FitSugar

Bike Riding and Back Pain: Part Two

FitSugar — Tue, 18 Mar 2008 13:30:00 -0700

Now that you have your bike set up to fit you to further prevent back, shoulder, and neck pain, you want to ride your bike correctly. These tips should help you have a smooth, pain-free ride.

Check your pedaling technique. If you glance at your knees while pedaling, they should be going straight up and down. Try to keep them from pointing out to the side as you pedal as this will make you pedal slower, could injure your knees or hips, and could be causing low-back pain.
Have good cycling posture. Your back should be slightly arched up like a hill, not swaybacked with your tailbone sticking up. This slight arch will allow you to engage your abs, and is also necessary when you hit bumps in the road. Your back will arch up a little more to absorb the shock. If your spine was arched down, hitting bumps would cause your back to bow in even more, which can cause low-back pain.
While pedaling, make sure not to have your bike set on a gear that makes pedaling really difficult. Switching to an easier gear could ease your back pain.
Be mindful of your shoulders. Consciously remind yourself to relax them away from your ears. Scrunching them up will cause tension, which in turn can cause neck and upper-back pain.

Want to see what else may help ease your back pain? Then read more.

Also make sure that your elbows have a slight bend in them to allow them to act as shock absorbers. This can relieve tension in the shoulders and upper back.
Wear the right sized helmet. One that doesn't fit well can wobble and cause neck pain.
Even though bikes have saddles so you can sit, periodically stand since sitting for long periods of time can make for a sore lower back.
Once your ride is over, be sure to stretch out your hips, hamstrings, and lower back.

Bike Riding and Back Pain: Part One

FitSugar — Fri, 07 Mar 2008 04:00:00 -0800

Bike riding is great exercise since it gets you outside into the fresh air, it works your heart and lungs, and many people find it to be easier on their bodies than running. Some people may experience pain in their lower back, upper back, and shoulders, and a lot of it has to do with their bike. Check out these tips to help prevent discomfort:

Make sure the bike is the right style for where you plan on riding. You don't want to be taking a road bike, that's made for speediness on flat surfaces, out mountain biking. The right kind of bike will support your body better.
Also make sure it's the right size for you. You'll know it's the right height, if you can stand with your feet flat straddling the bike, and the front bar and your lady business are about two to four inches apart. If you have a women's bike where the bar is slanted, imagine that the bar is horizontal and measure from that line.
Be sure the seat is the appropriate height. When sitting on the bike, your leg should be almost straight when on the down stroke. Having your knees lock can cause injury and a jarring feeling in your lower back.
Find a comfortable handlebar height. Start with your handlebar stem one inch lower than your seat. If this position bothers your lower back, you can raise the bars slightly until your back feels good. If you're riding on tough terrain, higher handlebars may be better.
Don't raise the handlebars so that your spine is in an upright position. A straight back doesn't allow any give when you hit road bumps, and will only make your vertebrae jam together, which will aggravate existing back pain.

Stay tuned for Part Two, all about riding technique and posture.

Source

Coronary artery disease

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Angioplasty Versus Drugs

Angioplasty works no better than drug therapy (high blood pressure, cholesterol, anti-platelet, and other medication) in preventing heart attack and stroke in patients with stable coronary artery disease (CAD), according to an important New England Journal of Medicine study. Experts still recommend angioplasty for patients with unstable or severe CAD.

Stents

Stents coated with drugs may have a slightly higher risk of causing blood clots than bare metal stents, according to FDA meetings held in late 2006. Researchers still need to conduct more research before reaching final conclusions.
Drug-coated stents work well when they are used for patients with specific types of heart conditions, indicate several studies published in the New England Journal of Medicine. However, problems may develop when these stents are used for “off-label” purposes. Experts are also concerned that both bare metal and drug-coated stents may be used too frequently.
Patients who receive a drug-coated stent must take both aspirin and an anti-platelet thienopyridine drug (usually clopidogrel) for at least 1 year after the stent is inserted, advises an important statement from the American Heart Association. Patients who cannot take a thienopyridine drug should receive a bare metal stent instead of a drug-coated stent.

Anti-Bleeding Drugs for Coronary Artery Bypass Graft (CAGB)

Aprotinin (Trasylol), a drug used to control bleeding during CABG, is more dangerous than other types of anti-bleeding drugs, according to a 2007 study in the Journal of the American Medical Association. Many experts now recommend against its use.

Diagnosis

Blood tests for biomarkers do not provide much more predictive information than standard disease risk factors, suggest several recent studies. In a 2006 study published in the New England Journal of Medicine, researchers found that risk factors such as high blood pressure, high cholesterol, and diabetes are still the best methods for predicting the likelihood of heart disease and heart-related death.

Introduction

The heart is the human body's hardest working organ. Throughout life it continuously pumps blood enriched with oxygen and vital nutrients through a network of arteries to all parts of the body's tissues.

The external structures of the heart include the ventricles, atria, arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The vessels colored blue indicate the transport of blood with relatively low content of oxygen and high content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high content of oxygen and low content of carbon dioxide.

In order to perform the difficult task of pumping blood to the rest of the body, the heart muscle itself needs a plentiful supply of oxygen-rich blood, which is provided through a network of coronary arteries. These arteries carry oxygen-rich blood to the heart's muscular walls (the myocardium).

Click the icon to see an image of the anterior heart arteries.

If blood flow to the myocardium is interrupted, an injury known as an infarct occurs. This is also known as myocardial infarction or, more commonly, a heart attack.

Click the icon to see an animation about coronary artery disease.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). This causes blockage of arteries (ischemia ) and prevents oxygen-rich blood from reaching the heart. There are many steps in the process leading to atherosclerosis, some not fully understood.

Click the icon to see an image of atherosclerosis.

Increasingly, however, researchers are studying the interactions between cholesterol and processes known as oxidation and the inflammatory response.

Cholesterol and Lipoproteins. The story begins with cholesterol and sphere-shaped bodies called lipoproteins that transport cholesterol.

Cholesterol is a white, crystalline substance that is found in all animal cells and in animal-based foods. It is critical for many functions, but under certain conditions cholesterol can have harmful effects.
The lipoproteins that transport cholesterol are referred to by their size. The most commonly known are low-density lipoproteins (LDL) and high density lipoproteins (HDL). LDL is often referred to as the "bad" cholesterol and HDL as the "good" cholesterol.

Click the icon to see an image of cholesterol inside an artery.

Oxidation. The damaging process called oxidation is an important trigger in the atherosclerosis story.

Oxidation is a chemical process in the body caused by the release of unstable particles known as oxygen-free radicals. It is one of the normal processes in the body, but under certain conditions (such as exposure to cigarette smoke or other environment stresses) these free radicals are overproduced.
In excess amounts, they can be very dangerous, causing damaging inflammation and even affecting genetic material in cells.
In heart disease, free radicals are released in artery linings and oxidize low-density lipoproteins (LDL). The oxidized LDL is the basis for cholesterol build-up on the artery walls and damage leading to heart disease.

Inflammatory Response. For the arteries to harden there must be a persistent reaction in the body that causes ongoing harm. Researchers now believe that this reaction is an immune process known as the inflammatory response. The following is one theory about how the inflammatory response contributes to heart disease:

The injuries to the arteries during oxidation signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. These factors initiate the inflammatory response.
Macrophages literally "eat" foreign debris, in this case oxidized LDL cholesterol.
The process converts LDL cholesterol into foamy material that attaches to the smooth muscle cells of the arteries. The cholesterol becomes mushy and accumulates on artery walls.
Over time the cholesterol dries and forms a hard plaque, which causes further injury to the walls of the arteries.
In response to this additional harm, the immune system releases other factors called cytokines. These are powerful inflammatory molecules that attract more white blood cells and perpetuate the whole cycle, causing persistent injury to the arteries.

Click the icon to see an image of atherosclerosis.

Evidence is growing that the inflammatory response may be present not only in local plaques in single arteries but also throughout the arteries leading to the heart.

Blockage in the Arteries. Eventually these calcified (hardened) arteries become narrower (a condition known as stenosis).

As this narrowing and hardening process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart.
Such oxygen deprivation in vital cells is called ischemia. When it affects the coronary arteries, it causes injury to the tissues of the heart.
Injured inner vessel walls also fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity. (Nitric oxide has complex effects and may increase inflammation in the arteries.)
These narrow and inelastic arteries not only slow down blood flow but also become vulnerable to injury and tears.

Click the icon to see an image of coronary artery blockage

The End Result: Heart Attack. Heart attack can occur as a result of one or two effects of atherosclerosis.

(1) If the artery becomes completely blocked and ischemia becomes so extensive that oxygen-bearing tissues around the heart die.

(2) If the plaque itself develops fissures or tears. Blood platelets adhere to the site to seal off the plaque, and a blood clot (thrombus) forms. A heart attack can then occur if the formed blood clot completely blocks the passage of oxygen-rich blood to the heart.

Click the icon to see an image of the developmental process of atherosclerosis.

Angina is the primary symptom of coronary artery disease and, in severe cases, of a heart attack. It is typically experienced as chest pain and occurs when the heart muscle does not get as much blood (hence as much oxygen) as it needs for a given level of work (ischemia). Angina is usually referred to as one of two states:

Click the icon to see an image about angina.

Stable Angina (which is predictable)
Unstable Angina (which is less predictable and a sign of a more serious situation)

Angina itself is not a disease. Much evidence indicates that onset of angina less than 48 hours before a heart attack may be protective, possibly by conditioning the heart to resist the damage resulting from the attack. Angina may be experienced in different ways and can be mild, moderate, or severe.

Click the icon to see an image of angina.

Specific factors are typically considered in determining whether symptoms indicate angina:

Quality of the pain. Angina pain is typically described by patients as squeezing, heavy, suffocating, or griplike. It is rarely described as stabbing or burning. Changing one's position or breathing in and out does not affect the pain. The intensity of the pain does not always relate to the severity of the medical problem. Some people may feel a crushing pain from mild ischemia, while others might experience only mild discomfort from severe ischemia. In some cases, the patient experiences shortness of breath, fatigue, or palpitations instead of pain. In others, the ischemia is entirely asymptomatic ("silent ischemia").
Duration. A typical angina attack lasts minutes. If it is more fleeting or lasts for hours, it is probably not angina.
Location. Pain is usually in the chest under the breast bone. It often radiates to the neck, jaw, or left shoulder and arm. Less commonly, patients report symptoms that radiate to the right arm or back.
Triggers of Angina. Angina is usually triggered by physical exertion, emotional stress, or exposure to cold.
Factors that Relieve Angina. Angina is usually relieved by rest or by taking nitroglycerine under the tongue.

Stable Angina. Stable angina is predictable chest pain. Although less serious than unstable angina, it can be extremely painful. It is usually relieved by rest and responds well to medical treatment (typically nitroglycerin). Any event that increases oxygen demand can cause an angina attack. Some typical triggers include:

Exercise
Cold weather
Emotional tension
Large meals

Angina attacks can occur at any time during the day, but most occur between 6 a.m. and noon.

Unstable Angina and Acute Coronary Syndrome. Unstable angina is a much more serious situation and is often an intermediate stage between stable angina and a heart attack, in which an artery leading to the heart (a coronary artery) becomes completely blocked. A patient is usually diagnosed with unstable angina under one or more of the following conditions:

Pain awakens a patient or occurs during rest.
A patient who has never experienced angina has severe or moderate pain during mild exertion (walking two level blocks or climbing one flight of stairs).
Stable angina has progressed in severity and frequency within a 2-month period, and medications are less effective in relieving its pain.

Unstable angina is now usually discussed as part of a condition called acute coronary syndrome (ACS). ACS also includes people with a condition called NSTEMI (non ST-segment elevation myocardial infarction) -- also referred to as non-Q wave heart attack. With NSTEMI, the blood tests suggest a developing heart attack. These conditions are less severe than heart attacks but may develop into full-blown attacks without aggressive treatment. [See In-Depth Report #12: Heart attack and acute coronary syndrome.]

Prinzmetal's Angina. A third type of angina, called variant or Prinzmetal's angina, is caused by a spasm of a coronary artery. It almost always occurs when the patient is at rest. About two-thirds of people with it have severe atherosclerosis in at least one major blood vessel. Irregular heartbeats are common, but the pain is generally relieved immediately with standard treatment.

Click the icon to see an image of a coronary artery spasm.

Silent Ischemia. Some people with severe coronary artery disease do not experience angina pain. This condition is known as silent ischemia, which some experts attribute to abnormal processing of heart pain by the brain. This is a dangerous condition because patients have no warning signs of heart disease. Some studies suggest that people with silent ischemia experience higher complication and mortality rates than those with angina pain. (Angina pain may actually protect the heart by conditioning it before a heart attack.)

Syndrome X. Syndrome X is a condition that occurs when patients have atypical angina chest pain. Their electrocardiograms are abnormal during a stress test, but they have no signs of blocked arteries. It is more likely to occur in women. Although it unclear what causes this condition, imaging tests suggest that Syndrome X may also be caused by ischemia, as is angina.

Prognosis

According to a 2007 report, nearly 16 million Americans have coronary artery disease. In the U.S., coronary artery disease is the leading killer of both men and women. In 2004, nearly 500,000 people died because of CAD. On the positive side, heart attack mortality rates have been declining. Half of men and 63% of women who die of heart disease do not have angina or other warning symptoms prior to their fatal attacks. Although at this time no tests can reliably predict whether a heart attack will occur, experts estimate that up to 30% of fatal attacks and many follow-up surgeries could be avoided with healthy lifestyle changes and by sticking to medical treatments. Two-thirds of patients who have suffered a first heart attack, however, do not take the necessary steps to prevent another.

The following syndromes suggest different degrees of severity among patients with heart disease.

Stable Angina. This condition can usually be managed with lifestyle measures and medications, such as low-dose aspirin. The more severe the angina, however, the greater the chance for progressing to a more serious condition.

Acute Coronary Syndromes (ACS). ACS includes severe and sudden heart conditions that require aggressive treatment but have not developed into a full-blown heart attack. ACS refers to either unstable angina or NSTEMI (non ST-segment elevation myocardial infarction). NSTEMI is also known as non Q-wave myocardial infarction.

Angina is a specific type of pain in the chest caused by inadequate blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).

Unstable angina is potentially serious and chest pain is persistent, but blood tests do not show markers for heart attack.
With NSTEMI, the blood tests suggest a developing heart attack, but, most likely, injury in the arteries is less serious than with a full-blown heart attack.

Most discussions of the treatment of unstable angina now refer to acute coronary syndrome. Doctors use the presence of a number of factors to help predict which ACS patients are most at risk for developing a heart attack.

First, patients are categorized by whether they have a history of heart disease or risk factors for heart disease (such as diabetes, high blood pressure, peripheral artery disease) or other complicating conditions (such as lung disease, heart failure). The doctor also evaluates the severity of the angina. Other factors that pose a high risk for ACS include:

Age 65 years or older
Evidence of severe heart tissue injury
Having a lighter weight
Having a history of severe chronic angina
Having abnormal lung sounds called rales (a bubbling or crackling sound) on examination
ST-segment deviation
Having either very slow or very fast heat beats
Having very low blood pressure

Heart Attack. A full-blown heart attack occurs with severe damage to the heart, which blocks oxygen.

ANYONE WHO BELIEVES THEY ARE HAVING A HEART ATTACK SHOULD IMMEDIATELY CALL THE EMERGENCY MEDICAL SYSTEM (911 IN THE UNITED STATES).

People with known heart disease and any unusual chest pain or other symptoms of heart attack that do not clear up with medications should go to the hospital. The degree of pain and the specific symptoms before a heart attack vary greatly among individuals. Symptoms can be abrupt, gradual, or intermittent.

Chest Pain. People with heart disease or risk factors should be concerned about any chest pain, usually precipitated by exercise or stress, that interrupts normal activities and does not clear up after resting or taking angina medications. Chest symptoms might be experienced as follows:

Pain is typically felt as a crushing weight against the chest, accompanied by profuse sweating. The pain may radiate to the left shoulder and arm, the neck or jaw, and even infrequently to the right arm. The arm may be tingling or numb.
Some people may have only a tingling sensation or a sense of fullness, squeezing, or pressure in the chest.
In some patients with a history of heart disease, chest pain is mild. Such patients may have experienced unexplained fatigue, depression, and ill health within a month of a heart attack. Although chest pain is the classic symptom, it occurs in only about half of patients with a heart attack.

Other Common Symptoms.

Nausea, vomiting, and cold sweats
A feeling of indigestion or heartburn
Fainting
A great fear of impending death, a phenomena known as angor animi

Atypical Symptoms. Some studies suggest that nearly half of patients with heart attack do not have chest pain as the primary symptom. Common atypical symptoms of a heart attack include:

Shortness of breath
Cardiac arrest
Dizziness, weakness, and fainting
Abdominal pain

Patients most likely to have atypical symptoms are women and the very elderly (although they can certainly have classic heart attack symptoms as well).

In one study, 52% of elderly people with acute coronary syndrome had atypical symptoms that included shortness of breath, nausea, profuse sweating, pain in the arms, and fainting. Such symptoms were more likely to occur in people with personal or family history of heart disease.
Before a heart attack, women are more likely than men to be nauseous and experience pain high in the abdomen or chest. Their first symptom may be extreme fatigue after physical activity rather than chest pain. Chest pain in women is also more likely to be caused by non-heart problems than in men.

Symptoms That Are Less Likely to Indicate a Heart Attack. The following symptoms are less likely to be due to a heart attack:

Sharp pain brought on by lung movements or coughing
Pain that is mainly or only in the middle or lower abdomen
Pain that can be pinpointed with the top of one finger
Pain that can be reproduced by moving or pressing on the chest wall or arms
Pain that is constant and lasts for hours (although no one should wait hours if they suspect they are having a heart attack)
Pain that is very brief and lasts for a few seconds
Pain that spreads to the legs

However, the presence of these symptoms does not always rule out a serious heart event.

Chest pain is a very common symptom in the emergency room, but heart problems account for only 10 - 33% of all episodes.

The most common causes of chest pain are muscular and bone problems. Problems affecting the ribs and chest muscles include injured muscles, fractures, arthritis, spasms, and infections.

Other causes of chest pain include:

Anxiety attacks
Gastrointestinal disorders (gallstone attacks, peptic ulcer disease, hiatal hernia, heartburn)
Asthma
Spasm in the coronary artery
Abnormalities of the heart muscle
Rupture of the aorta
Collapsed lung
Acute inflammation of the heart
Blood clot in the lung
High thyroid levels (hyperthyroidism)
Anemia
Vasculitis (a group of disorders that cause inflammation of the blood vessels)
Exposure to high altitudes (rare)

Individuals who experience symptoms of a heart attack should take the following actions:

For angina patients, take one nitroglycerin dose either as an under-the-tongue tablet or in spray form at the onset of symptoms. Take another dose every 5 minutes up to three doses or when the pain is relieved, whichever comes first.
Call 911 or the local emergency number. This should be the first action taken if angina patients continue to experience chest pain after taking the full three doses of nitroglycerin. However, only 20% of heart attacks occur in patients with long-standing angina. Therefore, anyone who has heart disease or risk factors for it and experiences heart attack symptoms should contact emergency services.
The patient should chew an aspirin (250 - 500 mg) and be sure that emergency health providers are informed of this so an additional dose is not given.
Patients with chest pain should go immediately to the nearest emergency room, preferably traveling by ambulance. They should not drive themselves.

Click the icon to see an image about heart attack symptoms.

Click the icon to see another image about heart attack symptoms.

Risk Factors

Over 13 million Americans have had angina, a heart attack, or both. Each year, about 1.2 million people will experience a serious heart event. About 25% of all Americans have one or more risk factors for heart disease. Most risk factors for heart disease are related to lifestyle and environmental factors.

Over the past decades, heart disease rates declined in both men and women as they quit smoking and improved dietary habits. This rate, however, has stabilized in recent years, most likely because of the dramatic increase in obesity in the U.S. and other industrialized nations. There have also been minimal changes in other risk factors, including smoking, sedentary behavior, and blood pressure control. Some risk factors cannot be changed, including age, gender, and genetics. Nevertheless, their effects can still be modified with healthy lifestyle changes.

Heart disease may be prevented with a healthy diet and regular exercise, and by quitting smoking if you smoke. Follow your health care provider's recommendations for the treatment and prevention of heart disease.

The American Heart Association guidelines for preventing heart disease recommend:

Improve Cholesterol. People with at least two risk factors and a 10-year risk for heart disease or stroke of more than 20% should aim for LDL levels of less than 100 mg/dl. Statins are now used in more cases.

Keep Blood Pressure Low. People in normal health should have a blood pressure reading of 120/80 mm Hg or less. According to the latest guidelines, blood pressure readings of 120/80 are considered normal, readings of 140/90 or higher indicate hypertension, and readings in between the two are called pre-hypertension. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 mm Hg or less, while others should be no higher than 140/90 mm Hg.

Exercise. Everyone in normal health should engage in at least moderate physical activity for a minimum of 30 minutes on most, if not all, days of the week.

Healthy Diet. Everyone should aim for a diet that contains a healthy balance of fruits, vegetables, grains, fish, nuts, legumes, poultry, lean meat, and low-fat dairy items. Avoid saturated fats and trans-fatty acids.

Quit Smoking. Also avoid exposure to secondhand smoke.

Maintain Weight. People should aim for a BMI index of 18.5 - 24.9.

Taking Aspirin. People whose risk for heart disease within 10 years is 10% or more should take a low-dose aspirin every day, unless they have medical reasons to avoid aspirin.

Control Diabetes. People with diabetes should aim for fast blood glucose levels of less than 110 mg/dl and hemoglobin A1C or less than 7%.

Control Atrial Fibrillation. People with atrial fibrillation should use anticoagulants to reduce the risk for blood clots.

Age. About 85% of people who die from heart disease are over the age of 65.

Gender. Coronary artery disease and heart attacks are much more common in middle-aged men. Women have, on average, 10 - 15 more years of heart disease-free life than do men, but as women age, they catch up to men. Women, in fact, are more likely to have angina than men. Younger women with heart disease often do not have the same symptoms as their male counterparts and may be less likely to be diagnosed correctly. They are also more likely than men to die after a heart attack.

In 2007, the American Heart Association issued updated guidelines focusing on prevention of heart disease in women. The new guidelines recommend:

Healthy diet (fresh fruits and vegetables, low-fat dairy products, salt and saturated fat restrictions, alcohol moderation)
Eating oily fish (such as salmon) at least twice a week. Women with existing heart disease should consider taking fish oil supplements of 850 – 1,000 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DPA).
Increased physical activity (60 – 90 minutes, preferably 7 days a week)
Quitting smoking
Low-dose aspirin therapy for all women age 65 years and older who can safely take aspirin. High-risk women may require 75 – 325 mg / day; lower-risk women may benefit from 81 mg a day or 100 mg every other day.

Genetic Factors. Genetics are involved in increasing the likelihood of developing important risk factors such as diabetes and high blood pressure. For example, one genetic variant called apolipoprotein E4 (ApoE4) affects cholesterol levels, particularly those associated with heart disease.

Ethnicity. African-American women face the highest risk for death from heart disease, and their rate of heart attacks is increasing. (Mortality rates in men do not differ much by race.) Native American men have a lower risk for heart disease than Caucasian men, and Hispanics have the lowest risk for heart disease of all major American population groups.

African-Americans face a number of biologic and social dangers to their hearts.

They have a higher prevalence of diabetes and hypertension than do Caucasians.
They tend to have poorer diets, higher stress levels, and less access to health care.
All African-Americans risk discrimination in obtaining optimal treatments, but women may be at particular risk for unequal treatment. In one study in which female actors portrayed heart patients, African-American women were 60% less likely to receive aggressive (and expensive) diagnostic tests than African-American men or any Caucasians, even though they presented with similar symptoms.
While African-Americans comprise 13% of the U.S. population, African-Americans have comprised only 2 - 9% of subjects in most major research trials, so knowledge about their specific risks is limited.
Some African-Americans with coronary artery disease appear to have a genetic trait that increases the danger of triglycerides, which may be particularly hazardous for women.

Click the icon to see an image about ethnicity and heart disease risks.

Cholesterol. In spite of its bad press, cholesterol is an essential nutrient necessary for many cellular functions. However, when certain cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol responsible for many heart problems. Triglycerides are another type of lipid (fat molecule) that can be bad for the heart. High-density lipoprotein (HDL) cholesterol is the "good" cholesterol that helps protect against heart disease. Doctors test for a "total cholesterol" profile that includes measurements for LDL, HDL, and triglycerides. The ratio of these lipids can affect heart disease risk.

For example, according to one study, men with total cholesterol levels over 240 mg/dl have a risk that is two to four times higher than men whose cholesterol is below 200. A number of studies have demonstrated that reducing LDL and total cholesterol levels and boosting high-density lipoprotein (HDL) levels can improve survival and prevent heart attacks in people with and without heart disease.

It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by the Friedewald formula: LDL=TC-HDL-TG/5. (LDL=low-density lipoprotein; TC= total cholesterol; HDL=high-density lipoprotein; TG=triglycerides.)

Click the icon to see an image about serum cholesterol.

Cholesterol Goals. In 2004, the National Cholesterol Education Program updated its clinical practice guidelines. The new recommendations set lower treatment goals for LDL levels based on a patient's risk factors for heart disease.

These risk factors include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides

Having two or more of these risk factors indicates a greater than 20% chance of having a heart attack within 10 years.


Risk Level	Goal (d/L)	Optimal Goal(d/L)
Very High Risk	70	70
High Risk	100	70
Moderate Risk	130	100
Low Risk	160	130

LDL cholesterol, together with other risk factors for heart disease, is the best determinant for whether cholesterol therapy is needed and whether it is working properly. In particular, the new guidelines emphasize lower LDL levels and earlier treatment for people with coronary artery disease, or other forms of atherosclerosis, and diabetes.


Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
Less than 200 mg/dL is desirable. Between 200 and 239 is borderline. Over 240 is high.	70 mg/dL or less is the new goal for very high-risk patients (recent heart attack; current active or unstable cardiovascular or cerebrovascular disease; or two multiple risk factors as defined above.) Below 100 mg/dl is optimal for everyone. It should be the goal for high-risk people including those with existing heart disease, diabetes, or two or more risk factors for heart disease; 70 mg/dL is an optimal goal for these individuals. 130 mg/dl or below for people with two or more risk factors; 100 mg/dL is the optimal goal. 160 mg/dl or less for people at less risk (one or zero risk factors); 130 mg/dL is the optimal goal. Anything over 160 is high with levels over 190 being very high. LDL levels over 190 require medication even with no other cardiac risk factors present.	Levels above 40 mg/dL are desirable; levels above 60 mg/DL are optimal.	Below 150 mg/dL is normal. 150-199 is borderline high. 200-499 is high. Over 500 is very high.
*Risk factors for heart disease include a family history of early heart problems before age 55 for men, before age 65 for women, smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dl. People with two or more of these risk factors may have a 10-year risk of heart attack that exceeds 20%, and may therefore need to aim for LDL levels of 100 mg/dL or below.

Other Lipids. Elevated levels of other fatty molecules (lipids) are also now thought to be important indicators of heart disease risk. Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), or lp(a). This lipoprotein falls somewhere in density between HDL and LDL and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause.

[See In-Depth Report #23: Cholesterol; and In-Depth Report #43: Heart-healthy diet.]

High blood pressure, or hypertension, has long been a proven cause of coronary artery disease. Blood pressure is categorized as normal, prehypertensive, and hypertensive (which is further divided as Stage 1 or 2 according to severity). High blood pressure is generally considered to be a blood pressure reading greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic). Blood pressure readings in the prehypertension category (120 - 139 systolic or 80 - 89 diastolic) indicate an increased risk for developing hypertension. [See Table Blood Pressure Ranges.]

A normal blood pressure reading is 120/80 mm Hg or lower. Most people with high blood pressure should aim for a goal of below 140/90 mm Hg. Patients with certain health problems should aim lower (blood pressure in patients with kidney disease, heart failure, or diabetes should be equal to or lower than 130/80 mm Hg.)

Click the icon to see an image about hypertension.


Blood Pressure Category	Ranges for Most Adults (systolic/diastolic)
Normal Blood Pressure (systolic/diastolic)	Systolic below 120 mm Hg Diastolic below 80 mm Hg
Prehypertension (Formerly Classified as Normal to High-Normal Blood Pressure)	Systolic 120 to 139 mm Hg Diastolic 80 to 89 mm Hg (NOTE: 139/89 or below should be the minimum goal for everyone. People with diabetes or chronic kidney disease should strive for 130/80 or less.)
Mild Hypertension (Stage 1)	Systolic 140 to 159 mm Hg Diastolic 90 to 99 mm Hg
Moderate-to-Severe Hypertension (Stage 2)	Systolic over 160 mm Hg and/or Diastolic over 100 mm Hg
Note: If one of the measurements is in a higher category than the other, the higher measurement is usually used to determine the stage. For example, if systolic pressure is 165 (Stage 2) and diastolic is 92 (Stage 1), the patient would still be diagnosed with Stage 2 hypertension. A high systolic pressure should be a major focus of concern in most adults.

American obesity is at epidemic levels in all age groups. 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 are usually high while HDL (beneficial cholesterol) levels tend to be low, both risk factors for heart disease. Obesity has other effects (hypertension, increase in inflammation) that pose major risks to the heart.

Click the icon to see an image of childhood obesity.

Obesity is particularly hazardous when it is one of the components of the metabolic syndrome. This syndrome is diagnosed when three of the following are present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. A 2002 study estimated that 24% of the population now has this condition. Obesity is highly linked with type 2 diabetes, and diabetes itself poses a significant risk for high cholesterol levels and heart disease.

Some obese patients with coronary artery disease may consider having bariatric surgery (stomach bypass) to lose excess weight. The weight lost after surgery can help improve blood pressure, cholesterol, blood sugar and other factors associated with CAD. A 2005 study reported that bariatric surgery is safe for patients with CAD who cannot lose weight with diet and exercise, which should always be tried first.

[See In-Depth Report #53: Weight control and diet.]

People who are sedentary are almost twice as likely to suffer heart attacks as are people who exercise regularly. Exercise has a number of effects that benefit the heart and circulation, including:

Improving cholesterol and lipid levels
Reducing inflammation in the arteries
Assisting weight loss programs
Helping to keep blood vessels flexible and open

Studies continue to show that physical activity and avoiding high-fat foods are the two most successful means of reaching and maintaining heart healthy levels of fitness and weight.

Experts have been attempting to define how much exercise is needed to produce heart benefits. In 2002, a well-conducted study on overweight adults confirmed previous research that reported beneficial changes in cholesterol and lipid levels even when people performed low amounts of moderate or high intensity exercise (walking or jogging 12 miles a week). However, more intense exercise is required to significantly change cholesterol levels, notably by increasing HDL (the so-called good cholesterol). Overweight people who have trouble losing pounds can still achieve considerable heart benefits by exercising. Resistance (weight) training has also been associated with heart protection. Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Click the icon to see an image about exercise.

Click the icon to see an image about hypertension and lifestyle changes.

Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise, which can be particularly helpful for older people.

Sudden strenuous exercise (such as snow shoveling and mowing lawns) puts many people at risk for angina and heart attack. Activities that involve raising the arms above the head may also be risky. Patients with angina should never exercise shortly after eating. People with risk factors for heart disease should seek medical clearance and a detailed exercise prescription. And all people, including healthy individuals, should listen carefully to their bodies for signs of distress as they exercise. [See In-Depth Report #29: Exercise.]

Heart disease and stroke are the leading causes of death in people with diabetes. People with diabetes are at risk for the following heart-risk conditions, and the more of these conditions they have, the worse the outlook.

High blood pressure (hypertension). Up to 75% of cardiovascular problems in people with diabetes may be due to hypertension.
Very unhealthy cholesterol and lipid balances (high triglyceride levels and lower HDL).
Blood clotting problems.
Impaired nerve function (neuropathy), which can also damage the heart. Some experts estimate that the mortality rates from neuropathy-related heart conditions range from 15 - 53%.

People with both diabetes and heart disease may have a higher risk for silent ischemia, a condition in which people have blocked arteries but do not experience the angina, the chest pain that signals heart disease. [See In-Depth Report #9: Diabetes - type 1; or In-Depth Report #60: Diabetes - type 2.]

Peripheral artery disease (PAD) occurs when atherosclerosis affects the extremities, particularly the feet and legs. The major risk factors for heart disease and stroke are also the most important risk factors for PAD. (The combination of such conditions with PAD also produces more severe forms of heart or circulatory disease.) Although signs of heart disease are detected in only 20 - 40% of patients with PAD after an initial diagnosis, studies suggest that when intense heart-diagnostics tests are performed, such as angiography or thallium stress tests, co-existing heart disease is detected in up to 90% of all PAD patients. [See In-Depth Report #102: Peripheral artery disease.]

Smokers in their 30s and 40s have a heart-attack rate that is five times higher than their nonsmoking peers. Cigarette smoking may be directly responsible for at least 20% of all deaths from heart disease, or about 120,000 deaths annually. Smoking cigars may increase the risk of early death from heart disease, although evidence is much stronger for cigarette smoking. Although heavy cigarette smokers are at greatest risk, a 2002 study suggested that people who smoke as few as three cigarettes a day are at higher risk for blood vessel abnormalities that endanger the heart. Regular exposure to passive smoke also increases the risk of heart disease in nonsmokers. [See In-Depth Report #41: Smoking.]

Eating habits can be protective or dangerous to the heart. Avoiding saturated fats and trans-fatty acids is particularly important for controlling cholesterol.

Diet plays an important role in the health of the heart. In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cut down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey.)
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Stress. The effects of mental stress on heart disease are controversial. Stress can affect the heart when it activates the sympathetic nervous system (the automatic part of the nervous system that affects many organs, including the heart). Some studies suggest an association between acute stress and a higher risk for serious cardiac events, such as heart rhythm abnormalities and heart attacks, in people with heart disease. However, not all studies report strong evidence that stress has any effect on the heart, particularly in people without any history of heart disease. [See In-Depth Report #31: Stress.]

Depression. Depression increases the severity of heart attack and may even worsen a patient's response to medication for heart disease. Although people with heart disease may become depressed, this does not explain entirely the link between the two problems. Data suggest that depression itself may be a risk factor for heart disease as well as its increased severity.

A number of studies indicate that depression has biologic effects on the heart, including blood clotting and heart rate. One study, for example, reported an association between depression and a greater risk for death from heart problems even in people without a history of heart disease. Even mild depression, which includes feelings of hopelessness experienced over many years, may harm the heart. A 2007 study suggested that depressive symptoms (fatigue, loss of appetite) may be a sign of thickening arteries, the early stage of coronary artery disease. [See In-Depth Report #8: Depression.]

Benefits of Moderate Drinking. Several studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate alcohol consumption can help boost HDL levels. Alcohol may also prevent blood clots and inflammation. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit.

Adverse Effects of Heavy Drinking. By contrast, heavy drinking harms the heart. In fact, heart disease is the leading cause of death in alcoholics. Evidence suggests that people who consume more than three drinks a day have abnormal blood clotting factors. Heavy alcohol consumption can raise blood pressure, and binge drinking may increase the risk for hemorrhagic stroke (caused by bleeding in the brain). Large doses of alcohol can trigger irregular heartbeats, which can be dangerous in people with existing heart disease.

Pregnant women and people who can't drink moderately should not drink at all.

Homocysteine and Vitamin B Deficiencies. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements do help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took B vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Click the icon to see the benefits of vitamin B.

Click the icon to see the food sources of vitamin B.

C-Reactive Protein. C-reactive protein is a product of the inflammatory process. Evidence increasingly suggests that high levels may predict future heart disease. It is not known if the protein plays any causal role or whether it is simply a marker for other factors in the disease process.

C. pneumoniae and Other Infectious Organisms. Some microorganisms and viruses have been under suspicion for triggering the inflammation and damage in the arteries that contribute to heart disease. The strongest evidence to date supports a possible role from Chlamydia (C.) pneumoniae (a non-bacterial organism that causes mild pneumonia in young adults). C. pneumoniae has been detected in plaques in the arteries of patients with heart disease. In some studies, evidence of previous infection has been associated with a higher risk for heart events.

Other studies also suggest that cytomegalovirus (CMV), a common virus, may have similar effects. Many people, however, have been infected with these organisms, and no clear association has been found with any of these infections.(H. pylori, the bacteria that causes peptic ulcers, has also been studied for heart effects, but evidence is very weak on any link.)

Erectile Dysfunction. Recent research suggests that erectile dysfunction may be a warning sign of coronary artery disease, even in men who are not considered at risk for the condition. Some studies indicate that men with erectile dysfunction have higher levels of C-reactive protein and more symptoms of atherosclerosis than men without erectile problems.

Periodontal Disease. A number of studies support an association between periodontal disease and cardiovascular disorders. According to a 2003 major analysis, periodontal (gum) disease is associated with a 20% higher risk for ischemic stroke and heart disease. (The added risk may be even higher in adults under 65.) Recent evidence is pointing to the inflammatory response as the common element.

Click the icon to see an image of gum disease.

Anemia. Anemia has adverse effects on the heart and increases the severity of cardiac conditions, including heart failure and heart attacks. A 2002 study suggested that anemia may even be a risk factor for heart disease itself. Blood transfusions after a heart attack improve survival rates in elderly patients who are anemic.

Iron Overload. An inherited disease called hemochromatosis, in which the intestinal tract absorbs too much iron from food, has been associated with atherosclerosis and heart attack. About 10% of Caucasians carry the gene for this condition. There is no strong evidence that excess iron levels in people without hemochromatosis can contribute to heart disease.

Sleep Apnea. Obstructive sleep apnea is a condition in which tissues in the upper throat collapse at intervals during sleep, thereby blocking the passage of air. It has been strongly associated with high blood pressure and obesity, but is also associated with heart disease and heart attacks, regardless of these risk factors. Some evidence suggests that obstructive apneas cause an increase in stiffness and inflammation in the arteries.

Some inborn or natural conditions are not risk factors themselves but have been associated with a higher incidence of heart disease or its consequences:

Factors Before Birth and In Infancy. Low weight at birth and in the womb has been associated with later heart disease in a few studies. Some suggest, however, that this may just reflect poor nutrition in the mother, which appears to affect life-long risk.

Seasonal Differences. More deaths from heart disease occur in December and January, and the fewest in the summertime. Although lower temperatures and snow shoveling may play a role in some cases, more winter deaths have been reported even in warm regions. Holiday stress or fewer daylight hours have been suggested as other reasons for these higher winter rates.

Physical Characteristics. Male pattern baldness, hair in the ear canals, and creased earlobes are associated with a higher risk for heart disease in Caucasian males.

Click the icon to see an image of an ear lobe crease.

Diagnosis

Many tests can diagnose possible heart disease. The choice of which (and how many) tests to perform depends on the patient's risk factors, history of heart problems, and current symptoms. Usually the tests begin with the simplest and may progress to more complicated ones.

Doctors routinely check for high blood pressure and unhealthy cholesterol levels in all older adults. Specific tests are also important in people who may have risk factors or symptoms of diabetes. Doctors may also test for homocysteine, the protein albumin, and blood clotting factors, especially fibrinogen.

An electrocardiogram (ECG) measures and records the electrical activity of the heart. Between 25 - 50% of people who suffer from angina or have silent ischemia, however, have normal ECG readings. The waves measured by the ECG correspond to the contraction and relaxation pattern of the different parts of the heart. Specific waves seen on an ECG are named with letters:

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

P. The P wave is associated with the contractions of the atria (the two chambers in the heart that receive blood from outside).
QRS. The QRS is a series of waves associated with ventricular contractions. (The ventricles are the two major pumping chambers in the heart.)
T and U. These waves follow the ventricular contractions.

The most important wave patterns in diagnosing and determining treatment for heart disease and heart attack are called ST elevations and Q waves.

A depressed or horizontal ST wave suggests some blockage and the presence of a heart disease, even if there is no angina present. (This finding, however, is not very accurate, particularly in women, and can occur without heart problems).
ST elevations and Q waves are the most important wave patterns in diagnosing and determining treatment for a heart attack. They suggest that an artery to the heart is blocked, and that the full thickness of the heart muscle is damaged. ST segment elevations do not always mean the patient has a heart attack. And, some heart attack patients do not have elevated ST segments. Other factors are important in making a diagnosis.

The primary value of exercise stress tests is not to detect coronary artery disease but to help determine the severity and predict the outcome of an existing heart condition. It is considered for the following people:

Patients with possible or probable angina and low or intermediate risk for adverse heart events.
Selected adults who do not have symptoms of heart disease but are at moderate risk to high risk for developing heart disease (a 10 - 20% chance within 10 years). Moreover, heart blockage without angina (silent ischemia) may suggest a more severe condition, at least in men.

Basic Procedure. A stress test (exercise tolerance test) monitors the patient's heart rhythms, blood pressure, and clinical status. It can tell how well the heart handles work and if parts of the heart have decreased blood supply. A typical stress test involves:

The patient walks on a treadmill or rides a stationary bicycle. Exercise continues until the heart is beating at least 85% of its maximum rate, until symptoms of heart trouble occur (changes in blood pressure, heart rhythm abnormalities, angina, fatigue), or the patient simply wants to stop.
For patients who cannot exercise, the doctor may administer dobutamine or arbutamine, which are drugs that simulate the stress of exercise.
An ECG is used to monitor heart rhythms during a stress test. (An echocardiogram or more advanced imaging technique may also be used to visualize the actions of the heart and blood flow.)

More than 25% of patients stop exercising before they reach their own maximum limits because of fear of a heart event. Patients should be reassured that the activities performed in the test under the guidance of a professional are safe.

Interpreting Results. To accurately assess heart problems, experts look at a number of findings derived from the ECG and other tools during exercise. They include:

Exercise capacity. This is a measure of a person's capacity to reach certain metabolic rates.
Heart rate and ST waves. On ECGs, doctors specifically look for abnormalities in part of the wave tracing called an ST segment. A certain type of ST segment depression may suggest the presence of heart disease. However, gender, drugs and other medical conditions can affect the ST segment. Using a measurement that adjusts the ST segment to heart rate improves accuracy.
Dukes Treadmill Score. This important score uses the number of minutes a patient can exercise and other factors that are present in patients with exercise-limiting angina.
Heart rate recovery.
Chronotropic index. This is the percentage of the heart-rate reserve that is used during the exercise. A result of 80% or less suggests a significant risk for serious heart problems in most patients.
Changes in systolic blood pressure.

Using these and other measures, doctors can determine risk fairly accurately, particularly for men of any age with chronic stable angina. The test has limitations, however, and some are significant. For example, a 2002 study indicated that in patients with suspected unstable angina the chances for a future adverse heart event remain high even if the exercise test shows low risk. In addition, for many reasons, the test is less accurate in women, and an echocardiogram may be a more accurate procedure for them. About 10% of patients, particularly younger people, will have false positive test results. In such cases, test results indicate abnormalities when there are no heart problems.

An echocardiogram is a noninvasive test that uses ultrasound images of the heart. This test is more expensive than an ECG, but it can be very valuable, particularly when used with a stress test, to detect the location and extent of heart muscle damage. It appears to be more accurate for women than ECG stress tests, but at this time it is not routinely recommended as a replacement for most women.

Computed tomography (CT) scans used alone or with ECG may be used to detect calcium deposits on the arterial walls, which are strong indicators of current and future coronary artery disease. The presence of calcium does not always signify narrowing of the arteries. But, the absence of calcification in the arteries indicates the patient has no risk for heart disease.

Advanced CT techniques are improving accuracy:

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

Electron Beam Computed Tomography. Electron beam computed tomography (EBCT) is a CT technique that scans the heart so quickly that the motion of the heart appears frozen. This procedure identifies calcification and stratifies cardiac risk accurately.
Multidetector Computed Tomography. Another CT technique called multidetector computed tomography (MDCT) is able to take pictures of the entire heart in 1 millimeter slices in the time it takes for a patient to hold one breath. A 2006 study indicated that MDCT tends to have a high “false-positive” rate (indicating disease when it is not actually there), but for some patients the test may be helpful in ruling out coronary artery disease.

Some expert groups recommend CT scans in selected patients who have an intermediate risk (10 - 20% chance of heart disease within 10 years). For some of these patients, EBCT may be preferred over exercise stress testing, but most experts recommend a stress test as the main diagnostic tool. In general, the use of these expensive imaging tests is probably not very helpful for people at low or high risk. (For people with high risk, the additional information from these tests would not add much value.) More research is needed to determine the benefits of CT scanning in specific individuals.

Radionuclide procedures use imaging techniques and computer analyses to plot and detect the passage of radioactive tracers through the region of the heart. Such tracing elements are typically given intravenously. Radionuclide imaging is useful for diagnosing and determining:

Severity of unstable angina when less expensive diagnostic approaches are unavailable or unreliable
Severity of chronic coronary artery disease
Success of surgeries for coronary artery disease.
Whether a heart attack has occurred

Various imaging techniques may be used with radionuclide procedures, including:

Planar scintigraphy uses a special overhead camera and is the oldest scanning technique.
Single-photon emission computed tomography (SPECT) uses a camera that rotates around the patient and takes pictures of "slices" of the heart. It is more accurate than planar imaging in precisely locating problems in the arteries.
Positron-emission tomographic (PET) scanners employ multiple rings that surround the patients, which detect and record atomic particles (photons) that are emitted by the tracer elements (such as radioactive oxygen, nitrogen, or carbon). It is more expensive and less widely available than SPECT.

Myocardial Perfusion (Blood Flow) Imaging Test (also called the Thallium Stress Test). This radionuclide test is typically used with an exercise stress test to determine blood flow to the heart muscles. It is a reliable measure of severe heart events. It may be useful in determining the need for angiography if CT scans have detected calcification in the arteries. About a minute before the patient is ready to stop exercising, the doctor administers a radioactive tracer into the intravenous line. (Tracers include thallium, technetium, or sestamibi.) Immediately afterwards, the patient lies down for a heart scan, usually with a planar scintigraphy or with SPECT. If the scan detects damage, more images are taken 3 or 4 hours later. Damage due to a prior heart attack will persist when the heart scan is repeated. Injury caused by angina, however, will have resolved by that time.

Radionuclide Angiography. This is a technique for visualizing the chambers and major blood vessels of the heart. It uses an injected radioactive tracer and can be performed during exercise, at rest, or with use of stress-inducing drugs. It is an excellent test for assessing the heart's pumping action and for determining the severity of coronary artery disease. It is an alternative to echocardiograms in certain situations.

Click the icon to see an internal view of the heart.

Magnetic Resonance Angiography (MRA). MRA is a very promising noninvasive imaging technique that can provide three-dimensional images of the major arteries to the heart and identify disease with high accuracy. Experts believe this approach will eventually be a good alternative to angiography.

Click the icon to see an image of a MRI.

Angiography is an invasive test. It is used for patients who show strong evidence for severe obstruction on stress and other tests, and for patients with acute coronary syndrome.

A narrow tube is inserted into an artery, usually in the leg or arm, and then threaded up through the body to the coronary arteries.
A dye is injected into the tube, and an x-ray records the flow of dye through the arteries.
This process provides a map of the coronary circulation, revealing any blocked areas.

Click the icon to see an image of dye in the coronary artery.

Major complications include stroke, heart attacks, and kidney damage. These risks are very low (about 0.1%), however, if the procedure is done in an experienced medical center (one that performs at least 300 of these operations every year). Allergic reactions can also occur. The procedure is expensive, and between 10 - 30% of patients who have this procedure have normal results.

When heart cells become damaged, they release different enzymes and other molecules into the bloodstream. Elevated levels of such markers of heart damage in the blood or urine may help predict a heart attack in patients with severe chest pain and help determine treatment. Some of these factors include:

Troponins. The proteins cardiac troponin T and I are released when the heart muscle is damaged. Both are proving to be among the best diagnostic indications of heart attacks. They help to identify many individuals with ACS who might otherwise be misdiagnosed.
Creatine kinase myocardial band (CK-MB). CK-MB has been a standard marker, but the MB fraction is not as accurate as troponin levels, since elevated levels can appear in people without heart injury.
Myoglobin. Myoglobin is a protein found in heart muscles. It is released early in the injured heart, and it may be useful in combination with CK-MB and the troponins.
Newer biomarkers, including C-reactive protein (CRP), homocysteine, B-type natriuretic peptide (BNP), urinary albumin, and fibrinogen.

Several 2006 studies that evaluated how well biomarkers predict risk of heart events concluded that they do not provide much more useful information than standard risk factors (high blood pressure, unhealthy cholesterol levels, diabetes). At this time, most experts feel that these standard disease risk factors provide the best predictors of the likelihood of developing coronary artery disease, heart attack, or stroke.

Managing Heart Disease

The approach for managing any degree of coronary artery disease involves lifestyle changes. Depending on severity and individual conditions, patients may need one or more medications, surgery, or both.

Healthy diet, regular exercise and quitting smoking if you are a smoker may prevent heart disease. Follow your health care provider's recommendations for treatment and prevention of heart disease.

Experts have come up with a mnemonic device (ABCDE) for remembering 10 factors that are fundamental for management of stable angina and coronary artery disease:

A. Aspirin and anti-angina drugs

B. Blood pressure and beta-blockers

C. Cholesterol-lowering drugs (typically statins) and cigarettes (stopping)

D. Diet and diabetes control

E. Exercise and education

Unstable angina is now usually classified with non-Q myocardial infarction as acute coronary syndrome (ACS) in professional discussions of treatments. ACS usually requires more aggressive treatments, including surgery. [ACS is more fully discussed in In-Depth Report #12: Heart attack and acute coronary syndrome.]

Click the icon to see an image about angina.

Anti-Clotting Medications

Anti-clotting drugs that inhibit or break up blood clots are used at every stage of heart disease. They are generally classified as either antiplatelets or anticoagulants. All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Antiplatelet Drugs. These drugs prevent formation of blood platelets. Platelets are very small disc-shaped blood cells that are important for blood clotting.

Aspirin. Aspirin is an antiplatelet. It is the most common anti-clotting drug. Nearly anyone with existing heart disease or at risk for it is advised to take a low-dose aspirin every day.
Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are thienopyridines, another type of anti-platelet drug.
Glycoprotein IIb/IIIa Inhibitors. These powerful blood-thinning drugs include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are used after angioplasty surgery and stent placement.

Click the icon to see an image about blood.

Anticoagulants. Anticoagulants help thin blood and include:

Heparin
Warfarin (Coumadin)
Direct thrombin inhibitors

Aspirin. Aspirin is known as a nonsteroidal anti-inflammatory drug (NSAID). It stops blood platelets, which are major clotting factors, from sticking together to form a blood clot. A daily low-dose aspirin (75 - 325 mg) is usually the first choice for preventing heart disease in high-risk individuals. Aspirin can prevent by 25 – 50% the risk of heart attacks and death in people with existing heart disease and a history of heart attack. It also reduces the risk for stroke. According to a 2006 review, aspirin works equally well for both men and women.

Click the icon to see an image about stomach ulcers.

Side effects from prolonged use of aspirin may include stomach ulcers and bleeding. (There may be a slight increased risk for bleeding-related strokes, which are very uncommon, however. Furthermore, this risk may be outweighed by protection against the more common type of stroke, which is caused by artery blockage.)

Clopidogreland Ticlopidine. Clopidogrel (Plavix) and ticlopidine (Ticlide) are anti-platelet drugs known as thienopyridines. When taken with aspirin, these drugs can significantly reduce the risk for heart attack and stroke in patients with acute coronary syndrome (unstable angina or early signs of heart attack). The combination of aspirin and a thienopyridine is essential for patients who have a drug-eluting stent. According to a 2007 American Heart Association advisory, patients who have a drug-eluting stent must take both aspirin and a thienopyridine for at least 1 year after the stent is inserted. Many experts recommend clopidogrel instead of ticlopidine because ticlopidine has been associated with dangerous blood disorders, particularly thrombocytopenia.

Clopidogrel is also recommended for patients who are undergoing angioplasty. For patients having coronary bypass surgery, it should be withheld for at least 5 -7 days prior to surgery because of a significant bleeding risk. Researchers are investigating whether clopidogrel and aspirin together are better than aspirin alone in reducing the risks following coronary bypass surgery. A 2006 study suggested that for some patients with heart disease, clopidogrel plus aspirin does not work better than aspirin alone for preventing a first heart attack or stroke.

Click the icon to see an image of the developmental process of atherosclerosis.

Click the icon to see an image about atherosclerosis.

Anticoagulants are drugs that prevent or delay blood coagulation and the formation of blood clots. Heparin has been the standard anticoagulant, but a number of drugs are now available that are proving to be better choices in many cases.

Standard (Unfractionated) Heparin. The heparin referred to as unfractionated heparin has been the standard for years and is used alone or in combination with aspirin for managing unstable angina. It is no longer the recommended first choice, however, for this patient group. It must be intravenously administered and monitored with frequent blood tests. The major complication is thrombocytopenia (a severe drop in platelets). This condition is extremely serious and can become life-threatening, particularly with bleeding in various body tissues. Alternatives include low-molecular weight heparin and direct thrombin inhibitors.

Low-Molecular Weight Heparin. Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep) are drugs known as low-molecular weight heparins (LMWHs). Many doctors now recommend these drugs over standard heparin for patients with unstable angina (unless bypass surgery is being planned). They have similar rates of survival, recurring angina, and bleeding as standard heparin. However, they pose lower risks for heart attack, repeat angioplasties, and thrombocytopenia. They require injections but do not require the ongoing monitoring that standard heparin does. Patients may even be able to self-administer LMWHs as people with diabetes do insulin.

Warfarin. Warfarin (Coumadin) is an oral anticoagulant. It prevents clots by inhibiting vitamin K. Warfarin is used with aspirin after a heart attack to prevent another one and to prevent blood clots in patients with atrial fibrillation. Warfarin is also proving to be more effective than aspirin for preventing heart attacks in patients with acute coronary syndromes. Warfarin therapy poses a dangerous risk for bleeding and blood coagulation must be monitored with frequent blood tests.

Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI was hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaparoid (Orgaran), lepirudin (Refludan), desirudin (Revasc), and ximelagatran (Exanta). Many of these drugs are used along with warfarin and may be good options for patients who develop thrombocytopenia with heparin use. DTIs may prove to be superior to standard heparin for patients with acute coronary syndrome.

Other Medications

Nitrates have been used in the treatment of angina for over 100 years. These drugs release nitric oxide, thereby relaxing the smooth muscles in blood vessels. Many nitrate preparations are available. The most commonly used are nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates can be absorbed from the gastrointestinal tract (oral tablet), skin (ointment or patch), or from under the tongue (sublingual tablet or spray).

Rapid Acting Nitrates. Rapid-acting nitrates are used to treat acute attacks. Nitroglycerin is the most widely used drug for this purpose. It can be administered under the tongue (sublingually or as a spray) or pocketed between the upper lip and gum (buccally) and can relieve angina within minutes. The procedure for taking nitroglycerin during an attack is as follows:

At the onset of an angina attack, the patient administers one sublingual or buccal tablet or one metered dose of the spray.
If the pain is not relieved within 5 minutes the patient takes a second dose; a third can be taken after another 5 minutes if symptoms persist.
If pain continues after a total of three doses in 15 minutes, the patient should go immediately to the nearest emergency room.

Nitroglycerin is very volatile so its potency can be easily lost. Patients should take the following precautions:

Keep no more than 100 tablets on hand, stored in their original container.
When first opened, the cotton filler should be discarded, and the cap screwed on tightly immediately after each use.
A supply should always be kept close at hand in case of an attack, with the rest kept in a cool dry place.

Intermediate to Long-Term Nitrates. Sublingual tablets of isosorbide dinitrate have a somewhat slower onset of action than nitroglycerin and are useful for preventing exercise angina. Ointments, patches, and oral tablets are used for longer-term prevention of angina attacks:

Transdermal patches are applied in the morning to any hair- or injury-free area on the chest, back, stomach, thigh, or upper arm. Hands should be washed after each patch or ointment application, and sites of application should be rotated to avoid skin irritation.
Nitroglycerin ointment is applied by measuring out an even amount on an applicator paper and then placing, not rubbing or massaging, it on the chest, stomach, or thigh. Any ointment that remains from the previous application should be removed.

Long-acting forms may lose their effectiveness over time, so doctors generally schedule nitrate-free breaks to prevent tolerance. Some concern exists that nitrate-free periods might increase the risk for angina and adverse heart events. One large study, however, found no increased danger when patients used a nitroglycerine patch with scheduled breaks. The use of high blood pressure drugs known as ACE inhibitors may help prevent tolerance to nitrates.

Side Effects. Nitrates have many side effects, some of which can be serious.

Common side effects of nitrates include headaches, dizziness, nausea and vomiting, blurred vision, fast heartbeat, sweating, and flushing on the face and neck. Low blood pressure and dizziness can be relieved by lying down with the legs elevated. These effects are significantly worsened by alcohol, beta-blockers, calcium channel blockers, sildenafil (Viagra), and certain antidepressants. The doctor may prescribe medicines to lessen these side effects. Patients should contact their doctor if these side effects are persistent or severe.

Serious side effects requiring immediate medical help include fever, joint or chest pain, sore throat, skin rash (especially on the face), unusual bleeding or bruising, weight gain, and swelling of the ankles.

Withdrawal. Withdrawal from nitrates should be gradual. Abrupt termination may cause angina attacks.

Beta-blockers are useful for preventing angina attacks and reducing high blood pressure. They reduce the heart's oxygen demand by slowing the heart rate and lowering blood pressure. They are recognized for reducing deaths from heart disease and from heart surgeries, including angiography and coronary bypass. Beta-blockers are the drugs of choice for older patients with stable angina and may also be beneficial for people with silent ischemia. They are, however, less useful for the treatment of Prinzmetal’s angina. Beta-blockers are often prescribed along with other drugs such as nitrates, calcium channel blockers, or statins. A 2006 study suggested that beta-blockers and statins may help stabilize coronary artery disease and prevent the development of heart attacks.

Specific Beta-blockers. Beta-blockers include propranolol (Inderal), carvedilol (Coreg), bisoprolol (Zebeta), acebutolol (Sectral), atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol-XL), and esmolol (Brevibloc). A nasal spray form of propranolol appears to be very helpful in reducing exercise-induced angina attacks.

Side Effects. Beta-blocker side effects include fatigue, lethargy, vivid dreams and nightmares, depression, memory loss, and dizziness. They can lower HDL (“good”) cholesterol. Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. These beta-blockers should not be used by patients with asthma, emphysema, or chronic bronchitis.

Patients should never abruptly stop taking these drugs. The sudden withdrawal of beta-blockers can rapidly increase heart rate and blood pressure. The doctor may advise a patient to slowly decrease the dose before stopping completely.

Calcium channel blockers reduce heart rate and slightly dilate the blood vessels of the heart, thereby decreasing oxygen demand and increasing oxygen supply. They also reduce blood pressure. CCBs vary chemically, however, and although some are helpful, others may even be dangerous for certain patients with angina.

Click the icon to see an image of the anterior heart arteries.

Long-acting nifedipine (Adalat, Procardia) and nisoldipine (Sular) and newer CCBs, such as amlodipine (Norvasc) and nicardipine (Cardene), may be beneficial for some patients with angina. They can be considered alone for patients who cannot tolerate beta-blockers, but may provide the best results when used in combination with a beta-blocker. Studies suggest that they reduce the need for repeat angioplasties. Their effects on other outcomes, including mortality rates and heart attack, are less clear.
Short-acting CCBs, including short-acting forms of verapamil, diltiazem, nifedipine, and nicardipine, are helpful for many patients with Prinzmetal's angina. However, short-acting forms of certain CCBs, such as nifedipine and nisoldipine, have been associated with severe and even dangerous side effects, including an increase in heart attacks and sudden death in some patients with unstable angina. They also increase the risk for adverse effects in patients with stable angina. Short-acting CCBs are, therefore, not used for stable or unstable angina.

There is no strong evidence that any calcium channel blockers improve survival rates. Overdose can cause dangerously low blood pressure and slow heart beats. Patients with heart failure have a higher risk for death with these drugs and should not take them. No one taking any calcium channel blocker should withdraw abruptly because such action could dangerously increase the risk of high blood pressure. Note: Grapefruit and Seville oranges boost the effects of CCBs, sometimes to toxic levels. (Regular oranges do not appear to pose any hazard.)

Angiotensin converting enzyme (ACE) inhibitors are important heart-protective drugs, particularly for people with diabetes and high blood pressure. They reduce the production of angiotensin, a chemical that causes arteries to narrow, and so are commonly used to lower blood pressure. They may also reduce risk for heart attack, stroke, complications of diabetes, and death in patients at high risk for heart disease.

ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril).

Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. In the past, doctors sometimes avoided giving aspirin to patients who were taking ACE inhibitors because the combination was believed to cause kidney problems. But, a 2005 study of patients with both coronary artery disease and heart failure found that taking aspirin and ACE inhibitord together is safe. The researchers also noted that taking aspirin with an ACE inhibitor can significantly reduce the risk of death for older patients with CAD and heart failure. [See In-Depth Report #14: High blood pressure.]

In 2004, the National Cholesterol Education Program issued updated recommendations on how to control cholesterol levels. These guidelines emphasize that patients should lower their LDL (“bad”) cholesterol and recommend that more people take LDL-lowering medication. Lowering LDL cholesterol and raising HDL (“good”) cholesterol can significantly reduce the risks of heart disease. Several different types of drugs (statins, bile-acid binding resins, niacin, and fibrates) are used to treat cholesterol. [See In-Depth Report #23: Cholesterol.]

Statins are the most important of these drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. A 2005 review found that the more that statins lower LDL, the more they reduce CAD and other heart disease risks.

An important 2006 study found that aggressive treatment with statins may have the potential to reverse coronary artery disease. In the study, rosuvastatin reduced fatty plaque in the arteries in addition to improving LDL and HDL cholesterol levels. However, a follow-up 2007 study of rosuvastatin indicated that while the drug slowed the rate of atherosclerotic progression, it did not reverse heart disease. Future studies will continue to investigate this issue.

Side effects of statins may include stomach upset, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The main safety concern with statins is an uncommon condition called myopathy, which can cause muscle and joint pain and possible muscle damage. Doctors will immediately stop statin therapy if myopathy occurs. Patients should talk to their doctor about any unusual muscle discomfort or weakness, or if their urine becomes brown-colored. Statins can also affect the liver, particularly at higher doses, so patients taking these drugs should receive regular liver function tests.

Click the icon to see an image of cholesterol.

Influenza Vaccinations (Flu Shots). Evidence suggests influenza vaccinations help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of at risk people are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.

Antibiotics. Researchers have investigated antibiotics for treating patients with heart disease and past infection of the bacteria Chlamydia pneumoniae. Results from several recent large-scale clinical trials suggest that antibiotic treatment provides no benefit in preventing heart attack or other cardiac events in patients with coronary artery disease. In addition, a 2006 study indicated that short-term treatment with the antibiotic clarithromycin may increase the risk for death in patients with coronary artery disease. While it is still possible that C. pneumoniae may play a role in triggering inflammatory responses associated with ACS, antibiotic therapy is no longer considered appropriate for treatment or prevention of heart disease.

Ranolazine (Ranexa) was approved in 2006 for treatment of chronic angina. It is recommended for patients who have not responded to other angina drugs. Ranolazine is taken in combination with amlodipine, beta blockers, or nitrates. The drug appears to work better in men than in women

Gene Therapy and Angiogenesis. Proteins known as growth factors are being investigated for their ability to grow new blood vessels for supplying oxygen to the heart. After promising small trials, two large studies of genetically engineered forms of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF [GenerX]) failed to detect any benefits. Studies on therapies that actually genetically encode these proteins are underway.

Testosterone Supplements. Some trials using testosterone supplements or patches have reported improved exercise-induced blood flow in the coronary arteries and improvement in angina in some cases. Supplements of this male hormone, however, may increase the risk for prostate cancer. Experts suggest that testosterone be used only in older men with significant deficiencies in testosterone.

Selective Estrogen-Receptor Modulators (SERMs). Selective estrogen-receptor modulators (SERMs), including raloxifene (Evista), have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. Raloxifene may have some heart benefits, although it poses a risk for deep vein blood clots, which may have long-term implications for patients with heart problems. A major study is underway to determine its effects on the heart.

Surgery

Surgery is usually recommended for patients who have:

Unstable angina that does not respond promptly to medical treatment
Severe recurrent episodes of angina that last more than 20 minutes
Acute coronary syndrome
Severe coronary artery disease (severe angina, multi-artery involvement, evidence of ischemia), particularly if abnormalities are evident in the left ventricle of the heart, the main pumping chamber

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Researchers have been investigating whether surgery offers any advantages if used as an early treatment for mild angina. A major analysis in 2003 reported that the use of angioplasty in patients with mild heart blockage did not reduce the risk for heart attack or death over the long term. A landmark 2007 study found that angioplasty was no better than drug therapy for preventing heart attack and stroke in patients with stable coronary artery disease. (For more information, see Angioplasty and Stents.)

Two effective surgical procedures for heart patients are:

Coronary artery bypass grafting (commonly called bypass or CABG)
Percutaneous coronary intervention (commonly called angioplasty or PCI), usually with coronary artery stent placement

Click the icon to see an image about bypass grafting.

Each of these procedures is described below.

Studies have generally reported similar survival rates with either procedure. There are some differences, however, and decision often depends on individual conditions. Patients considering surgery should discuss all options and risks with their doctor. No surgical procedure cures coronary artery disease, and patients must continue to rigorously maintain a healthy lifestyle and any necessary medications. For some patients, lifestyle changes and medications may be able to control the disease without surgery or angioplasty.

Considerations for Choosing Angioplasty with Stent Placement. Angioplasty has the following advantages for most patients. It is:

Less invasive than bypass. (Although a minimally invasive variation of bypass surgery may reduce this distinction.)
Less expensive than bypass. (Although the postoperative need for more medications and the high risk for repeat procedures to reopen the artery may reduce the long-term difference in cost between the two procedures.)
Life-saving emergency procedure for many patients with heart attacks. (The use of bypass after a heart attack has much higher mortality rates than when it is used electively and its use is controversial in heart attack patients.)

It has the following disadvantages:

The blood vessels can close up again (restenosis) so that patients require additional procedures. (New blood thinning drugs, coronary stent coatings, and radiation treatments may help to significantly reduce restenosis rates. However, there is also some indication that stents, especially drug-eluting stents, may increase the risk for blood clots.)
It is not as appropriate as bypass for many patients with angina (people with diabetes, elderly patients, or those with multi-vessel blockage). Increasingly, however, angioplasty is proving to be as safe and as effective as bypass in many high-risk patients. Patients should be sure to discuss with their doctors the relevant risks and benefits of angioplasty and bypass.

Considerations for Choosing Bypass. Bypass is usually the appropriate procedure in patients with high-risk conditions, such as:

Multi-vessel blockage. (In one report comparing surgery to angioplasty in patients with two or three blocked vessels, the mortality rate 1 year after bypass was 0.8% and after angioplasty was 2.5%. About 80% of patients in the study were men.)
Diabetes. (Bypass produces significantly higher survival rates in these patients. Some experts believe angioplasty should rarely, if ever, be used in this population.)
Being elderly.
Certain structural features, such as a left main artery narrowed by 50% or more or a very long diseased portion of the artery.

Considerations for Women. Studies have reported higher mortality rates in women than in men after any heart surgery. Some experts theorize that on average women may be older and sicker when they have a heart operation. A 2002 study, however, suggested that when women with acute coronary syndromes are given the same aggressive and early treatment as men are, their survival rates are equal or even better.

In addition to angioplasty and bypass procedures, a number of other procedures are available or under investigation for coronary artery disease. They include:

Atherectomy
Myocardial Laser Revascularization
Enhanced External Counterpulsation (EECP)

Coronary Artery Bypass Graft Surgery

Coronary artery bypass graft surgery (CABG) is a good alternative to angioplasty for many patients, but it is very invasive. The surgery involves the following processes:

Click the icon to see an animation about CABG.

The chest is opened, and the blood is rerouted through a lung-heart machine.
The heart is stopped during the procedure.
Large blood vessels supply the grafts, which are used to reroute the blood. The blood vessel grafts are transplanted in front of and beyond the blocked arteries, so the blood flows through the new vessels around the blockage.
The standard grafts now use arteries taken from the chest wall. Studies are reporting that with such grafts arteries remain open in 90% of cases after 15 years.
In general, patients with triple bypass procedures stay in the hospital for 5 days. Those with one-vessel bypass may be able to go home in 3 days.

Click the icon to see an illustrated series detailing a heart bypass surgery.

In spite of the invasive nature of this procedure, elective bypass procedures produce better long-term survival rates than angioplasty, particularly in patients with diabetes and multi-vessel blockage. Overall mortality rates after this procedure range from 1% to slightly over 2%. The risk for stroke or heart attack after a bypass operation ranges from 1.3 - 5%. Finding a surgeon who performs at least 100 of the procedures a year helps reduce the risk for complications.

Blood clots may form in the new graft, closing it up or narrowing the treated vessel over time. Therapy with aspirin and other anti-clotting drugs help keep the graft open and working properly. For long-term prevention of closure, as well as for slowing progression of atherosclerosis, aggressive treatment with cholesterol-lowering drugs may be more beneficial than standard anti-clotting drugs.

Bleeding is also a potential complication of CABG. Anti-bleeding (also called hemorrhage-sparing) drugs are sometimes used to limit blood loss in patients who undergo this surgery. In 2006, concerns were raised about one of these drugs, aprotinin (Trasylol). Data suggested that aprotinin seriously increased the risks for kidney failure, heart failure, and stroke.

An important study, published in 2007 in the Journal of the American Medical Association, compared aprotinin with two anti-fibrinolytic drugs, aminocaproic acid (Amicar) and tranexamic acid (Cyklokapron), which are also used to control blood loss. The study of nearly 4,000 patients who had CABG found that over a 5-year period, the death rate for patients who took aprotinin was 21%, and patients had a 48% increased risk of dying. By comparison, the death rate was 16% for aminocaproic acid, 15% for tranexamic acid, and 13% for no anti-bleeding drug. Because aprotinin is more expensive as well as potentially more dangerous than other anti-bleeding drugs, experts are now recommending against its use in CABG.

Minimally invasive bypass (also called buttonhole or keyhole bypass) surgeries are exciting advances in basic bypass surgery. Studies indicate good success of these procedures for patients with disease in single vessels. They are also being investigated for multiple vessels.

One variation of minimally invasive bypass uses a four-inch incision. The surgeon works on the front of the heart while it is beating slowly. To date, there have been no differences in cardiac events or later mental complications between this so-called off-pump procedure and the standard bypass procedure.
In another variation, the heart is stopped, and the patient is put on a machine that reroutes the blood through a device that keeps it oxygenated. Fiberoptic scopes and instruments are passed through a number of finger-sized incisions. The surgeon works on all sides of the heart, guided by a video image from a tiny camera inserted through a 4-inch incision.
Some advanced heart centers now use robotic systems, which allow the surgeon to perform extremely delicate maneuvers on tiny vessels through pencil-size incisions. They are not yet used for the whole bypass process.

Eventually, minimally invasive bypass procedures may prove to be less expensive, require a shorter hospital stay, and have fewer complications than conventional coronary artery bypass surgery -- or even angioplasty. At this time, however, they are experimental procedures, performed in only a few medical centers for select candidates. Long term-success rates are unknown.

Angioplasty and Stents

Percutaneous coronary intervention (PCI), also called angioplasty, involves procedures such as percutaneous transluminal coronary angioplasty (PTCA) that help open the blocked artery.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

A typical angioplasty procedure follows these steps:

The cardiologist threads a narrow catheter (a tube) containing a catheter into the blocked vessel.
The doctor opens the blocked vessel using balloon angioplasty, in which the surgeon passes a tiny deflated balloon through the catheter to the vessel.
The balloon is inflated to compress the plaque against the walls of the artery, flattening it out so that blood can once again flow through the blood vessel freely.
In order to keep the artery open afterwards, surgeons use a device called a coronary stent, an expandable metal mesh tube that is implanted during angioplasty at the site of the blockage. (In some cases, a stent may be used as the initial opening device instead of balloon angioplasty.)
Once in place, the stent pushes against the wall of the artery to keep it open.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

Complications occur in about 10% of patients (about 80% within the first day). Outcomes are better in hospital settings with experienced teams and backup.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty surgery.

The most important long-term complication is reclosure (restenosis), which can lead to heart attack if not treated with a repeat procedure. Stenting and other advances have helped significantly in preventing reclosure and reducing heart attack rates. Nevertheless, a repeat procedure is still needed to restore the opening in 10 - 15% of procedures that use stents.

PCI (angioplasty) has been proven to help reduce the frequency of angina attacks. It is commonly recommended for patients who have critically blocked arteries or have already had a recent, acute heart attack. PCI can also help improve survival and prevent heart attacks in patients with acute coronary syndrome (ACS). However, doctors have been uncertain about angioplasty’s benefits for survival and heart attack prevention in lower-risk patients with stable coronary artery disease.

In 2007, a landmark study was published in the New England Journal of Medicine and presented at the 2007 meeting of the American College of Cardiology. The COURAGE study found that PCI works no better than standard heart medication (drugs to control blood pressure, lower cholesterol, and prevent blood clots) in preventing heart attack, stroke, and hospitalization in patients with stable coronary artery disease. Based on this study’s findings, experts are now recommending angioplasty only for patients who have severe heart disease. For patients with stable heart disease, drug therapy may be sufficient enough treatment and allow them to safely defer having surgery.

Angioplasty is less invasive than bypass surgery, requiring only one night in the hospital. Recuperation takes about a week. Chest pain after the procedure is very common and usually due to problems other than ischemia. Mild chest pain is even more common when a stent is used, possibly because the artery is stretched.

Reclosure of the artery during or shortly after angioplasty often occurs. A number of anti-clotting drugs are used to help prevent this.

Aspirin and the anti-platelet drug clopidogrel (Plavix) are often used to prevent reclosure during the procedure.
A high dose of the anticoagulant heparin is typically given before the operation.
Intravenous glycoprotein IIb/IIIa inhibitors, powerful drugs that block platelets, also prevent reclosure after stenting in many high-risk patients, and evidence now strongly suggests that they reduce rates of heart attack and death. Eptifibatide (Integrilin) and tirofiban (Aggrastat) are the standard drugs used during angioplasty. They may be most effective if administered during angioplasty, rather than beforehand.

All of these drugs pose a risk for bleeding complications.

Narrowing or reclosing of the artery (restenosis) can occur within a year of angioplasty or even longer in 15 - 60% of angioplasty patients. Coronary stents, anti-clotting drugs, and other advances have reduced these events significantly, but have not eliminated the problem. Theories for the cause of restenosis include:

The release of oxidants (damaging unstable particles) at the surgical site may cause injury and activate immune factors that produce cellular overgrowth in smooth muscles of the blood vessels.
Other activities, including scarring, may remodel and narrow the blood vessels. (This is most likely the reason for restenosis in patients with stents.)

Symptoms of restenosis include chest pain on exertion. (Heart attacks, however, do not usually occur with such events.) The narrowing of the artery in this case is not due to blood clots, so anti-clotting drugs are not useful. Restenosis usually requires a repeat operation. A number of approaches, mostly investigative, have been developed to prevent restenosis after angioplasty.

Drug-Coated Stents. Stents coated with the drugs sirolimus (Rapamune) or paclitaxel (Taxol) have been increasingly used in the last several years. Drug-eluting stents (as they are also called) can help prevent restenosis. However, because drug-eluting stents reduce arterial tissue growth, they can increase the risks of blood clots. In late 2006, the FDA held several meetings to discuss the increased risks of blood clots associated with drug-eluting stents. The committees found that drug-eluting stents do appear to have a small increased risk of blood clots compared to bare metal stents, but not enough research has been conducted to fully determine their risks for heart attack and death.

Five studies published in the New England Journal of Medicine in March 2007 indicated that drug-eluting stents are safe and effective for patients with coronary artery disease when they are used for FDA-approved indications. Problems have arisen when these stents are used for “off-label” purposes in patients with more complicated health problems. There is still some concern as to whether all stents (both bare metal and drug eluting) are used too frequently for patients who may be better served by drugs or bypass surgery.

In February 2007, the American Heart Association and other professional organization issued an extremely important joint advisory statement. The statement advises that all patients who have drug-eluting stents must continue to take aspirin and clopidogrel (or, rarely, ticlopidine) for at least 1 year after the stent is inserted to reduce the risk of blood clots. Clopidogrel and ticlopidine are thienopyridine drugs that, like aspirin, help prevent blood platelets from clumping together. It is very important that patients who have drug-eluting stents take both aspirin and a thienopyridine drug. If for some reason patients cannot take a thienopyridine drug, they should receive a bare metal stent instead of a drug-eluting stent.

Coronary Artery Brachytherapy. Radiation treatment called coronary artery brachytherapy (Gamma One, Beta-Cath) can slow the cell growth in the arteries that causes restenosis. With this approach, any blockage in the stent is first removed, and a tube with an inflatable balloon is inserted. The surgeon then implants a temporary device that delivers radiation. Brachytherapy has shown excellent results in preventing restenosis and significantly reducing heart events and improving survival. Brachytherapy is also showing promise in preventing restenosis in stented artery grafts that were put in place after bypass surgery and later failed. However, several 2006 studies in the Journal of the American Medical Association indicated that drug-coated stents may work better than brachytherapy in preventing restenosis in failed stents. In these studies, the drug-coated stents were inserted inside the original bare metal stents.

Medications. A number of medications are being studied for prevention of restenosis, although benefits to date have been modest. Other drugs under investigation include statins, various anti-clotting drugs, and B vitamins.

Other Procedures. Other procedures under investigation to keep the arteries open use ultrasound, "soft" x-rays, and cryotherapy (very low temperatures).

Other Treatments

Transmyocardial laser revascularization (TMLR) applies laser energy directly to areas in the heart where blockage has occurred, creating 10 - 50 tiny channels. TMLR is recommended for patients with severe angina who have not responded to surgical bypass or angioplasty procedures. TMLR is not suitable for patients who have severely damaged heart muscles. A variant called percutaneous transmyocardial laser revascularization uses a small laser (a holmium YAG laser), which is smaller than the device used in TMLR and does not require open chest surgery and a general anesthetic.

Patients report improved symptoms and exercise tolerance. Both procedures carry risks for serious complications, however, including some that can be life-threatening. It is not clear if either TMLR procedure improves survival, and, in one study, the quality of life afterwards was less than with standard heart surgeries.

A noninvasive technique called enhanced external counterpulsation (EECP) has been used successfully by over a million people in China. The technique uses an air pump that inflates and deflates pressurized cuffs around the legs, causing blood to be pushed into the heart.

EECP may help patients with angina who have not had pain relief from nitrate drugs and who do not qualify as candidates for bypass or angioplasty. In different studies, it has relieved angina in over 75% of patients who used it and reduced the need for medication. The benefits persist, and there is some evidence that it produces actual cellular changes that benefit the heart. In 2002, the FDA approved EECP for the treatment of heart failure but some insurance companies still consider its use “experimental” and will not pay for it. EECP is not recommended for patients with arrhythmia, serious heart valve problems, or peripheral artery disease.

Atherectomy procedures clear the narrowed arteries by using an approach called debulking. All of these procedures use a catheter (a thin tube) that is inserted into an artery (usually in the groin) and threaded up to the blockage. Devices are inserted through the tube to remove the plaque. They include:

Rotational atherectomy, which uses a tiny cutter spinning at 2,500 rpm
Extractional atherectomy, which "shaves" the plaque
Directional atherectomy, which slices the plaques

Although they are successful in opening arteries, they offer no advantages over standard angioplasty and are used only for special cases.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology

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Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. Epub 2006 Dec 28.

Spaulding C, Daemen J, Boersma E, Cutlip DE, Serruys PW. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):989-97. Epub 2007 Feb 12.

Stewart JC, Janicki DL, Muldoon MF, Sutton-Tyrrell K, Kamarck TW. Negative emotions and 3-year progression of subclinical atherosclerosis. Arch Gen Psychiatry. 2007 Feb;64(2):225-33.

Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007 Mar 8;356(10):998-1008. Epub 2007 Feb 12.

Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006 Dec 21;355(25):2631-9.

Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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Crohn's disease

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

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.
As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.
Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.
The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

In 2006 and 2007, scientists achieved major breakthroughs in identifying specific genes associated with Crohn’s disease. Among these recent discoveries:

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.
The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.
Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

According to a 2007 review in Gut, inflammatory bowel disease significantly increases the risk for pregnancy complications, such as premature birth, low birth weight, and birth defects. Women who experience disease flares during pregnancy are especially at risk.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis (UC)
Crohn's disease (CD)

Some evidence suggests that these two diseases are part of a biologic continuum. At this time, however, they are considered distinct disorders with somewhat different treatment options. The basic distinctions between UC and CD are location and severity. However, as many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, sometimes referred to as the ileocecal region. Crohn's disease occurs less frequently in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon or form a string of contiguous ulcers in one part of the colon. It may also develop as multiple scattered clusters of ulcers throughout the gastrointestinal tract, skipping healthy tissue in between.

Click the icon to see an image of Crohn's disease.

Ulcerative Colitis. Ulcerative colitis is an inflammatory disease of the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and typically diminishes higher in the colon. The disease develops uniformly and consistently until, in some people, the colon becomes rigid and foreshortened. [See In-Depth Report #69: Ulcerative colitis.]

Click the icon to see an image of the structure of the colon.

The gastrointestinal tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted out through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long, that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the structure of the small intestine.

Click the icon to see an image of the structure of the colon.

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural process called apoptosis, in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to build up on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. These increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both forms of inflammatory bowel disease have common genetic defects.

Specific Genes Involved. The first important genetic discovery for Crohn’s disease was the identification of the genetic variant CARD15 (also called NOD2), which alters the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. However, this genetic factor only affects a small percentage of Crohn’s disease cases and is not involved with ulcerative colitis.

In 2006, scientists made a significant genetic research breakthrough by identifying the interleukin-23 receptor (IL23R) as a major link to the development of both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease. Further research in 2007 indicated that IL23R gene variants may also increase or decrease the risk for Crohn’s disease in children.

Also in 2007, scientists identified several other genetic risk factors for Crohn’s disease, including the genes PHOX2B, NCF4, and ATG16L1. Scientists are particularly interested in the ATG16L1 gene. This gene regulates autophagy, the process in which a cell digests its own cytoplasm, including cellular waste products such as bacteria. Problems with autophagy may lead to a build-up of unprocessed waste products within the cell. This build-up may then provoke the inflammatory response associated with Crohn’s disease. Mutations of the ATG16L1 gene have been linked to increased susceptibility to Crohn’s disease in both adults and children.

Future genetic research may help develop targeted drug therapy for treatment of inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles and is it important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

There are three body views (front, back and side) that may be helpful if you are uncertain of a body area. Many areas are referred to by both descriptive and technical names. For example, the back of the knee is called the popliteal fossa. However, areas like the "flank" may not have both names, so the location may be unclear.

Click the icon to see a depiction of an anorectal fistula.

Complications

The outlook for Crohn's disease varies widely. Crohn's disease can range from being benign (such as when limited Crohn's disease occurs only around the anus in older people) or it can be very severe. At the extreme end, some patients may experience only one episode and others suffer continuously. Although recurrences tend to be the norm, disease-free periods can last for years or decades in some patients. Although Crohn's disease cannot be cured even with surgery, treatments are now available that can offer significant help to most patients. Crohn's disease is rarely a direct cause of death, and most people can live a normal lifespan with this condition.

Mild Crohn's Disease. The fewer bowel movements, the milder the disease. In mild disease, abdominal pain is absent or minimal. The patient has a sense of well-being that is normal or close to normal. There are few, if any, complications outside the intestinal tract. The doctor does not detect any mass when pressing the abdomen. The red blood cell count is normal or close to normal, and the patient is not underweight.

Severe Crohn's Disease. In severe Crohn's disease, the patient has bowel movements frequent enough to require opiates or other potent anti-diarrhea medication. Abdominal pain is severe and usually located in the lower right quadrant of the abdomen. (The location of the pain might not indicate the site of the actual problem, a phenomenon known as referred pain.) The red blood cell count is low. The patient has a poor sense of well-being and experiences complications that may include weight loss, joint pain, inflammation in the eyes, reddened or ulcerated skin, fistulas, abscesses, and fever. The surgical and medical treatments of Crohn's disease, as with ulcerative colitis, have complications of their own that can be severe.

Malabsorption and malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition usually develops slowly and tends to become severe, with multiple nutritional deficiencies. It is very common, ranging from 25 - 80% of patients with Crohn's disease.

Ulcer, Fistulas, and Abscesses. Between 30 - 40% of patients with Crohn's disease experience complications around the anal area from inflammation. Fistulas (channels beneath the skin) frequently develop from the deep ulcers that can form with Crohn's. If fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. They often form pockets of infection or abscesses, which may become life threatening without treatment.

Bleeding. Massive bleeding can occur in 1 - 2% of cases and may be recurrent. Bleeding is usually from a localized area in the intestine. Surgery may be performed to remove the bleeding sites.

Colorectal Cancers. Patients with inflammatory bowel disease have a slightly higher risk for colorectal cancer. The risk is greater for patients with severe ulcerative colitis than for those with Crohn’s disease. Patients with Crohn’s disease do have a 40-fold increased risk for small bowel cancer. (However, small bowel cancer is a very rare type of cancer.) The risk increases with the severity of the condition and the length of time the patient has had Crohn’s. [See In-Depth Report #55: Colon and rectal cancers.]

Intestinal Blockage. Inflammation from Crohn's disease produces scar tissue known as strictures that can constrict the intestines, causing bowel obstruction with severe cramps and vomiting. Strictures usually occur in the small intestine but can also occur in the large intestine.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations

Eyes. Inflammation in the eyes may sometimes be an early sign of Crohn’s disease. Retinal disease, including detachment, can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints. The back is commonly affected. Patients with Crohn’s disease are also at risk for clubbing (abnormal thickening and widening at the ends of fingers and toes).

Click the icon to see an image of nail clubbing.

Bones. Crohn’s disease, and the corticosteroid drugs used to treat it, can cause osteopenia (low bone density) and osteoporosis (bone loss).

Anemia. Internal blood loss from ulcers in the intestine is a particular problem in Crohn's disease because of the impaired ability to absorb vitamins and minerals necessary for blood production.

Liver and Gallbladder Disorders. Patients have a higher than average risk for mild but not severe liver problems. They have double the normal risk for gallstones.

Click the icon to see an image of gallstones.

Mouth Sores. Canker sores are common, and when they occur they persist. Those at higher risk are males and younger people. Mouth yeast infections also common in people with Crohn's disease.

Skin Disorders. Patients with Crohn’s disease are likely to develop red knot-like swellings. Such swellings or other skin lesions, such as ulcers, may spread to sites far removed from the colon, (including the arms and legs). People with Crohn's disease have an increased risk for psoriasis.

Thromboembolism (Blood Clots). Clots may occur, most likely in the legs and pelvic area.

Click the icon to see an image of a thrombus.

Urinary Tract and Kidney Disorders. Urinary tract infections are common. Patients have an increased risk for kidney stones. Amyloidosis (deposits of a protein called amyloid in the kidney or other organs) is a rare but very serious kidney condition.

Click the icon to see an image of kidney stones.

Delayed Growth and Development in Children. Up to half of children with Crohn’s disease have impaired physical growth, and nearly all are underweight. About 30% reach puberty late, but once it occurs, hormonal cycles tend to be normal.

Infertility. Infertility rates are only slightly lower than average. Active disease at conception increases risk for miscarriage or prematurity. Men may have lower sperm count during active disease or because of impaired nutrition, but in general fertility is normal.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Menstrual Problems. Menstrual problems in women are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment side effects and complications of the disease, such as fistulas.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of UC cannot be overestimated, particularly in children. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD), and about 400,000 of these patients have Crohn's disease. (This wide variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) The number of people with Crohn's disease may be increasing, and Crohn's disease is now considered to be the second most common chronic inflammatory disorder (after rheumatoid arthritis).

IBD often runs in families. The incidence may vary depending on gender, age, and geography:

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.
IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.
IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.
IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.
People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

The doctor will take a history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children. In children, IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be performed:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis patients.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Standard Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are procedures that involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor can also insert instruments through it to remove tissue samples.

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

There are three basic tests for colon cancer: a stool test (to check for blood); sigmoidoscopy (inspection of the lower colon); and colonoscopy (inspection of the entire colon). All three are effective in catching cancers in the early stages, when treatment is most beneficial.

The procedures may help the doctor to distinguish between ulcerative colitis and Crohn's disease, as well as other diseases. A variation called chromoendoscopy uses a blue stain during the process to reveal fine details on the intestinal lining. It might prove to be useful for identifying areas that may be precancerous and need to be biopsied.

Wireless Capsule Endoscopy. Wireless capsule endoscopy (WCE) is a newer imaging approach that is very useful for diagnosing Crohn's disease. With WCE, the patient swallows a capsule containing a tiny camera that records and transmits images as it passes through the gastrointestinal tract. Some studies have found it to be much more accurate for evaluating small bowel disease than barium x-rays or CT scans. Patients also find it easier to tolerate than standard endoscopy.

Ultrasound. Intestinal wall ultrasound is proving to be useful for identifying the extent and severity of Crohn's disease. It is uncertain if ultrasound is useful for an initial diagnosis.

Upper and Lower Gastrointestinal Barium X-Rays. An upper gastrointestinal barium x-ray may be used if Crohn's disease is suspected in the small intestine. Swallowed barium passes into the small intestine and shows up on an x-ray image, which may reveal inflammation, ulcers, and other abnormalities.

Click the icon to see an image of the barium enema procedure.

Positron Emission Tomography (PET) and Computed Tomography (CT) Scans. PET/CT scans are proving to be extremely useful in evaluating active IBD. With Crohn's disease, CT scans may show thickened walls and complications, such as fistulas, which occur outside the intestine.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging is another advanced imaging technique that may be useful for detecting abscesses and other injuries related to Crohn's disease in the pelvis. A variant called magnetic resonance spectroscopy (MRS) may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis cause many of the same symptoms as inflammatory bowel disease (IBD). (However, it is NOT the same as inflammatory bowel disease.) Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with inflammatory bowel disease and is usually first noticed in children.

Click the icon to see foods to avoid if you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with interstitial cystitis is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before confirming a diagnosis of inflammatory bowel disease.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Click the icon to see an image of the appendix.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBD can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

The role of diet and nutrition is very important in Crohn's disease and should be considered for four separate situations:

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies
As primary treatment for reducing disease activity
As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome
For reversing growth-failure in children

Malnutrition is very common in Crohn's disease. In fact, patients with Crohn's appear to burn fat calories at a higher rate than the general population and most patients are underweight. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (non-caffeinated). Drinking plenty of water is extremely important. Vegetable juice and sports drinks may be helpful for restoring important minerals. People with inflammatory bowel disease (IBD) should avoid caffeinated beverages in general, although green tea may have some benefits for Crohn's disease.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency, and patients with inflammatory bowel disease may need more protein than the general population. Oily fish, such as salmon and tuna, may be particularly beneficial in Crohn's disease. Other options are poultry and lean meats. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of a patient's calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) may actually be specifically protective for IBD and may possibly reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so patients should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber, which may help reduce damage in the intestinal tract caused by inflammation. However, high-fiber foods can cause gas, bloating, and pain, particularly in IBD patients. Commercial products (such as Beano) are available that can reduce gas. Eating small, frequent meals can also help.

Liquid Supplements. Over-the-counter liquid diets that meet full nutritional needs and are absorbed in the upper intestine, such as Ensure, Sustacal, and other products, may be helpful for some patients with Crohn's. However, it is important to note that no studies have determined this.

Potassium-rich Foods. Examples are potatoes, avocados, and bananas.

Exclusion Diets. Exclusion diets are those that eliminate certain foods that may cause allergies or irritate the intestine. To determine these foods, patients use an "elimination/challenge" approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. This approach, however, may be very difficult, and studies are weak in confirming its value for maintaining remission.

Typical foods people with inflammatory bowel disease (IBD) may avoid include:

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.
Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine).
Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in inflammatory bowel disease (IBD), particularly in patients who have had intestinal surgery. IBD patients are at risk for the most common types of kidney stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendation is to increase fluid and restrict sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.
Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones need to be tailored to the dietary requirements of IBD. Patients should work with their doctors to develop a plan.

Researchers are currently investigating bacteria (called probiotics) and specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and are heavily marketed in Europe, Japan, and Australia. To date, however, no studies have determined any clear benefits of any specific organism or formulation.

Crohn's disease and surgical procedures that remove parts of the small intestine can inhibit absorption of vitamins, fats, and other important supplements. Taking certain supplements -- such as fish oil, antioxidants, and mineral supplements -- may be beneficial for patients with Crohn's disease.

Vitamins. Deficiencies of vitamins A, C, D, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with inflammatory bowel disease (IBD), particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which are scavengers of damaging particles in the body. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic at high doses, patients should discuss specific dosages with their doctors.

Omega-3 Fatty Acids. The role of fats in inflammatory bowel disease is complex and not fully known. Some evidence suggests that patients with Crohn's burn fat calories at a higher rate than the general population. Patients with IBD may be deficient in essential fatty acids, particularly omega-3 fatty acids (polyunsaturated fats found in oily fish and certain vegetable products such as flaxseed and canola oils). Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids, which are specific compounds found in fish oil.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with inflammatory bowel disease.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD.

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.
Selenium is a potent antioxidant.
Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.
Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

Enteral Nutrition. Enteral nutrition uses a feeding tube that is inserted either through the nose and down through the throat or directly through the abdominal wall into the gastrointestinal tract. It is the preferred method for feeding patients with malnutrition who cannot tolerate eating by mouth. The nutritional formulas used in enteral administration include:

Polymeric diets (containing a balance of standard nutrients).
Elemental diets (predigested nutrients that are absorbed in the first meter of the small intestine). These diets are used less commonly than polymeric diets.

In children, enteral nutrition is given for 6 - 8 weeks. Simple foods are then introduced (chicken, potato, rice), and more complex foods (milk, fiber, wheat-based foods) are then added gradually. However, relapse is still common.

Total Parenteral Nutrition. Total parenteral nutrition (TPN), or hyperalimentation, is the intravenous administration of nutrients through an indwelling catheter (tube). It is used for very severe IBD when patients cannot tolerate any nutrition by mouth or with a feeding tube, and may even be useful as a primary therapy for patients with Crohn's (although not for those with fistulas). It is usually given in the hospital, although increasingly people are giving it to themselves at home. The procedure carries a risk for complications, some serious, including infection, blood clots, and liver failure.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Patients with Crohn's disease benefit most from the combination.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and these drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Although no evidence exists to confirm that stress reduction techniques such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

The effects of exercise in Crohn's disease are uncertain. Some research indicates that moderate exercise may trigger excess production of chemicals that could cause flare-up. One small study, however, reported significant improvement in patients who had been sedentary but then embarked on a 12-week exercise program. They walked a little over 2 miles three times a week. During that period there were no flare-ups, and they felt physically and emotionally better than before.

Medications

The primary goal of drug therapy is to reduce inflammation in the intestine. Drugs are effective in reducing the inflammation and accompanying symptoms in up to 80% of patients. Unfortunately, relapses are still frequent, and researchers continue to look for the optimal treatments that will both control symptoms and prevent relapse.

Drugs Used for Crohn's Disease. Drug therapies for Crohn’s disease aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The drugs used depend on the severity of the condition:

Mild-to-moderate Crohn's disease is generally treated with antibiotics and an oral aminosalicylate, such as mesalamine or sulfasalazine. (Some researchers suggest, however, that corticosteroids may be more effective than these drugs in patients with disease in the small intestine and ascending colon. Furthermore, new forms of oral corticosteroids, such as budesonide, may have a lower risk for adverse effects.)

Moderate-to-severe Crohn's disease is treated with corticosteroids, immunosuppressants, or biologic drugs such as infliximab or adalimumab. These drugs may be used alone or in combinations. Some patients with severe Crohn's may be candidates for surgery.

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed, and symptoms, such as diarrhea, abdominal cramps, and tenesmus (painful defecation), are normal or close to normal. It is sometimes difficult to define remission in Crohn's disease because diagnostic test results do not always correlate with a patient's symptoms or complications outside the intestine.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy.

Corticosteroids are frequently combined with other drugs, such as 5-aminosalicylic acid (or 5-ASA) drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.

In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest possible dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.

Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. Recent studies suggest that budesonide can help prolong and maintain remission periods in patients with Crohn’s disease.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore its inflammatory response, which causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.

Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given by weekly injections and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects. Because of these pregnancy complications, both men and women who take methotrexate should use birth control.

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly.

Antibiotics are often used to induce remission in mild-to-moderate Crohn's disease. They are also important for treating fistulas, bacterial overgrowth, abdominal abscesses, and any infections around the anus and genital areas. Stopping antibiotics brings on relapse, so long-term therapy is required, carrying a risk for side effects.

The standard antibiotics used for inducing remission in Crohn's disease are ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice. Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with netronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.

Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. Of special interest for patients with Crohn's disease are drugs such as infliximab and adalimumab, which target the inflammatory immune factor known as tumor necrosis factor (TNF).

According to a 2007 consensus statement from the American Gastroenterological Association, biologic drugs are generally not used as first-line treatment for most patients with Crohn’s disease. However, some patients -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.

Infliximab (Remicade) acts against TNF and was the first biologic drug approved for treating adults with Crohn's disease. It is made from a genetically designed antibody called a monoclonal antibody (MAb) that blocks the activity of tumor necrosis factor-alpha (TNF-a). In 2006, the FDA approved infliximab for children with active Crohn’s disease.

Infliximab cannot cure Crohn’s disease, but it can help control symptoms and, possibly, keep the disease in remission. Studies suggest that up to 80% of patients respond initially, and about a third of all patients remain in remission after a single infusion. Remissions last a few weeks to several months. A 6-week course of infliximab helps close and heal fistulas in half of patients and reduces drainage in 70%. The drug is also being studied for maintenance therapy, although given some significant side effects, it will most likely be reserved for active disease that does not respond to other treatments.

Infliximab’s severe side effects may include tuberculosis, pneumonia, and other infections; lymphoma (a type of cancer); liver failure; and aplastic anemia.

Adalimumab (Humira) was approved early in 2007 for treating adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.

Adalimumab's label includes a boxed warning. The medicine has been associated with serious, sometimes fatal, infections, including tuberculosis and sepsis. Other severe side effects may include lymphoma, upper respiratory infections, sinusitis, and nausea.

Several other TNF modifiers are being investigated. Among the most promising, according to several 2007 studies in the New England Journal of Medicine, is certolizumab (Cimzia).

Selective adhesion molecule inhibitors block the genetic expression of cell adhesion molecules (CAMs). CAMs play an important role in the accumulation of immune factors that cause the inflammatory response. Natalizumab (Tysabri) is a monoclonal antibody that blocks alpha4 integrin, a protein that binds to CAMs. This drug is approved to treat multiple sclerosis and is also being studied for Crohn’s disease. Studies have suggested that natalizumab can help patients with Crohn’s disease achieve and maintain remission.

However, natalizumab is associated with severe side effects, including a rare neurological condition called progressive multifocal leukoencephalopathy (PML). A 2006 study found that patients who take natalizumab have a very low risk for PML. Still, the potential benefits of natalizumab need to be weighed against its risks for serious side effects. As of summer 2007, the FDA was considering approving natalizumab for treatment of moderate-to-severe Crohn’s disease in patients who have failed or cannot tolerate other therapies

Other Biologic Therapies. Investigators are researching other biologic therapies that target other types of immune factors that play a role in the inflammatory response. These factors include interferons, anti-interferon antibodies, anti-interleukin antibodies, p65 anti-sense oligonucleotides, growth factors, and others. Several 2006 studies indicated that fontolizumab (HuZaf), an anti-interferon gamma monoclonal antibody, shows promise as a treatment for Crohn’s disease. Sargramostim (Leukine), a granulocyte-macrophage colony stimulating factor, is another biologic drug that may help improve symptoms and quality of life for patients with active Crohn’s disease. Visilizumab (Nuvion), which targets the CD3 receptor on T cells, is another biologic drug being investigated. More research in each of these areas is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies have reported significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's. More research is needed.

Growth Factors. Growth factor hormones increase immune factors, so one would think they might be harmful for patients with Crohn's disease. However, some research suggests that growth factors may be helpful for speeding healing in certain patients, including children. More research, however, is needed.

Surgery

Between two-thirds to three-quarters of patients with Crohn's eventually need surgery when medication cannot control symptoms. Among children with Crohn's, half require surgery within 5 years of diagnosis.

In general, surgery is used to remove damaged areas of the colon:

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.
Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

Surgery is useful only for reducing symptoms. It cannot cure Crohn's disease because new disease can appear in other areas of the intestine. Surgery may be helpful for relieving symptoms and to correct blockage, perforation, fistulas, or bleeding.

Surgery has reportedly improved the quality of life in most patients, except for those who continued to have active disease. Many children with Crohn's who have suffered growth problems catch up to near-normal growth levels after surgery. Some experts urge, in fact, that many patients should consider surgery in the early stages of the disease.

Some patients may be candidates for a procedure called strictureplasty, which involves cutting and stitching only the areas obstructing the intestine, so that it widens the intestine without removing sections of it. It involves the following:

A balloon attached to a catheter (a thin tube) is passed along the intestine.
If it becomes blocked, then a stricture (an obstruction) is indicated.
The surgeon widens the intestine at the point, but does not remove sections of it.
The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

The invasiveness of the surgical procedure to remove damaged portions of the colon depends on the severity of the disease.

Resection of the Colon. In most cases of Crohn's disease, only a part of the colon needs to be removed, a procedure called resection.

Click the icon to see an illustrated series depicting large bowel resection surgery.

Subtotal Colectomy. Subtotal colectomy is more extensive than resection and removes more of the colon. Disease in the upper parts of the small intestine tends to require more extensive surgery than in the lower small intestine.

In general, either procedure requires a general anesthetic and involves the following:

An incision is made in the abdomen.
The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)
Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

Open Surgery or Laparoscopy. Resection or subtotal colectomy may be performed using one of two surgical approaches:

Open surgery, which requires a wide abdominal incision.
Laparoscopy, which uses a few small incisions through which a tube is inserted containing a tiny camera for viewing the area. To date, however, this procedure is best suited for patients with short-segment disease in the ileum who also have no other complications, such as fistulas and abscesses.

Click the icon to see an image of a laparoscopy procedure.

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.
Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).
Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

Proctocolectomy with ileostomy is removal of the entire colon and creation of an ileostomy. It involves the following:

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.
To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Recurrence of Crohn's disease is very common after any procedure. The risk may be 7 - 25% for each year after resection, with an average risk of 50% at 5 years after resection. (Even if the entire colon is removed, there is still a high chance of recurrence in the rectum and a somewhat lower risk for recurrence in the small intestine.)

Patients at highest risk for recurrence include:

Smokers
Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon
Those with abscesses or fistulas
Those have had previous surgeries

Various drugs are used to prevent recurrence. They include the antibiotic metronidazole (Flagyl), mesalamine, infliximab, and mercaptopurine. These drugs can have severe side effects. And, it is not clear if these or any other drugs are effective in preventing recurrence. Even if medications can help prevent recurrence in some patients, it is not yet known how to identify this subset of patients. (In any case, steroids do not appear to help prevent recurrence.)

In some cases, surgery is needed for emergency conditions that can occur with Crohn's disease. Emergency surgery is used to:

Stop severe intestinal bleeding
Clear small bowel obstruction
Drain and heal abscesses or fistulas
Repair perforation

Procedures for transplanting the small intestine in patients with intestinal failure are under investigation. These are still experimental and are being tested in patients who have lost so much of their small intestine that they must rely on total parenteral nutrition (intravenous administration of nutrition). Small-bowel transplantation is a more difficult procedure than some other transplants, because of the high rate of potential complications, including infection and organ rejection. Patients who have transplants must take immunosuppressant drugs for the rest of their lives. Furthermore, there is some evidence that Crohn's disease recurs in the transplanted bowel.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of the T300A non-synonymous variant of the ATG16L1 gene with susceptibility to paediatric Crohn's disease. Gut. 2007 Aug;56(:1171-1173.

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2007 Jul 5; [Epub ahead of print]

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23,2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Cummings JR, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, et al. Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene. Inflamm Bowel Dis. 2007 Aug;13(:941-6.

Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, et al. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007 May;13(5):511-5.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):228-238.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):239-250.

Tremaine WJ. Inflammatory bowel disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol. 2007 Mar;5(3):310-1.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007 May;132(5):1657-64. Epub 2007 Feb 24.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Ulcerative colitis

FitSugar — Wed, 08 Oct 2008 17:35:30 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the FDA approved LIALDA, the first once-daily mesalamine pill for treating mild-to-moderate ulcerative colitis. Other types of mesalamine need to be taken several times a day.

Genetic Research

Scientists have made an important discovery by identifying a gene associated with inflammatory bowel disease. In a 2006 paper published in Science, researchers announced that variations in the interleukin-23 receptor (IL23R) gene can either increase or decrease the risk for developing ulcerative colitis and Crohn’s disease.

Clostridium Difficile

Patients with ulcerative colitis are particularly susceptible to Clostridium difficile, a nasty bacterial infection that causes severe diarrhea. According to several 2007 studies, C. difficile is becoming increasingly common among these patients. Experts recommend that doctors monitor patients with ulcerative colitis for signs of this difficult-to-treat infection.

Pregnancy

Women with inflammatory bowel disease have twice the risk of pregnancy complications as healthy women, according to a 2006 review in Gut. Premature birth, low birth weight, and birth defects are among the complications. Active flares of disease during pregnancy especially increase the risks for problems.

Infliximab (Remicade)

Infliximab (Remicade) is helpful for promoting remission and healing in patients with moderate-to-severe ulcerative colitis who have not responded to other drugs, according to a 2006 review in the Cochrane Database.
Infliximab works by blocking the effects of tumor necrosis factor (TNF), a substance that plays a role in inflammatory diseases. Infliximab is the only biologic drug approved for treatment of ulcerative colitis. Researchers are studying other types of biologic drugs as well.
According to a 2007 consensus statement from the American Gastroenterological Association, infliximab should be used only for patients who have not been helped by other drugs, such as immunosuppressants and corticosteroids. It is not recommended as a first-line treatment for ulcerative colitis.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis
Crohn's disease

Some evidence suggests that they are part of a biologic continuum, but at this time they are considered distinct disorders with somewhat different treatment options. The basic distinctions are location and severity. As many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines that is usually confined to the ileum, the terminal portion of the small intestine. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other inflammatory bowel diseases have been linked with an increased risk of colorectal cancer.

Ulcerative Colitis. Ulcerative colitis occurs only in the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and usually diminishes higher in the colon. It is sometimes divided into one of four categories depending on the location of the disease:

Click the icon to see an image of the structure of the colon.

Proctitis. Disease only in the rectum (the lowest part of the large intestine that connects with the anus). Constitutes about 30% of cases.
Proctosigmoiditis. Disease in the rectum and sigmoid (the next portion of the intestine leading up from the rectum). Constitutes about 30% of cases.
Left-Sided Colitis. Disease in the left side of the large intestine. Constitutes about 40% of cases.
Pancolitis. Disease in entire colon. Very uncommon.

Click the icon to see an image of the types of ulcerative colitis.

In most patients the location of the disease does not change, but as many as 30% of patients with proctitis or proctosigmoiditis will experience some progression.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, which is sometimes referred to as the ileocecal region. Crohn's disease less frequently occurs in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon, form a string of contiguous ulcers in one part of the colon, or develop as multiple scattered clusters of ulcers skipping healthy tissue in between. [See In-Depth Report #103: Crohn's disease.]

The gastrointestinal (GI) tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections:

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they pass through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the small intestine.

Click the icon to see an image of the large intestine.

Causes

Inflammatory bowel disease (IBD) can have many causes. Often, genetic problems in the intestine allow viruses or bacteria to trigger an immune response that causes inflammation and injury in the intestines. In IBD, the defense systems appear to be impaired, either from defects in the mucosal lining that provides a barrier in the intestine or an inability to make repairs after injury.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

B cells produce antibodies, substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two-fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T Cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appears to occur in inflammatory bowel disease (IBD), although each disorder has a different balance:

Patients with ulcerative colitis favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These proteins affect mostly mucosal areas in the intestine.
Research indicates that Crohn's disease patients have increased activity in TH1 cells, which activates interleukin-2 (IL-2) and interferon-gamma. These substances affect intestinal cells. Tumor necrosis factor may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs. Interleukin 6 inhibits a natural process called apoptosis,in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. Such increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

In 2006, scientists identified variations in the interleukin-23 receptor (IL23R) as an important genetic link to both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the injurious processes that lead to inflammatory bowel disease.

Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. However, according to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD. In addition, studies conclusively report that the measles, mumps, and rubella (MMR) vaccine does not cause Crohn’s disease, ulcerative colitis, or autism.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles. It is important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis (UC)	Crohn's Disease (CD)
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal bleeding	Blood is almost always present in stools. It may be readily visible or visible using only a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Hallmark symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 -20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms of CD.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

Complications

Surgical removal of the colon is the only cure for ulcerative colitis, but the disease varies greatly in severity. In one 10-year study, 87% of patients went into complete remission after a single attack, and only 8% developed a chronic persistent condition. Mortality rates were about the same as in the general population, although they were higher in patients with UC with severe initial attacks or extensive disease. Surgical and medical treatments have complications of their own that can be very severe.

Ulcerative colitis is considered mild if a patient has the following symptoms:

Four or fewer bowel movements a day
Only occasional blood in the stool
A normal temperature and pulse rate
Normal hemoglobin or red blood cell count
No abnormalities observed on x-rays of the colon.

Ulcerative colitis is considered serious if the following symptoms are present:

More than six movements a day
Frequent-to-persistent blood and mucus in the stool (in serious cases, stool is liquid and looks like anchovy sauce)
Fever
A rapid pulse
Anemia
Abnormal x-rays of the colon
Tenderness in the abdomen when pressed, with possible distention

Malabsorption and Malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition typically develops rapidly after the condition has been present for some time.

Toxic Megacolon. Toxic megacolon is a serious complication that can occur if inflammation spreads into the deeper layers of the colon. In such cases, the colon enlarges and becomes paralyzed. In severe cases, it may rupture, which is a life-threatening event needing emergency surgery. Symptoms include weakness and abdominal pain and bloating. You may be disoriented or groggy. X-rays are needed to confirm the diagnosis, but barium enemas and colonoscopies should not be performed. Medications used for pain and diarrhea, such as opiates and drugs that reduce spasms of the colon, may increase the risk of toxic megacolon. People with ulcerative colitis have a higher than normal risk, although this is still not common. Its incidence is decreasing with treatment advances.

Toxic megacolon is characterized by extreme inflammation and distention of the colon. Common symptoms are pain, distention of the abdomen, fever, rapid heart rate, and dehydration. This is a life-threatening complication that requires immediate medical treatment.

Bleeding. Bleeding due to ulcers in the colon is a common complication of UC. It can increase the risk for anemia. In some cases, bleeding can be massive and dangerous, requiring surgery.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

Colorectal Cancers. Patients with ulcerative colitis have a higher than normal risk for cancers of the colon and rectum. About 5 - 8% of patients with ulcerative colitis will develop colorectal cancer within 20 years of their ulcerative colitis diagnosis. The risk of colorectal cancer increases with the duration and severity of the ulcerative colitis condition. The presence of inflammatory polyps (pseudopolyps) more than doubles the risk. Some research suggests that anti-inflammatory drugs, such as 5-ASA, may help reduce the risk of cancer. Doctors also advise that patients with ulcerative colitis receive regular (every 1 - 3 years) colonoscopy exams to help screen for cancer. According to a 2006 study, patients with ulcerative colitis who are diagnosed with colorectal cancer have a worse prognosis, and poorer survival, than those without ulcerative colitis. [See In-Depth Report #55: Colon and rectal cancers.]

Click the icon to see an image of the colonoscopy procedure.

People with inflammatory bowel disease (IBD) have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Eyes. Inflammation in parts of the eye is a common complication. Retinal disease, including detachment can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints.

Bones. Low body weight and calcium loss from corticosteroids contribute to osteoporosis (bone loss). However, ulcerative colitis itself causes less bone loss than Crohn’s disease.

Click the icon to see an image of osteoporosis.

Heart. People with IBD have more than three times the risk of developing pericarditis (inflammation of the sac enclosing the heart) than healthy people

Anemia. People with ulcerative colitis have a higher than normal risk for anemia.

Liver and Gallbladder Disorders. People have a higher than average risk for mild but not severe liver abnormalities. There is a higher risk (although rare) for primary sclerosing cholangitis, which is persistent inflammation of the bile duct that can later cause serious obstruction.

Skin Disorders. Patients with ulcerative colitis have a higher risk for skin disorders and may experience ulcer eruptions called pyoderma gangrenosum that heal in the center and spread.

Thromboembolism (Blood Clots). People with ulcerative colitis are at higher risk for blood clots, especially in the legs and pelvic area.

Click the icon to see an image depicting a thrombus.

Kidney Disorders. People with ulcerative colitis have a higher than normal risk for kidney stones.

Click the icon to see an image of kidney stones.

Lung Involvement. Lung involvement may develop but it can progress for years without symptoms.

Mouth Sores. There is a slightly higher than average risk for mouth sores and infections in people with ulcerative colitis , but they are uncommon and lower than those with Crohn's disease.

Delayed Growth and Development in Children. Children with ulcerative colitis are at slightly higher than average risk for delayed growth, but their risk is lower than the risk is for people with Crohn's disease.

Fertility. Fertility rates in women are close to normal, but ulcerative colitis surgery can increase the risk for infertility. Prematurity rates are high with both types of IBD.

Hodgkin's Disease. Patients with ulcerative colitis may be at higher risk for Hodgkin's disease, according to a 2000 study. The risk of other cancers was not increased, however.

Menstrual Problems in Women. Menstrual problems are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment of side effects and complications of the diseases, such as fistulas.

Emotional Factors. The emotional consequences of ulcerative colitis cannot be overestimated. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. ulcerative colitis takes a serious toll on work, family, and social activities. According to a 2005 survey, 40% of patients report incapacitating symptoms at least 180 days per year. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD). Crohn's disease was once thought to be far less common than ulcerative colitis, but the two conditions are now estimated to occur about equally. The incidence may vary depending on gender, age, and geography:

Men and women have equal risk for ulcerative colitis.
IBD is diagnosed most often in young people ages 10 - 19, but it can occur at any age. A smaller peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10.
Ulcerative colitis is most common among people of European descent. People of African descent have a lower incidence than Caucasians. Low incidence regions include Asia and South America. Ethnically, Ashkenazi Jewish people have a particularly high risk.
Ulcerative colitis may disproportionately affect people of higher socioeconomic classes, but evidence for this is inconclusive.

Smoking. Smokers have lower than average rates of ulcerative colitis (but higher than average rates of Crohn's disease). Some patients with ulcerative colitis, in fact, have reported that their disorder began after they quit smoking, and many studies have reinforced the association between smoking and protection against ulcerative colitis. (This information is certainly no encouragement to smoke. Rather, patients should ask their doctor about trials using nicotine replacement aids.)

Breast-feeding. Breast-feeding appears linked to lower risk for ulcerative colitis.

Left-Handedness. People who are left-handed have a significantly higher risk for both inflammatory bowel diseases as well as for certain other diseases associated with immune system abnormalities.

Depression. One study reported that patients with ulcerative colitis were more likely to have a history of depression or anxiety than those without inflammatory bowel disease. Some researchers suggest that depression may alter the immune system and make people more susceptible to ulcerative colitis.

Diagnosis

The doctor will take your medical history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children, in whom inflammatory bowel disease (IBD) may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be taken, such as the following:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis cases.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are endoscopic procedures. They are important in the diagnosis of both ulcerative colitis and Crohn's disease. Both procedures involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor may also insert instruments through the endoscope to remove a tissue sample for a biopsy.

Sigmoidoscopy, which is used to examine the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful. Ulcerative colitis almost always involves the lower left colon and rectum and is diagnosed using sigmoidoscopy. The doctor usually observes an evenly distributed inflamed surface lining the intestine, and the bowel wall bleeds easily when touched with a swab.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is helpful for distinguishing between Crohn's disease and ulcerative colitis and in screening for colon cancer.

Patients diagnosed with ulcerative colitis may also need periodic endoscopies to evaluate their condition when symptoms flare up. However, a 2005 study suggested that these routine endoscopies may not be necessary. The study found that doctors can get as much information about a person's disease when patients self-report their symptoms as they can from endoscopies.

X-rays and Barium Enema. The double-contrast barium enema, which uses an x-ray image, is less expensive than a colonoscopy for viewing the entire colon. Although not as accurate as colonoscopy, it is very valuable in diagnosing both Crohn's disease and ulcerative colitis in early stages. In patients with active ulcerative colitis, this procedure may increase the risk for toxic megacolon.

A barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). A barium enema, along with colonoscopy, remains standard in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

X-rays of the abdomen are also useful when a patient has a severe attack of ulcerative colitis. In such cases, the edges of the colon are swollen and irregular. X-rays may also reveal thickened walls and other signs of severity.

Ultrasound. Intestinal wall ultrasound may be useful for identifying the extent and severity of Crohn's disease. Although it is unclear if ultrasound is useful for an initial diagnosis, one study indicated that, when used by experienced professionals, it is effective for identifying Crohn's disease or ulcerative colitis.

Other Imaging Procedures. Magnetic resonance spectroscopy (MRS) is a variant of magnetic resonance imaging (MRI) that may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.

Positron emission tomography (PET) and computed tomography (CT) scans may be useful for determining the extent of the disease on the intestine and for detecting abscesses and other complications of advanced IBD.

A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. The procedure involves pumping air into the colon and scanning the intestine using computed tomography (CT) or magnetic resonance imaging (MRI). It is very safe, requires no sedation, and takes only about 10 minutes.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of tests for antibodies in people with UC will show perinuclear-staining antineutrophil cytoplasmic antibodies. Over 50% of Crohn's people have anti-Saccharomyces cerevisiae antibodies. Such tests are expensive and infrequently performed, but they may be useful in cases of uncertainty.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis, cause many of the same symptoms as inflammatory bowel disease. Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a lot of people with inflammatory bowel disease (IBD) and is usually first noticed in children.

Click the icon to see foods to avoid when you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of a patient with IC is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before a diagnosis of inflammatory bowel disease can be confirmed.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to irritabel bowel syndrome can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

Malnutrition is very common in ulcerative colitis, although it tends to be more severe in Crohn's disease. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (Non-Caffeinated). Drinking plenty of water is extremely important. It not only benefits the intestine but also helps prevent kidney stones, which are common in inflammatory bowel disease (IBD). Vegetable juice and sports drinks may be helpful for restoring important minerals.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency and so patients may need more protein than the general population.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of your calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) might be specifically protective for IBD and may also reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so you should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber. Fiber may help reduce damage in the intestinal tract caused by UC, and may even help protect against cancer. Oat bran is of particular interest. In the intestinal tract, this whole grain increases levels of a fatty acid called butyrate, which may help reduce GI symptoms due to ulcerative colitis. However, high-fiber foods can cause gas, bloating, and pain, particularly in people with IBD. Available commercial products (Beano) can reduce gas. Eating small, frequent meals can also help.

Potassium-rich Foods. Potassium rich foods help protect the intestine. They may also reduce the risk for kidney stones. Such foods include bananas, oranges, pears, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation, including in the intestinal tract. Some studies have even reported lowered use of anti-inflammatory medications in people who consume fish oil. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however.

Omega-3 fatty acids, found plentifully in oily fish, flaxseed, and canola oils, may help people with inflammatory bowel disease.

Exclusion diets are those that eliminate certain allergenic foods or those that might irritate the intestine. To determine these foods, patients use a so-called elimination-and-challenge approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. Elimination diets, however, are very difficult to maintain, and it is not clear if they prevent relapse.

Typical foods to avoid are:

Saturated fats, found in animal and dairy products. People with inflammatory bowel disease should limit fats. Some studies have found an association between high-fat intake and later development of ulcerative colitis. Animal (saturated) fats are often suspected in IBD.
Milk products. Some people with inflammatory bowel disease are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant people are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine). Fruits may be protective, but you should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in people with inflammatory bowel disease (IBD), particularly in people who have had intestinal surgery. People with IBD are at risk for the most common types of stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendations for reducing the risk for kidney stones are increasing fluid and restricting sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Sufficient protein, particularly in children with IBD, is very important and should be weighed against any risk for stones.
You should increase intake of potassium-rich foods.
You should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. You should avoid or limit intake oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
People who have stones associated with short-bowel syndrome should eat less fat and foods containing oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones must be tailored to the dietary requirements of IBD. You should work with your doctor to develop an individualized plan.

Researchers are currently investigating a mix of bacteria (called probiotics), specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms, such as by excreting certain acids (lactate, acetate) that inhibit harmful bacteria or competing with them for nutrients. Evidence is now suggesting that probiotics may help maintain remission in patients with IBD. They are also proving to be effective in people with pouchitis -- a common surgical complication. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, such as bifidobacteria and GG lactobacilli, however, may prove to be more important in inflammatory bowel disease (IBD). Other probiotics include lactobacilli rhamnosus, casel, plantarium, bulgaricus, salivarius, Enterococcus faecium, and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods themselves can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and overseas. To date, however, no studies have determined any clear benefits from any specific organism or formulation.

Vitamins. Deficiencies of vitamins A, C, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with IBD, particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which protect the body against damaging particles. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer in patients with ulcerative colitis. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic in high doses, patients should discuss specific dosages with their doctors.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD. Zinc is specifically important for gastrointestinal health. Calcium and magnesium are critical for health and strong bones. Selenium is a potent antioxidant. Iron supplements may be required for anemia. A doctor should advise patients carefully on the correct dosages since minerals can be toxic in high levels.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

To reduce mild-to-moderate diarrhea, take one teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Anti-diarrhea drugs, such as loperamide (Imodium) and atropine/diphenoxylate (Lomotil), may help. In very ill patients, large doses of some drugs, such as Lomotil, can trigger the onset of toxic megacolon.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous (IV) iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in inflammatory bowel disease that does not respond to iron alone. Crohn's disease patients benefit from the combination. Patients with ulcerative colitis usually improve on IV iron alone.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and such drugs will not affect the basic illness.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Patients with inflammatory bowel disease (IBD), in fact, may have a more exaggerated physical response to stressful events than people without IBD. Although no evidence exists to confirm that stress reduction techniques, such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

Castor Oil Pack. Some people report relief from the use of a castor oil pack for 3 consecutive days. The oil is applied directly to the skin and then covered with a clean soft cloth and plastic wrap. A hot water bottle or heating pad is then placed over the pack for 30 - 60 minutes.

Acupuncture. Acupuncture may help relieve symptoms in some patients.

Medications

Drugs cannot cure inflammatory bowel disease, but they can help reduce the inflammation and accompanying symptoms in up to 80% of patients. The primary goal of drug therapy is to reduce inflammation in the intestine.

Drugs Used. Drug therapies for ulcerative colitis aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission).

Aminosalicylates. Mild-to-moderate ulcerative colitis is usually treated with aspirin-like medications called aminosalicylates, or 5-ASAs. These drugs are also used to treat relapses. They may be administered rectally in patients who have mild-to-moderate disease that occurs only in the lower intestine. They may also be taken by mouth.
Corticosteroids. Corticosteroids (steroids) may be added or used alone to reduce acute inflammation. (Because of their significant side effects, they are not recommended for long-term use and maintenance therapy). Steroids may be administered rectally as an alternative to an aminosalicylate if the disease is limited to the lowest parts of the intestine. Forms taken by mouth may treat moderate-to-severe cases. People who do not respond to less aggressive treatments may need intravenous steroids.
Immunosuppressants. Drugs that suppress the immune system (immunosuppressants) are useful, either alone or in combinations, for disease that does not respond to other treatments or for maintenance of remissions.
Biologic Drugs. Unlike drugs that are made from chemicals, biologic drugs are produced from living organisms. Biologics are designed to stimulate the immune system and interfere with specific proteins (cytokines) involved with the inflammatory response. Infliximab (Remicade) is the first biologic drug approved for ulcerative colitis. It blocks a cytokine called tumor necrosis factor (TNF).

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed and symptoms such as diarrhea, abdominal cramps, and tenesmus (straining painfully or ineffectively to defecate or urinate) are normal or close to normal.

Patients who cannot tolerate sulfazine or who are allergic to sulfa drugs have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are taken as pills several times a day. In 2007, the Food and Drug Administration approved LIALDA, the first once-daily mesalamine pill for patients with ulcerative colitis. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)
Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children and women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs. They are used only for active ulcerative colitis. Steroids are frequently combined with other drugs to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time. Because they have serious long-term effects, steroids are not useful for maintenance therapy. Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

Immunosuppressant drugs are now being used for long-term therapy, especially for very active inflammatory bowel disease that does not respond to standard treatments. Such drugs suppress or restrain actions of the immune system and therefore its inflammatory response, which causes ulcerative colitis. Immunosuppressants can prevent relapse, even when used alone, and in some studies have proved to help maintain remissions in ulcerative colitis for up to 2 years.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). Cyclosporine A is also given intravenously to patients with severe ulcerative colitis. These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. Methotrexate (MTX, Rheumatrex) is another fast-acting type of injectable immunosuppressant that is effective for Crohn’s disease. However, methotrexate does not appear to be helpful for ulcerative colitis. (Antibiotics, which are used to treat Crohn's disease, are also not helpful for ulcerative colitis.)

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. One such drug, infliximab (Remicade), was approved in 2005 for treatment of moderate-to-severe ulcerative colitis in patients who have not responded to other drugs, such as corticosteroids. In 2006, infliximab was approved to help maintain as well as induce remission. Doctors do not recommend infliximab as a first-line drug for ulcerative colitis.

Infliximab targets an inflammatory immune factor known as tumor necrosis factor (TNF). Studies indicate that infliximab may reduce ulcerative colitis symptoms and help patients achieve remission. Infliximab may also help heal ulcers and inflammation of the colon’s inner lining (mucosa). Some patients who take infliximab may be able to avoid surgical removal of the colon.

Infliximab is given as a 2-hour intravenous infusion in a doctor’s office. After the first dose, the patient receives a second dose 2 weeks later, and a third dose 6 weeks after that. After these three doses, the drug is given every 8 weeks.

Common side effects may include a skin reaction at the injection site, stomach pain, and coughing. Potential serious side effects include tuberculosis, pneumonia, and other respiratory infections; lymphoma (a type of cancer); liver failure; and aplastic anemia. Infliximab is not appropriate for most patients with heart failure.

Researchers are currently studying other biologic drugs for treatment of ulcerative colitis. These investigational drugs include adalimumab (Humira), which is approved for Crohn’s disease, and visilizumab (Nuvion), rituximab (Rituxan), basiliximab (Simulect), and golimumab (CNTO 148). To date, however, infliximab is the only biologic drug approved for treatment of ulcerative colitis.

Interferon. Interferons suppress important inflammatory factors in the immune system. They are used in treating multiple sclerosis. Research suggests that the drug interferon (IFN) beta-1a (Avonex, Rebif) may help patients with ulcerative colitis. Side effects include flu-like symptoms and reactions at the site of injection. More research is needed.

Rosiglitazone. The diabetes drug rosiglitazone (Avandia) is being studied as a short-term treatment for mild-to-moderate ulcerative colitis in patients who are not helped by 5-aminosalicylic acid (5-ASA) drugs. Research presented at the 2007 Digestive Disease Week conference indicated that rosiglitazone may have some benefit for select patients. However, this drug has been associated with increased risk for heart failure, and possibly heart attack, in patients with diabetes. More research is needed.

Alicaforsen. Antisense drugs bind to target RNA and block the production of key proteins. Alicaforsen is an antisense drug that inhibits an intercellular adhesion molecule (ICAM-1) thought to play a pivotal role in the inflammatory process. Several clinical trials of alicaforsen enemas have reported encouraging results for improvement of ulcerative colitis symptoms. More research is needed.

Adsorptive Granulocyte and Monocyte Apheresis (GMA). Adsorptive apheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves withdrawing blood from the patient, filtering it through a device, and then infusing the filtered blood back into the patient. The process removes inflammatory antibodies and other immunologically active substances. It is used for patients with rheumatoid arthritis and may be helpful for patients with ulcerative colitis. Some clinical trials have reported promising results for treatment of refractory ulcerative colitis. More research is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies are reporting significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger inflammatory bowel disease. More research, however, is needed.

Surgery

In 20% of people with ulcerative colitis, drug therapy is not effective, and surgery to remove diseased sections is necessary. In these people, part, or all ,of the colon is removed, depending on the extent of the disease. Surgeries may also be required because of hemorrhage, chronic illness, perforation of the colon, or to prevent colon cancer. Studies report that surgery improves the quality of life in most patients. Some experts are urging, in fact, that many patients should consider intestinal surgery in the early stages of the disease.

Proctocolectomy is removal of the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements. It can achieve a complete cure, but it is a last resort. There are different variations that may be performed depending on various factors. The procedure must be performed only on patients in whom it is absolutely clear that ulcerative colitis, and not Crohn’s disease, is causing the inflammatory bowel disease (IBD). Discovering underlying Crohn's disease or other problems during the procedure can increase the risk for complications.

Ileostomy. In some proctocolectomies, the surgeon creates an opening in the abdominal wall (called a stoma) to allow passage of waste material. This part of the procedure is referred to as an ileostomy, and the stoma is created in the lower right corner of the abdomen. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Ileoanal Anastomosis. Ileal pouch anal anastomosis (IPAA), also simply called ileoanal anastomosis, has now largely replaced ileostomy because it preserves part of the anus and allows for more normal bowel movements. The procedure creates a natural pouch to collect waste, rather than using an ileostomy bag. The standard procedure involves:

The colon is removed as in proctocolectomy, but the surgeon only strips the superficial diseased inner layer of the rectum, leaving the sphincter muscles intact.
The anus is then attached to the ileum (the final portion of the small intestine leading to the colon).
A pouch is constructed out of the small bowel above the anus. The pouch is able to collect waste material, and the patient can pass bowel movements normally through the anus, although they are watery and more frequent than normal (five or six times a day). Closing the pouch with a staple, rather than hand-sewn stitches, achieves better continence rates.
A temporary abdominal opening (ileostomy) is usually required, but it is typically closed up in a second operation a few months later.

Flatulence is the most socially distressing problem. Unfortunately many of the fiber rich vegetables and whole grains that can benefit patients with ulcerative colitis can also cause gas. (Surgical patients should avoid or chew thoroughly insoluble fiber foods, such as popcorn, olives, and vegetable skins, which can obstruct the stoma.) Some pouching systems have filters that can help limit flatulence. Typically, flatulence occurs 2 - 4 hours after eating, which may help patients time their meals to ensure privacy afterward.

Patients must increase fluid intake, and include not only water but also broth, sports drinks, and vegetable juice to maintain appropriate levels of sodium and potassium.

Patients should avoid time-released, coated, or large pills, which often are not completely absorbed and may block the stoma.

The ileostomy does not interfere with bathing or showering or most physical activity. (Patients should avoid contact sports.) As a rule, the surgeries do not impair sexual function. If it does, according to one study, taking sildenafil (Viagra) restores sexual function to near or complete improvement in 80% of men.

Complications are common with any intestinal operation. In about 5 - 10% of IPAA procedures, complications occur that require conversion to an ileostomy. In general, patient satisfaction is very high with this procedure. Over 80% of patients report better or much better quality of life 5 years after the procedure. According to one study, 90% of patients can expect to have a functioning pouch for at least 20 years. Most patients can postpone their bowel movements until they are convenient. Bowel movements still average about seven a day.

Pouchitis. Inflammation of the pouch (pouchitis) is the most common complication of the pouch procedures, and one study reported its occurrence in up to 60% of patients. Symptoms include rectal bleeding, cramps, and fever. It can usually be easily treated. According to one study, however, in about 10% of these patients the condition becomes chronic, and the pouch may need to be removed. Metronidazole (Flagyl) is effective in treating active flare-ups of pouchitis. Evidence also suggests that the use of a probiotic (VSL-3) helps maintain remission in chronic pouchitis.

Irritable Pouch Syndrome. Irritable pouch syndrome is a problem that includes frequent movements, an urgent need to defecate, and abdominal pain. There are no signs of inflammation, however, as there are with pouchitis. Stress and diet play a role in this condition, and it is usually relieved after a bowel movement.

Fecal Incontinence. About 70% of patients are fully continent indefinitely after the procedure. (In other words, they experience no leakage.) The other patients typically experience occasional spotting and minor leakage, which is manageable.

Infertility. IPAA triples the risk of infertility in women with ulcerative colitis. The surgery may cause scarring or blocking of fallopian tubes, which increases the risk of infertility. About 48% of women who undergo this procedure become infertile

Severe scarring at the incision occurs in more than half of patients. One study found that placing an experimental absorbable membrane made from hyaluronate (a natural lubricating substance) along the incision reduced the rate of scarring up to 15%. When the rectum is removed, there is a small danger of injury to the nerves that control erection and bladder function.

Small bowel obstruction may occur with some of the procedures. If this occurs in pouch procedures, the pouch may need to be removed.

Pelvic infection occurs in less than 10% of pouch procedures (more often after hand-sewn than stapled anastomoses), and it occurs almost four times more often in men than in women. It is also more common in patients with ulcerative colitis who also have toxic megacolon.

Valve leakage may occur or the catheter may become blocked in continent ileostomies. In at least 10% of these procedures, the valve needs to be repaired later on.

Some studies have also reported that appendectomy (removal of the appendix) protects against ulcerative colitis. It may be that removing the appendix alters the T cell balance in the immune system that then works in favor of people with UC. One study suggested, however, that specific inflammatory conditions leading to appendicitis were the protective factors -- and only in people under age 20. (An appendectomy may actually increase the risk for Crohn's disease.)

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

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Lawson MM, Thomas AG, Akobeng AK. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2006 Jul 19;3:CD005112.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Infertility in men

FitSugar — Wed, 08 Oct 2008 17:35:50 -0700

In This Report

Highlights
Introduction
Male Reproductive System...
Sperm Abnormalities
Causes
Diagnosis
Treatment
Assisted Reproductive Techn...
Complications of Assisted R...
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test Kit

Fertell, the first at-home fertility test kit, became commercially available in June 2007. The Fertell kit contains tests to screen for both male and female infertility. Men can test their semen for concentrations of motile sperm, while women can test their urine for levels of follicle-stimulating hormone (a marker for egg quality). Results are available in fewer than 90 minutes and, according to the test kit's manufacturer, are 95% accurate. However, Fertell does not screen for all types of infertility problems and should not be used as a replacement for a complete evaluation by a doctor.

Intracytoplasmic Sperm Injection May Be Overused

Use of intracytoplasmic sperm injection (ICSI), in combination with in vitro fertilization (IVF), has increased 5-fold over the past decade, even though the proportion of men treated for male infertility has remained the same. This increase suggests that doctors are now using ICSI to treat problems other than male infertility, according to a 2007 study in the New England Journal of Medicine. Some doctors recommend ICSI for women who have failed IVF cycles or who have few or poor-quality eggs. According to the Society for Assisted Reproductive Technology, there is little evidence that ICSI can help couples conceive when male infertility is not a factor.

Infertility and Birth Defects

Although there has been concern that assisted reproductive technologies (ART) may increase the risk for birth defects, infertility itself may be a risk factor, regardless of whether ART is used. Even children born to infertile couples who do not use ART have a slightly increased risk for birth defects, indicates a 2006 study in the British Medical Journal.

Varicocele Embolization

Varicocele embolization, a minimally invasive surgical approach to varicocele repair, can help improve sperm count and motility, according to research presented at the 2006 annual meeting of the Radiological Society of North America. Varicoceles (varicose veins in the testicles) are often linked to male infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond week 20. In many cases, infertility is caused by a combination of problems in both partners that conspire to prevent conception from occurring.

About 8 - 10% of couples of reproductive age experience infertility, and in around 40% of these cases male infertility is the major factor. Another 40% of infertility problems are caused by abnormalities of the woman's reproductive system, and the remaining 20% involve couples who both suffer reproductive difficulties.

Infertility affects one in 25 American men. More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. Whether sperm counts are declining overall in industrialized countries is a controversial issue. However, over the last few years the number of assisted reproductive procedures that target male infertility have increased, while female procedures have declined.

The male reproductive system creates sperm that is manufactured in the seminiferous tubules within each testicle. The head of the sperm contains the DNA, which when combined with the egg's DNA, will create a new individual. The tip of the sperm head is the portion called the acrosome, which enables the sperm to penetrate the egg. The midpiece contains the mitochondria which supplies the energy the tail needs to move. The tail moves with whip-like movements back and forth to propel the sperm towards the egg. The sperm have to reach the uterus and the fallopian tube in order to fertilize a woman's egg.

Male Reproductive System

Male fertility depends on the proper function of a complex system of organs and hormones:

The process begins in the area of the brain called the hypothalamus-pituitary axis, a system of glands, hormones, and chemical messengers called neurotransmitters, all of which are critical for reproduction.
The first step in fertility is the production of gonadotropin-releasing hormone (GnRH) in the hypothalamus, which prompts the pituitary gland to manufacture follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
FSH maintains sperm production, and LH stimulates the production of the male hormone testosterone.
Both sperm and testosterone production occurs in the two testicles, or testes, which are contained in the scrotal sac (the scrotum). (This sac develops on the outside of the body because normal body temperature is too high to allow sperm production.)

The male reproductive structures include the penis, the scrotum, the seminal vesicles, and the prostate.

Sperm are manufactured in several hundred microscopic tubes, known as seminiferous tubules, which make-up most of the testicles.

Surrounding these tubules are clumps of tissue containing so-called Leydig cells. Here, testosterone is manufactured.

Sperm Development. The life cycle of sperm consists of a remarkable journey that depends on hormonal signals combined with a mechanical process. It takes about 74 days:

Sperm begin partially embedded in nurturing amoebae-like cells known as Sertoli cells, which are located in the lower parts of the seminiferous tubules.
As they mature and move along, they are stored in the upper part of the tubules. Young sperm cells are known as spermatids.
When the sperm has completed the development of its head and tail, it is released from the cell into the epididymis. This remarkable C-shaped tube is 1/300 of an inch in diameter and about 20 feet long. It loops back and forth on itself within a space that is only about one and a half inches long. The sperm's journey through the epididymis takes about 3 weeks.
The fluid in which the sperm is transported contains sugar in the form of fructose, which provides energy as the sperm matures. In the early stages of its passage, the sperm cannot swim in a forward direction and can only vibrate its tail weakly. By the time the sperm reaches the end of the epididymis, however, it is mature and looks like a microscopic squirming tadpole.
At maturity, each healthy sperm consists of a head that contains the man's genetic material, his DNA, and a tail that lashes back and forth at great speed to propel the head forward at about four times its own length every second. The ability of a sperm to move forward rapidly and straight is probably the most significant determinant of male fertility.

Ejaculation. When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract, which forces the sperm out through the penis:

In the penis, the sperm first pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles. These are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates, but during orgasm, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally shot out of the penis.

Click the icon to see an image of the vas deferens.

Semen. In addition to providing the fluid that transports the sperm, semen also has other benefits:

It provides a very short-lived alkaline environment to protect sperm from the harsh acidity of the female vagina. (If the sperm do not reach the woman's cervix within several hours, the semen itself becomes toxic to sperm and they die.)
It contains a gelatin-like substance that prevents it from draining from the vagina too quickly.
It contains sugar in the form of fructose to provide instant energy for sperm locomotion.

The Path to the Egg. The sperm's passage to the egg is a perilous journey.

Usually about 100 - 300 million sperm are delivered into the ejaculate at any given time. Even under normal conditions, however only about 15% of these millions of sperm are sound enough to fertilize an egg.
To compound the problem, after the stress of ejaculation, only about 400 sperm survive the orgasm to complete the journey.
Out of this number, a mere 40 or so sperm survive the toxicity of the semen and the hostile environment of the vagina to reach the vicinity of the egg. Normally, the cervical mucus forms an impenetrable barrier to sperm. However, when a woman ovulates (releases her egg, the oocyte), the mucous lining thins to allow sperm penetration.
Sperm that manage to reach the mucous lining in the woman's cervix (the lower part of her uterus) must survive about four more days to reach the woman's fallopian tubes. (Here, the egg is positioned for fertilization for only 12 hours each month.)
The few remaining sperm that penetrate the cervical mucus and are able to reach the fallopian tubes become capacitated.
Capacitation is a one-time explosion of energy that completes the sperm's journey. It boosts the motion of the sperm and triggers the actions of the acrosome, a membrane that covers the head of the sperm and resembles a warhead. The acrosome is dissolved, and enzymes contained within it are released to allow the sperm to drill a hole through the tough outer coating of the egg.
In the end, only one sperm gets through to fertilize the egg.

Click the icon to see an image of the uterus.

Sperm Abnormalities

More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. In 30 - 40% of cases of sperm abnormalities, the cause is unknown. It may be the end result of one or more factors that include chronic illness, malnutrition, genetic defects, structural abnormalities, and environmental factors. Partial obstruction anywhere in the long passages through which sperm pass can reduce sperm counts. In one study, obstruction was believed to be a contributing factor in over 60% of low sperm count cases. Obstruction itself can be caused by many factors.

Sperm abnormalities are categorized by whether they affect sperm count, sperm quality, or sperm shape.

In the past, a sperm count of less than 40 million/mL in the ejaculate was believed to cause infertility. Now, however, if the woman is fertile and young, a count as low as 10 million can often accomplish conception over time, even without treatment. In fertilization clinics, men with low sperm counts report fertilization rates of about 30%, while those with average sperm counts have rates between 60 - 80%. Sperm count varies widely over time, and temporary low counts are common. Therefore, a single test that reports a low count may not be a representative result.

Sperm motility is the sperm's ability to move. If movement is slow, not in a straight line, or both, the sperm have difficulty invading the cervical mucous or penetrating the hard outer shell of the egg. If 60% or more of sperm have normal motility, the sperm is at least average in quality. If less than 40% of sperm are able to move in a straight line, the condition is considered abnormal. Sperm that move sluggishly may also have genetic or other defects that render them incapable of fertilizing the egg. An important 2001 study identified a protein in the tail of the sperm called CatSper, which might play a central role in the ability of the sperm to swim and penetrate the egg.

Morphology refers to the shape and structure of an object. Morphology may be even more important than count or motility in determining potential fertility. Abnormally shaped sperm cannot fertilize an egg. About 60% of the sperm should be normal in size and shape for adequate fertility.

The perfect structure is an oval head and long tail. Abnormally shaped sperm may include a number of variations:

A very large round head. (In one study, if 14% or more of sperm had round enlarged heads, the chances for pregnancy fell to about 20%. Such an abnormality indicates early unraveling of genetic material.)
An extremely small pinpoint head
A tapered head
A crooked head
Two heads
A tail with kinks and curls

Sperm carry half the genetic material necessary to make a complete human being. (The egg holds the other half.) Genes are contained in the rod-like structures called chromosomes. The genes themselves are made up of chains of molecules called DNA, which carry the information that defines a human. Genetically fragile sperm are important factors in male infertility. Such sperm have fragmented DNA chains, which make them less capable of fertilization and may also contribute to low quality.

Causes

In one study, the causes of infertility in men seeking to conceive included:

Vasectomy. In the study, 56% of men were seeking a reversal of this procedure. Thirty years ago, this was a factor in only 5% of men seeking help for fertility.
Varicocele (14%). A network of veins carries blood away from the testicles and back up into the body. If these veins become enlarged, twisted, and swollen (similar to varicose veins in the leg), this condition is termed a varicocele. Varicoceles can impair testicular function and fertility.
Unknown infertility (8%).
Absence of sperm (6%). There are many biologic and environmental factors that can lead to low sperm count. For instance, abnormalities in production or obstruction of the tubes that carry sperm can reduce sperm levels. A condition called Sertoli cell-only syndrome is one in which the cells that produce sperm (the Sertoli cells) are absent. This can be a congenital problem that a man is born with or caused by infection, injury, medication, radiation, or genetics. In addition, other conditions may cause infertility in men.

The effect of aging on male fertility is not totally clear. However, growing evidence suggests that it may be a factor (although not to the extent that it is in women). This evidence indicates that age-related sperm changes in men are not abrupt, but are a gradual process. Aging can adversely affect sperm counts and sperm motility (the sperm's ability to swim quickly and move in a straight line). A 2006 study also suggested that the genetic quality of sperm declines as a man ages. The researchers found that poor sperm motility was associated with DNA fragmentation. This led to some older men having an increased risk of passing on gene mutations that cause dwarfism and possibly other genetic diseases.

Nearly any major physical or mental stress can temporarily reduce sperm count. Some common conditions that lower sperm count, temporarily in nearly all cases, include:

Emotional Stress. Stress may interfere with the hormone GnRH and reduce sperm counts.

Sexual Issues. In fewer than 1% of cases, impotence, premature ejaculation, or psychological or relationship problems contribute to male infertility, although these conditions are usually very treatable. Lubricants used with condoms, including spermicides, oils, and Vaseline, can affect fertility. Astroglide, Replens, or mineral oil may not be as harmful to sperm. However, oil-based lubricants can damage latex condoms and should be avoided.

Testicular Overheating. Overheating, such as from high fevers, saunas, and hot tubs, may temporarily lower sperm count. Persistent exposure to high temperatures during work may impair fertility. Several studies have found no negative effects on fertility from wearing tight trousers, briefs, or athletic supports, even every day.

Substance Abuse. Cocaine or heavy marijuana use appears to temporarily reduce the number and quality of sperm by as much as 50%. Sperm actually have receptors for certain compounds in marijuana that may impair the sperm's ability to swim and also inhibit their ability to penetrate the egg. Alcohol does not appear to affect fertility, unless it is so abused that it causes liver damage.

Smoking. Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that affect the offspring. One study found that men or women who smoke have lower success rates with assisted reproductive technologies. Another study reported that men who smoke also have lower sex drives and less frequent sex.

Malnutrition and Nutrient Deficiencies. Deficiencies in certain nutrients, such as vitamin E, vitamin C, selenium, zinc, and folate, may be particular risk factors for infertility

Obesity. Obesity may be a risk factor for male infertility. A 2006 epidemiological study found that a 20-pound increase in a man's weight increased the chance for infertility by about 10%.

Bicycling. Bicycling has been linked to impotence in men and also may affect fertility. Pressure from the bike seat may damage blood vessels and nerves that are responsible for erections. Mountain biking, which involves riding on off-road terrain, exposes the perineum (the region between the scrotum and the anus) to more extreme shocks and vibrations and increases the risk for injuries to the scrotum. One study found that men who mountain bike are far more likely to have scrotal abnormalities, including calcium deposits, cysts, and twisted veins. Men who cycle can reduce such risks by:

Taking frequent rests while biking
Wearing padded bike shorts
Using a padded or specially contoured bike seat that is raised high enough and sits at the proper angle

Problems in the genes that regulate male fertility and in the genetic material of sperm itself are important contributors to infertility problems in men. In fact, even in men with no known fertility problems, 19% of the sperm are genetically defective. Certain inherited medical conditions also contribute to male infertility. Defective genes themselves can be inherited, produced by environmental assaults (such radiation exposure), or both. Of some concern is the possibility that these mutations will be passed to offspring in men who undergo fertilization techniques that retrieve sperm and directly fertilize the egg. (Under natural conditions, genetically abnormal sperm would be very unlikely to reach and fertilize the egg.)

Defective Genetic Material. Sperm carry half the genetic material necessary to make a human being. Infertile men have been reported to have a relatively high percentage of sperm with broken or damaged DNA (the molecular chain that makes up a gene).

Genetic Factors Specifically Affecting Sperm Production or Quality. Abnormalities in genes that specifically regulate sperm production and quality are major factors in male infertility. Some research suggests that about 10% of cases of male infertility may be due to problems, most likely genetic, in the acrosome. The acrosome is the enzyme-filled membrane cap on the sperm -- its warhead -- that is critical for piercing the egg. In one study, pregnancy was impaired if 7% or more of sperm had abnormalities in the acrosome.

Inherited Disorders that Affect Fertility. Certain inherited disorders can impair fertility. Examples include:

Cystic fibrosis patients often have missing or obstructed vas deferens (the tubes that carry sperm). In fact, men whose infertility is caused by an inborn missing vas deferens have a 60% chance that they carry the gene for cystic fibrosis (even if they don't have the disease itself).
Klinefelter syndrome patients carry two X and one Y chromosomes (the norm is one X and one Y), which leads to the destruction of the lining of the seminiferous tubules in the testicles during puberty, although most other male physical attributes are unimpaired.
Kartagener syndrome, a rare disorder that is associated with a reversed position of the major organs, also includes immotile cilia (hair-like cells in lungs and sinuses that have a structure similar to the tails of sperm). Sperm motility may also be impaired by this condition.
Polycystic kidney disease, a relatively common genetic disorder that causes large cysts to form on the kidneys and other organs during adulthood, may cause infertility as the first symptom if cysts develop in the reproductive tract.

Exposure to toxins, chemicals, or infections may reduce sperm count by either affecting testicular function or altering hormone systems. The extent of the impact and specific environmental assaults involved, however, are often controversial. Some researchers believe environmental toxins are contributing to a general worldwide decline in male fertility. Data indicate that testosterone levels in American men may have declined over the last several decades. The reasons for this decline have not yet been determined. However, even if testosterone levels are declining, the proportion of men treated for fertility problems has not changed much over the past decade.

Free Radicals (Oxidants). The primary suspects in the link between environmental assaults and infertility are free radicals, also called oxidants. These are unstable molecules, usually containing oxygen, that are released as a by-product of many natural chemical processes in the body. Infections, chemicals, and other environmental assaults can produce high levels of these particles. High levels may even affect the genetic material in cells. Sperm are particularly vulnerable to the damaging effects of this oxidation process. There have been reports that significant levels of oxidants occur in the semen of about 25% of infertile men.

Exposure to Estrogen-Like and Hormone-Disrupting Chemicals. European studies have increasingly reported a worsening in male reproductive health and an increase in testicular and prostate cancers. Many investigators strongly suspect environmental causes, particularly excessive chemicals that disrupt hormones, as a major cause for both these events. Estrogen-like chemicals found in pesticides and other chemicals are of particular concern. Overexposure to estrogen in male animals reduces the number of Sertoli cells (the cells necessary for the initial development of sperm). Some hormone-disrupting chemicals under investigation include:

Treatment of prostate cancer varies depending on the stage of the cancer and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Bisphenol A is a widely used chemical found in plastic food containers and bottles that has provoked concern. It has potent estrogen-like effects in low dose. Use of the chemical in female rats has produced prostate abnormalities in their male offspring.
Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phylates of special concern include dibutyl phthalate (DBP), which is found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phylates have significantly impaired sperm count and abnormalities in their reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring,
Organochlorines are compounds that combine chlorine and organic substances -- usually petrochemicals. Many have estrogen-like effects, including those previously used to make plastics (PCBs) and pesticides (DDT and p,p-DDE). Some, such as dioxins and furans, are byproducts of many chemical processes. Fortunately, most of these chemicals have been banned, but they were heavily used in manufacturing before 1970 and are still widespread in the environment. Studies report that when men had a history of moderate or high on-the-job exposure to pesticides containing organochlorines, their fertility rates were lower than men without such exposures. Studies have found a strong correlation between high levels of polychlorinated biphenyls (PCBs) or p,p-DDE with reduced sperm quality and quantity. In one of the studies, even men with healthy sperm with high organochlorine levels had a lower sperm count than those with lower levels of these compounds.

Most evidence on the hormone of chemical estrogens has occurred in animals and birds. Tests of single chemicals containing estrogen have reported little danger for people. Some studies suggest, however, that exposure to more than one of these chemicals may be very harmful. At this time, there is no strong evidence supporting a serious harmful effect in people who have normal exposure to these chemicals. Major efforts are underway to determine the extent of any possible harm from these chemicals.

Exposure to Heavy Metals. Chronic exposure to heavy metals such as lead, cadmium, or arsenic may affect sperm quality. Trace amounts of these metals in semen seem to inhibit the function of enzymes contained in the acrosome, the membrane that covers the head of the sperm.

Radiation Treatments. X-rays and other forms of radiation affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to 2 years to resume normal sperm production and, in severe circumstances, may never recover.

Men with fertility problems because of low semen levels when they ejaculate may have a structural abnormality in the tubes transporting the sperm. (A normal amount of semen is 2.5 - 5 mL, or about 1/2 - 1 teaspoon.)

A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men, although it is not clear how or even if they affect fertility. They tend to occur more commonly (85%) on the left side. Some theories supporting their possible effect on infertility include:

Click the icon to see an image of a varicocele.

Varicoceles may partially obstruct the passages through which sperm pass.
Varicoceles may elevate temperature in the testes.
Varicoceles may produce higher levels of nitric oxide, a substance that has beneficial effects on blood flow and other functions but which might, in excess, injure sperm.
Varicoceles may block oxygen supply to the sperm.
Varicoceles have been associated with abnormalities in cellular material in the sperm. One study suggested that some men with fertility problems may have genetic defects that cause both varicoceles and impaired sperm.

Some reports indicate that only varicoceles that are large enough to be felt (or palpable) may impact fertility. On the other hand, however, an 8-year study of men with and without varicoceles found no differences in sperm quality or in the ability to conceive. Furthermore, the few well-conducted studies on repair of varicoceles suggest that the procedure does not improve pregnancy rates. Their effect on fertility remains unclear.

Hypogonadism is the general name for a severe deficiency in gonadotropin-releasing hormone (GnRH), the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones. Low levels of testosterone from any cause may result in defective sperm production.

Hypogonadism is uncommon and is most often present at the time of birth, usually the result of rare genetic diseases affecting the pituitary gland that may include selective deficiencies of the hormones FSH and LH, Kallman syndrome, or panhypopituitarism, in which the pituitary gland fails to make almost all hormones. It can also develop later in life from brain or pituitary gland tumors or as a result of radiation treatments. Defects in the gene on the X chromosome that regulates receptors that bind to androgens (male hormone) may also prove to be very important causes of male infertility.

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

Autoimmunity is a condition in which antibodies of the immune system attack specific cells in the body, mistaking them for foreign microinvaders. In the case of male infertility, these so-called autoantibodies ("self" antibodies) target the sperm. Antibodies bind to specific parts of the sperm, such as the head or tail and, depending on the site of attachment, cause various problems:

Sperm may stick together (agglutinate)
They may fail to interact with cervical mucous
They may be unable to penetrate the egg

Some experts believe that in most cases the presence of these antibodies will not prevent conception unless a large percentage of sperm are affected.

Vasectomy and Anti-Sperm Antibodies. Vasectomy, the primary sterility procedure in men, is the most common cause of sperm autoantibodies (also called anti-sperm antibodies). Their typical development may be as follows:

Vasectomy works by severing the vas deferens, the tube that carries sperm from the testicles to the urethra (which leads out of the penis).
After vasectomy, sperm continue to be produced but, instead of being confined to the reproductive passages, they leak out into the body.
Here, the immune system may perceive them as foreign invaders and develop antibodies to attack them.

Such antibodies often persist, even if a man restores sperm flow by a successful reversal procedure (vasovasostomy). The persistence of anti-sperm antibodies may result in infertility.

Click the icon to see an illustrated series detailing vasectomy.

Other Causes of Autoantibodies. Antibodies to sperm can also appear in men without previous vasectomies and have been reported to be present in 10% of all men with fertility problems. They may be linked to genital infections or injury, although the cause is usually not known.

Retrograde ejaculation occurs when the muscles of the urethra do not pump properly during orgasm and sperm are forced backward into the bladder instead of forward out of the urethra. Sperm quality is often impaired.

Retrograde ejaculation can be the consequence of several conditions:

Surgery to the lower part of the bladder or prostate (the most common cause of retrograde ejaculation)
Diabetes
Multiple sclerosis
Back surgery
Spinal cord injury

Medications such as tranquilizers, certain antipsychotics, or hypertension medications also may cause temporary retrograde ejaculation.

Any structural abnormalities that affect the testes, tubes, or other reproductive structures can have a profound effect on fertility.

Testicular Dysgenesis Syndrome. Testicular dysgenesis syndrome is a recently observed occurrence of three conditions -- impaired sperm production and quality, testicular cancer, and genital tract abnormalities. Environmental factors that increase damage from oxidants are believed to be responsible.

The genital abnormalities identified with this syndrome are undescended testes and hypospadias, each of which is associated with infertility:

Undescended Testes (Cryptorchidism). In some cases, there is a failure of the testes to descend from the abdomen into the scrotum during fetal life. Cryptorchidism is associated with mild to severe impairment of sperm production. In one survey, 38% of men who as youngsters had two undescended testicles and 10% of men with one undescended testicle were infertile, compared with 5% of men who had normal testes. Even one undescended testicle may impair fertility. In cryptorchidism, the testes are exposed to the higher internal body heat, but this may not totally explain the damage in sperm production that can occur. (Men who suffer from this condition should be aware that even if the testicle is surgically moved to the scrotum, their risk of testicular cancer is significantly increased, warranting careful self-exams and regular follow-up with a doctor.)
Hypospadias. This is a birth defect in which the urinary opening is on the underside of the penis, can prevent sperm from reaching the cervix if not surgically corrected.

Click the icon to see an image of an undescended testicle.

Click the icon to see an image of hypospadias.

Blockage in the Tubes that Transport Sperm. Some men are born with a blockage in the epididymis or ejaculatory ducts or other problems that later affect fertility. One center reported that 2% of men seeking treatment had no vas deferens.

Anorchia. In the very rare condition known as anorchia, a man is born without any testes.

Syringomyelia. This is a disease of the spinal cord that results in no ejaculate at all (aspermia).

Birth rates among cancer survivors are only 40 - 85% of normal rates. Certain cancers, particularly testicular cancer, impair sperm production, often severely. Cancer treatments such as chemotherapy and radiation can damage sperm quality and quantity, causing infertility. The closer radiation treatments are to reproductive organs, the higher the risk for infertility. Fortunately, while men may fail to produce sperm for as long as 5 years after radiation therapy, many men eventually recover their sperm production ability. Chemotherapy with drugs that harm reproductive function tends to affect fertility more severely in men than in women. New drug regimens are helping to improve fertility rates.

Adolescents and adult men undergoing cancer treatments who may want to father children should consider banking and freezing their sperm for later use in assisted reproductive therapies. This technique is called sperm cryopreservation. Sperm cryopreservation is recommended by the American Society of Clinical Oncology as the method with the highest likelihood of success for male cancer survivors. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.

There is some controversy over the effect of infections on infertility. Simply detecting the presence of an infection in infertile men does not necessarily mean that it has any relationship to the infertility itself. The immune response to some infections may release inflammatory factors and oxidants, chemically unstable particles that can damage sperm. The exact impact of this process on sperm is unclear, however. Infections may alter the liquidity of semen and sperm motility, although these are likely to be temporary effects. Among the infections most implicated in infertility are:

Sexually Transmitted Diseases. Repeated Chlamydia trachomatis or gonorrhea infections are most often associated with male infertility. Such infections can cause scarring and block sperm passage. Human papilloma viruses, the cause of genital warts, may also impair sperm function.

Mycoplasma. Mycoplasma is an infectious organism that appears to fasten itself to sperm cells and render them less motile.

Mumps. When mumps develops after puberty, it damages the testicles in 25% of men afflicted with the disease. (Interferon, an anti-viral drug, may help prevent infertility in adult males with active mumps, but the drug is highly toxic and caution is essential.)

Glandular Infections in the Urinary Tract or Genitals. Glandular infections that may affect fertility include prostatitis (in the prostate gland), orchitis (in the testicle), semino-vesculitis (in the glands that produce semen), or urethritis (in the urethra), perhaps by altering sperm motility. Even after successful antibiotic treatment, infections in the testes may leave scar tissue that blocks the epididymis.

Medical Conditions. Other medical conditions that can affect male fertility include any severe injury or major surgery, diabetes, HIV, thyroid disease, Cushing syndrome, heart attack, liver or kidney failure, and chronic anemia.

The effects of medications on sperm quality and count have not been rigorously studied, and many medicines are commonly prescribed without knowing whether they impair fertility. Anabolic steroids (which are often abused by weight lifters and other athletes) deserve special notice because they are known to severely impair sperm production. Among the other drugs that can affect male fertility are cimetidine (Tagamet), sulfasalazine (Azulfidine), salazopyrine, colchicine, methadone, methotrexate (Folex), phenytoin (Dilantin), corticosteroids, spironolactone (Aldactone), thioridazine (Mellaril), and calcium channel blockers.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over age 35 or if either partner has known risk factors for infertility. A work-up can not only uncover the causes of infertility but also detect other potentially serious medical problems as well, including genetic mutations, cancer, or diabetes.

The patients will provide the doctor with a detailed history of any medical or sexual factors that might affect fertility:

Frequency and timing of sexual intercourse
Duration of infertility and any previous fertility events
Childhood illnesses and any problems in development
Any serious illness (diabetes, respiratory infections, cancer, previous surgeries)
Sexual history, including any sexually transmitted diseases
Any exposure to toxins, such as chemicals or radiation
History of any medications and allergies
Any family history of reproductive problems

A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.

Varicoceles large enough to possibly interfere with fertility can be felt during examination of the scrotum. In such cases, they are described as feeling like "a bag of worms." They disappear or are greatly reduced when the patient lies down, so the patient should be examined for varicocele while standing.
Checking the size of the testicles is helpful. Smaller-sized and softer testicles along with tests that show low sperm count are strongly associated with problems in sperm formation. Normal testicles accompanied by a low sperm count, however, suggest possible obstruction. The doctor may also take the temperature of the scrotum with a test called scrotal thermography.
The doctor will also check the prostate gland for abnormalities.
The penis is checked for warts, discharge from the urinary tract, and hypospadias (incorrect location of the urethra opening).

A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.

The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following steps:

A man should abstain from ejaculation for several days before the test because each ejaculation can reduce the number of sperm by as much as a third. To ensure an accurate sample, most doctors recommend abstaining from ejaculation for at least 2 days, but not more than 5 days, prior to semen collection.
A man collects a sample of his semen in a collection jar during masturbation either at home or at the doctor's office. Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. Specially designed condoms are also available that enable collection of a sample during sexual intercourse. (Regular condoms are not useful, since they often contain substances that kill sperm.)
The sample should be kept at body temperature and delivered promptly. If the sperm are not analyzed within 2 hours or kept reasonably warm, a large proportion may die or lose motility.
A semen analysis should be repeated at least three times over several months.

The sperm count test is performed if a man's fertility is in question. It is helpful in determining if there is a problem in sperm production or quality of the sperm as a cause of infertility. The test may also be used after a vasectomy to make sure there are no sperm in the semen.

The man and woman should both be present when the doctor discusses the results of this analysis so that both partners understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen. However, semen analysis alone is not necessarily a definitive indicator of either infertility or fertility.

In June 2007, the first at-home fertility test kit became commercially available. Fertell includes both male and female tests that allow couples to test sperm motility (for men) and follicle-stimulating hormone (for women). Results are available in less than 90 minutes, and are 95% accurate. The test is available on-line and at some pharmacies. It does not require a prescription. However, Fertell does not screen for all types of fertility problems and should not be used as a substitute for a professional evaluation by a doctor.

Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. Although in a large analysis sperm counts below 13.5 million were considered a strong indication of infertility, pregnancy was possible so long as any motile sperm were present. If there are no sperm cells at all in the semen, the doctor checks for obstruction in the tubes or for Sertoli cell-only syndrome, in which there are no sperm-producing cells in the testes. An at-home test (FertilMARQ) is now available to help gauge sperm quantity.

Sperm Motility. Motility (the speed and quality of movement) is graded on a 1 - 4 ranking system. For fertility, motility should be greater than 2.

Grade 1 sperm wriggle sluggishly and make little forward progress. (Sperm that, in fact, clump together may indicate that antibodies to the sperm are present.)
Grade 2 sperm move forward, but they are either very slow or do not move in a straight line.
Grade 3 sperm move in a straight line at a reasonable speed and can home in on an egg accurately.
Grade 4 sperm are as accurate as Grade 3 sperm, but move at terrific speed.

More than 63% of sperm should be motile for normal fertility, but even men whose motile sperm constitutes only about a third of the total sperm count should not rule out conception. Testing for sperm motility is particularly valuable for predicting the success of artificial insemination and which men might be candidates for the intracytoplasmic sperm injection (ICSI) fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.

Sperm Morphology. Morphology is the shape and structure of the sperm and, of the three main sperm values, may be the best predictor of fertility. Older reports indicated that about 60% of the sperm should be normal in size and shape for adequate fertility. However, one major analysis used a much broader range of criteria for sperm morphology and concluded that values over 12% were good predictors of fertility. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Seminal Fluid. The seminal fluid (semen) itself is analyzed for abnormalities. The color is checked and should be whitish-gray.

The amount of semen is important. Most men ejaculate 2.5 - 5 milliliters (mL) or cubic centimeters (cc) (1/2 - 1 teaspoon) of semen. Either significantly higher or lower amounts can be a sign of trouble:

Amounts greater than 1 cc but lower than 2.5 cc may indicate prostate problems or frequent intercourse.
A semen sample that is less than 1 cc could indicate a blockage of the ejaculatory ducts or other tubular abnormalities.
No ejaculate at all may signal retrograde ejaculation.
High amounts of ejaculate may, in some cases, also contribute to infertility.

The semen will be tested for how liquid it is. (Normal semen is liquefied within 20 minutes after adding certain enzymes.) Abnormal results suggest the following:

Overly sticky fluid suggests problems in the prostate gland (which adds fluid to sperm)
Overly watery fluid suggests lack of sperm

The amount of sugar (fructose) in sperm will be measured:

Since fructose is added to the semen in the epididymis, an absence of fructose indicates that an obstruction has occurred either in the vas deferens or the epididymis.
Conversely, if there is fructose in the semen but no sperm, then the channel from the epididymis is open but there is a defect in sperm production.

Other factors may also be measured:

White blood cell counts are taken to detect infection.
Low levels of a substance called inhibin B, which appears to be produced only in the testes, may indicate blockage or other defects in the seminiferous tubules.
Low levels of another compound, alpha-glucosidase, may also indicate blockage in the epididymis.

Blood tests are used for measuring several factors that might affect fertility:

Hormonal Levels. Tests for certain hormone levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.

Blood tests for testosterone and follicle-stimulating hormone (FSH) levels are usually taken first.
If testosterone levels are low, then luteinizing hormone (LH) are measured.

Low levels of FSH, LH, and testosterone indicate a diagnosis of hypogonadotropic hypogonadism. Very high FSH levels with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome, in which sperm-manufacturing cells are absent. Other hormones, such as prolactin, estrogen, or stress hormones may be measured if there are symptoms of other problems, such as low sexual drive or the presence of breasts.

Infections. Blood tests can also determine the presence of any infections that might affect fertility, including HIV, hepatitis, and Chlamydia.

The postcoital test, also known as the cervical mucus penetration test, is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the doctor's office within 2 - 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the doctor observes no surviving sperm or no sperm at all, the cervical mucus should then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.

If a man has had a vasectomy reversed and still cannot conceive or if semen analysis shows sperm clumping together, blood tests for anti-sperm antibodies will be conducted. Anti-sperm antibodies may also develop after genital infection or injury to the testes. The primary negative effect of these antibodies is to bind the sperm to the woman's cervical mucus, preventing the sperm from swimming further up.

Occasionally, a testicle biopsy may be performed, particularly for the following:

If Sertoli cell-only syndrome is suspected, in which sperm-producing cells in the testes are absent. It should be noted that specific cellular patterns can determine whether this condition is congenital (inborn) or caused by some later injury. This distinction is important in predicting the potential success of later sperm retrieval procedures.
For detecting obstruction in the transport system when sperm production looks normal but the count is low.

The standard biopsy procedure requires incisions (called an open approach) under anesthesia. It can be painful afterward. More than one biopsy may be needed in the case of suspected Sertoli cell-only syndrome, since one area may not have cell-producing cells, but other regions may contain normal sperm. Biopsies of both testes are more accurate than one. (Doctors must be careful to avoid the epididymis during a biopsy, since it is a continuous tiny tube and would be destroyed.) Patients may consider freezing any sperm retrieved during biopsy for later use.

Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little or no effect on fertility). It also can detect testicular cancer, which some experts believe make it worthwhile as a routine procedure for any male infertility work-up.

Click the icon to see an image of testicular ultrasound.

Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the intracytoplasmic sperm injection (ICSI) procedure. One study of men attending a fertility clinic showed that a third had genetic defects. If genetic abnormalities are suspected in either partner, counseling is recommended. Researchers are testing techniques such as preimplantation genetic diagnosis (PGD) that can examine all the chromosomes in a human embryo and detect defective genes, such as those for cystic fibrosis, at the very earliest stages. If it proves useful, it may help identify numerous abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring. In fact, a 2003 study suggested that performing an initial genetic analysis to determine DNA fragmentation in sperm may be a better way of predicting whether conception will succeed than analyzing semen.

In men who wish to undergo fertility treatments, certain tests will help determine the right strategies.

The Hamster Test. The hamster test, or micro-penetration assay test, uses the sperm sample to fertilize hamster eggs that have had their covering removed to allow penetration. If fewer than 5 - 20% of the eggs are fertilized, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.

The Human Zona Penetration Test. The human zona penetration test uses sperm to fertilize dead human eggs, which are usually obtained from an ovary that was removed for medical purposes. (Like the hamster test, the procedure cannot result in a living embryo.) Results may provide the same information as the hamster test and also indicate whether the sperm can penetrate the outer coating of an egg.

Acrosome Reaction Test. Tests that induce the ability of the sperm's enzyme-rich covering (acrosome) to dissolve can be very useful.

Other Tests. Additional advanced laboratory tests to measure sperm function, such as computer-aided sperm motility analysis, may also be performed. Some of these tests assess such factors as level of cell-damaging oxidants.

Treatment

Many men diagnosed with infertility in the past would be considered treatable now, even some men with spinal cord injuries. Unless a man produces no sperm at all, recent developments in treatment have made fertility possible for many men willing to undergo treatment and bear the expense. Before undergoing more advanced procedures, most couples trying to conceive should attempt some simple lifestyle changes.

Both male and female hormone levels fluctuate according to the time of day, and they also vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. In one study of men, their sexual activity was highest in October, when conception rates were also high.

Fertility and Seasonal Changes. Different studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.

Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. Couples must try to avoid becoming fixated on the chart, however, in scheduling their sexual activity. Spontaneity can be lost, and the stress on the relationship can be quite severe.

Hormone Monitoring Systems for Women. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine are also available. They are less costly than the saliva test but are messier. Monitoring hormone levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some experts say that having sex more than 2 days a week adds no benefits. And, in fact, frequent sexual activity lowers sperm count per ejaculation. Some studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

Everyone should eat a healthy diet rich in fresh fruits, vegetables, and whole grains. Replace animal fats with monounsaturated oils, such as olive oil. Fish is also a good choice, and fish oils may have benefits for men with infertility. Certain specific nutrients, vitamins and minerals may also improve fertility.

Higher antioxidant intakes of vitamin C, vitamin E, and beta-carotene may help improve sperm numbers and motility, according to a 2005 study. The study included both food and supplement sources.
Vitamins C and E may also help repair DNA damage to sperm. According to a 2005 study, men who took 1 gram per day of these vitamins significantly reduced their percentage of DNA sperm fragmentation within 2 months.
The dietary supplements L-carnitine and L-acetylcarnitine may help improve sperm motility, according to several recent clinical trials.

A man who wants to increase his sperm count should also pursue a healthy lifestyle.

Avoid cigarettes and any drugs that may affect sperm count or reduce sexual function.
Overweight men should try to reduce their weight.
Get sufficient rest, and exercise moderately but regularly. (Those who exercise excessively might cut back, but not stop altogether.)
Stress may contribute to reduced sperm quality. It is not known if stress reduction techniques can improve fertility, but they may help couples endure the difficult processes involved in fertility treatments.
Although studies now indicate that tight underwear and pants pose no threat to male fertility, there is no harm in wearing looser clothing.
To prevent overheating of the testes, men should avoid hot baths, showers, and steam rooms.

The fertility process is a roller coaster of emotions that are present throughout both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other seemingly fertile couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions in both men and women can be viewed as important as medical treatment. The process of fertility evaluation can be very difficult for many men. In a 2003 study, over 10% of men who required a second semen sample were unable to collect a semen sample using masturbation. Such men had had no problems with a first collection, but after being asked for additional samples they suffered severe anxiety during both masturbation in the fertility clinic and during regular sexual activity at home. Numerous studies reported a significant association between psychologic factors, particularly anxiety, and fertility treatment failure in women.

Managing the Emotional Effects of the Outcome. After enduring the process of fertility evaluation, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. Needless to say, the emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple's own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% from 1996 - 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Choosing a good fertility clinic is important. The government does not always regulate centers offering assisted reproductive techniques, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure. The clinics offering them are often significantly more expensive than those that don't.

Artificial insemination it is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. Artificial insemination either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard artificial insemination procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive.
When donor sperm are required.
If the man's sperm count is very low (although it is preferable if at least 5 million per milliliter are motile).
When unexplained infertility exists in both partners.

Those in whom artificial insemination fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8 - 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although in vitro fertilization procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The artificial insemination procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with time of ovulation. One study suggested that women who lay quietly for 10 minutes after sperm were implanted had a significantly higher rate of pregnancy than those who got up immediately.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main factor. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days and then is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While other studies have shown a higher number of birth defects in children conceived with ICSI, the results may have more to do with the genetic background of the parents than ICSI itself. A 2006 study of 8-year-old children conceived with ICSI, meanwhile, found no important differences between these children and children who were conceived naturally.

A 2007 study in the New England Journal of Medicine indicated that ICSI use has increased 5-fold over the past decade, even though the proportion of men receiving treatment for male infertility has remained the same. In 1995, 11% of IVF cycles used ICSI. By 2004, 57.5% of IVF cycles used ICSI.

While ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

About 71% of ART procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place and the eggs can be examined for defects before implantation.)

Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technology success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer) and the lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In one study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over age 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

In Vitro Maturation. A new technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. About 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard 2- or 3-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, 5-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

Ooplasmic Transfer. Ooplasmic transfer is a controversial experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures are currently conducted outside the United States.

Before fertilization using intrauterine insemination (IUI) or advanced assisted reproductive technologies (ART) can take place, the sperm must be collected and prepared for optimal chances for success.

Retrieval Procedures

When a man has no available sperm in the ejaculate (usually from blockage, vasectomy, or lack of vas deferens), the sperm must be retrieved from the testes or the epididymis. Various microsurgical techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques.

Surgical Biopsy. In men without obstruction, sperm can be retrieved using a surgical testicular biopsy.

Testicular Fine Needle Aspiration. With testicular fine needle aspiration (TFNA), the surgeon uses a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (MESA) uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risks of complications, such as bleeding or infection.

Percutaneous Epididymal Sperm Aspiration. Percutaneious epididymal sperm aspiration (PESA) uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often, it can cause permanent alterations in testicular function that may even reduce male hormone levels.

Testicular Sperm Aspiration. Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm, and it is not as effective or as safe as TESE, although imaging techniques using ultrasound may improve results.

Sperm Washing

A sperm's energy output is 20 times greater once it is removed from the seminal fluid. Methods for washing sperm can have a dramatic effect on the ability of sperm to move towards the egg. The simplest method involves:

The sperm is mixed with a nutrient-rich fluid (or culture media) in a test tube.
They are then centrifuged (spun very rapidly) for about 5 minutes.
The sperm, which are heavy, settle on the bottom, forming a dense button of millions of pure sperm. The fluid left on top is siphoned off.
This procedure may be repeated.

This simple method of sperm washing, however, does not eliminate heavy debris, such as dead sperm, white blood cells, or bacteria, which may impair fertility. Scientists are developing new techniques, such as adding a substance called platelet-activating factor during the sperm washing process, which may enhance pregnancy rates.

Swim-Up Technique

The swim-up technique is not only a useful diagnostic procedure for testing the ability of sperm to escape from the semen into the cervical mucus, but it also achieves the goal of removing sperm from semen.

A specially prepared semen sample is placed in a tube.
A culture media (a nutrient-rich substance in which cells thrive) is placed on top of the sample.
The medium is a hospitable environment for sperm, and those that are healthy will swim up to it.
After an hour or more, the culture is examined, and the number of sperm that have reached the medium is compared to the number still remaining in the semen.

The result gives a fair estimation of the number of sperm potentially capable of fertilization. It is superior to sperm washing because the live sperm will swim up to the culture media, leaving behind most of the debris, although some may float up into the medium. There is also some evidence that such sperm may have fewer genetic abnormalities than those retrieved through sperm washing. The strongest sperm, which are those at the top of the medium, can be collected for in vitro fertilization or artificial insemination. A good swim test yields about half a million very active sperm.

Freezing Sperm

Sperm can be fresh or frozen in advance. Studies are reporting that frozen sperm provide excellent results and can be used confidently for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.

Complications of Assisted Reproductive Technology

Since assisted reproductive technology (ART) procedures have become more widespread since 1980, multiple births have significantly increased. About 35% of all ART births are multiple ones, with 4.3% being triplets or more. Multiple births increase the risk of complications, for both the mother and the child.

Assisted reproductive technology (ART), and multiple births, increase the risks for pregnancy complications. According to a 2005 study, the type of complications may depend on the infertility treatment:

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (placental abruption), third trimester miscarriage, and gestational diabetes.
IVF. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (placenta previa), dangerously high blood pressure during pregnancy (pre-eclampsia), and Caesarean sections.

Multiple births can also increase the risk of pregnancy death. A 2006 study indicated that women who carry multiple fetuses have a 3.6 times greater risk of dying from pregnancy complications than women with singleton pregnancies. The leading causes of death were blood clot (embolism), high blood pressure complications, excessive bleeding (hemorrhage), and infections.

The main risks for children conceived with assisted reproductive technology (ART) are complications associated with pregnancy problems and multiple births. Children conceived with ART are more likely to be born premature and to have extremely low birth weight. These conditions increase the risk for heart and lung problems, as well as learning and developmental disabilities. Premature delivery is also associated with cerebral palsy, a brain injury condition that affects muscle coordination. A 2006 study indicated that children born after in vitro fertilization have an increased risk for cerebral palsy.

However, unlike earlier research, recent studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with fertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

Preimplantation genetic diagnosis (PGD) is now available in a few fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Experts are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly and it too reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Other Treatments

Hormone therapy has been effective for women with infertility problems, but has been disappointing in men except in a few specific cases:

Gonadotropin-releasing hormone (GnRH) is often very helpful in restoring fertility in men with gonadotropin deficiency and hypogonadism.
GnRH may be useful for restoring sperm production after chemotherapy treatments.
Sperm production occasionally responds to low doses of estrogen and testosterone or testosterone alone, menotropins (Pergonal, Repronal), clomiphene citrate (Clomid), human chorionic gonadotropin (hCG), or human follicle-stimulating hormone (r-hFSH, Gonal-F).
Prolonged treatment with follicle-stimulating hormone (FSH) prior to intracytoplasmic sperm injection (ICSI) may improve implantation rates.
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole. (Femara). They may be helpful for specific men whose infertility is associated with abnormal testosterone-to-estrogen ratios.

Bromocriptine. Bromocriptine (Parlodel) is used in men whose infertility is related to excess prolactin manufactured by the pituitary.

Antibiotics. Infections interfering with fertility may be successfully treated with antibiotics.

Mast Cell Blocking Antihistamines. Studies report that certain antihistamines that block mast cells may be beneficial for some men with low sperm counts. Mast cells are inflammatory immune factors that may play a role in lower sperm quality. Studies have reported that two such drugs used overseas, ebastine and tranilast, improved pregnancy rates. Similar antihistamines in the U.S. are fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec).

Repair of a varicocele (varicocelectomy) in men with infertility problems is a common surgical practice. Nevertheless, although many urologists favor varicocele repair, the few well-conducted studies on this procedure suggest that it does not improve the chances for a successful pregnancy. Some experts argue that such studies were not using the most advanced techniques, which may be more effective. Some studies report that repair may improve the success rate of assisted reproductive technologies, such as intrauterine insemination (IUI). Still, the overall benefits remain uncertain, and additional rigorous trials are needed. In any case, the procedure does not appear to be beneficial for improving fertility in men whose varicoceles are very small.

Varicocele repair for fertility is sometimes considered when the following conditions are met:

When the varicocele can be felt during a physical examination.
Surgical treatment of varicoceles may be important in boys and adolescents to prevent later testicular damage.
When the male partner with varicoceles has abnormal semen quality or abnormal sperm function test results.
When the couple has known infertility, and the man has varicoceles but the woman is either fertile or can be treated for her infertility.

Varicocelectomy. Varicocelectomy, the standard repair procedure, involves tying off the swollen and twisted veins. Recovery takes 6 days, and most men cannot resume full activity for about 3 weeks. This technique eliminates 90% of varicoceles.

Recent surgical techniques use laparoscopy, which only requires tiny incisions (less than an inch). This approach allows for quicker recovery, although the procedure itself takes longer. It also has a higher rate of complications than the standard approach.

Varicocele Embolization. A nonsurgical technique called varicocele embolization may eventually prove to be an effective and less painful treatment for varicoceles, including those in young boys. It involves inserting a narrow tube (catheter) through a small incision in the neck or leg. Tiny steel plugs are passed through the catheter to block off the affected veins. The procedure takes 15 - 45 minutes to perform and uses local anesthetic. Some studies suggest that recurrence occurs in more than 10% of men, often requiring conventional surgery. This procedure is not yet widely available, and it may not be appropriate for some men.

Men with retrograde ejaculation and failure of emission caused by surgery, severe disease, or spinal cord injury are treated with various methods.

Drugs known as alpha-adrenergic agonists, including pseudoephedrine (Sudafed, Actifed), stimulate muscle contraction and help ejaculation. The tricyclic antidepressant imipramine (Tofranil) has similar effects, and in one analysis of 35 studies was more effective than pseudoephedrine. Promising investigational drugs include amezinium, which increases blood pressure.
If drugs are not effective, a technique called electrovibration (or electrical stimulation) is often beneficial. (Drugs in any case are not helpful for men with complete failure of emission.)

With any of these methods, the sperm can be collected for intrauterine insemination or assisted reproductive techniques. Spontaneous conception is possible, but not common, even with these treatments.

To prepare sperm for in vitro fertilization (IVF), men with retrograde ejaculation typically use sodium bicarbonate four times a day to reduce the acidity of the urine. After ejaculation, the man urinates or has a catheter (a tube) inserted to withdraw urine, which is then submitted for washing techniques to separate out the sperm.

Procedures that assist ejaculation are helping men with spinal cord injury conceive children. Vibratory or electronic stimulation is proving to be very beneficial for many of these men. The sperm retrieved using these methods are inserted into the women using self-insemination, intrauterine insemination, in vitro fertilizaiton, or intracytoplasmic sperm injection. Nearly a third of couples achieve pregnancy, a success rate that approaches natural conception.

Vasovasostomy. For men who wish to conceive after vasectomy, reversal surgery (vasovasostomy) may restore fertility. In vasovasostomy the severed ends of the vas deferens (which were cut during vasectomy) are reconnected to reestablish the flow of sperm. The reversal procedure is difficult. It involves sewing together the two ends of both tubes, each with pinhead sized openings. [See In-Depth Report #37: Vasectomy and vasovasostomy.]

Pregnancy Rates After Vasovasostomy. An Australian study reported that pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after a vasovasostomy. One study indicated that when successful conception occurs, it does at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long
The original procedure was performed on straight sections of the vas deferens
The pieces joined during the vasovasostomy are of equal size

The closer in time the vasovasostomy is to the original vasectomy, the better. In one large study, the pregnancy rates were 76% for those who had vasectomy less than 3 years before reversal surgery, but decreased to 30% for those men who had a vasectomy more than 15 years earlier. The decrease in rates as time goes by is probably due to an increase in the chance for obstruction of the epididymis and the development of anti-sperm antibodies. Success rates, according to some studies, are slightly better if the male partner does not change female partners after the procedure. Other studies suggest that it makes no difference if the man has a new female partner. The age of the woman is an important factor, and the chances of achieving pregnancy are best for women younger than age 35. Some research suggests that men who have a vasectomy reversal may have a greater rate of sperm chromosomal abnormalities than normal fertile men.

Reversal Versus Assisted Reproductive Technologies. Even though newer techniques such as ICSI are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was 25 - 30% (ICSI is the ART treatment of choice for men who have had vasectomy). Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

ART may, however, be a better approach than reversal for men with evidence of anti-sperm autoantibodies due to vasectomy. ICSI may also be more effective than reversal surgeries in men whose vasectomy was conducted at least 15 years or more beforehand.

Surgical Treatment of Obstructions. Obstructions in the area of the ejaculatory ducts have been successfully treated by excising or scraping the area where the prostate gland surrounds the urethra and by reconstructing the ducts.

Correcting Undescended Testicles. Undescended testicles of young boys may be repositioned surgically to prevent later infertility. It is important to perform the operation before 15 - 18 months of age to prevent the destruction of most of the sperm-producing cells, which occurs if the testicles remain in the abdomen.

Stem Cells. Researchers are investigating using sperm stem cells to treat male infertility. The research is still in its earliest stages. In 2004, researchers announced that they had successfully grown sperm progenitor cells in the laboratory. These types of cells could potentially develop into sperm cells capable of fertilizing an egg. This discovery was an important first step for developing stem cell infertility treatments.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.urologyhealth.org -- American Urological Association
www.afafamilymatters.com -- American Fertility Association
www.ssmr.org -- Society for the Study of Male Reproduction
www.sart.org -- Society for Assisted Reproductive Technology
www.cdc.gov/ART/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Report

References

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2007 Jan;92(1):196-202. Epub 2006 Oct 24.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Osteoporosis

admin — Wed, 03 Sep 2008 17:49:08 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Osteoporosis is the thinning of bone tissue and loss of bone density over time.

Alternative Names

Thin bones

Causes, incidence, and risk factors

Osteoporosis is the most common type of bone disease. An estimated 10 million Americans have osteoporosis, as well as another 18 million who have low bone mass, or osteopenia, which may eventually lead to osteoporosis if not treated.

Researchers estimate that about 1 out of 5 American women over the age of 50 have osteoporosis. About half of all women over the age of 50 will have a fracture of the hip, wrist, or vertebra (bones of the spine).

Osteoporosis occurs when the body fails to form enough new bone, when too much old bone is reabsorbed by the body, or both.

Calcium and phosphate are two minerals that are essential for normal bone formation. Throughout youth, your body uses these minerals to produce bones. If you do not get enough calcium, or if your body does not absorb enough calcium from the diet, bone production and bone tissues may suffer.

As you age, calcium and phosphate may be reabsorbed back into the body from the bones, which makes the bone tissue weaker. This can result in brittle, fragile bones that are more prone to fractures, even without injury.

Usually, the loss occurs gradually over years. Many times, a person will have a fracture before becoming aware that the disease is present. By the time this occurs, the disease is in its advanced stages and damage is severe.

The leading causes of osteoporosis are a drop in estrogen in women at the time of menopause and a drop in testosterone in men. Women, especially those over age 50, get osteoporosis more often than men.

Other causes include:

Being confined to a bed
Cushing syndrome
Excess corticosteroid levels due to ongoing use of medicines for asthma, certain forms of arthritis or skin diseases, and COPD.
Hyperthyroidism
Hyperparathyroidism
Rheumatoid arthritis and other inflammatory conditions

White women, especially those with a family history of osteoporosis, have a greater-than-average risk of developing osteoporosis. Other risk factors include:

Absence of menstrual periods (amenorrhea)
Drinking large amount of alcohol
Early menopause
Eating disorders
Family history of osteoporosis
Low body weight
Smoking
Too little calcium in the diet
Use of certain medications, including steroids and antiseizure drugs

Symptoms

There are no symptoms in the early stages of the disease.

Symptoms occurring late in the disease include:

Bone pain or tenderness
Fractures with little or no trauma
Loss of height over time
Low back pain due to fractures of the spinal bones
Neck pain due to fractures of the spinal bones
Stooped posture

Signs and tests

Bone mineral density testing (specifically a densitometry or DEXA scan) measures how much bone you have. This test has become the gold standard for osteoporosis evaluation. For specific information on such testing, see bone density test.

A spine CT can show loss of bone mineral density. Quantitative computed tomography (QCT) can evaluate bone density. However, it is not as available and is more expensive than a DEXA scan.

In severe cases, a spine or hip x-ray may show fracture or collapse of the spinal bones. However, simple x-rays of bones are not very accurate in predicting whether someone is likely to have osteoporosis.

You may need other blood and urine tests if your osteoporosis is thought to be due to a medical condition, rather than simply the usual bone loss seen with older age.

Treatment

The goals of osteoporosis treatment are to:

Control pain from the disease
Slow down or stop bone loss
Prevent bone fractures with medicines that strengthen bone
Minimize the risk of falls that might cause fractures

There are several different treatments for osteoporosis, including a variety of medications.

BISPHOSPHONATES

Bisphosphonates are a type of drug used for both the prevention and treatment of osteoporosis in postmenopausal women. Several bisphosphonates are approved for the treatment of osteoporosis in the United States, including alendronate (Fosamax), ibandronate (Boniva), and risedronate (Actonel). Most are taken by mouth, usually once a week or once a month. Bisphosphonates given through a vein (intravenously) are taken less often.

CALCITONIN

Calcitonin is a medicine that slows the rate of bone loss and relieves bone pain. It comes as a nasal spray or injection. The main side effects are nasal irritation from the spray form and nausea from the injectable form.

While calcitonin slows bone loss and reduces the risk of fractures, it appears to be less effective than bisphosphonates.

HORMONE REPLACEMENT THERAPY

Estrogens are still used to prevent osteoporosis but are not approved to treat a woman who has already been diagnosed with the condition.

Sometimes, if estrogen has helped a woman, and she cannot take other options for preventing or treating osteoporosis, the doctor may recommend she continue using hormone therapy. If you are considering taking hormone therapy to prevent osteoporosis, discuss the risks with your doctor.

Over the past decade, several major studies evaluated the health benefits and the risks of hormone therapy, including the risk of developing breast cancer, heart attacks, strokes, and blood clots. Evidence from these studies raised concerns for an increased risk for stroke, heart disease, breast cancer, and blood clots, depending on several factors that include the types of hormones used

Some women may still wish to consider hormone therapy for short-term treatment of menopausal symptoms. The key is to weigh the risks associated with taking hormone therapy against a particular woman's risk of heart disease or osteoporosis without taking hormone therapy. Other factors to consider include:

A woman's age
The age menopause started
The dose of hormone therapy being considered
Prior hormone replacement therapy taken in the past
Quality of life issues

Every woman is different. Your doctor should be aware of your entire medical history when considering hormone therapy.

PARATHYROID HORMONE

Teriparatide (Forteo) is approved in the United States for the treatment of postmenopausal women who have severe osteoporosis and are considered at high risk for fractures. The medicine is given through daily shots underneath the skin. You can give yourself the shots at home.

RALOXIFENE

Raloxifene (Evista) is used for the prevention and treatment of osteoporosis. Raloxifene is similar to the breast cancer drug tamoxifen. Raloxifene can reduce the risk of spinal fractures by almost 50%. However, it does not appear to prevent other fractures, including those in the hip. It may have protective effects against heart disease and breast cancer, though more studies are needed.

The most serious side effect of raloxifene is a very small risk of blood clots in the leg veins (deep venous thrombosis) or in the lungs (pulmonary embolus).

EXERCISE

Regular exercise can reduce the likelihood of bone fractures associated with osteoporosis. Some of the recommended exercises include:

Weight-bearing exercises -- walking, jogging, playing tennis, dancing
Resistance exercises -- free weights, weight machines, stretch bands
Balance exercises -- tai chi, yoga
Riding stationary bicycles
Using rowing machines
Walking
Jogging

Avoid any exercise that presents a risk of falling.

DIET

Get at least 1,200 milligrams per day of calcium, and 800 - 1,000 international units of vitamin D3. Vitamin D helps your body absorb calcium.Your doctor may recommend a supplement to give you the calcium and vitamin D you need.

Follow a diet that provides the proper amount of calcium, vitamin D, and protein. While this will not completely stop bone loss, it will guarantee that a supply of the materials the body uses to form and maintain bones is available.

High-calcium foods include:

Cheese
Ice cream
Leafy green vegetables, such as spinach and collard greens
Low-fat milk
Salmon
Sardines (with the bones)
Tofu
Yogurt

STOP UNHEALTHY HABITS

Quit smoking, if you smoke. Also limit alcohol intake. Too much alcohol can damage your bones, as well as put you at risk for falling and breaking a bone.

PREVENT FALLS

It is critical to prevent falls. Avoid sedating medications and remove household hazards to reduce the risk of fractures. Make sure your vision is good. Other ways to prevent falling include:

Avoiding walking alone on icy days
Using bars in the bathtub, when needed
Wearing well-fitting shoes

MONITORING

Your response to treatment can be monitored with a series of bone mineral density measurements taken every 1-2 years. However, such monitoring is controversial and expensive.

Women taking estrogen should have routine mammograms, pelvic exams, and Pap smears.

RELATED SURGERIES

There are no surgeries for treating osteoporosis itself. However, a procedure called vertebroplasty can be used to treat any small fractures in your spinal column due to osteoporosis. It can also help prevent weak vertebra from becoming fractured by strengthening the bones in your spinal column.

The procedure involves injecting a fast-hardening glue into the areas that are fractured or weak. A similar procedure, called kyphoplasty, uses balloons to widen the spaces that need the glue. (The balloons are removed during the procedure.)

Expectations (prognosis)

Some persons with osteoporosis become severely disabled as a result of weakened bones. Hip fractures leave about half of patients unable to walk independently. This is one of the major reasons people are admitted to nursing homes.

Although osteoporosis is debilitating, it does not affect life expectancy.

Complications

Compression fractures of the spine
Disability caused by severely weakened bones
Hip and wrist fractures
Loss of ability to walk due to hip fractures

Calling your health care provider

Call your health care provider if you have symptoms of osteoporosis or if you wish to be screened for the condition.

Prevention

Calcium is essential for building and maintaining healthy bone. Vitamin D is also needed because it helps your body absorb calcium. Following a healthy, well-balanced diet can help you get these and other important nutrients throughout life.

Other tips for prevention:

Avoid drinking excess alcohol
Don't smoke
Get regular exercise

A number of medications are approved for the prevention of osteoporosis.

References

Cranney A, Papaioannou A, Zytaruk N, et al. Clinical Guidelines Committee of Osteoporosis Canada. Parathyroid hormone for the treatment of osteoporosis: a systematic review. CMAJ. 2006 Jul 4;175(1):52-9.

Gass M, Dawson-Hughes B. Preventing osteoporosis-related fractures: an overview. Am J Med. 2006 Apr;119(4 Suppl 1):S3-S11. Review.

Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause. July/August 2008;15(4)584-602.

Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause. 2006 May-Jun;13(3):340-67.

National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Feb. 2008. Accessed July 23, 2008. Available online at http://www.nof.org/professionals/Clinicians_Guide.htm

Review Date: 8/4/2008

Reviewed By: Elizabeth H. Holt, MD, PhD, Assistant Professor of Medicine, Section of Endocrinology and Metabolism, Yale University. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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Source Doc: 1_000360

Liposuction

admin — Thu, 04 Sep 2008 19:03:08 -0700

Overview

Definition
Alternative Names
Description
Indications
Risks
Expectations after surgery
Convalescence

Illustrations

Fat layer in skin

Liposuction - series

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Liposuction is the removal of excess body fat by suction using special surgical equipment. A plastic surgeon typically does the surgery.

Alternative Names

Fat removal - suctioning

Description

Liposuction is a popular type of cosmetic surgery. It removes unwanted deposits of excess fat, to improve body appearance and to smooth irregular or distorted body shapes. The procedure is sometimes called body contouring.

Liposuction may be useful for contouring under the chin, neck, cheeks, upper arms, breasts, abdomen, buttocks, hips, thighs, knees, calves, and ankle areas.

However, liposuction is a serious surgical procedure and may involve a painful recovery. Because liposuction can have serious or occasionally fatal complications, you should carefully think about your decision to have this surgery.

Before your surgery, you will have an initial patient consultation, which will include a history, physical exam, and a psychological evaluation. You may need to bring someone (such as your spouse) with you during the visit. You may need a second consultation to give you time to think over the surgery.

You should feel free to ask questions, and to feel satisfied with the answers to those questions. A properly informed person makes a better patient. You must understand fully the pre-operative preparations, the liposuction procedure, and the post-operative care. Understand that liposuction may enhance your appearance and self-confidence, but it will probably not give you your ideal body.

Several different liposuction procedures exist:

Tumescent liposuction (fluid injection) is the most common type of liposuction. It involves injecting a large amount of medicated solution into the areas before the fat is removed (sometimes, the solution may be up to three times the volume of fat to be removed). The fluid is a mixture of local anesthetic (lidocaine), a drug that contracts the blood vessels (epinephrine), and an intravenous (IV) salt solution. The lidocaine in the mixture helps to numb the area during and after surgery, and may be the only anesthesia needed for the procedure. The epinephrine in the solution helps reduce the loss of blood, the amount of bruising, and the amount of swelling from the surgery. The IV solution helps remove the fat more easily and it is suctioned out along with the fat. This type of liposuction generally takes longer than other types.

The super-wet technique is similar to tumescent liposuction. The difference is that not as much fluid is used during the surgery--the amount of fluid injected is equal to the amount of fat to be removed. This technique takes less time; however, it often requires sedation with an IV or general anesthesia.

Ultrasound-assisted liposuction (UAL) is a fairly new technique, used in the U.S. since 1996. During this technique, ultrasonic vibrations are used to liquefy fat cells. After the cells are liquefied, they can be vacuumed out. UAL can be done in two ways, external (above the surface of the skin with a special emitter) or internal (below the surface of the skin with a small, heated cannula). This technique may help remove fat from dense, fiber-filled (fibrous) areas of the body such as the upper back or enlarged male breast tissue. UAL is often used together with the tumescent technique, in follow-up (secondary) procedures, or for greater precision. In general, this procedure takes longer than the super-wet technique.

Before the day of surgery you may have blood drawn and be asked to provide a urine sample. This allows the health care provider to rule out potential complications. If you are not hospitalized, you will need a ride home after the surgery.

A liposuction machine and special instruments are used for this surgery. The surgical team first preps the operative site and administers either local or general anesthesia. Through a small skin incision, a suction tube with a sharp end is inserted into the fat pockets and swept through the area where fat is to be removed. The dislodged fat is "vacuumed" away through the suction tube. A vacuum pump or a large syringe provides the suction action. Several skin punctures may be needed to treat large areas.

After the fat is removed, small drainage tubes may be inserted into the defatted areas to remove blood and fluid that gather during the first few days after surgery. If you lose a lot of fluid or blood during the surgery, you may meed fluid replacement (intravenously) or a blood transfusion.

After the surgery, bandages are applied to keep pressure on the area and stop any bleeding, as well as to help maintain shape. Bandages are usually kept in place for at least 2 weeks. Your doctor may call you from time to time to check on your health and to monitor your healing. A visit back to the surgeon after 5-7 days is often recommended. Sometimes people gain weight after liposuction. This is due to the increased fluid from surgery.

Liposuction may or may not require a hospital stay, depending on the location and extent of surgery. Liposuction can be done in an office-based facility, in a surgery center on an outpatient basis, or in a hospital. For reasons of cost and convenience, liposuction of smaller volumes is usually done as an outpatient. You may need to stay in a hospital if a larger volume of fat is being removed, or if you are having other procedures done at the same time.

Indications

The following are some of the uses for liposuction:

Cosmetic reasons, including "love handles," fat bulges, or an abnormal chin line.
To improve sexual function by reducing abnormal fat deposits on the inner thighs, thus allowing easier access to the vagina.
Body shaping for people who are bothered by fatty bulges or irregularities that cannot be removed by diet and/or exercise.

Liposuction is generally NOT appropriate for these uses:

As a substitute for exercise and diet, or as a cure for general obesity. However, it may be used to remove fat from isolated areas at different points in time.
As a treatment for cellulite (the uneven, dimpled appearance of skin over hips, thighs, and buttocks).
In certain areas of the body, such as the fat on the sides of the breasts, because the breast is a common site for cancer.

Many alternatives to liposuction exist, including a tummy tuck (abdominoplasty), removal of fatty tumors (lipomas), breast reduction (reduction mammaplasty), or a combination of plastic surgery approaches.

Risks

Certain pre-existing conditions should be checked and brought under control before liposuction, including:

History of heart problems (heart attack)
High blood pressure
Diabetes
Allergic reactions to medications
Pulmonary problems (shortness of breath, air pockets in bloodstream)
Allergies (antibiotics, asthma, surgical prep)
Smoking, alcohol, or drug use

There are also risks associated with liposuction, including:

Shock (usually when not enough fluid is replaced during the surgery)
Fluid overload (usually from the procedure)
Infections (strep, staph)
Bleeding, blood clot
Tiny globules of fat in the bloodstream that block blood flow to tissue (fat embolism)
Nerve, skin, tissue, or organ damage or burns from the heat or instruments used in liposuction
Uneven fat removal (asymmetry)
Drug reactions or overdose from the lidocaine used in the procedure
Scarring (skin surface may be irregular, asymmetric, or even "baggy," especially in older people)

Finally, make sure to review and sign any informed consent (legal) and permission forms for photographs.

Expectations after surgery

Most informed patients are satisfied with the cosmetic result of their surgery. Informed patients understand that there are limits to what liposuction can accomplish.

If you are having a large amount of fat removed, or you are being put to sleep (general anesthesia) for the procedure, you should expect to be admitted to the hospital. If you are having a smaller amount of fat removed with just the area numbed (local anesthesia), you may be able to have it done on an outpatient, same-day basis, as long as the office has the proper equipment and oxygen on hand.

Convalescence

The liposuctioned area may appear larger than before surgery because of swelling. You must wear a tight stocking, girdle, or snug elastic dressing over the treated area to reduce swelling and bleeding, and to help shrink the skin to fit the new contour. You should wear this garment continuously for 2 to 3 weeks.

You will likely have swelling, bruising, numbness, and pain, but it can be managed with medications. The stitches will be removed in 5 to 10 days. Antibiotics may be prescribed to prevent infection.

You may feel sensations such as numbness or tingling, as well as pain, for weeks after the surgery. Walk as soon after surgery as possible to help prevent blood clots from forming in your legs. Avoid more strenuous exercise for about a month after the surgery.

You will start to feel better after about 1 or 2 weeks following liposuction surgery. You may return to work within a few days of the surgery. Bruising and swelling usually go away within three weeks; however, you may still have some swelling several months later.

Your doctor will check your progress through follow-up visits. If you have any questions or problems between office visits, call your doctor. Your new body shape will begin to emerge in the first couple of weeks; however, the improvement won't become more visible until about 4 to 6 weeks after surgery. By exercising regularly and eating a healthy diet, you can help maintain your new shape.

Review Date: 5/3/2007

Reviewed By: Robert A. Cowles, M.D., Assistant Professor of Surgery, Columbia University College of Physicians and Surgeons, New York, NY. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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Source Doc: 1_002985