignant primary brain tumors are classified according to tumor grade. Grade I is the least cancerous, and Grades IV and V are the most dangerous. Grading a tumor attempts to predict its tendency to spread and its growth rate. It is based on the appearance of the tumor cells as seen under a microscope.

Lower-grade (I and II) tumor cells are well defined and almost normal-shaped. (Some primary low-grade brain tumors are curable by surgery alone, and some are curable by surgery and radiotherapy. Low-grade tumors tend to have the most favorable survival rates and high-grade the least. However, this is not always the case. For example, some low-grade II gliomas are at very high risk for progression.)
Higher-grade (III and IV) tumor cells are abnormally shaped and are more diffuse, which indicates more aggressive behavior. (High-grade brain tumors usually require surgery, radiotherapy, chemotherapy, and possibly investigational treatments.)
In tumors that contain a mixture of different-grade cells, the tumor is graded using the highest-grade cells in the mixture, even when there are very few of them.

Biologic Markers. Elevated levels of certain cancer-associated molecules or compounds may be correlated with prognosis. For example, evidence of genetically mutated p53 indicates a poorer prognosis in younger patients with glioblastoma multiforme.

Elevations of epidermal growth factors (EGF) or vascular endothelial growth factors (VEGF) suggest aggressive tumors. High levels of the receptor for EGF (EGFR), in fact, are found in 70% of glioblastoma specimens.

Genetic Profiles of Cancer Cells. Analyses that identify genetic types may soon help clinicians determine if patients with specific brain tumor cells might respond better to one treatment than another. For example, specific genetic profiles of oligodendrogliomas can help predict how patients respond to nitrosourea alkylating drugs such as carmustine. Genetic variation tests are also being used to determine how patients may respond to epidermal growth factor receptor (EGFR) kinase inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa).

A genetic profile can also help give doctors a better idea of a patient’s prognosis and survival. In a 2006 study of patients with anaplastic oligodendroglioma, the status of specific chromosomal deletions within tumors was a better predictor of survival than which kind of treatment patients received. In fact, the researchers suggested that gliomas be classified according to chromosomal deletion status, and recommended that chromosomal testing be a regular part of diagnosis and treatment decisions.

Common Brain Tumors


GENERAL DESCRIPTION OF ASTROCYTOMAS: Derived from star-shaped glial cells called astrocytes.

Low-Grade (Usually I) Astrocytomas. Pilocytic gliomas.	Pilocytic gliomas occur mostly in children. Tumors are well differentiated. Cells are relatively normal and rarely metastasize. They grow relatively slowly. Pilocytic astrocytomas have the highest 5-year survival rates (greater than 70%). However, even well differentiated astrocytomas are life threatening if they are inaccessible.	Cancer may sometimes be completely removed through surgery, particularly if it occurs in the cerebellum. For recurrence or residual tumors, reoperation, radiotherapy, or chemotherapy may be given, depending on the circumstances. Repeat surgery for cerebellar astrocytoma is often very successful. For those who fail radiotherapy and chemotherapy, investigative drugs are used.
Low-Grade (II) Astrocytomas. Fibrillary, protoplasmic, and protoplasmic astrocytomas. Some pleomorphic xanthoastrocytomas.	Tumors are well differentiated. Cells are relatively normal and less malignant than those in higher grades. They grow relatively slowly but can spread. Survival rates average 5 years, but people can survive for a decade or more. Pleomorphic xanthoastrocytomas have a relatively favorable prognosis, but can recur and demonstrate aggressive clinical behavior. Low-grade astrocytomas generally occur in young adulthood, with a peak incidence in 30s and 40s.	Surgery, if possible, plus radiotherapy. Surgery alone in certain children, if possible. Trials on postoperative radiotherapy include the following: radiotherapy with or without chemotherapy; low-versus-high radiotherapy doses (studies suggest results are the same and high-dose causes more side effects); deferring radiotherapy until tumor progresses and symptoms occur. (A major study confirmed earlier ones that suggest that this approach has the same 5-year survival benefits -- about 65% -- as immediate postoperative radiotherapy.)
Malignant (High-grade III and IV) Astrocytomas. Anaplastic astrocytoma (gemistocytic and some pleomorphic xanthoastrocytomas). Usually mid-grade (III).	Tumors grow more rapidly than lower grades and infiltrate other nearby healthy cells. Not well-differentiated. Five-year survival rates are about 30%. Recurrence is common.	Treatment same for all high-grade malignant astrocytomas. Surgery, with removal of as much of tumor as possible followed by radiotherapy, with or without chemotherapy. The addition of chemotherapy, particularly being able to take more than 6 cycles, appears to improve survival rates. Carmustine (BCNU) most effective drug at this time. Other drugs and treatment sequences are under investigation. For example, temozolomide is showing promise for many patients, including the elderly. Topotecan may also be useful with other drugs or with radiation. For recurring gliomas, surgery with placement of wafers that release carmustine (Gliadel wafers) is the only proven beneficial therapy to date. Combinations, such as procarbazine and carmustine, provide benefits for recurrent anaplastic astrocytomas. Single drugs may be less toxic and as helpful for other recurrent gliomas. Temozolomide has been approved in Europe for high-grade recurrent gliomas and is proving to be beneficial. Other trials include the following: drugs that block small molecules involved in tumor growth; radioimmunotherapy using monoclonal antibodies; advanced radiotherapy techniques; intraarterial chemotherapy.
High-grade (IV and V). Glioblastoma (notably glioblastoma multiforme or GBM).	Very rapidly growing tumors that spread quickly. Represents about 25% of all primary brain tumors. Most common in older adults (over age 55) and affect more men than women. Recurrences are common in patients who achieve long-term survival.


GENERAL DESCRIPTION OF EPENDYMOMAS: Derived from cells that line the ventricles (fluid-filled brain cavities) and spinal cord central canal. Do not usually spread into normal brain tissue. Can block exits for cerebrospinal fluid and cause hydrocephalus. They constitute about 4% of all central nervous system tumors in adults and 10% of these tumors in children. About 30% of ependymomas develop in the spinal column.

Low-grade (I). Myxopapillary ependymoma (found in the spine). Subependymoma (found in one of the ventricles).	No or very slow growth. In addition to grade, risk is also based on location of the tumor. Tumors on the spinal cord are more accessible than those in the fourth ventricle or in the middle of the lower back portion of the brain.	Can often be removed and cured with surgery, particularly those on spinal cord. Radiation may be needed. Chemotherapy (avoid radiation, if possible) in children under age 6).
Low-grade (II). Papillary, cellular, and clear cell ependymomas.	Slow growth. Usually affect adults.	Surgery alone or followed by radiotherapy. For those who fail radiotherapy, possible use of nitrosourea-based chemotherapies or investigative drugs.
Grade III. Anaplastic ependymomas.	Spreads to the spinal fluid.	Surgery followed by radiotherapy to brain and spinal cord. Possible shunt.
Grade IV. Primitive neuroecto-dermal tumor (PNET). Composed of malignant forms of early, undeveloped nerve cells called neuroblasts. (This malignancy is also referred to as neuroblastoma.)	Very rare, but more common in children. Primitive nerve cells that grow very rapidly. Usually occur in cerebellum.	Surgery followed by radiotherapy to brain and spinal cord. Chemotherapy in young children. Investigative high-dose chemotherapy with stem cell rescue for children with relapsed cancer.


DESCRIPTION OF OLIGODENDROGLIOMAS: They develop from oligodendrocyte glial cells. These cells form the protective coatings around nerve cells. Pure cell types are rare. Most often occur in mixed gliomas. Categorized as either low- or high-grade. Most are low-grade II.

Low-grade: Low grade difficult to tell from astrocytomas, although they are usually calcified. Very likely to bleed. Usually spread along nerve pathways of the brain and spine and rarely outside this area. In spite of difficulty in removing surgically, in some patients survival can be 30 - 40 years. Usually have better prognosis than astrocytomas of equal grade. Occur mostly in middle-aged adults, although there is also a small peak of incidence in children.	Treatment usually delayed until progression causes symptoms. Surgery to remove whole tumor. Radiotherapy often follows in all adults over age 40 or in anyone in which tumor cannot be completely removed. Solid evidence is lacking on this approach, however, and there is some debate on its benefits. Trials using chemotherapy after radiation are promising. Two-thirds of patients respond to PCV (combination of procarbazine, lomustine and vincristine.) Sustained remissions averaging 16 years often achieved. Pure oligodendrogliomas respond better than mixed gliomas. Temozolomide is showing promise as second-line treatment. Others under investigation. Trials of additional chemotherapy for less well-differentiated tumors or for residual tumors after surgery.
High-grade. Anaplastic oligodendrogliomas.	Immediate treatment. Surgery to remove the whole tumor, if possible. Radiation typically follows surgery. Chemotherapy treatments either before or with radiation. Standard drugs are limited. Experts recommend trying investigative drugs. Temozolomide and retinoic acid may be useful. Possible additional drugs include melphalan, thiotepa, carboplatin, cisplatin, and etoposide. (Numerous biologic markers may help identify specific oligodendrogliomas that will respond better or worse to specific treatments.)


GENERAL DESCRIPTION OF MIXED GLIOMAS: Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

Grade determined by the highest-grade cell present in the tumor.	Same as for oligodendroglioma.



Meningiomas	They are found in the membranes around the brain and spinal column. They are usually benign and rarely invasive. In such cases, long-term outlook is very favorable. (Malignant forms, anaplastic meningiomas, and hemangiopericytomas are uncommon and occur in about 2% of cases.)	Usually watchful waiting. Aggressive surgery the treatment of choice, if possible, although 20% recur after 10 years. Malignant forms and those at the base of the skull difficult to impossible to remove surgically. Stereotactic radiosurgery or fractionated external beam radiotherapy showing promising results for some patients.
Cerebellar astrocytomas (located in cerebellum)	Located in the cerebellum. Usually low-grade, but depends on cell type. If surgical removal is complete, up to 90% survival rates. More common in children than adults.	Surgery primary treatment. Radiotherapy if removal is incomplete.
Brain Stem Gliomas	About 60 - 70% of brain stem tumors are diffuse, which are likely to spread and have a rapid onset of symptoms. Focal tumors tend to be solid or cyst-like. They generally develop gradually. Occurs in both children and young adults.	Radiation is usual treatment. Tumors in this area are rarely removed surgically since the nerve tissue in this area is responsible for vital life functions. Slow-growing tumors may only require watchful waiting. Trials using advanced radiotherapy techniques, gene therapy, immunotherapy, and other experimental drugs.
Medulloblastomas	Occurs in cerebellum (the lower portion of the brain), brainstem, and spinal cord. Usually fast-growing aggressive cells. Most common brain tumors in children and young people, causing between 15 - 20% of brain tumors. With aggressive therapy, in children 5-year survival rates between 60 - 80%. In patients who survive for 2 years after diagnosis, long-term survival rate is nearly 80%.	Treatment is usually surgery and radiotherapy followed by chemotherapy. A 2005 study found that a combination chemotherapy regimen may replace radiation for very young children. A 2006 study suggested that radiation and chemotherapy doses should be adjusted based on disease severity.
Optic Tract Gliomas	Spread along the optic nerve. Usually slow growing. Most often in children under age 10. Children with these tumors often have vision and hormonal problems.	Usually surgery if one eye is involved. Possible chemotherapy or radiation.

Treatment

The approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation treatment (also called radiotherapy), chemotherapy, or investigative procedures. Such treatments are used alone or, more commonly, in combinations. With some very slow-growing cancers, such as those that occur in the midbrain or optic nerve pathway, patients may be closely observed and not treated until the tumor shows signs of growth. The intensity, combination, and sequence of these treatments depends on the glioma subtype, its size and location, and patient age, health status, and medical history.

Recent advances in surgical and radiation treatments have significantly extended average survival times compared to those of standard therapy. Investigative treatments, such as monoclonal antibodies, are also showing promise. Patients or their caretakers should discuss all options thoroughly with a specialist in brain cancer. Different specialists may be needed to help manage symptoms.

Because of the low-cure rates of most malignant brain tumors, support for the patients and their families is a critical component of treatment and management. In response to one survey of patients with gliomas, experts made several recommendations to help both patients and caregivers:

Any physical impairment that could benefit from home equipment or physical therapy should be identified and treated.
Patients should discuss emotional as well as physical issues with their doctors. Depression, for instance, can be medically treated. Caregivers should also seek help for the inevitable stress, depression, and tension arising from their difficult role.
Relaxation techniques, meditation, and spiritual resources can be extremely helpful. Support groups are beneficial, but experts recommend separate groups for patients and their families.

Surgery

Surgery is usually the first step in treating most brain tumors. In some cases, however, such as most brain stem gliomas, it may be too dangerous to perform surgery. The object of most brain tumor surgeries is to remove or reduce as much of its bulk as possible. By reducing the size, other therapies, particularly radiotherapy, can be more effective. (Although there have been significant advances in brain surgeries, some experts argue that in high-grade gliomas extensive surgery may not improve survival rates at all and patients are best served by radiation therapy.)

The standard procedure is called craniotomy.

The neurosurgeon removes a piece of skull bone to expose the area of brain over the tumor.
The tumor is located and then removed.

Click the icon to see an illustrated series detailing craniotomy surgery.

There are various surgical options for breaking down and removing the tumor. They include:

Standard surgical procedures
Laser microsurgery (which produces great heat and vaporizes tumor cells)
Ultrasonic aspiration (which uses ultrasound to break the glioma tumor into small pieces, which are then suctioned out)

Relatively benign, grade I gliomas may be treated only by surgery. Some controversy exists over whether surgery for low-grade astrocytomas improves survival, although insufficient research has been conducted to prove its benefits for these gliomas. Most malignant tumors require additional treatments, including repeat surgery.

The surgeon's skill in removing the tumor as completely as possible is critical to survival. No one should be shy about asking the surgeon the number of similar procedures they have performed. (Asking for complication rates may not be useful, since a very experienced surgeon might operate on many high-risk patients.)

In most cancers outside the brain, surgical removal of a tumor usually involves taking out surrounding healthy tissue to be sure all cancer cells are gone. In the brain, however, removing healthy nearby nerve tissue can be as disastrous for the patient as the cancer itself. Special techniques have been developed to allow maximum removal of tumors while protecting healthy brain cells.

Stereotaxy. Stereotaxy has become a useful adjunct to both surgery (stereotactic surgery) and radiotherapy (stereotactic radiotherapy).

Cortical Localization. Cortical localization, or stimulation, uses a probe that passes a tiny electrical current to delicately stimulate a specific area of the brain. This produces a visible response of the body part (such as a twitch in a leg), which the stimulated region of the brain controls. The surgeon then knows to avoid those areas during the operation.

Image-Guided Surgery. Image guided surgery uses a three-dimensional picture of the patient's brain derived from computed tomography (CT) or magnetic resonance imaging (MRI) scans. An advanced technique called high-field interventional MR imaging (iMRI) is particularly accurate in identifying the tumor, but it is not widely available. The image, with various views of the brain, is displayed on a monitor in the operating room. During surgery, as the surgeon's instrument touches a part of the brain, a camera sends the image to a computer, which calculates the position of the surgical tool and displays it in its proper location on the 3-D image. The surgeon then can look at the monitor and see what structures to avoid.

Magnetic-Tipped Catheters. Neurosurgeons are investigating a technique in which external magnetic fields direct a magnet-tipped flexible catheter to the tumor site through a path that avoids harming certain important areas of the brain.

Heparin. Heparin, a blood-thinning drug, should be given at the time of surgery to help prevent blood clots.

Radiotherapy

Radiotherapy plays a central role in the treatment of most brain tumors, whether benign or malignant.

Radiotherapy after Surgery. Even when it appears that the entire tumor has been surgically removed, microscopic cancer cells often remain in the surrounding brain tissue. Radiation targets the residual tumor with the goal of reducing its size or stopping its progression. If the entire tumor cannot be removed safely, postoperative radiotherapy is often recommended. Even some benign gliomas may require radiation, since they may be life-threatening if their growth is not controlled.

Radiotherapy When Surgery Is not Appropriate. Radiotherapy may be used instead of surgery for inaccessible tumors or for tumors that have properties that are particularly responsive to radiotherapy.

Radiotherapy and Chemotherapy (Radiochemotherapy). Combining chemotherapy with radiotherapy is beneficial in some patients with high-grade tumors.

Various radiation treatments are now available.

Conventional radiotherapy uses external beams aimed directly at the tumor and is usually recommended for large or infiltrating tumors. It begins about a week after surgery and continues 5 days per week for 6 weeks. Older adults tend to have a more limited response to external-beam radiation therapy than younger people. According to a 2007 study in the New England Journal of Medicine, radiotherapy leads to a modest improvement in survival in elderly patients (70 years or older) with glioblastoma, and causes few negative impacts on quality of life or cognition.

For tumors that are highly localized, the radiation therapist has a choice of other radiation treatments:

Brachytherapy (also called interstitial radiation) uses radioactive "seeds" implanted directly in the tumor site. It is used as a booster to external beam radiation for patients with malignant astrocytoma. Brachytherapy appears to prolong survival in some aggressive gliomas. It may also be a safe and effective treatment for some children.
Intensity-modulated radiation therapy (IMRT) uses high-dose radiation beams that conform to the three-dimensional shape of the tumor.
Hyperfractionated radiation uses many small radiation doses to deliver a high total dosage of radiation.
A balloon catheter (GliaSite) that delivers radiation to the tumor cavity after surgery is showing promise.

Stereotactic radiosurgery has been developed to allow highly targeted radiation to be delivered directly to the small tumors while avoiding healthy brain tissue. The term radiosurgery is used because the destruction is so precise that it acts almost like a surgical knife. Some studies suggest that stereotactic radiosurgery improves survival, even in patients with the highly aggressive glioblastoma multiforme brain cancer. The procedure is being tested to boost standard radiotherapy.

Benefits of Stereotaxy. There are numerous benefits for stereotaxy:

Stereotaxy allows precisely focused, high-dose beams to be delivered to gliomas less than 1.25 inch in diameter.
Investigators have found that stereotactic radiosurgery can help them reach small tumors located deep in the brain that were previously considered inoperable.
Sometimes with stereotaxy only a single treatment may be needed.
Unlike traditional radiotherapy, stereotactic radiotherapy can be repeated, so it is useful for recurrent tumors when a patient has already received standard radiation treatments.
Combining stereotaxy with techniques that gauge speech and other mental functions in patients who are awake during the procedure can allow removal of brain tissue with a lower risk for complications in areas that affect such functioning.

The Planning Procedure. Stereotactic radiosurgery usually begins with a series of steps designed to plan the radiation target:

First, the patient is given a local anesthetic. In the standard operation, the patient's head must be totally immobilized by screwing a device known as a stereotactic frame into the patient's skull. (The frame procedure is effective only on brain tumors that have regular margins.) The frame is removed as soon as the whole procedure has been completed (about 3 - 4 hours).
A three-dimensional map, usually using magnetic resonance imaging (MRI) scans, is made of the patient's brain.
A computer program calculates dosage levels and specific areas for radiation targeting.

Advanced imaging techniques are now allowing frameless stereotaxy, which eliminates the frame and may be effective on more tumors. For example, high-field interventional MR imaging (iMRI) uses a guidance system based on cruise-missile technology to calculate the slightest variations in movements of the head and the location of the tumor relative to these movements. These calculations are then used to target the radiation beams directly on the tumor, even if the patient's head is moving slightly.

Delivery of Radiation Beams. Once the preliminary planning stage has been completed, treatment begins. Several advanced machines, such as the gamma knife, adapted linear accelerator (LINAC), and cyclotron, are being used with stereotaxy and can deliver very focused beams of radiation. Actual treatment takes 10 minutes to 1 hour.

The gamma knife uses gamma rays that are sent from multiple points to converge at a single point on the tumor. Although each gamma-ray beam is very low dosage, when the beams converge, the intensity and destructive power is very high. The gamma knife is limited to very small tumors and so is generally useful as a booster after standard radiation, surgery, chemotherapy, or combinations.
The linear accelerator (LINAC) produces photons (positively-charged atomic particles) in patterns that are matched to the tumor shape. The patient is positioned on a bed that can be moved to allow flexible positioning. It allows treatment over multiple sessions of small doses (fractionated stereotactic radiotherapy), instead of a single session. This means that larger tumors can be treated.
The cyclotron is basically an atom smasher, which produces protons that can be directed toward the tumor. As part of this procedure, some researchers are using boron neutron capture therapy (BNCT). BNCT employs intravenous administration of a boron compound, which is picked up more selectively by tumor cells than by normal brain tissue. The cyclotron delivers a single dose of radiation that triggers the release of high-energy particles from the boron to destroy nearby tumor cells. The cyclotron is available only in a very few locations, and there have been few trials to date.

Researchers are studying drugs that may be used along with radiation to increase the effectiveness of the treatment.

Radioprotectors. Drugs such as amifosistine (Ethyol) may protect healthy cells during radiation.

Radiosensitizers. Drugs such as fluorouracil (5-FU) and cisplatin (Platinol) may help make cancerous cells more sensitive to radiation.

Common Side Effects. Side effects of radiotherapy may vary depending on the tumor type and radiation treatment. Side effects may include hair loss, fatigue, and nausea and vomiting. Skin irritation and sensitivity may develop in the areas being treated. To prevent further irritation, avoid scratching or rubbing, avoid direct sunlight and heating pads, and do not attempt to treat the symptoms yourself. (Ask your doctor or radiation therapist for advice.) Brain swelling (edema) is another common radiotherapy side effect, which can sometimes cause an increase in brain tumor symptoms. Edema can be treated with steroids.

Tissue Injury. Radiation necrosis (total destruction of nearby healthy tissue) occurs in about 25% of patients treated with intensive radiation. Radiation necrosis can cause brain swelling and reduction in mental functions. The condition is treated with steroids. If steroids prove ineffective, surgery may be required to remove the damaged tissue.

New Tumors. Radiation therapy for childhood cancer is the most important risk factor for developing new brain and spinal column tumors, according to a 2006 study. The risk appears greatest for children who received radiation therapy before age 5. Researchers found that the risk of second primary tumors increased in relation to the radiation dose used to treat the first cancer.

Stroke. Survivors of childhood brain tumors who were treated with high doses of cranial radiation (especially doses greater than 50Gy) may be at increased risk of having a stroke later in life. In a study of nearly 2,000 brain tumor survivors, the average length of time from cancer diagnosis to stroke was 14 years.

Chemotherapy

Chemotherapy involves the use of drugs to kill or alter cancer cells. Chemotherapy is not an effective initial treatment for low-grade brain tumors, mostly because standard drugs cannot pass through the blood-brain barrier, the functional system that protects the brain by preventing certain molecules from reaching the central nervous system. In addition, not all types of brain tumors respond to chemotherapy. In general, chemotherapy for brain tumors is usually administered following surgery or radiation therapy.

The type of drug determines how it is administered. "Systemic delivery" drugs, which pass to the brain from the bloodstream, may be given by mouth, injected into a vein through an IV, or injected into an artery or a muscle. "Local delivery" drugs are placed within or around the brain tumor.

Scientists are working on several approaches to overcome the blood-brain barrier. Newer delivery methods include:

Interstitial chemotherapy uses disc-shaped polymer wafers (known as Gliadel wafers) soaked with carmustine, the standard chemotherapeutic drug for brain cancer. The surgeon implants the wafer directly into the surgical cavity after a tumor is removed.
Intrathecal chemotherapy delivers chemotherapeutic drugs directly into the spinal fluid.
Intraarterial chemotherapy delivers high-dose chemotherapy into arteries in the brain using tiny catheters. In one study, this approach was used within 2 weeks of radiotherapy in patients with high-grade astrocytomas, and the survival rates for glioblastoma multiforme tripled (20 months) compared to those who had chemotherapy and radiation at the same time.
Convection-enhanced delivery (CED) involves placing catheters into the brain tumor or nearby brain tissue to deliver slowly and continuously a cancer drug over several days.

Many different drugs, and drug combinations, are used for chemotherapy. Standard ones include:

Temozolomide (Temodar). Temozolomide, the first new drug approved for brain tumors in several decades, is taken by mouth as a pill. Temozolomide was first approved in 1999 for adult patients with anaplastic astrocytoma that did not respond to other treatments. In 2005, it was approved for use during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. The current first-line treatment for patients with glioblastoma is combined radiotherapy and temozolomide, followed by monthly doses of temozolomide after radiation treatment ends. A 2005 study, published in the New England Journal of Medicine, reported that adults with newly diagnosed glioblastoma who received temozolomide during and after radiation therapy had a higher rate of 2-year survival than patients who received radiation alone. A 2007 study in Neurology suggested that temozolomide works best for patients who are missing a particular gene (1p/19q). Temozolomide’s side effects are relatively minor, but may include constipation, nausea and vomiting, fatigue, and headache.

Carmustine (BCNU, BiCNU). Carmustine is used to treat many types of brain tumors, including glioblastoma, medulloblastoma, and astrocytoma. Carmustine is usually administered into the vein by IV. It can also be delivered through a wafer implant (Gliadel), which is surgically placed into the brain cavity after tumor removal. If carmustine is administered intravenously, side effects may include nausea and vomiting, fatigue, respiratory problems, and lung scarring (pulmonary fibrosis). Intravenous carmustine may cause bone marrow impairment, which results in decreased production of blood cells (a condition called myelosuppression). If carmustine is delivered through a wafer, side effects may include seizures, brain swelling, and infection within the brain cavity.

PCV Drug Regimen. PCV is an abbreviation for a chemotherapy regimen that combines procarbazine (Matulane), lomustine (CCNU), and vincristine (Oncovin). PCV is commonly used to treat oligodendrogliomas and oligoastrocytomas. The drugs may also be used alone or in other combinations. Procarbazine and lomustine are taken by mouth. Vincristine is given by either injection or IV. These drugs can cause significant side effects, including a drop in blood cell counts, nausea and vomiting, constipation, fatigue, and mouth sores. Procarbazine can cause high blood pressure when taken with foods high in tyramine. Patients should avoid foods such as beer, red wine, cheese, chocolate, processed meat, yogurt, and certain fruits and vegetables.

Platinum-Based Drugs. Cisplatin (Platinol) and carboplatin (Paraplatin) are standard cancer drugs that are sometimes used to treat glioma, medulloblastoma, and other types of brain tumors. These drugs are delivered by IV. In addition to nausea and vomiting, carboplatin can cause hair loss, and cisplatin can cause muscle weakness.

Patients with brain tumors, especially tumors that are in advanced stages, should consider enrolling in clinical trials. Many clinical trials are conducted through academic medical centers. Some promising areas of drug research include:

Other Chemotherapy Drugs. Researchers are investigating whether drugs used to treat other types of cancer may have benefits for brain tumors. These drugs include tamoxifen (Nolvadex) and paclitaxel (Taxol), which are used to treat breast cancer; topotecan (Hycamtin), which is used to treat ovarian and lung cancers; and vorinostat (Zolinza), which is approved for treatment of cutaneous T-cell lymphoma. Research presented at the 2007 meeting of the American Society of Clinical Oncology indicated that vorinostat may help patients with glioblastoma multiforme. Irinotecan (Campath) is another cancer drug that is being studied in combination treatment.

Molecular Targeted Therapy Drugs. One of the most promising developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotypes.

Promising targeted therapies for brain tumors include:

Anti-angiogenesis drugs block molecules involved with the growth of blood vessels that feed the tumor (a process called "angiogenesis," which is particularly important in the growth of glioblastomas.) These drugs starve tumors of vital nutrients and oxygen. Bevacizumab (Avastin) is being studied in combination with irinotecan for treatment of recurrent malignant gliomas. Bevacizumab targets vascular endothelial growth factor (VEGF), a specific angiogenesis growth factor. Cediranib (Recentin, AZD2171) is another VEGF inhibitor. In 2007 clinical trials, cediranib appeared to help make recurrent glioblastomas more responsive to chemotherapy and radiation treatment.
Tyrosine kinase inhibitor drugs block proteins involved in tumor cell growth and production. Drugs that specifically target epidermal growth factor receptors (EGFR) are a type of tyrosine kinase inhibitor of special interest in brain tumor research. These drugs include erlotinib (Tarceva), imatinib (Gleevac), and gefitinib (Iressa).
Farnesyl protein transferase inhibitors, such as tipifarnib (Zarnestra) and lonafarnib (Sarasar), are drugs that target a protein involved in the functioning of the cancer-causing Ras protein. Lonafarnib is being studied in combination with temozolomide, and tipifarnib in combination with radiation therapy.
MTOR inhibitors target other enzymes involved in cell growth and replication. Everolimus (RAD-001) is being studied for glioblastoma multiforme and astrocytoma. Everolimus is related to rapamycin (Siroliumus) and tacrolimus (Prograf), which are also being investigated for brain tumor treatment. These drugs are commonly used to suppress the immune system to prevent rejection after organ transplantation.

Other Treatments

Researchers are testing several drugs that target specific mechanisms associated with brain cancer. Combinations of some of these drugs, with or without standard chemotherapy and radiotherapy, may prove to be more effective than the use of any one treatment. It should be noted that none of these drugs at this time are producing cures, although some are improving survival.

Immunotherapy aims at using modalities that boost the patient's own immune system's ability to seek out and destroy cancerous cells.

Radioimmunotherapy with Monoclonal Antibodies. Radioimmunotherapy is showing special promise as a treatment approach to brain tumors. It typically uses monoclonal antibodies (MAbs), genetically engineered drugs designed to work against a specific target. MAbs are bound with radioactive substances and delivered directly into the brain and sometimes into the tumor. The MAbs are specifically designed to lock with the surface of certain cells in the tumor. Once they do so, the radioactive substances destroy the cell. The approach is essentially mini-radiation therapy without the damage or severe side effects of standard radiation treatments. Numerous different radioimmunotherapies are being investigated, and trials of some are reporting improved survival rates in high-grade gliomas. Some doctors believe this approach could prove to be the most effective therapy against these cancers.

Interleukins. Interleukins are natural proteins created by the immune system. Certain tumor cells carry receptors for specific interleukins, which are being investigated for a possible therapeutic role. For example, some drugs combine an interleukin with a drug that is toxic to cancer cells. The interleukin locks onto the receptor on the cancer cell, and the toxic chemical enters the tumor with the intent to kill it. Some interleukins are also being investigated alone for their own tumor-cell killing properties.

Tumor Vaccines. Tumor vaccines are being created, in which tumor cells are removed from the patient and inactivated. When the tumor cells are transferred back to the patient, they are harmless but can elicit a powerful immunologic response against the tumor. Vitespan (Oncophage) is a tumor vaccine that is showing promise against recurrent high-grade glioma, according to preliminary results from early trials presented at the 2007 annual meeting of the American Association of Neurological Surgeons.

Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Such drugs, when effective, would starve tumors of vital nutrients and oxygen. Angiogenesis is particularly important in the growth of glioblastomas, the most malignant brain tumors. Of particular promise are drugs that inhibit enzymes called tyrosine kinase, farnesyl protein transferase, and matrix metalloproteinase, which play critical roles in angiogenesis.

Farnesyl Protein Transferase Inhibitors. Farnesyl protein transferase inhibitors, such as tipifarnib, also called R115777 (Zarnestra) and lonafarnib (Sarasar), are drugs in a new class that block a mutated gene called the Ras gene, which is responsible for about 30% of cancers. Lonafarnib is in early trials in combination with temozolomide. Tipifarnib is also currently in early trials and may prove to be effective.

Tyrosine Kinase Inhibitors. Drugs that target growth factor receptors, such as tyrosine kinase, interfere with the pathway leading to angiogenesis. Some tyrosine kinase inhibitors -- including erlotinib (Tarceva), imatinib (Gleevac), gefitinib (Iressa), and others -- are being investigated in early trials for brain tumor treatment. Side effects include rash, diarrhea, nausea and vomiting. Some of these drugs may reduce white blood cell count or cause liver damage. Researchers are trying to identify biomarkers that could help predict which patients would best respond to tyrosine kinase inhibitor therapy.

Matrix metalloproteinase Inhibitors. Matrix metalloproteinase is an important enzyme in angiogenesis. Inhibitors of these enzymes, including marimastat, metastat, and prinomastat, are in early trials. Marimastat has been studied and has shown some benefits in early trials for patients with recurrent glioblastoma and anaplastic gliomas, particularly in combination with temozolomide.

Phophoinositide 3-Kinse (Pi3K) Inhibitors. Rapamycin and its analog (CCI-779) inhibit Pi3K, an enzyme involved in cell growth. Early trials using CCI-779 are underway. (Another rapamycin analog, everolimus, has different effects but is also being studied for its actions in inhibiting cell growth.)

Other Drugs that Block Angiogenesis. Thalidomide was one of the first drugs used to inhibit angiogenesis and has undergone several trials. There is some evidence that it may work more effectively for metastasized brain tumors than primary tumors. Other drugs in early trials with various effects on tumor growth include suramin, cilengitide, semaxanib, PTK787, and atrasentan.

Retinoids. Retinoids are vitamin A derivatives and act as differentiating drugs in cancer treatments. That is, they can convert immature, dividing tumor cells into mature cells, stopping tumor growth. Studies suggest that they have little benefits as single drugs. Combination with radiotherapy and other drugs may hold promise.

Inactivated Viruses. Investigators are finding that certain genetically inactivated viruses, such as the poliovirus or herpes virus, may prove to be valuable fighters of brain cancers. Such viruses can enter cells and destroy them but do not pose any danger for infection. For example, one specially designed herpes virus targets the enzyme thymidine kinase (an enzyme that promotes tumor growth). Some researchers believe that a combination of this virus with retinoids may be effective with few serious side effects. Other viruses are being investigated. A drug based on this model is years away, however.

Immunotoxins. Drugs called immunotoxins use natural toxins to kill malignant brain cells.

Drugs that use diphtheria toxins, including TransMID-107R and DAB(389)EGF), are the first immunotoxins to show some promise. Clinical trials are investigating them for gliomas and metastatic brain cancers. Other toxins under investigation include irofulven (a mushroom toxin) and chlorotoxin (a substance derived from scorpions).

Taurolidine. Taurolidine is a unique drug that prevents tumor formation and growth in animals. An early clinical trial in patients with high-grade gliomas is under way.

Protein-Blocking Drug. Another development is the discovery of a protein called BEHAB (Brain-Enriched Hyaluronan Binding Protein). BEHAB is produced only by invasive glioma tumor cells, not by normal brain tissue or noninvasive tumor cells. Breakdown of BEHAB releases a substance called HABD (hyaluronan-binding domain), which appears to give glioma cells the ability to invade other areas of the brain. Both BEHAB and HABD represent potential targets for new therapies.

Chemotherapy destroys not only cancer cells but also healthy cells, including special blood cells in the bone marrow called stem cells. Stem cells are immature cells from which all blood cells develop. Transplantation procedures using bone marrow or stem cells allow high-dose chemotherapy to be administered while protecting blood cells. The procedures are being tested for patients with recurrent brain tumors, such as medulloblastoma, primitive neuroectodermal tumors, and germ cell tumors. A 2003 study reported long-term survival in some patients who underwent this procedure

Photodynamic therapy uses a special drug (Photofrin) that is absorbed by the tumor and causes the cancer cells to become fluorescent when a laser is directed at them. It is being investigated in trials in combination with other treatments. A 2003 study reported encouraging results, notably in patients with recurring glioblastoma multiforme. In the study, more than half of these patients survived for at least a year.

Treatment of Complications

Some tumors, particularly medulloblastomas, interfere with the flow of cerebrospinal fluid and cause hydrocephalus (accumulation of fluid in the skull). This causes a build-up fluid in the ventricles (the cavities) in the brain. Symptoms include nausea and vomiting, severe headaches, lethargy, difficulty staying awake, seizures, visual impairment, irritability, and tiredness.

The ventricles of the brain are hollow chambers filled with cerebrospinal fluid (CSF), which supports the tissues of the brain.

Corticosteroids (commonly called steroids) such as dexamethasone (Decadron), prednisolone, and prednisone are used to treat hydrocephalus. Side effects include high blood pressure, mood swings, increased risk of infection, stronger appetite, facial swelling, and fluid retention.

Human corticotropin-releasing factor (hCRF), a naturally occurring neurohormone, appears to possess substantial anti-swelling properties and thus has been proposed as an alternative to corticosteroids in brain edema, with potentially fewer side effects. A hCRF drug called Xerecept is currently in clinical trials.

A shunt procedure may be performed to drain fluid. Shunts are flexible tubes used to reroute and drain the fluid.

Seizures are common in brain tumor cases, with younger patients having higher risks than older ones. Anti-epileptic medications, such as carbamazepine or phenobarbital, may treat seizures and are helpful in preventing recurrence. These drugs are not useful in preventing a first seizure, however, and they should not be used routinely to treat patients with newly diagnosed brain tumors. Anti-seizure medications should be used only for patients who are experiencing seizures. Despite these guidelines, a 2005 study in the Journal of the American Medical Association reported that nearly 90% of patients with newly diagnosed malignant glioma are treated with anti-epileptic drugs, although only 32% of the patients actually have seizures. Anti-seizure medications can interact with some of the chemotherapies used to treat brain cancers, including paclitaxel, irinotecan, interferon, and retinoic acid. Patients should discuss these interactions with their doctors.

Antidepressants are very useful for treating the emotional side effects of this disease. However, according to a 2005 Journal of the American Medical Association study, only 8% of patients with malignant gliomas receive antidepressant medication even though over 90% report depressive symptoms. Support groups can also have great benefit for both patients and families.

Resources

www.abta.org -- American Brain Tumor Association
www.cbtf.org -- Children's Brain Tumor Foundation
www.virtualtrials.com -- Musella Foundation for Brain Tumor Research and Information
www.braintumor.org -- National Brain Tumor Foundation
www.neurosurgery.org -- American Association of Neurologic Surgeons
www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.asco.org -- American Society for Clinical Oncology
www.cancer.gov/clinicaltrials -- Find clinical trials
www.radiologyinfo.org -- RadiologyInfo
www.plwc.org -- People Living with CAncer

References

Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2006 Nov 20;24(33):5277-82. Epub 2006 Nov 6.

Dunlap SM, Celestino J, Wang H, Jiang R, Holland EC, Fuller GN, et al. Insulin-like growth factor binding protein 2 promotes glioma development and progression. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11736-41. Epub 2007 Jul 2.

Flint-Richter P, Sadetzki S. Genetic predisposition for the development of radiation-associated meningioma: an epidemiological study. Lancet Oncol. 2007 May;8(5):403-10.

Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, et al. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology. 2007 May 22;68(21):1831-6.

Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12;356(15):1527-35.

Neglia JP, Robison LL, Stovall M, Liu Y, Packer RJ, Hammond S, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006 Nov 1;98(21):1528-37.

Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, et al. Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res. 2007 Feb 1;67(3):890-900.

Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA,et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Ask Someone Dealing With Depression: Should I Be Mad at My Friend For Telling People I'm Depressed?

TresSugar — Mon, 31 Aug 2009 04:00:00 -0700

Conventional Wisdom is a different kind of advice column. Your questions will be answered by people from all walks of life rather than by advice experts. This week, someone who deals with depression gives advice to a woman who is mad at her friend for telling people in her circle that she is depressed. If you have a question, you can submit them here.

This week's question:

I shared my struggles with depression with my closest female friend and told her that I did not want anyone else to know about it. She decided that because I wasn't answering her calls she would call the wife of a leader in our church and ask her for my husband's cell phone number so she could call him, asking about me. My "best friend" told the woman that I was going through something serious and when the woman said, "At least she's not seeking outside help" my friend said, "Well, I don't know for sure if she is or isn't."

Why else would she call her and say those things unless her intentions were to let her know about my situation and to inform her I "might" be seeking outside help for my depression? I found out about this conversation from the leader's wife and she only admitted to it after she knew that I knew about it. She insists that she only had my good in mind.

The thing is, it was a really huge deal to me that these people not be in on it because I know that they would attack me for being depressed in the first place, and also if I sought help outside of the church. The last thing I needed at that time was some church discipline. I was really suffering! I am so mad at my best friend for saying anything; should I forgive her?

Signed,

Angry and Depressed

To hear what someone dealing with depression has to say, read more.

Dear Angry and Depressed,

There seem to be three related but separate issues here: one is your anger at your friend, the second is the question of how your church is handling this, and the third is how to actually manage your struggle with depression.

As someone who has been through a lot with both depression and anxiety, I empathize with your situation. Depression hurts. As for your friend, I think you need to assess who this friend is to you, and whether she reached out to others because she was simply worried and didn't know how to handle it. While the outcome might have been a problem, if she did it out of legitimate concern I think she may be a real friend who just handled things badly because she cares and was confused about what to do.

My major concern with what you have said is that your church community thinks there is something wrong with getting outside help. Admittedly, I am not religious and have never belonged to a church, but I strongly feel that a community of any kind that is truly concerned with one of their members' well-being will support them in what they need, and not be judgmental about what that support might be. I think it would be worth explaining to your friend that what she might have considered finding you support actually feels like discipline, and that she needs to be more sensitive to what you need.

Finally there is the question of your depression itself. I do not want to assume you are in a situation where professional help from a therapist or doctor would be appropriate, but severe depression is something you need to talk to a professional about. If you feel like you are not getting help from your friends, family, or church, you're taking care of yourself by asking for outside help. Doctors are legally required to respect your privacy, and you could ask if they would refer you to a therapist.

Far more people struggle with depression than we can imagine when we are sitting alone with our thoughts, and there is support out there for you. You may just have been going through a rough patch and not need anything further, but depression is too serious a condition not to explore your options. Don't be discouraged if it doesn't seem like you can't find the right person to help you right away, but there are also lots of great people out there who can help. As for your friend, tell her how her action made you feel, give her the benefit of the doubt, and seek some relief for your pain from professionals. Good luck!

What Happens to Stuff You Forget on the Plane

SavvySugar — Mon, 17 Aug 2009 08:30:54 -0700

Kim Kardashian was lucky when she recovered the passport she left on the plane in South Africa last month, but most travelers aren't so fortunate in retrieving their forgotten valuables. If you've ever left something on the plane and wondered what happened to it, chances are it didn't end up in a black hole or even in someone else's possession; it's probably in the airline's lost and found warehouse.

Southwest has a warehouse where it collects all the stuff passengers forget, including coats, books, car seats, electronics (they find about five iPods every day), hundreds of cell phones, and the number one forgotten item - sunglasses. The warehouse estimates that 120,000 items come through every year, and only 10 percent of the belongings find their way back to their owners because few passengers call to track down lost items. After a few months, items are donated to the Salvation Army. Check out Southwest's enormous lost and found in the video below.

Source: Flickr User aaronescobar

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Biological and Medical Caus...
Cultural and Emotional Caus...
Risk Factors
Complications
Weight Loss and Maintenance...
Weight Management
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M. Copyright

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Urinary tract infection

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Urinary Tract Infections (UTIs) in the United States

According to Urologic Diseases in America, a report published in 2007 by the U.S. National Institutes of Health:

UTIs are the most expensive of all urologic diseases, accounting for about $3.5 billion a year in medical costs, including $96.4 million in prescriptions.
Over 60% of women will experience a UTI at least once in their lifetime. At least a third of women experience a UTI by the time they are 24 years old.
Only 20% of UTIs occur in men. However, men are far more likely than women to be hospitalized for an infection.
Childhood risk for UTIs is 2% for boys and 8% for girls. Vesicouretereal reflux, a condition in which urine backs up into the kidneys, affects about 10% of all children.

Circumcision Prevents UTIs

Baby boys who are uncircumcised are 10 - 12 times more likely than circumcised boys to develop UTIs during their first year of life, indicates the Urologic Diseases in America report.

High Doses of Zinc Increase UTI Risk

People who take very high daily doses of zinc supplements may face an increased risk for UTIs and other urologic problems, suggests a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc.
In general, the upper limit for zinc supplements should not exceed 40 mg/day. Eight mg/day for women and 11 mg/day for men are the recommended average doses. However, very high doses of zinc are sometimes prescribed for certain medical conditions, such as age-related macular degeneration.

Introduction

A urinary tract infection (UTI) is a condition where one or more structures in the urinary tract become infected after bacteria overcome its strong natural defenses. In spite of these defenses, UTIs are the most common of all infections and can occur at any time in the life of an individual. Almost 95% of cases of UTIs are caused by bacteria that typically multiply at the opening of the urethra and travel up to the bladder (known as the ascending route). Much less often, bacteria spread to the kidney from the bloodstream.

The male and female urinary tracts are relatively the same except for the length of the urethra.

Different classifications have been devised to help doctors choose treatments and determine the causes of UTIs.

Primary or Recurrent UTIs. UTIs are classified as primary or recurrent, depending on whether they are the first infection or whether they are repeat events.

Community- or Hospital-Acquired. UTIs are also sometimes grouped according to where they are acquired:

Community-Acquired Infections. Most UTIs are thought to develop in the community at large. It is unclear how primary community-acquired infections occur or how they are spread. Although most cases have been thought to arise sporadically, a rare outbreak in 1996 - 2000 caused by drug-resistant bacteria suggests epidemic spread of community-acquired infections could be more common than previously thought and may be spread via contaminated food. Most community-acquired infections are not serious and probably develop when the intestines become colonized with bacteria that are also predisposed to infecting the urinary tract.
Hospital-Acquired Infections. UTIs are also commonly acquired in the hospital, often due to contaminated urinary catheters. Hospital-acquired infections (known as nosocomial infections) tend to be more serious because the bacteria that cause them are often resistant to drug treatment and patients are often in poor general health.

Uncomplicated and Complicated. UTIs are also sometimes further defined as either being uncomplicated or complicated depending on the factors that trigger the infections.

Uncomplicated infections are only associated with bacterial infection, most often Escherichia coli (E. coli). They affect women much more often than men.
Complicated infections, which occur nearly as often in men as women, are also caused by bacteria but they occur as a result of some anatomical or structural abnormality. Often they are associated with catheter use in the hospital setting, bladder and kidney dysfunction, or kidney transplant (especially in the first three months after transplant). Recurrences occur in up to 50 - 60% of patients with complicated UTI if the underlying structural or anatomical abnormalities are not corrected.

Classifications Based on Symptoms and Levels of Infection. UTIs can also occur without symptoms and with symptoms but very low bacterial levels.

When bacteria are present and there are no symptoms it is called asymptomatic UTI or also bacteriuria.
Some patients can also have symptoms of infection with very low bacterial counts. In such cases, the condition is called acute urethral syndrome.

Cystitis. Cystitis is the most common urinary tract infection and is sometimes referred to as acute uncomplicated UTI. It occurs in the lower urinary tract (the bladder and urethra) and nearly always in women. In most cases, the infection is brief and acute and only the surface of the bladder is infected. Deeper layers of the bladder may be harmed if the infection becomes persistent, or chronic, or if the urinary tract is structurally abnormal.

Pyelonephritis (Kidney Infection). When infection spreads to the upper tract (the ureters and kidneys) it is called pyelonephritis, or more commonly, kidney infection. As many as half of all women with cystitis may have infections of the upper urinary tract at the same time as cystitis.

Click the icon to see an image of the kidney.

Urethritis. When infection is limited only to the urethra, the infection is known as urethritis. This is a common sexually transmitted disease in men.

Complicated UTIs may develop because of any one of a number of physical problems and affect any gender and age group. The common feature in most complicated UTIs is the inability of the urinary tract to clear out bacteria because of a physical condition that causes obstruction to the flow of urine or problems that hinder treatment success.

Most women who have had an uncomplicated UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one. Between 3 - 5% of women have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode.

Recurrence is often categorized as either reinfection or relapse:

Reinfection. About 80% of recurring UTIs are reinfections. A reinfection occurs several weeks after antibiotic treatment has cleared up the initial episode and can be caused by the same bacterial strain that caused the original episode or a different one. The infecting organism is usually introduced through the rectal region from fecal matter and moves up through the urinary tract.
Relapse. Relapse is the less common form of recurrent urinary tract infection. It is diagnosed when a UTI recurs within 2 weeks of treatment of the first episode and is due to treatment failure. Relapse usually occurs in kidney infection (pyelonephritis) or is associated with obstructions such as kidney stones, structural abnormalities or, in men, chronic prostatitis.

When a person has no symptoms of infection but significant numbers of bacteria have colonized the urinary tract, the condition is called asymptomatic UTI (also called asymptomatic bacteriuria). (In general, there must be at least 100,000 bacteria per milliliter of urine.) The condition is harmless in most people and rarely persists, although it does increase the risk for developing symptomatic UTIs.

Screening for asymptomatic bacteriuria is not necessary during most routine medical examinations, with the following exceptions:

Pregnant women. Pregnant women with asymptomatic bacteriuria have a 30% risk for acute pyelonephritis in their second or third trimester. Therefore, they need screening and treatment for this condition.
People undergoing urologic surgery (such as prostate surgery in men). The presence of an infection during surgery can lead to serious consequences.

Some groups recommend screening women with diabetes for asymptomatic bacteriuria. However, a 2003 study suggested that treating women who test positive for this condition does not reduce their risk of complications from UTIs. Asymptomatic bacteriuria may be an indicator for serious health problems in the elderly, but screening for the condition is not warranted in this group.

Some people have symptoms of cystitis but have a bacterial count lower than that ordinarily found in UTI. Such patients are sometimes diagnosed with acute urethral syndrome. This condition is usually caused by E. coli or other bacteria that cause cystitis, but in lower numbers, or by a sexually transmitted disease such as Chlamydia or gonorrhea.

Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. The average age of patients with IC is 40 years, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. These women often complain of experiencing pain during sex. Pelvic pain, depression, and stress may intensify symptoms. Women with IC also frequently suffer from other conditions, including allergies, urinary incontinence, sinusitis, and irritable bowel syndrome (IBS). Some doctors think that IC may be related to autoimmune diseases such as fibromyalgia and lupus.

IC is difficult to diagnose and treat. Pentosan (Elmiron) is the most frequent drug treatment, but doctors prescribe other medications as well (see Medications section). Some evidence suggests that diet can worsen IC symptoms. For instance, patients should avoid coffee (both caffeinated and decaf), alcohol, cola, vinegar, citrus fruits, tomatoes, chili, strawberries, pineapple, onions, pizza, chocolate, and apples, according to research presented at the 2006 American Urological Association scientific meeting.

The Urinary System. The urinary system helps maintain proper water and salt balance throughout the body and also expels urine from the body. It is made up of the following organs and structures:

The two kidneys, located on each side below the ribs and toward the middle-back, play the major role in this process. They filter waste products, water, and salts from the blood to form urine.
Urine passes from each kidney to the bladder through thin tubes called ureters.
Ureters empty into the bladder, which rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine, which is then eliminated from the body via another tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)

Defense Systems Against Bacteria. Infection does not always occur when bacteria are introduced into the bladder. A number of defense systems protect the urinary tract against infection-causing bacteria:

Urine itself functions as an antiseptic, washing potentially harmful bacteria out of the body during normal urination. (Urine is normally sterile, that is, free of bacteria, viruses, and fungi.)
The ureters are structurally designed to prevent urine from backing up into the kidney.
The prostate gland in men secretes infection-fighting substances.
The immune system in both sexes continuously fights bacteria and other harmful micro-invaders. In addition, immune system defenses and antibacterial substances in the mucous lining of the bladder eliminate many organisms.
In normal fertile women, the vagina is colonized by lactobacilli, beneficial microorganisms that maintain a highly acidic environment (low pH). Acid is hostile to other bacteria. Lactobacilli also produce hydrogen peroxide, which helps eliminate bacteria and reduces the ability of E. coli to adhere to vaginal cells. (E. coli is the major bacterial culprit in urinary tract infections.)
Some interesting research suggests that when bacteria infect the bladder, the cells that line the bladder literally sacrifice themselves and self-destruct (a process called apoptosis). In so doing, they fall away from the lining, carrying the bacteria with them. This eliminates about 90% of the E. coli.
Some researchers have identified a possible natural antibiotic called human beta-defensin-1 (HBD-1), which fights E. coli within the female urinary and reproductive tracts.

Click the icon to see an image of the prostate gland.

Causes

The bacterial strains that cause UTIs include:

Escherichia (E.) coli is responsible for 75 - 90% of uncomplicated cystitis cases in younger women and in more than half the cases in older women (over age 50). In most cases of UTI, E. coli, which originates as a harmless microorganism in the intestines, spreads to the vaginal passage, where it invades and colonizes the urinary tract. Some bacteria may be able to invade into deeper tissue in the bladder, where they survive to reinfect the patient after resolution of the previous infection.
Staphylococcus saprophyticus accounts for 5 - 15% of UTIs, mostly in younger women. Infections caused by this bacterium tend to have a seasonal variation, with a higher incidence in the summer and fall than in the winter and spring.
Klebsiella, Enterococci bacteria, and Proteus mirabilis account for most of remaining bacterial organisms that cause UTIs. They are generally found in UTIs in older women.
Rare bacterial causes of UTIs include ureaplasma urealyticum and Mycoplasma hominis, which are generally harmless organisms.

The bacteria that cause kidney infections (pyelonephritis) are generally the same bacteria that cause cystitis. There is some evidence, however, the E. coli strains in pyelonephritis are more virulent (able to spread and cause illness).
Complicated UTIs that are related to physical or structural conditions are apt to be caused by a wider range of organism. E. coli is still the most common organism, but others have also been detected, including Klebsiella, P. mirabilis, and Citrobacter.
Fungal organisms, particularly Candida species. (Candida albicans, for example, causes the so-called "yeast infections" that also occur in the mouth, digestive tract, and vagina.)
Other bacteria associated with complicated or severe infection include Pseudomonas aeruginosa, Enterobacter, and Serratia species, gram-positive organisms (including Enterococcus species), and S. saprophyticus.

Recurring infections are often caused by different bacteria than those that caused a previous or first infection.

Even if the reinfecting bacterium is still E. coli, it may be a variant of the original infecting E. coli strain. Such strains produce substances, such as one called P fimbriae, which tend to make the bacteria more infectious. Uncommon causes of reinfection include Ureaplasma and Mycoplasma hominis, which are sometimes associated with acute urethral syndrome.

The bacteria that cause most UTIs are very common. Nearly everyone harbors them. It is not clear how they proliferate and break down the natural defenses of the body. Among the possible ways this occurs are:

Changes in the Acid-Alkaline Balance of the Urinary Tract. Changes in the amount or type of acid within the genital and urinary tracts are major contributors to lowering the resistance to infection. For example, beneficial organisms called lactobacilli increase the acidic environment in the urinary tract. Reductions in their number (which, for example, occurs with estrogen loss after menopause), increases pH and therefore the risk of infection.

Biofilm. One theory, called the biofilm mode of growth, suggests that sometimes bacteria form capsules that adhere to the urinary tract, protecting them from many of the body's normal defenses.

Symptoms

Symptoms of lower urinary tract infections usually begin suddenly and may include one or more of the following signs:

The urge to urinate frequently, which may recur immediately after the bladder is emptied.
A painful burning sensation. (If this is the only symptom, then the infection is most likely urethritis.)
Discomfort or pressure in the lower abdomen. The abdomen can feel bloated.
Cramping in the pelvic area or back.
The urine often has a strong smell, looks cloudy, or contains blood. This is a sign of pyuria, or a high white blood cell count in the urine, and is a very reliable indicator of urinary tract infections.
Occasionally, fever develops.

Symptoms of kidney infections tend to affect the whole body and be more severe than those of cystitis. They may include:

Symptoms of lower UTIs that persist longer than a week. (Sometimes lower UTI symptoms may be the only signs of kidney infection. People at highest risk for such "silent" upper urinary tract infections include patients with diabetes, impaired immune systems, or a history of relapsing or recurring UTIs.)
An increased need to urinate at night.
Chills and persistent fever (typically lasting more than 2 days).
Pain in the flank (pain that runs along the back at about waist level).
Vomiting and nausea.

UTIs in infants and preschool children tend to be more serious than those that occur in young women, in part because they are more likely to occur in the kidneys and upper urinary tract. (Older children are more likely to have lower urinary tract infections and standard symptoms.) Infants and young children should always be checked for UTIs if the following symptoms are present:

A persistent high fever of otherwise unknown cause, particularly if it is accompanied by signs of feeding problems and debility, such as listlessness and fatigue. (Studies have reported that up to 5% of infants and toddlers who are brought to the emergency room with fevers have UTIs. Scarring is a risk so very young children with UTIs need to be screened.)
Painful, frequent, and foul smelling urine. (Parents are generally unable to identify a UTI just by the smell of their child's urine. Medical tests are needed.)
Cloudy urine. (If the urine is clear, the child most likely has some other ailment, although it is not absolute proof that the child is UTI-free.)
Abdominal and low back pain may be present.
Vomiting and abdominal pain (usually in infants).
Jaundice (yellowing of the skin and the whites of the eyes) in infants, particularly if it develops after 8 days of age.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing the skin and whites of the eyes to have a yellowish appearance. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The classic lower UTI symptoms of pain, frequency, or urgency and upper tract symptoms of flank pain, chills, and tenderness may be absent or altered in older patients with UTIs. In one study, only 20% of these patients had new urinary complaints, and many have no symptoms at all.

Symptoms of UTIs that may occur in seniors but not in younger adults may include mental changes or confusion, nausea or vomiting, abdominal pain, or cough and shortness of breath. Concomitant illness may further confuse the picture and make diagnosis difficult.

Risk Factors

After the flu and common cold, urinary tract infections (UTIs) are the most common medical complaint among women in their reproductive years. Women are 30 times more likely to have UTIs than men. At least a third of American women are diagnosed with a UTI by the time they are 24 years old. Every year, 11% of American women have at least one such infection, and up to 60% of all women will develop a UTI at some time in their lives. A third of these women will have a recurrence within a year. Furthermore, each year about 250,000 women develop kidney infections (pyelonephritis) and 100,000 are hospitalized for treatment.

According to a 2007 report from the U.S. National Institutes of Health, urinary tract infections in both women and men are the most expensive of all urologic problems. Nationally, UTIs account for about $3.5 billion a year in medical costs.

Structure of the Female Urinary Tract. In general, the higher risk in women is mostly due to the shortness of the female urethra, which is 1.5 inches compared to 8 inches in men. Bacteria from fecal matter can be easily transferred to the vagina or the urethra.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Sexual Behavior. Frequent or recent sexual activity is the most important risk factor for urinary tract infection in young women. Nearly 80% of all urinary tract infections occur within 24 hours of intercourse. (Sexual activity is less associated with cystitis in women after menopause.)

UTIs are very rare in celibate women. It is important to stress, however, that UTIs are NOT sexually transmitted infections, although these infections ( Chlamydia trachomatis, gonorrhea, or herpes simplex virus) may increase the risk for UTIs.

In general, however, it is the physical act of intercourse itself that produces conditions that increase susceptibility to the UTI bacteria, with some factors increasing the risk:

Women having sex for the first time or who have intense and frequent sex after a period of abstinence are at risk for a condition called "honeymoon cystitis."
A sudden increase in the frequency of sexual intercourse poses a significant risk for UTI, particularly if a diaphragm is used.
Sexual position (such as the woman on top) can contribute to the risk.

Click the icon to see an image of a diaphragm.

Contraceptives may also contribute to risk in a number of ways:

The spring-rim of the diaphragm may bruise the area near the bladder neck, making it susceptible to bacteria.
Unlubricated condoms may injure vaginal tissue and make it vulnerable to infections. (Using a sterile water-based lubricant, such as KY jelly, may help reduce this risk. Petroleum-based lubricants should be avoided because they weaken latex condoms.)
Some women experience UTI as an allergic reaction to latex in condoms or to oral contraceptives.
Use of spermicide, such as nonoxynol-9, doubles or triples a women's risk for UTI, regardless of whether it is used with a condom or diaphragm. Spermicides also pose a risk for sexually transmitted infections, and experts warn against their use.

Pregnancy. Although pregnancy does not increase the rates of asymptomatic bacteriuria, it does increase the risk that it will progress to a full-blown infection. About 2 - 11% of pregnant women have asymptomatic bacteriuria and, of those, 13 - 27% will develop a kidney infection late in their term. (However in early pregnancy, frequent urination -- a common symptom of UTI -- is most likely due to pressure on the bladder.)

Although all pregnant women should be tested for UTIs, women at highest risk have the following conditions or situations:

Diabetes
Sickle cell trait
Low-income
Have had many children
History of childhood UTIs
Have undergone a cesarean section with catheterization of the bladder
Have received epidural anesthesia

Women who have had a UTI before or during pregnancy also have a higher risk of developing recurrent urinary tract infections after delivery. About 25 - 33% of women who experience bacteriuria during pregnancy will have another urinary tract infection, sometimes as many as 10 - 14 years later.

Menopause. The risk for UTIs, both symptomatic and asymptomatic, is highest in women after menopause. Studies indicate that between 20 - 25% of women over 65 years old have UTIs, and 10 - 15% have asymptomatic bacteriuria (compared to 2 - 5% of young women). Sexual activity plays a lesser role in UTIs in older women than in younger women. In general, biologic changes due to menopause put older women at particular risk for primary and recurring UTIs:

With estrogen loss, the walls of the urinary tract thin, weakening the mucous membrane and reducing its ability to resist bacteria. The bladder may lose elasticity and fail to empty completely.
Estrogen loss has also been associated with reduction in certain immune factors in the vagina that help block E. coli from adhering to vaginal cells.
Levels of lactobacilli (protective bacteria) decline after menopause, perhaps also due to drops in estrogen.

Some women carry the blood group P1, which, as they get older, is associated with high levels of specific cells in the vagina and urethra that bind to a specific strain of E. coli that is resistant to normal infection-fighting mechanisms.

Other Risk Factors in Women. Women who have skin allergies to ingredients in soaps, vaginal creams, bubble baths, or other chemicals that are used in the genital area are at high risk for UTIs. In such cases, the allergies may cause small injuries that can introduce bacteria.

Most women who have had one UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one.

Between 3 - 5% of women, however, have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode. The major groups of women who are at highest risk for recurrent infections are young highly sexually active women and postmenopausal women. It might be argued that nearly all women who have a urinary tract infection are at risk for another, particularly if they are not treated for the first one.

Lifestyle Factors Increasing the Risk for Recurrence. Why urinary tract infections become chronic and recurring in many women is not entirely clear, but researchers are identifying certain lifestyle factors that may increase the risk in specific women:

Engaging in sexual intercourse more than four times a month.
Recent changes in sexual partners.
Having a mother with a history of UTIs.
Having a first UTI before age 15.
Use of spermicides.
Smoking and taking tub baths may also increase the risk for recurrent urinary tract infections, but they are less significant than other risk factors.

Biologic and Physical Factors. Some women may also have certain biologic or anatomical factors that increase the risk for recurring UTIs:

Having a shorter than average distance between the urethra and the anus.
Certain women may carry a compound called sialosyl galactosyl globoside (SGG) on the surface of kidney cells, which is a highly powerful receptor for E. coli bacteria.
Certain women have a genetic susceptibility to becoming infected in the vaginal area with greater numbers of disease-causing organisms that adhere to the lining.
Certain women may be deficient in human beta-defensin-1 (HBD-1), believed to be a naturally occurring antibiotic.

Risk Factors for Recurrence in the Aging Woman. In addition to menopause, other very strong risk factors for recurrences in older women include urinary incontinence and previous operations on the genital or urinary tracts. Additional risk factors for UTIs in older women include diabetes, vaginal itching or dryness, having had children, and poor overall health.

Each year, about 3% of American children develop urinary tract infections. During the first few months of life, UTIs are more common in boys than in girls. Boys who are uncircumcised are about 10 - 12 times more likely than circumcised boys to develop UTIs by the time they are 1 year old. After the age of 2 years, UTIs are far more common in girls. Throughout childhood, the risk of UTIs is about 2% for boys and 8% for girls. As with adults, Escherichia coli (E. coli) is the most common cause of UTIs in children.

Vesicoureteral Reflux (VUR). Vesicoureteral reflux (VUR) affects about 10% of all children. It is the source of urinary tract infections in 30 - 50% of childhood cases. This is a structural defect of the valve-like mechanism between the ureter and bladder that allows urine to flow backward, carrying infection from the bladder up into the kidneys. VUR also puts children at risk for recurrence. Such recurrences nearly always occur within the first 6 months after the first UTI.

Click the icon to see an image of vesicoureteral reflux.

Men become more susceptible to UTIs after 50 years of age, when they begin to develop prostate problems. Benign prostatic hyperplasia (BPH), enlargement of the prostate gland, can produce obstruction in the urinary tract and increase the risk for infection. In men, recurrent urinary tract infections are also associated with prostatitis, an infection of the prostate gland that is caused by E. coli. Although only about 20% of UTIs occur in men, these infections can cause more serious problems than they do in women. Men with UTIs are far more likely to be hospitalized than women. [See In-Depth Report #71: Benign prostatic hyperplasia.]

Hospitalizations and Catheters. About 40% of all infections that develop in hospitalized patients are in the urinary tract. The organisms that cause infections in hospitals (called nosocomial infections) are usually different from those that commonly cause UTIs. They are also more likely to be resistant to standard antibiotics. Hospitalized patients at highest risk for such infections are those with in-dwelling urinary catheters, patients undergoing urinary procedures, long-stay elderly men, and patients with severe medical conditions.

About 80% of UTIs in the hospital are due to catheters. Nearly all patients who need urinary catheters develop high levels of bacteria in their urine, and the longer the catheter is in place, the higher the risk for infection. Catheterized patients who develop diarrhea are nine times more likely to develop UTIs than are patients without diarrhea. In most cases of catheter-induced UTIs, the infection produces no symptoms. Because of the risk for wider infection, however, anyone requiring a catheter should be screened for infection. Catheters should be used only when necessary and should be removed as soon as possible.

Nursing Homes. All older adults who are immobilized, catheterized, or dehydrated are at increased risk for UTIs. Nursing home residents, particularly those who are incontinent and demented, are at very high risk. Up to 40% of elderly patients who live in nursing homes will contract a urinary tract infection.

Some people have structural abnormalities of the urinary tract that cause urine to stagnate or flow backward into the upper urinary tract. Such conditions include:

A prolapsed bladder (cystocele) can result in incomplete urination so that urine collects, creating a breeding ground for bacteria.
Tiny pockets called diverticula sometimes develop inside the urethral wall and can collect urine and debris, further increasing the risk for infection.

Click the icon to see an image of a cystocele.

Antibiotics often eliminate lactobacilli, the protective bacteria, along with harmful bacteria. This causes an overgrowth of E. coli in the vagina. In one study, the risk for UTI increased during the 15 - 28 days that women were taking antibiotics. In fact, some research suggests that taking antibiotics for a urinary tract infection increases the risk for a subsequent infection.

Diabetes. Diabetes puts women at significantly higher risk for asymptomatic bacteriuria. The longer a woman has diabetes, the higher the risk. (Control of blood sugar has no effect on this condition.) The risk for UTI complications is also higher in people with diabetes. In fact, certain UTI-related abscesses are reported only in patients with diabetes. These patients are also at higher risk for fungal-related UTIs.

Kidney Problems. Nearly any kidney disorder increases the risk for complicated UTIs.

AIDS and Immunosuppressed Patients. Any infection is dangerous in people whose immune systems are damaged, and UTIs are no exception, particularly pyelonephritis.

Sickle-Cell Anemia. Patients with sickle-cell anemia are particularly susceptible to kidney damage from their disease, and UTIs put them at even greater risk.

Kidney Stones. In some cases, kidney stones can cause urinary tract obstruction that leads to infection, particularly pyelonephritis. Symptoms of severe urinary tract infection in people with a history of kidney stones may indicate obstruction, which is a serious condition.

Click the icon to see an image of kidney stones.

Zinc. High doses of zinc supplements may increase the risk for urinary tract infections and other urologic problems, according to a 2007 study. Researchers found that hospitalizations for urinary complications were far more common among patients who took high doses of zinc than those who did not take this mineral supplement. Patients in the study took 80 mg of zinc daily. In general, the recommended daily amount for zinc is 8 mg/day for women and 11 mg/day for men. Higher doses of zinc are sometimes prescribed for people with certain medical conditions, such as age-related macular degeneration (an eye disease). However, no one should take more than 40 mg/day of zinc without talking to a doctor.

Complications

Urinary discomfort and emotional distress are the primary concerns in most women with recurrent UTIs. One study reported significant impairment of a woman's quality of life during symptom periods, which affected social function, vitality, and emotional well-being.

Nearly all urinary tract infections are mild, treatable, and have no long-term consequences. Serious physical complications can occur in some cases, however, most often in hospitalized patients.

Obstruction and Widespread Infection. Very severe upper urinary tract infections may cause obstruction that results in widespread and even life-threatening infection. Patients who develop UTIs in the hospital are at higher risk for such infections than those outside the hospital. In one particularly dangerous form of kidney infection that obstructs the ureter, mortality rates exceed 40%. This specific condition should be suspected in people with diabetes who have severe UTIs.

Kidney Damage. In high-risk adults, recurrent UTIs may cause scarring in the kidneys, which over time can lead to hypertension and eventual kidney failure. People with UTIs who develop serious kidney disease from UTIs are likely to have other predisposing diseases or structural abnormalities. (Recurrent urinary tract infections, even in the kidney, almost never lead to progressive kidney damage in otherwise healthy women.)

Urge Incontinence. Recurrent UTIs may increase the risk for urge incontinence after menopause. (People with urge incontinence experience leakage and the need to urinate frequently.) [See In-Depth Report #50: Urinary incontinence.]

Kidney Stones. Kidney stones can be caused by urinary tract infections (as well as increase the risk for UTIs in the first place). Those known as struvite stones are almost always caused by urinary tract infections due to bacteria that secrete certain enzymes. These enzymes raise urine concentrations of ammonia, which composes the crystals forming struvite stones. The stone-promoting bacterium is usually Proteus, but others include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci.

Urinary tract infections during pregnancy pose particular risks for both mother and child:

If asymptomatic bacteriuria is not detected and treated promptly in pregnant women, as many as 25% develop kidney infection (pyelonephritis), which in turn increases the risk for premature birth, infant mortality, and later chronic kidney disease.
Even if kidney infection does not develop, untreated UTIs occurring in the first and third trimester of pregnancy slightly increase the risk for mental retardation and developmental delay in the infant.
Certain strains of E. coli can increase the risk for complications during pregnancy, including miscarriage or premature delivery, even if pyelonephritis does not develop.
Infants of women who harbor Ureaplasma urealyticum also have an increased risk for respiratory infections.

Urinary tract infections are a major cause of hospitalization in children. Untreated, they can be very serious, particularly in children under 4 years old. Fortunately, with prompt treatment, childhood cases of upper urinary tract infections rarely cause any serious consequences.

Spread of Infection. Widespread infection is a major complication of a primary infection. Although laboratory tests in some infants with UTI may suggest the presence of meningitis (inflammation of the spinal column), in most of these UTI cases the outcome is good with treatment, and there appear to be no neurological symptoms afterward.

Kidney Scarring. Kidney scarring is the major concern in children who develop serious or recurrent UTIs. Scarring in young growing kidneys is much more serious than in the mature kidney. Over the years, it increases the risk for hypertension and kidney failure. In one study, evidence of scarring developed in 6% of children who had been hospitalized for a urinary tract infection. Children most at risk for this complication include:

Children with vesicoureteral reflux (VUR). (Carefully managed vesicoureteral reflux without scarring is not associated with serious complications.)
Abnormally structured urinary tracts
Recurrent kidney infections
A delay in treating an acute UTI

One encouraging study followed children with evidence of kidney scarring for 16 - 26 years. On average, their total kidney function was well preserved, although the scarred kidney had signs of lower function and patients with scarring in both kidneys were at higher risk for future problems. Earlier studies have shown poorer results, which suggests that outcomes are now improving with early detection and better follow-up.

Women with diabetes have more frequent and more severe UTIs than women without the disease. They also are more frequently hospitalized for kidney infections. In fact, the most serious, but rare, complications of urinary tract infections (pyelonephritis, widespread infections, abscesses, inflammation of the bladder wall) occur mostly in patients with diabetes.

Diagnosis

In younger women, UTI symptoms plus positive results on an over-the-counter dipstick test are often enough to make a diagnosis. Symptoms include frequent urination and vaginal burning, without other complications such as fever, chills, and pain in the kidney. In such cases, young women can usually receive treatment by calling a health professional (usually a nurse) who will prescribe antibiotics. A good response to antibiotic therapy usually eliminates the need for further tests.

This course is recommended only for nonpregnant women at low risk for recurrent infection who do not have symptoms suggesting other problems, such as vaginitis. In some centers, women who are treated over the phone have to be younger than 55 years old; other patients need to see a doctor for evaluation. Pregnant women should be screened for E. coli because of the risk of complications, including miscarriage, from certain strains of these bacteria.

About half of women with symptoms of a UTI actually have some other condition, such as irritation of the urethra, vaginitis, interstitial cystitis, or sexually transmitted diseases (STDs). Some of these problems may also accompany or lead to UTIs.

Vaginitis. Vaginitis is a common vaginal infection that can be caused by a fungus (candidiasis) or bacteria. Occasionally, the infection causes frequent urination, mimicking cystitis. The typical symptoms of vaginitis are itching and an abnormal discharge.

Sexually Transmitted Diseases. Women with painful urination whose urine does not exhibit signs of bacterial growth in culture may have a sexually transmitted disease. The most common culprit is the organism Chlamydia trachomatis. Other STDs that may be responsible include gonorrhea and genital herpes.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost predominantly in women. The average age of patients with IC is 40 years old, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Bladder Cancer. Bladder cancer is a rare cause of painful urination and is more common in men than in women.

Kidney Stones. The pain of kidney stones along with blood in the urine can resemble the symptoms of pyelonephritis. There are no bacteria present with kidney stones, however.

Thinning Urethral and Vaginal Walls. After menopause, the vaginal and urethral walls become dry and fragile, causing pain and irritation that can mimic a UTI.

Disorders in Children that Mimic UTIs. Problems that might cause painful urination in children include reactions to chemicals in bubble bath, diaper rashes, and infection from the pinworm parasite.

Prostate Conditions in Men. Prostate conditions, including prostatitis (inflammation of the prostate) and benign prostatic hyperplasia, can cause symptoms similar to urinary tract infections.

Click the icon to see an image of benign prostatic hypertrophy.

During an exam, the doctor should examine the pelvic and vaginal area in women. Men require a digital rectal examination to determine if prostate enlargement is present. The doctor will also examine the male genitals for signs of infection. In both men and women, the doctor should also check the abdomen and areas around the kidneys for swelling and tenderness.

With the exception of skin cancer, prostate cancer is the most common type of cancer among men in the United States. Early detection may result from a blood test called a PSA (prostate-specific antigen) or a digital rectal exam. The digital rectal exam checks the rear surface of the prostate gland for any abnormalities. A lump or hardness found during the exam might be a sign of prostate cancer.

Dipstick tests, available over the counter, are quite reliable in making a reasonable diagnosis of UTIs in women with symptoms. Dipstick tests may also be useful for identifying UTIs in children and infants. The test uses a chemical on a stick that when dipped in urine reacts to nitrites, substances produced by many of the bacteria that cause UTIs. A positive test (which indicates that an infection is present) often eliminates the need for urine cultures, a more expensive test used to detect bacteria. A negative dipstick test helps to avoid unnecessary antibiotics, which are contributing to the growing problem of antibiotic resistance. These tests are not entirely accurate, however, and studies report that they may miss up to 25% of actual UTIs. If a woman has persistent UTI symptoms, and the dipstick test is negative, she should check with her doctor to see if more accurate tests are needed.

A urine sample is needed for most extensive testing. In most cases, the doctor requests a clean-catch sample. There are also other methods for collecting urine, depending on the patient's condition.

Clean-Catch Sample. A clean-catch sample for UTI depends on a sample free of contaminants normally present at the opening of the urethra (white blood cells and bacteria unrelated to UTIs). To obtain an untainted urine sample, doctors usually request a so-called midstream, or clean-catch, urine sample. To provide this, the following steps are taken:

Patients must first wash their hands thoroughly, then wash the penis or vulva and surrounding area four times, with front-to-back strokes, using a new soapy sponge each time.
The patient must then begin urinating into the toilet and stop after a few drops.
The patient then positions the container to catch the middle portion of the stream. Ideally, this urine will contain only the bacteria and other evidence of the urinary tract infection.
The patient then urinates the remainder into the toilet.
The patient securely screws the container cap in place without touching the inside of the rim.

The sample is generally given to the doctor or sent to the laboratory for analysis.

Incontinence Pads. Testing and diagnosing UTIs in elderly patients who are incontinent is especially difficult, because of the similarities in symptoms. Researchers have found that pressing a dipstick into an incontinence pad is an effective way to screen for urinary tract infections in incontinent patients.

Collection with a Catheter. Some patients (small children, elderly people, or hospitalized patients) cannot provide a urine sample. In such cases, a catheter may be inserted into the bladder to collect urine. This is the best method for providing a contaminant-free sample.

A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. A urinalysis offers a number of valuable clues for an accurate diagnosis:

Color and cloudiness of urine
Acidity
White blood cells (leukocytes). A high count of white cells in the urine is referred to as pyuria. (A leukocyte count over 10 per microliter is considered to indicate pyuria.) Pyuria is usually sufficient for a diagnosis of UTI in nonhospitalized patients if other standard symptoms (or just fever in small children) are also present.

Treatment can be started without the need for further tests if the following urinalysis results are present in patients with symptoms and signs of UTIs:

A high white cell count
Cloudy urine

A urine culture uses a urine specimen that is placed on an agar plate, then incubated in the laboratory for 24 - 48 hours. It is then examined for the presence of bacterial growth. Urinary tract infection is nearly always caused by a single species of bacteria, notably E. coli. Cultures have limitations, however. If a mix of different species is found, the test is considered contaminated and is redone. In addition, even if E. coli is identified, researchers are also looking for variants of these bacteria. Certain types may indicate a higher risk for a second infection, while others may even be protective against recurring infections. Furthermore, some organisms, such as Chlamydia, which is a sexually transmitted organism, may not be detected.

A urine culture is usually performed if the dipstick results are positive, but even if the results are negative, a culture may still be helpful under certain circumstances:

If urinalysis or dipstick is negative but the patient has UTI symptoms, particularly if the patient has recurring infections or is in a high-risk group.
If the doctor suspects complications.
In girls less than 2 years of age with a high fever of unknown origin that lasts 2 days or more.

Even if bacteria are present in the culture, a diagnosis of UTI depends on symptoms and gender:

The presence in a culture of at least 100,000 bacteria per milliliter of urine usually provides conclusive evidence of infection in women with symptoms.
A count of 100,000 bacteria per milliliter in a woman without symptoms indicates asymptomatic bacteriuria. The decision to treat depends on the woman's risk factors for complications.
In young women with symptoms of cystitis, a diagnosis of infection can reasonably be made with counts as low as 1,000 bacteria per milliliter.
Men are considered to have an infection with a count of only 1,000.

If doctors suspect that bacteria other than E. coli may be present, a Gram stain is used to help predict the species. This is a staining procedure used to make bacteria visible through a microscope. Many bacteria are categorized by the terms Gram-positive and Gram-negative.

Bacteria that turn pink from staining are called Gram-negative
Those that turn blue are called Gram-positive

Escherichia coli bacteria are Gram-negative and the most common cause of UTIs. If doctors suspect that bacteria other than E. coli are causing a UTI, a Gram stain is useful for identifying other species.

Because of the expense and the limited accuracy of imaging procedures, these techniques are used only for the following:

Serious and recurrent cases of pyelonephritis
When structural abnormalities are suspected
If infections do not respond to treatment
If a doctor suspects obstruction or an abscess
After a first urinary tract infection in children age 2 - 24 months to detect possible obstruction or vesicoureteral reflux. Tests include ultrasound and a voiding cystourethrogram and possibly scans. Some evidence suggests that ultrasound is probably not necessary, but at this time it is recommended by major medical groups.

Ultrasound. Ultrasound is a noninvasive, risk-free imaging test that can be used to screen for hydronephrosis (obstructions of the flow of urine), kidney stones that predispose to infection, and kidney abscesses. In men, ultrasound can detect enlargement or abscesses of the prostate and, when combined with x-rays, is an accurate method for detecting incomplete emptying of the bladder, a common cause of UTI in men over age 50. In children with urinary tract infections, it also can be used to detect vesicoureteral reflux, the defect of the valve-like mechanism between the ureter and bladder. Ultrasounds are not as accurate as voiding cystourethrograms.

Nuclear Scans. Imaging techniques called nuclear scans may be useful in certain complicated cases, such as detecting kidney scarring after pyelonephritis in children. They produce better images and expose the patient to far less radiation than x-rays. One such scan called dimercaptosuccinic acid (DMSA) scintigraphy uses injections of tiny amounts of radioactive tracers. A scanning machine (scintillation or gamma camera) is then used to detect pictures of the tracer in the kidney. This information is recorded on a computer screen or on film.

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). Magnetic resonance imaging (MRI) and computed tomography (CT) scans are noninvasive advanced imaging techniques that are sometimes used when nuclear scans are inconclusive. A CT scan is useful for ruling out kidney stones or obstructions in women with recurrent UTIs.

X-Rays. Special x-rays can be used to screen for structural abnormalities, urethral narrowing, or incomplete emptying of the bladder, which can cause stagnation of urine and predispose to infection.

Voiding cystourethrogram is an x-ray of the bladder and urethra. To obtain a cystourethrogram, a dye, called contrast material, is injected through a catheter inserted into the urethra and passed through the bladder.
An intravenous pyelogram (IVP) is an x-ray of the kidney. For a pyelogram, the contrast matter is injected into a vein and eliminated by the kidneys. In both cases, the dye passes through the urinary tract and reveals any obstructions or abnormalities on x-ray images. Due to the possible risks to the fetus, x-rays are not performed on pregnant women.

Click the icon to see an image of a voiding cystourethrogram.

Click the icon to see an image of an intravenous pyelogram.

Cystoscopy. Cystoscopy is used to detect structural abnormalities, interstitial cystitis, or masses that might not show up on x-rays during an IVP. The patient is given a light anesthetic, and the bladder is filled with water. The procedure uses a cystoscope, a flexible, tube-like instrument that the urologist inserts through the urethra into the bladder.

Click the icon to see an image of cystoscopy.

No noninvasive test will differentiate between upper and lower urinary tract infections. This is a particular problem because of the high percentage of women whose cystitis symptoms mask infections that also exist in the upper tract.

Antibiotic Trial. The best current test for pyelonephritis is the short-term antibiotic therapy given for cystitis. If the infection returns within 2 weeks after treatment, upper urinary tract infection is usually present.

Blood Cultures. If symptoms are severe, blood cultures will be taken to determine if the infection is in the bloodstream and threatening other parts of the body.

Treatment

Although antibiotics should be used as a cure for most urinary tract infections, severe symptoms can persist for several days until treatment effectively eliminates the bacteria. A number of options are available for relieving symptoms until the antibiotics take action.

Important Note. All of the drugs discussed below treat only symptoms and are not cures. They should never be used to replace antibiotics.

Phenazopyridine (Pyridium, Uristat, Barodium, Eridium, AZO Standard) relieves pain and burning caused by the infection. It should not be taken for more than 2 days and should be discontinued when symptoms are relieved.

Side effects include headache and stomach distress. The drug turns urine a red or orange color, which can stain fabric and be difficult to remove. In rare cases, it can cause serious side effects, including shortness of breath, a bluish skin, a sudden reduction in urine output, shortness of breath, and confusion. In such cases, patients should immediately call the doctor.

Methenamine (Atrosept, Prosed, Urised) or flavoxate (Urispas) reduce bladder spasms, which may occur with some UTIs. These drugs can have severe side effects, however, that the patient should discuss with the doctor.

Medications

Antibiotics are the mainstay treatment for all UTIs. A variety of antibiotics are available, and choices depend on many factors, including whether the infection is complicated or uncomplicated or primary or recurrent. Treatment decisions are also based on the type of patient (man or woman, a pregnant or nonpregnant woman, child, hospitalized or nonhospitalized patient, person with diabetes). Treatment should not necessarily be based on the actual bacteria count. For example, if a woman has symptoms, even if bacterial count is low or normal, infection is probably present and antibiotic treatment should be considered.

Bacterial Resistance to Antibiotics. Antibiotic-resistant strains of E. coli, the most common cause of UTIs, are increasing. The prevalence of such bacteria has dramatically increased worldwide, in large part due to widespread use of antibiotics in humans and animal feed. In a 2003 report, 42% of E. coli were resistant to one or more of the 12 antibiotics that researchers investigated. As more bacteria have become resistant to the standard UTI treatment trimethoprim-sulfamethoxazole (TMP-SMX), more doctors have been prescribing quinolone antibiotics to treat UTIs. A 2006 study found that quinolones have now overtaken TMP-SMX as the most commonly prescribed antibiotic for UTIs. Experts are concerned that resistance may develop to these drugs as well.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins, cephalosporins, and some newer similar drugs. Their primary actions to interfere with bacterial cell walls. Many have been important in the treatment of urinary tract infections.

Penicillins (Amoxicillin). Until recent years, the standard treatment for a UTI was 10 days of amoxicillin, a penicillin antibiotic, but it is now ineffective against E. coli bacteria in up to 25% of cases. A combination of amoxicillin-clavulanate (Augmentin) is sometimes given for drug-resistant infections. Amoxicillin or Augmentin may be useful for UTIs caused by Gram-positive organisms, including Enterococcus species and S. saprophyticus.

Cephalosporins. Antibiotics known as cephalosporins are also alternatives for infections that do not respond to standard treatments or for special populations. They are often classed as:

First generation, including cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation, including cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation, including cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria.

Other Beta-Lactam Drugs. Other beta-lactam antibiotics have been developed. For example, pivmecillinam (a form of mecillinam), is commonly used in Europe for UTIs. It appears to be safe during pregnancy.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

The typical treatment is a 3-day course of the combination drug trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). A 1-day course is somewhat less effective but poses a lower risk for side effects. Longer courses (7 - 10 days) work no better than the 3-day course and have a higher rate of side effects. TMP-SMX should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious. Trimethoprim (Proloprim, Trimpex) is sometimes used alone in those allergic to sulfa drugs. TMP-SMX can interfere with the effectiveness of oral contraceptives. High rates of bacterial resistance to TMP-SMX exist in many parts of the United States. Still, even when regional rates approach 30%, cure rates with TMP-SMX reach 80 - 85%.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) are now becoming as widely used as TMP-SMX. These drugs interfere with the bacteria's genetic material so they cannot reproduce. They are the standard alternatives to TMP-SMX. Examples of quinolones include ofloxacin (Floxacin), ciprofloxacin (Cipro), norfloxacin (Noroxin), levofloxacin (Levaquin), gatifloxacin (Tequin), and sparfloxacin (Zagam). These antibiotics are effective against a wide range of organisms but are expensive and, in general, used in the following circumstances:

In patients with complicated or catheter-induced UTIs
In patients who do not respond or who are allergic to TMP-SMX
In communities where there are high rates of bacteria resistant to TMP-SMX
In elderly patients. A 2001 study of older women with UTIs (mean age 80), about half of whom were living in nursing homes, found that 96% responded to ciprofloxacin, compared with 87% to TMP-SMX.

Pregnant women should not take fluoroquinolone antibiotics. They also have more adverse effects in children than other antibiotics and should not be the first-line option in most situations.

Antibiotics Used Specifically for UTIs

Nitrofurantoin. Nitrofurantoin (Furadantin, Macrodantin) is a relatively inexpensive antibiotic that is used specifically for urinary tract infections. It is an effective alternative to TMP-SMX or a quinolone. Unlike many of the other drugs, however, it must be given 7 - 10 days, even in cases of simple cystitis. (Shorter course treatments are being investigated.) It is not useful for treating kidney infections. Nitrofurantoin frequently causes stomach upset and interacts with many drugs. Other chronic or serious medical conditions may also affect its use. It should not be used in pregnant women within 1 - 2 weeks of delivery, in nursing mothers, or in those with kidney disease.

Fosfomycin. The antibiotic fosfomycin (Monurol), which comes in an orange-flavored, soluble powder, is proving to be another good alternative. It can be an effective 1-dose treatment for many women, including those who are pregnant. To date, bacterial resistance rates to this antibiotic are very low.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. Long-term treatment with tetracycline or doxycycline may be used for infections that are caused by Mycoplasma or Chlamydia. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Gentamicin is the most commonly used aminoglycoside for serious UTIs. They can have very serious side effects, including damage to hearing, sense of balance, and kidneys.

UTIs in low-risk women can often be successfully treated over the phone. In such cases, a health professional provides the patients with 3-day antibiotic regimens without even requiring an office urine test. This course is recommended only for women at low risk for recurrent infection and who do not have symptoms suggesting other problems, such as vaginitis.

Antibiotic Regimen. Oral antibiotic treatment cures 94% of uncomplicated urinary tract infections, although the rate of recurrence remains high. The following antibiotics are commonly used for uncomplicated UTIs:

The standard regimen has traditionally been a 3-day course of trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). TMP-SMX combines an antibiotic with a sulfa drug. A single dose of TMP-SMX is sometimes prescribed in mild cases, but cure rates are generally lower than with the 3-day regimens.
Fluoroquinolone antibiotics, also called quinolones, have usually been a second choice. However, in geographic areas that have a high resistance to TMP-SMX, quinolones are now the first-line treatment for UTIs. Ciprofloxacin (Cipro) is the quinolone antibiotic most commonly prescribed. Quinolones are usually given over a 3–day period. Pregnant women should not take these drugs.
Nitrofurantoin (Furadantin, Macrodantin) is a third option. This drug must be given for longer than 3 days.
Fosfomycin (Monurol) is not as effective as other antibiotics but may be used during pregnancy. Resistance rates to this drug are very low.
Many other effective antibiotics are available, including amoxicillin (with or without clavulanate) and cephalosporins. Doxycycline is often effective but cannot be given to children or pregnant women.

After a week of antibiotic treatment, most patients are free of infection. If the symptoms do not clear up within the first few days of therapy, doctors generally suggest that women discontinue their antibiotic and provide a urine sample for culturing in order to identify the specific organism causing the condition.

Treatment for Relapsing Infection. A relapsing infection (caused by treatment failure) occurs within 3 weeks in about 10% of women. Relapse is treated similarly to a first infection, but the antibiotics are continued for at least 2 weeks. (Relapsing infections may be due to structural abnormalities, abscesses, or other problems that may require surgery, and such conditions should be ruled out.)

Preventive antibiotics may be required for women who experience two or more symptomatic UTIs within 6 months or three or more over the course of a year. A woman's own perception of discomfort can generally guide her decisions on whether to use preventive antibiotics or not. All women should use lifestyle measures to prevent recurrences.

Intermittent Self Treatment. Many, if not most, women with recurrent UTIs can effectively self-treat recurrent UTIs without going to a doctor. In general, this requires the following steps:

As soon as the patient develops symptoms, she takes the antibiotic. Infections that occur less than twice a year are usually treated as if they were an initial attack, with single-dose or three-day antibiotic regimens.
At that time, she also performs a clean-catch urine test and sends it to the doctor for culturing to confirm the infection.

A doctor should be consulted under the following circumstances:

If symptoms have not completely resolved within 48 hours
If there is a change in symptoms
If the patient suspects that she is pregnant
If the patient has more than four infections a year

Women who are not good candidates for self-treatment are those with impaired immune systems, previous kidney infections, structural abnormalities of the urinary tract, or a history of infection with antibiotic-resistant bacteria.

Postcoital Antibiotics. If recurrent infections are clearly related to sexual activity and episodes recur more than two times within a 6-month period, a single preventive dose taken immediately after intercourse is very effective. Antibiotics for such cases include TMP-SMX, nitrofurantoin, cephalexin, or a fluoroquinolone (such as ciprofloxacin). (Fluoroquinolones are not appropriate during pregnancy.)

Continuous Preventive Antibiotics (Prophylaxis). Continuous preventive (prophylactic) antibiotics are an option for some women who do not respond to other measures. With this approach, low-dose antibiotics are taken continuously for 6 months or longer.

Typical prophylactic regimens include one dose of nitrofurantoin (50 mg), 1/2 tablet of TMP-SMX, or cephalexin (250 mg) daily. Taking the antibiotic at bedtime may be most effective. Studies suggest that continuous prophylactic antibiotics reduces recurrences by up to 95% and may prevent kidney infection.

Adverse effects mostly include gastrointestinal problems and yeast infections. (Taking probiotic supplements or eating yogurt may help prevent yeast infections.) Although there is concern that continuous risk increases the risk for bacteria that are resistant to the antibiotics, studies to date have not reported any significant risk even up to 5 years of use.

Treating Uncomplicated Kidney Infections. Patients with uncomplicated kidney infections (pyelonephritis) may be treated at home with oral antibiotics. Such patients are healthy and nonpregnant. They typically are experiencing fever, chills, and flank pain. However, they are not nauseous or vomiting and show no symptoms or signs of kidney involvement or complicated infection.

The standard treatment for uncomplicated pyelonephritis is a 14-day course of oral antibiotics, usually trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone. Sometimes patients with uncomplicated pyelonephritis are first given an antibiotic injection, if indicated.

Oral amoxicillin or amoxicillin-clavulanate (Augmentin) may be prescribed for women with bacteria (Gram-positive organisms, including Enterococcus species and S. saprophyticus) that do not respond to standard regimens.

A urine culture may be obtained within 1 week of completion of therapy and again 4 weeks later.

Treating Moderate-to-Severe Kidney Infections. Patients with moderate-to-severe acute kidney infection and those with severe symptoms or other complications may need to be hospitalized. In such cases, antibiotics (ceftriaxone and gentamicin) are usually given intravenously for 3 - 5 days or until symptoms are relieved and patients have not shown any signs of fever for 24 - 48 hours.

If fever and back pain persist after 72 hours of antibiotic administration, the doctor will usually order imaging tests to see if abscesses, obstructions, or other abnormalities are present.

Treating Chronic Kidney Infections. Patients with chronic pyelonephritis are often treated with long-term antibiotics, even during periods when they have no symptoms.

The two approved treatments for interstitial cystitis are pentosan polysulfate (Elmiron), and dimethyl sulfoxide (DMSO). Patients generally prefer Elmiron because it can be taken by mouth. A DMSO solution is instilled into the bladder through a catheter. Elmiron is a type of blood thinner that helps to coat the bladder lining and prevent infections. It may take several months before having an effect on symptoms, but the benefits increase the longer the drug is used.

Doctors sometimes also prescribe other types of medications to help interstitial cystitis symptoms. These drugs include antihistamines, such as hydroxyzine (Atarax), and low doses of the tricyclic antidepressant amitriptyline (Elavil). Drugs that reduce bladder spasms (hyoscine, oxybutynin) are also sometimes used. Other treatments are being investigated, including hyperbaric oxygen therapy. This treatment involves having a patient breathe pure oxygen inside a sealed pressurized chamber.

Some doctors think that interstitial cystitis may be related to immune disorders. Researchers are investigating various drugs that block immune and inflammatory responses.

Treating the Pregnant Woman. Pregnant women should be screened for UTIs, since they are at high risk for UTIs and their complications. The antibiotics used during pregnancy are amoxicillin, ampicillin, nitrofurantoin, or an oral cephalosporin. Fosfomycin (Monurol) is not as effective as others but may be used during pregnancy. Pregnant women should not take fluoroquinolones.

Pregnant women with even asymptomatic bacteriuria (evidence of infection but no symptoms) have a 30% risk for acute pyelonephritis in their second or third trimester. They need screening and treatment for this condition. In such cases, they should be treated with a short course of antibiotics (3 - 5 days). For an uncomplicated UTI, pregnant women may need longer-term antibiotics (7 - 10 days).

Treating Women with Diabetes. Women with diabetes have more frequent and more severe UTIs than women without the disease. Many experts recommend that patients with diabetes and UTI, even an uncomplicated infection, be treated with antibiotics for 7 - 14 days. People with diabetes have higher than average rates of asymptomatic bacteriuria, but it is unclear whether they should be screened and treated for this condition. A 2003 study indicated that treating this condition had little value in these women and did not prevent complications.

Treating Urethritis in Men. Urethritis in men has typically been treated with a 7-day regimen of doxycycline. Some research suggests that a single dose of azithromycin may be just as effective while causing fewer side effects. One-dose treatment also improves compliance, so cure rates may even be better than with a long-term regimen. However, once an infection spreads to the prostate gland it is harder to treat, so most doctors still prefer the longer regimen. Patients with urethritis should also be tested for an accompanying sexually transmitted disease such as gonorrhea.

Treating Children with UTIs. Children with UTIs are generally treated with TMP-SMX or cephalexin (Keflex). These drugs are usually taken by mouth in either liquid or pill form. Doctors sometimes give them as a shot or IV. Children usually respond to treatment within a few days. Antibiotic resistance to cephalosporin antibiotics such as cephalexin is increasing, and some doctors prefer to prescribe an aminoglycoside antibiotic. Gentamicin (Garamycin) is the aminoglycoside antibiotic that is most commonly used. It is given intravenously.

Vesicoureteral reflux (VUR) is a concern for children with UTIs. About a third of children with UTIs develop this condition, in which urine backs up into the kidneys. VUR can lead to kidney infection (pyelonephritis), which can cause kidney damage. Either long-term antibiotics or surgery are options to correct vesicoureteral reflux (VUR) and prevent infection. Many experts recommend surgery over antibiotics, especially due to concerns of antibiotic resistance. Antibiotic treatment usually continues for years with the idea that the condition will resolve when the child has grown. However, a 2006 study suggested that long-term antibiotics are not useful for preventing VUR. Furthermore, the study found that mild-to-moderate VUR does not increase the likelihood of UTIs or pyelonephritis.

Children with acute kidney infection are treated with oral cefixime (Suprax) or a short course (2 - 4 days) of an intravenous (IV) antibiotic (typically gentamicin, given in one daily dose). An oral antibiotic then follows the IV.

Preventing Catheter-Induced Infections

Catheter-induced urinary tract infections are very common, and preventive measures are extremely important. Catheters should not be used unless absolutely necessary, and they should be removed as soon as possible. Reducing the risk for infections during long-term catheter use, however, remains problematic.

Catheter Coatings. Catheter coatings, such as silver nitrate, antibiotics, and other substances, are being tested and are showing some benefits, but the problem is still not resolved. One promising catheter (LoFric) uses a so-called hydrophilic coating consisting of PVP (polyvinyl pyrrolidone) and salt. It attracts water to the catheter surface, putting up a water barrier to reduce friction. In a 2003 study, it was associated with significantly fewer UTIs.

Intermittent Use of Catheters. If a catheter is required for long periods, it is best to use it intermittently if possible (as opposed to an indwelling catheter). Some doctors recommend replacing it every 2 weeks to reduce the risk of infection and irrigating the bladder with antibiotics between replacements.

Daily Hygiene. A typical catheter is one that has been preconnected and sealed and uses a drainage bag system. To prevent infection, some of the following tips may be helpful:

Drink plenty of fluids, including 3 glasses of cranberry juice a day.
The catheter tube should be free of any knots or kinks.
Clean the catheter and the area around the urethra with soap and water daily and after each bowel movement. (Women should be sure to clean front to back.)
Wash hands before touching the catheter or surrounding area.
Never disconnect the catheter from the drainage bag without careful instructions from a health professional on strict methods for preventing infection.
Keep the drainage bag off the floor.
Stabilize the bag against the leg using tape or some other system.

Antibiotics for Catheter-Induced Infections

Patients using catheters who develop UTIs with symptoms should be treated for each episode with antibiotics and the catheter should be removed, if possible. A major problem in treating catheter-related UTIs is that the organisms involved are constantly changing. Because there are likely to be multiple species of bacteria, experts generally recommend an antibiotic that is effective against a wide variety of microorganisms. These medications include those in the fluoroquinolone group and drug combinations such as ampicillin plus gentamicin or imipenem plus cilastatin.

Although high bacteria counts in the urine (bacteriuria) occur in most catheterized patients, administering antibiotics to prevent a UTI is rarely recommended. Many catheterized patients do not develop symptomatic urinary tract infections even with high bacteria counts. If bacteriuria occurs without symptoms, antibiotic therapy has little benefit if the catheter is to remain in place for a long period.

Catheterization is accomplished by inserting a catheter (a hollow tube, often with an inflatable balloon tip) into the urinary bladder. This procedure is performed for urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured. Catheterization in males is slightly more difficult and uncomfortable than in females because of the longer urethra.

Other Treatments

The following are hygiene tips. Although there is no evidence that good hygiene makes a real difference in preventing UTIs, it is always a wise practice.

Clean the genital and urinary areas from front to back with soap and water after each bowel movement.
Keep the genital and anal areas clean before and after sex. Urinate before and after intercourse to empty the bladder and cleanse the urethra of bacteria.
Avoid tight-fitting pants.
Wear cotton-crotch underwear and panty hose, changing both at least once a day. (Mild detergents are best for washing underwear.)
Take showers rather than baths.
Avoid bath oils, feminine hygiene sprays, douches, and powders. As a general rule, do not use any product containing perfumes or other possible allergens near the genital area. Douching in is never recommended. It may destroy the natural antiviral organisms normally present in the vagina, making women more susceptible to human papillomavirus (HPV), a risk factor for cervical cancer.
Choose sanitary napkins instead of tampons (which some doctors believe encourage infection). Napkins and tampons, in any case, should be changed after each urination.
Urinate frequently.

Appropriate hygiene and cleanliness of the genital area may help reduce the chances of introducing bacteria through the urethra. Females are especially vulnerable to this, because the urethra is in close proximity to the rectum. The genitals should be cleaned and wiped from front to back to reduce the chance of dragging E. coli bacteria from the rectal area to the urethra.

The following recommendations may reduce the risks from sexual activity:

In women using contraceptives, consider alternatives, particularly if exposed to spermicides from condoms or diaphragms. Discuss the best contraceptive choice with a doctor.
Avoid sex with multiple partners. This can cause many health problems, including sexually transmitted diseases and UTIs.

Postmenopausal women with recurrent UTIs may consider the use of an estrogen vaginal cream or estrogen-releasing vaginal ring (Estring). Estrogen may resist infection by increasing the number of lactobacilli, the microorganism that fights infection by lowering the vaginal pH levels and preventing E. coli from adhering to vaginal cells. Estrogen creams and estrogen-releasing rings may help reduce the risk of recurring urinary tract infections. Oral hormone replacement therapies that contain estrogen do not seem to provide the same benefit as the topical forms. Estrogen HRT carries many health risks, including an increased risk for breast cancer and heart disease. It is not clear if vaginal forms of estrogen are associated with these risks.

Many doctors believe that emptying the bladder frequently will help prevent bladder irritation and therefore recommend drinking plenty of water daily and urinating often.

Cranberries, blueberries, and lignonberry, a European relative of the cranberry, are three fruits that may have protective properties. Researchers are finding that red pigments in these closely related fruits called tannins (or proanthocyanadins) prevent E. coli bacteria from adhering to cells in the urinary tract, thereby inhibiting infection. Fructose, which is commonly used to sweeten fruit juices, may also interfere with bacterial adhesion.

Cranberry juice offers well-known protection against urinary tract infections. In one study, only 15% of elderly women who drank cranberry juice daily for 6 months experienced UTIs, compared with 28% of women who did not drink the juice. Its effects were stronger in helping the body rid itself of infections than in preventing them in the first place, but it showed benefits in both situations.

Studies suggest that for protection, it is necessary to drink at least one to two cups of 30% cranberry or lignonberry juice daily, or to take at least 300 - 400 mg in tablet form twice daily.

Important research has targeted probiotics (essentially friendly organisms), which may protect against infections in the genital and urinary tracts. They may have other health benefits as well. The best-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products (kefir). The probiotics bifidobacteria and GG lactobacilli may prove to be even more important. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Lactobacilli have the potential to help protect women from UTIs in a number of ways:

Maintain a low pH environment
Hinder E. coli growth
Produce hydrogen peroxide, which produces an environment hostile for bacteria

In a 2003 study, drinking fermented milk reduced the risk for UTIs. Not all studies show benefits from drinks containing lactobacilli, but more research is warranted.

Researchers are studying several different herbal treatments for urinary tract infections. Studies on these herbs have only been conducted on animals and cell samples -- not in humans:

Forskolin, an extract from the Indian coleus plant, may help flush out bacteria hiding in the lining of the bladder.
Green tea contains compounds that may help prevent inflammation in bladder cells.
St. John’s wort, a popular herbal remedy for depression, may help relieve pain associated with interstitial cystitis.

It is important to inform your doctor of any herbs, dietary supplements, or vitamins and minerals that you take or are considering taking. Some of these remedies may actually increase your chance of developing urinary tract infections. For example, high doses of zinc have been associated with increased risk of UTIs.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Biofeedback is a technique that provides visual and auditory clues in response to specific exercises. Some research indicates that biofeedback teaches children who are prone to UTIs to relax and control their pelvic muscles, resulting in fewer recurrences of infection.

Resources

http://kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Clearinghouse
www.urologyhealth.org -- American Urological Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.ichelp.com -- Interstitial Cystitis Association

References

Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med. 2007 May;13(5):625-30. Epub 2007 Apr 8.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Take a Hike to Entertain and Engage Your Youngster

LilSugar — Wed, 13 May 2009 09:00:38 -0700

Fresh air, green leaves and singing birds can put anyone in the mood for a good hike. In addition to the aerobic exercise hiking provides, it's a great way to spend some quality time with family and friends. Given a tot's natural curiosity about their surroundings, kids make excellent hiking partners, if parents go into the activity realizing that they might not reach their end point, mileage or exercise goals during the outing.

Hiking with children involves frequent stops, sedate trails and some extra gear. Youngsters normally focus on the excitement of a new experience rather than the destination so finding a local trail or creek to walk along will suffice.

To capture their curiosity, be sure to bring along "tools" that will help your lil one gain the most from the experience. Butterfly nets, assorted plastic containers for storing pebbles and leaves, a canteen and a magnifying glass will add intrigue to the excursion. The outing should also provide many opportunities for capturing memories – either through the eye of a camera or a notebook where kids sketch their surroundings.

For more information on what parents should pack when hiking with their offspring, read more.

Packing for a hike with kids is no easy feat. Depending on the ages of the tots, diapers, snacks and changes of clothing should be packed – even for the shortest of outings. Safe Kids USA also recommends the following precautions.

Keep first aid supplies and emergency phone numbers handy, and know where the nearest phone is located. Cell phones might not work in remote areas. Let friends and relatives know where you’re going and when you’re coming home.
Dress children in layers of clothing to help prevent heat-related illness and hypothermia. A child’s body temperature changes faster than an adult’s.
Never let children hike alone.
Don’t push kids to go on a longer or more strenuous hike than they can handle. Exhausted children are more likely to fall, wander off or otherwise get injured. Bring plenty of drinking water or sports drinks and high-energy snacks.
Kids should wear hiking boots and clothing that offers protection from scrapes, bites and poisonous plants. Following the manufacturer’s instructions, apply insect repellent to a child’s clothing and exposed skin.
Apply sunscreen rated SPF 15 or higher to your child’s exposed skin 15 to 30 minutes before going out, and reapply frequently. (It is possible to get a sunburn in cloudy conditions.)

Most of all, it's important to remember that the hike is a journey. Getting out in the great outdoors with your wee ones is an ideal way to spend the day.
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